Favorable Outcome Research Articles

Umbilical Cord Blood Transplantation for Fanconi Anemia With a Special Focus on Late Complications: a Study on Behalf of Eurocord and SAAWP-EBMT

Hematopoietic cell transplantation (HCT) remains the sole available curative treatment for Fanconi anemia (FA), with particularly favorable outcomes reported after matched sibling donor (MSD) HCT. This study aimed to describe outcomes, with a special focus on late complications, of FA patients who underwent umbilical cord blood transplantation (UCBT). In this retrospective analysis of allogeneic UCBT for FA performed between 1988 and 2021 in European Society for Blood and Marrow Transplantation (EBMT)-affiliated centers, a total of 205 FA patients underwent UCBT (55 related and 150 unrelated) across 77 transplant centers. Indications for UCBT were bone marrow failure in 190 patients and acute leukemia/myelodysplasia in 15 patients. The median age at transplantation was 9 years (range, 1.2 to 43 years), with only 20 patients aged >18 years. Among the donor-recipient pairs, 56% (n = 116) had a 0 to 1/6 HLA mismatch. Limited-field radiotherapy was administered to 28% (n = 58) and 78% (n = 160) received a fludarabine (Flu)-based conditioning regimen. Serotherapy consisted of antithymocyte globulin (n = 159; 78%) or alemtuzumab (n = 12; 6%). The median follow-up was 10 years for related UCBT and 7 years for unrelated UCBT. Excellent outcomes were observed in the setting of related UCBT, including a 60-day cumulative incidence (CuI) of neutrophil recovery of 98.1% (95% confidence interval [CI], 93.9% to 100%), a 100-day CuI of grade II-IV acute graft-versus-host disease (GVHD) of 17.3% (95% CI, 9.5% to 31.6%), and a 5-year CuI of chronic GVHD (cGVHD) of 22.7% (95% CI, 13.3% to 38.7%; 13% extensive). Five-year overall survival (OS) was 88%. In multivariate analysis, none of the factors included in the model predicted a better OS. In unrelated UCBT, the 60-day CuI of neutrophil recovery was 78.7% (95% CI, 71.9% to 86.3%), the 100-day CuI of grade II-IV aGVHD was 31.4% (95% CI, 24.6% to 40.2%), and the 5-year CuI of cGVHD was 24.3% (95% CI, 17.8% to 32.2%; 12% extensive). Five-year OS was 44%. In multivariate analysis, negative recipient cytomegalovirus serology, Flu-based conditioning, age <9 years at UCBT, and 0 to 1/6 HLA mismatch were associated with improved OS. A total of 106 patients, including 5 with acute leukemia/myelodysplasia, survived for >2 years after UCBT. Nine of these patients developed subsequent neoplasms (SNs), including 1 donor-derived acute myelogenous leukemia and 8 solid tumors, at a median of 9.7 years (range, 2.3 to 21.8 years) post-UCBT (1 related and 8 unrelated UCBT). In a subset of 49 patients with available data, late nonmalignant complications affecting various organ systems were observed at a median of 8.7 years (range, 2.7 to 28.8 years) post-UCBT. UCB is a valid source of stem cells for transplantation in patients with FA, with the best results observed after related UCBT. After unrelated UCBT, improved survival was observed in patients who underwent transplantation at a younger age, with Flu-based conditioning, and with better HLA parity. The incidence of organ-specific complications and SNs was relatively low. The incidence of SNs, mostly squamous cell carcinoma, increases with time. Rigorous follow-up and lifelong screening are crucial in survivors of UCBT for FA.

