bluuebunny/crossref_metadata_2025 huggingface dataset:
The Retrospective Stressor Analysis (RSA): a novel qualitative tool for identifying causes of burnout and mitigation strategies during residency
Authors: Chrouser Kristin L. , Zebib Laura , Webb Blake F. , Bagian Tandi , Arnold Timothy
Published: May 2024

Background

Resident physicians are at an increased risk of burnout due to their high-pressure work environments and busy schedules which can lead to poor mental health outcomes and decreased performance quality. Given variability among training programs and institutions across the United States, stressors likely differ, and interventions must be tailored to the local context, but few tools exist to assist in this process.

Methods

A tool commonly used in adverse event analysis was adapted into a “retrospective stressor analysis” (RSA) for burnout prevention. The RSA was tested in a group of chief residents studying quality improvement and patient safety in veteran’s hospitals across the United States. The RSA prompted them to identify stressors experienced during their residencies across four domains (clinical practice, career development, personal life, and personal health), perceived causes of the stressors, and potential mitigation strategies.

Results

Fifty-eight chief residents completed the RSA. Within the clinical domain, they describe the stress of striving for efficiency and clinical skills acquisition, all while struggling to provide quality care in high pressure environments. In the career domain, identifying mentors and opportunities for research engagement was stressful. Within their personal lives, a lack of time-constrained their ability to maintain hobbies, relationships, and attend meaningful social events while also reducing their engagement in healthy behaviors such as exercise, optimal nutrition, and attending medical appointments. Within each of these domains, they identified and described stress mitigation strategies at the individual, departmental, and national levels.

Conclusion

The RSA is a novel tool that can identify national trends in burnout drivers while simultaneously providing tailored prevention strategies for residents and their training sites.
Association between regulator inspection and ratings on primary care prescribing: an observational study in England 2014 to 2019
Authors: Allen Thomas , Walshe Kieran , Proudlove Nathan , Sutton Matt
Published: May 2024

Background

Healthcare regulators in many countries undertake inspections of healthcare providers and publish inspection outcomes with the intention of improving quality of care. Comprehensive inspections of general practices in England by the Care Quality Commission began for the first time in 2014. It is assumed that inspection and rating will raise standards and improve care, but the presence and extent of any improvements is unknown. We aim to determine if practice inspection ratings are associated with past performance on prescribing indicators and if prescribing behaviour changes following inspection.

Methods

Longitudinal study using a dataset of 6771 general practices in England. Practice inspection date and score was linked with monthly practice-level data on prescribing indicators relating to antibiotics, hypnotics and non-steroidal anti-inflammatory drugs. The sample covers practices receiving their first inspection between September 2014 and December 2018. Regression analysis and the differential timing of inspections is used to identify the impact on prescribing.

Results

Better-rated practices had better prescribing in the period before inspections began. In the six months following inspections, no overall change in prescribing was observed. However, the differences between the best and worse rated practices were reduced but not fully. The same is also true when taking a longer-term view. There is little evidence that practices responded in anticipation of inspection or reacted differently once the ratings were made public.

Conclusion

While some of the observed historic variation in prescribing behaviour has been lessened by the process of inspection and ratings, we find this change is small and appears to come from both improvements among lower-rated practices and deteriorations among higher-rated practices. While inspection and rating no doubt had other impacts, these prescribing indicators were largely unchanged.
Expression of glucocorticoid receptor and HDACs in airway smooth muscle cells is associated with response to steroids in COPD
Authors: Zhou Liang , Roth Michael , Papakonstantinou Eleni , Tamm Michael , Stolz Daiana
Published: May 2024

Background

Steroid insensitivity in Chronic Obstructive Pulmonary Disease (COPD) presents a problem for controlling the chronic inflammation of the airways. The glucocorticoid receptor (GR) mediates the intracellular signaling of inhaled corticosteroids (ICS) by interacting with transcription factors and histone deacetylases (HDACs). The aim of this study was to assess if COPD patients’ response to ICS in vivo, may be associated with the expression of GR, the complex of GR with transcription factors, and the expression of various HDACs in vitro.

Methods

Primary airway smooth muscle cells (ASMC) were established from endobronchial biopsies obtained from patients with asthma (n = 10), patients with COPD (n = 10) and subjects that underwent diagnostic bronchoscopy without pathological findings and served as controls (n = 6). ASMC were also established from 18 COPD patients, 10 responders and 8 non-responders to ICS, who participated in the HISTORIC study, an investigator-initiated and driven clinical trial that proved the hypothesis that COPD patients with high ASMC in their endobronchial biopsies respond better to ICS than patients with low ASMC. Expression of GR and its isoforms GRα and GRβ and HDACs was investigated in primary ASMC in the absence or in the presence of dexamethasone (10− 8M) by western blotting. The complex formation of GR with transcription factors was assessed by co-immunoprecipitation.

Results

Expression of GR and its isoform GRα but not GRβ was significantly reduced in ASMC from COPD patients as compared to controls. There were no significant differences in the expression of GR, GRα and GRβ between responders and non-responders to ICS. However, treatment with dexamethasone upregulated the expression of total GR (p = 0.004) and GRα (p = 0.005) after 30 min in responders but not in non-responders. Τhe formation of the complex GR-c-Jun was increased 60 min after treatment with dexamethasone only in responders who exhibited significantly lower expression of HDAC3 (p = 0.005) and HDAC5 (p < 0.0001) as compared to non-responders.

