Entire Cohort Research Articles

Medical Therapy for Large Idiopathic Full-Thickness Macular Holes.

To describe the characteristics and outcomes of eyes with idiopathic full-thickness macular holes (FTMH) that underwent initial medical management. This retrospective study included eyes with FTMH that were initially managed with one month of topical therapy. Eligible subjects were treated with dorzolamide 2% three times a day, nepafenac 0.1% twice a day, and prednisolone acetate 1% four times a day. The primary endpoints was hole closure at one month and secondary endpoint was change in best-corrected visual acuity (BCVA). Ten subjects (mean age: 62.80 years; female: 50%) with unilateral FTMH were studied. The mean basal diameter of the entire cohort at baseline was 824.1 µm (median 828 µm). Four (40%) of the smaller holes (mean 698 µm; median 698.50 µm) closed after one month of topical therapy, whereas larger holes (mean 908.17µm; median 889.50 µm) did not close. In one eye, the hole reopened 4 months after stopping the medication, but closed again at one month after re-starting the topical treatment. Median BCVA improved from 0.35 logMAR at baseline to 0.05 logMAR in eyes that closed but remained at 0.70 logMAR at one month in eyes that did not close. Topical corticosteroid, non-steroidal anti-inflammatory, and carbonic anhydrase inhibitor therapy may promote closure of small FTMHs, but large holes are less likely to respond. One month of topical therapy might avoid subjecting some patients to complex vitreo-retinal surgery without compromising visual outcomes. Macular hole may re-open after stopping the topical therapy.

Endovascular thrombectomy first-pass reperfusion and ancillary device placement

BackgroundRecent randomized trials have demonstrated the efficacy of mechanical thrombectomy in treating acute ischemic stroke, however, further research is required to optimize this technique. We aimed to evaluate the impact...

Is human height based on a Lucas sequence relationship between the foot height, tibial length, femur length and upper body length?

This is a retrospective chart and radiographic review of 145 patients who underwent full-body EOS imaging; 109 males and 36 females. The mean ages of the female and male subsets are 28.8 (SD = 11.6) years and 29.5 (SD = 11.8) years, respectively. The sum of the foot height (Ft) and the tibial length (T) for each subject was compared to their femur length (Fe). Subsequently, the sum of the tibial (T) and femoral lengths (Fe) were compared to their respective upper body lengths (UB), as measured from the tops of the femoral heads. A linear regression test was performed to determine whether a Lucas sequence-based relationship exists between Ft + T and Fe, and between T + Fe and UB. The regression for the relationship between Ft + T and Fe for the entire cohort (R = 0.82, R2 = 0.70), the female subset (R = 0.94, R2 = 0.88) and the male subset (R = 0.75, R2 = 0.57), all demonstrated a strong positive correlation between Ft + T and Fe and showed that Ft + T is a likely predictor of Fe. The regression test for the entire cohort demonstrated a moderately positive correlation between T + Fe and UB (R = 0.41, R2 = 0.17, F(1, 145) = 29.42, p = 2.4E-07). A stronger correlation was found for the relationship between T + Fe and UB (R = 0.57, R2 = 0.32, F(1,35) = 16.64, p = 2.5E-05) for the female subset relative to the male subset (R = 0.20, R2 = 0.038, F(1, 35) = 4.37, p = 0.04). There appears to be a Lucas sequence relationship between the lengths of the foot height, tibial length, femoral length and upper body length, which together make up standing height. This mathematical proportion relationship is stronger in females than males.

PCV Adjuvant Therapy as a Preferred Treatment Option for Oligodendroglioma Patients: A Comparative Study With Temozolomide and Concurrent Radiotherapy

