bluuebunny/crossref_metadata_2025 huggingface dataset:
P-769. A chromosome 4p14 locus associates with higher protection from Leprosy in close family contacts of Lepromatous Leprosy cases in endemic regions
Authors: Mitra Debdeep
Published: January 2025

Background

Leprosy presents as an infectious disease with intricate genetic and immunological underpinnings. Genetic variations affecting cytokine genes and immune receptors, such as Toll-like receptor 1 (TLR1), may influence disease susceptibility. Close family contacts of individuals with slit skin positive lepromatous leprosy face a notably heightened risk of transmission. It is crucial to implement rigorous screening and early intervention protocols to promptly identify and manage latent infections, thereby curtailing potential disease dissemination within households and communities.

Methods

We conducted a genome-wide association study involving close family contacts of individuals with positive slit skin smears for Mycobacterium leprae. Our study comprised 131 lepromatous leprosy patients from prospective cohorts in an endemic region. Genotyping was performed using real-time polymerase chain reaction (RT-PCR) on the 7500 Real Time PCR System, employing SNP genotyping assays for pre-selected SNPs (rs7842033 and rs4167826) with specific primers and probes corresponding to the SNP of interest.

Results

Two-locus analyses of association of variants near rs7842033 showed a haplotype comprised of rs977477 and an IL9 missense variant, rs943138945, had the most significant association (p = 1.26x10-12).Our results showed no association between the SNP rs4052176 in NOD2 and leprosy in this population.

Conclusion

Situated on chromosome four (4p14), the TLR1 gene encodes a receptor that identifies glycolipids and lipopolysaccharides of M. leprae, stimulating the transcription factor nuclear factor-kappa B (NF-kβ) and enhancing the expression of pro-inflammatory genes. This gene may confer a degree of protection to close contacts against Leprosy.

Disclosures

All Authors: No reported disclosures
P-799. Eravacycline in the Management of Nontuberculous Mycobacteria (NTM) Infections: A Single-Centre Experience
Authors: Koomanan Narendran , Yvonne Zhou Peijun , Andrea Kwa Lay Hoon , Chung Shimin Jasmine
Published: January 2025

Background

Ubiquitous in nature, nontuberculous mycobacteria (NTM) have been associated with a wide spectrum of clinical infections. Treatment often requires the use of multiple antibiotics for a prolonged course. However, due to inherent drug resistance & treatment-limiting adverse events (AE), clinical outcomes are often suboptimal. In vitro studies have suggested that eravacycline (ERV) might be an effective component of NTM treatment regimens. However, clinical studies showing its safety & efficacy are limited. Hence, this study aims to assess the safety & efficacy of ERV treatment in NTM infections.Table 1:Clinical Characteristics of Patients Receiving Eravacycline (ERV) for the Treatment of NTM Infections

Methods

A retrospective, single-centre observation study reviewing the electronic medical records of all patients prescribed at least 48 hours of ERV from May 22 to April 23 for the treatment of NTM infections was conducted. For each course of ERV, demographic, microbiological & clinical outcome data was collected. Efficacy outcomes included treatment outcome at end of therapy. Safety outcomes included presence of any AE that led to discontinuation of ERV.

Results

During the study period, 16 patients received ERV containing regimens for the treatment of NTM infections (Table 1). A majority (75%) were being treated for pulmonary NTM infections & M. abscessus was the most isolated mycobacterium (87.5%). Treatment consisted of ERV, in combination with 2-3 antibiotics, for a median duration of 30 days (IQR: 20.3-35.5 days). To facilitate outpatient antimicrobial therapy (OPAT), most patients were transitioned from 1mg/kg q12h to 1.5mg/kg q24h dosing, with half (50%) eventually completing treatments via OPAT. At the end of ERV therapy, all patients demonstrated clinical improvement. AE led to discontinuation of ERV in 7 (43.8%) patients & dose reduction in 2 (12.5%) patients. Gastrointestinal (GI) AE was most prevalent (8/9, 88.9%) with improvements observed in both patients with dose reductions. Despite the truncated therapy, clinical improvement was still observed amongst patients with AE.

Conclusion

ERV would bolster the armamentarium of antibiotics against NTM infections, especially with its OPAT compatibility. However, in our population, a considerable proportion could not tolerate ERV. Dose reduction maybe be considered to improve ERV tolerability.

Disclosures

All Authors: No reported disclosures
P-800. High prevalence of treatment initiation delays among people diagnosed with multidrug-resistant tuberculosis-Dushanbe, Tajikistan—2019-2021
Authors: Tilloeva Zulfiya H , Horth Roberta , Mirzoev Azamdjon , Sharifov Rajabali , Nabirova Dilyara , Pirmahmadzoda Bobochon
Published: January 2025

Background

Multidrug resistant TB (MDR-TB) incidence is increasing in Central Asia, especially in Tajikistan, which is among the top 30 high-burden countries. Delays in treatment initiation are associated with increased transmission and poor health outcomes. In Dushanbe, the capital, the numbers and characteristics of people experiencing treatment delays are unknown. This information was needed to improve treatment programs and reduce transmission.Table 1.Characteristics of people with confirmed pulmonary MDR-TB experiencing treatment delays, Dushanbe, Tajikistan, 2019-2021

Methods

We conducted a cross-sectional study of all persons, ages ≥15 years old, diagnosed with pulmonary MDR-TB in 2019-2021. We abstracted data in 2022 from the national electronic TB database OpenMRS. Treatment delay was defined as >3 days from MDR-TB diagnosis to treatment initiation. MDR-TB confirmation was based on molecular tests (including line probe assay and GeneXpert) and phenotypic drug sensitivity tests. We calculated treatment delay percentage by group and percent difference and prevalence ratio; statistical testing is not applicable in our study, which captures the entire population.