Conclusions

These data suggest that ASMC from COPD patients who do not respond to treatment with ICS, are characterized by reduced GR-c-Jun complex formation and increased expression of HDAC3 and HDAC5.

Trial registration

ISRCTN11017699 (Registration date: 15/11/2016).
Is GFR decline induced by SGLT2 inhibitor of clinical importance?
Authors: Günes-Altan Merve , Bosch Agnes , Striepe Kristina , Bramlage Peter , Schiffer Mario , Schmieder Roland E. , Kannenkeril Dennis
Published: May 2024

Background

Use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors often causes an initial decline in glomerular filtration rate (GFR). This study addresses the question whether the initial decline of renal function with SGLT2 inhibitor treatment is related to vascular changes in the systemic circulation.

Methods

We measured GFR (mGFR) and estimated GFR (eGFR) in 65 patients with type 2 diabetes (T2D) at baseline and after 12 weeks of treatment randomized either to a combination of empagliflozin and linagliptin (SGLT2 inhibitor based treatment group) (n = 34) or metformin and insulin (non-SGLT2 inhibitor based treatment group) (n = 31). mGFR was measured using the gold standard clearance technique by constant infusion of inulin. In addition to blood pressure (BP), we measured pulse wave velocity (PWV) under standardized conditions reflecting vascular compliance of large arteries, as PWV is considered to be one of the most reliable vascular parameter of cardiovascular (CV) prognosis.

Results

Both mGFR and eGFR decreased significantly after initiating treatment, but no correlation was found between change in mGFR and change in eGFR in either treatment group (SGLT2 inhibitor based treatment group: r=-0.148, p = 0.404; non-SGLT2 inhibitor based treatment group: r = 0.138, p = 0.460). Noticeably, change in mGFR correlated with change in PWV (r = 0.476, p = 0.005) in the SGLT2 inhibitor based treatment group only and remained significant after adjustment for the change in systolic BP and the change in heart rate (r = 0.422, p = 0.018). No such correlation was observed between the change in eGFR and the change in PWV in either treatment group.

Conclusions

Our main finding is that after initiating a SGLT2 inhibitor based therapy an exaggerated decline in mGFR was related with improved vascular compliance of large arteries reflecting the pharmacologic effects of SGLT2 inhibitor in the renal and systemic vascular bed. Second, in a single patient with T2D, eGFR may not be an appropriate parameter to assess the true change of renal function after receiving SGLT2 inhibitor based therapy.

Trial registration

clinicaltrials.gov (NCT02752113).
Correlation between the triglyceride-glucose index and left ventricular global longitudinal strain in patients with chronic heart failure: a cross-sectional study
Authors: Zhang Shuai , Liu Yan , Liu Fangfang , Ye Qing , Guo Dachuan , Xu Panpan , Wei Tianhao , Zhang Cheng , Lu Huixia
Published: May 2024

Background

Left ventricular global longitudinal strain (GLS) holds greater diagnostic and prognostic value than left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. The triglyceride-glucose (TyG) index serves as a reliable surrogate for insulin resistance (IR) and is strongly associated with several adverse cardiovascular events. However, there remains a research gap concerning the correlation between the TyG index and GLS among patients with chronic heart failure (CHF).

Method

427 CHF patients were included in the final analysis. Patient demographic information, along with laboratory tests such as blood glucose, lipids profiles, and echocardiographic data were collected. The TyG index was calculated as Ln [fasting triglyceride (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2].

Results

Among CHF patients, GLS was notably lower in the higher TyG index group compared to the lower TyG index group. Following adjustment for confounding factors, GLS demonstrated gradual decrease with increasing TyG index, regardless of the LVEF level and CHF classification.

Conclusion

Elevated TyG index may be independently associated with more severe clinical left ventricular dysfunction in patients with CHF.
Long non-coding RNA PXN-AS1 promotes glutamine synthetase-mediated chronic myeloid leukemia BCR::ABL1-independent resistance to Imatinib via cell cycle signaling pathway
Authors: Li Yifei , Yuan Shiyi , Zhou Ying , Zhou Jingwen , Zhang Xuan , Zhang Ping , Xiao Wenrui , Zhang Ying , Deng Jianchuan , Lou Shifeng
Published: May 2024

Background

Chronic myeloid leukemia (CML) is a common hematological malignancy, and tyrosine kinase inhibitors (TKIs) represent the primary therapeutic approach for CML. Activation of metabolism signaling pathway has been connected with BCR::ABL1-independent TKIs resistance in CML cells. However, the specific mechanism by which metabolism signaling mediates this drug resistance remains unclear. Here, we identified one relationship between glutamine synthetase (GS) and BCR::ABL1-independent Imatinib resistance in CML cells.

Methods

GS and PXN-AS1 in bone marrow samples of CML patients with Imatinib resistance (IR) were screened and detected by whole transcriptome sequencing. GS expression was upregulated using LVs and blocked using shRNAs respectively, then GS expression, Gln content, and cell cycle progression were respectively tested. The CML IR mice model were established by tail vein injection, prognosis of CML IR mice model were evaluated by Kaplan–Meier analysis, the ratio of spleen/body weight, HE staining, and IHC. PXN-AS1 level was blocked using shRNAs, and the effects of PXN-AS1 on CML IR cells in vitro and in vivo were tested the same as GS. Several RNA-RNA tools were used to predict the potential target microRNAs binding to both GS and PXN-AS1. RNA mimics and RNA inhibitors were used to explore the mechanism through which PXN-AS1 regulates miR-635 or miR-635 regulates GS.