Effects of Perforated Plates on Shock Structure Alteration for NACA0012 Airfoils

This research investigated a passive flow control technique to mitigate the adverse effects of shock wave–boundary layer interaction on a NACA 0012 airfoil. A perforated plate with a strategically positioned cavity beneath the shock wave anchoring spot was employed. Airfoils with perforated plates of varying orifice sizes (ranging from 0.5 to 1.2 mm) were constructed using various manufacturing techniques. Experimental analysis utilized an “Eiffel”-type open wind tunnel and a Z-type Schlieren system for flow visualization, along with static pressure measurements obtained from the bottom wall. Empirical observations were compared with steady 3D density-based numerical simulations conducted in Ansys FLUENT for comprehensive analysis and validation. The implementation of the perforated plate induced a significant alteration in shock structure, transforming it from a strong normal shock wave into a large lambda-type shock. The passive control case exhibited a 0.2% improvement in total pressure loss and attributed to the perforated plate’s capability to diminish the intensity of the shock wave anchored above. Significant fluctuations in shear stress were introduced by the perforated plate, with lower stress observed in the plate area due to flow detachment from cavity blowing. Balancing shock and viscous losses proved crucial for achieving a favorable outcome with this passive flow control method.

Chasing Comfort in the Chill: Simulating the Impact of Opened Streamlines on Microclimatic Conditions, Thermal Comfort and Building Facades in Cold Climate Cities

This project aims to evaluate the impact of water surfaces on urban microclimate change and the presence of water in dense urban areas on the heating and cooling loads of buildings by proposing the rehabilitation of urban water resources. It mainly questions whether favorable outcomes for urban microclimate may be expected at the local level with the rehabilitation of water bodies and the contribution of repaired water lines to energy savings in nearby buildings. The analyses are made for Erzurum, the coldest climate city in Türkiye, by using the ENVI-met program, a dynamic simulation tool widely used for microclimate analysis. The analyses use the meteorological data recorded on the site during the same years’ summer and winter periods. The microclimate change caused by the green areas, which involve the opening of covered streamlines, was estimated, and the change in the energy load of buildings was quantitatively analyzed. The findings show that rehabilitation of water lines in urban areas improved microclimate conditions and provided energy-saving opportunities for buildings. Thus, policy-makers should produce more green spaces, including water surfaces, in urban areas to improve the adaptation capacity of cities and mitigate the negative effects of climate change.

Rahnella Aquatilis Endophthalmitis after Intravitreal Injection in an Immunocompetent Patient.

To present a novel case of exogenous Rahnella aquatilis endophthalmitis following an intravitreal injection. Case report. A 74-year-old male presented with acute progressive vision loss and pain in the left eye, 5 days after an intravitreal injection for diabetic macular edema. The patient was diagnosed with exogenous endophthalmitis and empirically treated with intravitreal injections of vancomycin and ceftazidime as well as topical and oral ciprofloxacin. In follow up two days later, the patient was treated with preoperative povidone-iodine followed by prompt vitrectomy with additional vancomycin and ceftazidime due to pharmacy sterile hood issues that delayed antibiotic availability. Microbiological cultures and two mass spectrometry identification tests confirmed the diagnosis of exogenous Rahnella aquatilis endophthalmitis. Despite the presence of scattered retinal hemorrhagic infarcts involving the macula and subsequent full-thickness atrophic macular holes seen in follow up, the patient achieved a favorable anatomical and functional outcome of BCVA 20/80 at 1 year of follow-up. This case highlights the occurrence of exogenous Rahnella aquatilis endophthalmitis following an intravitreal injection for diabetic macular edema. Prompt diagnosis and treatment produced a favorable outcome relative to other typical Gram-negative Enterobacteriaceae organisms.

Surgical strategies in acute subdural hematoma: a meta-analysis of decompressive craniectomy vs. craniotomy.

Acute subdural hematoma (ASDH) stands as a significant contributor to morbidity after severe traumatic brain injuries (TBI). The primary treatment approach for patients experiencing progressive neurological deficits or notable mass effects is the surgical removal of the hematoma, which can be achieved through craniotomy (CO) or decompressive craniectomy (DC). Nevertheless, the choice between these two procedures remains a subject of ongoing debate and controversy. We conducted a comprehensive literature review, utilizing prominent online databases and manually searching references related to craniotomy and craniectomy for subdural hematoma evacuation up to November 2023. Our analysis focused on outcome variables such as the presence of residual subdural hematoma, the need for revision procedures, and overall clinical outcomes. We included a total of 11 comparative studies in our analysis, encompassing 4269 patients, with 2979 undergoing craniotomy and 1290 undergoing craniectomy, meeting the inclusion criteria. Patients who underwent craniectomy displayed significantly lower scores on the Glasgow Coma Scale (GCS) during their initial presentation. Following surgery, the DC group exhibited a significantly reduced rate of residual subdural (P = 0.009). Additionally, the likelihood of a poor outcome during follow-up was lower in the CO group. Likewise, the mortality rate was lower in the CO group compared to the craniectomy group (OR 0.63, 95% CI 0.41-0.98, I2 = 84%, P = 0.04). Our study found that CO was associated with more favorable outcomes in terms of mortality, reoperation rate, and functional outcome while DC was associated with less likelihood of residual subdural hematoma. Upon further investigation of patient characteristics who underwent into either of these interventions, it was very clear that patients in DC cohort have more serious and low pre-op characteristics than the CO group. Nonetheless, brain herniation and advanced age act as independent factor for predicting the outcome irrespective of the intervention.

