Inferior Outcomes Research Articles

Comparison of clinical outcomes in women with surgically treated early primary cervical cancer: Lymphadenectomy versus sentinel lymph node biopsy.

The primary objective of this study was to elucidate the impact of sentinel lymph node (SLN) mapping and biopsy techniques on the clinical outcomes of women with early primary cervical cancer. All consecutive women with clinically determined stage I-IIA cervical cancer who underwent lymph node assessment with either SLN mapping or conventional pelvic/para-aortic lymphadenectomy were reviewed. Women in the SLN group (n=33) had fewer total dissected pelvic nodes (8.3±5.9 versus 17.4±7.7, p<0.001), less intraoperative blood loss (513±332mL versus 1228±1170mL, p<0.001), a shorter length of hospital stay (7.1±2.4 versus 10.2±6.1 days, p=0.004) and a trend toward a lower incidence of lymphocysts (3% versus 14%, p=0.090) than women in the conventional lymphadenectomy group (n=74). The rates of recurrence-free survival (3-year: 87.6% vs. 82.9%) and overall survival (3-year: 100% vs. 91.0%) did not differ between the SLN group and the conventional lymphadenectomy group (p=0.846 and p=0.254, respectively). SLN biopsy does not seem to be associated with an inferior survival outcome compared with conventional lymphadenectomy in women with early primary cervical cancer. In addition, it is associated with less blood loss and a shorter length of hospital stay.

A critical review of management of allogeneic transplant-eligible adults with Ph+ acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) in 20%-30% of adult patients contains the Philadelphia (Ph+) chromosome. Historically, Ph+ ALL denoted a markedly inferior outcome and long-term survival in the absence of an allograft was uncommon. However, the advent of targeted therapy directed against the BCR::ABL1 fusion protein with various tyrosine kinase inhibitors (TKIs) has markedly improved the prognosis, resulting in a number of treatment controversies in allograft-eligible patients. Which is the best TKI to use in induction? What is the clinical relevance of the subdivision of Ph+ ALL into multilineage vs lymphoid types? Do all patients in first morphological complete remission (CR1) after induction and consolidation with chemotherapy/TKI require an allograft? If not, what risk factors predict a poor outcome without an allograft? Can chemotherapy-free approaches, such as blinatumomab in conjunction with more potent TKIs, obviate the need for an allograft in high-risk patients? What is the best strategy to deal with persistent or emerging minimal residual disease both pre- and post-transplant? Is maintenance TKI indicated in all patients post allograft? Can salvage therapy and a subsequent allograft cure patients who relapse after not being transplanted in CR1? This manuscript reviews the latest data influencing contemporary management and discusses these controversies.

Abstract PR-17: Genomic and transcriptomic characterization of pancreatic cancer patients on the PASS-01 trial

Abstract Overall survival for patients with advanced PDAC remains less than 1 year. Biomarkers are needed to select chemotherapy regimens, either alone or in combination with novel agents. PASS-01 compared mFOLFIRINOX and Gemcitabine/nab-Paclitaxel in a phase II randomised control trial while prospectively exploring tissue, liquid and organoid biospecimens to interrogate putative biomarkers of chemotherapy response and resistance. Methods PASS-01 was conducted across 6 sites in North America. Patients with de novo metastatic disease and a lesion amenable to core biopsy were included. Cases with germline pathogenic variants in BRCA1/2 or PALB2 were excluded. Up to 6 core biopsies were obtained with priorities for clinical diagnosis, patient derived organoids (PDOs), and whole genome and transcriptome sequencing (WGTS). WGTS were performed at a single site following laser capture microdissection. WGS reports were clinically (CAP) accredited and annotated mutations, copy number alterations, mutational signatures, TMB and structural variant patterns. KRAS allelic states were documented with major imbalances in mutant KRAS (KRASmaj) defined as mutant: WT copy number &amp;gt;3. Transcriptomic subtypes (classical vs. basal-like) were classified as previously described (Moffitt et al., 2015). WGTS results were discussed at a molecular tumor board with PDO pharmacotyping to determine best second line options. Results: 160 patients were included in the intention to treat population, of these WGS was available in 127 (79%) and additional NGS reports in 20 (13%). RNA-seq was successful in 119 (74%) and the basal-like subtype accounted for 29% and was associated with inferior outcomes. KRASm were evident in 91% and KRASG12D represented 45%. Tumor suppressors TP53, CDKN2A and SMAD4 were lost in 81%, 76% and 39% respectively. MTAP deletion was present in 40%, largely synonymous with CDKN2A deletions. Commonly co-altered genes in the dataset included epigenetic regulators (ARID1A, KMT2C, KDM6A) and TGFBR2. KRASmaj was present in 30% of cases and polyploid tumors in 50%. 50% of basal-like PDAC harboured KRASmaj compared to 22% of classical PDAC, p&amp;lt;0.01. Dominant signatures (SBS) included age related SBS1, 5 and 8. Additionally, we saw a prevalence of SBS17 and APOBEC SBS2/13, signatures which occurred more frequently compared to a similarly characterised resected cohort. Unstable genotypes were present in 24% with somatic-HRD evident in 3%. Of KRASWT PDAC, 58% harboured class I-II BRAF variants. KRAS WT PDAC had fewer co-mutations and in one case where an NGS report did not find a driver, a novel fusion in SLC4A4-RASGRF2 was identified. 28 molecular tumor boards took place throughout the trial influencing 50% obtaining a 2nd-line treatment. Conclusion: The PASS-01 cohort exhibits a heterogeneous group of genotypes and molecular subgroups. Certain mutational processes are more evident in advanced compared to resected PDAC. The impact of subgroups on survival and chemotherapy response is ongoing with a planned data lock on July 15th. Results will be presented at the meeting. Citation Format: Grainne M O'Kane, Gunho Jang, Trevor J Pugh, Julie Wilson, Stephanie Ramotar, Daniel A King, Dan Laheru, Ken H Yu, Kimberly J Perez, Amber Habowski, Erica S Tsang, Robert C Grant, Andrew J Aguirre, Raymond W-J Jang, Craig E Devoe, Eileen M O'Reilly, Anna Dodd, Brian M Wolpin, Xiang Y Ye, Elizabeth M Jaffee, David Tuveson, Steven Gallinger, Jennifer J Knox, Faiyaz Notta. Genomic and transcriptomic characterization of pancreatic cancer patients on the PASS-01 trial [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-17.

