bluuebunny/crossref_metadata_2025 huggingface dataset:
Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model
Authors: Qiu Xia , Zhang Hedong , Tang Zhouqi , Fan Yuxi , Yuan Wenjia , Feng Chen , Chen Chao , Cui Pengcheng , Cui Yan , Qi Zhongquan , Li Tengfang , Zhu Yuexing , Xie Liming , Peng Fenghua , Deng Tuo , Jiang Xin , Peng Longkai , Dai Helong
Published: November 2023

Background:

Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.

Methods:

Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation.

Results:

HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days (P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4+ and CD8+ T cells in the spleen (P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes (CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF)-β pathway-related genes and Treg signature genes (CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4+ Foxp3+ cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs.

Conclusions:

HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.
Tumour regression predicts better response to interferon therapy in melanoma patients: a retrospective single centre study
Authors: Mezőlaki Noémi E. , Baltás Eszter , Ócsai Henriette L. , Varga Anita , Korom Irma , Varga Erika , Németh István B. , Kis Erika G. , Varga János , Kocsis Ádám , Gyulai Rolland , Bukva Mátyás , Kemény Lajos , Oláh Judit
Published: November 2023

We hypothesise that regression may have an impact on the effectiveness of adjuvant IFN therapy, based on its role in the host immune response. Our purpose is to investigate regression and ulceration as prognostic factors in case of interferon-alpha (IFN)-treated melanoma patients. We followed 357 IFN-treated melanoma patients retrospectively, investigating progression-free survival (PFS) and overall survival (OS) depending on the presence of ulceration and regression. A Kaplan–Meier analysis was performed, and we used a Cox regression analysis to relate risk factors. The survival function of the Cox regression was used to measure the effect of regression and ulceration on PFS and OS depending on the Breslow thickness (T1–T4) of the primary tumour. Regression was significantly positively related to PFS (P = 0.0018, HR = 0.352) and OS (P = 0.0112, HR = 0.380), while ulceration showed a negative effect (PFS: P = 0.0001, HR = 2.629; OS: P = 0.0001, HR = 2.388). They influence survival independently. The most favourable outcome was measured in the regressed/non-ulcerated group, whereas the worse was in the non-regressed/ulcerated one. Of risk factors, Breslow thickness is the most significant predictor. The efficacy of regression is regardless of Breslow thickness, though the more favourable the impact of regression was in the thicker primary lesions. Our results indicate that regression is associated with a more favourable outcome for IFN-treated melanoma patients, whereas ulceration shows an inverse relation. Further studies are needed to analyse the survival benefit of regression in relation to innovative immune checkpoint inhibitors.
Neuromuscular Ultrasound Findings of Myokymia in a Young Woman With Generalized Anti-LGI-1 and Anti-Caspr2 Antibodies Negative Isaac Syndrome
Authors: Prado Mario B. , Moalong Kevin Michael C. , Adiao Karen Joy B.
Published: November 2023

Isaac syndrome is one of the rare peripheral nerve hyperexcitability (PNH) syndromes, which manifests with gross fasciculations, muscle undulation, twitching, and cramps, with or without autonomic and sensory symptoms. The diagnosis relies on characteristic electromyogram findings and the presence of anti–leucine-rich glial inactivated 1 and anti–contactin-associated protein 2 antibodies in the serum. Here, we report the case of a 21-year-old woman, who presented with extremities and tongue myokymia whose electromyogram findings were compatible with PNH, albeit seronegative for antibodies. Neuromuscular ultrasound was performed showing high-frequency rotatory, to-and-fro, high-amplitude movement of superficial and deep muscle fascicles, more prominent in the proximal than distal muscles. Neuromuscular ultrasound may be a useful adjunct in the diagnosis of PNH.
Patterns of Clinical Progression Among Patients With Autosomal Recessive Limb-Girdle Muscular Dystrophy: A Systematic Review
Authors: Cheung Antoinette , Audhya Ivana F. , Szabo Shelagh M. , Friesen Michael , Weihl Conrad C. , Gooch Katherine L.
Published: November 2023

Objectives:

As the clinical course of autosomal recessive limb–girdle muscular dystrophy (LGMDR) is highly variable, this study characterized the frequency of loss of ambulation (LOA) among patients by subtype (LGMDR1, LGMDR2, LGMDR3–6, LGMDR9, LGMDR12) and progression to cardiac and respiratory involvement among those with and without LOA.

Methods:

Systematic literature review.

Results:

From 2929 abstracts screened, 418 patients were identified with ambulatory status data (LOA: 265 [63.4%]). Cardiac and/or respiratory function was reported for 142 patients (34.0%; all with LOA). Among these, respiratory involvement was most frequent in LGMDR3–6 (74.1%; mean [SD] age 23.9 [11.0] years) and cardiac in LGMDR9 (73.3%; mean [SD] age 23.7 [17.7] years). Involvement was less common in patients without LOA except in LGMDR9 (71.4% respiratory and 52.4% cardiac).

