bluuebunny/crossref_metadata_2025 huggingface dataset:
Current treatment options for erectile dysfunction in kidney transplant recipients
Authors: Dell’Atti Lucio
Published: May 2024

Introduction

Erectile dysfunction (ED) and kidney dysfunction share common risk factors linked to conditions involving endothelial impairment, such as coronary artery disease, dyslipidemia, diabetes mellitus, hypertension, smoking, and obesity. Men with chronic kidney disease experience a high incidence and prevalence of ED. While a functional renal graft can alleviate the issue for some patients, a significant portion of recipients still experience ED (20%-50%).

Objectives

This narrative review describes the variety of current treatments modalities on ED in kidney transplant recipients (KTRs) and their clinical outcomes.

Methods

MEDLINE, Web of Science, PubMed, and Google Scholar were used to find eligible articles pertaining to the treatment options of ED in KTRs. A total of 64 articles were evaluated.

Results

In KTRs, ED stems from a multifaceted etiology: anxiety, drug side effects, interference with penile vascularity, or the response of cavernosal muscle to neurotransmitters, along with changes in the endocrine milieu. A diverse range of treatments to restore erectile function has proven to be safe and effective for KTRs. Options include drug therapy, surgical interventions, intracavernosal injection therapies, vacuum erection devices, and extracorporeal shockwave therapy.

Conclusion

The initial treatment approach may involve the use of a phosphodiesterase type 5 inhibitors at a low dosage, especially if testosterone-circulating levels align with the diagnosis of hypogonadism. The consideration of a combination therapy involving testosterone and phosphodiesterase type 5 inhibitors should be contemplated due to the associated beneficial effects. Extracorporeal shockwave therapy has shown positive short-term clinical and physiological effects on erectile function in patients who did not respond to first-line treatments, resulting in spontaneous erections sufficient for sexual penetration in 50% of cases. Penile implants should be considered as third-line options based on specific patient needs and compliance with clinical conditions.
State-of-the-art and upcoming trends in RAS-directed therapies in gastrointestinal malignancies
Authors: Vanclooster Pieterjan , Seghers Sofie , Prenen Hans
Published: May 2024

Purpose of review

Overall, the review underscores the evolving landscape of KRAS-targeted therapy and the potential for these approaches to improve outcomes for patients with gastrointestinal malignancies. It highlights the importance of ongoing research and clinical trials in advancing precision medicine strategies for KRAS-driven cancers. This review provides a comprehensive overview of the RAS signaling pathway and its significance in gastrointestinal malignancies.

Recent findings

The introduction of KRAS inhibitor represents a significant advancement in the treatment landscape for KRAS-mutant cancers. In this review, we discuss upcoming trends in KRAS-targeted therapy, including the development of mutant-specific direct KRAS inhibitors like MRTX1133 and pan-RAS inhibitors such as RMC-6236. It also explores indirect RAS inhibitors targeting upstream and downstream components of the RAS pathway. Additionally, the review examines other upcoming strategies like combination therapies, such as CDK4/6 and ERK MAPK inhibitors, as well as adoptive cell therapy and cancer vaccines targeting KRAS-mutant cancers.

Targeting RAS has become an important strategy in treating gastrointestinal cancer. These findings in this review underscore the importance of a multidisciplinary approach, integrating advances in molecular profiling, targeted therapy, immunotherapy, and clinical research to optimize treatment strategies for patients with KRAS-mutant gastrointestinal malignancies.
Hearing loss prevalence and burden of disease in China: Findings from provincial-level analysis
Authors: Wang Yu , Xie Yang , Wang Minghao , Zhao Mengdan , Gong Rui , Xin Ying , Ke Jia , Zhang Ke , Zhang Shaoxing , Du Chen , Duan Qingchuan , Wang Fang , Pan Tao , Ma Furong , Hu Xiangyang
Published: May 2024

Background:

Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China’s aging society.

Methods:

We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China.

Results:

An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015.

Conclusions:

The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
An indocyanine green-based liquid biopsy test for circulating tumor cells for pediatric liver cancer
Authors: Espinoza Andres F. , Kureti Pavan , Patel Roma H. , Do Susan L. , Govindu Saiabhiroop R. , Armbruster Bryan W. , Urbicain Martin , Patel Kalyani R. , Lopez-Terrada Dolores , Vasudevan Sanjeev A. , Woodfield Sarah E.
Published: May 2024

Background:

Hepatoblastoma and HCC are the most common malignant hepatocellular tumors seen in children. The aim of this study was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide real-time information about tumor response to therapy.

Methods:

For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye used clinically to identify malignant liver cells during surgery. We assessed ICG accumulation in cell lines using fluorescence microscopy and flow cytometry. For our CTC test, we developed a panel of liver tumor-specific markers, including ICG, Glypican-3, and DAPI, and tested it with cell lines and noncancer control blood samples. We then used this panel to analyze whole-blood samples for CTC burden with a cohort of 15 patients with hepatoblastoma and HCC and correlated with patient characteristics and outcomes.

Results:

We showed that ICG accumulation is specific to liver cancer cells, compared to nonmalignant liver cells, non-liver solid tumor cells, and other nonmalignant cells, and can be used to identify liver tumor cells in a mixed population of cells. Experiments with the ICG/Glypican-3/DAPI panel showed that it specifically tagged malignant liver cells. Using patient samples, we found that CTC burden from sequential blood samples from the same patients mirrored the patients’ responses to therapy.