INTRODUCTION: When treating oligodendroglioma patients, choosing between temozolomide (TMZ) and procarbazine, lomustine, and vincristine (PCV), with concurrent radiotherapy still poses a challenge. Given the commonality of tumor recurrence, optimizing progression-free survival while minimizing adverse effects is crucial to improving quality of life. METHODS: 87 patients treated for oligodendroglioma between 1994-2022 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) from initial resection were compared between PCV-based or TMZ-based treatment groups using Kaplan-Meier and multi-variable Cox survival analysis. RESULTS: The median age at diagnosis was 41 years and 62% were male. After initial resection, 42.8% received PCV-based treatment and 57.2% received TMZ-based treatment. Treatment groups were balanced in terms of age, tumor genetic profiling, extent of resection, or KPS score, however, the TMZ-based group had more patients receiving concurrent radiation. The entire cohort had a 6.3-year PFS and 21.0-year OS. The median time to recurrence was significantly longer in those treated with PCV (12 years) compared to those treated with TMZ (4.7 years). PFS [HR = 0.46, p = 0.04] and OS [HR = 0.26, p = 0.04] were significantly longer for those receiving PCV-based treatment compared to TMZ-based treatment. After adjusting for factors mentioned above, Cox regression analysis revealed no difference in OS between PCV- and TMZ-based treatment. The overall adverse effect rate did not significantly differ between PCV-based and TMZ-based treatment (25% vs. 28.1%, p > 0.99). CONCLUSIONS: PCV confers improved progression-free survival than TMZ-based treatment for oligodendroglioma patients, noting that most patients in our series received concurrent radiation with TMZ, and those receiving PCV not having received upfront radiation. As we anticipate the results of the CODEL trial, our findings suggest PCV-based therapy warrants consideration as a preferred therapeutic option for oligodendroglioma patients.

No Difference in Clinical and Hospital Quality Outcomes in Treatment of Reverse Obliquity Intertrochanteric Hip Fractures (AO/OTA 31.A3) Based on Cephalomedullary Nail Length

IntroductionThe purpose of this study was to evaluate outcomes following reverse obliquity (RO) intertrochanteric hip fractures based on the use of short cephalomedullary nails (CMNs) compared to long CMNs for fixation. MethodsAn IRB-approved prospectively collected hip fracture registry at an urban academic medical center was queried for all AO/OTA 31A3.1-3 reverse obliquity intertrochanteric (RO) fractures. One hundred and seventy patients with age > 55 years old and minimum 6-month follow-up were identified for analysis. Data was collected for patient demographics, injury details, intraoperative radiographic parameters, perioperative physiologic parameters, hospital quality measures, and outcomes including radiographic time to healing, need for reoperation, nonunion, and mortality. Comparative analyses were conducted between cohorts. Additional multivariable binary logistic and linear regression analyses were performed to evaluate for factors independently associated with short and long nail usage. ResultsThe mean age of the entire cohort was 80.91±10.09 years: 103 patients had a long CMN implanted, and 67 patients had a short CMN implanted. There were no demographic differences or differences in radiographic time to healing, rates of mortality, readmission, nonunion, and need for reoperation. Univariable analysis revealed that short CMN had lower intraoperative blood loss (111.19±83.97mL vs 176.72±161.45mL, p=0.002), decreased need for transfusion (37% vs. 55%, p=0.022), and shorter procedures (118.67±57.87min vs. 148.95±77.83min, p=0.002. Multivariable analysis revealed that short nail usage was associated with decreased intraoperative blood loss, decreased need for transfusion, and shorter operative times. ConclusionNail length does not affect healing or hospital quality outcomes in the treatment of RO hip fractures. The use of short CMNs for these fractures did correlate with lower intraoperative blood loss, operative time, and need for blood transfusion, with non-inferior outcomes and similar hospital quality measures when compared to long CMNs.

Maximizing efficiency and ensuring safety: Exploring the outcomes of 2 consecutive open radical cystectomies by the same team within a single surgical day

BackgroundThe purpose of this study was to evaluate the outcomes of performing 2 consecutive open radical cystectomies (RCs) within 1 day by the same surgical team. Patients and MethodsA retrospective analysis was conducted on data from patients who underwent RC at a single tertiary care center from January 2015 to February 2023. Patient characteristics, perioperative outcomes and endpoints were analyzed. Univariable and multivariable logistic regression models were created to predict major complications. ResultsA total of 657 patients were included in the final cohort, containing 64 paired RCs (32 RC1 and 32 RC2) and 593 single RCs. Major complications occurred in 24.7% of the entire cohort, with no significant differences between single RC vs. RC1 and RC2. Paired RCs showed significantly shorter operative time (OT; p = 0.001) and length of stay (LOS; p = 0.047) compared to single RCs. There were no significant differences in transfusion rates, 30-day readmission, 30-day mortality, or histopathological results between paired and single RCs. Multivariable analysis identified patient characteristics such as age (OR = 1.67, p = 0.03), sex (OR = 0.45, p = 0.008), BMI (OR = 1.98, p = 0.007), ASA-score (OR = 1.61, p = 0.04), and OT (OR = 1.87, p = 0.008) as independent predictors of major complications. ConclusionPerforming 2 consecutive open RCs within 1 day by the same surgical team is a safe approach in experienced hands. This strategy optimizes the utilization of surgical resources and addresses the growing demand for urologic care while maintaining high-quality patient care. Preoperative planning should consider patient-specific factors to minimize risks associated with major complications. Micro AbstractThis study evaluates the outcomes of performing 2 consecutive open radical cystectomies (RC) in a single day by the same surgical team. Data from 657 patients who underwent RC at a single tertiary medical center proved that this approach is safe, with no significant differences in major complications. Preoperative planning should consider patient-specific factors for efficient utilization of surgical resources.