Conclusions:

This study described the co-occurrence of LOA, cardiac, and respiratory involvement in LGMDR and provides greater understanding of the clinical progression of LGMDR.
Aggressive Acquired Demyelinating Neuropathy Caused by NF-155: Initially Treatment-Resistant
Authors: Jamall Selene , Baker Nancy , Peterson Gordon , Tsao Bryan , Rosenfeld Jeffrey
Published: November 2023

Objectives:

Anti–neurofascin-155 IgG4 (NF-155) antibody disease has previously been associated with a subset of patients with chronic inflammatory demyelinating polyradiculoneuropathy. We report a case of NF-155 positive polyneuropathy that initially presented as an acute inflammatory demyelinating polyradiculoneuropathy. The patient responded appropriately to treatment but subsequently progressed over a 3-month period, resulting in quadriplegia, areflexia, and oculobulbar paralysis.

Methods:

Case report and literature review.

Results:

A 40-year-old male presented with acute bilateral arm and thigh weakness, areflexia, and distal sensory loss. Treatment with intravenous immunoglobulin (IVIg) for acute acquired demyelinating neuropathy resulted in initial improvement but subsequent decline. Lack of response to additional IVIg and plasmapheresis (PLEX) prompted testing for NF-155. Treatment with rituximab and steroids resulted in virtually complete recovery.

Conclusions:

Early testing for nodal and paranodal proteins is indicated in patients who present with acute acquired demyelinating neuropathy but fail to respond to conventional treatments, such as IVIg or PLEX. Identification of nodal and paranodal antibodies should prompt treatment with rituximab and steroids to increase likelihood of recovery.
The Severity of Fecal Problems Is Negatively Associated With Quality of Life in a Non-Patient Dutch Population
Authors: ten Hoor Maaike B.C. , Trzpis Monika , Broens Paul M.A.
Published: November 2023

BACKGROUND:

Constipation and fecal incontinence have a negative influence on quality of life. The association between the severity of fecal problems and quality of life has not been investigated in a non-patient population.

OBJECTIVE:

To investigate the association between the severity of constipation and fecal incontinence and quality of life in non-patients.

DESIGN:

A population-based, cross-sectional study.

SETTINGS:

The study involved 3668 Dutch non-patients.

PATIENTS:

A survey company conducted a population-wide study of the general Dutch population. Altogether, 5000 Dutch citizens completed the Groningen Defecation and Fecal Continence and Short-Form 36 questionnaires. The data on 3668 respondents without comorbidities that could influence bowel function were included for analysis.

MAIN OUTCOME MEASURES:

The severity of constipation (Agachan score) and fecal incontinence (Wexner score) in relation to the quality-of-life scores.

RESULTS:

In the non-patient population (n = 3668), 487 (13.3%) had constipation, 116 (3.2%) had fecal incontinence, and the two fecal problems coexisted in 64 (1.7%). In the multivariable analysis, all quality-of-life domains were negatively associated with the severity of constipation and fecal incontinence. The associations between the severity of constipation and quality of life were stronger (highest: ß = -2.413, 95% CI, -2.681 to -2.145, p = < 0.001) than those of fecal incontinence (highest: ß = -1.280, 95% CI, -1.681 to -.880, p = < 0.001). We also found that a longer duration of bowel complaints coincided with higher severity scores, especially for constipation. Mostly, respondents rated their defecation health as positive, regardless of the severity of their fecal problems.

LIMITATIONS:

Cross-sectional design.

CONCLUSIONS:

The severity of constipation and fecal incontinence is significantly associated with reduced quality of life, with the severity of constipation having stronger associations than fecal incontinence. Given respondents' unawareness of their fecal problems and the progressive character thereof, timely intervention is advocated.
Modified Approach for Extraperitoneal Colostomy Creation in Laparoscopic Abdominoperineal Resection
Authors: Zhang Xiang , Li Xin , Cheng Zhiqiang , Wang Kexin , Dai Yong , Wang Yanlei
Published: November 2023

BACKGROUND:

Parastomal hernia is a major long-term complication after abdominoperineal resection. Extraperitoneal colostomy has been proposed as an effective step for parastomal hernia prevention but it has not been widely used as it is technically-demanding and time-consuming. We proposed a modified approach for extraperitoneal colostomy creation by entering the extraperitoneal space through the arcuate line of the posterior rectus sheath.

OBJECTIVE:

To evaluate the safety, difficulty and efficacy for long-term parastomal hernia prevention of the modified approach for extraperitoneal colostomy creation compared with conventional transperitoneal colostomy approach.

DESIGN:

This was a retrospective evaluation of a surgical and video database.

SETTINGS:

This was a single-institution retrospective study.

PATIENTS:

Clinical data of 74 patients who underwent laparoscopic abdominoperineal resection surgery from January 2019 to January 2020 in the Department of General Surgery, Qilu Hospital of Shandong University were retrospectively reviewed.

MAIN OUTCOME MEASURES:

Baseline characteristics, time required for colostomy creation (from skin incision to colostomy maturation), perioperative complications, and long-term colostomy-related complications were compared.

RESULTS:

Baseline characteristics did not differ between the 2 approaches. The body mass index level ranged from 19.5 to 29.4 kg/m 2 for patients undergoing extraperitoneal approach. Time required for colostomy creation [22 (21-25) min for extraperitoneal vs. 23 (21-25) min for transperitoneal, p = 0.861] were comparable between the two approaches. The cumulative incidence of parastomal hernia was significantly greater with transperitoneal colostomy than extraperitoneal colostomy at 2 and 3 years postoperatively (16.2% vs. 0, p = 0.025, and 21.6% vs. 0, p = 0.005). The rest perioperative complications and long-term colostomy-related complications did not differ between the two approaches.

