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1.
Eye (Lond) ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38710940

ABSTRACT

OBJECTIVES: The long-term risk of developing glaucoma after vitrectomy remains uncertain. This retrospective population-based cohort study aimed to explore this risk following vitrectomy for macular pucker or hole. METHODS: Utilizing Taiwan's National Health Insurance Research Database (NHIRD), we included patients who were older than 18 years and had undergone vitrectomy surgery between 2011 and 2019. Exclusions were made for patients with prior diagnoses of glaucoma, congenital or secondary glaucoma, as well as those who had received previous vitreoretinal treatments or had undergone multiple vitrectomies. RESULTS: After an average follow-up period of 51 and 53 months respectively for the vitrectomized and non-vitrectomized group, our results showed a relative risk of 1.71 for glaucoma development in the vitrectomized group. Higher adjusted hazard ratios were also observed for open-angle glaucoma and normal tension glaucoma. Increased risks were associated with male sex, obstructive sleep apnoea, and migraine. In the subgroup analysis, phakic eyes at baseline and those who had undergone cataract surgery post-vitrectomy were associated with a lower risk of glaucoma development during follow-up. Among all glaucoma events, pseudophakic status at baseline had the shortest interval to glaucoma development following vitrectomy. CONCLUSIONS: These findings underscore the potential relationship between vitrectomy and glaucoma onset, emphasizing the need for vigilant monitoring and early detection of glaucoma in post-vitrectomy patients.

2.
Pathology ; 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38719770

ABSTRACT

The use of next-generation sequencing (NGS) for monitoring measurable residual disease (MRD) in acute lymphoblastic leukaemia (ALL) has been gaining traction. This study aimed to investigate the utility of NGS in MRD monitoring for the three major fusion transcript (FT) subtypes of B-precursor ALL (B-ALL). The MRD results for 104 bone marrow samples from 56 patients were analysed through NGS and real time quantitative reverse transcription PCR (RT-qPCR) for the three major FTs: BCR::ABL1, TCF3::PBX1, and ETV6::RUNX1. To validate the NGS approach, NGS-MRD was initially compared with allele-specific oligonucleotide-qPCR-MRD, and the coefficient of determination was good (R2=0.8158). A subsequent comparison of NGS-MRD with FT-MRD yielded a good coefficient of determination (R2=0.7690), but the coefficient varied by subtype. Specifically, the R2 was excellent for TCF3::PBX1 ALL (R2=0.9157), good for ETV6::RUNX1 ALL (R2=0.8606), and subpar for BCR::ABL1 ALL (R2=0.5763). The overall concordance between the two methods was 83.7%, and an excellent concordance rate of 95.8% was achieved for TCF3::PBX1 ALL. Major discordance, which was defined as a >1 log difference between discordant NGS-MRD and FT-MRD, occurred in 6.7% of the samples, with all but one sample being BCR::ABL1 ALL. Among the four non-transplanted patients with BCR::ABL1-MRD (+)/NGS-MRD (-), three did not relapse after long-term follow-up. Our finding indicates that NGS-MRD has a better prognostic impact than RT-qPCR-MRD in ETV6::RUNX1 and BCR::ABL1 ALL, whereas in TCF3::PBX1 ALL, both methods exhibit comparable efficacy.

