Low Rate Research Articles

Prognosis of Fragment Reattachment in Anterior Crown Fractures: A Retrospective Study.

Although several studies have compared fragment attachment with resin build-ups in anterior crown fractures, none have specifically investigated the outcome of reattached fragments. This retrospective study aimed to evaluate long-term outcomes of fragment reattachment in anterior crown fractures and determine the prognostic affecting their success. We retrospectively analyzed clinical records of patients who underwent fragment reattachment for crown fractures in anterior teeth (maxillary and mandibular central and lateral incisors) between 2008 and 2023. All procedures were performed by experienced professors and residents following a standardized protocol. Kaplan-Meier survival curves and Cox proportional hazards regression analyses were performed to evaluate fragment retention outcomes and identify potential prognostic factors. Among 75 anterior crown fractures, the estimated fragment retention rates were 83.7% at 2 years, 75.2% at 5 years, and 56.4% at 10 years. Multivariate Cox regression analyses identified patient age and extent of crown fracture as significant factors affecting outcomes. The 5-year estimated fragment retention rates were 82.8% and 67.0% for uncomplicated and complicated crown fractures, respectively. Fragment reattachment remains a viable treatment option for anterior crown fractures. Treatment success decreased with patient age, and complicated crown fractures demonstrated lower retention rates than uncomplicated ones. Fragment reattachment can provide predictable outcomes in anterior crown fractures when cases are carefully selected, particularly considering the patient's age and the type of crown fracture.

Frequency of Port Site Infection in Laparoscopic Cholecystectomy, Evaluation by Southampton Score: A Prospective Study

Objective: To evaluate the frequency of Port-Site Infections (PSIs) following Laparoscopic Cholecystectomy (LC) using the Southampton Scoring System and identify associated risk factors. Methodology: This prospective cross-sectional study was conducted over two years in the Department of General Surgery at Hayatabad Medical Complex, Peshawar. Data were collected using a standardized proforma and analyzed using IBM SPSS version 23.0, with a significance value set at p<0.05. The Southampton Scoring System was used to monitor and grade wound infections at discharge, 2nd week and 4th weeks post-surgery. Results: After exclusion, 841 patients were included in the study, with 471 males (56%) and 370 females (44%). The average age was 45.9 ± 12.7 years. Significant intraoperative findings included symptomatic gallbladder stones (82.5%), acute cholecystitis (26%), thick-walled gallbladder (44.4%), bile spillage into peritoneum (41.5%), and gallbladder perforation (54.6%). The frequency of port site infection with Southampton scores of 3 and above was 9.9% for the umbilical port and 27.3% for the epigastric port. Significant risk factors for SSI included symptomatic gallbladder stones, acute cholecystitis, gangrenous gallbladder, spillage into the wound, gallbladder perforation, and surgery duration exceeding 90 minutes (p<0.05). Conclusions: The Southampton Scoring System effectively identified and tracked wound infections, underscoring the need for meticulous surgical techniques and thorough postoperative care to reduce SSIs. Although wound healing was initially good, complications increased by the 2nd and 3rd week, especially at the epigastric port. Most patients show significant improvement of wound healing by 4th week. Regular monitoring and timely interventions are essential to lower SSI rates in laparoscopic surgeries.

Enhancing Patients Satisfaction and their outcomes through implementing Nurse-Caring Behavior Protocols in Acute Diabetic Crisis Management

Background: Integrating nurse-caring behavior protocols in acute diabetic crisis management enhances patient satisfaction and outcomes by addressing both clinical and emotional care needs. Aim: evaluate the effect of implementing nurse-caring behavior protocols on enhancing patients’ satisfaction and their outcomes in acute diabetic crisis management. Design: Quasi-experimental research design was used in the present study. Setting: ICU and emergency care unit at Aswan university hospital. Sample: This study was performed on 60 patients who were not randomly selected and assigned in to control and study group. Tools: Tree tools were used to collect data include Tool (I): Patient assessment tool contained personal characteristic. Tool (II): Patients satisfaction with NCBs evaluation scale. Tool (III) Patients Outcomes assessment tool. Results: the majority being aged 50-60 years in study and control group (70.1% and 66.7% respectively), Gender distribution was nearly equal, with slightly more females in (56.0 % and 50%) respectively, a higher percentage of participants with higher education (33.3% and 50%) respectively. A higher percentage of patients in the study group reported satisfactory levels of satisfaction (73.3%) compared to the control group (33.3%) Conversely. The study group had a significantly higher percentage of patients staying less than 5 days (63.3%). The study group had significantly more patients discharged to home (76.7%). A significantly lower rates of complications, including hypoglycemia, hypokalemia, cerebral edema, arrhythmia and acidosis among study group. Conclusion: The nurse-caring behaviors have a positive impact on patient satisfaction, outcomes, and a reduction in complications associated with acute diabetic crises. Recommendation: Implementing and evaluating nurse-caring behavior protocols, to enhance early discharge and complication management in acute diabetic crisis management