Socioeconomic inequalities in patients undergoing abdominal wall reconstruction in the North-West of England, UK: a three-centre retrospective cohort study

PurposePatients from deprived areas are more likely to experience longer waiting times for elective surgery, be multimorbid, and have inferior outcomes from elective and emergency surgery. This study aims to investigate how surgical outcomes vary by deprivation for patients undergoing elective abdominal wall reconstruction.MethodsA three-centre retrospective cohort study was conducted across three hospitals in North-West England, including patients with complex ventral hernias undergoing abdominal wall reconstruction between 2013 and 2021. Demographic data, comorbidities, and index of multiple deprivation quintiles were recorded.Results234 patients (49.6% female), age 57 (SD 13) years, underwent elective abdominal wall reconstruction. Significantly higher unemployment rates were found in the most deprived quintiles (Q1 and Q2). There were more smokers in Q1 and Q2, but no significant deprivation related differences in BMI, diabetes, chronic kidney disease or ischaemic heart disease. There were also higher rates of Clavien-Dindo 1–2 complications in Q1 and Q5, but no difference in the Clavien-Dindo 3–4 outcomes. Patients in Q1 and Q5 had a significantly greater hospital length of stay.ConclusionThe association between deprivation and greater unemployment and smoking rates highlights the potential need for equitable support in patient optimisation. The lack of differences in patient co-morbidities and hernia characteristics could represent the application of standardised operative criteria and thresholds. Further research is needed to better understand the relationship between socioeconomic status, complications, and prolonged hospital length of stay.

The impact of trial inclusion criteria on outcomes in DLBCL patients treated with R-CHOP in the first line: a Danish nationwide study

Up to 50% of diffuse large B-cell lymphoma (DLBCL) patients are ineligible for participation in clinical trials. Ineligible patients have inferior outcomes, but less is known about the impact of commonly used organ-function-based inclusion criteria on drug efficacy estimates. Data on DLBCL patients treated with CHOP+/-rituximab were retrieved from the Danish Lymphoma Registry. Trial inclusion criteria were extracted from four international DLBCL trials (REMoDL-B, GOYA, POLARIX, and HOVON-84). Differences in overall survival (OS) and 5-year restricted mean survival differences (5 y-RMSDs) between trial eligible and ineligible patients were computed. The effectiveness of adding rituximab to CHOP was quantified by the 5 y-RMSD between CHOP and R-CHOP-treated patients and the impact of individual trial criteria on estimated effectiveness was quantified by Shapley-values. In total, 4,083 R-CHOP-treated and 890 CHOP-treated DLBCL patients were included. Across the trials, 18.6-29.3% of the included R-CHOP-treated patients were deemed ineligible for trial based on organ function and performance status alone. Ineligible patients had significantly worse survival, with adjusted absolute differences in 5-year OS of 9-15%. The impact of individual criteria on the estimated effectiveness of adding rituximab to CHOP was small (Shapley-value range, −2.74-0.31). Using a smaller set of criteria derived from a data-driven approach, the number of eligible patients increased by 16-38% and the 5 y-RMSD increased by 0.7-3.1 months. In conclusion, OS among trial ineligible DLBCL patients is inferior as expected, but relaxing trial criteria would have increased the number of trial participants without making major changes in estimated efficacy for a hypothetical CHOP versus R-CHOP trial. This does not necessarily imply that trial findings based on selected patients are unreliable, as the estimated effectiveness of adding rituximab to CHOP was only slightly affected by omitting selected inclusion criteria.