3.
Surg Obes Relat Dis ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38782611

ABSTRACT

BACKGROUND: The American Society for Metabolic and Bariatric Surgery (ASMBS) textbook serves as a comprehensive resource for bariatric surgery, covering recent advancements and clinical questions. Testing artificial intelligence (AI) engines using this authoritative source ensures accurate and up-to-date information and provides insight in its potential implications for surgical education and training. OBJECTIVES: To determine the quality and to compare different large language models' (LLMs) ability to respond to textbook questions relating to bariatric surgery. SETTING: Remote. METHODS: Prompts to be entered into the LLMs were multiple-choice questions found in "The ASMBS Textbook of Bariatric Surgery, second Edition. The prompts were queried into 3 LLMs: OpenAI's ChatGPT-4, Microsoft's Bing, and Google's Bard. The generated responses were assessed based on overall accuracy, the number of correct answers according to subject matter, and the number of correct answers based on question type. Statistical analysis was performed to determine the number of responses per LLMs per category that were correct. RESULTS: Two hundred questions were used to query the AI models. There was an overall significant difference in the accuracy of answers, with an accuracy of 83.0% for ChatGPT-4, followed by Bard (76.0%) and Bing (65.0%). Subgroup analysis revealed a significant difference between the models' performance in question categories, with ChatGPT-4's demonstrating the highest proportion of correct answers in questions related to treatment and surgical procedures (83.1%) and complications (91.7%). There was also a significant difference between the performance in different question types, with ChatGPT-4 showing superior performance in inclusionary questions. Bard and Bing were unable to answer certain questions whereas ChatGPT-4 left no questions unanswered. CONCLUSIONS: LLMs, particularly ChatGPT-4, demonstrated promising accuracy when answering clinical questions related to bariatric surgery. Continued AI advancements and research is required to elucidate the potential applications of LLMs in training and education.

4.
Acta Cardiol Sin ; 40(3): 331-339, 2024 May.
Article in English | MEDLINE | ID: mdl-38779166

ABSTRACT

Background: The Laceration of the Anterior Mitral leaflet to Prevent Outflow ObtructioN (LAMPOON) procedure may be performed from the leaflet tip to base to prevent left ventricular outflow tract obstruction (LVOTO) in patients with high-risk anatomy undergoing valve-in-valve (VIV) or valve-in-(complete)-ring (VIR) transcatheter mitral valve replacement (TMVR). Methods and Results: Thirteen consecutive patients (6 females, average age 67.7 years) with a mean left ventricular ejection fraction of 60%, a median STS score of 3.2%, and degenerative surgical mitral bioprosthesis or ring were treated with a combined, single-stage procedure of preventive LAMPOON and trans-septal TMVR with SAPIEN 3 valves (Edwards Lifesciences, Irvine, CA). Under real-time 3-dimensional transesophageal echocardiography (RT 3D-TEE) guidance, we included the rendezvous technique in the LAMPOON procedure, and all 13 patients were successfully treated by tip-to-base LAMPOON and TMVR. The use of a modified LAMPOON procedure, aided by a rendezvous technique and guided by RT 3D-TEE imaging, offers precise guidance for positioning and aligning the guidewire. This approach not only reduces the need for fluoroscopy and shortens procedure times, but also significantly increases the likelihood of a successful outcome. Importantly, none of the patients in our study experienced unintentional aortic or aortic valve injuries, nor did they develop significant LVOTO following TMVR. In 11 of the 13 (85%) patients, we used a transcatheter SENTINELTM cerebral protection device (Boston Scientific, Marlborough, MA) for stroke prevention and capture of debris ≥ 2 mm were detected in 8/11 (73%) of the cases. Conclusions: Utilizing intra-operative RT 3D-TEE in conjunction with the rendezvous technique can make the tip-to-base LAMPOON procedure even safer and more effective for patients undergoing VIV or VIR TMVR. Our study also suggests that cerebral protection is indicated in patients undergoing TMVR.