Results

GS was highly expressed in the bone marrow samples of CML patients with Imatinib resistance. In addition, the lncRNA PXN-AS1 was found to mediate GS expression and disorder cell cycle in CML IR cells via mTOR signaling pathway. PXN-AS1 regulated GS expression by binding to miR-635. Additionally, knockdown of PXN-AS1 attenuated BCR::ABL1-independent Imatinib resistance in CML cells via PXN-AS1/miR-635/GS/Gln/mTOR signaling pathway.

Conclusions

Thus, PXN-AS1 promotes GS-mediated BCR::ABL1-independent Imatinib resistance in CML cells via cell cycle signaling pathway.

Graphic Abstract
Ownership and use of insecticide-treated nets in Myanmar: insights from a nationally representative demographic and health survey
Authors: Win Kyawt Mon , Show Kyaw Lwin , Sattabongkot Jetsumon , Aung Pyae Linn
Published: May 2024

Background

Malaria poses a substantial public health threat in Myanmar, indicating the need for rigorous efforts to achieve elimination of the disease nationwide by 2030. The use of insecticide-treated nets (ITNs) forms part of a pivotal strategy for preventing transmission. This study explored the ownership and use of ITNs in Myanmar and identified factors associated with non-use of ITNs.

Methods

Household datasets from the 2015–2016 Myanmar Demographic and Health Survey were utilised, which encompassed all household members except children under the age of five. Descriptive statistics and inferential tests, including simple and multiple logistics regression models and Pearson correlations, were employed for analysis. All analyses, taking the two-stage stratified cluster sampling design into account, used weighting factors and the “svyset” command in STATA. The ownership and use of bed nets were also visualised in QGIS maps.

Results

Among the 46,507 participants, 22.3% (95% CI 20.0%, 24.5%) had access to ITNs, with only 15.3% (95% CI 13.7, 17.1%) sleeping under an ITN the night before the survey. Factors associated with the non-use of ITNs included age category (15–34 years—aOR: 1.17, 95% CI 1.01, 1.30; 50+ years—aOR: 1.19, 95% CI 1.06, 1.33), location (delta or lowland—aOR: 5.39, 95% CI 3.94, 7.38; hills—aOR: 1.80, 95% CI 1.20, 2.71; plains—aOR: 3.89, 95% CI 2.51, 6.03), urban residency (aOR: 1.63, 95% CI 1.22, 2.17), and wealth quintile (third—aOR: 1.38, 95% CI 1.08, 1.75; fourth—aOR: 1.65, 95% CI 1.23, 2.23; fifth—aOR: 1.47, 95% CI 1.02, 2.13). A coherent distribution of the ownership and use of ITNs was seen across all states/regions, and a strong correlation existed between the ownership and use of ITNs (r: 0.9795, 95% CI 0.9377, 0.9933, alpha < 0.001).

Conclusions

This study identified relatively low percentages of ITN ownership and use, indicating the need to increase the distribution of ITNs to achieve the target of at least one ITN per every two people. Strengthening the use of ITNs requires targeted health promotion interventions, especially among relatively affluent individuals residing in delta or lowland areas, hills, and plains.
Prevalence of Leber hereditary optic neuropathy in the Community of Madrid (Spain), estimation with a capture-recapture method
Authors: Esteban-Vasallo María D. , Domínguez-Berjón M. Felicitas , Chalco-Orrego Juan Pablo , González Martín–Moro Julio
Published: May 2024

Background

Leber hereditary optic neuropathy (LHON) typically presents in young adults as bilateral painless subacute visual loss. Prevalence data are scarce. The aim of this study was to examine the validity of different ascertainment sources used in population-based rare diseases registries to detect cases, and to explore the impact of a capture-recapture method in the estimation of the prevalence of LHON in the Autonomous Community of Madrid (ACM) in 2022.

Methods

Descriptive cross-sectional population-based study. Potential LHON cases were detected by automatic capture from the healthcare information sources usually explored for the Regional Registry for Rare Diseases (SIERMA). Ophthalmologists provided data from their clinical registry. Positive predictive values (PPV) and sensitivity with 95% confidence intervals (CI) were estimated. Global and by sex prevalences were calculated with confimed cases and with those estimated by the capture-recapture method.

Results

A total of 102 potential LHON cases were captured from healthcare information sources, 25 of them (24.5%) finally were confirmed after revision, with an overall PPV of 24.5% (95%CI 17.2–33.7). By source, the electronic clinical records of primary care had the highest PPV (51.2, 95%CI 36.7–65.4). The ophthalmologists clinical registry provided 22 cases, 12 of them not detected in the automatic capture sources. The clinical registry reached a sensitivity of 59.5% (95%CI 43.5–73.6) and the combination of automatic capture sources reached a 67.6% (95%CI: 51.5–80.4). The total confirmed cases were 37, with a mean age of 48.9 years, and a men: women ratio of 2.4:1. Genetic information was recovered in 27 cases, with the m.3460 mutation being the most frequent (12 cases). The global prevalence was 0.55 cases/100,000 inhabitants (95%CI 0.40–0.75), and with the capture-recapture method reached 0.79 cases/100,000 (95%CI 0.60–1.03), a 43.6% higher, 1.15 cases/100,000 (95%CI 0.83–1.58) in men and 0.43 cases/100,000 (95%CI 0.26–0.70) in women.