Results

Of 100 people diagnosed with MDR-TB in 2019-2021, 6% had extensively drug-resistant (XDR) and 14% pre-XDR TB (Table 1). Also, 16% had diabetes, 8% had HIV, and 4% had hepatitis B and C. The median number of days from MDR-TB diagnosis to treatment initiation was 3 days (IQR: 1-7 days, Max: 225 days). Half (49%) experienced treatment delays. Proportion with delay was highest in 2020 (55%), the 1st year of the COVID-19 pandemic. Also, 2 of 6 people with XDR-TB, had delayed treatment. The proportion experiencing delay was 11% greater for males than females, 12% greater for older populations than younger, 15% greater for larger households ( >7 people) compared to smaller (3 or less), and 17% greater for those primary/secondary compared university education. There was a 42% difference in the proportion of patients with delays between the district with the highest and lowest proportion of delay (60% and 18%, respectively).

Conclusion

Half of people diagnosed with MDR-TB had treatment delays, including people with XDR-TB. Our findings highlight the need for immediate interventions that reduce time from diagnosis to treatment initiation, especially in districts and population groups with highest proportion of delayed treatment.

Disclosures

All Authors: No reported disclosures
P-802. The Predictive Accuracy of Clinical Covariates in Differentiating Staphylococcus aureus Bacteremia with and without Deep-Seated Foci of Infection via Application of Different Variable Selection Methodologies
Authors: Brunton Amanda E , Strnad Luke
Published: January 2025

Background

Staphylococcus aureus bacteremia (SAB) is a common bloodstream infection with a mortality rate of 20-30%. SAB is frequently associated with deep-seated foci of infection (DSFI) for which IDSA/ESCMID draft guidelines propose using clinical features early in evaluation to risk stratify for DSFI. However, literature for using combinations of clinical features to identify DSFI is limited, and the best process of variable selection is not defined. We explored variable selection methods to identify a combination of clinical features with the best predictive accuracy for identifying SAB with DSFI.

Methods

242 adults admitted to a 500-bed teaching hospital in Portland, Oregon with incident SAB between January 1, 2016 and December 31, 2017 were included. Patients who died, transitioned to comfort or discharged before medically advised within 7 days, or without an infectious disease consultation were excluded. Clinical information was abstracted from electronic medical records. We performed four variable selection methods: best subset, forward and backward stepwise regression, and the LASSO. Variables were selected using 5-fold cross-validation. We estimated the area under the receiver operating curve (AUC) and fit a multivariable logistic regression model to evaluate the expected performance of the predictor combinations.

Results

The cohort is described in Table 1 and 2. SAB with one or more DSFI was diagnosed in 65% (n=158). Predictors selected by the four methods are described in Table 3. The combination of bacteremia duration, hospital acquired SAB (haSAB), central venous catheter (CVC), skin and soft tissue infection (SSTI), and any cardiac device had the highest predictive accuracy with an AUC of 82%. The odds of DSFI is estimated to increase by 32% (95% CI; 15% to 53%) for every 1 day increase in bacteremia after adjusting for haSAB, CVC, SSTI and any cardiac device (Table 4).

Conclusion

Duration of bacteremia, haSAB, and CVC were included regardless of the variable selection method. Our model shows that combinations of clinical features are more predictive of DSFI than any single feature. Larger studies in different cohorts are needed to verify the predictive accuracy of these variables used in combinations to risk stratify for SAB with DSFI.

Disclosures

All Authors: No reported disclosures
P-803. A 10-year Retrospective Analysis of Staphylococcus aureus Bacteremia in a Philippine Tertiary Hospital
Authors: Navarro Alfred Daniel M , Henson Karl Evans R , Abad Cybele Lara R
Published: January 2025

Background

Staphylococcus aureus is a frequent cause of bacteremia in community and health care settings. There is limited data on S. aureus bacteremia (SAB) in the Philippines. This study describes the demographic profile and clinical characteristics of adult patients with SAB and their association with in-hospital mortality.

Methods

Patients aged ≥ 18 years with SAB from 1/1/2013 to 12/31/2023 were reviewed for study inclusion. SAB was defined as at least one blood culture result positive for S. aureus. Clinical characteristics, comorbidities, sources of infection, and clinical outcomes were recorded. Stepwise regression analysis was performed using STATA 13.1.

Results

314 patients with SAB were included; over half were male (185/314, 59%) and majority (62.5%) had Methicillin Susceptible Staphylococcus aureus (MSSA) bacteremia. The most common comorbidities were diabetes mellitus (146/314, 46.5%) and end stage renal disease (92/314, 29.3%). Mortality was high at 24.5% (77/314). Deceased patients were significantly older than survivors (65.7 years vs 59.0 years, p = 0.004). Among deceased patients, pleuropulmonary and intravascular catheter-related infections were the most common sources of infection comprising 29/77 (37.7%) and 12/77 (15.6%), respectively. Most patients (252/314, 80.3%) were referred to infectious diseases (ID) specialists. Clinical factors significantly associated with in-hospital mortality in the bivariate analysis included older age (OR=1.02, 95% CI 1.01-1.04), active malignancy (OR=3.25, 95% CI 1.68-6.26), hepatic failure (OR=3.25, 95% CI 1.01-10.51), hospital-acquired SAB (OR=3.97, 95% CI 2.09-7.53), septic shock (OR=54.0, 95% CI 7.2-404), and ICU admission (OR=22.17, 95% CI 9.16-53.69). In the multivariate regression model, hospital-acquired SAB (OR = 3.79, 95% CI 1.05 – 13.72, p = 0.002) and septic shock (OR = 1972.07, 95% CI 120.25 – 32339.3, p = < 0.001) increased the odds of in-hospital mortality, while referral to ID was protective (OR=0.11, 95% CI 0.01 – 0.90, p = 0.40).