Ustekinumab Drug Clearance Is Better Associated with Disease Control than Serum Trough Concentrations in a Prospective Cohort of Inflammatory Bowel Disease

Background/Objectives: This study aimed to compare the association of ustekinumab (UST) drug clearance (CL) and trough drug concentrations with disease activity in patients with inflammatory bowel diseases (IBDs). Methods: A prospective cohort of 83 patients with IBD receiving maintenance therapy with 90 mg subcutaneous UST was analyzed using Bayesian PK modeling. UST concentrations and antibodies to UST (ATU) were collected at the trough and measured using a drug-tolerant homogenous mobility shift assay (HMSA). CL was estimated using Bayesian estimation methods with priors from a previous population pharmacokinetic study specifically reparametrized using HMSA. Outcomes were combined clinical and biochemical remission and endoscopic healing index (EHI) score, a validated marker of endoscopic active disease in IBD. Statistical analysis consisted of linear and nonlinear mixed effect models for repeated time-to-event analysis. Results: A total of 83 patients with IBD were enrolled (median age 42 years, 52% female) and evaluated across 312 dose cycles (median follow-up: 279 days, median of 3 cycles/patient). Median concentrations and CL were 5.0 µg/mL and 0.157 L/day, respectively. Most patients (89%) were exposed to other biologics before starting UST, which was associated with lower rates of clinical and biochemical remission (p = 0.01). Longitudinal changes in concentrations were not associated with remission (p = 0.53). Conversely, higher CL was associated with a lower likelihood of remission (p < 0.01). EHI > 50 points (endoscopic active disease, n = 303 cycles) was associated with higher UST CL (p < 0.01). Conclusions: UST CL was more strongly associated with clinical and biochemical outcomes than trough concentrations, highlighting its potential role in therapy optimization.

Factors associated with patient no-show rates in an academic pain management practice.

Chronic pain is a debilitating, multifactorial condition. The purpose of this study was to examine patient characteristics of those who did not show up for their scheduled first pain medicine appointment in order to identify factors that may improve access to care. This was a retrospective analysis of 810 patients from a single-center academic pain management clinic between January 1, 2022, and December 31, 2023. Overall no-show rate was 57%. There was a mean of 133 days (4.3 months) from scheduling to the appointment date. Patients age ≤ 30 years had the highest no-show rate (69%), and those ≥81 years had the lowest (49%). Hispanic and Caucasian patients had similar no-show rates (59% and 57%, respectively) and Asian patients had lower rate (41%). Referral from another specialty had a significantly lower no-show rate (36% vs. 89%, p < 0.001). The presence of referral (p < 0.001) was a significant predictor of lower no-show rates. Of the 191 patients with low back pain, internal medicine (38.7%) was the most referring specialty. High no-show rates were present particularly among younger patients. Having a referral from another specialty was an independent predictor of lower no-show rates.

Disparities and barriers in germline testing among patients with early-onset gastrointestinal cancers.