Comparative analysis of surgical outcomes in children with type 3 and type 4 lateral physeal condylar humerus fractures in China: Closed Reduction-PerCutaneous Pinning (CRPP) vs. Open Reduction-Internal Fixation (ORIF)

BackgroundLateral physeal condylar humerus fractures in pediatric patients aged 1–13 rank as the second most common elbow injury, occurring with a frequency ranging from 5% to 16.8%. There exists an ongoing debate regarding the surgical management of these fractures. This study aims to evaluate the efficacy of Open Reduction and Internal Fixation (ORIF) and Closed Reduction and Percutaneous Pinning (CRPP) as suitable surgical treatments for displaced unstable fractures of the lateral condyle physeal humerus in children. The comparison encompasses the results of ORIF and CRPP, alongside clinical and radiographic outcomes and complication rates. MethodA retrospective review was conducted at the Department of Orthopedic Surgery in the research hospital. A cohort of 27 patients treated between 2016 and 2023 were analyzed, 19 patients meeting inclusion criteria. The fracture pattern and degree of displacement were assessed, with specialized radiologists, doctors, and surgeons in agreement. Among the patients, 11 underwent CRPP 7 type 3and 4 type 2, while 16 received ORIF 12 type 4 and 4 type 5. Data collection included fracture type, surgical method, operation time, pre and post-operative displacement, casting period, bone union condition, follow-up records, range of motion, complications, delayed union, lateral spurring, and pin removal records. ResultsFor CRPP, the mean time for pin removal was 5.42 weeks, with excellent bone union and an average operation time of 34.57 min. Criteria of Hardacre showed 28.57% of cases as good and 71.42% as excellent. Similarly, ORIF demonstrated a mean operation time of 42.5 min, with the fracture healing within 5.33 weeks and the pin being removed after 15 days on average. Criteria of Hardacre indicated 25% of cases as good and 75% as excellent. Both groups showed satisfactory outcomes, with no complications such as osteomyelitis, nonunion, malunion, delayed union, myositis ossificans, physeal growth arrest, tardy ulnar nerve palsy, cubitus valgus, or varus, and no cases requiring re-surgery. ConclusionBoth CRPP and ORIF are effective surgical methods for treating lateral physeal condylar humeral fractures (types 3 and 4 according to the Song classification) in children, demonstrating satisfactory outcomes. Notably, regardless of displacement (2 mm and >2 mm), both methods yield similar results, albeit with CRPP offering the advantage of avoiding incisions. Overall, both procedures are safe, with favorable bone healing outcomes.

(025) Laparoscopic Assisted Reservoir Removal of an Infected Inflatable Penile Prosthesis in a Patient with Ipsilateral Inguinal Hernia Mesh Implant