Comparing oncological outcomes of robotic versus open surgery in the treatment of endometrial cancer.

Robotic surgery has been incorporated in the treatment of endometrial cancer, with evidence suggesting that minimal access surgery offers advantages over laparotomy including less blood loss, lower rate of perioperative complications, and accelerated postoperative recovery. The laparoscopic approach to cervical cancer (LACC) study has recently demonstrated inferior survival outcomes in cervical cancer patients treated with minimal access surgery including robotic surgery. It is, therefore, imperative that further evaluation of the latter in endometrial cancer is performed. A retrospective analysis of clinical data was performed. We compared two different types of surgery performed for the treatment of FIGO stage 1 to 3 endometrial cancer; open surgery performed in the years 2013-2015 vs robotic surgery performed in 2017-2019, after the implementation of the robotic program in our institution. Main outcome measures were recurrence-free survival and overall survival, with secondary outcomes including surgical morbidity and postoperative recovery. We compared 123 patients who had open surgery with 104 patients who underwent robotic surgery. One case from the second group was converted to open surgery due to the inability to complete it robotically. After a median follow-up of 68months, there was no difference in recurrence-free survival or overall survival between the two groups. Length of stay after an operation was significantly different with mean hospital stay of 1.6days after robotic surgery and 5days after open surgery (p = 0.001). No significant difference was identified in the rate of complications (p = 0.304). Our analysis has demonstrated that robotic surgery offers better perioperative outcomes without compromising the oncological safety.

Relationship between CT-derived cervical muscle mass and quality, systemic inflammation, and survival in symptomatic patients undergoing carotid endarterectomy.

Sarcopenia appears to be associated with inferior outcomes in surgical conditions. Chronic systemic inflammation confers an inferior long-term prognosis in cardiovascular disease and is associated with the development of sarcopenia. The aim of this study was to describe the prognostic role of sarcopenia assessed using computed tomography (CT)-derived body composition analysis and systemic inflammation in patients undergoing carotid endarterectomy for symptomatic carotid stenosis. In this retrospective cohort study, patients undergoing carotid endarterectomy for symptomatic carotid stenosis between 1 January 2011 and 1 October 2021 at four referral centres were included. The C3 skeletal muscle index and C3 skeletal muscle density were recorded from preoperative CT images. Systemic inflammation was assessed using the preoperative systemic inflammatory grade (SIG). The primary outcome was overall mortality during the study interval. A total of 618 patients were included, with a median follow-up of 69 (interquartile range 34-85) months. On univariable analysis, age greater than or equal to 75 years (P < 0.001), American Society of Anesthesiologists (ASA) grade greater than II (P < 0.001), low C3 skeletal muscle index (P = 0.002), low C3 skeletal muscle density (P < 0.001), SIG greater than or equal to 2 (P < 0.001), and low L3 derived skeletal muscle index (P < 0.001) were associated with increased mortality, whereas body mass index greater than or equal to 25 kg/m2 was associated with decreased mortality (P = 0.023). On multivariable analysis, age 75 years or older (HR 2.17 (95% c.i. 1.58 to 2.97), P < 0.001), ASA grade greater than II (HR 2.06 (95% c.i. 1.35 to 3.12), P < 0.001), low C3 skeletal muscle density (HR 1.84 (95% c.i. 1.33 to 2.54), P < 0.001), and SIG greater than or equal to 2 (HR 1.63 (95% c.i. 1.33 to 1.99), P < 0.001) were independently associated with increased mortality. Cervical CT-derived muscle mass and density, and markers of systemic inflammation, such as systemic inflammatory grade, may be associated with an inferior long-term prognosis after carotid endarterectomy.

Kidney re-transplantation in the ipsilateral iliac fossa: a surgeon's perspective on perioperative outcome.