Conclusions

The prevalence of LHON estimated in the ACM was lower than in other European countries. Population-based registries of rare diseases require the incorporation of confirmed cases provided by clinicians to asure the best completeness of data. The use of more specific coding for rare diseases in healthcare information systems would facilitate the detection of cases. Further epidemiologic studies are needed to assess potential factors that may influence the penetrance of LHON.
Social media threats and health among adolescents: evidence from the health behaviour in school-aged children study
Authors: Lahti Henri , Kokkonen Marja , Hietajärvi Lauri , Lyyra Nelli , Paakkari Leena
Published: May 2024

Background

Social media are immensely popular among adolescents. Thus, concerns have been raised about the threats adolescents encounter on social media and the possible negative health consequences, such as depressive symptoms and anxiety. This study investigated the prevalence of nine social media threats: (1) cyberbullying, (2) sexual harassment, (3) racism, (4) unauthorized distribution of sensitive material, (5) phishing attempts, (6) misinformation, (7) the sale or distribution of drugs, (8) harmful or dangerous social media challenges, (9) content causing appearance pressures. The study also investigated how individual and social factors, problematic social media use (PSMU), and online communication with strangers are associated with social media threat exposure, as well as the association between social media threats and self-rated health, depressive feelings, and anxiety symptoms.

Methods and findings

Nationally representative Health Behaviour in School-aged Children (HBSC) data from Finland were obtained from 2288 respondents aged 11, 13, and 15 years. Fixed effects regression models were applied. The most common threat, encountered daily and weekly, was misinformation. Regression models showed that individual and social factors, PSMU, and online communication with strangers explained adolescent exposure to social media threats in differing ways. Furthermore, certain factors (e.g., emotional intelligence, family support) were associated with encountering social media threats less frequently, whereas other factors (e.g., PSMU, online communication with strangers) were associated with more frequent encounters. Daily and weekly exposure to social media threats was systematically associated with poor self-rated health, frequent depressive feelings, and anxiety symptoms.

Conclusions

Our study highlights the need for intervention and health promotion efforts to mitigate adolescent exposure to social media threats and ensuing negative health consequences.
Late-onset dyshormonogenic goitrous hypothyroidism due to a homozygous mutation of the SLC26A7 gene: a case report
Authors: Sciarroni Elisabetta , Montanelli Lucia , Di Cosmo Caterina , Bagattini Brunella , Comi Simone , Pignata Luisa , Brancatella Alessandro , De Marco Giuseppina , Ferrarini Eleonora , Nencetti Chiara , Sessa Maria Rita , Latrofa Francesco , Santini Ferruccio , Tonacchera Massimo , Agretti Patrizia
Published: May 2024

Background

In this study, we used targeted next-generation sequencing (NGS) to investigate the genetic basis of congenital hypothyroidism (CH) in a 19-year-old Tunisian man who presented with severe hypothyroidism and goiter.

Case presentation

The propositus reported the appearance of goiter when he was 18. Importantly, he did not show signs of mental retardation, and his growth was proportionate. A partial organification defect was detected through the perchlorate-induced iodide discharge test. NGS identified a novel homozygous mutation in exon 18 of the SLC26A7 gene (P628Qfs*11), which encodes for a new iodide transporter. This variant is predicted to result in a truncated protein. Notably, the patient's euthyroid brother was heterozygous for the same mutation. No renal acid–base abnormalities were found and the administration of 1 mg of iodine failed to correct hypothyroidism.

Conclusions

We described the first case of goitrous CH due to a homozygous mutation of the SLC26A7 gene diagnosed during late adolescence.
MiR-653-5p drives osteoarthritis pathogenesis by modulating chondrocyte senescence
Authors: Lin Yucheng , Zhang Lu , Ji Mingliang , Shen Sinuo , Chen Yuzhi , Wu Shichao , Wu Xiaotao , Liu Nancy Q. , Lu Jun
Published: May 2024

Background

Due to the unclear pathogenesis of osteoarthritis (OA), effective treatment for this ailment is presently unavailable. Accumulating evidence points to chondrocyte senescence as a key driver in OA development. This study aims to identify OA-specific microRNAs (miRNAs) targeting chondrocyte senescence to alleviate OA progression.

Methods

We screened and identified miRNAs differentially expressed in OA and normal cartilage, then confirmed the impact of miR-653-5p on chondrocyte functions and senescence phenotypes through in vitro experiments with overexpression/silencing. We identified interleukin 6 (IL-6) as the target gene of miR-653-5p and confirmed the regulatory influence of miR-653-5p on the IL-6/JAK/STAT3 signaling pathway through gain/loss-of-function studies. Finally, we assessed the therapeutic efficacy of miR-653-5p on OA using a mouse model with destabilization of the medial meniscus.

Results

MiR-653-5p was significantly downregulated in cartilage tissues and chondrocytes from OA patients. Overexpression of miR-653-5p promoted chondrocyte matrix synthesis and proliferation while inhibiting chondrocyte senescence. Furthermore, bioinformatics target prediction and the luciferase reporter assays identified IL-6 as a target of miR-653-5p. Western blot assays demonstrated that miR-653-5p overexpression inhibited the protein expression of IL-6, the phosphorylation of JAK1 and STAT3, and the expression of chondrocyte senescence phenotypes by regulating the IL-6/JAK/STAT3 signaling pathway. More importantly, the cartilage destruction was significantly alleviated and chondrocyte senescence phenotypes were remarkably decreased in the OA mouse model treated by agomiR-653-5p compared to the control mice.