Abstract Introduction Infection is a devastating complication of penile prosthesis implantation ranging from 0.33 to 11.4%. 1 Although a salvage procedure is an option in case of infection, the rule of thumb is to remove all device components. 2 Special considerations and pre-operative planning are essential for better outcome in the management of such condition. We are presenting a video case presentation demonstrating the use of laparoscopic assisted approach to aid in the extraction of the reservoir of an infected penile prosthesis from a patient who had ipsilateral inguinal hernia mesh implant Objective To demonstrate the feasibility and efficacy laparoscopic assisted approach in the removal of difficult to extract inflatable penile prosthesis (IPP) reservoir. Methods A 72-year-old gentleman with past medical history of Diabetes and hypertension presented to our clinic 3 weeks after an IPP insertion that was done in another center. He was complaining of right inguinal bulge and scrotal pain. The bulge developed suddenly without any preceding event. Examination confirmed a prosthesis reservoir herniation in to the right groin. Plan CT abdomen&amp; pelvis confirmed the diagnosis. In three days, the herniated reservoir was managed by inguinal exploration, repositioning of the same reservoir in the right Retzius space and posterior inguinal canal wall repair using a mesh. The patient was discharged on post-operative day 1 in a stable condition, but unfortunately, he developed persistent scrotal pain that progressed into an overt scrotal infection over the early follow up period. During the examination, a scrotal collection was observed, swap was taken from the draining pus and results showed moderate growth of pseudomonas aeruginosa. On the other hand, the inguinal scar showed good healing with no tenderness, indicating the presence of an intact and non-infected inguinal mesh. Therefore, the decision was made to remove all components of the prosthesis without removing the mesh. Considering the anticipated challenges associated with removing the reservoir of the IPP through a scrotal approach, a decision was made to incorporate an additional laparoscopic-assisted abdominal approach for reservoir removal. Results Removal of the IPP cylinders and pump was performed through a scrotal incision, then a laparoscopic assisted abdominal approach was used successfully to remove the reservoir. After the IPP explant procedure, patient had an uneventful smooth recovery at the two and four weeks follow up visits, he was advised to use Vacuum erection device (VED) to alleviate possible penile fibrosis/shortening. A penile prosthesis reimplantation procedure was planned in a 6 months period Conclusions Laparoscopic assisted approach for penile prosthesis reservoir extraction is a feasible and safe technique that can be used in anticipated cases of difficult reservoir extraction. Pre-operative assessment, planning and counselling are crucial in obtaining a favorable outcome in such complex cases. Disclosure No.

(022) Penile Implant Reservoir Placement: The Current Utilized Various Techniques and the Associated Outcome: Systematic Review and Meta-Analysis

Abstract Introduction Many innovations in the field of inflatable penile prosthesis (IPP) has been emerged. Since the introduction of the IPP, reservoir positioning in the space of Retzius (SOR) was considered the classical approach that had been utilized for many years. However, in certain group of patients, reservoir insertion in such space might be difficult or even risky. As a result, many alternatives for the reservoir placement outside the SOR has emerged with the intent of safe and reliable reservoir placement. Objective To conduct a systematic review for the studies evaluating the outcomes of different techniques used for IPP reservoir placement to look for possible superiority of any approach over others. Methods A systemic review was performed utilizing (PRISMA) statement. The PubMed and Google scholar were used to look for articles published up to January 2023. Original articles reporting different techniques for IPP reservoir placement and evaluating the associated outcomes were included. Data regarding study design, sample size, approach of reservoir placement, surgical technique, device type and reported outcomes (infection rate, bladder/bowel/vascular injury, reservoir herniation, mechanical failure, auto-inflation, reservoir palpability and patients’ satisfaction) were collected. Pooled proportion was calculated and included in the meta-analysis. The Newcastle-Ottawa scale was used for assessing the quality of the studies. Results A total of 23 articles meeting the inclusion criteria, all were retrospective reviews. 11 compared more than one technique for reservoir placement whereas 12 described a single technique. In total, techniques for 6 main different reservoir locations has been reported, including SOR (7 studies), submuscular/subrectus (6 studies), Lateral retroperitoneal (1 study), subcutaneous (1 study), sub external oblique (1 study) and intraperitoneal (1 study). Another 7 modifications have been described for the SOR technique (traditional SOR, accessing SOR using blunt scissor in post-prostatectomy patients, accessing SOR using blunt scissor in virgin cases, dilating SOR using catheter balloon, accessing SOR under direct vision, accessing SOR through external oblique fascia incision, and the addition of The Tubing Hitch&amp;Lasso, Intussusception Anchor technique (THALIA)). Another 6 modifications for the submuscular/subrectus approach have been described (posterior to transversalis fascia (PTF), anterior to transversalis fascia (ATF), high submuscular, subrectus using counter incision, subrectus with the addition of THALIA, low submuscular with trans-fascial-fixation (TFF)). None of the studies have proven the superiority of one technique over others, with most of the techniques has comparable intra-operative and post-operative outcomes (table 1). The addition of anchoring step (THALIA or TFF) resulted in neglected risk of reservoir herniation, however, related studies has small sample size with no comparison groups. Meta-analysis for the studies of SOR (n=7) and submuscular/subrectus (n=6) groups showed a statistically significant difference only in the herniation rates (figure 1). 10 studies were of strong quality (8 stars) while the remaining 13 studies were of poor quality. Conclusions Modest evidence suggests a comparable favorable outcome of various approaches used for IPP reservoir placement. The lack of enough prospective trials, short term follow up, and diversity in the techniques prescribed prevent the ability to build strong evidence. For the purpose of supporting the superiority of any technique, further prospective studies on a larger number of patients with long-term follow up are needed to reach a solid verdict. Disclosure No.