Association Between Years of Education and Amyloid Burden in Patients With Subjective Cognitive Decline, MCI, and Alzheimer Disease.

Higher-educated patients with Alzheimer disease (AD) can harbor greater neuropathologic burden than those with less education despite similar symptom severity. In this study, we assessed whether this observation is also present in potential preclinical AD stages, namely in individuals with subjective cognitive decline and clinical features increasing AD likelihood (SCD+). Amyloid-PET information ([18F]Flutemetamol or [18F]Florbetaben) of individuals with SCD+, mild cognitive impairment (MCI), and AD were retrieved from the AMYPAD-DPMS cohort, a multicenter randomized controlled study. Group classification was based on the recommendations by the SCD-I and NIA-AA working groups. Amyloid PET images were acquired within 8 months after initial screening and processed with AMYPYPE. Amyloid load was based on global Centiloid (CL) values. Educational level was indexed by formal schooling and subsequent higher education in years. Using linear regression analysis, the main effect of education on CL values was tested across the entire cohort, followed by the assessment of an education-by-diagnostic-group interaction (covariates: age, sex, and recruiting memory clinic). To account for influences of non-AD pathology and comorbidities concerning the tested amyloid-education association, we compared white matter hyperintensity (WMH) severity, cardiovascular events, depression, and anxiety history between lower-educated and higher-educated groups within each diagnostic category using the Fisher exact test or χ2 test. Education groups were defined using a median split on education (Md = 13 years) in a subsample of the initial cohort, for whom this information was available. Across the cohort of 212 individuals with SCD+ (M(Age) = 69.17 years, F 42.45%), 258 individuals with MCI (M(Age) = 72.93, F 43.80%), and 195 individuals with dementia (M(Age) = 74.07, F 48.72%), no main effect of education (ß = 0.52, 95% CI -0.30 to 1.58), but a significant education-by-group interaction on CL values, was found (p = 0.024) using linear regression modeling. This interaction was driven by a negative association of education and CL values in the SCD+ group (ß = -0.11, 95% CI -4.85 to -0.21) and a positive association in the MCI group (ß = 0.15, 95% CI 0.79-5.22). No education-dependent differences in terms of WMH severity and comorbidities were found in the subsample (100 cases with SCD+, 97 cases with MCI, 72 cases with dementia). Education may represent a factor oppositely modulating subjective awareness in preclinical stages and objective severity of ongoing neuropathologic processes in clinical stages.

Abstract 2545: KRAS co-mutational landscape dictates treatment outcomes in pancreatic cancer (PC) patients