Conclusion

The high mortality rate of SAB in this study is comparable to published data. Hospital-acquired SAB and the presence of septic shock significantly affect in-hospital mortality. Referral to ID specialist is associated with improved survival.

Disclosures

Karl Evans R. Henson, MD, FIDSA, BSV Biosciences: Honoraria|Cathay Drug Company, Inc: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria
P-804. Shorter vs. Longer Duration of Antibiotics in Pediatric Uncomplicated Gram Negative Bacteremia
Authors: Wesolowski Alec , Fernandez Marisol , Gilroy Kavitha
Published: January 2025

Background

Guidelines for uncomplicated gram negative bacteremia recommend 7-14 days of antibiotics; however there is limited pediatric evidence on duration of therapy. Studies in adult patients support a shorter duration of treatment and earlier transition to oral antibiotics. The primary objective of this study was to describe the local practice of a free standing children’s hospital in treating uncomplicated gram negative bacteremia in pediatric patients.

Methods

This single-center, retrospective study included pediatric patients from January 2022 to December 2023 with uncomplicated gram negative bacteremia. Those with chronic medical conditions, immunocompromised status, and polymicrobial bacteremia with mixed gram positive and gram negative organisms were excluded. Short-course antibiotic duration was defined as 7-10 days and long-course antibiotic duration was defined as > 10 days. Outcomes assessed included recurrent infection, readmission, length of stay, and adverse events between the two groups.

Results

156 positive blood cultures were identified and 31 patients met inclusion criteria. 16 patients had a total antibiotic duration of 7-10 days (mean 7.8 days) compared to 15 patients with an antibiotic duration >10 days (mean 14.6 days). The average length of hospitalization was 6.8 days in the 7-10 day group and 14.2 days in the >10 day group. The primary organism identified was E. coli (64.5%) from a urinary source (77.4%) with a majority of patients transitioning to oral antibiotics (61.3%) to complete therapy. Neither group developed a recurrent infection within 30 days; however, 3 patients in the >10 day group had a readmission within 30 days. More adverse events occurred in patients that received a longer duration of therapy (20%) vs those that received a shorter duration of therapy (6.3%).

Conclusion

7-10 days of total antibiotics may be appropriate in immunocompetent pediatric patients with uncomplicated gram negative bacteremia. Shorter duration of antimicrobial therapy is associated with decreased length of hospitalization and fewer adverse reactions without increased risk of recurrent infection.

Disclosures

All Authors: No reported disclosures
The evening complex component ELF3 recruits H3K4me3 demethylases to repress PHYTOCHROME INTERACTING FACTOR4 and 5 in Arabidopsis
Authors: Tian Shiyu , Zhang Shen , Xu Fan , Sun Qingbin , Xu Gang , Ni Min
Published: January 2025

In Arabidopsis (Arabidopsis thaliana), light and circadian clock signaling converge on PHYTOCHROME-INTERACTING FACTORS (PIFs) 4 and 5 to produce a daily rhythm of hypocotyl elongation. PIF4 and PIF5 expression is repressed at dusk by the evening complex (EC), consisting of EARLY FLOWERING3 (ELF3), ELF4, and LUX ARRHYTHMO (LUX). Here, we report that ELF3 recruits the JUMONJI (JMJ) H3K4me3 demethylases JMJ17 and JMJ18 to the PIF4 and PIF5 loci in the evening to remove their H3K4me3 marks. The association of JMJ17 and JMJ18 with the 2 genomic loci depends on the EC, and the H3K4me3 marks are enriched in the elf3 and jmj17 jmj18 mutants. Half of the globally differentially expressed genes are overlapping in elf3 and jmj17 jmj18. Cleavage Under Targets and Tagmentation sequencing analysis identified 976 H3K4me3-enriched loci in elf3. Aligning the H3K4me3-enriched loci in elf3 to genes with increased expression in elf3 and jmj17 jmj18 identified 179 and 176 target loci, respectively. Half of the loci are targeted by both ELF3 and JMJ17/JMJ18. This suggests a strong connection between the 2 JMJ proteins and EC function. Our studies reveal that an array of key genes in addition to PIF4 and PIF5 are repressed by the EC through the H3K4me3 demethylation pathway.
What Rose and Fell in Imperial China? State Strength, the Civil Service Examination and Inventiveness
Authors: Hui Victoria Tin-bor
Published: January 2025

Yuhua Wang's The Rise and Fall of Imperial China and Yasheng Huang's The Rise and Fall of the EAST (Exams, Autocracy, Stability, and Technology) take on grand history with big social science data. While both analyze China's rise and decline, they fundamentally disagree on what rose and fell, whether the imperial state was weak or strong, and whether the driving forces were social terrains or the emperor's designs. Wang's central puzzle is the “sovereign's dilemma” that presents a negative correlation between the emperor's duration and state strength. He uses elite social networks to explain why the Tang-Song transition brought about longer imperial reigns but weaker state strength. A closer look at Wang's data, however, suggests that state strength as fiscal capacity went up alongside the emperor's longevity in the Song. Huang offers a different “emperor's dilemma”: how the rational autocrat could ensure a competent yet loyal staff. Huang features “trailblazing emperors” who crafted the civil service examinations, called keju, to assert “end-to-end controls over the entire pipeline—nomination, evaluation, and final selections.” Keju also dissolves Wang's “sovereign's dilemma” by simultaneously enhancing ruler survival and state strength. For Huang, what rose and rose were keju and state strength; what rose and fell were societal diversity and inventiveness. Imperial China collapsed when the Qing abandoned keju. Both books inform today's China: if the autocrat's relentless pursuit of power through fragmenting the elites was “the final culprit” for imperial China's fall, readers should be deeply concerned about Xi Jinping's China.
Ultrasound-guided synovial tissue biopsy for people with rheumatoid arthritis: a micro-costing study
Authors: Chang Sainan , Rivellese Felice , Payne Katherine , Ide Zoë , Barton Anne , Pitzalis Costantino , Gavan Sean P
Published: January 2025