Abstract P02: Uncovering Tailored Therapies for Acute Myeloid Leukemia in Children with Down Syndrome

Abstract P02: Uncovering Tailored Therapies for Acute Myeloid Leukemia in Children with Down Syndrome

Thoraflex Hybrid Prosthesis (THP): the profile

ABSTRACT Introduction With the incidence of thoracic aortic disease on the rise, total arch replacement (TAR) with frozen elephant trunk (FET) remains the gold-standard management strategy due to optimal results. Several FET devices exist commercially on the global market. However, the mainstay and most commonly used and reported device is the Thoraflex Hybrid Prosthesis (THP), with several recent reports suggesting its superiority. Areas covered This review aims to collate and summarize the evidence in the literature on the clinical outcomes of TAR with FET using THP, with a focus on mortality, neurological complications, endoleak, distal stent-induced new entry (dSINE), aortic remodeling, coagulopathy, and graft kinking. In addition, the design features of THP is discussed, and an overview of market competitors is also highlighted. Expert opinion THP consistently demonstrates its effectiveness in treating complex thoracic aortic pathology through favorable clinical outcomes, which can be attributed to its unique and innovative design. Rates of early mortality ranged 0.6–14.2%, neurological complications 0–25%, endoleak 0–8.4% and dSINE 0–14.5%, with minimal incidence of graft kinking and coagulopathy. Aortic remodeling is favorable and comparable to competitors. All this evidence solidifies THP as the leading FET device, particularly when combined with appropriate patient selection and surgical planning.

Utilizing imaging parameters for functional outcome prediction in acute ischemic stroke: A machine learning study.

We aimed to predict the functional outcome of acute ischemic stroke patients with anterior circulation large vessel occlusions (LVOs), irrespective of how they were treated or the severity of the stroke at admission, by only using imaging parameters in machine learning models. Consecutive adult patients with anterior circulation LVOs who were scanned with CT angiography (CTA) and CT perfusion were queried in this single-center, retrospective study. The favorable outcome was defined as a modified Rankin score (mRS) of 0-2 at 90 days. Predictor variables included only imaging parameters. CatBoost, XGBoost, and Random Forest were employed. Algorithms were evaluated using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPRC), accuracy, Brier score, recall, and precision. SHapley Additive exPlanations were implemented. A total of 180 patients (102 female) were included, with a median age of 69.5. Ninety-two patients had an mRS between 0 and 2. The best algorithm in terms of AUROC was XGBoost (0.91). Furthermore, the XGBoost model exhibited a precision of 0.72, a recall of 0.81, an AUPRC of 0.83, an accuracy of 0.78, and a Brier score of 0.17. Multiphase CTA collateral score was the most significant feature in predicting the outcome. Using only imaging parameters, our model had an AUROC of 0.91 which was superior to most previous studies, indicating that imaging parameters may be as accurate as conventional predictors. The multiphase CTA collateral score was the most predictive variable, highlighting the importance of collaterals.

Thirty-eight cases of paraovarian cysts in children and adolescents: a retrospective study.