Conclusions:

Our novel ICG-based liquid biopsy test for CTCs can be used to specifically detect and quantify CTCs in the blood of pediatric patients with liver cancer.
Complex Buccal Graft Urethroplasty Combined With HoLEP in the Setting of Concomitant Urethral Stricture Disease and Severe Benign Prostatic Hyperplasia: A Case Report
Authors: Garabed Laurianne Rita , Wang Stephanie , Meskawi Malek , Bhojani Naeem , Liberman Daniel
Published: May 2024

Background:

Urethral strictures and benign prostatic hyperplasia (BPH) are 2 common causes of urinary obstruction and urinary emptying symptoms. While urethroplasty and endoscopic management of BPH have been extensively discussed in the literature when performed on their own, a case of simultaneous urethroplasty and endoscopic management of BPH has not been previously described in the literature.

Case Description:

We present the case of a 75-year-old man with significant BPH and concomitant bulbar obliterative urethral stricture. After discussion of treatment options with the patient, we elected to perform both holmium LASER enucleation of the prostate (HoLEP) of a 200cc prostate and buccal graft urethroplasty during the same surgery. The HoLEP was performed through a dorsal urethrotomy in anticipation of urethroplasty. Nontransecting anastomotic repair was then combined with the buccal graft urethroplasty. The patient did not have any acute postoperative complications and had no recurrence. He reported improvements in outcome questionnaire scores and uroflow parameters at the 12-month follow-up.

Conclusions:

This case presentation is the first to report on simultaneous complex urethroplasty and endoscopic management of BPH, specifically HoLEP. It shows that this approach can lead to positive urinary outcomes without added complications and with lasting outcomes, thereby allowing the use of a combined surgical approach.
Robotic Ureterolithotomy for Retained Stent With Massive Encrustation: Case Report and Review of the Literature
Authors: Kong Lily , Coddington Nathaniel D. , Shahinyan Gary K. , Kukreja Janet B. , Flynn Brian J.
Published: May 2024

Massive encrustation is a rare complication of retained foreign bodies in the urinary tract. Large stone size and coexisting artificial material can limit endoscopic options, necessitating surgical removal. We present a case of massive encrustation of a retained ureteral stent treated with robotic-assisted laparoscopic ureterolithotomy.
Partial Versus Radical Nephrectomy: Comparison of Postoperative Complications and Contribution to Mortality
Authors: Houjaij Ali , Darwish Oussama M. , Rubin Jacob , Pominville Raymond , Arora Pradeep , Shiekh Mohsin , Gajdos Csaba , Nader Nader D.
Published: May 2024

Background:

Partial nephrectomy is the preferred treatment method for certain kidney tumors owing to its nephron-preserving benefit. We aimed to compare the occurrence and importance of complications after radical (RN) or partial (PN) nephrectomy for localized renal cell carcinoma (RCC) and contribution to patient mortality.

Methods:

All RCC cases were extracted from the National Surgical Quality Improvement Program between 2005 and 2017. All-cause mortality was the primary endpoint that defined a failure to rescue (FTR) after the occurrences of complications. Propensity score matching (PSM) was performed to adjust for confounding variables between the 2 groups. The exclusion criteria included patients on dialysis, those with distant metastases, and those with concurrent procedures. Null hypotheses were rejected when P-values were < .05.

Results:

The database included 24,830 patients, with 22,015 in the RN group and 2815 in the PN. After PSM, 2226 patients after PN were matched 1:1 to an equal number of patients who underwent RN. Overall, postoperative complications occurred in 20.5% after RN, more frequent than 15.9% after PN (P < .001). While the mortality rates were similar, patients were more likely to experience blood transfusion and reintubation, as well as longer hospital stay after RN, while they were likely to have more infectious complications, including abdominal abscess, and more likely to return to the operating room after PN. In both groups, cardiac and respiratory complications were associated with FTR, leading to mortality. Excessive bleeding (requiring transfusion) was also a significant cause of death after RN but not after PN.

Conclusion:

When planning PN or RN, patients should be counseled on the risks of their selective procedure and the potential increased mortality risk with certain complications. These risks should be weighed against the benefit of those cancer surgeries.
Liver paired exchange: A US single-center experience—Pairs, chains, and use of compatible pairs
Authors: Klair Tarunjeet , Fritze Danielle , Halff Glenn , Patnaik Ronit , Thomas Elizabeth , Abrahamian Gregory , Cullen Jonathan M. , Cigarroa Francisco
Published: May 2024