5.
Aging (Albany NY) ; 162024 May 16.
Article in English | MEDLINE | ID: mdl-38761181

ABSTRACT

BACKGROUND: Valvular heart disease (VHD) is becoming increasingly important to manage the risk of future complications. Electrocardiographic (ECG) changes may be related to multiple VHDs, and (AI)-enabled ECG has been able to detect some VHDs. We aimed to develop five deep learning models (DLMs) to identify aortic stenosis, aortic regurgitation, pulmonary regurgitation, tricuspid regurgitation, and mitral regurgitation. METHODS: Between 2010 and 2021, 77,047 patients with echocardiography and 12-lead ECG performed within 7 days were identified from an academic medical center to provide DLM development (122,728 ECGs), and internal validation (7,637 ECGs). Additional 11,800 patients from a community hospital were identified to external validation. The ECGs were classified as with or without moderate-to-severe VHDs according to transthoracic echocardiography (TTE) records, and we also collected the other echocardiographic data and follow-up TTE records to identify new-onset valvular heart diseases. RESULTS: AI-ECG adjusted for age and sex achieved areas under the curves (AUCs) of >0.84, >0.80, >0.77, >0.83, and >0.81 for detecting aortic stenosis, aortic regurgitation, pulmonary regurgitation, tricuspid regurgitation, and mitral regurgitation, respectively. Since predictions of each DLM shared similar components of ECG rhythms, the positive findings of each DLM were highly correlated with other valvular heart diseases. Of note, a total of 37.5-51.7% of false-positive predictions had at least one significant echocardiographic finding, which may lead to a significantly higher risk of future moderate-to-severe VHDs in patients with initially minimal-to-mild VHDs. CONCLUSION: AI-ECG may be used as a large-scale screening tool for detecting VHDs and a basis to undergo an echocardiography.

6.
Virchows Arch ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733379

ABSTRACT

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.

7.
Nat Commun ; 15(1): 4343, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773197

ABSTRACT

Prodrugs have been explored as an alternative to conventional chemotherapy; however, their target specificity remains limited. The tumor microenvironment harbors a range of microorganisms that potentially serve as tumor-targeting vectors for delivering prodrugs. In this study, we harness bacteria-cancer interactions native to the tumor microbiome to achieve high target specificity for prodrug delivery. We identify an oral commensal strain of Lactobacillus plantarum with an intrinsic cancer-binding mechanism and engineer the strain to enable the surface loading of anticancer prodrugs, with nasopharyngeal carcinoma (NPC) as a model cancer. The engineered commensals show specific binding to NPC via OppA-mediated recognition of surface heparan sulfate, and the loaded prodrugs are activated by tumor-associated biosignals to release SN-38, a chemotherapy compound, near NPC. In vitro experiments demonstrate that the prodrug-loaded microbes significantly increase the potency of SN-38 against NPC cell lines, up to 10-fold. In a mouse xenograft model, intravenous injection of the engineered L. plantarum leads to bacterial colonization in NPC tumors and a 67% inhibition in tumor growth, enhancing the efficacy of SN-38 by 54%.


Subject(s)
Lactobacillus plantarum , Prodrugs , Xenograft Model Antitumor Assays , Prodrugs/pharmacology , Prodrugs/therapeutic use , Animals , Humans , Mice , Cell Line, Tumor , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/microbiology , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/pathology , Tumor Microenvironment/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Mice, Nude , Female , Mice, Inbred BALB C
8.
Int J Environ Health Res ; : 1-11, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38590026

ABSTRACT

The roles of aryl hydrocarbon receptor (AhR), AhR-nuclear translocator (ARNT), and AhR repressor (AhRR) genes in the elevation of cord blood IgE (CbIgE) remained unclear. Our aims were to determine the polymorphisms of AhR, ARNT, and AhRR genes, cord blood AhR (CBAhR) level, and susceptibility to elevation of CbIgE. 206 infant-mother pairs with CbIgE>=0.35 IU/ml and 421 randomly selected controls recruited from our previous study. Genotyping was determined using TaqMan assays. Statistical analysis showed AhR rs2066853 (GG vs. AA+AG: adjusted OR (AOR)=1.5, 95%CI=1.10-2.31 and AOR=1.60, 95%CI=1.06-2.43, respectively) and the combination of AhR rs2066853 and maternal total IgE (mtIgE)>=100 IU/ml were significantly correlated with CbIgE>=0.35 IU/ml or CbIgE>=0.5 IU/ml. CBAhR in a random subsample and CbIgE levels were significantly higher in infants with rs2066853GG genotype. We suggest that infant AhR rs2066853 and their interactions with mtIgE>=100 IU/ml significantly correlate with elevated CbIgE, but AhRR and ARNT polymorphisms do not.