Objective

Identify and quantify the resource use and cost per patient of performing a US-guided synovial tissue biopsy for people with RA within a routine healthcare setting.

Method

A micro-costing study was performed from a healthcare system perspective (National Health Service England). A service pathway conceptual model described how the procedure will be embedded within routine care to inform management decisions. Consumables were estimated from existing standard operating procedures for synovial biopsies. Staff time was estimated by expert input (clinical rheumatologist and patient). The time for tissue sample acquisition was obtained from data within the biopsy-driven R4RA trial. Unit costs were sourced from historic purchase prices, published salary scales and public-facing list prices. One-way sensitivity analysis identified key drivers of total cost per patient. Scenario analyses explored the cost impact if less senior healthcare staff performed the biopsy or if an additional outpatient appointment was required to identify joint suitability.

Results

The total cost of US-guided synovial tissue biopsy was £356.24/patient (best-case estimate: £185.30; worst-case estimate: £812.46). The key driver of total cost was the time taken to perform tissue sample acquisition. The total cost was lower if a registrar performed the biopsy (£294.24) and higher if an additional outpatient appointment was required for joint selection (£438.98).

Conclusion

Interventions requiring synovial tissue samples to inform treatment selection or prognosis are emerging. The findings can inform cost parameters for future cost-effectiveness analyses. These results will help resource allocation and clinical decisions to improve the value of treatments for RA.
Foot peripheral sensory neuropathy: a frequent disabling manifestation in systemic sclerosis
Authors: Alcacer-Pitarch Begonya , Di Battista Marco , Redmond Anthony C , Keenan Anne-Maree , Di Donato Stefano , Buch Maya H , Del Galdo Francesco
Published: January 2025

Objectives

Peripheral sensory neuropathy (PSN) is an under-recognized feature in SSc. Moreover, SSc foot involvement is frequent but poorly investigated. We aimed to provide a detailed characterization of foot PSN in a large cohort of SSc patients, describing its associations with disease-specific features, physical disability and quality of life (QoL).

Methods

SSc patients and healthy controls (HCs) comparable for age and gender were enrolled in a cross-sectional observational case-control study. All subjects underwent a detailed quantitative sensory testing of feet evaluating touch, vibratory, thermal and pain sensitivity, ultimately investigating the presence of large and small fiber neuropathy. Patient-reported outcomes (Scleroderma Health Assessment Questionnaire, Manchester Foot Pain and Disability Index and Systemic Sclerosis Quality of Life Questionnaire) were administered to assess neuropathic symptoms, foot disability and QoL.

Results

A total of 109 SSc patients (88.1% female, median age 59.0 years) and 51 HC were enrolled. SSc patients presented with a significant impairment in each sensory parameter assessed (P ≤ 0.01 for all). Foot PSN was present in 85.3% of the patients, with 80% having small fiber and 57% large fiber neuropathy, co-existing in 51.4% of the cases. PSN was associated with age, smoking, foot ulceration, disease duration and corticosteroids use. Precisely, 80.6% subjects with PSN reported at least one neuropathic symptom. Patients with neuropathic symptoms reported worse physical function, worse foot disability and more impaired QoL.

Conclusion

Foot PSN presents as a common and disabling manifestation in SSc patients, involving small and large fibres. Hence, foot PSN assessment should be included as a part of the SSc workup.
The Association of Race, Rurality, and Neighborhood Disadvantage with Disease Severity at Initial Presentation in Cervical Spondylotic Myelopathy
Authors: Laskay Nicholas M.B. , Sun Yifei , Gross Evan G. , Hamo Mohammad A. , Howell Sasha , Mooney James , Godzik Jakub
Published: January 2025

Study Design.

Retrospective Cohort Study

Objectives.

To examine the impact of neighborhood-level socioeconomic factors on the delay of care and severity of disease among DCM patients at initial presentation.

Summary of Background Data.

Degenerative Cervical Myelopathy (DCM) is the most common etiology for spinal cord dysfunction among adults worldwide. Previous literature has suggested that social determinants of health including neighborhood-level socioeconomic status such as Area of Deprivation Index (ADI) may impact spine surgery outcomes in DCM.

Methods.

We performed a single-institution retrospective analysis of all patients undergoing spine surgery for the treatment of DCM from 2010 to 2022. Patients were identified using CPT and ICD9/10 codes. Data was collected via review of the electronic medical record. ADI was extracted from patients addresses. Multivariate and univariate analysis was used to assess the relationship between socioeconomic variables and myelopathy characteristics.

Results.

A total of 490 patients (Mean age: 60.3±11.3 y) were identified. Residence in rural areas was associated with higher Nurick score (OR 2.48,P=0.011), and lower mJOA score (OR 2.51, P=0.014) at presentation, and longer times to presentation (HR 0.48, P=0.003). Having high ADI was independently associated with shorter times to presentation (HR 1.46,P<0.001), but predicted higher Nurick score (OR 1.6, P=0.021) and lower mJOA score (OR 1.86,P=0.002). Unemployment was associated with longer times to presentation (HR 0.66,P<0.001), higher Nurick score (OR 4.5,P<0.001), and lower mJOA score (OR 4.51, P<0.001), while race was not.