Abstract Background: KRAS is commonly mutated in PC patients, with a prevalence of ~80%. A holistic understanding of the landscape of KRAS mutations, co-occurring mutations (co-mutations) in other driver genes, and their impact on patient outcomes treated with current standard-of-care (SoC) therapies may inform better treatment decisions. Methods: In this study, we use a real-world clinico-genomics PC database (ConcertAI’s Genome360TM PC dataset; N=1302) to:1.Examine the distribution of KRAS mutations.2.Identify the genes most frequently co-mutated with KRAS, both positively and negatively, based on their odds ratios.3.Evaluate patient outcomes (overall survival (OS) and progression-free survival (PFS)) for the two most common first-line SoC therapies (FOLFIRINOX: folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin, and GEMPAC: gemcitabine, paclitaxel) stratified by the mutational status of KRAS and TP53. Results: The top 5 most observed KRAS mutations and the top 3 positively (OR>1) and negatively (OR<1) KRAS co-mutated genes are shown in Table 1. 80%, 71%, and 65% of PC patients had pathogenic mutations in KRAS, TP53, and both genes, respectively. In the entire cohort, FOLFIRINOX (n=327, OS/PFS=1.26/0.58 years) was more effective (p-value<0.05) than GEMPAC (n=305, OS/PFS=0.79/0.44 years). However, the underlying genetic makeup (mutational status of KRAS and TP53) significantly affects these outcomes (Table 1). The KRAS+/TP53− (pathogenic mutations in KRAS, but not in TP53) cohort has the worst prognosis, and the advantage of FOLFIRINOX as the treatment of choice is not observed in this cohort. Table 1. Evaluation of KRAS mutational landscape in PC and its impact on treatment outcomes. Top 5 KRAS mutations KRAS mutations G12D G12V G12R Q61H Q61R % PC patients tested positive 42.51 32.52 14.33 4.62 1.79 Top 3 positively and negatively co-mutated genes with KRAS KRAS co-mutated genes Positive association Negative association TP53 CDKN2A SMAD4 BRAF TERT PTEN Odds Ratio 8.56 6.93 6.66 0.05 0.27 0.32 Treatment outcomes for various genetic states of KRAS and TP53 Mutational status OS (years) PFS (years) FOLFIRINOX GEMPAC FOLFIRINOX GEMPAC KRAS+ TP53+ (850) 1.13 (196) 0.68 (188) 0.58 (196) 0.39 (188) KRAS− TP53− (155) 2.08 (40) 1.11 (27) 0.66 (40) 0.51 (27) KRAS+ TP53− (190) 0.77 (33) 0.93 (37) 0.51 (33) 0.33 (37) KRAS− TP53+ (81) 2.14 (15) 0.84 (24) 0.54 (15) 0.4 (24) Conclusions: This study provides insights into the genetic makeup of patients with KRAS mutations and how co-mutation with TP53 affects outcomes of SoC treatments. It highlights the need for comprehensive genetic profiling to make better therapy decisions. Citation Format: Pritha Ghosh, Rohini George, Neeraj Singh, Smita Agrawal. KRAS co-mutational landscape dictates treatment outcomes in pancreatic cancer (PC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2545.

Abstract 4849: Mosaic chromosomal alterations in a prospective cohort of Mexican Americans for cancer risk and genetic insights

Abstract Introduction: In this study, we aim to explore mosaic chromosomal alterations (mCA) and their implications in cancer risk among Mexican Americans (MA) - an expanding yet historically underrepresented ethnic minority in the U.S. In addition, we propose to develop a novel method that identifies high mutant cell fraction (MCF) copy-neutral Loss of heterozygosity (cn-LOH). At sufficiently high MCF, these will look like runs of homozygosity (ROH) and may be missed by current mCA detection techniques that rely on identified germline heterozygote genotypes. Our preliminary findings revealed frequent and widespread homozygosity across the genome, predominantly in short regions (<10 Mb), although some exceeded 100 Mb. Our objective is to advance mCA detection techniques, differentiating cn-LOH from ROH, to deepen our understanding of mCA. Methods: We analyzed SNP array data from blood and saliva samples of 1657 individuals, focusing on cancer and chronic disease risk ages, from the Mano a Mano Mexican American Cohort Study. We applied hapLOH and MoChA, both haplotype-based methods, to detect mCA. To identify high-MCF cn-LOH, we first scanned for observed ROH using PLINK. Separately, we develop a statistical framework through simulations to differentiate high-MCF cn-LOH from ROH. We considered multiple methods; initially, we built a statistical framework using a hypothesis-testing approach (H0: ROH; H1: cn-LOH), where we compared the “B allele” frequency information within observed ROH. To split this information and obtain our groups, we used population genetic principles. Secondly, we classified our events, calculating the likelihood ratio of our statistical hypotheses. Finally, we explored a haplotype-based imputation approach that leverages flanking diploid region information. Results: We identified numerous mCA, predominantly in individuals without cancer. Simulations showed effective classification in larger homozygosity regions (>10 Mb), guiding our methodological focus on detecting shorter high-MCF regions. Not surprisingly, extremely high MCFs (0.99-1) presented challenges in accurate identification. Conclusion and Future Directions: To improve our mCA results description, we will thoroughly characterize and study their association with cancer phenotypes and environmental exposures. We are in the process of genotyping the entire cohort, which consists of over 25,000 participants. To date, our cohort includes 909 cancer cases, of which 262 are hematological malignancies. We sought to design a unique method that differentiates high-MCF cn-LOH from observed ROH, improving current mCA discovery. Our focus is on small regions as they provide limited information to infer event types. Our next step is to characterize and validate our results, especially in pathologically normal samples, as a way of identifying potential biomarkers of interest. Citation Format: Jessica Valdebenito, Justin Wong, Dahwei Chang, Henry Gomez, Kevin T Nead, Yasminka Jakubek, Paul Scheet. Mosaic chromosomal alterations in a prospective cohort of Mexican Americans for cancer risk and genetic insights [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4849.

