bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal imaging for cardiac follow-up and management of giant coronary aneurysm related to Kawasaki disease in childhood: a case report
Authors: Werner Oscar , Pommier Victor , Guillaumont Sophie , Vincenti Marie
Published: October 2023

Background

Kawasaki disease (KD) is a rare paediatric condition that can lead to giant coronary aneurysms. Follow-up of such complex coronary lesions remains a challenge, and their management is difficult to standardize.

Case summary

Our present case concerns a 17-year-old boy who suffered a giant aneurysm of the left coronary artery, complicated by an asymptomatic stenosis. During regular follow-up, his annual cardiopulmonary exercise test revealed signs of ischaemia (ST depression and premature ventricular complexes). After several further stress tests with inconsistent results, he underwent invasive coronary angiography that revealed significant stenosis with a positive fractional flow reserve (FFR).

Discussion

We discuss the challenges of diagnosing and managing coronary artery stenosis in paediatric patients with KD, particularly in cases with calcified and thrombosed lesions. A multimodal approach is crucial, including non-invasive imaging, and coronary angiography with optical coherence tomography and FFR. The evaluation of the lesion and its follow-up is an important factor in anticipating the best therapeutic choice for each patient.
Child disability as a family issue: a study on mothers’ and fathers’ health in Italy
Authors: Balbo Nicoletta , Bolano Danilo
Published: October 2023

Background

Disability does not simply affect the health status of the individual who directly experiences that condition, but it has important consequences on the health and well-being of the other family members as well. Focusing on Italy, an extremely interesting test-bed due to its strong familialist welfare regime, we show significant spillover effects of children’s disability on parental health and well-being.

Methods

We use data from a nationally representative household survey on almost 13 000 mothers and fathers and adopt a multivariate regression setting providing evidence that the disability of a child is negatively associated with parents’ health and life satisfaction.

Results

Parents of a disabled child report lower levels of general and mental health, as well as lower levels of well-being compared with parents with a healthy child. Strong heterogeneity by gender and socio-economic characteristics is observed, with mothers being more affected by the disability status of the child than fathers. The estimated coefficients suggest that education remains an important protective factor even for parents of a disabled child.

Conclusion

This study claims and documents that child disability is an overlooked source of health disadvantage for parents. Such disadvantage is especially relevant for mothers and lower-educated parents, evidence that suggests the importance of taking an intersectional approach to study health disparities.
2. Human Rights in International Law
Authors: Smith Rhona K. M.
Published: October 2023

This chapter focuses on human rights within international law. It discusses the principal monitoring systems that ensured states complied with their international human rights treaty obligations. Some human rights agreements involved the abolition of slavery, humanitarian law, and labour rights. The chapter then lists treaties, customary international law, and soft law as the sources of international human rights law. States generally indicate their acceptance of international human rights law by agreeing to treaties, but they could avoid the full impact of legal obligations through reservations, derogations, and declarations. Thus, the existing mechanisms for monitoring human rights have a light touch that encouraged states to comply with treaties through constructive dialogue instead of any court processes.
9. Humanitarian Intervention
Authors: Kuperman Alan J.
Published: October 2023

This chapter highlights the distinction between human rights and humanitarianism. Humanitarian intervention refers to the use of diplomatic, economic, and/or military resources by states or international organizations to protect civilians who are endangered in another state. The chapter notes the impossibility of attaining impartiality and neutrality when commencing humanitarian work during a civil war. Modern intervention often confronts human rights violations by naming, shaming, and coercing those who harm civilians. The chapter then recognizes the obstacles to effective and timely intervention such as political will and large-scale violence against civilians. It covers the case of Kosovo that showed how the international community should utilize its leverage to persuade oppressive states to meet the legitimate demands of nonviolent groups in an effort to simultaneously promote human rights and humanitarianism.
11. Treaties, Monitoring, and Enforcement
Authors: Ritter Emily Hencken
Published: October 2023

This chapter explores the monitoring and enforcement of treaties, which is the foundation of international human rights law. The international nature of human rights treaties (HRT) makes it difficult to monitor and enforce states' compliance with treaty obligations. The chapter looks at how international organizations, domestic institutions, nongovernmental organizations (NGOs), and civilians monitor state compliance and invoke enforcement when necessary. It then explains the difficulty of constraining a state with the power to harm while demonstrating the power of collective action to change government practices. The process of compliance with international law involves standard setting, state compliance behaviour, monitoring, and enforcement. The chapter also highlights the difference between de jure and de facto rights protections. It looks into the social movements, such as the Black Lives Matter Movement, monitoring and enforcing state accountability to international HRT obligations.
Real-world treatment outcomes of metastatic biliary tract cancer patients in Japan: the Tokushukai REAl-world data project 04 (TREAD 04)
Authors: Shimoyama Rai , Imamura Yoshinori , Uryu Kiyoaki , Mase Takahiro , Taguri Masataka , Okuda Tadahisa , Fujimura Yoshiaki , Hayashi Maki , Tanaka Satomi , Sawamukai Keiji , Minami Hironobu
Published: October 2023

Objectives

To investigate temporal trends in treatment patterns and prognostic factors for overall survival in patients with metastatic biliary tract cancer.