35 Background: Early-onset gastrointestinal cancers (EOGIC) are strongly associated with hereditary predisposition, making germline testing essential for treatment and familial risk management. Disparities in germline testing persist. This study investigates disparities and barriers to germline testing in EOGIC. Methods: This IRB-approved retrospective analysis included 864 patients aged 18-49 with GI cancers at the University of Chicago (2018-2023). Data collected included race, gender, age, insurance, family cancer history, and subtype. Outcomes were physician referrals for germline testing and completion. Chi-square tests and logistic regression models assessed predictors of recommendations and completion. Results: Of 864 patients, 473 (54.7%) received germline testing recommendations, and 323 (37.4%) completed testing. Completion rates: 30.2% for no insurance, 29.1% for Medicare/Medicaid, and 40.3% for private insurance (p=0.032). Patients with family history of cancer were more likely to be recommended for testing (62.9% vs. 39.5%, p&lt;0.001) and complete it (44.0% vs. 23.7%, p&lt;0.001). In our cohort, no significant racial disparities were observed (p=0.712 and p=0.358). Females were more likely to receive recommendations (59.1%) and complete testing (41.2%) than males (50.9% referral, 34.0% completion, p=0.016 and p=0.029). Patients under 30 had the highest rates of testing recommendation (66.1%) and completion (46.4%), followed by 30-39 (61.7%, 44.4%) and 40-49 (51.2%, 34.0%), p=0.006 and p=0.009. By cancer subtype, colorectal cancer (CRC) patients had the highest referral (66.1%) and completion (45.9%) rates, while anal cancer had the lowest (13.2% referral, 5.3% completion, OR 0.08, p&lt;0.0001). Gastric cancer (52.3% referral, 29.2% completion, OR 0.49, p=0.005) and esophageal cancer (36.9% referral, 20.0% completion, OR 0.31, p&lt;0.0001) also had lower testing rates. Liver cancer (35.4% referral, 27.1% completion, OR 0.38, p&lt;0.0001) and cholangiocarcinoma (45.5% referral, 22.7% completion, OR 0.28, p=0.016) showed similarly low rates. Conclusions: Disparities in germline testing were seen among uninsured patients, males, and those with public insurance. CRC had the highest testing rates, while anal, esophageal, liver, and cholangiocarcinoma had lower rates, likely due to lower suspicion of hereditary predisposition. Targeted interventions are needed to improve testing uptake and completion, especially among uninsured and underrepresented populations.

Cardiac resynchronization therapy in heart failure based on Strauss criteria for left bundle branch block.

The left bundle branch block (LBBB) is a strong predictor of response to cardiac resynchronization therapy (CRT). However, a significant number of patients do not respond to the treatment. The study sought to evaluate the impact of the stricter Strauss criteria for left bundle branch block (St-LBBB) on CRT response, hospitalizations, ventricular arrhythmia (VA) events and mortality. This study is a retrospective analysis of prospectively collected data on heart failure (HF) patients with LBBB admitted for CRT implantation. Patients were divided into two groups according to the fulfilment or not of St-LBBB criteria. The study included 82 patients with ischaemic (ICM) and non-ischaemic (NICM) cardiomyopathy [46 (56%) with St-LBBB and 36 (44%) with non-St-LBBB]. Patients with St-LBBB showed higher CRT response rates compared with those with non-St-LBBB (P<0.01), while the group with NICM exhibited the greatest benefit (P<0.01). St-LBBB CRT responders displayed significantly lower rates of HF hospitalization (P<0.0001) compared with the non-St-LBBB group. According to Kaplan-Meier time curves, this was primarily evident in patients with NICM (P<0.0001). CRT responders displayed significantly fewer VA events (P<0.001) and lower mortality rates (P<0.0001) than non-responders. Kaplan-Meier estimates demonstrated a significantly lower incidence of VAs in NICM patients with St-LBBB (P=0.049) compared with ICM patients with St-LBBB (P=0.25). Lower mortality rates were observed in CRT responders than non-responders (P<0.0001), with the group of NICM with St-LBBB criteria exhibiting the greatest benefit (P=0.0238). Patients with NICM and St-LBBB present the greatest benefit concerning CRT response, HF hospitalizations, VA events and mortality. Although St-LBBB criteria seem to improve patient selection for CRT, more data are needed to elucidate the role of St-LBBB criteria in this setting.

Real-world genomic testing performance in colorectal cancer (CRC): The MultiTEAM Systems Framework Precision Oncology Reflex Testing (TEAMSPORT).