Conclusions

MiR-653-5p showed a significant decrease in cartilage tissues of individuals with OA, leading to an upregulation of chondrocyte senescence phenotypes in the articular cartilage. AgomiR-653-5p emerges as a potential treatment approach for OA. These findings provide further insight into the role of miR-653-5p in chondrocyte senescence and the pathogenesis of OA.
The effect of illness perception on psychosocial adjustment of patients with breast cancer and their spouses: actor–partner independence model
Authors: Wang Yan-feng , Liu An-kang , Dai Jin-zhen , Zhang Ji-ping , Chen Hui-hua , Jiang Xiao-hao , Tang Lu , He Yong-yue , Yang Qiao-hong
Published: May 2024

Objective

With the increase in the prevalence rate and improvements in the survival of breast cancer patients, there is a growing interest in understanding the level of psychosocial adjustment in these patients. The study aimed to describe the illness perception and psychosocial adjustment levels of both breast cancer patients and their spouses, to use the Actor-Partner Interdependence Model (APIM) to clarify the actor-partner relationships between spouses, and to explore the impact of illness perception on psychosocial adjustment to the disease within the joint actions of both spouses.

Methods

A total of 216 female patients with breast cancer and their spouses participated in the study. They were selected from two tertiary hospitals in Guangdong Province, China from October 2022 to May 2023 using a convenience sampling method. The participants were assessed using the Brief Illness Perception Questionnaire and the Psychosocial Adjustment to Illness Scale to examine the relationship between illness perception and psychosocial adjustment. AMOS24.0 was used to test and analyze the actor-partner interdependence model.

Results

The illness perception score (57.75 ± 10.91) was slightly higher than that of the spouse (57.10 ± 11.00), and the psychosocial adjustment score (64.67 ± 6.33) was slightly lower than that of the spouse (64.76 ± 7.49). The results of the actor-partner interdependence model indicated that there was a couple partner between breast cancer patients and their spouses: the spouse’s illness perception significantly affected the patient’s psychosocial adjustment (β = 0.095, p = 0.015); the patient’s illness perception also significantly affected the spouse’s psychosocial adjustment (β = 0.106, p = 0.033). Among them, the patient’s psychosocial adjustment was found to be related to the patient’s illness comprehensibility or coherence of illness (β = 0.433, p = 0.009), the spouse’s emotional illness representation (β = 0.218, p = 0.037), and the spouse’s illness comprehensibility or coherence of illness (β = 0.416, p = 0.007), while the spouse’s psychosocial adjustment was only related to the spouse’s illness comprehensibility or coherence of illness (β = 0.528, p = 0.007).

Conclusions

The psychosocial adjustment of breast cancer patients is affected by both their own and spouse’s illness perception. Therefore, in the future, the healthcare staff can implement early psychological interventions for patients diagnosed with breast cancer and their spouses as a unit to promote the psychosocial adjustment of them.
Laparoscopic surgery for De Garengeot’s hernia in a man after inguinal hernia surgery with a mesh plug: a case report and review of literature
Authors: Fujihata Shiro , Kuzuya Hiromasa , Kurimoto Masaaki , Shibata Tadashi , Sawai Hirozumi , Takiguchi Shuji
Published: May 2024

Background

De Garengeot’s hernia is a rare case of a femoral hernia that contains the appendix. Here we report a case of De Garengeot’s hernia that occurred in a male patient who had a history of inguinal hernia surgery using a mesh plug. There were no reports of De Garengeot’s hernia with a history of surgery for inguinal hernia, and the surgical question was whether we could successfully treat a patient with minimally invasive laparoscopic surgery using a mesh.

Case presentation

This case involved 75-year-old man with a history of right indirect inguinal hernia surgery using a mesh plug without on-lay mesh, who presented with a 5-day history of a right groin lump. Abdominal CT revealed an incarcerated appendix within the right femoral hernia and fluid collection around the appendix. Laparoscopic surgery was initiated and the incarcerated appendix was released with traction. There was no contamination around the appendix or the femoral ring, the appendix was removed, and the femoral hernia was repaired using mesh. Laparoscopic surgery was useful in first evaluating the inflammatory status of the appendix. As it was determined that there was little inflammation around the appendix and femoral ring, it was possible to repair the hernia using mesh.

Conclusions

De Garengeot’s hernias are rare and there is currently no standardized approach. Even if it is a recurrent hernia in the groin, laparoscopic surgery can be useful for diagnosis and treatment, but the use of mesh requires further careful consideration.
Interaction between urbanization and carbon emission in Guizhou Province
Authors: Jia Jingjing
Published: May 2024