Methods

From the Tokushukai REAl-world Data project, we identified 945 patients with metastatic biliary tract cancer treated with gemcitabine, tegafur/gimeracil/oteracil, gemcitabine plus cisplatin, gemcitabine plus tegafur/gimeracil/oteracil or gemcitabine plus cisplatin and tegafur/gimeracil/oteracil between April 2010 and March 2022. Stratified/conventional Cox regression analyses were conducted to examine the association between overall survival and patient- and tumour-related factors, study period, hospital volume, hospital type and first-line chemotherapy regimen. Using inverse probability of treatment weighting with propensity scores, overall survival was also compared between monotherapy and combination therapy groups.

Results

We enrolled 366 patients (199 men; median age, 72 years). Over a median follow-up of 5.2 months, the median overall survival was 7.0 months (95% confidence interval 6.2–9.0), and the median time to treatment failure was 3.5 months (95% confidence interval 3.1–4.5). Median overall survival and time to treatment failure for gemcitabine/tegafur–gimeracil–oteracil/gemcitabine plus cisplatin/gemcitabine plus tegafur–gimeracil–oteracil/gemcitabine plus cisplatin and tegafur–gimeracil–oteracil regimen were 6.2/6.6/7.9/16.2/15.1 and 2.8/3.4/4.1/15.3/7.4 months, respectively. Primary disease site, previous surgery, previous endoscopic procedures and hospital type were identified as significant prognostic factors. Inverse probability of treatment weighting analysis demonstrated that combination therapy had a significantly better prognosis than monotherapy (hazard ratio 0.61, 95% confidence interval 0.43–0.88, P = 0.006).

Conclusions

Our real-world data analysis showed that standard care for metastatic biliary tract cancer is widely used in hospitals throughout Japan and verified the survival benefits of combination therapy over monotherapy observed in prior clinical trials.

Clinical trial number

UMIN000050590 (http://www.umin.ac.jp/ctr/index.htm).
Suárez’s Argument against Real Universals
Authors: Adriaenssen Han Thomas
Published: October 2023

In his Metaphysical Disputation 5, Francisco Suárez offers a concise argument to the effect that all that does or can possibly exist is singular and individual, and that a commitment to real universals would entail what he calls a ‘manifest contradiction’. According to a recent interpretation of this Master Argument against realism, it reveals that Suárez was committed to a hylomorphic version of the principle of the identity of indiscernibles, and ruled out the possibility of perfectly similar yet numerically distinct entities. In this paper, however, I argue that (1) at least for fundamental items in his ontology such as immaterial forms and matter-form compounds, Suárez was not committed to the identity of indiscernibles, and (2) a reading of the Master Argument that does justice to this is available. On the basis of this reading I provide a reappraisal of the argument, and conclude that (3) it rests on a premise that the realist would have good reasons to challenge. Hence, while the argument seems consistent with the possibility of indiscernible yet numerically distinct immaterial forms and matter-form compounds Suárez wishes to allow for, it is doubtful whether it can accomplish what it sets out to do, and undermine the case for realism.
Designing a Situational Judgment Test for Use in Medical School Admissions
Authors: Berardi-Demo Linda , Cunningham Tara , Dunleavy Dana M. , McClure Stephanie C. , Richards Boyd F. , Terregino Carol A.
Published: October 2023

It has long been acknowledged that professional competencies are required for success in medical school, residency training, and medical practice. Over the last decade, medical schools have begun to introduce standardized assessments of professional competencies, but many still rely on interviews to assess these competencies, which occur after about half of the applicant pool has already been screened out. In this article, the authors discuss the development, evaluation, and launch of the Association of American Medical Colleges (AAMC) situational judgment test (SJT) for use in medical school admissions. The AAMC SJT is designed to assess an examinee’s understanding of effective and ineffective behaviors related to the core competencies for entering medical students, including service orientation, social skills, cultural competence, teamwork, ethical responsibility to self and others, reliability and dependability, resilience and adaptability, and capacity for improvement. The authors evaluate the evidence for the need for SJTs in medical school admissions by exploring common derailers in medical school, gaps in the admissions process regarding information about professional competencies, and the challenge of conducting holistic review in a high-volume context. They summarize existing research from the employment, international medical education, and residency selection contexts suggesting that SJT scores are positively associated with subsequent performance and may add value to the admissions process. The authors discuss 5 goals that were the foundation for developing the AAMC SJT: (1) assess the professional competencies needed for success in medical school using a proven method, (2) enable holistic review in a high-volume admissions context, (3) create and share a program of research to support the appropriate use of SJT scores, (4) signal the need for preparation in professionalism to learners, and (5) balance the need for a new assessment with minimizing the burden and risk for applicants.
Impact of Posterior Cervical Foraminotomy Before or After Cervical Disk Replacement
Authors: Young Mason W. , Abtahi Amir M.
Published: October 2023

Study Design:

Narrative review.

Objectives:

The purpose of this study was to provide a review of the current evidence on the impact of posterior cervical foraminotomy (PCF) performed before or after cervical disk replacement (CDR).

Summary of Background Data:

The impact of PCF on outcomes in the setting of CDR is an evolving field, given the recent widespread adoption of CDR and the relative rarity of patients who have undergone both procedures.

Methods:

A literature search was conducted using PubMed to determine current evidence regarding the indications, outcomes, and biomechanical effects of CDR and PCF when performed alone or in combination.