108 Background: Genomic testing plays a pivotal role in personalizing treatment for CRC patients. Despite recommendations from NCCN, adoption remains uneven. Research indicates that only 64.7% of patients with metastatic CRC (mCRC) underwent molecular testing nationwide. TEAMSPORT seeks to address this gap by evaluating the feasibility of reflex testing and examining how pathology and oncology teams integrate genomic testing into routine practice. Methods: This quasi-experimental study tracks testing over time. Eligible patients were 18 years or older, with a histological diagnosis of adenocarcinoma, who received treatment at the University of Kansas Health System (TUKHS). Exclusion criteria included patients discharged to hospice after diagnosis, those whose last contact with TUKHS occurred within 30 days of diagnosis, and patients who passed away within 30 days of diagnosis. Testing rates were calculated as the number of tests performed divided by the number of testing opportunities, where "testing opportunities" refer to NCCN-recommended tests based on cancer stage. An intervention to increase adherence to NCCN-recommended testing began in December 2022. Results: From January 2022 to December 2023, 564 colorectal cancer (CRC) cases were eligible for genomic testing, resulting in 1,525 testing opportunities. In localized CRC, testing rates steadily improved, from 92% in January-June 2022 to 98% by July-December 2023 for patients diagnosed outside of TUKHS. At TUKHS, the rates remained high, reaching 100% in the first two periods and staying over 90% in subsequent periods. Patients with mCRC saw similar trends, particularly in the control arm where rates went from 61% to 71%. Specific molecular NCCN-recommended tests were assessed. At TUKHS, testing rates were high for microsatellite instability (MSI - 98%) which is caused by deficiency of the DNA mismatch repair (dMMR) system. Lower testing rates were observed for other markers like KRAS (70%), BRAF (67%) and HER2 (48%). Testing rates were assessed based on primary insurance. At TUKHS, the testing rates for Medicaid patients reached 94%, private insurance patients at 78%, and Tricare/VA at 100%. Outside of TUKHS, Medicaid patients had lower testing rates at 21%, private insurance patients at 74%, and CMS patients at 66%. Time to test by processing lab will be presented at the meeting. Conclusions: Despite the high testing rates for MSI/dMMR, the overall genomic testing in CRC remains imperfect, with lower rates for BRAF and HER2 . This discrepancy may be related to the fact that targeted therapies for BRAF and HER2 are not yet part of first-line treatment for CRC. Causes for the discrepancy in testing rates by primary insurance have yet to be determined. Future research should address these gaps to enhance precision oncology in CRC management.

Comparative temporal response of toxicity for the neonicotinoid clothianidin and organophosphate dimethoate insecticides in two species of solitary bee (Osmia bicornis and Osmia cornuta).

Solitary bees provide essential pollination services. Concerns for the decline of these wild bee species have led to calls for their inclusion in pesticide risk assessment. Solitary bees differ from honey bees in their physiology and ecology and this may affect how they respond to pesticide exposure. Here we investigate the life-time toxicity of two insecticides, the organophosphate dimethoate and neonicotinoid clothianidin, for two mason bee species, Osmia bicornis and O. cornuta using a toxicokinetic/toxicodynamic stochastic death model taken from Dynamic Energy Budget (DEBtox) theory. Both species showed concentration and exposure duration dependent effects for each chemical. LC50 values estimated from the model parameters at 48 h were ≥ 14 fold and 6 fold those at 480 h for dimethoate and clothianidin respectively. Survival modelling indicated greater sensitivity in O. bicornis than for O. cornuta to dimethoate, whilst for clothianidin, O. cornuta females but not males, were more sensitive than both sexes of O. bicornis. These sensitivity differences were not related to body size. Toxicokinetic and toxicodynamic traits derived from modelling indicated lower elimination rates in O. bicornis and higher killing rates for O. cornuta females for dimethoate and lower elimination rates for clothianidin in O. cornuta females that were related to sensitivity. This study shows the near life-time testing is possible for solitary bees and that combining adult life-time toxicity tests with toxicokinetic/toxicodynamic modelling provides a more mechanistic understanding of pesticide effects in solitary bee species.

Hybrid versus vaccine immunity of mRNA-1273 among people living with HIV in East and Southern Africa: a prospective cohort analysis from the multicentre CoVPN 3008 (Ubuntu) study.

With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak. Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months. The ongoing Ubuntu study is registered on ClinicalTrials.gov (NCT05168813) and this work was conducted from December 2021 to March2023. Between December 2021 and September 2022, 14,237 participants enrolled, and 14,002 (83% PLWH, 69% SARS-CoV-2 seropositive) were included in the analyses. Vaccinations were safe and well tolerated. Common adverse events were pain or tenderness at the injection site (26.7%), headache (20.4%), and malaise (20.3%). Severe adverse events were rare (0.8% of participants after the first and 1.1% after the second vaccination), and none were life-threatening or fatal. Among PLWH, the median CD4 count was 635cells/μl and 18.5% had HIV viraemia. The six-month cumulative incidences in the hybrid immunity and vaccine immunity groups were 2.02% (95% confidence interval [CI] 1.61-2.44) and 3.40% (95% CI 2.30-4.49) for COVID-19, and 0.048% (95% CI 0.00-0.10) and 0.32% (95% CI 0.59-0.63) for severe COVID-19. Among all PLWH the hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44-0.77; p<0.001) and a 73% lower hazard rate of severe COVID-19 (HR 0.27; 95% CI 0.07-1.04; p=0.056) than the vaccine immunity group, but this effect was not seen among PLWH with CD4 counts <350cells/μl or HIV viraemia. Twenty PLWH had persistent SARS-CoV-2 virus at least 50 days. Hybrid immunity was associated with superior protection from COVID-19 compared to vaccine immunity with the ancestral mRNA-1273 vaccine. Persistent infections among immunocompromised PLWH may provide reservoirs for emerging variants. National Institute of Allergy and Infectious Diseases.