LIMITATIONS:

This study is limited by its retrospective design and small sample size.

CONCLUSIONS:

The modified approach for extraperitoneal colostomy creation is safe, technically simple and effective for long-term parastomal hernia prevention in patients with a body mass index of 19.5 - 29.4 kg/m 2.
The Novel Checkpoint Target Lymphocyte-Activation Gene 3 Is Highly Expressed in Cutaneous Squamous Cell Carcinoma
Authors: Dany Mohammed , Doudican Nicole , Carucci John
Published: November 2023

BACKGROUND

Lymphocyte activation-gene 3 (LAG-3) is an emerging next-generation immune checkpoint molecule. We aim to define the expression pattern of LAG-3 in cutaneous squamous cell carcinoma (cSCC) as a first step to understand the role of LAG-3 in cSCC prognosis and therapy.

OBJECTIVE

To define the expression pattern of LAG-3 in cSCC as a first step to understand the role of LAG-3 in cSCC prognosis and therapy.

METHODS

To test whether LAG-3 is expressed on cSCC infiltrating lymphocytes, we isolated CD8+ T lymphocytes from three SCC tumors using flow cytometry and performed single-cell RNA sequencing for LAG-3 and programmed cell death protein -1 (PD-1). In addition, we evaluated LAG-3 mRNA expression in formalin-fixed, paraffin-embedded tissue using NanoString technology.

RESULTS

Single-cell RNA sequencing showed that LAG-3 is expressed more than PD-1 in CD8+ tumor infiltrating lymphocytes (50.8% vs 35.2%, respectively). Quantifying LAG-3 mRNA expression showed that compared with normal skin, LAG-3 mRNA is approximately 8 fold higher in immunocompetent associated SCC tumors and approximately 2 fold higher in transplant associated SCC tumors (p-values <.05). In addition, LAG-3 mRNA was expressed 7.2 fold higher in T2a SCC tumors compared with normal skin (p-value <.05).

CONCLUSION

Lymphocyte activation-gene 3 is expressed on SCC infiltrating T lymphocytes at a higher percentage than PD-1. In addition, LAG-3 mRNA expression is significantly higher in SCC tumors. Ongoing studies will be performed to define its role as an immune-related biomarker and as a therapeutic target.
Incidence and Survival Outcomes of Dermatofibrosarcoma Protuberans From 2000 to 2020: A Population-Based Retrospective Cohort Analysis
Authors: Xiong David D. , Bordeaux Jeremy S.
Published: November 2023

BACKGROUND

Recent changes in the incidence and survival of dermatofibrosarcoma protuberans (DFSP) have not been described.

OBJECTIVE

To characterize the incidence and survival of DFSP.

MATERIALS AND METHODS

A retrospective cohort study of patients with DFSP from 2000 to 2020 in the Surveillance, Epidemiology, and End Results database was performed. Cox and Fine–Gray regression models were used to assess overall and DFSP-specific survival.

RESULTS

The incidence of DFSP has not changed from 2000 to 2020 with 4.6 cases/million person-years, with higher rates in dark-skinned and middle-age individuals. Factors associated with overall mortality in DFSP patients include advanced age (p < .0001), male sex (hazard ratio [HR] 1.8, p < .0001), larger tumors (HR 1.002 per millimeter, p < .001), lower household income (HR 1.8, p = .0002), and lower extremity location (HR 1.7, p = .008). Mohs surgery is associated with improved overall survival (HR 0.4, p = .02). Large tumor size (6.0+ cm, HR 6.7, p = .01) and advanced age (age 80+ years, HR 21.3, p = .003) were associated with worse DFSP-specific mortality.

CONCLUSION

Dermatofibrosarcoma protuberans incidence has remained constant from 2000 to 2020. Increasing age and tumor size, decreased income, male sex, and lower extremity location are associated with worsened survival. Mohs surgery is associated with improved overall survival. Increased age and tumor size are associated with worsened DFSP-specific mortality.
Intraocular lens power calculation: angle κ and ocular biomechanics
Authors: Marques João Heitor , Baptista Pedro Manuel , Ribeiro Bruno , Menéres Pedro , Beirão João Melo
Published: November 2023

Purpose:

To study the effect of ocular biomechanics on the prediction error of intraocular lens (IOL) power calculation.

Setting:

Centro Hospitalar Universitário do Porto, Porto, Portugal.

Design:

Prospective longitudinal study.

Methods:

This study included 67 subjects. Before cataract surgery subjects underwent biometry with IOLMaster 700 and biomechanical analysis with Corvis Scheimpflug technology. The targeted spherical equivalent was calculated with SRK-T and Barrett Universal II. Associations between prediction error (PE), absolute prediction error (AE), and biometric and biomechanical parameters were performed with stepwise multivariate linear correlation analysis.

Results:

Using the SRKT formula, there was association between PE and Corvis Biomechanical Index (CBI, B = −0.531, P = .011) and between AE and the horizontal offset between the center of the pupil and the visual axis (angle κ, B = −0.274, P = .007). Considering the Barret Universal II formula, PE was independently associated with anterior chamber depth (B = −0.279, P = .021) and CBI (B = −0.520, P = .013) and AE was associated with angle κ (B = −0.370, P = .007).