Compared with primary transplantation, ipsilateral renal re-transplantation is associated with an increased risk of surgical complications and inferior graft outcomes. This study investigates whether an ipsilateral re-transplantation approach per se is an independent risk factor for surgical complications and early graft loss. In this retrospective, single-centre analysis, surgical complications and early graft outcomes of ipsilateral kidney re-transplantations from January 2007 to December 2017 were compared with primary transplantations and contralateral re-transplantations. Univariate and multivariate binary logistic regression analyses were performed to identify risk factors for surgical complications requiring surgical revision and graft loss within the first year after transplantation. Of the 1489 kidney transplantations, 51 were ipsilateral, 159 were contralateral re-transplantations and 1279 were primary transplantations. Baseline characteristics did not differ between the ipsilateral and contralateral re-transplant recipients except for current and highest panel reactive antibody levels. Major complications requiring surgical revision were significantly more frequent in ipsilateral re-transplantations (P=.010) than in primary transplantations but did not differ between ipsilateral and contralateral re-transplantations (P=.217). Graft loss within the first year after transplant was 15.7% in the ipsilateral versus 8.8% in the contralateral re-transplant group (P=.163) versus 6.4% in the primary transplantation group (P=.009). In a multivariate regression model, ipsilateral re-transplantation was not identified as an independent risk factor for complications requiring surgical revision or first-year graft loss. Ipsilateral renal re-transplantation is not a risk factor for inferior outcomes. Graft implantation into a pre-transplanted iliac fossa is a feasible and valid therapeutic option.

Outcomes After Extracorporeal Shockwave Therapy for Chronic Noninsertional Achilles Tendinopathy Compared With Chronic Insertional Achilles Tendinopathy: A Retrospective Review.

Extracorporeal shockwave therapy (ESWT) is a noninvasive treatment modality that is used in the treatment of chronic Achilles tendinopathy (AT). To (1) retrospectively assess outcomes after ESWT for both noninsertional AT (NAT) and insertional AT (IAT) at >1-year follow-up and (2) identify potential predictors of outcomes. Cohort study; Level of evidence, 3. Chart review was conducted to identify patients who underwent ESWT for AT with a minimum of 1-year follow-up. Data collected and assessed included patient demographic characteristics, pathological characteristics including the location of AT (NAT or IAT), presence of a Haglund deformity, and severity of tendon degeneration on magnetic resonance imaging (MRI), in addition to treatment characteristics including number of sessions and intensity of ESWT. The Victorian Institute of Sports Assessment-Achilles (VISA-A) and visual analog scale (VAS) pain scores were obtained before ESWT, 6 months after ESWT, and at final follow-up. Failures were also recorded, which were defined as no improvement in VISA-A or VAS scores or need for surgical intervention. Linear regression was performed to identify potential predictors of inferior subjective clinical outcomes and failures. Survival analysis was conducted using Kaplan-Meier curves. The study included 52 patients with IAT and 34 patients with NAT. The mean follow-up in the NAT cohort was 22.3 ± 10.2 months and the mean follow-up in the IAT cohort was 26.8 ± 15.8 months. Improvements in VISA-A and VAS scores were observed in the NAT cohort at 6-month follow-up and at final follow-up (P < .05). Improvements in VISA-A and VAS scores were recorded in the IAT cohort at 6-month follow-up, which subsequently deteriorated at final follow-up. In the NAT cohort, the failure rate at 6-month follow-up was 11.8%, which increased to 29.4% at final follow-up. In the IAT cohort, the failure rate at 6-month follow-up was 32.7%, which increased to 59.6% at final follow-up. Predictors of inferior subjective clinical outcomes and failures in the NAT cohort included pre-ESWT subjective clinical score, male sex, presence of a cardiovascular risk factor, and more severe MRI grading of tendinopathy. Predictors of inferior subjective clinical outcomes and failures in the IAT cohort included pre-ESWT subjective clinical score and more severe MRI grading of tendinopathy. Superior subjective clinical outcomes together with a lower failure rate were maintained for >1 year in the NAT cohort compared with the IAT cohort, calling into question the long-term benefit of ESWT for patients with IAT.

Comprehensive sequential genetic analysis delineating frequency, patterns, and prognostic impact of genomic dynamics in a real-world cohort of patients with lower-risk MDS.

The acquisition of subsequent genetic lesions (clonal evolution, CE) and/or the expansion of existing clones (CEXP) contributes to clonal dynamics (CD) in myelodysplastic syndromes (MDS). Although CD plays an important role in high-risk patients in disease progression and transformation into acute myeloid leukemia (AML), knowledge about CD in lower-risk MDS (LR-MDS) patients is limited due to lack of robust longitudinal data considering the long clinically stable courses of the disease. In this retrospective analysis, we delineate the frequency and the prognostic impact of CD in an unselected real-world cohort of LR-MDS patients. We screened 68 patients with a median follow-up of 40.5 months and a median of 7.5 (range: 2-22) timepoints for CE and CEXP detected by chromosomal banding analysis, fluorescence in situ hybridization, sequencing, and molecular karyotyping. In 30/68 patients, 47 CE events and a CD rate of 1 event per 4 years were documented. Of note, patients with at least 1 CE event had an increased probability for subsequent treatment. Unexpectedly, CE did not correlate with inferior outcomes, which could be reasonably explained by CD detection triggering the subsequent start of a disease-modifying therapy.