Investigating interplay between urbanization and carbon emissions is crucial for reaching carbon peak objective. This study employs a VAR model to examine correlation between the urbanization rate and carbon emissions specifically within Guizhou Province, VAR model has obvious advantages in studying the dynamic relationship between them. The findings indicate that: (1) In Guizhou Province, there is a nuanced interplay between the urbanization rate and carbon emissions, with the magnitude and direction of their influence varying across different time intervals. (2) Carbon emissions in Guizhou Province exhibit a notable self-propelling effect, while concurrently, the urbanization rate demonstrates an inertia effect, which also contributes to its own advancement. (3) The influence of the urbanization rate on carbon emissions in Guizhou Province experiences gradual rise before plateauing, suggesting that the high-quality advancement of new urbanization in the region facilitates the achievement of carbon reduction objectives. Finally, policy recommendations are put forward: (1) Conscientiously implement the central ecological environment zoning control policies, such as: Guizhou Province Ecological environment zoning control Plan and Guizhou Province Urban and Rural Construction Carbon peak Implementation Plan and other policies. (2) Pay attention to the quality of Guizhou’s urbanization process. Solve the relationship between urbanization and carbon emissions, and realize the coordination and unification of urbanization and the carrying capacity of resources and environment. (3) Develop a new type of urbanization rich in Guizhou’s mountainous characteristics and promote the construction of low-carbon cities. Give full play to the regional characteristics of Guizhou’s mountainous areas, build a new type of urbanization with Guizhou’s mountainous characteristics, promote the construction of low-carbon cities in the process of urbanization development, and strengthen the coordinated development of ecological environment construction and urbanization.
To compare the HOMA-IR and metabolic profile in lean and obese subjects with non-alcoholic fatty liver disease
Authors: Nair Meenu C. , Stanley Lanord , Sivan Gisha , Kumar Janardanan Subramonia
Published: May 2024

Background and objective

Non-alcoholic fatty liver disease (NAFLD) is primarily perceived as a condition prevalent among obese individuals. Its pathogenesis is closely intertwined with metabolic syndrome components. However, the association between insulin resistance and NAFLD in nonobese individuals remains ambiguous. Observational studies have scrutinized the prevalence of insulin resistance and metabolic syndrome in lean NAFLD patients.

Materials and methods

This is an observational study, and NAFLD screening was carried out among inpatient and outpatient attendees at SRM Medical College’s General Medicine Department. Out of 200 screened patients meeting inclusion and exclusion criteria, 80 were diagnosed with non-alcoholic fatty liver disease (NAFLD). The assessment of metabolic syndrome was performed using the NCEP-ATP III criteria, allowing for comparison between groups concerning insulin resistance and metabolic parameters.

Results

Among NAFLD patients, those in the obese age group exhibited a higher prevalence of hypertension (57.8%; p < 0.001) and metabolic syndrome (75.6%; p < 0.0001). The lean NAFLD group showed elevated HOMA-IR levels (4.16) compared to obese NAFLD patients (2.92), with a significant statistical disparity (p < 0.0001). Additionally, the HSI value significantly increased in obese NAFLD patients (p < 0.00001).

Conclusion

Insulin resistance, a key factor in metabolic syndrome, is prevalent in lean individuals with non-alcoholic fatty liver disease (NAFLD), playing a pivotal role in its development. This resistance, linked to metabolic syndrome, promotes hepatic triglyceride and fatty acid accumulation, leading to NAFLD. Moreover, insulin resistance correlates significantly with weight gain in NAFLD patients.
Primary results from PATRICIA cohort C (SOLTI-1303), a randomized phase II study evaluating palbociclib with trastuzumab and endocrine therapy in pretreated HER2-positive and PAM50 luminal advanced breast cancer.
Authors: Ciruelos Eva , Pascual Tomás , Villacampa Guillermo , Pernas Sonia , Sanchez-Bayona Rodrigo , Ponce-Lorenzo Jose Juan , Cantos Sanchez de Ibarguren Blanca , Escrivá-de-Romaní Santiago , Perello Antonia , Montaño Alvaro , Martinez Eduardo , López González Ana , Melé Olivé Mireia , De La Haba Juan , Cortes Javier , Oliveira Mafalda , Villanueva Lorea , Gonzalez Xavier , Villagrasa Patricia , Prat Aleix
Published: May 2024

1008

Background: The PATRICIA trial (cohorts A-B) demonstrated that palbociclib plus trastuzumab (T) is safe and active in patients (pts) with T-pretreated HER2-positive Hormone Receptor-positive (HR+/HER2+) PAM50 Luminal advanced breast cancer (ABC). Here, we present the primary efficacy analysis of the randomized cohort C from the PATRICIA trial that compares the efficacy of palbociclib + T + endocrine therapy (ET) with treatment of physicians’ choice (TPC). Methods: PATRICIA (cohort C) is a randomized, open-label, phase II study conducted at 34 sites in Spain recruiting from August 2019 to August 2023. Pts with HER2+/HR+ and centrally tested PAM50 Luminal A or B intrinsic subtype ABC who had received at least one prior line of anti-HER2 based regimens were eligible. Pts were randomized 1:1 to Cohort C1 (Palbociclib 125 mg/day orally 3 weeks/1 week off + T + ET) or Cohort C2 (TPC, including T + any ET or chemotherapy (CT) + T, or T-DM1). The stratification factors were number of previous regimens for ABC and presence of visceral disease. The primary endpoint was progression-free survival (PFS). The trial was designed to recruit a total of 102 pts, having an 80% power with one-sided alpha=0.1 to detect a HR of 0.62 in favor of the palbociclib cohort. The study was closed after 73 pts were randomized due to slow recruitment. Results: At data cut-off, 264 pts were pre-screened, and 73 pts were randomized. Baseline pts characteristics are summarized in Table 1. In cohort C1, 50% of the pts received fulvestrant and 50% aromatase inhibitor as ET. In cohort C2, 37.1% of pts were treated with TDM-1, 45.7% with CT+ T, 11.4 % with ET + T and two pts withdrew their consent before starting the treatment. Palbociclib + T + ET was associated with longer PFS compared to TPC (median 9.1 vs 7.5 months, stratified HR=0.52 [95%CI 0.29-0.94]; two-sided p=0.031); 12-months PFS rates were 43.7% and 21.4%, respectively. The overall response rate was 18.9% (95% CI 8.6-35.7) in cohort C1 and 8.3% (95% CI 1.4-28.5) in cohort C2. Grade ≥3 adverse events occurred in 63.2% of pts in C1 and 45.5% in C2 cohort. The most frequent grade ≥3 adverse event in the experimental arm was neutropenia (55.3%). Conclusions: The combination of palbociclib, T and ET showed a statistically significant improvement in PFS in patients with previously treated PAM50 luminal A or B HER2+ advanced breast cancer, as compared to TPC. Clinical trial information: NCT02448420 . [Table: see text]
Real-world and clinical trial validation of a deep learning radiomic biomarker for PD-(L)1 immune checkpoint inhibitor response in stage IV NSCLC.
Authors: Sako Chiharu , Duan Chong , Maresca Kevin , Kent Sean , Aerts Hugo , Parikh Ravi Bharat , Simon George R. , Jordan Petr
Published: May 2024