In the United States, the discrepancy between organ availability and need has persisted despite changes in allocation, innovations in preservation, and policy initiatives. Living donor liver transplant remains an underutilized means of improving access to timely liver transplantation and decreasing waitlist mortality. Liver paired exchange (LPE) represents an opportunity to overcome living donor liver transplant pair incompatibility due to size, anatomy, or blood type. LPE was adopted as a strategy to augment access to liver transplantation at our institution. Specific educational materials, consent forms, and selection processes were developed to facilitate LPE. From 2019 through October 2023, our center performed 11 LPEs, resulting in 23 living donor liver transplant pairs. The series included several types of LPE: those combining complementary incompatible pairs, the inclusion of compatible pairs to overcome incompatibility, and the use of altruistic nondirected donors to initiate chains. These exchanges facilitated transplantation for 23 recipients, including 1 pediatric patient. LPE improved access to liver transplantation at our institution. The ethical application of LPE includes tailored patient education, assessment and disclosure of exchange balance, mitigation of risk, and maximization of benefit for donors and recipients.
Repeat Radiosurgery for Sporadic Vestibular Schwannoma After Primary Radiosurgical Failure: An International Multi-institutional Investigation
Authors: Khandalavala Karl R. , Herberg Hans A. , Kay-Rivest Emily , Moore Lindsay S. , Yancey Kristen L. , Marinelli John P. , Lund-Johansen Morten , Kosaraju Nikitha , Lohse Christine M. , Kutz Walter , Santa Maria Peter L. , Golfinos John G. , Kondziolka Douglas , Carlson Matthew L. , Tveiten Øystein V. , Link Michael J.
Published: May 2024

Objective

To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) after primary SRS failure.

Study Design

Multi-institutional historical cohort study.

Setting

Five tertiary care referral centers.

Patients

Adults ≥18 years old with sporadic VS.

Intervention

Primary and repeat treatment with SRS.

Main Outcome Measure

Microsurgery-free survival after repeat SRS.

Results

Across institutions, 32 patients underwent repeat SRS after primary SRS. Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size, 13.5 mm [interquartile range, 7.5–18.8] mm). After primary SRS, patients underwent repeat SRS at a median of 4.8 years (interquartile range, 3.2–5.7 yr). For treatment modality, 30 (94%) patients received gamma knife for primary treatment and 31 (97%) patients received gamma knife as their repeat treatment. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in two patients after primary SRS and in two patients after repeat SRS. There were no instances of intracranial complications after repeat SRS. Microsurgery-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after repeat SRS were 97% (90–100%, 24), 84% (71–100%, 13), and 68% (48–96%, 6), respectively. There was one occurrence of malignancy diagnosed after repeat radiosurgery.

Conclusion

Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared with primary SRS.
Gene association analysis to determine the causal relationship between immune-mediated inflammatory diseases and frozen shoulder
Authors: Zhou Yuhang , Yin Xiuping , Wang Chenyu , Yu Donglin
Published: May 2024

Multiple studies have indicated a potential correlation between immune-mediated inflammatory diseases (IMIDs) and Frozen shoulder (FS). To explore the genetic causal relationship between IMIDs and FS using 2-sample Mendelian randomization (MR) analysis. Genome-wide association study (GWAS) summary data for FS were obtained from Green’s study, while data for 10 IMIDs were sourced from the FinnGen Consortium. The MR analysis was performed using inverse variance weighting, MR Egger, and weighted median methods. IVW, as the primary MR analysis technique, was complemented with other sensitivity analyses to validate the robustness of the results. Additionally, reverse MR analysis was further conducted to investigate the presence of reverse causal relationships. In the forward MR analysis, genetically determined 4 IMIDs are causally associated with FS: rheumatoid arthritis (odds ratio [OR] (95% confidence interval [95% CI]) = 1.05 [1.02–1.09], P < .01); type 1 diabetes (OR [95% CI] = 1.06 [1.03–1.09], P < .01); hypothyroidism (OR [95% CI] = 1.07 [1.01–1.14], P = .02); and Celiac disease (OR [95% CI] = 1.02 [1.01–1.04], P = .01). However, no causal relationship was found between 6 IMIDs (autoimmune hyperthyroidism, Crohn disease, ulcerative colitis, psoriasis, sicca syndrome and systemic lupus erythematosus) and FS. Sensitivity analyses did not detect any heterogeneity or horizontal pleiotropy. In the reverse MR analysis, no causal relationship was observed between FS and IMIDs. In conclusion, this MR study suggests a potential causal relationship between rheumatoid arthritis, type 1 diabetes, hypothyroidism, and Celiac disease in the onset and development of FS. Nevertheless, more basic and clinical research will be needed in the future to support our findings.
Association of inflammatory markers based on routine blood with prognosis in patients underwent percutaneous coronary intervention
Authors: Huo Li Kun , Chen Kang Yin , Tse Gary , Liu Tong
Published: May 2024

Inflammation contributes to the pathophysiological processes of coronary artery disease. We evaluated the association between inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), systemic inflammatory index, platelet-lymphocyte ratio, and 1-year all-cause mortality in patients underwent percutaneous coronary intervention (PCI). In this retrospective cohort, we consecutively enrolled 4651 patients who underwent PCI. Baseline demographic details, clinical data, and laboratory parameters on admission were analyzed. The primary outcome was 1-year all-cause mortality after PCI. We performed Cox regression and restricted cubic spline analysis to assessed the association between the inflammatory biomarkers and the clinical outcome. The area under the curve from receiver operating characteristic analysis was determined for the ability to classify mortality outcomes. A total of 4651 patients were included. Of these, 198 (4.26%) died on follow-up. Univariate Cox regression showed that NLR (heart rate [HR]: 1.070, 95% confidence interval [CI]: 1.060–1.082, P < .001), RDW (HR: 1.441, 95% CI 1.368–1.518, P < .001), systemic inflammatory index (HR: 1.000, 95% CI 1.000–3.180, P < .001), platelet-lymphocyte ratio (HR: 3.812, 95% CI 1.901–3.364, P < .001) were significant predictors of 1-year all-cause mortality. After adjusting for other confounders in multivariate analysis, NLR (HR: 01.038, 95% CI 1.022–1.054, P < .001) and RDW (HR: 1.437, 95% CI 1.346–1.535, P < .001) remained significant predictors. Restricted cubic spline analysis showed the relationship between RDW, NLR, and 1-year all-cause mortality was linear after adjusting for the covariables (P for non-linearity < 0.001). The multivariable adjusted model led to improvement in the area under the curve to 0.83 (P < .05). Nomogram was created to predict the probability of 1 year mortality. Among the laboratory indices, RDW and NLR showed the best performance for mortality risk prediction. Multivariate predictive models significantly improved risk stratification.
The role of claudins in renal transepithelial transport and kidney disease
Authors: Tsamo Tetou Arnold , Günzel Dorothee
Published: May 2024