Results:

When radicular symptoms persist following PCF, a CDR can be safely performed to provide further decompression. Conversely, a PCF can be safely performed following CDR for these same indications. The biomechanical effects of these procedures in combination demonstrate maintained stability when the facetectomy is less than 50% of the facet joint. Studies demonstrate that stability is not significantly decreased by the presence, amount, or level of posterior foraminotomies in the setting of CDR.

Conclusions:

A PCF can be safely performed before or after cervical disk arthroplasty for recurrent radicular symptoms.

Level of Evidence:

Level V.
Patient-specific Cervical Deformity Corrections With Consideration of Associated Risk
Authors: Passias Peter G. , Pierce Katherine E. , Williamson Tyler K. , Lebovic Jordan , Schoenfeld Andrew J. , Lafage Renaud , Lafage Virginie , Gum Jeffrey L. , Eastlack Robert , Kim Han Jo , Klineberg Eric O. , Daniels Alan H. , Protopsaltis Themistocles S. , Mundis Gregory M. , Scheer Justin K. , Park Paul , Chou Dean , Line Breton , Hart Robert A. , Burton Douglas C. , Bess Shay , Schwab Frank J. , Shaffrey Christopher I. , Smith Justin S. , Ames Christopher P. ,   on Behalf of the International Spine Study Group
Published: October 2023

Study Design/Setting:

This was a retrospective cohort study.

Background:

Little is known of the intersection between surgical invasiveness, cervical deformity (CD) severity, and frailty.

Objective:

The aim of this study was to investigate the outcomes of CD surgery by invasiveness, frailty status, and baseline magnitude of deformity.

Methods:

This study included CD patients with 1-year follow-up. Patients stratified in high deformity if severe in the following criteria: T1 slope minus cervical lordosis, McGregor’s slope, C2–C7, C2–T3, and C2 slope. Frailty scores categorized patients into not frail and frail. Patients are categorized by frailty and deformity (not frail/low deformity; not frail/high deformity; frail/low deformity; frail/high deformity). Logistic regression assessed increasing invasiveness and outcomes [distal junctional failure (DJF), reoperation]. Within frailty/deformity groups, decision tree analysis assessed thresholds for an invasiveness cutoff above which experiencing a reoperation, DJF or not achieving Good Clinical Outcome was more likely.

Results:

A total of 115 patients were included. Frailty/deformity groups: 27% not frail/low deformity, 27% not frail/high deformity, 23.5% frail/low deformity, and 22.5% frail/high deformity. Logistic regression analysis found increasing invasiveness and occurrence of DJF [odds ratio (OR): 1.03, 95% CI: 1.01–1.05, P=0.002], and invasiveness increased with deformity severity (P<0.05). Not frail/low deformity patients more often met Optimal Outcome with an invasiveness index <63 (OR: 27.2, 95% CI: 2.7–272.8, P=0.005). An invasiveness index <54 for the frail/low deformity group led to a higher likelihood of meeting the Optimal Outcome (OR: 9.6, 95% CI: 1.5–62.2, P=0.018). For the frail/high deformity group, patients with a score <63 had a higher likelihood of achieving Optimal Outcome (OR: 4.8, 95% CI: 1.1–25.8, P=0.033). There was no significant cutoff of invasiveness for the not frail/high deformity group.

Conclusions:

Our study correlated increased invasiveness in CD surgery to the risk of DJF, reoperation, and poor clinical success. The thresholds derived for deformity severity and frailty may enable surgeons to individualize the invasiveness of their procedures during surgical planning to account for the heightened risk of adverse events and minimize unfavorable outcomes.
KAT6A::EP300 fusion in congenital myeloid sarcoma: Yet another novel molecular marker indicating spontaneous remission?: A case report
Authors: Hosahalli Vasanna Smitha , Shah Sonal D. , Rohr Bethany R. , Roche Breanne , Meyerson Howard , Pateva Irina
Published: October 2023

Rationale:

Acute myeloid leukemia (AML)/myeloid sarcoma (MS) is risk-stratified based on cytogenetics. Although most congenital AML/MS have a dismal prognosis, certain genetic variants such as t (8, 16) [KAT6A::cAMP response element-binding protein (CREB) - binding protein fusion] and more recently t (8, 22) [KAT6A::EP300 fusion] have shown spontaneous remissions. KAT6A located on chromosome 8p11 encodes KAT6A protein, a histone/lysine acetyltransferase enzyme. Numerous partner genes associated with KAT6A include cAMP response element-binding protein (CREB) - binding protein (16p13), EP300 (22q13), LEUTX (9q13), NCOA2, NCOA3, and ASXL2.

Patient concerns:

In this article, we describe an otherwise healthy infant who presented with skin nodules on the face and scalp without any systemic or CNS involvement. A biopsy of the cutaneous lesion was consistent with congenital MS.

Diagnoses:

Through molecular testing, we found that our patient had the KAT6A::EP300 mutation. This is one of the rare recurrent cytogenetic abnormalities that are linked to congenital AML.

Intervention:

Our patient underwent spontaneous remission with watchful waiting.

Outcome:

Our patient has remained in spontaneous remission for 24 months.