Conclusions.

This is the first single institution study investigating the influence of neighborhood-level measures such as ADI on presentation status and disease burden in patients with DCM. High ADI predicts shorter disease duration but more severe DCM symptoms. Rural residence, unemployment, and non-private insurance were independently associated with prolonged and more severe DCM symptoms while race was not.

Level of Evidence.

3
Establishment of Scoring to Predict Severe Complication After Pyogenic Spondylodiscitis Surgery
Authors: Ukon Yuichiro , Takenaka Shota , Hirai Hiromasa , Sugiura Tsuyoshi , Sakai Yusuke , Fujimori Takahito , Furuya Masayuki , Kanie Yuya , Okada Seiji , Kaito Takashi
Published: January 2025

Study Design:

Retrospective cohort study using prospective database.

Objective:

This study aimed to establish a risk-scoring system for predicting severe complications after pyogenic spondylodiscitis surgery.

Summary of Background data:

Pyogenic spondylodiscitis surgery can cause severe complications.

Methods:

Grades III, IV, and V complications in the CD classification were defined as severe complications. A predictive scoring system for severe complications was developed using 7 risk factors identified from a cohort of 143 PS surgery patients from January 2013 to December 2017 described in a previous study. External validation used a separate cohort of 70 patients from 9 institutions identified from January 2018 to December 2021.

Results:

This first study proposed a risk predictive scoring system for severe complications [updated Charlson comorbidity index (≥3), 2; chronic pulmonary disease, 3; diabetes, 1; Gram-negative bacteria, 3; pyogenic osteoarthritis, 3; preoperative white blood count (≥1.0×104/μL), 2; preoperative platelet count (≤2.4×105/μL), 2]. The scoring system could well predict severe complications [area under the receiver operating curve (AUROC) value of 0.851]. There was classification into 3 risk groups: low–moderate risk (≤4), high risk (5 or 6), and very high risk (≥7), further simplified by the scoring system. Complication rates were 5.2% (low–moderate), 40.1% (high), and 84.2% (very high). In addition, external validation showed a very good AUROC value of 0.820.

Conclusions:

We developed a simple, externally validated scoring system for predicting severe complications after pyogenic spondylodiscitis surgery that will be helpful for clinicians involved in informed consent and intensive care unit management of high-risk patients.
A phase II study of anlotinib as first-line maintenance therapy for advanced ovarian cancer
Authors: Li Siyuan , Zhang Yanqin , Yang Rong , Yang Qingfan , Han Shuangyan , Li Dan , Zhang Zhenhua , Wen Qinglian
Published: January 2025

Anlotinib, a tyrosine kinase inhibitor, has shown encouraging antitumor activity in platinum-resistant/refractory ovarian cancer. The efficacy of anlotinib as maintenance therapy in advanced ovarian cancer remains unclear. Therefore, we designed this study to evaluate the efficacy and safety of anlotinib maintenance therapy following first-line treatment with paclitaxel and platinum-based chemotherapy in advanced ovarian cancer. In this single-arm, phase II clinical trial, patients with newly diagnosed advanced ovarian cancer were received anlotinib monotherapy as maintenance therapy once after a response to platinum-based chemotherapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival. From April 2020 to June 2021, 24 patients were enrolled in this study. The median follow-up was 40.17 months (interquartile range, 32.40–47.93 months). Of 21 patients with efficacy value, the median progression-free survival and median overall survival were 15.8 months (95% confidence interval, 6.8–24.8 months) and 43.8 months (95% confidence interval, 25.45–62.15 months). The quality-adjusted progression-free survival was 14.4 months and there were no observed treatment-related deaths or serious treatment-emergent adverse events, demonstrating the safety of anlotinib in maintenance therapy. Anlotinib shows significant potential as a first-line maintenance therapy for advanced ovarian cancer, extending survival and providing a reliable treatment option.
Introduction to the Wellness Mini-series. Burnout, Disengagement, and Other Psychological Quagmires: It’s Not All in Your Head
Authors: Khansa Ibrahim
Published: January 2025

Surgery is a state of mind. The brain controls the hands. As a result, “technical skills” are more mental than technical. In fact, physician burnout and poor well-being are independent predictors of major medical errors. Part of becoming a better surgeon is caring for one’s mind, and making sure one’s brain is healthy and happy. Therefore, the reader of this mini-series should read every article with the perspective that it can (and will) make them a better physician and surgeon. In this mini-series, 45 unique authors and 2 expert discussants compiled a comprehensive, evidence-based resource on physician wellness, including topics such as wellness during residency, oral board examination and every other career stage, the interface between work life and home life, physical well-being, self-awareness, mindfulness, mentorship, and dealing with aging parents and microaggressions. This mini-series truly covers the entire spectrum of physician wellness. In this article, I will provide a brief introduction to some important concepts, and the subsequent articles in the mini-series will go into much more practical detail.
The Intersection of a Life Partner and Professional Wellness for the Plastic Surgeon
Authors: Guest Rachel , Kapadia Kailash , Ledbetter Kelly , Martinez Carlos , Lin Ines C.
Published: January 2025