Conclusions:

A large angle κ may reduce the predictability of IOL power calculation. Ocular biomechanics likely influence the refractive outcomes after IOL implantation. This study showed that eyes with softer corneal biomechanics had more myopic PE. This may relate to anteriorization of the effective lens position. Dynamic measurements may be the way to progress into future formulas.
Effects of a fortified balanced salt solution and Ringer’s lactate solution on anterior chamber inflammation after phacoemulsification in diabetes
Authors: Ma Mingming , Wang Manqiao , Zhang Xiaomin , Shao Yan , Li Xiaorong
Published: November 2023

Purpose:

To compare the effects of a fortified balanced salt solution (fSS) and Ringer's lactate solution (Ringer) on anterior chamber (AC) inflammation in patients undergoing phacoemulsification.

Setting:

Tianjin Medical University Eye Hospital, Tianjin, China.

Design:

Prospective masked controlled trial.

Methods:

80 patients (40 patients with regular cataract and 40 cataract patients with diabetes mellitus [DM]) were randomized to receive either fSS (n = 40) or Ringer's solution (n = 40). Anterior-segment optical coherence tomography was used to evaluate AC cells and flare. Transepithelial electrical resistance (TEER) and zonula occludens-1 (ZO-1) immunofluorescence were used for tight junction examination. Monocytic leukemia cell line (Tohoku Hospital Pediatrics-1 [THP-1]) transmigration assay was performed to observe the effects of the 2 perfusates on the inflammatory response in vitro.

Results:

In patients with regular cataracts, postoperative AC cells and flare on the 1st and 7th days were not significantly different between the Ringer and fSS groups. However, in cataract patients with DM, AC cells were higher in the Ringer group than in the fSS group (P = .003) on postoperative day 1. The AC flare was also significantly higher in the Ringer group than in the fSS group (P < .0001). No significant differences between the groups were observed on day 7. Compared with Ringer, fSS increased the TEER value and ZO-1 content and reduced the adhesion of THP-1 cells.

Conclusions:

The results of this study indicated that early postoperative AC inflammation is more severe in patients with cataracts and DM. In addition, fSS attenuates inflammation by protecting the blood–aqueous barrier and inhibiting the exudation of inflammatory cells.
A phenotypic screening platform for chronic pain therapeutics using all-optical electrophysiology
Authors: Liu Pin W. , Zhang Hongkang , Werley Christopher A. , Pichler Monika , Ryan Steven J. , Lewarch Caitlin L. , Jacques Jane , Grooms Jennifer , Ferrante Jean , Li Guangde , Zhang Dawei , Bremmer Nate , Barnett Adam , Chantre Romina , Elder Amy E. , Cohen Adam E. , Williams Luis A. , Dempsey Graham T. , McManus Owen B.
Published: November 2023

Chronic pain associated with osteoarthritis (OA) remains an intractable problem with few effective treatment options. New approaches are needed to model the disease biology and to drive discovery of therapeutics. We present an in vitro model of OA pain, where dorsal root ganglion (DRG) sensory neurons were sensitized by a defined mixture of disease-relevant inflammatory mediators, here called Sensitizing PAin Reagent Composition or SPARC. Osteoarthritis-SPARC components showed synergistic or additive effects when applied in combination and induced pain phenotypes in vivo. To measure the effect of OA-SPARC on neural firing in a scalable format, we used a custom system for high throughput all-optical electrophysiology. This system enabled light-based membrane voltage recordings from hundreds of neurons in parallel with single cell and single action potential resolution and a throughput of up to 500,000 neurons per day. A computational framework was developed to construct a multiparameter OA-SPARC neuronal phenotype and to quantitatively assess phenotype reversal by candidate pharmacology. We screened ∼3000 approved drugs and mechanistically focused compounds, yielding data from over 1.2 million individual neurons with detailed assessment of functional OA-SPARC phenotype rescue and orthogonal “off-target” effects. Analysis of confirmed hits revealed diverse potential analgesic mechanisms including ion channel modulators and other mechanisms including MEK inhibitors and tyrosine kinase modulators. Our results suggest that the Raf-MEK-ERK axis in DRG neurons may integrate the inputs from multiple upstream inflammatory mediators found in osteoarthritis patient joints, and MAPK pathway activation in DRG neurons may contribute to chronic pain in patients with osteoarthritis.
Choice over placebo administration enhances open-label placebo hypoalgesia
Authors: Tang Biya , Livesey Evan , Colagiuri Ben
Published: November 2023

Many studies indicate that deceptively administered placebos can improve pain outcomes. However, the deception involved presents an ethical barrier to translation because it violates informed consent and patient autonomy. Open-label placebos (OLPs), inert treatments that are openly administered as placebos, have been proposed as an ethically acceptable alternative. Early studies have suggested that OLP can improve pain outcomes, but important questions remain as to how to maximise OLP hypoalgesia to improve treatment outcomes in pain patients. This study investigated whether providing choice over when to administer an OLP treatment has the capacity to enhance OLP hypoalgesia using an electrocutaneous pain paradigm. One hundred thirty-two healthy volunteers were randomised to 3 types of treatment: OLP with choice, OLP without choice, and no treatment (natural history). The OLP groups were further randomised such that half were tested with a consistent pain intensity and the other half were tested with variable pain intensity to mimic day-to-day variability in pain intensity in health settings. The results indicated that treatment provided with choice exhibited greater OLP hypoalgesia than that provided without choice and that greater expectancy mediated this effect. Of interest, there was no evidence for OLP hypoalgesia without choice relative to natural history. Furthermore, variability in pain intensity did not affect OLP hypoalgesia. The current findings present novel evidence that choice over treatment administration may be a cheap and effective strategy for boosting the efficacy of OLPs in the clinical care of pain.
Otoprotection against aminoglycoside- and cisplatin-induced ototoxicity focusing on the upstream drug uptake pathway
Authors: Hsieh Cheng-Yu , Tsai Cheng-Yu , Chou Yi-Fan , Hsu Chuan-Jen , Wu Hung-Pin , Wu Chen-Chi
Published: November 2023