Lessons:

Even though the KAT6A::EP300 mutation in adults is a poor prognostic marker, a similar mutation in congenital AML has a higher likelihood of spontaneous remission. Hence, conservative management might be an initial management strategy for clinically stable patients.
Cost-effectiveness of virtual reality and wet laboratory cataract surgery simulation
Authors: Ng Danny S. , Yip Benjamin H. K. , Young Alvin L. , Yip Wilson W. K. , Lam Nai M. , Li Kenneth K. , Ko Simon T. , Chan Wai H. , Aryasit Orapan , Sikder Shameema , Ferris John D. , Pang Chi P. , Tham Clement C.
Published: October 2023

Purpose:

To evaluate the cost-effectiveness of phacoemulsification simulation training in virtual reality simulator and wet laboratory on operating theater performance.

Methods:

Residents were randomized to a combination of virtual reality and wet laboratory phacoemulsification or wet laboratory phacoemulsification. A reference control group consisted of trainees who had wet laboratory training without phacoemulsification. All trainees were assessed on operating theater performance in 3 sequential cataract patients. International Council of Ophthalmology Surgical Competency Assessment Rubric—phacoemulsification (ICO OSCAR phaco) scores by 2 masked independent graders and cost data were used to determine the incremental cost-effectiveness ratio (ICER). A decision model was constructed to indicate the most cost-effective simulation training strategy based on the willingness to pay (WTP) per ICO OSCAR phaco score gained.

Results:

Twenty-two trainees who performed phacoemulsification in 66 patients were analyzed. Trainees who had additional virtual reality simulation achieved higher mean ICO OSCAR phaco scores compared with trainees who had wet laboratory phacoemulsification and control (49.5 ± standard deviation [SD] 9.8 vs 39.0 ± 15.8 vs 32.5 ± 12.1, P < .001). Compared with the control group, ICER per ICO OSCAR phaco of wet laboratory phacoemulsification was $13,473 for capital cost and $2209 for recurring cost. Compared with wet laboratory phacoemulsification, ICER per ICO OSCAR phaco of additional virtual reality simulator training was US $23,778 for capital cost and $1879 for recurring cost. The threshold WTP values per ICO OSCAR phaco score for combined virtual reality simulator and wet laboratory phacoemulsification to be most cost-effective was $22,500 for capital cost and $1850 for recurring cost.

Conclusions:

Combining virtual reality simulator with wet laboratory phacoemulsification training is effective for skills transfer in the operating theater. Despite of the high capital cost of virtual reality simulator, its relatively low recurring cost is more favorable toward cost-effectiveness.
The Effect of Affective Temperament, Pain Catastrophizing, and Anxiety Sensitivity on Pain Severity in Patients With Chronic Pelvic Pain: A Pilot Study
Authors: Kayacik Günday Özlem , Harmanci Hatice , Şenol Yiğit
Published: October 2023

Objective:

The goals of this study were to investigate whether there was a dominant temperament type, and to assess the effect of temperament, pain catastrophizing, and anxiety sensitivity on pain severity, in female patients diagnosed with chronic pelvic pain (CPP) compared with healthy controls.

Methods:

This cross-sectional study involved 51 patients 18 to 65 years of age who were diagnosed with CPP without a history of psychiatric treatment and 97 healthy volunteer women with sociodemographic characteristics similar to those of the study group. A sociodemographic form prepared by the researchers, the Anxiety Sensitivity Index, the Pain Catastrophizing Scale, a temperament scale (Temperament Evaluation of Memphis, Pisa, Paris, and San Diego–Autoquestionnaire), and a visual analog pain scale (VAS) were completed. The results were compared between the patient and control groups. Multiple regression analyses were performed to examine the predictive effects of temperament characteristics, pain catastrophizing, and anxiety sensitivity on pain severity.

Results:

Scores on the Pain Catastrophizing Scale and the VAS were statistically significantly higher in the CPP group (P<0.001). The frequency of depressive, cyclothymic, and irritable temperaments was found to be significantly higher in the CPP group (CPP: 7.78±3.32 vs. controls: 6.54±3.19; P=0.027; CPP:10.61±4.41 vs. controls: 8.82±4.21; P=0.017; CPP: 5.22±4.29 vs. controls: 3.75±3.41; P=0.025). According to the model established by temperament traits, anxiety sensitivity, and pain catastrophizing level, pain catastrophizing level explained 11.6% of the variance in pain severity. A 1-unit change in the score for pain catastrophizing level caused a 0.278-point change in the VAS total score (P<0.01).

Conclusions:

Cyclothymic, depressive, and irritable temperament types that increase the risk of affective disease are more common in patients with CPP. The level of pain catastrophizing in patients with CPP affects their perception of the severity of the pain.
Borrmann Type IV Gastric Cancer: Computed Tomography Features and Corresponding Pathological Findings
Authors: Ji Changfeng , Ma Yi , Zheng Zhong , Liu Song , Zhou Zhengyang
Published: October 2023

Objective

We aimed to analyze the association between computed tomography (CT) features and the corresponding pathological findings in Borrmann type IV (BT-4) gastric cancers and explore the pathological basis of the characteristic CT features.

Methods

This retrospective study included 84 patients with BT-4 gastric cancers who underwent contrast-enhanced CT and surgical resection. Preoperative CT features were evaluated, including the major location, range, circumferential invasion, perigastric fat infiltration, enlarged lymph nodes, layered enhancement, degree of enhancement, and peak enhanced phase. Postoperative pathological findings were also recorded. Differences in CT features according to different World Health Organization types, surgical margin, adjacent organ invasion, and peritoneal status were assessed using the χ2 or Fisher exact test (n < 5).