9.
Cancer Med ; 13(7): e7166, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38572926

ABSTRACT

BACKGROUND: Studies have shown that some single nucleotide polymorphisms (SNPs) could serve as excellent markers in foretelling the treatment outcome of interferon (IFN) in myeloproliferative neoplasms (MPN). However, most work originated from western countries, and data from different ethnic populations have been lacking. METHODS: To gain insights, targeted sequencing was performed to detect myeloid-associated mutations and SNPs in eight loci across three genes (IFNL4, IFN-γ, and inosine triphosphate pyrophosphatase [ITPA]) to explore their predictive roles in our cohort of 21 ropeginterferon alpha-2b (ROPEG)-treated MPN patients, among whom real-time quantitative PCR was also performed periodically to monitor the JAK2V617F allele burden in 19 JAK2V617F-mutated cases. RESULTS: ELN response criteria were adopted to designate patients as good responders if they achieved complete hematological responses (CHR) within 1 year (CHR1) or attained major molecular responses (MMR), which occurred in 70% and 45% of the patients, respectively. IFNL4 and IFN-γ gene SNPs were infrequent in our population and were thus excluded from further analysis. Two ITPA SNPs rs6051702 A>C and rs1127354 C>A were associated with an inferior CHR1 rate and MMR rate, respectively. The former seemed to be linked to grade 2 or worse hepatotoxicity as well, although the comparison was of borderline significance only (50%, vs. 6.7% in those with common haplotype, p = 0.053). Twelve patients harbored 19 additional somatic mutations in 12 genes, but the trajectory of these mutations varied considerably and was not predictive of any response. CONCLUSIONS: Overall, this study provided valuable information on the ethnics- and genetics-based algorithm in the treatment of MPN.


Subject(s)
Myeloproliferative Disorders , Neoplasms , Humans , Myeloproliferative Disorders/drug therapy , Myeloproliferative Disorders/genetics , Treatment Outcome , Haplotypes , Germ Cells , Interferon Lambda , Interleukins/genetics
10.
Colorectal Dis ; 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38576076

ABSTRACT

AIM: Preoperative frailty has been associated with adverse postoperative outcomes in various populations, but of its use in patients with inflammatory bowel disease (IBD) remains sparse. The present study aimed to characterize the impact of frailty, as measured by the modified frailty index (mFI), on postoperative clinical and resource utilization outcomes in patients with IBD. METHODS: This retrospective population-based cohort study assessed patients from the National Inpatient Sample database from 1 September 2015 to 31 December 2019. Corresponding International Classification of Diseases 10th Revision Clinical Modification codes were used to identify adult patients (>18 years of age) with IBD, undergoing either small bowel resection, colectomy or proctectomy. Patient demographics and institutional data were collected for each patient to calculate the 11-point mFI. Patients were categorized as either frail or robust using a cut-off of 0.27. Primary outcomes were postoperative in-hospital morbidity and mortality, whilst secondary outcomes included system-specific morbidity, length of stay, in-hospital healthcare costs and discharge disposition. Logistic and linear regression models were used for primary and secondary outcomes. RESULTS: Overall, 7144 patients with IBD undergoing small bowel resection, colectomy or proctectomy were identified, 337 of whom were classified as frail (i.e., mFI < 0.27). Frail patients were more likely to be women, older, have lower income and a greater number of comorbidities. After adjusting for relevant covariates, frail patients were at greater odds of in-hospital mortality (adjusted odds ratio [aOR] 5.42, 95% CI 2.31-12.77, P < 0.001), overall morbidity (aOR 1.72, 95% CI 1.30-2.28, P < 0.001), increased length of stay (adjusted mean difference 1.3 days, 95% CI 0.09-2.50, P = 0.035) and less likely to be discharged to home (aOR 0.59, 95% CI 0.45-0.77, P < 0.001) compared to their robust counterparts. CONCLUSIONS: Frail IBD patients are at greater risk of postoperative mortality and morbidity, and reduced likelihood of discharge to home, following surgery. This has implications for clinicians designing care pathways for IBD patients following surgery.