Our literature review describes the complicated intersection of the physician/surgeon’s professional practice and their spouse/domestic partner, acknowledging that the existing literature specific to plastic surgeons is limited. Nevertheless, the broader research of physicians and other surgical fields identifies many risk factors for work-home conflicts, which can negatively impact the surgeon and the spouse. Furthermore, certain studied groups have other unique challenges and considerations, such as women surgeons, residents, and dual-physician couples. Fortunately, the presence of a domestic partner has been shown to benefit the surgeon in multiple ways. Finally, we summarize some strategies to support and maintain this important relationship.
Importance of Exercise for Career Longevity: Maintaining Fitness, Strength, and Flexibility as a Plastic Surgeon
Authors: Rogoff Hunter M. , Byrnes Yasmeen M. , Kauffman Christian A.
Published: January 2025

The benefits of exercise for the general population are well established, although there is limited information focusing on its importance for plastic surgeons. Plastic surgery is arguably one of the most physically taxing fields within medicine due to lengthy operations that often require putting oneself in uncomfortable positions for the majority of the case, all while maintaining mental focus and discipline. It is essential to incorporate regular routines that can optimize a plastic surgeon’s mental and physical capacity both short- and long-term. Exercise provides multiple physical benefits and simultaneously contributes to better mental and emotional health. Unfortunately, it is rather uncommon for those within our profession to exercise on a regular basis, with lack of available time being a major contributor. Considering the physical nature of our specialty, plastic surgeons are susceptible to and frequently have debilitating musculoskeletal pain and injuries. In this article, we discuss the benefits of exercise on mental health and physician burnout, its potential for injury prevention, and strategies for implementing physical activity on a regular basis to sustain long and fulfilling careers as plastic surgeons.
Practicing Emotional Self-awareness to Build Surgeon Resilience
Authors: Tandon Damini , Taylor Ruby L. , Bialowas Christie , Johnson Anna Rose , Orr Jonah , Said Abdullah , Currie Kelly , Feinmann Marcie , Ridley Clare H. , Mackinnon Susan E.
Published: January 2025

As surgeons, we work in a high-stress, high-stakes environment to take care of our patients. In this setting, it is not uncommon for us to experience microaggressions—subtle or indirect actions or statements that communicate a demeaning or exclusionary message, often unintentionally. Microaggressions can bring us down, taking away from the fulfillment that attracted many of us to this profession. In this article, we introduce the Institute for Professional Excellence in Coaching energy leadership framework as a tool to understand and address microaggressions. We then apply it to real-life scenarios surgeons may encounter, demonstrating how this framework can help us to build resilience and recover our joy for our profession.
Internal Breast Lift: A New Method for Performing Internal Mastopexy
Authors: Duarte Getulio , Coelho Duarte Fabio , Federerigh Baisi Chagas Eduardo , Cervantes André
Published: January 2025

Background:

Mastopexy combined with implant placement is a complex cosmetic surgery due to the dual nature of the procedure. Various mammoplasty techniques and implant types add to its intricacy. This study aimed to evaluate the effectiveness of an internal breast lift in correcting pseudoptosis, grade 1 breast ptosis, and asymmetries, thereby offering a safer alternative with reduced morbidity and avoiding the creation of an inverted T scar.

Methods:

From January 2020 to January 2022, 20 female patients with pseudoptosis, grade I breast ptosis as per the Regnault classification, and a subareolar-to-mammary groove distance less than 7 cm were selected. For those with breast tissue hypertrophy, internal tissue resection maintained a minimum thickness of 3 cm. Patients with areolar asymmetries but without breast ptosis were also included. Surgical access was achieved via the mammary fold or periareolar approach. The procedure involved internal mastopexy between the mammary gland and the pectoralis major muscle’s superomedial portion, coupled with polyurethane implant insertion.

Results:

Significant elevations in the areola and breast tissue were noted in patients with pseudoptosis and grade I breast ptosis, with a notable pre- and postoperative difference (Student t test, P ≤ 0.050). Additionally, there was an improvement in areolar and breast tissue positioning in asymmetrical cases. Patient satisfaction and a 1-year follow-up were also part of the assessment.

Conclusions:

The internal breast lift emerges as a safe and aesthetically pleasing alternative for patients with pseudoptosis and grade I breast ptosis. It effectively enhances areolar symmetry without the need for an inverted T scar.
Prevalence and predictors of cirrhosis and portal hypertension in the United States
Authors: Younossi Zobair M. , de Avila Leyla , Racila Andrei , Nader Fatema , Paik James , Henry Linda , Stepanova Maria
Published: January 2025

Background and Aims:

There is a paucity of data about the prevalence of cirrhosis and portal hypertension in the US general population.

Approach and Results:

We used National Health and Nutrition Examination Surveys (NHANES 2017–2020) to estimate the prevalence of cirrhosis and clinically significant (CS)-portal hypertension in alcohol-associated liver disease (ALD), MetALD, viral hepatitis to include chronic hepatitis B (CHB) and chronic hepatitis C (CHC), and metabolic dysfunction–associated steatotic liver disease (MASLD). Cirrhosis was evaluated using liver stiffness measurement by transient elastography or FIB-4 score; CS-portal hypertension was defined through liver stiffness measurement and platelet count or the use of nonselective beta-blockers in the presence of cirrhosis.

The prevalence of chronic liver disease etiologies was ALD 0.85%, MetALD 3.38%, CHB 0.23%, CHC 0.73%, ALD + viral hepatitis 0.16%, and MASLD 33.05%. In the general population, the prevalence of ALD-cirrhosis was 0.08%, MetALD-cirrhosis 0.19%, CHB-cirrhosis 0.01%, CHC-cirrhosis 0.10%, MASLD-cirrhosis 1.27%, ALD + viral hepatitis-cirrhosis 0.08%, and other cirrhosis 0.87%. The prevalence of CS-portal hypertension in chronic liver disease was 1.31% in MetALD, 1.60% in CHB, 4.73% in CHC, 2.00% in MASLD, and 0.35% in controls, to yield a population prevalence of 0.98%. In multivariate analysis, excessive alcohol use, CHC, male sex, obesity, type 2 diabetes, and hypertension were independently associated with an increased risk of cirrhosis (all p<0.05). Predictors of having CS-portal hypertension in chronic liver disease included CHC, obesity, and type 2 diabetes (all p<0.05).