102

Background: Immune checkpoint inhibitor (ICI) therapy is standard-of-care for treatment of mutation-negative advanced non-small cell lung cancer (NSCLC). However, given known inaccuracy of PD-(L)1 markers, there is an unmet need to better identify patients most likely to derive clinical benefit from ICI. We developed and externally validated a generalizable CT imaging-based biomarker to predict response to ICI. Methods: We developed and validated a deep learning radiomic biomarker using an internally curated real-world dataset (RWD) of 2,010 stage IV NSCLC patients treated with PD-(L)1 ICIs in academic and community settings from US and Europe. Patients with missing baseline imaging, missing follow-up data, or EGFR/ALK oncogenic driver mutations were excluded, resulting in a total of 1,188 subjects. This RWD consisted of a discovery cohort (Dataset A, N=844) and a temporally distinct holdout cohort (Dataset B, N=344), which were used to generate performance metrics of the biomarker. To test generalizability, we validated our biomarker in a prospective clinical trial dataset evaluating Sasanlimab in PD-(L)1 therapy-naïve, advanced NSCLC patients (NCT02573259, Dataset C, N=54). We utilized a two-stage learning approach to model 6-month PFS. First, we used an independent multi-task deep-learning feature extractor trained on 19,184 whole chest CT scans. Second, we input the extracted features into a Cox proportional hazard (CoxPH) model along with age, sex, and baseline lesion measurements (sum of longest diameter and distant metastases counts), and the model generated a time-dependent PFS function and a response score. We performed 6-fold cross-validation on Dataset A to train and evaluate the models, which were subsequently ensembled and applied to independent Datasets B and C. To assess independence from PD-L1 status and key demographic covariates, we herein report multivariate adjusted hazard ratios (HR) for the group identified as low-risk based on the biomarker. Results: In Dataset A, the biomarker showed a cross-validation PFS adjusted HR of 0.49 (95% CI 0.38-0.63) in the all-comers cohort and 0.28 (0.17-0.46) in the first-line ICI monotherapy cohort (1LMono). In Dataset B, the PFS adjusted HRs were 0.54 (0.35-0.83) in all-comers and 0.18 (0.05-0.61) in 1LMono. In Dataset C, the adjusted HRs were 0.30 (0.14-0.68) for PFS, 0.29 (0.10-0.83) for OS, 0.31 (0.14-0.72) for TTP. Conclusions: In our validations in RWD and clinical trial cohorts, a deep-learning radiomic biomarker based on routine pre-treatment CT scans predicted response to ICI and stratified patients independently from PD-L1 status. This tool may inform clinical decision-making, such as to help guide whether concomitant chemotherapy may not be needed. In future work, we plan to further validate our approach in larger prospective datasets and expand its use to new indications.
Efficacy of alpelisib (ALP) + fulvestrant (FUL) with rational use of metformin (MET) in patients with HR+/HER2- advanced breast cancer (ABC).
Authors: Filonenko Daria , Orlova Rashida , Gluzman Mark , Vakhitova Almira , Goryainova Alla , Grechukhina Katerina , Bykonya Irina , Zhukova Lyudmila
Published: May 2024