Aminoglycoside- and cisplatin-induced ototoxicity, which is a significant issue owing to the widespread use of these drugs in clinical practice, involves the entry of aminoglycosides and cisplatin into the endolymph and hair cells via specific channels or transporters, followed by reactive oxygen species (ROS) generation and hair cells apoptosis. Current strategies focalize primarily on interference with downstream ROS effects; however, recent evidence has demonstrated that inhibiting the uptake of aminoglycosides and cisplatin by hair cells is another promising strategy for tackling the upstream drug uptake pathway. With advances in structural biology, the conformations of certain aminoglycoside and cisplatin channels and transporters, such as the mechanoelectrical transduction channel and organic cation transporter-2, have been largely elucidated. These channels and transporters may become potential targets for the introduction of new otoprotective strategies. This review focuses on the strategies for inhibiting ototoxic drugs uptake by auditory hair cells and provides potential targets for recent developments in the field of otoprotection. Molecular dynamics (MD) simulations of these proteins could help identify the molecules that inhibit the uptake of aminoglycosides and cisplatin by hair cells. Integrating upstream drug uptake pathway targets and MD simulations may help dissect molecular mechanisms and develop novel otoprotective strategies for aminoglycoside- and cisplatin-induced ototoxicity.
Physician Assistant Program Accreditation Analysis and Survey of Program Directors
Authors: Lewis Jon , Peacock Jeff , Miller Paul M.
Published: November 2023

Introduction

To inform physician assistant program directors through citation analysis after implementation of the Accreditation Review Commission on Education for the Physician Assistant (ARC-PA) Accreditation Standards, 5th edition.

Methods

This research used descriptive statistics, Pearson correlation, and the coefficient of determination to analyze the citations reported by ARC-PA during January 2021 to February 2023. Concurrent first-time taker Physician Assistant National Certifying Exam (PANCE) results were used to determine whether a correlation exists between pass rates and citations. In addition, a survey was sent to each institution’s current program director to investigate leadership concerns and differences between programs placed on a provisional, continued, or probation status by ARC-PA.

Results

Of the 98 program submissions for accreditation, 13 submissions resulted in a probation status outcome. For these 13 programs placed on probation, 46.2% and 30.8% were cited for being noncompliant with leadership Standards A2.09 and A1.02, respectively. Pearson correlation analysis indicates a significant negative correlation between ARC-PA citations and first-time taker PANCE pass rates (P = .023, 95% confidence interval [CI] = [−0.49 to −0.04]). This is particularly true for programs with continued accreditation (P = .007, 95% CI = [−0.67 to −0.13]) and programs that performed below the 85% benchmark (P = .013, 95% CI = [−0.94 to −0.22]) for first-time taker PANCE pass rates. Although a negative correlation is observed between the number of levied citations and PANCE pass rates, the coefficient of determination does not indicate that the number of citations can predict PANCE pass rates (R
2 = 0.0368). Regarding survey data, 42.86% of programs placed on probation cited institutional support as their biggest program weakness or threat. Conversely, 22.22% of programs with provisional status and 12.5% of programs with continued status reported institutional support as their biggest weakness or threat.

Discussion

This research identifies leadership as a deficit of concern associated with programs placed on probation. In addition, a significant negative correlation exists between the number of citations and first-time taker PANCE pass rates—especially for programs with first-time taker PANCE pass rates below 85% or for programs with continued accreditation status.
Colposcopy—A Valuable Diagnostic Tool for Pregnant Women With Unexplained Vaginal Bleeding
Authors: Sgayer Inshirah , Shmueli Maskit , Lowenstein Lior , Frank Wolf Maya
Published: November 2023

Objectives

We aimed to examine the diagnostic value of colposcopy in a large cohort of pregnant women with unexplained vaginal bleeding during the second or third trimester.

Materials and Methods

This retrospective study included women who underwent colposcopy due to vaginal bleeding in the second and third trimesters during 2012–2022 at a tertiary care hospital. Demographics, obstetric data, bleeding characteristics, colposcopy results, cervical cytology testing, a sonogram directed at the placenta, and birth details were collected.

Results

In total, 364 women were included. The mean maternal age was 29.7 years and the mean gestational age at examination was 30.7 weeks. Vaginal bleeding was mild in 80.8%, moderate in 14.6%, and severe in 4.7%. Only 3.3% had been vaccinated against human papilloma virus and 25.5% underwent a Pap smear study before pregnancy. Colposcopy diagnosed the bleeding source in 83 women (22.8%). The colposcopic examination revealed vaginal bleeding due to contact bleeding from ectropion in 46 (12.6%), a decidual/cervical polyp in 37 (10.2%), acetowhite epithelium in 12 (3.3%), herpes genetalis in 2 (0.5%), and bleeding from vaginal varices in 2 (0.5%). Of those who were recommended a follow-up examination after the postpartum period, only 49.1% completed such.