Purpose of review

25 years after the discovery of claudins as the central constituents of tight junctions, the “hunter-gatherer phase” of claudin research is coming to an end. Deficiency in individual claudins as a cause of rare hereditary diseases is well documented. However, knowledge about the involvement of renal claudins in common kidney diseases and strategies to utilize claudins or their regulators for intervention are still scarce. The present review summarizes novel approaches to address these questions.

Recent findings

Publicly accessible omics data provide new insights not only into general claudin expression patterns along the nephron, but also into sex-specific differences in claudin expression and into claudin dysregulation in renal injury. Computational association studies identify claudin variants as risk factors for kidney disease such as nephrolithiasis or loss of filtration capacity. The establishment of innovative cell culture and organoid models contributes to a better understanding of junctional and extra-junctional functions of individual claudins.

The current studies lay the foundation for the identification of upstream regulators of renal claudin expression and thus for the development of new concepts for the treatment of kidney disease.
Fluorine-18 fluorodeoxyglucose uptake change in liver, mediastinal blood pool, and lymphoid cell–rich organs during programmed cell death-1 immunotherapy in lymphoma
Authors: Guo Linlin , Wang Rang , Shen Guohua
Published: May 2024

Purpose

The aim of this study was to evaluate metabolism change in reference organs (liver and mediastinum) and lymphoid cell–rich organs (spleen and bone marrow) during programmed cell death-1 immunotherapy in relapsed or refractory lymphoma patients.

Methods

A total of 66 patients with baseline and serial monitoring fluorodeoxyglucose (FDG) PET/computed tomography scans were retrospectively enrolled. Mean standardized uptake value (SUV) and maximum SUV of evaluated organs were obtained by two reviewers, and their association with tumor burden and clinical response were evaluated. Immune-related adverse events detected by FDG PET/computed tomography were also recorded.

Results

The SUV values of reference organs and lymphoid cell–rich organs did not change significantly during the immunotherapy process. The intersubject variability of these values ranged from 13.0 to 28.5%. Meanwhile, metabolism of reference organs was affected by neither the tumor burden nor clinical response. SUV change of lymphoid cell–rich organs was associated with clinical response to immunotherapy. Responders showed decreased metabolism, while nonresponders showed a reverse trend (spleen SUVmax: −0.30 ± 0.47 vs. 0.18 ± 0.39, P = 0.001, spleen SUVmean: −0.24 ± 0.39 vs. 0.14 ± 0.31, P = 0.001; and bone marrow SUVmax: −0.14 ± 0.37 vs. 0.07 ± 0.46, P = 0.042, respectively). The influence of immune-related adverse events on the SUV change in evaluated organs was not significant.

Conclusion

During programmed cell death-1 immunotherapy, metabolism change of reference organs is influenced neither by tumor burden nor by clinical response, while FDG uptake change of lymphoid cell–rich organs is significantly associated with clinical response.
Evaluating the Effectiveness of Expert Modeling Videos on Nursing Student Competency Behaviors
Authors: Dodson Tracy M. , Reed Janet M.
Published: May 2024

Background:

Expert modeling videos (EMVs) have shown promise in improving students’ performance in simulation. However, research evaluating the impact of EMVs is limited to major performance areas, lacking exploration into specific student competency behaviors.

Purpose:

This study evaluated the effect of an EMV intervention on undergraduate nursing students’ behavioral competencies as measured by the Creighton Competency Evaluation Instrument (CCEI).

Methods:

Using a quasi-experimental pragmatic evaluation design, students in a medical surgical nursing course (n = 160) viewed either an expert model demonstration video (experimental) or expert model discussion video (control). Students’ behavioral competencies were measured and compared between groups using the CCEI.

Results:

Students who viewed an expert model demonstration video performed at a higher level of competency in 11 of the 18 CCEI behaviors.

Conclusion:

Using EMVs in nursing simulation may improve students’ ability to achieve clinical competency in nursing specific behaviors.
Effect of Propolis on Salivary Glands After Radiotherapy
Authors: Erdim Ibrahim , Colak Sefa , Demirsoy Mustafa Sami , Avci Gulhan Guler , Gevrek Fikret , Ozmen Zeliha Cansel
Published: May 2024

Objectives:

To investigate the effects of increasing propolis doses on salivary glands exposed to radiotherapy (RT).