Catheter ablation using pulsed-field energy: Advantages and limitations compared with conventional energy.

Atrial fibrillation (AF) poses significant risks of heart failure and stroke, emphasizing effective treatment. Catheter ablation using thermal energy sources, such as radiofrequency or cryoballoon ablation, has shown greater success in maintaining sinus rhythm compared with drug therapy. However, thermal ablation (TA) is associated with serious complications, such as atrial-esophageal fistula, phrenic nerve palsy, and pulmonary vein stenosis. Pulsed-field ablation (PFA) is an emerging ablation energy source that uses electroporation to selectively target cardiac tissue while sparing adjacent structures such as nerves and blood vessels. Two randomized controlled trials have demonstrated that PFA is comparable to TA in both efficacy and safety at a 1-year follow-up and had shorter procedure times. A review of six meta-analyses consistently showed shorter procedural times for PFA across all studies. Additionally, three out of the four recent studies with large samples reported lower recurrence rates with PFA. Regarding complication rates, four out of four studies showed lower incidences of phrenic nerve injury with PFA, and two out of three studies reported lower rates of esophageal injury with PFA. However, four out of four studies indicated higher incidences of cardiac tamponade with PFA, highlighting the need for caution among early-career operators. Furthermore, careful monitoring is required considering the possible unforeseen complications specific to PFA and the lack of long-term follow-up data. Despite these concerns, PFA shows promise as a safer, more effective, and efficient alternative to TA for AF, particularly as operator experience and device technology continue to advance.

Regionality and Temporal Dynamics of Sequestration and Relocation of Cardenolides in the Monarch Butterfly, Danaus plexippus

The adaptation of monarch butterflies (Danaus plexippus) to milkweed plants and their ability to sequester toxic cardenolides is a model system for plant-herbivore coevolution. However, the physiological mechanisms underlying cardenolide sequestration and its temporal dynamics remain largely unknown. Here, we show that the polar cardenolide ouabain passes through the isolated midgut epithelium of D. plexippus in vitro and is also absorbed into the body cavity of monarch caterpillars. Remarkably, the same pattern was observed in caterpillars of the related, but non-sequestering milkweed butterfly Euploea core, and even in the non-adapted Solanaceae specialist Manduca sexta, although uptake across gut epithelia occurred at a lower rate. Furthermore, we demonstrated that cardenolides begin to cross the epithelium in the anterior part of the intestine and can be detected in body tissues as soon as one minute after ingestion. Finally, we show that not all cardenolides are translocated into butterfly tissues during metamorphosis, and that the most apolar cardenolides are removed with the last caterpillar exuviae. As a result, adult butterflies contain no cardenolides less polar than the milkweed cardenolide calactin. We conclude that uptake by the intestinal epithelium is a very rapid process and that quantitative differences in cardenolide sequestration among lepidopteran caterpillars are only partially mediated by the gut epithelium, likely involving additional mechanisms such as metabolism or excretion. In addition, the translocation of cardenolides from the caterpillar is a selective process which may be due to the limited mobility of highly apolar cardenolides.

Transition symptom management careers: Historical patterns of mental health symptoms and service use among young adults experiencing a psychiatric crisis.