Among women with compared to without postcoital bleeding (N = 72), the risk of abnormal colposcopic findings was higher (24 [33.3%] vs 54 [19.7%], p = .017) and the rate of abnormal Pap smear was higher (7 [13.2%] vs 7 [3.2%], p = .008).

Conclusions

Colposcopy can be a valuable diagnostic tool for women with unexplained vaginal bleeding in the second or third trimester.
Developing an Integrated Longitudinal Dataset for Patient-Centered Outcome Measures in Cost-Related Medication Nonadherence
Authors: Zhang James X. , Meltzer David O.
Published: November 2023

Background:

Cost-related medication nonadherence (CRN) is an important patient-centered outcome measure. Longitudinal follow-up of CRN is rare.

Objective:

We propose to develop a novel integrated dataset to study CRN longitudinally.

Research Design:

A dataset of 2000 Medicare beneficiaries at high risk of hospitalization surveyed quarterly on CRN and followed up individually for 8 quarters between 2013 and 2018 was linked to Medicare files. A metric of CRN categorizing persistent, intermittent, and transient CRN during the 8 quarters was developed. An ordered logit model and a logit model were developed to assess the factors influencing CRN overall and persistent CRN, respectively.

Results:

A total of 1761 patients were included in the analysis, among whom 869 (49.3%) reported CRN at least once in the 8-quarter study period, 178 (10%) reported persistent CRN, 395 (22.4%) reported intermittent CRN, and 296 (16.8%) reported transient CRN. The conditional effect in the logit model for persistent CRN revealed that baseline dual eligibility was negatively associated (adjusted odds ratio = 0.45, P < 0.01) and depression positively associated (adjusted odds ratio = 1.55, P = 0.01) with persistent CRN. The marginal analysis in the ordered logit model revealed a clear pattern of higher probabilities of persistent and intermittent CRN at younger ages while transient CRN was flat. Among the 252 subjects who were deceased, 31 (12.3%) reported persistent CRN, compared with 147 (9.74%) who were alive (P = 0.21 by χ2 test).

Conclusions:

A significant number of patients reported persistent CRN, including those who were at the end of life. Research is critically needed to understand behavioral patterns among the younger Medicare population.
Enhancing Cancer Economic Data Resources
Authors: Halpern Michael T. , Ekwueme Donatus U. , Yabroff K. Robin
Published: November 2023

Background:

Cancer diagnosis and treatment can substantially affect health and financial outcomes for patients and families. Research in health care delivery across the cancer control continuum includes diverse activities led by multiple government and private sector organizations. Assessing the economic drivers and influencing factors associated with costs across this continuum is challenging as organizations leading research efforts often do not have forums to share data, develop linkages, and explore collaborative opportunities.

Objective:

To describe the objectives, activities, and goals of the Interagency Consortium to Promote Health Economics Research on Cancer (HEROiC) to strengthen data resources and capacity for collaborative patient-focused cancer health economics research.

Main Argument:

HEROiC’s goals include assessing the economic burden of cancer; examining the effects of policies, health care setting/system factors, and health service delivery approaches across the cancer control continuum; and enhancing collaborations among researchers and organizations.

Conclusions:

Data resources to study economic outcomes associated with cancer control are highly fragmented; HEROIC provides a forum to collaboratively develop, enhance, and utilize data resources and infrastructure for patient-centered cancer health economics research. This includes sharing data resources, developing linkages, identifying new data collection venues, and creating and supporting the dissemination of evidence-based information to diverse stakeholders. These efforts provide critical information to address the economic burden of cancer.

Relevance to the Special Issue:

Cancer diagnosis and treatment affect patient health and financial outcomes. This commentary describes how HEROiC will enhance research data infrastructure and collaborations to support patient-centered research with the goal of reducing the economic burden of cancer.
Cancer-Related Financial Hardship Screening as Part of Practice Transformation
Authors: Williams Courtney P. , Liang Margaret I. , Rocque Gabrielle B. , Gidwani Risha , Caston Nicole E. , Pisu Maria
Published: November 2023

Background:

Data on financial hardship, an “adverse event” in individuals with cancer, are needed to inform policy and supportive care interventions and reduce adverse economic outcomes.

Methods:

Lay navigator–led financial hardship screening was piloted among University of Alabama at Birmingham oncology patients initiating treatment in October 2020. Financial hardship screening, including reported financial distress and difficulty, was added to a standard-of-care treatment planning survey. Screening feasibility and completion and proportions of reported financial distress and difficulty were calculated overall and by patient race and rurality. The risk of financial distress by patient sociodemographics was estimated.

Results:

Patients who completed a treatment planning survey (N=2741) were 18% Black, Indigenous, or persons of color (BIPOC) and 16% rural dwelling. The majority of patients completed financial hardship screening (90%), surpassing the target feasibility completion rate of 75%. The screening revealed 34% of patients were experiencing financial distress, including 49% of BIPOC and 30% of White patients. Adjusted models revealed BIPOC patients had a 48% higher risk of financial distress compared with those who were White (risk ratio 1.48, 95% CI, 1.31–1.66). Large differences in reported financial difficulties were seen comparing patients who were BIPOC and White (utilities: 33% vs. 10%, upfront medical payments: 44% vs. 23%, transportation: 28% vs. 12%, respectively).