1049

Background: Hyperglycemia (HG) is an on-target effect of ALP, and prophylactic with metformin was shown to decrease the rate and severity of HG. Here we present efficacy and safety of ALP in a large cohort of patients with rational approach to metformin usage based on risk factors of HG. Methods: Patients (pts) with HR+/HER2- PIK3CAmut ABC were treated with ALP 300mg orally and FUL 500mg IM until disease progression or intolerance. The primary endpoints were progression free survival (PFS) and rate of grade 3/4 HG in different risk groups. Pts were stratified to risk groups of HG based on the algorithm (table 1) before starting ALP and received MET for prevention of HG. Results: A cohort comprised 139 pts, median lines of previous treatment in ABC was 3 (1-9): 88% received CDK4/6i, 60% - FUL, and 55% - chemotherapy (77) prior to ALP. The median PFS (mPFS) on ALP - was 7.0 (CI 95%: 5.0-8.9). The risk of HG was assessed in 138 pts: low (47), moderate (46), and high (42) risk, and 3 pts with type 2 diabetes mellitus. Any grade HG was reported in 62% pts, no cases HG G4 were detected. HG G3 was reported in 13% pts; 10% pts required ALP dose reduction to 250 mg due to HG G3; 3 pts (2%) discontinued ALP due to HG. The mPFS in our analysis was longer than in BYlieve trial in cohort C: 7.0 vs 5.6 mo. We suggest that prophylactic of HG allowed maintenance of full dose of ALP in most patients and thus increased the efficacy of ALP. Furthermore, in contrast to the METALLICA trial we distinguished a low risk group (33%) of pts who don’t need the prophylactic use of MET. Conclusions: Rational use of MET in pts with moderate and high risk of HG reduces the frequency and severity of HG, decreases the rate of ALP dose reductions and as a result may increase the efficacy of ALP. Pts with low risk of HG don’t need MET for HG prevention. [Table: see text]
Association of immune checkpoint inhibitor introduction and changes in survival disparities by health insurance coverage among individuals newly diagnosed with advanced cancers in the US.
Authors: Zhao Jingxuan , Graetz Ilana , Howard David , Yabroff Robin , Lipscomb Joseph
Published: May 2024

1580

Background: First approved by the US Food and Drug Administration (FDA) in 2011, immune checkpoint inhibitors (ICIs) have transformed treatment options for many cancers. Unfortunately, due to their high cost, individuals without health insurance coverage may not be able to afford them. Therefore, the introduction of ICIs may lead to greater disparities in cancer survival between patients with and without health insurance. This study examined the association of health insurance with changes in survival disparities associated with the introduction of ICIs. Methods: We identified individuals newly diagnosed at age 18-64 years at stage IV with any one of the following cancers with FDA approval for ICI treatment, including melanoma (first approved 03/25/2011, n=9992); HR+ HER- female breast cancer (02/03/2015, n=13632); non-small cell lung cancer (NSCLC; 03/04/2015, n=113866); and renal cell carcinoma (RCC; 11/23/2015, n=15403) from the National Cancer Database. Individuals with private health insurance or who were uninsured at the time of the cancer diagnosis were included. For each cancer, we applied a difference-in-differences (DD) approach to examine the changes in two-year overall survival before and after the ICI FDA approval date among individuals without health insurance compared to those with private health insurance, using flexible parametric survival models and controlling for key sociodemographic factors. Results: As shown (Table), among patients diagnosed with melanoma, 2-year survival rate increased from 16.33% pre-ICI approval to 27.04% after ICI approval among patients who were uninsured and increased from 28.22% to 45.45% among patients with private health insurance, with the disparity by health insurance status widened by 4.58 (95% confidence interval [CI] = 0.02 to 9.14) percentage points (ppt) after adjusting for sociodemographic factors. For patients diagnosed with stage IV NSCLC, the disparity by health insurance widened by 1.58 (95% CI = 0.52 to 2.64) ppt. Conclusions: The introduction of ICIs increased disparities in survival by health insurance status. Policies to improve health insurance coverage options or make new treatments more affordable to uninsured patients are needed. [Table: see text]
Post mastectomy reconstruction choice: Do race and ethnicity play a role?
Authors: Chappuis Catherine , Bernik Stephanie , Mohabbatizadeh Borna , Huang Lillian , Chen Mu-Hsun , Billman Elle , Shah Reanna , Amenta Jacquelyn , Mazumdar Madhu , Port Elisa R. , Balija Tara
Published: May 2024

1586

Background: The choice regarding reconstruction after mastectomy is based on multiple factors. We hypothesized that race and ethnicity are associated with decision making regarding reconstruction and choice for bilateral mastectomy among a diverse patient population with equal access to reconstructive options. Methods: A retrospective cohort study was performed of patients who underwent mastectomy with or without reconstruction for cancer or prophylaxis from 1/1/2019-12/31/2020 within a single health care system. Clinical and demographicfeatures were recorded. Study endpoints included reconstruction and contralateral prophylactic mastectomy (CPM) choice. Chi square and logistic regression analyses were performed with hypotheses tested at 5% significance level. Results: A total of 663 patients underwent mastectomy for cancer or prevention. Mean age was 54 (range: 24-93) and median BMI 25 (15-58). The majority of women included identified as Non-Hispanic White (NHW) (52%), with other women identifying as Hispanic, Asian, Non-Hispanic Black (NHB), or Other (Table). Of the total cohort, 647 (98%) patients had surgery for cancer, while 16 (2%) had surgery for prophylaxis. Among those with unilateral cancer (N=602, 91%), NHW women were more likely to get CPM (OR 2.12, p<.001), while NHB (OR 0.58, p=.02) and Asian women (OR 0.47, p=.01) were less likely to choose CPM. Asian women were less likely to undergo reconstruction compared to non-Asian women (OR=0.42, p=.01), while Hispanic women were almost twice as likely to undergo reconstruction compared to non-Hispanic women (OR 1.93, p=.016). Hispanic women were more likely to undergo a DIEP flap (OR 2.77, p <.001), while NHW women were more likely to choose implant reconstruction (OR 2.35, p<.001). Conclusions: In our hospital system, choice for reconstruction or CPM was found to differ based on race and ethnicity. NHW women were more likely to choose CPM and undergo implant-based reconstruction, Asian women were more likely to forgo reconstruction, and Hispanics were more likely to undergo DIEP flaps. Future analysis in this cohort will include other factors such as BMI, insurance status, religion, marital status, and employment status.[Table: see text]