Results

The most common World Health Organization type of BT-4 gastric cancer was poorly cohesive carcinoma (65.5%), which tended to show circumferential invasion, fewer enlarged lymph nodes, and layered enhancement. Although 82 patients with BT-4 gastric cancer (97.6%) had positive lymph nodes, only 26 (31.0%) had enlarged lymph nodes. Lesions originating from the gastroesophageal junction had a higher rate of positive margins (P < 0.05). Adjacent organ invasion was more likely to occur in lesions with perigastric fat infiltration (P < 0.05). Patients with circumferential invasion tended to show peritoneal metastasis (P < 0.05).

Conclusions

The characteristic CT features of BT-4 gastric cancer may be attributed to the corresponding pathological findings. Recognizing the association between CT features and pathological findings may help evaluate the aggressiveness of BT-4 gastric cancers.
Association of Systemic Lupus Erythematosus Disease Activity With Choroidal Thickness
Authors: Lee Iris , Gomez Andrea Ramirez , Kim Alfred H.J. , Coble Dean W. , Marshall Brigid , Shah Aaditya , Eisen Seth , Apte Rajendra S. , Li Tingting
Published: October 2023

Objective

To determine the association between disease activity and choroidal thickness in patients with systemic lupus erythematosus (SLE).

Methods

We conducted a cohort study of 24 SLE patients and 13 healthy controls recruited at Washington University School of Medicine between June 2019 and November 2021. SLE disease activity was assessed using the SLE Disease Activity Index-2000 Responder Index-50 (S2K RI-50). Patients were divided into four groups: high disease activity/no lupus nephritis (HDA/no LN; S2K RI-50 > 4), HDA/active LN (HDA/active LN; S2K RI-50 > 4), low disease activity/inactive LN (LDA/inactive LN; S2K RI-50 ≤ 4), and LDA/no LN (LDA/no LN; S2K RI-50 ≤ 4). LDA/no LN patients were age-, sex-, and race-matched to healthy controls and patients in other SLE groups. Choroidal thickness of the right eye was measured blinded to disease activity on a horizontal section through the fovea on optical coherence tomography images taken within a week of disease assessment.

Results

Patients with HDA had choroidal thickening compared with matched patients with LDA. After controlling for multiplicity, choroidal thinning remained statistically significant at 1000 μm nasal to the fovea (308 ± 68 vs 228 ± 64 μm, p = 0.001). Choroidal thickness was not different between LDA/no LN and LDA/inactive LN or healthy controls.

Conclusion

HDA in patient with SLE is associated with increased choroidal thickness whereas comorbid inactive LN did not affect choroidal thickness. Additional studies in a larger longitudinal cohort are needed to study whether choroidal thickness may be used as a noninvasive, adjunctive measure for disease activity in SLE.
Quantification of Torque Teno Virus Load to Monitor Short-term Changes in Immunosuppressive Therapy in Kidney Transplant Recipients
Authors: Benning Louise , Reineke Marvin , Bundschuh Christian , Klein Julian A. F. , Kühn Tessa , Zeier Martin , Bartenschlager Ralf , Schnitzler Paul , Morath Christian , Speer Claudius
Published: October 2023

Background.

Quantification of torque teno virus (TTV) has been proposed as a surrogate parameter to monitor immunocompetence in kidney transplant recipients (KTRs) early after transplantation. However, its use in monitoring short-term changes of immunosuppression in KTRs late after transplantation requires further investigation.

Methods.

In this post hoc analysis, we quantified TTV load in sera of 76 KTRs, with 43 pausing mycophenolic acid (MPA) 1 wk before to 4 wk after COVID-19 vaccination to increase vaccine response. TTV load was quantified before, 4 wk, and 3 mo postvaccination. Results were compared to 33 KTRs with continued standard immunosuppressive therapy and with 18 hemodialysis as well as 18 healthy control subjects.

Results.

TTV load before vaccination was with a median (interquartile range) of 1.39 × 104 copies/milliliter (c/mL) (9.17 × 101–2.66 × 105 c/mL) highest in KTRs compared to 1.73 × 103 c/mL (1.07 × 103–1.31 × 104 c/mL) in hemodialysis patients and 1.53 × 102 c/mL (6.38–1.29 × 103 c/mL) in healthy controls. In KTRs with MPA withdrawal, TTV load decreased significantly from a median (interquartile range) of 1.11 × 104 c/mL (4.75 × 102–1.92 × 105 c/mL) to 5.24 × 103 c/mL (6.92 × 102–6.91 × 104 c/mL) 4–5 wk after initiation of MPA withdrawal (P = 0.003). In patients with MPA withdrawal, TTV load was significantly inversely correlated with COVID-19 or SARS-CoV-2–specific antibodies 4 wk and 3 mo postvaccination (P = 0.009 and P = 0.004).

Conclusions.