Conclusions:

The prevalence of cirrhosis in the United States is 2.6% while the prevalence of CS-portal hypertension is 0.98%. Individuals with MASLD comprise the majority of US residents with cirrhosis.
Femtosecond Laser–Assisted Pterygium Surgery Using a Customized Algorithm for Trapezoidal Conjunctival Grafts
Authors: Tan Shayne S. , Liu Yu-Chi , Han Evelina J. Y. , Ong Hon Shing , Ang Marcus , Riau Andri K. , Mehta Jodhbir S.
Published: January 2025

Purpose:

Conjunctival autografts (CAGs) are the gold standard treatment after pterygium resection, but it is challenging to achieve consistently thin Tenon-free CAGs with manual dissection. We herein report the reproducibility and clinical outcomes of a novel algorithm to produce customizable trapezoidal CAGs using femtosecond laser (femtosecond lasers)-assisted pterygium surgery.

Methods:

We first tested this algorithm in 4 pig eyes to show reproducibility. We then treated 15 pterygia of 14 patients using this algorithm. After manual pterygium excision, 7-mm x 10-mm preset trapezoidal CAGs were dissected with the Ziemer FEMTO LDV Z8 laser set at a 60 μm depth. The achieved thickness was measured with intraoperative optical coherence tomography, and the achieved area was calculated.

Results:

For the pig eyes, the average CAG length and width were 9.8 ± 0.1 mm and 7.3 ± 0.04 mm, respectively, with a mean deviation of 7.3% ± 3.2% and 7.5% ± 4.1%, respectively. The mean age of the patients was 56.8 ± 7.3 years. The programmed and achieved CAG areas were 70 mm2 and 72.5 ± 3.9 mm2, respectively, with a mean deviation of 4.7% ± 4.6%. The eventual CAG thickness was 59.5 ± 3.9 μm, with a minimal deviation of 4.4% ± 4.6%. The average time to remove the FSL-prepared CAG to unfold it onto the cornea was 19.9 ± 14.9 seconds. At the postoperative month 3 follow-up, no postoperative complications or recurrences occurred, and all donor CAG sites had completely healed.

Conclusions:

This novel algorithm using the FEMTO LDV Z8 in Femtosecond Laser–Assisted Pterygium Surgery provides consistent and customizable trapezoid ultrathin CAGs. Longer follow-up and larger cohorts will need to be studied for recurrence and complication rates.
Comparison of the efficacy of neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients: meta-analysis of randomized controlled trials
Authors: Zeng De-Xing , Liu Ruo-Nan , Ren Xian-Kun , Zhang Peng , Tang Ling-Han , Tan Ling , Ur Rehman Zia , Zhao Mao-Ru , Guo Peng , Zhang Pan , Du Jun , Qin Xian , Wan Shi-Yan , Deng Lu-Qian , Luo Ya-Jun , Liu Zi-Lin , Xiao Jiang-Wei
Published: January 2025

Background:

Preoperative neoadjuvant chemoradiotherapy (nCRT) is considered to be the standard treatment strategy for locally advanced rectal cancer (LARC); however, the risk of adverse events and postoperative recurrence remains significant. This study aimed to evaluate the non-inferiority of neoadjuvant chemotherapy (nCT) compared with nCRT in patients with LARC and to assess the possibility of eliminating radiotherapy on the basis of guaranteed efficacy.

Materials and methods:

We searched the PubMed, Embase, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing the efficacy of nCRT and nCT for LARC. The study protocol was registered with the Prospective Register of Systematic Reviews (PROSPERO).

Results:

A total of 2706 patients from 7 studies were included in the meta-analysis. There was no significant difference in overall survival (OS) or disease-free survival (DFS) between the nCT and nCRT groups. This study demonstrated a lower rate of infection (OR = 0.53, 95% CI = 0.34–0.82; P = 0.005), anastomotic leak (OR = 0.55, 95% CI = 0.34–0.87; P = 0.01), tumor regression grade (TRG) 0-1 (OR = 0.50, 95% CI = 0.36–0.69; P < 0.0001), preventive diverting ileostomy (OR = 0.41, 95% CI = 0.17–1.02; P = 0.05) and leukopenia (OR = 0.50, 95% CI = 0.25–1.01; P = 0.05) in the nCT group. However, there was no significant difference in the other toxic events, such as intestinal obstruction, urinary complications, diarrhoea, and surgical or pathological outcomes, such as clinical fistula, sphincter preservation, postoperative mortality (≤ 60 d), R0 resection, ypStage 0-I, positive circumferential resection margin (CRM +) or pathological complete response (pCR) between the two groups.

Conclusion:

This study indicated that OS and DFS were not lower in the nCT group than in the nCRT group. In addition, the nCT group had fewer complications. Preoperative nCT is expected to become a standard treatment option for most patients with stage II-III LARC. It is worth noting that radiotherapy can not be ignored for some patients who need to ensure the conversion effect of neoadjuvant therapy and strongly request to preserve organ function.
Utilizing explainable machine learning for progression-free survival prediction in high-grade serous ovarian cancer: insights from a prospective cohort study
Authors: Chen Zhuo , Ouyang Hui , Sun Botao , Ding Jiashan , Zhang Yu , Li Xinying
Published: January 2025

Background:

High-grade serous ovarian cancer (HGSOC) remains one of the most challenging gynecological malignancies, with over 70% of ovarian cancer patients ultimately experiencing disease progression. The current prognostic tools for progression-free survival (PFS) in HGSOC patients have limitations. This study aims to develop an explainable machine learning (ML) model for predicting PFS in HGSOC patients.