Methods:

Thirty-seven rats were divided into 4 groups: The control group (G0, n: 7), G1 group (n: 10), G2 group (n: 10), and G3 group (n: 10). The rats in the G1 group received 15 Gray (Gy) RT only to the head and neck area. The rats in the G2 and G3 groups received 15 Gy RT for the head and neck area along with 100 mg/kg/ml and 200 mg/kg/ml of propolis. The parotid, submandibular, and sublingual glands of rats were immunohistochemically stained with aquaporin-1 (AQP-1) and aquaporin-5 (AQP-5). They were also evaluated for malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPO), total antioxidant (TAS), and total oxidant status (TOS).

Results:

AQP-1 and AQP-5 values were highest in G0 group followed by G3, G2, and G1 groups in decreasing order. The MDA and TOS values were highest in G1 group, which was followed by G2, G3, and G0 groups. The highest GPO, SOD, and TAS values were observed in G0 group followed by G3, G2, and G1 groups in decreasing order.

Conclusion:

It was found that propolis increased antioxidant products and decreased oxidative products in the salivary glands receiving RT in parallel with the dose increase. Similarly, in the groups receiving propolis, an increase in the immune expression of aquaporin molecules was detected in a dose-dependent manner. Based on these data, it could be stated that propolis has a healing effect on the salivary glands exposed to RT.
Lifestyle of Cleft Lip/Palate Patients in Korea Before the Introduction of the Millard Technique
Authors: Jung Sung Gyun , Hwang Kun , Joong Hwang Young
Published: May 2024

The authors introduce a short story about the lifestyle of a cleft lip woman in Korea, published in 1936, about 2 decades before Dr Millard operated on his first patient in Korea. A short story entitled “Ugly Thing,” written by Yao-hsieh Chu, analyzed by Eonnyeon, a girl born in a rural area with a cleft lip and palate who excelled at household tasks such as sewing. Her forehead was bulging, and her eyes were protruding. She had a low-profile nose with wide nostrils. She had a left unilateral complete primary cleft, including an alveolar cleft. There was midface retraction, accompanied by a relatively prominent chin. Her voice exhibited hypernasality. People often laugh when they see Eonnyeon eating her food, exclaiming, “She’s eating like a rabbit!” However, she married a young man who deserted her on their wedding night because of her appearance. Subsequently, she moved to an urban area and found work as a housemaid. One day, she was raped by a middle-aged water delivery man, who then fled. Ten months later, she gave birth to a girl who also had a cleft lip. In a moment of despair, Eonnyeon attempted to smother her baby with a pillow but stopped herself. She resolved to raise her daughter despite the challenges ahead. The mockery directed at her could be viewed as an expression of the latent sadism inherent in human nature. It is remarkable to consider the progress made since Millard performed his first cleft lip surgery in Korea in 1954.
Barriers of Three-Dimensional Printing in Craniofacial Plastic Surgery Practice: A Pilot Study and Literature Review
Authors: Kim Erin , Vishwanath Neel , Foppiani Jose , Escobar-Domingo Maria J. , Lee Daniela , Francalancia Stephanie , Lin Gavin J. , Woo Albert S. , Lin Samuel J.
Published: May 2024

Objective:

Three-dimensional printing (3Dp) and modeling have demonstrated increasing utility within plastic and reconstructive surgery (PRS). This study aims to understand the prevalence of how this technology is utilized in craniofacial surgery, as well as identify barriers that may limit its integration into practice.

Methods:

A survey was developed to assess participant demographics, characteristics of 3Dp use, and barriers to utilizing three-dimensional technologies in practice. The survey was distributed to practicing craniofacial surgeons. A secondary literature review was conducted to identify solutions for barriers and potential areas for innovation.

Results:

Fifteen complete responses (9.7% response rate) were analyzed. The majority (73%) reported using three-dimensional modeling and printing in their practice, primarily for surgical planning. The majority (64%) relied exclusively on outside facilities to print the models, selecting resources required to train self and staff (55%), followed by the cost of staff to run the printer (36%), as the most common barriers affecting 3Dp use in their practice. Of those that did not use 3Dp, the most common barrier was lack of exposure (75%). The literature review revealed cost-lowering techniques with materials, comparability of desktop commercial printers to industrial printers, and incorporation of open-source software.

Conclusions:

The main barrier to integrating 3Dp in craniofacial plastic and reconstructive surgery practice is the perceived cost associated with utilizing the technology. Ongoing literature highlights the cost-utility of in-house 3Dp technologies and practical cost-saving methods. The authors’ results underscore the need for broad exposure for currently practicing attendings and trainees in 3Dp practices and other evolving technologies.
Health Expenditures After Bariatric Surgery
Authors: Smith Valerie A. , Zepel Lindsay , Kawatkar Aniket A. , Arterburn David E. , Baecker Aileen , Theis Mary K. , Sloan Caroline , Clark Amy G. , Saurabh Shireesh , Coleman Karen J. , Maciejewski Matthew L.
Published: May 2024

Objective:

To compare expenditures between surgical and matched nonsurgical patients in a retrospective cohort study.

Background:

Bariatric surgery leads to substantial improvements in weight and weight-related conditions, but prior literature on postsurgical health expenditures is equivocal.