TTV load reflects changes in immunosuppressive therapy even late after transplantation, supporting its use to monitor immunocompetence in KTRs.
Analysis of possible pathways on the mechanism of action of minocycline and doxycycline against strains of Candida spp. resistant to fluconazole
Authors: da Silva Cecília Rocha , Silveira Maria Janielly Castelo Branco , Soares Giulia Caetano , de Andrade Claudia Roberta , Cabral Vitória Pessoa de Farias , Sá Lívia Gurgel do Amaral Valente , Rodrigues Daniel Sampaio , Moreira Lara Elloyse Almeida , Barbosa Amanda Dias , da Silva Lisandra Juvêncio , da Silva Anderson Ramos , Gomes Akenaton Onassis Cardoso Viana , Cavalcanti Bruno Coêlho , de Moraes Manoel Odorico , Nobre Júnior Hélio Vitoriano , de Andrade Neto João Batista
Published: October 2023

Species of the genus Candida, characterized as commensals of the human microbiota, are opportunistic pathogens capable of generating various types of infections with high associated costs. Considering the limited pharmacological arsenal and the emergence of antifungal-resistant strains, the repositioning of drugs is a strategy used to search for new therapeutic alternatives, in which minocycline and doxycycline have been evaluated as potential candidates. Thus, the objective was to evaluate the in vitro antifungal activity of two tetracyclines, minocycline and doxycycline, and their possible mechanism of action against fluconazole-resistant strains of Candida spp. The sensitivity test for antimicrobials was performed using the broth microdilution technique, and the pharmacological interaction with fluconazole was also analysed using the checkerboard method. To analyse the possible mechanisms of action, flow cytometry assays were performed. The minimum inhibitory concentration obtained was 4–427 µg ml−1 for minocycline and 128–512 µg ml−1 for doxycycline, and mostly indifferent and additive interactions with fluconazole were observed. These tetracyclines were found to promote cellular alterations that generated death by apoptosis, with concentration-dependent reactive oxygen species production and reduced cell viability. Therefore, minocycline and doxycycline present themselves as promising study molecules against Candida spp.
The Impact of Physician-Patient Gender Match on Healthcare Quality: An Experiment in China
Authors: Si Yafei , Chen Gang , Su Min , Zhou Zhongliang , Yip Winnie , Chen Xi
Published: October 2023

Despite growing evidence of gender disparities in healthcare utilization and health outcomes, there is a lack of understanding of what may drive such differences. Designing and implementing an experiment using the standardized patients’ approach, we present novel evidence on the impact of physician-patient gender match on healthcare quality in a primary care setting in China. We find that, compared with female physicians treating female patients, the combination of female physicians treating male patients resulted in a 23.0 percentage-point increase in correct diagnosis and a 19.4 percentage-point increase in correct drug prescriptions. Despite these substantial gains in healthcare quality, there was no significant increase in medical costs and time investment. Our analyses suggest that the gains in healthcare quality were mainly attributed to better physician-patient communications, but not the presence of more clinical information. This paper has policy implications in that improving patient centeredness and incentivizing physicians’ efforts in consultation (as opposed to treatment) can lead to significant gains in the quality of healthcare with modest costs, while reducing gender differences in care.
Chrysin directing an enhanced solubility through the formation of a supramolecular cyclodextrin-calixarene drug delivery system: a potential strategy in antifibrotic diabetes therapeutics
Authors: Hermenean Anca , Dossi Eleftheria , Hamilton Alex , Trotta Maria Consiglia , Russo Marina , Lepre Caterina Claudia , Sajtos Csilla , Rusznyák Ágnes , Váradi Judit , Bácskay Ildikó , Budai István , D’Amico Michele , Fenyvesi Ferenc
Published: October 2023

Calixarene 0118 (OTX008) and chrysin (CHR) are promising molecules for the treatment of fibrosis and diabetes complications but require an effective delivery system to overcome their low solubility and bioavailability. Sulfobutylated β-cyclodextrin (SBECD) was evaluated for its ability to increase the solubility of CHR by forming a ternary complex with OTX008. The resulting increase in solubility and the mechanisms of complex formation were identified through phase-solubility studies, while dynamic light-scattering assessed the molecular associations within the CHR-OTX008-SBECD system. Nuclear magnetic resonance, differential scanning calorimetry, and computational studies elucidated the interactions at the molecular level, and cellular assays confirmed the system’s biocompatibility. Combining SBECD with OTX008 enhances CHR solubility more than using SBECD alone, by forming water-soluble molecular associates in a ternary complex. This aids in the solubilization and delivery of CHR and OTX008. Structural investigations revealed non-covalent interactions essential to complex formation, which showed no cytotoxicity in hyperglycemicin vitroconditions. A new ternary complex has been formulated to deliver promising antifibrotic agents for diabetic complications, featuring OTX008 as a key structural and pharmacological component.
The Trajectory of Depression and Anxiety Among Children and Adolescents over Two Years of the COVID-19 Pandemic
Authors: Korczak Daphne J. , Lo Ronda F. , Rizeq Jala , Crosbie Jennifer , Charach Alice , Anagnostou Evdokia , Birken Catherine S. , Monga Suneeta , Kelley Elizabeth , Nicolson Rob , Arnold Paul D. , Maguire Jonathon L. , Schachar Russell J. , Georgiades Stelios , Burton Christie L. , Cost Katherine Tombeau
Published: October 2023