Paraovarian cysts in children and adolescents can be challenging to accurately diagnose prior to surgery. Our objective is to outline the clinical characteristics of paraovarian cysts and enhance the precision of diagnosing paraovarian cysts in this age group. We retrospectively analyzed all patients with paraovarian cysts who underwent surgery in our department from 2013 to 2021. The review focused on demographic characteristics, clinical manifestations, intraoperative findings, and postoperative pathology of these patients. This cohort was composed of 38 children with paraovarian cysts. The average diameter of the cysts was 4.8cm (range 0.5-10cm). Among the cases, 25 (65.8%) had adnexal torsion. Postoperative pathology showed that all cases were simple cysts with serous fluid. After the procedure, the patients were monitored for a period ranging from 12 to 108 months. B-ultrasound and physical examination did not reveal any significant abnormalities. B-ultrasound can help diagnose paraovarian cysts by detecting slight deviation movement between the cyst and the uterus. The presence of adnexa torsion in children and adolescents with paraovarian cysts does not depend on BMI, but rather on the size of cysts. Laparoscopic cyst removal has proven to be an effective surgical approach with favorable outcomes.

Clinical features and prognostic analysis of testicular relapse in pediatric acute lymphoblastic leukemia

Objective: To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL). Methods: Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. Results: The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis (HR=3.09, 95%CI 1.10-8.72), combined relapse (HR=4.26, 95%CI 1.34-13.52) and CAR-T cell therapy after relapse (HR=0.15,95%CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions: The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

Uncommon de novo EGFRT790M-Mutant NSCLC characterized with unique genetic Features: Clinical response and acquired resistance to the third-generation EGFR-TKIs treatment

IntroductionThe literature on de novo EGFRT790M-mutant patients diagnosed with lung cancer is limited, and there is currently no consensus concerning the most effective treatment protocols. This study aimed to investigate the genomic characteristics of de novoEGFRT790M-mutant non-small cell lung cancer (NSCLC) and provide insights into its clinical response and resistance mechanism to third-generation EGFR-TKIs. MethodsNext-generation sequencing was utilized to screen a substantial cohort of 4,228 treatment-naïve patients from the Mygene genomic database to identifythe de novo EGFR-T790M mutation. Meanwhile, we recruited 83 individuals diagnosed with lung cancer who harbored de novo EGFRT790M mutation in the real world. In addition, 166 patients who acquired EGFR-T790M mutation after becoming resistant to first- or second-generation EGFR-TKIs were included as a comparison cohort. ResultsDe novo EGFRT790M mutation identified by next-generation sequencing is rare (∼1.3 %) in Chinese lung cancer patients. The relative variant allele frequency (VAF) of de novo EGFRT790M mutation was either comparable to or significantly lower than those of EGFR-activating mutations. Patients with de novo-T790M mutations exhibited less favorable clinical outcomes when administered third-generation EGFR-TKIs as first-line therapy thanthose with 19del mutationsdue to a high overlap rate in EGFR p.L858R mutation. In patients with a de novo EGFRT790M mutation, no correlation was observed between T790M clonality and treatment outcomes with third-generation EGFR-TKIs. In contrast, the sub-clonality of the T790M mutation detrimentally affected the third-generation EGFR-TKI treatment efficacy in patients with acquired T790M mutation. Potential resistance mechanisms of third-generation EGFR TKIs in NSCLC patients with de novo or acquired EGFRT790M mutations included EGFR p.C797S in cis or EGFR p.E709X mutation, as well as activation of bypass pathways. ConclusionsThe present study characterized the uncommon but unique de novo EGFRT790M-mutant NSCLC and laid a foundation for designing future clinical trials in the setting of uncommon EGFR mutation.