Reference values for serum calcium in neonates should be established in a population of vitamin D-replete subjects.

Serum calcium is frequently measured during the neonatal period, and is known to be influenced by the vitamin D status. We hypothesized that the 25OHD concentration may influence the lower limit of the serum calcium normal range in neonates. We included in our prospective cohort study 1002 mother-newborn pair recruited from April 2012 to July 2014, in two centers located in the neighborhoods of Paris, France, whose serum calcium was measured at 3 days of life. We established, after exclusion of outliers, a 95% confidence interval (CI) for serum calcium 1) in our whole population of 1002 neonates, 2) in neonates with a cord blood 25OHD concentration ≥ 30 nmol/L, and 3) in those with a 25OHD ≥ 50 nmol/L. The mean serum total calcium was 2.46 ± 0.13 nmol/L [95% CI: 2.19-2.72 mmol/L], 2.47 ± 0.25 mmol/L [95% CI: 2.22-2.72 mmol/L], and 2.50 ± 0.25 mmol/L [95% CI: 2.25-2.75 mmol/L] in the whole group, in the 514 neonates with 25OHD ≥ 30 nmol/L, and in the 202 neonates with 25OHD ≥ 50 nmol/L respectively. The lower limit of the 95% range was significantly higher in neonates with 25 OHD ≥ 30 nmol/L (p<0.05) and ≥ 50 nmol/L (p<0.001) than in the entire cohort. We show that the lower limit of the normal serum calcium range is higher in groups with a higher 25OHD than in unselected subjects. We propose that the reference range for serum calcium in neonates is 2.25 to 2.75 mmol/L.

Virtual range of motion is a safe and acceptable alternative to intra-operative manual range of motion testing in direct anterior robotic total hip arthroplasty

IntroductionIn robotic total hip arthroplasty (THA), virtual range of motion (VROM) modeling allows the surgeon to account for spinopelvic motion and create an impingement-free range of motion that is patient-specific. The primary purpose of this study was to evaluate the risk of dislocation in patients undergoing direct anterior THA using VROM rather than manual ROM trialing. MethodsProspectively collected data was reviewed retrospectively of all consecutive anterior THAs performed by a single fellowship-trained surgeon. No patients were excluded from the study. VROM identified bone and implant impingement, which was recorded in degrees of hip external rotation(ER) at 0° of hip extension (standing), and in degrees of hip internal rotation(IR) at 90° of hip flexion (sitting). No patients had manual ROM trialing performed. Dislocation events were recorded during the first 3 months of follow-up. 362 patients, with a mean age of 67 and mean BMI of 28.8, were included. ResultsThis cohort, including 154 patients (42.5%) with abnormal spinopelvic motion, demonstrated zero dislocations using VROM. The average ER impingement occurred at 60.9° ER (range 20-90°), and 50.8° IR (range 25-90°). Patients with ER impingement <55° had significantly less acetabular anteversion (16.4° ±3.3°, p < 0.001). Compared to the entire cohort, anteversion of the acetabulum was also decreased in the stuck-sitting subgroup (17.4° ±3.3°, p < 0.001) and increased in the stuck standing subgroup (20.5° ±3.6°, p < 0.001). ER impingement was a stronger predictor of acetabular anteversion than spinopelvic motion category (r = 0.458). Patients with ER impingement <45° (6.4%) or IR impingement <35° (6.6%) were “early impingers”. ConclusionIn this cohort of anterior THA patients with a high proportion of abnormal spinopelvic motion, a technique utilizing only VROM produced no dislocations. An impingement-free zone of 45° ER standing and 35° IR sitting is recommended.

Frequency of Clinically Significant Findings in the Surgical Pathology Specimen Following Laparoscopic Sleeve Gastrectomy and Concordance with Preoperative Endoscopy: Insights from a Large Single-Center Experience.