11.
Eye (Lond) ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632472

ABSTRACT

OBJECTIVES: To evaluate the morphology of lamina cribrosa (LC) in preterm school-aged children. METHODS: A study of 120 eyes from 120 patients, including 42 full-term children (control group), 41 preterm children without retinopathy of prematurity (ROP), 16 children with ROP treated with intravitreal bevacizumab (IVB), and 21 children with ROP treated with laser. Five parameters of LC were measured by optical coherence tomography, including Bruch's membrane opening (BMO) diameter, minimum rim width (MRW), LC depth, prelaminar tissue (PLT) thickness, and LC curvature index (LCCI). RESULTS: The PLT thickness increased with age in full-term and preterm children (ß = 30.1, P = 0.003 and ß = 19.6, P < 0.001, respectively). LC depth and LCCI showed no differences between full-term and preterm children. Worse refractive errors in preterm children were associated with greater MRW and PLT thickness (ß = -17.1, P = 0.001 and ß = -5.7, P = 0.03, respectively). However, this relationship was not found in full-term children. Laser-treated children had greater MRW, PLT, temporal peripapillary retinal nerve fibre layer, and foveal thickness than full-term or other preterm children (all P < 0.05). CONCLUSIONS: Prematurity and ROP treatment may have an impact on the structural development of the LC. Refractive status plays a vital role in the LC structure of preterm children. This highlights the refractive errors of preterm children at school age that merit greater attention.

12.
Surg Obes Relat Dis ; 2024 Mar 24.
Article in English | MEDLINE | ID: mdl-38644078

ABSTRACT

BACKGROUND: The formulation of clinical recommendations pertaining to bariatric surgery is essential in guiding healthcare professionals. However, the extensive and continuously evolving body of literature in bariatric surgery presents considerable challenge for staying abreast of latest developments and efficient information acquisition. Artificial intelligence (AI) has the potential to streamline access to the salient points of clinical recommendations in bariatric surgery. OBJECTIVES: The study aims to appraise the quality and readability of AI-chat-generated answers to frequently asked clinical inquiries in the field of bariatric and metabolic surgery. SETTING: Remote. METHODS: Question prompts inputted into AI large language models (LLMs) and were created based on pre-existing clinical practice guidelines regarding bariatric and metabolic surgery. The prompts were queried into 3 LLMs: OpenAI ChatGPT-4, Microsoft Bing, and Google Bard. The responses from each LLM were entered into a spreadsheet for randomized and blinded duplicate review. Accredited bariatric surgeons in North America independently assessed appropriateness of each recommendation using a 5-point Likert scale. Scores of 4 and 5 were deemed appropriate, while scores of 1-3 indicated lack of appropriateness. A Flesch Reading Ease (FRE) score was calculated to assess the readability of responses generated by each LLMs. RESULTS: There was a significant difference between the 3 LLMs in their 5-point Likert scores, with mean values of 4.46 (SD .82), 3.89 (.80), and 3.11 (.72) for ChatGPT-4, Bard, and Bing (P < .001). There was a significant difference between the 3 LLMs in the proportion of appropriate answers, with ChatGPT-4 at 85.7%, Bard at 74.3%, and Bing at 25.7% (P < .001). The mean FRE scores for ChatGPT-4, Bard, and Bing, were 21.68 (SD 2.78), 42.89 (4.03), and 14.64 (5.09), respectively, with higher scores representing easier readability. CONCLUSIONS: LLM-based AI chat models can effectively generate appropriate responses to clinical questions related to bariatric surgery, though the performance of different models can vary greatly. Therefore, caution should be taken when interpreting clinical information provided by LLMs, and clinician oversight is necessary to ensure accuracy. Future investigation is warranted to explore how LLMs might enhance healthcare provision and clinical decision-making in bariatric surgery.