Integrating molecular subtype and CD8+ T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer

BackgroundLuminal and Basal are the primary intrinsic subtypes of muscle-invasive bladder cancer (MIBC). The presence of CD8+ T cells infiltration holds significant immunological relevance, potentially influencing the efficacy of antitumor responses. This study aims to synergize the influence of molecular subtypes and CD8+ T cells infiltration in MIBC.MethodsThis study included 889 patients with MIBC from Zhongshan Hospital, The Cancer Genome Atlas, IMvigor210 and NCT03179943 cohorts. We classified the patients into four distinct groups, based on the interplay of molecular subtypes and CD8+ T cells and probed into the clinical implications of these subgroups in MIBC.ResultsAmong patients with Luminal-CD8+Thigh tumors, the confluence of elevated tumor mutational burden and PD-L1 expression correlated with a heightened potential for positive responses to immunotherapy. In contrast, patients featured by Luminal-CD8+Tlow displayed a proclivity for deriving clinical advantages from innovative targeted interventions. The Basal-CD8+Tlow subgroup exhibited the least favorable three-year overall survival outcome, whereas their Basal-CD8+Thigh counterparts exhibited a heightened responsiveness to chemotherapy.ConclusionsWe emphasized the significant role of immune-molecular subtypes in shaping therapeutic approaches for MIBC. This insight establishes a foundation to refine the process of selecting subtype-specific treatments, thereby advancing personalized interventions for patients.

Two-stage total joint replacement for hip or knee septic arthritis: post-traumatic etiology and difficult-to-treat infections predict poor outcomes.

Septic arthritis (SA) is a rare but significant clinical challenge in orthopedics that can impact patients' quality of life. This study aims to examine the clinical outcomes of patients undergoing two-stage total joint replacement (TJR) in hip and knee SA and analyze potential predictors of treatment failure. A retrospective analysis was conducted using data from a prospectively collected institutional arthroplasty registry from January 1st, 2012, to January 1st, 2019. Patients with hip or knee SA who underwent a two-stage TJR and had at least two years of follow-up were included. Demographic characteristics, surgical variables, and outcomes were collected and analyzed from clinical and surgical data. Statistical analysis was performed using IBM SPSS Statistics, with statistical significance at p < 0.05. One hundred and fourteen patients (61 with hip SA, 53 with knee SA) were included in the study. The mean follow-up was 72.8 months. Postoperatively, both clinical and functional outcomes significantly improved, as indicated by the Hip Society Score (HHS) and Knee Society Score (KSS). The overall success rate of the two-stage protocol was 89.5%. Complications that did not require revision occurred in 21% of cases. The most identified pathogen was methicillin-sensitive Staphylococcus aureus (MSSA). Difficult-to-treat (DTT) infections and post-traumatic etiology were identified as predictors of treatment failure in patients undergoing two-stage TJR for hip and knee SA. Two-stage TJR in hip and knee SA demonstrated favorable clinical outcomes at mid-term follow-up. The procedure significantly improved functional scores and achieved a high success rate, while DTT infections and post-traumatic etiology were associated with a higher risk of treatment failure.

Subjective religiosity and mental health service utilization: a descriptive study of the help-seeking attitudes and behaviors of students attending an HBCU

ABSTRACT This study sought answers to two questions; Do high levels of subjective religiosity negatively impact collegiate utilization of professional mental health services? Do college students with high levels of subjective religiosity report favorable outcomes when they engage in professional counseling? Forty percent of students reporting high levels of subjective religiosity were either currently receiving counseling or therapy or had received counseling or therapy previously. Surprisingly, 94.8% of students reporting high levels of subjective religiosity identified counseling or therapy as helpful. Consistent with what has been reported in the literature, high levels of subjective religiosity were associated with lower rates of suicidal thoughts. Findings suggest an opportunity for collaboration with clergy to enhance delivery of mental health services to BIPOC groups reporting high levels of subjective religiosity. Implications for future research are also discussed.

Association Between Early Mobilization and Functional Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Propensity Score-Matched Study.

Early mobilization has been shown to promote functional recovery and prevent complications in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the efficacy of early mobilization in patients with aSAH remains unclear. This study aimed to investigate the association between early mobilization and functional outcomes in patients with aSAH. This multicenter retrospective study was conducted in Japan and included patients with aSAH who received physical therapy with or without occupational therapy from April 2014 to March 2019. The primary outcome was the modified Rankin Scale (mRS) score, with a favorable functional outcome defined as an mRS score of 0-2 and an unfavorable outcome with an mRS score of 3-5. Patients initiating walking training within 14days of aSAH onset were classified into the early mobilization group, whereas those initiating training after 14days were classified into the delayed mobilization group. Propensity score matching analysis was performed to assess the association between early mobilization and favorable outcomes. A total of 718 patients were screened, and 450 eligible patients were identified. Before matching, 229 patients (50.9%) were in the early mobilization group and 221 (49.1%) were in the delayed mobilization group. After matching, each group consisted of 122 patients, and the early mobilization group exhibited a higher proportion of favorable outcomes than did the delayed mobilization group (81.1% vs. 52.5%, risk difference 28.7%, 95% confidence interval 17.4-39.9, p < 0.001). This multicenter retrospective study suggests that initiating walking training within 14days of aSAH onset is associated with favorable outcomes.