Conclusions:

The collection of patient-reported financial hardship data via routine clinical care was feasible and identified racial inequities at treatment initiation. Efforts to collect patient economic data should support the design, implementation, and evaluation of patient-centered interventions to improve equity and reduce the impact of financial hardship.
Multilevel Quality Indicators
Authors: Roessler Martin , Schulte Claudia , Repschläger Uwe , Hertle Dagmar , Wende Danny
Published: November 2023

Background:

Quality indicators are frequently used to assess the performance of health care providers, in particular hospitals. Established approaches to the design of such indicators are subject to distortions due to indirect standardization and high variance of estimators. Indicators for geographical regions are rarely considered.

Objectives:

To develop and evaluate a methodology of multilevel quality indicators (MQIs) for both health care providers and geographical regions.

Research Design:

We formally derived MQIs from a statistical multilevel model, which may include characteristics of patients, providers, and regions. We used Monte Carlo simulation to assess the performance of MQIs relative to established approaches based on the standardized mortality/morbidity ratio (SMR) and the risk-standardized mortality rate (RSMR).

Measures:

Rank correlation between true provider/region effects and quality indicator estimates; shares of the 10% best and 10% worst providers identified by the quality indicators.

Results:

The proposed MQIs are: (1) standardized hospital outcome rate (SHOR); (2) regional SHOR; and (3) regional standardized patient outcome rate. Monte Carlo simulations indicated that the SHOR provides substantially better estimates of provider performance than the SMR and risk-standardized mortality rate in almost all scenarios. The regional standardized patient outcome rate was slightly more stable than the regional SMR. We also found that modeling of regional characteristics generally improves the adequacy of provider-level estimates.

Conclusions:

MQIs methodology facilitates adequate and efficient estimation of quality indicators for both health care providers and geographical regions.
Change in Hospital Risk-Standardized Stroke Mortality Performance With and Without the Passive Surveillance Stroke Severity Score
Authors: Yu Amy Y.X. , Kapral Moira K. , Park Alison L. , Fang Jiming , Hill Michael D. , Kamal Noreen , Field Thalia S. , Joundi Raed A. , Peterson Sandra , Zhao Yinshan , Austin Peter C.
Published: November 2023

Background:

Adjustment for baseline stroke severity is necessary for accurate assessment of hospital performance. We evaluated whether adjusting for the Passive Surveillance Stroke SeVerity (PaSSV) score, a measure of stroke severity derived using administrative data, changed hospital-specific estimated 30-day risk-standardized mortality rate (RSMR) after stroke.

Methods:

We used linked administrative data to identify adults who were hospitalized with ischemic stroke or intracerebral hemorrhage across 157 hospitals in Ontario, Canada between 2014 and 2019. We fitted a random effects logistic regression model using Markov Chain Monte Carlo methods to estimate hospital-specific 30-day RSMR and 95% credible intervals with adjustment for age, sex, Charlson comorbidity index, and stroke type. In a separate model, we additionally adjusted for stroke severity using PaSSV. Hospitals were defined as low-performing, average-performing, or high-performing depending on whether the RSMR and 95% credible interval were above, overlapping, or below the cohort’s crude mortality rate.

Results:

We identified 65,082 patients [48.0% were female, the median age (25th,75th percentiles) was 76 years (65,84), and 86.4% had an ischemic stroke]. The crude 30-day all-cause mortality rate was 14.1%. The inclusion of PaSSV in the model reclassified 18.5% (n=29) of the hospitals. Of the 143 hospitals initially classified as average-performing, after adjustment for PaSSV, 20 were reclassified as high-performing and 8 were reclassified as low-performing. Of the 4 hospitals initially classified as low-performing, 1 was reclassified as high-performing. All 10 hospitals initially classified as high-performing remained unchanged.

Conclusion:

PaSSV may be useful for risk-adjusting mortality when comparing hospital performance. External validation of our findings in other jurisdictions is needed.
Association Between ICD-10 Codes for Social Needs and Subsequent Emergency and Inpatient Use
Authors: Liss David T. , Kang Raymond H. , Cherupally Manisha , Cooper Andrew J. , Barreto-Parra Paula-Natalia , Aikman Cassandra , O’Brien Matthew J.
Published: November 2023

Background:

International Classification of Diseases, 10th revision Z codes capture social needs related to health care encounters and may identify elevated risk of acute care use.

Objectives:

To examine associations between Z code assignment and subsequent acute care use and explore associations between social need category and acute care use.

Research Design:

Retrospective cohort study.

Subjects:

Adults continuously enrolled in a commercial or Medicare Advantage plan for ≥15 months (12-month baseline, 3–48 month follow-up).

Outcomes:

All-cause emergency department (ED) visits and inpatient admissions during study follow-up.

Results:

There were 352,280 patients with any assigned Z codes and 704,560 sampled controls with no Z codes. Among patients with commercial plans, Z code assignment was associated with a 26% higher rate of ED visits [adjusted incidence rate ratio (aIRR) 1.26, 95% CI: 1.25–1.27] and 42% higher rate of inpatient admissions (aIRR 1.42, 95% CI: 1.39–1.44) during follow-up. Among patients with Medicare Advantage plans, Z code assignment was associated with 42% (aIRR 1.42, 95% CI: 1.40–1.43) and 28% (aIRR 1.28, 95% CI: 1.26–1.30) higher rates of ED visits and inpatient admissions, respectively. Within the Z code group, relative to community/social codes, socioeconomic Z codes were associated with higher rates of inpatient admissions (commercial: aIRR 1.10, 95% CI: 1.06–1.14; Medicare Advantage: aIRR 1.24, 95% CI 1.20–1.27), and environmental Z codes were associated with lower rates of both primary outcomes.