Young adults access mental health services at lower rates than both older and younger age groups despite high levels of need. Mental health service use is known to be influenced by prior experiences with treatment, with episodes of symptoms and treatment producing patterns of service use over time, or what we call a "symptom management career". This qualitative study examined the symptom management careers of 55 young adults (ages 18-25) who were admitted to an inpatient, short term, crisis stabilization unit. Participants completed research interviews at the hospital following a psychiatrist's assessment. During semi-structured qualitative interviews, participants retrospectively narrated their experiences of mental health symptoms and service use from symptom onset to the current episode. The research team used an inductive qualitative approach to identify distinct patterns of symptom management, while also examining factors that contributed to service use. Six distinct types of symptom management careers were identified based on the timing of symptom onset and service participation. Notably, none of the participants experienced an uninterrupted pattern of service use from adolescence into young adulthood. The team identified a set of themes that influenced these patterns including traumatic experiences, social supports, social service systems, and substance use. Findings highlight the developmental nature of service connection and disconnection and suggest potential points of intervention in non-specialty settings, such as schools, child welfare, and the juvenile legal system. Findings also demonstrate the need for flexible services that respond to the developmental need for autonomy and self-determination as youth transition into young adulthood.

Comprehensive landscape of FGFR variations and prognosis revelance in colorectal cancer from circulating tumor DNA and tissue gene analyses in 2083 patients.

278 Background: FGFR genomic alterations have been identified, and several FGFR inhibitors are approved for various malignancies, including bladder and cholangiocarcinoma. However, limited studies have shown FGFR alterations and their prognostic impact in colorectal cancer (CRC). Methods: This retrospective analysis involved tissue and blood samples from a single-institute cohort (The Sixth Affiliated Hospital of Sun Yat-sen University) of stage I-IV CRC patients from 2014 to 2024. FGFR genomic alterations were analyzed using tissue NGS and plasma ctDNA. Disease-free survival (DFS) for stages I-III and progression-free survival (PFS) for stage IV were compared between FGFR-altered and negative CRC patients, matched in a 1:2 ratio. Validation of genomic alterations and their prognostic impact was conducted using cBioPortal and TCGA data. Results: FGFR alterations were found in 7.89% of 608 tissue samples and 10.95% of 2083 ctDNA samples. The most frequent alteration was FGFR1 amplification in all cohorts, along with FGFR2 p.R165W and FGFR3 p.A634T mutations in ctDNA. FGFR alterations correlated with younger age, left-sided colon tumors, adenocarcinomas, poor differentiation, advanced TNM staging, and multi-organ metastasis. Prognostic analysis showed a higher proportion of FGFR alterations in stage IV patients (66.23% vs. 59.14%), lower rates of no evidence of disease (NED) (6.62% vs. 17.68%), and significantly shorter PFS (median 17 vs. 20 months, HR 2.184, p=0.007). In stages I-III, FGFR-altered patients also had a lower NED rate (79.22% vs. 82.19%) and significantly shorter DFS (median 13 vs. 29 months, HR 2.833, p=0.002). Among frequent alterations, FGFR1 amplification was significantly associated with poor prognosis (PFS 17 vs. 20 months, HR 2.221, p=0.014; DFS 13 vs. 29 months, HR 2.964, p=0.002), while others showed no significant correlation. In stage IV patients receiving bevacizumab, FGFR1 alteration was linked to significantly shorter PFS (p=0.0021). KEGG analysis indicated FGFR1 was associated with angiogenesis pathways. FGFR alteration profiles and prognostic outcomes were consistent across tissue samples, ctDNA analyses, and databases. Conclusions: Our study outlines the genomic landscape and prognostic significance of FGFR in CRC, highlighting FGFR1 amplification as the dominant alteration. FGFR alterations were associated with poorer outcomes, as reflected in lower NED rates and shorter DFS and PFS. FGFR1 amplification was notably linked to reduced DFS and PFS, and it correlated with shorter PFS in patients receiving bevacizumab, indicating a potential link to resistance against bevacizumab. ctDNA n=2083 Tissue genen=608 cBioPortal Databasen=6998 FGFR Total 228/10.95% 48/7.89% 528/8.0% FGFR1 76/3.65% 29/4.77% 264/4.0% FGFR2 78/3.74% 10/1.64% 125/1.9% FGFR3 104/4.99% 10/1.64% 139/2.1%

Dose-escalated radiation for locally advanced unresectable pancreatic cancer.