Methods:

In a retrospective study, total outpatient, inpatient, and medication expenditures 3 years before and 5.5 years after surgery were compared between 22,698 bariatric surgery [n = 7127 Roux-en-Y gastric bypass (RYGB), 15,571 sleeve gastrectomy (SG)] patients from 2012 to 2019 and 66,769 matched nonsurgical patients, using generalized estimating equations. We also compared expenditures between patients receiving the 2 leading surgical procedures in weighted analyses.

Results:

Surgical and nonsurgical cohorts were well matched, 80% to 81% females, with mean body mass index of 44 and mean age of 47 (RYGB) and 44 (SG) years. Estimated total expenditures were similar between surgical and nonsurgical groups 3 years before surgery ($27 difference, 95% CI: −42, 102), increased 6 months before surgery for surgical patients, and decreased below preperiod levels for both groups after 3 to 5.5 years to become similar (difference at 5.5 years = -$61, 95% CI: −166, 52). Long-term outpatient expenditures were similar between groups. Surgical patients’ lower long-term medication expenditures ($314 lower at 5.5 years, 95% CI: −419, −208) were offset by a higher risk of hospitalization. Total expenditures were similar between patients undergoing RYGB and SG 3.5 to 5.5 years after surgery.

Conclusions:

Bariatric surgery translated into lower medication expenditures than matched controls, but not lower overall long-term expenditures. Expenditure trends appear similar for the two leading bariatric operations.
Preoperative COVID-19 Vaccination is Associated with Decreased Perioperative Mortality after Major Vascular Surgery
Authors: Ratner Molly , Garg Karan , Chang Heepeel , Nigalaye Anjali , Medvedovsky Steven , Jacobowitz Glenn , Siracuse Jeffrey J. , Patel Virendra , Schermerhorn Marc , DiMaggio Charles , Rockman Caron B.
Published: May 2024

Objective:

The objective of this study was to examine the effect of corona virus 2019 (COVID-19) vaccination on perioperative outcomes after major vascular surgery.

Background Data:

COVID-19 vaccination is associated with decreased mortality in patients undergoing various surgical procedures. However, the effect of vaccination on perioperative mortality after major vascular surgery is unknown.

Methods:

This is a multicenter retrospective study of patients who underwent major vascular surgery between December 2021 through August 2023. The primary outcome was all-cause mortality within 30 days of index operation or prior to hospital discharge. Multivariable models were used to examine the association between vaccination status and the primary outcome.

Results:

Of the total 85,424 patients included, 19161 (22.4%) were unvaccinated. Unvaccinated patients were younger compared to vaccinated patients (mean age 68.44 +/- 10.37 y vs 72.11 +/- 9.20 y, P<0.001) and less likely to have comorbid conditions, including hypertension, congestive heart failure, chronic obstructive pulmonary disease, and dialysis. After risk factor adjustment, vaccination was associated with decreased mortality (OR 0.7, 95% CI 0.62 - 0.81, P<0.0001). Stratification by procedure type demonstrated that vaccinated patients had decreased odds of mortality after open AAA (OR 0.6, 95% CI 0.42-0.97, P=0.03), EVAR (OR 0.6, 95% CI 0.43-0.83, p 0.002), CAS (OR 0.7, 95% CI 0.51-0.88, P=0.004) and infra-inguinal lower extremity bypass (OR 0.7, 95% CI 0.48-0.96, P=0.03).

Conclusions:

COVID-19 vaccination is associated with reduced perioperative mortality in patients undergoing vascular surgery. This association is most pronounced for patients undergoing aortic aneurysm repair, carotid stenting and infrainguinal bypass.
Cost Analysis of Bladder Catheterization After Pelvic Floor Surgery
Authors: Benseler Anouk , Zhao Zi Ying , Sheikh Muhammad Harris , Chan Brian , Tomlinson George , McDermott Colleen D.
Published: May 2024

Importance

Approximately 15–45% of female patients develop transient postoperative urinary retention (POUR) following pelvic reconstructive surgery. Catheter options for bladder drainage include transurethral indwelling catheter (TIC), intermittent self-catheterization (ISC), and suprapubic tube (SPT). Each strategy has risks and benefits; none have been shown to be clinically superior, and to date, no comprehensive comparative economic analysis has been published.

Objective

The objective of this study was to evaluate the cost of these different bladder catheterization strategies after transvaginal pelvic surgery.

Study Design

A Canadian universal single-payer (government funded) health system perspective was taken, and a decision tree model was constructed to evaluate the costs associated with each catheterization strategy over a 6-week horizon. Base-cases were set based on recently published clinical data of our institutions, 2 academic tertiary care centers, and based on systematic reviews and meta-analyses. Costs were established in consultation with process stakeholders, in addition to published values.

Results

The average cost calculated for management of transient POUR after outpatient pelvic reconstructive surgery was 150.69 CAD (median 154.86; interquartile range [IQR] 131.30–176.33) for TIC, 162.28 CAD (median 164.72; IQR 144.36–189.39) for ISC and 255.67 CAD (median 270.63; IQR 234.32–276.82) for SPT. In costing inpatient surgical data, the average cost calculated was 134.22 CAD (median 123.61; IQR 108.87–151.85) for TIC and 224.61 CAD (median 216.07; IQR 203.86–231.23) for SPT.