Endoscopy prior to bariatric surgery is not always performed, and in sleeve gastrectomy (SG), the surgical specimen is not always sent for pathological examination. There is limited data on the frequency of clinically significant findings in SG specimens or correlation with preoperative endoscopy. We reviewed 426 consecutive SG patients to determine the concordance of preoperative endoscopy findings in patients with clinically significant postoperative pathology. Preoperative endoscopy was performed on 397 patients (93.2%). Three hundred seventy-three patients had preoperative endoscopy and surgical pathology results available. Then, 20/373 (5.4%) patients had potentially significant postoperative pathology, including intestinal metaplasia, autoimmune metaplastic atrophic gastritis (AMAG), gastrointestinal stromal tumors, and/or gastric cancer. The overall incidence of AMAG in the entire cohort was 2.3%. Preoperative gastric biopsies (to include gastric body) identified AMAG in nearly 1/2 of patients. Patients with clinically significant postoperative pathology results had a median [interquartile range] of 3 [3-5] tissue blocks examined as compared to 3 [1-3] for the remainder of the cohort (p < 0.001). This is one of the largest studies describing clinically significant postoperative pathology after SG. AMAG, in particular, is of particular importance as it is associated with a 3-fivefold increase in risk for gastric cancer. The incidence of significant postoperative pathology in this population is small but potentially clinically significant and requires validation in larger studies. We recommend wider sampling in preoperative endoscopy (body and antrum), especially in patients being planned for gastric bypass, consideration for routine pathological examination of SG surgical specimens, with careful gross examination and targeted sampling.

Outcome of patients with relapsed or refractory nonrhabdomyosarcoma soft tissue sarcomas enrolled in phase 2 cooperative group clinical trials: A report from the Children's Oncology Group.

The aim of this study was to estimate the event-free survival (EFS) of children and young adults with relapsed or refractory nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) treated in nonrandomized phase 2 studies conducted by the Children's Oncology Group (COG) and predecessor groups to establish a benchmark EFS for future phase 2 NRSTS trials evaluating the activity of novel agents. A retrospective analysis of patients with recurrent or refractory NRSTS prospectively enrolled in nonrandomized phase 2 COG and predecessor group trials between 1994 and 2015 was conducted. EFS was defined as disease progression/relapse or death and calculated via the Kaplan-Meier method. The log-rank test and relative risk regression were used to compare EFS distribution by age at enrollment, sex, race, NRSTS histology, prior lines of therapy, calendar year of trial, and type of radiographic response. In total, 137 patients were enrolled in 13 phase 2 trials. All trials used radiographic response rate as a primary outcome, and none of the agents used were considered active on the basis of trial-specified thresholds. The estimated median EFS and 6-month EFS of the entire study cohort was 1.5 months (95% confidence interval [CI], 1.3-1.8 months) and 19.4% (95% CI, 12.7%-26%), respectively. No difference in EFS was observed by age at enrollment, sex, race, NRSTS histology subtype, prior lines of therapies, and trial initiation year. EFS significantly differed by radiographic response. The EFS for children and young adults with relapsed or refractory NRSTS remains suboptimal. Established EFS can be referenced as a benchmark for future single-agent phase 2 trials incorporating potentially active novel agents in this population.

Dermatological patients with itch report more stress, stigmatization experience, anxiety and depression compared to patients without itch: Results from a European multi-centre study.

Itch as the most common symptom in dermatology has been shown to be related to psychological factors such as stress, anxiety and depression. Moreover, associations were found between perceived stigmatization and itch. However, studies investigating the differences between patients with dermatoses with and without itch regarding perceived stress, stigmatization, anxiety and depression are missing. Therefore, one of the aims of the second study of the European Society for Dermatology and Psychiatry (ESDaP study II) was to investigate these relationships in a large cohort of patients with different itchy dermatoses. 3399 patients with 14 different itchy dermatoses were recruited at 22 centres in 17 European countries. They filled in questionnaires to assess perceived stigmatization, stress, signs of clinically relevant anxiety or depression, itch-related quality of life, the overall health status, itch duration, frequency and intensity. The most significant association between the severity of itching and the perception of stress was observed among individuals with rosacea (correlation coefficient r = 0.314). Similarly, the strongest links between itch intensity and experiences of stigmatization, anxiety, and depression were found in patients with seborrheic dermatitis (correlation coefficients r = 0.317, r = 0.356, and r = 0.400, respectively). Utilizing a stepwise linear regression analysis, it was determined that within the entire patient cohort, 9.3% of the variation in itch intensity could be accounted for by factors including gender, levels of anxiety, depression, and perceived stigmatization. Females and individuals with elevated anxiety, depression, and perceived stigmatization scores reported more pronounced itch intensities compared to those with contrary attributes. This study underscores the connection between experiencing itch and its intensity and the psychological strain it places on individuals. Consequently, psychological interventions should encompass both addressing the itch itself and the interconnected psychological factors. In specific cases, it becomes imperative for dermatologists to direct individuals towards suitable healthcare resources to undergo further psychological assessment.