750 Background: Patients with unresectable locally advanced pancreatic cancer have limited therapeutic options. Historical treatments have included systemic chemotherapy or palliative radiation. New advanced radiotherapy treatment techniques have allowed dose escalated ablative radiotherapy to be delivered for patients with cancer limited to the pancreas. This study retrospectively reviews the long term outcomes of patients receiving dose escalated radiation for unresectable localized pancreatic cancer. Methods: Patients with locally advanced unresectable pancreatic underwent neoadjuvant chemotherapy with either gemcitabine or FOLFIRINOX based regimens. When maximum response was achieved with chemotherapy or this was no longer tolerated, patients were reassessed with imaging. Patients with localized unresectable disease then proceeded to definitive dose escalated radiation with either SBRT radiosurgery (40Gy in 5 fractions) or IMRT radiation (65-70Gy in 30-35 fractions) with concurrent 5FU. Surveillance of disease was performed with CT imaging and Ca19-9 biomarker assessment. Results: A total of 38 patients (21 male, 17 female) underwent definitive radiation. Radiation technique was determined by treating physician based on patient anatomy, with 7 patients having SBRT and 31 IMRT/5FU. Average patient age at diagnosis was 71. All patients underwent at least 6 months of follow up and mean follow up was 14 months. At time of latest follow up, 30 patients had no evidence of local progression and 12 patients had no evidence of progression at any site. The most common side effect at last follow up was grade 2/3 duodenal ulcer experienced by 7 patients. Conclusions: Advances in systemic chemotherapy have increased the population of patients with locally advanced unresectable pancreatic cancer who have persistent pancreatic disease after induction chemotherapy. Definitive dose escalated radiation is a new and effective technique to provide local control in this setting. This approach is well tolerated with manageable toxicity and effective durable local control. Patients continue to experience distant disease failure despite improving local control rates, though at a lower rate than historical controls. Control of primary pancreatic malignancy with dose escalated radiation can potentially improve quality of life and function for these patients for whom additional chemotherapy or surgery is not indicated.

What Does Our Tolerance of Poor Management of Patients' Pain Have to Do With Reimbursement Inequity for Office-Based Gynecologic Procedures?

Office-based gynecologic procedures (OBGPs) are reimbursed at lower rates than similar office urology and dermatology procedures. But there is a broader "hidden curriculum" in health professions training that perpetuates clinicians' and organizations' acceptance of these patterns of poor reimbursement, disincentivizes research on improving OBGP pain management, and exacerbates tolerance of poor control of patients' OBGP pain. This article suggests strategies for equitable reimbursement that would also likely motivate better, more equitable OBGP pain control.

Earthquake Damage Susceptibility Analysis in Barapani Shear Zone Using InSAR, Geological, and Geophysical Data

The identification of areas that are susceptible to damage due to earthquakes is of utmost importance in tectonically active regions like Northeast India. This may provide valuable inputs for seismic hazard analysis; however, it poses significant challenges. The present study emphasized the integration of Interferometric Synthetic Aperture Radar (InSAR) deformation rates with conventional geological and geophysical data to investigate earthquake damage susceptibility in the Barapani Shear Zone (BSZ) region of Northeast India. We used MintPy v1.5.1 (Miami INsar Timeseries software in PYthon) on the OpenSARLab platform to derive time series deformation using the Small Baseline Subset (SBAS) technique. We integrated geology, geomorphology, gravity, magnetic field, lineament density, slope, and historical earthquake records with InSAR deformation rates to derive earthquake damage susceptibility using the weighted overlay analysis technique. InSAR time series analysis revealed distinct patterns of ground deformation across the Barapani Shear Zone, with higher rates in the northern part and lower rates in the southern part. The deformation values ranged from 6 mm/yr to about 18 mm/yr in BSZ. Earthquake damage susceptibility mapping identified areas that are prone to damage in the event of earthquakes. The analysis indicated that about 46.4%, 51.2%, and 2.4% of the area were low, medium, and high-susceptibility zones for earthquake damage zone. The InSAR velocity rates were validated with Global Positioning System (GPS) velocity in the region, which indicated a good correlation (R2 = 0.921; ANOVA p-value = 0.515). Additionally, a field survey in the region suggested evidence of intense deformation in the highly susceptible earthquake damage zone. This integrated approach enhances our scientific understanding of regional tectonic dynamics, mitigating earthquake risks and enhancing community resilience.

Where Do Clients Receive Methadone Treatment? Exploring Bypassing Behaviors in Methadone Treatment Clients: Temporal, Geographic, and Demographic Factors.