13.
Anal Sci ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649628

ABSTRACT

Analyzing new psychoactive substances (NPSs) in forensic laboratories present a formidable challenge globally. Within illicit drug analysis, gas chromatography-mass spectrometry (GC-MS) emerges as a robust analytical tool. This study endeavors to assess and compare peak resolution in the analysis of illicit drugs, specifically focusing on 21 synthetic cathinones, encompassing 9 cathinone isomers. Varied GC-MS operating conditions, including distinct GC-MS columns and thermal gradients, were systematically employed for the simultaneous analysis of these synthetic cathinones. The study utilized HP-1 nonpolar and HP-5MS low-bleed columns to achieve optimal analyte resolution through modulation of GC-MS oven conditions. Mass spectra were meticulously recorded within a mass-to-charge (m/z) range spanning from 40 to 500 in full scan mode. The data showed that the cathinone isomers slightly differed in retention times and mass spectra. The GC oven conditions affected the peak resolution for chromatographic separation even with the same column. The peak resolution improved using a slower thermal gradient heat speed with a prolonged analysis time. Conclusively, the interplay of GC columns and thermal gradients emerged as pivotal factors impacting peak resolution in the analysis of illicit drugs. These empirical insights contribute to a nuanced understanding of peak resolution dynamics and facilitate the identification of synthetic cathinones, including their isomers, in seized materials through the judicious application of GC-MS methodologies.

14.
Blood ; 2024 04 30.
Article in English | MEDLINE | ID: mdl-38687605

ABSTRACT

Mutations in UBA1, which are disease-defining for VEXAS syndrome, have been reported in patients diagnosed with myelodysplastic syndromes (MDS). Here, we define the prevalence and clinical associations of UBA1 mutations in a representative cohort of patients with MDS. Digital droplet PCR profiling of a selected cohort of 375 male patients lacking MDS disease-defining mutations or established WHO disease classification identified 28 patients (7%) with UBA1 p.M41T/V/L mutations. Using targeted sequencing of UBA1 in a representative MDS cohort (n=2,027), we identified an additional 27 variants in 26 patients (1%), which we classified as likely/pathogenic (n=12) and unknown significance (n=15). Among the total 40 patients with likely/pathogenic variants (2%), all were male and 63% were classified by WHO2016 as MDS-MLD/SLD. Patients had a median of one additional myeloid gene mutation, often in TET2 (n=12), DNMT3A (n=10), ASXL1 (n=3), or SF3B1 (n=3). Retrospective clinical review where possible showed that 83% (28/34) UBA1-mutant cases had VEXAS-associated diagnoses or inflammatory clinical presentation. The prevalence of UBA1-mutations in MDS patients argues for systematic screening for UBA1 in the management of MDS.

16.
Br J Haematol ; 204(4): 1344-1353, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38479427

ABSTRACT

This study investigates the potential utility of IKZF1 deletion as an additional high-risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD-guided TPOG-ALL-2013 protocol using 412 newly diagnosed B-ALL patients aged 1-18. IKZF1 status was determined using multiplex ligation-dependent probe amplification. IKZF1 deletions, when co-occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1plus. Both IKZF1 deletion (14.6%) and IKZF1plus (7.8%) independently predicted poorer outcomes in B-ALL. IKZF1plus was observed in 4.1% of Philadelphia-negative ALL, with a significantly lower 5-year event-free survival (53.9%) compared to IKZF1 deletion alone (83.8%) and wild-type IKZF1 (91.3%) (p < 0.0001). Among patients with Day 15 MRD ≥0.01%, provisional high-risk patients with IKZF1plus exhibited the worst outcomes in event-free survival (42.0%), relapse-free survival (48.0%) and overall survival (72.7%) compared to other groups (p < 0.0001). Integration of IKZF1plus and positive Day 15 MRD identified a subgroup of Philadelphia-negative B-ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment.