Prosthetic conduits have worse outcomes compared with great saphenous vein conduits in femoropopliteal and infrapopliteal bypass in patients with chronic limb-threatening ischemia

ObjectiveSingle segment great saphenous vein (SSGSV) traditionally has been considered the gold standard conduit for infrainguinal bypass. There are data supporting similar outcomes with prosthetic femoral-popliteal bypass. Moreover, some investigators have advocated for prosthetic conduit for femoral tibial bypass when GSV is inadequate or unavailable. We sought to evaluate long-term outcomes of infrainguinal bypass based on conduit type for treating chronic limb-threatening ischemia (CLTI). MethodsData from the Best Endovascular vs Best Surgical Therapy of Patients with CLTI multicenter, prospective, randomized controlled trial, comparing infrainguinal bypass with endovascular therapy in patients with CLTI, were evaluated. In this as-treated analysis, we compared outcomes of infrainguinal bypass using prosthetic, alternative autogenous vein (AAV), and cryopreserved vein (Cryo) with SSGSV bypass. Kaplan-Meier and multivariable analyses were performed to examine the associations of conduit type with major adverse limb events (MALE), reinterventions, above-ankle amputations, and all-cause death rates. ResultsIn total, 784 bypasses were analyzed (120 prosthetic, 33 AAV, 21 Cryo, AND 610 SSGSV). For prosthetic and SSGSV, the distribution was 357 femoropopliteal (93 prosthetic and 264 GSV) and 373 infrapopliteal (27 prosthetic and 346 GSV). The mean age for the overall cohort was 67.1 years; 27.4% were female, 29.9% were non-White, and 11.5% were of Hispanic ethnicity. Patients undergoing prosthetic bypass were older (69.2 years vs 66.7 years); more likely to have chronic obstructive pulmonary disease (22.5% vs 14.0%), prior coronary artery bypass grafting (88.9% vs 66.5%), and prior stroke (23.3% vs 14%); but less often were of Hispanic ethnicity (5.8% vs 12.6%) and had diabetes (59.2% vs 71.3%) (P < .05 for all). For femoropopliteal bypass, use of prosthetic conduit was associated with increased major reinterventions at 3 years overall (19.0% vs 11.5%; P = .06) and on risk-adjusted analysis (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.09-4.2; P = .028). No significant differences in MALE or death, above-ankle amputation, or death were observed. Outcomes were similar for bypasses to above-knee popliteal targets and below-knee popliteal targets. For infrapopliteal bypass, the use of a prosthetic conduit was associated with increased major reintervention (25.3% vs 10.3%; P = .005), death (68.6% vs 34.8%; P < .001), and MALE or death (90.0% vs 48.1%; P < .001) at 3 years. After risk adjustment, infrapopliteal bypass with prosthetic conduit was associated with higher major reintervention (HR, 4.14; 95% CI, 1.36-12.6; P = .012), above-ankle amputation (HR, 4.64; 95% CI, 1.59-13.5; P = .005), death (HR, 2.96; 95% CI, 1.4-6.2; P = .004), and MALE or death (HR, 3.59; 95% CI, 1.64-7.86; P = .001) compared with bypass with SSGSV. Overall, AAV had similar outcomes at 3 years as SSGSV; however, Cryo had significantly higher above-ankle amputation (50.0% vs 12.8%) (HR, 4.2; 95% CI, 1.68-10.5; P = .002), major reintervention (41.9% vs 10.7%) (HR, 3.12; 95% CI, 1.18-8.22; P = .02), and MALE/death (88.8% vs 37.8%) (HR, 2.96; 95% CI, 1.43-6.14; P = .004). ConclusionsThe use of a prosthetic conduit in infrainguinal bypass is associated with inferior outcomes compared with bypass using SSGSV, particularly for bypass to infrapopliteal targets. Cryo grafts were infrequent and also demonstrated inferior outcomes. SSGSV remains the preferred conduit of choice for infrainguinal bypass.

Cochlear Implantation in Post-Meningitis Deafness: Audiological, Imaging, and Postoperative Outcomes: A Systematic Review With Qualitative Synthesis.