Conclusion

TIC and ISC were found to be significantly less costly than SPT in managing transient POUR following transvaginal pelvic reconstructive surgery.
Pharmacist-prescriber collaborative models of care for opioid use disorder: an overview of recent research
Authors: Cheetham Ali , Grist Elizabeth , Nielsen Suzanne
Published: May 2024

Purpose of review

Collaborative models of care where pharmacists work alongside physicians have been developed for a range of physical health conditions, with benefits including improved patient outcomes and increased access to ongoing care. Opioid agonist treatment (methadone and buprenorphine) is a clinically effective and cost-effective treatment for opioid use disorder that is under-utilized in many countries due to a shortage of prescribers. In recent years, there has been increased interest in the development of collaborative models that utilize pharmacists to overcome barriers to treatment. In this article, we present a narrative review to synthesise recent work in this rapidly developing area.

Recent findings

Two key aspects of opioid agonist treatment were identified: Collaborative models have utilized pharmacists to facilitate buprenorphine induction, and collaborative models provide increased capacity for delivering ongoing care in a variety of settings and patient groups where prescriber access is limited. Pharmacists have undertaken direct patient care responsibilities with varying degrees of autonomy, with benefits including a reduction in prescriber workload, and improvements in treatment retention and continuity of care.

Collaborative models in which pharmacists are responsible for buprenorphine induction and ongoing management with methadone and buprenorphine have been shown to reduce demands on prescribers while improving or maintaining patient outcomes, and appear feasible and acceptable in a wide range of outpatient settings.
Ottowia cancrivicina sp. nov., isolated from human stomach
Authors: Song Yu , Yuan Xiao-Yan , Cong Hai-Yan , Liu Yuan , Liu Peng , Wang Ming-Yi , Du Zong-Jun
Published: May 2024

A Gram-negative, facultative anaerobic, non-motile and rod-shaped bacterium, designated 10c7w1T, was isolated from a human gastrointestinal tract. Colonies on agar plates were small, circular, smooth and beige. The optimal growth conditions were determined to be 37 °C, pH 7.0–7.5 and 0 % (w/v) NaCl. Comparative analysis of complete 16S rRNA gene sequences revealed that strain 10c7w1T showed the highest sequence similarity of 95.8 % to Ottowia beijingensis MCCC 1A01410T, followed by Ottowia thiooxydans (95.2 %) JCM 11629T. The average amino acid identity values between 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were above 60 % (71.4 and 69.5 %). The average nucleotide identity values between strain 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were 76.9 and 72.5 %, respectively. The dominant fatty acids (≥10 %) were straight chain ones, with summed feature 3 (C16 : 1
 ω7c/C16 : 1
 ω6c), summed feature 8 (C18 : 1
 ω7c/C18 : 1
 ω6c) and C16 : 00 being the most abundant. Q-8 was the only respiratory quinone. The major polar lipids of strain 10c7w1T were phosphatidylethanolamine, diphosphatidylglycerol and unknown lipids. The DNA G+C content of strain 10c7w1T was 63.6 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic data, strain 10c7w1T is considered to represent a novel species within the genus Ottowia, for which the name Ottowia cancrivicina sp. nov. is proposed. The type strain is 10c7w1T (=MCCC 1H01399T=KCTC 92200T).
Biological aging of different blood cell types
Authors: Marttila Saara , Rajić Sonja , Ciantar Joanna , Mak Jonathan KL , Junttila Ilkka S , Kummola Laura , Hägg Sara , Raitoharju Emma , Kananen Laura
Published: May 2024

A biological age (BA) indicator is intended to capture detrimental age-related changes occurring with passing time. To date, the best-known and used BA indicators include DNA-methylation-based epigenetic ages (epigenetic clocks) and telomere length. The most common biological sample material for epidemiological aging studies is composed of different cell types, whole blood. We aimed to compare differences in BAs between blood cell types and assessed BA indicators’ cell type-specific associations with donor’s calendar age.

Analysis on DNA methylation-based BA indicators including telomere length, methylation level at cg16867657 (a CpG-site inELOVL2) and the Hannum, Horvath, DNAmPhenoAge and DunedinPACE epigenetic clocks was performed in 428 biological samples from 12 blood cell types. BA values were different (p<0.05) in the majority of pairwise comparisons between the cell types. Most cell types also displayed differences as compared to whole blood (p<0.05). Some of the observed differences persisted across blood donor’s calendar ages from 20 to 80 years (50-years-difference in DNAmPhenoAge between naïve CD4+ T cells and monocytes), while others did not (up to four-fold difference in DunedinPACE values between monocytes and B cells). All BA indicators, except DunedinPACE, had mostly a very strong correlation with donor’s calendar age within a cell type.

Our findings demonstrate that DNA methylation-based indicators of biological age exhibit cell type-specific characteristics, underscoring the importance of accounting for cell composition in related studies. Our results have implications for understanding the molecular mechanisms underlying epigenetic clocks and and provide guidance for utilizing them as indicators for success of aging interventions.
Microglia regulate motor neuron plasticity via reciprocal fractalkine/adenosine signaling
Authors: Marciante Alexandria B. , Tadjalli Arash , Burrowes Kayla A. , Oberto Jose R. , Luca Edward K. , Seven Yasin B. , Nikodemova Maria , Watters Jyoti J. , Baker Tracy L. , Mitchell Gordon S.
Published: May 2024