High Systemic Inflammatory Protein Index Is Associated with Clinically Ineffective Reperfusion in Acute Anterior Circulation Ischemic Stroke Patients Undergoing Endovascular Treatment.

Nearly half of the patients undergoing endovascular treatment (EVT)do not have favorable outcomes despite successful recanalization of the occluded artery, which is also known as clinically ineffective reperfusion. We proposed a novel index-the systemic inflammatory protein index (SIPI), based on albumin, globulin, and C-reaction protein (CRP). We aimed to evaluate the relationship between inflammatory biomarkers at varying time points and the 90-day functional outcomes and investigate inflammatory biomarkers' dynamic changes during hospitalization in acute ischemic stroke (AIS) patients of anterior circulation undergoing EVT. We retrospectively recruited consecutive patients diagnosed with AIS of anterior circulation and treated with EVT from January 2018 to June 2022 in Nanfang Hospital. Albumin, globulin, and CRP were recorded on admission, 1day, 3days, and 7days after EVT. An unfavorable functional outcome was defined as 90-day modified Rankin Scale (mRS) of 3-6. Albumin-to-globulin ratio (AGR), C-reactive protein-to-albumin ratio (CAR), and SIPI were calculated as follows: AGR = albumin/globulin; CAR = CRP/albumin; SIPI = CRP × globulin/albumin. A total of 238 consecutive anterior circulation AIS patients with EVT were included, among which 145 (60.9%) patients had unfavorable outcomes. After adjusting for confounding factors, admission globulin, admission AGR, 1-day AGR, 3-day albumin, 3-day CRP, 3-day CAR, 3-day SIPI, 7-day albumin, 7-day CRP, 7-day CAR, and 7-day SIPI showed an independent association with 90-day functional outcome. Of them, 3-day SIPI had the most robust discriminative ability with an area under the curve of 0.719 (CI 0.630-0.808, p < 0.001). There were differences in the dynamic change of inflammatory biomarkers between the subjects with favorable and unfavorable functional outcomes. Inflammatory biomarkers, including albumin, globulin, CRP, AGR, CAR, and SIPI, are independent predictors of 90-day unfavorable outcomes in anterior circulation AIS patients with EVT. SIPI of day 3 has the highest predictive value.

Can Machine Learning Predict Favorable Outcome After Radiofrequency Ablation of Hepatocellular Carcinoma?

The standard practice for limited-stage hepatocellular carcinoma (HCC) is the resection or the use of local ablative techniques, such as radiofrequency ablation (RFA). The outcome after RFA depends on a complex interaction between the patient's general condition, hepatic function, and disease stage. In this study, we aimed to explore using a machine learning model to predict the response. A retrospective study was conducted for patients with RFA for a localized HCC between 2018 and 2022. The collected clinical, radiologic, and laboratory data were explored using Python and XGBoost. They were split into a training set (70%) and a validation set (30%). The primary end point of this study was to predict the probability of achieving favorable outcomes 12 months after RFA. Favorable outcomes were defined as the patient was alive and HCC was controlled. One hundred and eleven patients were eligible for the study. Males were 78 (70.3%) with a median age of 57 (range of 43-81) years. Favorable outcome was seen in 62 (55.9%) of the patients. The 1-year survival rate and control rate were 94.6%, and 61.3%, respectively. The final model harbored an accuracy and an AUC of 90.6% and 0.95, respectively, for the training set, while they were 78.9% and 0.80, respectively, for the validation set. Machine learning can be a predictive tool for the outcome after RFA in patients with HCC. Further validation by a larger study is necessary.