Longitudinal Changes in Choroidal Thickness Varied With Refractive Progression in Myopic and Non-Myopic Children: A Two-Year Cohort Study.

To evaluate the longitudinal changes in subfoveal choroidal thickness (SFCT) in children with different refractive status. A total of 2290 children 3 to 14years old who attended the first year of kindergarten (G0), first year of primary school (G1), fourth year of primary school (G4), or first year of junior high school (G7) in Guangzhou, China, were recruited and followed up for 2years. All participants received cycloplegic autorefraction, axial length measurement and SFCT measurement using a CIRRUS HD-OCT device. Children were divided into groups of persistent non-myopia (PNM), persistent myopia (PM), or newly developed myopia (NDM). Children in the PNM and PM groups were further divided into subgroups of stable refraction (absolute mean annual spherical equivalent refraction [SER] change < 0.5D) and refractive progression (absolute mean annual SER change ≥ 0.5D). The mean ± SD ages for the G1 to G7 cohorts were 3.89 ± 0.30, 6.79 ± 0.47, 9.71 ± 0.34, and 12.54 ± 0.38, years, respectively. SFCT consistently decreased in the NDM group across the G1 to G7 cohorts (all P<0.001) and exhibited variability across different age cohorts in the PNM and PM groups. Further subgroup analysis revealed significant thickening of SFCT in the PNM-stable group among the G0, G1, and G7 cohorts (all P<0.05), whereas it remained stable among all cohorts in the PM-stable group (all P>0.05). Conversely, SFCT exhibited thinning in the G4 and G7 cohorts in the PM-progressive group (both P<0.01) and for the entire cohort of children in the PNM-progressive group (P=0.012). SFCT increased in nonmyopic children with stable refraction, remained stable in myopic children maintained stable refraction, and decreased in those with refractive progression, whether they were myopic or not.

Learning curve for intracorporeal robotic Padua ilealbladder: 10-year functional assessment from a high-volume single-centre series.

To assess the impact of the learning curve (LC) on perioperative and long-term functional outcomes of a consecutive single-centre series of robot-assisted radical cystectomy with Padua intracorporeal orthotopic neobladder. Patients treated between 2013 and 2022 were included, with ≥1 year of follow-up. The entire cohort was divided in tertiles. Categorical and continuous variables were compared. Joinpoint regression analysis was used to identify significant changes over the decade in linear slope of the 1-year day- and night-time continence. Uni- and multivariable Cox regression analyses identified predictors of day- and night-time continence recovery. Day-time continence was defined as 'totally dry' (no pads), night-time continence as pad wetness ≤50 mL (one safety pad). Overall, 200 patients were included. The mean hospital stay (P = 0.002) and 30-day complications (P = 0.04) significantly reduced over time; the LC significantly impacted on Trifecta achievement (P < 0.001). The 1-year day- and night-time continence probabilities displayed a significant improving trend (day-time continence annual average percentage change [AAPC] 11.45%, P < 0.001; night-time continence AAPC 10.05%, P = 0.009). The LC was an independent predictor of day- (hazard ratio [HR] 1.008; P < 0.001) and night-time continence (HR 1.004; P = 0.03) over time. Patients at the beginning of the LC had significantly longer hospitalisations, more postoperative complications, and lower Trifecta rates. At the 10-year analyses, we observed a significant improving trend for both the 1-year day- and night-time continence probabilities, highlighting the crucial role of the LC. However, we are unable to assess the case volume needed to achieve a plateau in terms of day- and night-time continence rates.

Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood. To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles. Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed. In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively). PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies.

Very Early Recurrence After Curative Resection for Pancreatic Ductal Adenocarcinoma: Proof of Concept for a "Biological R2 Definition".