Longitudinal research examining children’s mental health (MH) over the course of the COVID-19 pandemic is scarce. We examined trajectories of depression and anxiety over two pandemic years among children with and without MH disorders. Parents and children 2-18 years completed surveys at seven timepoints (April 2020 to June 2022). Parents completed validated measures of depression and anxiety for children 8-18 years, and validated measures of emotional/behavioural symptoms for children 2-7 years old; children ≥10 years completed validated measures of depression and anxiety. Latent growth curve analysis determined depression and anxiety trajectories, accounting for demographics, child and parent MH. Data were available on 1315 unique children (1259 parent-reports; 550 child-reports). Trajectories were stable across the study period, however individual variation in trajectories was statistically significant. Of included covariates, only initial symptom level predicted symptom trajectories. Among participants with pre-COVID data, a significant increase in depression symptoms relative to pre-pandemic levels was observed. Children and adolescents experienced elevated and sustained levels of depression and anxiety during the two-year period. Findings have direct policy implications in the prioritization and of maintenance of educational, recreational, and social activities with added MH supports in the face of future events.
Daily variation in blood glucose levels during continuous enteral nutrition in patients on the Intensive Care Unit: a retrospective observational study
Authors: Hiemstra Floor W. , Stenvers Dirk Jan , Kalsbeek Andries , de Jonge Evert , van Westerloo David J. , Kervezee Laura
Published: October 2023

Background

The circadian timing system coordinates daily cycles in physiological functions, including glucose metabolism and insulin sensitivity. Here, the aim was to characterize the 24-hour variation in glucose levels in critically ill patients during continuous enteral nutrition after controlling for potential sources of bias.

Methods

Time-stamped clinical data from adult patients who stayed in the Intensive Care Unit (ICU) for at least 4 days and received enteral nutrition were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Linear mixed-effects and XGBoost modelling were used to determine the effect of time of day on blood glucose values.

Findings

In total, 207,647 glucose measurements collected during enteral nutrition were available from 6,929 ICU patients. Using linear mixed-effects modelling, time of day had a significant effect on blood glucose levels (p<0·001), with a peak of 9·6 [9·5 – 9·6; estimated marginal means, 95% CI] mmol/L at 10:00 in the morning and a trough of 8·6 [8·5 – 8·6] mmol/L at 03:00 at night. A similar impact of time of day on glucose levels was found with the XGBoost regression model.

Interpretation

These results revealed marked 24-hour variation in glucose levels in ICU patients even during continuous enteral nutrition. This 24-hour pattern persists after adjustment for potential sources of bias, suggesting it may be the result of endogenous biological rhythmicity.

Funding

This work was supported by a VENI grant (2020-09150161910128) from the Netherlands Organization for Health Research and Development (ZonMw), an institutional project grant, and by the Dutch Research Council (NWO).
Tumor Purity-Related Genes for Predicting the Prognosis and Drug Sensitivity of DLBCL Patients
Authors: Ye Zhenbang , Huang Ning , Fu Yongliang , Tian Rongle , Huang Wenting
Published: October 2023

Background

Diffuse large B-cell lymphoma (DLBCL) is the predominant type of malignant B-cell lymphoma. Although various treatments have been developed, the limited efficacy calls for more and further exploration of its characteristics.

Methods

Datasets from Gene Expression Omnibus (GEO) database were used for identifying the tumor purity of DLBCL. Survival analysis was employed for analyzing the prognosis of DLBCL patients. Immunohistochemistry was conducted to detect the important factor that influenced the prognosis. Drug sensitive prediction was performed to evaluate the value of the constructed model.

Results

VCAN, CD3G and C1QB were identified as three key genes that impacted the outcome of DLBCL patients both in GEO datasets and samples from our center. Among them, VCAN and CD3G+ T cells were correlated with favorable prognosis, and C1QB was correlated with worse prognosis. The ratio of CD68+ macrophages and CD8+ T cells was associated with better prognosis. In addition, CD3G+ T cells ratio was significantly correlated with CD68+ macrophages, CD4+ T cells and CD8+ T cells ratio, indicating it could play an important role in the anti-tumor immunity in DLBCL. The riskScore model constructed based on the RNASeq data of VCAN, C1QB and CD3G work well in predicting the prognosis and drug sensitivity.

Conclusion

VCAN, CD3G and C1QB were three key genes that influenced the tumor purity of DLBCL, and could also exert certain impact on drug sensitivity and prognosis of DLBCL patients.
Modelling the health and economic impacts of M72/AS01Evaccination and BCG-revaccination: estimates for South Africa
Authors: Sumner Tom , Clark Rebecca A. , Mukandavire Christinah , Portnoy Allison , Weerasuriya Chathika K. , Bakker Roel , Scarponi Danny , Hatherill Mark , Menzies Nicolas A. , White Richard G.
Published: October 2023

Background

Tuberculosis remains a major public health problem in South Africa, with an estimated 300,000 cases and 55,000 deaths in 2021. New tuberculosis vaccines could play an important role in reducing this burden. Phase IIb trials have suggested efficacy of the M72/AS01Evaccine candidate and BCG-revaccination. The potential population impact of these vaccines is unknown.

Methods

We used an age-stratified transmission model of tuberculosis, calibrated to epidemiological data from South Africa, to estimate the potential health and economic impact of M72/AS01Evaccination and BCG-revaccination. We simulated vaccination scenarios over the period 2025–2050 with a range of product characteristics and delivery strategies. We calculated reductions in tuberculosis cases and deaths and costs and cost-effectiveness from health-system and societal perspectives.