Conclusions:

Z code assignment was independently associated with higher subsequent emergency and inpatient utilization. Findings suggest Z codes’ potential utility for risk prediction and efforts targeting avoidable utilization.
Errors in measurement of glomerular filtration rate using the slope-intercept technique and their identification
Authors: Oliveira Ana , Conway Lauren , Heraghty Neil , Peters A. Michael
Published: November 2023

Background

GFR measured from plasma sampling may be expressed as slope-intercept GFR (SI-GFR) and scaled to body surface area (mGFR/BSA) or as GFR per unit extracellular fluid volume (mGFR/ECV), which is based only on half-time. Measurement errors comprise 3 categories. Pre-injection error arises from error in administered marker and is suspected when mGFR/BSA and mGFR/ECV disagree. Injection errors include ‘tissued’ injections. Post-injection errors include inaccurate sample timing, inaccurate pipetting, sample haemolysis and sampling through long IV lines through which marker was administered. The aim of the study was to evaluate the impact of errors on mGFR.

Methods

We compared mGFR/BSA with mGFR/ECV in 898 patients undergoing routine investigation. To investigate post-injection error, we took two further patient datasets with r values (correlation coefficient of the 3-sample fit) of 1.0 and introduced errors, in isolation, into each of the 3 recorded sample values, as follows: pipetting (volume) errors of −20%, −10%, −5%, 5%, 10% and 20%, and timing errors of −15 min, −10 min, −5 min, 5 min, 10 min and 15 min.

Results

The correlation between mGFR/BSA and mGFR/ECV was close and independent of r. Post-injection error depended on the time of the sample in which it occurred. r correlated poorly with error magnitude for both volume and timing errors. When a ‘rogue’ sample is suspected its error needed to be substantial for it to be identified by single sample estimates applied to the other samples.

Conclusion

SI-GFR is resistant to post-injection timing and volume errors but not to pre-injection error.
Restoring the barrier of chronically damaged urothelium using chondroitin sulfate glycosaminoglycan-replenishment therapy
Authors: Rozenberg Boy B. , van Ginkel Charlotte J. , Janssen Dick A.W.
Published: November 2023

Purpose of review

This study aims to further understand the physiological mechanism of chondroitin sulfate treatment on the urinary bladder in cases of inflammation, by investigating the effect of chondroitin sulfate therapy on recovery of urothelial barrier in an in-vitro chronic injury model.

Recent findings

With inflammatory bladder conditions, the urothelial barrier seems decreased. Glycosaminoglycan (GAG) replacement therapy is supposed to help restore this barrier. Clinical studies on inflammatory bladder conditions are complicated because of the heterogeneous patient population, hence the need for preclinical models.

In a model using porcine urothelial cells, functional barrier (TEER) and barrier markers were assessed. Chronic urothelial damage was simulated through protamine sulfate instillations with and without subsequent chondroitin sulfate instillations during 3 days. Chondroitin sulfate instillations significantly improved TEER compared to protamine sulfate treatment only (TEER difference 310 Ω.cm2, P < 0.001). This consistent effect over 3 days resulted in a significant higher mean TEER value in the chondroitin sulfate treated group (difference 1855 Ω.cm2, P < 0.001). Enhanced recovery of chondroitin sulfate and other barrier markers was observed.

Chondroitin sulfate therapy shows promise in facilitating the recovery of the urothelial barrier in cases of chronic damage. This preclinical study lends support to the use of clinical GAG replenishment therapy for patients with a chronically impaired urothelium.
Nephrometry Scoring Systems for Nephron Sparing Surgery in Children
Authors: Mrad Chaima , Chamouni Alexandre , Guerra Xavier , Tordjman Mickaël , Tabone Marie-Dominique , Audry Georges , Irtan Sabine
Published: November 2023

The surgical decision to attempt nephron-sparing surgery (NSS) in children with renal tumors can be difficult. In adults, nephrometric tools are used for decision-making. More than 90% of low-complexity tumors are eligible for NSS, and high-complexity tumors often require total nephrectomy. We retrospectively applied those nephrometric tools [Radius, Exophytic, Nearness to the sinus or collecting system, Anterior/posterior, Location relative to polar lines (RENAL), Preoperative Aspects and Dimensions Used for an Anatomical classification (PADUA), and Renal Tumor Invasion Index (RTII) scoring systems] to the preoperative imaging of children operated for renal tumors in our institution from 2015 to 2019 and correlated them with the type of surgery. The scores were assessed by 2 independent surgeons and 1 radiologist. Forty-four tumors were removed, including 16 NSS, 38 after neo-adjuvant chemotherapy, and 6 upfront surgeries, in 30 children. More than 50% of patients in the low and medium-risk population for RENAL, PADUA, and RTII scores, and ~15% in the high-complexity categories underwent NSS. Tumors removed through NSS were significantly less complex according to each score. Interobserver reliability was good for 3 scores. The application of the RENAL, PADUA, and RTII was able to accurately classify most of the pediatric tumors, according to their complexity. These scores could help increase the indications of NSS in renal tumor surgery.