Post-meningitis deafness (PMD) is a potentially devastating cause of hearing loss among pediatric and adult patients, for which hearing rehabilitation with cochlear implants (CIs) remains the standard of care. To date, there have been limited systematic studies on the impact of cochlear ossification (CO) and time-to-implantation (TTI) on audiological outcomes. An online database search was performed on the PubMed, Embase, and Scopus databases for articles within the past 20 years pertaining to audiological outcomes among pediatric and adult patients with PMD. Information on study characteristics, patient demographics, clinical outcomes, and postoperative complications was collected and analyzed. From 8,325 articles generated in the original search, 11 were included in the final analysis, representing 376 patients in total. Of the articles discussing TTI, the majority (3 of 4) found that a shorter TTI of 6 months on average led to improved audiological outcomes compared with control groups with a longer TTI. Of the articles that discussed the impact of preoperative CO, the majority (4 of 6) found that the presence of CO had a detrimental effect on postoperative audiological outcomes after CI. Finally, of the articles that discussed long-term audiological outcomes for PMD compared with the non-PMD control group after CI, the majority (4 of 7) found that PMD patients had inferior long-term outcomes. CI is a safe and effective treatment modality for PMD, with the majority of literature demonstrating improved long-term outcomes for patients without CO and a reduced TTI.

Effect of Medial or Lateral Graft Failure on Graft Volume and Clinical Outcomes After Superior Capsule Reconstruction for Irreparable Rotator Cuff Tears

Background: Graft failure is a common complication after superior capsule reconstruction (SCR). The graft in SCR is fixed on the greater tuberosity and superior glenoid, and graft failure has been reported on both sides. Purpose: To evaluate the clinical manifestations of patients with graft failure after SCR and identify the clinical and radiological differences between medial and lateral graft failure. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent SCR with a dermal allograft for symptomatic irreparable rotator cuff tears between March 2018 and September 2021 were retrospectively reviewed. All patients had minimum 2-year follow-up and underwent magnetic resonance imaging at 6 months postoperatively. Patients with graft failure were divided into 2 groups: those with lateral graft failure on the greater tuberosity side (group I) and those with medial graft failure on the glenoid side (group II). Patients with intact grafts were included in group III as a control group. Intergroup differences in clinical and radiological characteristics were analyzed, and multiple regression analysis was performed. Results: Among the 93 patients included, there were 18 patients in group I, 15 in group II, and 60 in group III. Overall, 11 patients (61.1%) in group I and 9 patients (60.0%) in group II had a partial graft rupture at one anchor. The postoperative graft volume was significantly lower in group I than in groups II and III (2514.0 ± 564.3 mm3, 3183.5 ± 547.1 mm3, and 3198.0 ± 584.8 mm3, respectively; P = .002 for group I vs II; P < .001 for group I vs III). The acromiohumeral distance (AHD) was significantly increased at 6 months postoperatively compared with before surgery in group I (6.6 ± 1.6 mm vs 4.3 ± 1.9 mm, respectively; P < .001) and group II (7.4 ± 1.3 mm vs 5.7 ± 1.7 mm, respectively; P = .002). However, group I exhibited a significantly greater decrease in the AHD over time than group II (P < .001) and a significantly lower AHD at the final follow-up than the other groups (P < .001). The postoperative American Shoulder and Elbow Surgeons score was significantly lower in group I than in the other groups (P < .001). On multiple regression analysis, fatty infiltration of the infraspinatus muscle, Hamada grade, and graft width were independent factors for lateral graft failure. Conclusion: Patients with lateral graft failure had inferior clinical outcomes and lower postoperative graft volumes than those with medial graft failure after SCR using a dermal allograft. The AHD of patients with lateral graft failure improved postoperatively; however, it deteriorated over time.

Feasibility and safety of EUS-guided biliary drainage in inexperienced centers: a multicenter study in southwest Japan

Background and AimsEndoscopic ultrasound-guided biliary drainage (EUS-BD) has shown promising procedural outcomes in high-volume centers. While inferior procedural outcomes were reported in inexperienced centers during the early days of EUS-BD, the current outcomes are unknown. This study aimed to clarify the feasibility and safety of EUS-BD in centers that recently introduced EUS-BD. MethodsThis multicenter retrospective study was conducted at 22 centers that introduced EUS-BD between 2017 and 2022. A maximum of 20 initial EUS-BD cases at each center were evaluated. The clinical outcomes and experience of 84 endoscopists who performed these procedures were examined. The primary outcomes were the rate of technical success and adverse events (AEs). The secondary outcomes were risk factors associated with technical failure and procedure-related AEs. ResultsA total of 255 patients were enrolled. The technical success rate was 91.4% (233/255). Among technical failure cases (n=22), guidewire manipulation failure was the most common cause (n=12), followed by tract dilation failure (n=5). The AE rate was 10.2% (26/255). Multivariate analysis identified a puncture target diameter of <5 mm (odds ratio, 3.719; 95% confidence interval, 1.415-9.776; p=0.008) and moderate ascites extending to the liver surface (odds ratio, 3.25; 95% confidence interval, 1.195-8.653; p=0.021) as independent risk factors for technical failure and procedure-related AEs, respectively. Endoscopists’ procedural experience was not a risk factor for technical failure or procedure-related AEs. ConclusionsThe feasibility and safety of EUS-BD were maintained during the induction phase at inexperienced centers. These will be helpful in better understanding the current status of EUS-BD.