Microglia are innate CNS immune cells that play key roles in supporting key CNS functions including brain plasticity. We now report a previously unknown role for microglia in regulating neuroplasticity within spinal phrenic motor neurons, the neurons driving diaphragm contractions and breathing. We demonstrate that microglia regulate phrenic long-term facilitation (pLTF), a form of respiratory memory lasting hours after repetitive exposures to brief periods of low oxygen (acute intermittent hypoxia; AIH) via neuronal/microglial fractalkine signaling. AIH-induced pLTF is regulated by the balance between competing intracellular signaling cascades initiated by serotonin vs adenosine, respectively. Although brainstem raphe neurons release the relevant serotonin, the cellular source of adenosine is unknown. We tested a model in which hypoxia initiates fractalkine signaling between phrenic motor neurons and nearby microglia that triggers extracellular adenosine accumulation. With moderate AIH, phrenic motor neuron adenosine 2A receptor activation undermines serotonin-dominant pLTF; in contrast, severe AIH drives pLTF by a unique, adenosine-dominant mechanism. Phrenic motor neuron fractalkine knockdown, cervical spinal fractalkine receptor inhibition on nearby microglia, and microglial depletion enhance serotonin-dominant pLTF with moderate AIH but suppress adenosine-dominant pLTF with severe AIH. Thus, microglia play novel functions in the healthy spinal cord, regulating hypoxia-induced neuroplasticity within the motor neurons responsible for breathing.
RESOLVING BIOLOGY’S DARK MATTER: SPECIES RICHNESS, SPATIOTEMPORAL DISTRIBUTION, AND COMMUNITY COMPOSITION OF A DARK TAXON
Authors: Hartop Emily , Lee Leshon , Srivathsan Amrita , Jones Mirkka , Peña-Aguilera Pablo , Ovaskainen Otso , Roslin Tomas , Meier Rudolf
Published: May 2024

Background

Zoology’s dark matter comprises hyperdiverse, poorly known taxa that are numerically dominant but largely unstudied, even in temperate regions where charismatic taxa are well understood. It is everywhere, but high diversity, abundance, and small size have historically stymied its study. We demonstrate how entomological dark matter can be elucidated using high-throughput DNA barcoding (“megabarcoding”). We reveal the high abundance and diversity of scuttle flies (Diptera: Phoridae) in Sweden using 31,800 specimens from 37 sites across four seasonal periods. We investigate the number of scuttle fly species in Sweden and the environmental factors driving community changes across time and space.

Results

Swedish scuttle fly diversity is much higher than previously known, with 549 mOTUs (putative species) detected, compared to 374 previously recorded species. Hierarchical Modelling of Species Communities reveals that scuttle fly communities are highly structured by latitude and strongly driven by climatic factors. Large dissimilarities between sites and seasons are driven by turnover rather than nestedness. Climate changes are predicted to significantly affect the 47% of species that show significant responses to mean annual temperature. Results were robust whether using haplotype diversity or species-proxies (mOTUs) as response variables. Additionally, species-level models of common taxa adequately predict overall species richness.

Conclusions

Understanding the bulk of the diversity around us is imperative during an era of biodiversity loss. We show that dark insect taxa can be efficiently characterized and surveyed with megabarcoding. Undersampling of rare taxa and choice of operational taxonomic units do not alter the main ecological inferences, making it an opportune time to tackle zoology’s dark matter.
Immunocompetent murine model of Ewing sarcoma reveals role for TGFβ inhibition to enhance immune infiltrates in Ewing tumors during radiation
Authors: Daley Jessica D. , Mukherjee Elina , Tufino A Carolina , Bailey Nathanael , Bhaskar Shanthi , Periyapatna Nivitha , MacFawn Ian , Kunning Sheryl , Hinck Cynthia , Bruno Tullia , Olson Adam C. , McAllister-Lucas Linda M. , Hinck Andrew P. , Cooper Kristine , Bao Riyue , Cillo Anthony R. , Bailey Kelly M.
Published: May 2024

Ewing sarcoma (ES) is an aggressive cancer diagnosed in adolescents and young adults. The fusion oncoprotein (EWSR1::FLI1) that drives Ewing sarcoma is known to downregulateTGFBR2expression (part of the TGFβ receptor). BecauseTGFBR2is downregulated, it was thought that TGFβ likely plays an inconsequential role in Ewing biology. However, the expression of TGFβ in the Ewing tumor immune microenvironment (TIME) and functional impact of TGFβ in the TIME remains largely unknown given the historical lack of immunocompetent preclinical models. Here, we use single-cell RNAseq analysis of human Ewing tumors to show that immune cells, such as NK cells, are the largest source of TGFβ production in human Ewing tumors. We develop a humanized (immunocompetent) mouse model of ES and demonstrate distinct TME signatures and metastatic potential in these models as compared to tumors developed in immunodeficient mice. Using this humanized model, we study the effect of TGFβ inhibition on the Ewing TME during radiation therapy, a treatment that both enhances TGFβ activation and is used to treat aggressive ES. Utilizing a trivalent ligand TGFβ TRAP to inhibit TGFβ, we demonstrate that in combination with radiation, TGFβ inhibition both increases ES immune cell infiltration and decreases lung metastatic burdenin vivo. The culmination of these data demonstrates the value of humanized models to address immunobiologic preclinical questions in Ewing sarcoma and suggests TGFβ inhibition as a promising intervention during radiation therapy to promote metastatic tumor control.