Subject(s)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Gene Deletion , Ikaros Transcription Factor/genetics , Neoplasm Recurrence, Local , Neoplasm, Residual/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Risk Assessment , Transcription Factors , Infant , Child, Preschool , Adolescent
17.
J Surg Res ; 297: 71-82, 2024 May.
Article in English | MEDLINE | ID: mdl-38447338

ABSTRACT

INTRODUCTION: Studies identifying predictors of postoperative outcomes in adhesive small bowel obstruction are limited. This study investigates the efficacy of the modified frailty index (mFI)to predict postoperative morbidity and mortality among patients undergoing surgery for adhesive small bowel obstruction. METHODS: A multicentre retrospective cohort study including patients undergoing surgery for adhesive small bowel obstruction after failed trial of nonoperative management between January 2015 and December 2020 was performed. Impact of frailty status using the mFI, stratified as frail (≥0.27) and robust (<0.27), on postoperative morbidity, mortality, length of stay, and discharge destination was evaluated using multiple logistic regression. RESULTS: Ninety-two robust patients (mean age 62.4 y, 68% female) and 41 frail patients (mean age 81.7 y, 63% female) were included. On simple stratification, frail patients had significantly increased 30-d morbidity (overall morbidity 80% versus 49%) and need for higher level of care on discharge (41% versus 9%). However, on multiple regression, functional dependence but not the mFI, was independently associated with worse 30-d overall morbidity (odds ratio [OR] 3.97, confidence interval [CI] 1.29-12.19) and lower likelihood of returning to preoperative disposition (OR 0.21, CI 0.05-0.91). The delay in operation beyond 5 d was independently associated with worse 30-d outcomes including overall morbidity and mortality (OR 7.54, CI 2.13-26.73) and decreased return to preoperative disposition (OR 0.14, CI 0.04-0.56). CONCLUSIONS: The mFI, although promising, was not independently predictive of outcomes following surgery for adhesive small bowel obstruction. Further adequately powered studies are required.


Subject(s)
Frailty , Intestinal Obstruction , Humans , Female , Middle Aged , Aged, 80 and over , Male , Retrospective Studies , Intestinal Obstruction/surgery , Morbidity , Postoperative Complications , Risk Factors , Risk Assessment
18.
Int J Behav Nutr Phys Act ; 21(1): 27, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38438945

ABSTRACT

BACKGROUND: Parental practices and neighbourhood environmental factors may influence children's movement behaviours. We aimed to investigate the cross-sectional and prospective associations of parental practices and neighbourhood environmental factors with accelerometer-measured 24-hour movement behaviours (24 h-MBs) among school-aged children in Singapore. METHODS: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study collected information on dimensions of parental practices and neighbourhood environment at age 5.5 years. Confirmatory factor analyses were performed to generate latent variables and used to compute overall parental practices [involvement in PA + support for PA + control of screen viewing context] and environmental scores [facilities for active play + active mobility facilitators + barriers*-1]. Children wore an accelerometer on their non-dominant wrist for seven consecutive days at ages 5.5 and 8 years. The R-package GGIR 2.6 was used to derive moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), inactivity, and total-sleep (napping+night sleep) minutes per day. Associations were determined using compositional data analysis with multivariate linear regression models, taking into account potential confounders. RESULTS: Among 425 children (48% girls, 59% Chinese), higher parental involvement in PA, parental support for PA and overall parental practices were associated with 24 h-MBs at ages 5.5 and 8 years, specifically with greater time spent in MVPA and less time being inactive relative to the remaining movement behaviours. The corresponding mean changes in the overall 24 h-MB for increasing parental practices from lowest to highest scores (- 2 to + 2 z-scores) indicated potential increases of up to 15-minutes in MVPA, 20-minutes in LPA, 5-minutes in sleep duration, and a reduction of 40-minutes in inactivity at age 5.5 years. At age 8 years, this could translate to approximately 15-minutes more of MVPA, 20-minutes more of LPA, a 20-minute reduction in sleep duration, and a 20-minute reduction in inactivity. Parental control of screen viewing contexts and neighbourhood environmental factors were not associated with 24 h-MBs. CONCLUSIONS: Parental practices but not environmental factors were associated with higher MVPA and lower inactivity among Singaporean children, even at a later age. Further research may provide insights that support development of targeted public health strategies to promote healthier movement behaviours among children. STUDY REGISTRATION: This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.