Methods:

Nine ML algorithms for PFS prediction were developed using a prospective cohort of 310 HGSOC patients consecutively enrolled from a large Chinese tertiary hospital between January 2017 and December 2020. The optimal model was internally validated using the 1000 bootstrap method. The SHapley Additive exPlanations (SHAP) method was employed to interpret the model in terms of feature importance and feature effects. The final model, constructed with the optimal feature subset, was deployed as an interactive web-based Shiny app.

Results:

The random survival forest (RSF) model demonstrated superior predictive performance compared to other ML models, the RFS model constructed with an optimal feature subset in the optimal imputed dataset achieved a superior 1000 bootstrap C-index of 0.755 (95% CI: 0.750–0.780) and a Brier score of 0.183 (95% CI: 0.175–0.190). SHAP analysis identified tumor residual, HE4, FIGO stage, T stage, CA125, age, ascites volume, platelet counts, and BMI as the top nine contributing factors. It also revealed potential nonlinear relationships and important thresholds between HE4, CA125, age, ascites volume, platelet counts, the body mass index, and PFS risk. Additionally, interaction effects were found between tumor residual and age, HE4, and CA125. Finally, an interactive web-based Shiny app for the model was developed and accessible at https://rsfmodels.shinyapps.io/ocRSF/.

Conclusion:

An explainable ML model for PFS prediction in HGSOC patients was developed with superior results. The publicly accessible web tool based on the optimized model facilitates its utility in clinical settings, potentially improving individualized patient management and treatment decision-making in HGSOC.
Effectiveness and safety of radionuclide synovectomy with Yttrium-90 hydroxyapatite in patients with inflammatory arthritis: a longitudinal study
Authors: Bonga Krishna Nikhila , Agrawal Kanhaiyalal , Tripathy Sujit Kumar , Meher Bikash Ranjan , Mishra Archana , Padhy Biswa Mohan
Published: January 2025

Background and objective

Yttrium-90 plays a significant role in managing drug-resistant inflammatory arthritis through radionuclide synovectomy, where the radioisotope is injected into the affected joint to alleviate pain and inflammation by targeting the synovial tissue. This study aims to evaluate the effectiveness and safety of Yttrium-90 hydroxyapatite radionuclide synovectomy in improving joint functionality, as judged by physicians, in patients with inflammatory arthritis who had not responded to conventional treatments.

Methods

Patients with inflammatory arthritis were recruited from the orthopedics department and referred to the nuclear medicine department for evaluation. A three-phase bone scan was conducted to identify eligible patients, who then received intra-articular injections of Yttrium-90 hydroxyapatite along with triamcinolone. After 48 h, patients underwent PET-CT imaging, followed by two follow-ups at 2 and 6 months to assess improvements in joint functionality and monitor for adverse reactions.

Results

Fifteen patients underwent radionuclide synovectomy. Significant improvements were observed between baseline and 2 months in joint restriction (P = 0.001), pain severity (P = 0.037), visual analog scale (VAS) (P = 0.004), and swelling (P = 0.002). At 6 months, further improvements were noted in joint restriction (P = 0.002), pain severity (P = 0.019), VAS (P = 0.013), and swelling (P = 0.023). However, no significant changes occurred between the 2- and 6-month follow-ups. One patient experienced radiation-induced skin necrosis, which resolved with conservative treatment, and another had self-limited skin rashes.

Conclusion

Yttrium-90 hydroxyapatite radionuclide synovectomy proved to be an effective and safe treatment for improving joint functionality in patients with drug-resistant inflammatory arthritis of the knee for up to 6 months.
Synergistic effects of doxorubicin and coumarin on colorectal cancer cell proliferation and EMT modulation: in silico and in vitro study
Authors: Khakbaraghi Mahsa , Nejati Majid , Abed Atena , Karimi Merat , Heydari Azhdar , Mirzaei Hamed
Published: January 2025

Background

Colorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related deaths globally. Doxorubicin (DOX), an anti-metabolite and anti-cancer agent, has shown promise in CRC treatment, while coumarin, a natural antioxidant, may help slow CRC growth. Although the combination of coumarin and DOX has been studied in other cancer types, its effectiveness in CRC remains unexamined. This study explores the impact of DOX and coumarin, individually and combined, on CRC cell growth and death, specifically focusing on C26 cells in vitro.

Methods

The MTT assay was used to assess cell proliferation, and RT-qPCR was employed to measure the expression of β-catenin, Twist, Cyclin D1, and ZEB-1.

Results

Both DOX and coumarin independently inhibited C26 cell growth, and their combination had a synergistic effect. RT-qPCR analysis indicated a reduction in Twist, Cyclin D1, and ZEB-1 expression following combination treatment, suggesting these molecules are involved in the observed anti-cancer effects. Molecular docking revealed that coumarin can target Twist, Cyclin D1, and ZEB-1 at the protein level.

Conclusion

Our findings validate the synergistic effect of DOX and coumarin in inhibiting the proliferation of C26 cells and propose the involvement of the Wnt pathway as a downstream mediator in this treatment. Future research is required to confirm the clinical applicability of this combined treatment for CRC and to elucidate its mechanisms within the body.