Hospital volume does not mitigate the impact of area socioeconomic deprivation on heart transplantation outcomes.

While structural socioeconomic inequity has been linked with inferior health outcomes, some have postulated reduced access to high-quality care to be the mediator. We assessed whether treatment at high-volume centers(HVC) would mitigate the adverse impact of area deprivation on heart transplantation(HT) outcomes. All HT recipients ≥18years were identified in the 2005-2022 Organ Procurement and Transplantation Network. Neighborhood socioeconomic deprivation was assessed using the previously validated Area Deprivation Index. Recipients with scores in the highest quintile were considered Most Deprived (others: Less Deprived). Hospitals in the highest quartile by cumulative center volume (≥21 transplants/year) were classified as HVC. The primary outcome was post-transplant survival. Of 38,022 HT recipients, 7,579 (20%) were considered Most Deprived. Following risk adjustment, Most Deprived demonstrated inferior survival at 3(hazard ratio[HR] 1.14, 95%confidence interval[CI] 1.06-1.21) and 5 years following transplantation (HR 1.13, CI 1.07-1.20). Similarly, Most Deprived faced greater graft failure at 3(HR 1.14, CI 1.06-1.22) and 5 years (HR 1.13, CI 1.07-1.20). Evaluating patients transplanted at HVC, Most Deprived continued to face greater mortality at 3(HR 1.10, CI 1.01-1.21) and 5 years (HR 1.10, CI 1.01-1.19). The interaction between Most Deprived status and care at HVC was not significant, such that transplantation at HVC did not ameliorate the survival disparity between Most and Less Deprived. Area socioeconomic disadvantage is independently associated with inferior survival. Transplantation at HVC did not eliminate this inequity. Future efforts are needed to increase engagement with longitudinal follow-up care and address systemic root causes to improve outcomes.

Disseminated tumor cells in bone marrow as predictive classifiers for small cell lung cancer patients

BackgroundSmall cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Aneuploid CD31- disseminated tumor cells (DTCs) and CD31+ disseminated tumor endothelial cells (DTECs) residing in the bone marrow are generally considered as the initiators of metastatic process. However, the clinical significance of DTCs and DTECs in SCLC remains poorly understood. The aim of this study is to investigate the clinical implications of diverse subtypes of highly heterogeneous DTCs and DTECs in SCLC patients. MethodsSubtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) was applied to enrich and perform comprehensive morphologic, karyotypic, and phenotypic characterization of aneuploid DTCs and DTECs in 30 patients. Additionally, co-detection of circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) was conducted on 24 of the enrolled patients. Proof-of-concept of the whole exon sequencings (WES) on precisely selected different subtypes of CTCs or DTCs, longitudinally detected from a representative case with pathologically confirmed bone marrow metastasis, was validated to feasibly reveal genetic mutations in these cells. ResultsDTCs, DTECs and their subtypes were readily detectable in SCLC patients. Comparative analysis revealed that the number of DTCs and DTECs was significantly higher than that of their corresponding CTCs and CTECs (P < 0.001 for both). Positive detection of disseminated tumor microemboli (DTM) or disseminated tumor endothelial microemboli (DTEM) was associated with inferior survival outcomes (P = 0.046 and P = 0.048). Patients with EpCAM+ DTCs detectable displayed significantly lower disease control rate (DCR) (16.67 % vs 73.33 %, P = 0.019), reduced median progression-free survival (mPFS) and median overall survival (mOS) compared with those with EpCAM- DTCs (P = 0.028 and P = 0.002, respectively). WES analysis indicated that post-treatment DTCs isolated from bone marrow at the time of disease progression shared more homologous somatic gene mutations with pre-treatment CTCs compared with post-treatment CTCs. ConclusionsOur findings suggest that bone marrow sampling and characterization of DTC subtypes provided a valuable tool for predicting treatment response and the prognosis in SCLC. Moreover, DTCs inherit a greater amount of homologous somatic information from pre-treatment CTCs, indicating their potential role in disease progression and treatment resistance.

Multidisciplinary Team Discussions and the Inclusion of Individualized Patient Factors May Improve Informed Consent in Sports Medicine

Informed consent allows for the maintenance of patient autonomy and is essential in establishing trusting relationships between physicians and their patients. This process involves thorough discussion of the risks and alternatives, as well as the short- and long-term outcomes, of proposed treatment options. Inadequacies with informed consent can lead to inferior patient outcomes and may be subject to severe legal consequences. Individualized discussions are warranted to address the questions of these patients, whether it be the high-level athlete or the weekend warrior. This review highlights factors, identifies barriers, and proposes potential solutions to improve informed consent within orthopaedic sports medicine.