Subject(s)
Asian People , Sedentary Behavior , Child , Child, Preschool , Female , Humans , Male , Cross-Sectional Studies , Data Analysis , Parents
19.
J Gastrointest Surg ; 28(3): 205-214, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38445910

ABSTRACT

BACKGROUND: There are limited data identifying predictors of postoperative outcomes in adhesive small bowel obstruction (ASBO). This study used the National Inpatient Sample (NIS) to assess the efficacy of the modified frailty index (mFI) to predict postoperative morbidity among patients undergoing an operation for ASBO. METHODS: A retrospective analysis of the NIS between September 1, 2015, and December 31, 2019, was performed to identify adult patients who underwent nonelective operative intervention for ASBO. The mFI was used to stratify patients as either frail (mFI value ≥ 0.27) or robust (mFI value < 0.27). The primary outcomes were overall in-hospital postoperative morbidity and mortality. The secondary outcomes were system-specific morbidity, length of stay (LOS), total in-hospital healthcare cost, and discharge disposition. Univariable and multivariable regressions were used. RESULTS: Overall, 23251 robust patients and 6122 frail patients were included. Adjusted analyses demonstrated that frail patients had increased in-hospital mortality (adjusted odds ratio [aOR], 2.16; 95% CI, 1.80-2.60), postoperative morbidity (aOR, 1.63; 95% CI, 1.52-1.74), postoperative LOS (adjusted mean difference [aMD], 0.97 days; 95% CI, 0.73-1.21), and total in-hospital healthcare costs (aMD, $18,921; 95% CI, $14,608-$23,235) and were less likely to be discharged home (aOR, 0.59; 95% CI, 0.55-0.63). The findings were unchanged on subgroup analysis of patients undergoing open operation and those older than 65 years of age. CONCLUSION: The mFI may predict postoperative outcomes for ASBO. Stratifying patients based on frailty may assist clinicians and patients in making informed decisions, setting realistic expectations, and proactively planning postoperative disposition.


Subject(s)
Frailty , Intestinal Obstruction , Adult , Humans , Inpatients , Frailty/complications , Retrospective Studies , Decision Making , Intestinal Obstruction/surgery , Morbidity
20.
Surg Obes Relat Dis ; 20(6): 564-570, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38316579

ABSTRACT

BACKGROUND: Roux-en-Y gastric bypass (RYGB) effectively treats severe obesity, but some patients may require revisional surgery like limb lengthening (LL) for postoperative weight gain. OBJECTIVES: This study aims to compare 30-day serious complications and mortality rates between LL and primary RYGB, given limited safety data on LL. METHODS: Patients who underwent LL and RYGB were identified from the 2020 and 2021 MBSAQIP databases, the only years in which LL data were available. Baseline characteristics and 30-day rates of serious complications and mortality were analyzed. RESULTS: A total of 86,990 patients underwent RYGB and 455 underwent LL. Patients undergoing RYGB were younger (44.4 versus 49.8 yr, P < .001), had a higher body mass index (BMI) (45.5 versus 41.8 kg/m2, P < .001) and higher rates of comorbidities including diabetes (30.0 versus 13.6%, P < .001). RYGB and LL had similar operative duration (125.3 versus 123.2 min, P = .5). There were no statistical differences between cohorts for length of stay (LOS) (1.6 RYGB versus 1.6 LL d, P = .6). After LL, there were higher 30-day rates of reoperation (3.3 versus 1.9%, P = .03) and deep surgical site infections (1.3 versus .5%, P = .03) compared to RYGB. There were no differences in overall serious complications (5.1 LL versus 5.0% RYGB, P = 1.0) and mortality (.2 LL versus .1% RYGB, P = .5). Multivariable logistic regression adjustment found that previous venous thromboembolism was associated with serious complications after LL. CONCLUSIONS: When compared to primary RYGB, LL has a favorable safety profile with similar 30-day rates of serious complications and mortality.


Subject(s)
Gastric Bypass , Obesity, Morbid , Postoperative Complications , Reoperation , Humans , Gastric Bypass/adverse effects , Gastric Bypass/statistics & numerical data , Gastric Bypass/methods , Female , Male , Adult , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Obesity, Morbid/surgery , Reoperation/statistics & numerical data , Databases, Factual , Retrospective Studies
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