Results

M72/AS01Evaccination may have a larger impact than BCG-revaccination, averting approximately 80% more cases and deaths by 2050. Both vaccines were found to be cost-effective (compared to no new vaccine) across a range of vaccine characteristics and delivery strategies. The impact of M72/AS01Eis dependent on the assumed efficacy of the vaccine in uninfected individuals. Extending BCG-revaccination to HIV-infected individuals on ART had minimal effect on the health impact, but increased costs by approximately 70%.

Conclusions

Our results show that M72/AS01Evaccination or BCG-revaccination could be cost-effective in South Africa. However, there is considerable uncertainty in the estimated impact and costs due to uncertainty in vaccine characteristics and the choice of delivery strategy.
The Effects of Decreased Frame Rate During Cardiac Catheterization on Patient and Radiation Safety Outcomes
Authors: Oredegbe Al-Ameen , Derakhshesh Matthew , Vuthoori Ravi , Torosoff Mikhail , Nappi Anthony , Yager Neil
Published: October 2023

Objective

Coronary artery disease (CAD) is an important cause of morbidity and mortality all over the world. Cardiac catheterization is one of the most important treatment modalities in managing CAD. Unfortunately, cardiac catheterization is associated with significant ionizing radiation exposure to both patients and personnel. This study aimed to compare the safety and efficacy of a lower video frame rate of 7.5-fps compared with the standard frame rate of 15-fps.

Materials and Methods

We retrospectively collected and reviewed data from 84 cardiac catheterizations performed between January and February 2020 at a single tertiary center. The patients were divided into two groups based on frame rate: 15-fps (n=42) and 7.5-fps (n=42). We compared the two groups in terms of demographic data, procedural characteristics, radiation dose, and patient outcomes.

Results

Cumulative air kerma was significantly lower in the 7.5-fps group (266.576 mGy) compared to the 15-fps group (524.140 mGy), p=0.0018. Similarly, total dose area product was lower in the 7.5-fps group (15335.617 mGy × cm2compared to the 15-fps group (34784.095 mG × cm2), p = 0.0003. Despite this, total fluoroscopic time did not differ between the two groups 7.74 minutes in the 15-fps group and 8.462 minutes in the 7.5-fps group, p = 0.4023). In addition, 30-day mortality 0% in both groups and there were no differences in the number of repeat PCIs performed within 30 days (6 in 7.5-fps and 3 in the 15-fps group), p = 0.2899.

Conclusion

During cardiac catheterization, a fluoroscopy rate of 7.5-fps is associated with lower radiation dose compared to 15-fps without an associated increase in fluoroscopy time, mortality or repeat PCI. Therefore, interventionalists should consider using a fluoroscopy rate of 7.5-fps during cardiac catheterization.
High-riskEscherichia coliclones that cause neonatal meningitis and association with recrudescent infection
Authors: Nhu Nguyen Thi Khanh , Phan Minh-Duy , Hancock Steven J. , Peters Kate M. , Alvarez-Fraga Laura , Forde Brian M. , Andersen Stacey B. , Miliya Thyl , Harris Patrick N.A. , Beatson Scott A. , Schlebusch Sanmarie , Bergh Haakon , Turner Paul , Brauner Annelie , Westerlund-Wikström Benita , Irwin Adam D. , Schembri Mark A.
Published: October 2023

Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae.Escherichia coliis the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974-2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence factor was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75 and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggests that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.
Patients with chronic cluster headache may show reduced activity energy expenditure on ambulatory wrist actigraphy recordings during daytime attacks
Authors: Vandenbussche Nicolas , Van Der Donckt Jonas , Brouwer Mathias De , Steenwinckel Bram , Stojchevska Marija , Ongenae Femke , Hoecke Sofie Van , Paemeleire Koen
Published: October 2023

Structured Abstract

Objective

To investigate the changes in activity energy expenditure throughout daytime cluster headache attacks in patients with chronic cluster headache, and to evaluate the usefulness of actigraphy as a digital biomarker of cluster headache attacks.

Background

Cluster headache is a primary headache disorder characterized by attacks of severe to very severe unilateral head pain with ipsilateral cranial autonomic symptoms and/or a sense of restlessness or agitation. We hypothesized increased activity energy expenditure from hyperactivity during attacks measured by actigraphy.

Methods

An observational study including patients with chronic cluster headache was conducted. During 21 days, patients wore an actigraphy device on the non-dominant wrist and recorded cluster headache attack-related data in a dedicated smartphone application. Accelerometer data was used for the calculation of activity energy expenditure before and during daytime cluster headache attacks that occurred in ambulatory settings, and without restrictions on acute and preventive headache treatment. We compared the activity and movements during the pre-ictal, ictal, and postictal phases with data from wrist-worn actigraphy with time-concordant intervals during non-headache periods.

Results

Four patients provided 34 attacks, of which 15 attacks met the eligibility criteria for further analysis. In contrast with the initial hypothesis of increased energy expenditure during cluster headache attacks, a decrease in movement was observed during the pre-ictal phase (30 min before onset to onset) and during the headache phase. A significant decrease (p<0.01) in the proportion of high-intensity movement during headache attacks, of which the majority were oxygen-treated, was observed. This trend was less present for low-intensity movements.

Conclusion

The results of our analysis may shift the initial hypothesis for future research towards a decrease in activity energy expenditure during the pre-ictal and headache phase of daytime attacks in patients with chronic cluster headache under acute and preventive treatment in ambulatory settings.