Very early recurrence after radical surgery for pancreatic ductal adenocarcinoma (PDAC) has been poorly investigated. This study was designed to evaluate this group of patients who developed recurrence, within 12 weeks after surgery, defined as "biological R2 resections (bR2)." Data from patients who underwent surgical resection as upfront procedure or after neoadjuvant treatment for PDAC between 2015 and 2019 were analyzed. Disease-free, disease-specific survival, and independent predictors of early recurrence were examined. The same analysis was performed separately for upfront and neoadjuvant treated patients. Of the 573 patients included in the study, 63 (11%) were classified as bR2. The rate of neoadjuvant treatment was similar in bR2 and in the remaining patients (44 vs. 42%, p = 0.78). After a median follow-up of 27 months, median DFS and DSS for the entire cohort were 17 and 43 months, respectively. Median DSS of bR2 group was 13 months. The only preoperative identifiable independent predictor of very early recurrence was body-tail site lesion, whereas all other were pathological: higher pT (8th classification), G3 differentiation, and high lymph node ratio. These predictors were confirmed for patients undergoing upfront surgery, whereas in the neoadjuvant group the only independent predictor was pT. One of ten patients with "radical" resected PDAC relapses very early after surgery (bR2); hence, imaging must be routinely repeated within 12 weeks. Despite higher biological aggressiveness and worse pathology, this bR2 cluster eludes our preoperative examinations.

Pregnancies and births in women with previous abdominal myomectomy

Background: Uterine leiomyoma may cause pelvic symptoms and may also interfere with the reproductive desires of many women. Consequently, some women may undergo myomectomy as a fertility sparring method to relieve symptoms or as a method to improve their fertility. Objective: We aimed to assess pregnancies and deliveries in women with previously myomectomy both in spontaneous pregnancies and with use of assisting reproductive techniques. Also, we aimed to asses if the reproductive prognosis differed between different surgical approaches. Study design: In this historical cohort study we collected data regarding myomectomies, pregnancies, use of assisting reproductive techniques and births from national health registries. All Danish women were followed from 1996 through 2017. Results: Of 5.281 women undergoing myomectomy, 97% had one and 3% had two or more myomectomies. Median age at first surgery was 38.5 years (interquartile range 34.1-44.6 years). Of 5.430 myomectomies conducted, 71% were done by laparotomy and 29% by laparoscopy. Of the 5.281 women treated with myomectomy, 1.586 (30%) became pregnant and 1.145 (22%) gave birth. In the entire cohort of 5.281 women, 1.056 (20%) were treated with assisting reproductive techniques. Of these 1.056 women, 659 (62%) got pregnant and 461 (44%) delivered. Median time from surgery to pregnancy was 1.2 years. Significantly more women became pregnant and gave birth when treated with laparotomy as compared to laparoscopy. However, the effect was only significant for women younger than 30 years or older than 40 years at first surgery. Conclusion: As the proportion of women attempting pregnancy was unknown, the overall figure of 30% pregnancy rate is a minimum estimate of the real chance of achieving pregnancy after myomectomy.

Clinical outcomes of spinal cord stimulation in patients with intractable leg pain in Japan.

Neuromodulation through spinal cord stimulation (SCS) is a therapeutic option for relieving leg pain and improving the chances of limb salvage in patients with intractable chronic limb-threatening ischemia (CLTI); however, there is no consensus on its indications. The aim of this study was to assess the clinical outcomes of SCS in patients with intractable leg pain caused by various diseases treated in the department of cardiovascular medicine in Japan. This was a retrospective study of patients who underwent SCS for pain management. Patients were considered eligible for the therapy if they met the following criteria: (1) intractable leg pain (numerical rating scale [NRS] score of 10), (2) no revascularization option, and (3) no septicemia. Twenty patients (mean age: 77 years; men/women: 11/9) were included in this study. The NRS score of the patients significantly reduced from 10 ± 0 before procedure to 4 ± 3 at discharge (p < 0.001). The clinical response rate of the entire cohort was 65% (13/20) at 17 ± 14 months after implantation; however, patients with intractable CLTI showed a low response rate (45%), whereas those with subacute limb ischemia showed a high response rate (100%). A multivariable regression analysis showed that hemoglobin level was significantly associated with treatment response, even after adjusting for age and sex (p = 0.026). The area under the receiver operating characteristic curve for the correlation between hemoglobin level (cutoff, 11.4 g/dL) and clinical response to SCS was 0.824 (0.619-1). SCS can reduce clinical symptoms in majority of patients with intractable leg pain. Although implantation of an SCS device has been shown to improve microvascular perfusion insufficiency, the correlation between hemoglobin level and the clinical effect of SCS indicates that a preserved microcirculatory vascular bed is essential for the therapy to be effective.