Few studies have examined where clients receive methadone treatment for opioid use disorder relative to their residences. Commuting time affects access to care, and anecdotal evidence suggests clients often bypass closer methadone providers. This study quantifies (a) bypass patterns in Los Angeles County, (b) gender, age, and ethnoracial differences in bypassing, and (c) links between bypassing and facility attributes. Using retrospective multiyear analysis, we matched opioid treatment episodes with commuting times between clients' ZIP codes and treatment facilities. From 16 972 outpatient episodes (2010-2017), data were paired with Google Maps commuting estimates. The study covered 32 methadone facilities and 8627 unique clients. We determined the difference in driving time (a proxy for commuting time) from the nearest (bypassed) provider to the provider where the client was treated, deriving bypass and extended commute rates. We compared the rates of a scaled bypassing variable across racial, ethnic, and gender groups. We examined rates by grouping and by facility characteristics of the closest provider. Bypassing occurred in 48.9% of episodes; 21.0% involved extra commute time of 5+ minutes beyond the closest facility. Bypass rates varied significantly across racial, ethnic, and gender groups. Black or African American clients showed higher bypass rates than non-Latino white clients. Latino female clients had lower rates and shorter commutes than Latino male clients (P < .01). Larger methadone facilities experienced fewer bypassing and Black clients were found to typically bypass in favor of providers with longer wait times than other groups in the study. This is the first study investigating client and facility characteristics relating to methadone treatment bypassing in a major U.S. care system. The results highlight significant bypass rates affecting efficient access. Findings have implications for opioid treatment system design, particularly to improve access to quality care for underserved communities.

Dietary Patterns Among Canadian Caucasians and Their Association With Chronic Conditions.

Understanding the dietary patterns of populations is crucial in addressing chronic health conditions that are influenced by diet and lifestyle. We aimed to identify the dietary patterns among adult Caucasian Canadians and examine their associations with socioeconomic and sociodemographic factors and chronic health conditions. We used two comprehensive national nutrition surveys: Canadian Community Health Survey (CCHS)2015 and CCHS Cycle 2.2 Nutrition 2004, which encompass sociodemographic and socioeconomic profiles, nutrient-rich food diet quality scores and prevalence of chronic conditions. Through cluster analysis, dietary patterns were identified among Caucasians and further analysed with stratification by age/sex groups. Our analysis of dietary patterns among Caucasian adults showed a transition from "High-Fibre" and "Mixed" patterns in 2004 to "Unhealthy," "Healthy-like" and "Potato, Beef and Vegetables" in 2015. In 2004, the "Mixed" pattern was prevalent, but by 2015, a shift towards the "Unhealthy" pattern was notable, with a significant portion of the population, 18.8%, reporting chronic diseases and 19.6% being classified as obese. The "Healthy-like" pattern in 2015 saw lower rates of chronic diseases (6.8%) and obesity (6.1%). Gender-specific patterns showed women favoring healthier options like "Healthy-like" in 2015. The prevalence of chronic diseases and obesity varied significantly with dietary patterns. The "High-Fibre" pattern in 2004 showed lower prevalence rates of chronic diseases (6.6%) and obesity (5.8%) compared to the "Unhealthy" pattern in 2015. The findings highlight the impact of dietary choices on health outcomes over time, underscoring the importance of promoting healthier eating habits to mitigate the risk of chronic diseases and obesity.

Conversion therapy strategy: A novel GPC3-targeted multimodal organic phototheranostics platform for mid-late-stage hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is typically diagnosed at intermediate to advanced stage, making surgical treatment unfeasible. Conversion therapy aims to reduce tumor stage, improve hepatic resection feasibility, and lower recurrence rates. Since traditional therapies are often accompanied by uncertainty of efficacy, there is an urgent need to explore new treatment strategies. Near-infrared phototheranostics technology provides a new way for HCC diagnosis and treatment by its excellent optical properties. However, complex preparation and poor biocompatibility of phototheranostics probes limit clinical application. In this study, we developed a fluorescence/magnetic resonance dual-modality imaging (FLI/MRI) as well as photothermal/photodynamic therapy (PTT/PDT) GPC3-targeted multifunctional phototheranostics probe, IR820-GPC3-Gd NPs (IGD NPs), to improve the efficiency of conversion therapy for HCC. The IGD NPs were simply prepared with the IR820 as the core. Conjugating the HCC-specific targeting molecule GPC3 peptide and the MRI agent DOTA-Gd through click chemistry. IGD NPs target HCC cells through GPC3, releasing heat and reactive oxygen species (ROS) under noninvasive 808nm laser irradiation to reduce tumor size and achieve downstaging. High-sensitivity FLI/MRI precisely delineates tumor boundaries, providing real-time surgical navigation and prognosis assessment. This novel probe offers a feasible and effective treatment option for advanced HCC.