Arthroscopic selective approach to dynamic posterior shoulder instability: long-term follow-up insights

AimsEvaluate outcomes of arthroscopic capsulolabral repair in patients with structural dynamic posterior instability (Moroder classification B2), analyzing factors associated with inferior clinical outcomes or recurrence. The primary hypothesis is that this surgical approach in patients without static structural changes such as excessive glenoid retroversion or dysplastic glenoids will result in satisfactory clinical outcomes and low failure rates. MethodsObservational retrospective analysis in patients diagnosed with posterior structural dynamic instability who underwent arthroscopic capsulolabral repair. Demographic, clinical and radiologic characteristics were registered as well as patient reported outcomes, satisfaction, complications and failure with a minimum 2-year follow-up. Association between these outcomes and preoperative factors was investigated. Results21 patients were included, with an average age of 38.1 years (range 27-51) and a mean follow-up of 68.7 months (range 24-127). At final follow-up the degree of instability was 0 in 19 (90.5%) patients. Overall outcome assessment demonstrated a mean SSV of 82.3 (±15.2), mean WOSI score of 460.1 (±471) and a mean 91.5 (±13) ROWE score. Furthermore, a significant portion of patients returned to sport 71.4% at any level and 57.1% at previous level, and 71.4% reported satisfaction with treatment, while 5 patients (23.8%) had criteria for failure. ConclusionArthroscopic capsulolabral repair in selected patients with type B2 posterior shoulder instability without static posterior findings yielded satisfactory clinical outcomes and low failure rates.

PEDICLE TRANSPOSITION FLAP, INVERTED FLAP, FREE FLAP, AND STANDARD PEEL FOR LARGE FULL-THICKNESS MACULAR HOLES: A Comparative Study.

To compare anatomical and functional outcomes of four different techniques for the treatment of large idiopathic full-thickness macular holes. This single-center retrospective study included 129 eyes of 126 patients with large (>500 µ m) full-thickness macular holes who presented between January 2018 and October 2022. All patients underwent 23/25 G vitrectomy and gas with standard internal limiting membrane (ILM) peel, pedicle transposition, inverted, or free flap technique. Postoperative optical coherence tomography images were assessed by two independent masked graders. Mean age was 73.2 years (SD 8.4) with a median F/U of 5 months (IQR 8). The overall anatomical success rate was 81%; it was significantly lower (59%) for the standard ILM peel ( P < 0.0001). The pedicle transposition flap showed superior visual recovery compared with the free flap (+27 vs. +12 ETDRS letters, P = 0.02). At 3 months, restoration of the external limiting membrane was significantly better for the pedicle transposition flap compared with free flap and standard ILM peel ( P = 0.008 and P = 0.03) and superior to all the other techniques at 6 months ( P = 0.02, P = 0.04, and P = 0.006). Standard ILM peel alone offers inferior outcomes for the management of large full-thickness macular holes. Of the alternative ILM techniques, despite similar closure rates, foveal microstructural recovery is most complete following the pedicle transposition flap and least complete following the free flap.

Biomechanical analysis of the effect of postero-latero-central tibial plateau fractures in the knee joint: Can posterior soft tissues prevent instability? A finite element study.

BackgroundAlmost 86 % of all tibial plateau fractures involves the failure of the postero-latero-central region of the tibial plateau. Surgical treatment of this region is technically demanding and in case of limited depression, it's occasionally chosen to leave them untreated. The aim of the study is to numerically check to what extent this choice can be accepted avoiding inferior outcomes (i.e. joint instability), and to analyze posterior soft tissues role in presence of this fractures. MethodsStarting from a previous validated finite element model with baseline structures, several configurations were developed by inserting posterior soft tissues and postero-latero-central fracture, with different articular depressions. Squat motion was numerically simulated and tibio-femoral kinematics were compared among configurations. FindingsAn increasing step-off led to a progressive joint instability, especially in the first 35°-40° of flexion. Posterior soft tissues showed to be beneficial in initial stabilization and early flexion. Tibial Axial Rotation didn't show any restorative effect of posterior soft tissues on knee kinematics. Tibial Antero-Posterior Translation is the most significant biomechanical parameter, showing posterior soft tissues restoring native antero-posterior translation, completely for 1-mm step-off fracture, only partially for 2-mm step-off fracture, and not sufficiently for 3-mm step-off fracture, at least in the first 30° of flexion. InterpretationThe results suggest that postero-latero-central fractures with step-off ≥2 mm should be treated to restore articular kinematic, whereas fractures with step-off <2 mm need a broad evaluation to assess the effective need of surgery. These information can be valuable for surgeons, to aid their decision to surgically operate or not.