Selection Criteria For Treatment Research Articles

Pancreatic ductual carcinoma with isolated liver metastases: is it worth performing surgical resection?

Pancreatic ductal cancer is one of the most aggressive malignancy with a high incidence of advanced stages at the time of diagnosis and unsatisfactory long-term treatment results. It is believed that pancreatic ductal cancer in the presence of distant metastases identified at the stage of intraoperative revision or before surgery is a contraindication to surgical treatment. There is currently renewed interest in surgical treatment of patients with oligometastatic pancreatic cancer.Material and Methods. The search for sources was carried out in the PubMed and Elibrary systems from January 1995 to January 2024. Of the 1321 sources found, 37 were used to write the review. Data from both retrospective and prospective clinical studies that focused on the results of combined modality treatment of pancreatic cancer with isolated liver metastases were included.Results. To date, a standard treatment strategy for patients with oligometastatic pancreatic cancer has not yet been established; there are no definitive criteria for selecting patients who may benefit from surgical treatment. The current selection criteria for surgery for metastatic pancreatic cancer are far from ideal, extremely heterogeneous and, as a rule, are based only on certain clinical and instrumental data. The starting point for developing selection criteria for surgical treatment of patients with metastatic pancreatic cancer is a common understanding of what “oligometastatic pancreatic cancer” is.

Catheter-directed treatment in acute pulmonary embolism

Abstract Background Pulmonary embolism (PE) is a potentially life-threatening emergency. PE occurs when venous thrombi embolize to the pulmonary circulation, resulting in vascular occlusion, impairing gas exchange and circulation. Initial risk stratification of acute PE is based on clinical symptoms, cardiac adaptations, comorbidities, and, in particular signs of haemodynamic instability. The primary aim of the treatment is to restore blood flow to the affected areas of the lungs, resolving/removing embolus burden and preventing further clot formation. In patients with severe PE, comprising decompensation or intended hemodynamic compromise, immediate reperfusion is recommended. Catheter-directed therapies (CDT) are an innovative treatment option for patients with severe PE to resolve embolus and restore pulmonic perfusion. These procedures are less invasive and are supposed to have a lower risk of bleeding complications compared to systemic thrombolysis or surgical embolectomy. Recent studies have shown that CDT are safe and effective treatment options for PE. Purpose Nevertheless, CDT have to demonstrate their non-inferiority and benefits regarding patients’ outcomes in real-world settings. Methods The German nationwide inpatient sample was used to identify and include all hospitalizations of patients with PE 2005-2020 in Germany. PE patients were stratified for use of CDT. Temporal trends of the usage and the impact of CDT on case-fatality and other outcomes were investigated (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005-2020, own calculations). Results Overall, 1,373,084 hospitalisations of patients with PE (55.9% aged ≥70 years; 53.0% females) were included in this study 2005-2020. Among these, 427,238 (31.1%) were categorized as severe PE and 3330 (0.2%) were treated with CDT with an annual increase from 0.17% (2005) to 0.51% (2020). PE patients of younger age, male sex, with previous surgery, and with severe PE were more often treated with CDT. In patients with severe PE, CDT was attributed to lower MACCE (28.2% vs. 34.2%, P<0.001) and in-hospital case-fatality rate (24.9% vs. 31.0%, P<0.001), but higher prevalence of major bleeding (29.5% vs. 17.5%, P<0.001). CDT was associated with reduced MACCE (OR 0.91 [95%CI 0.83-0.99], P=0.031), a trend towards lower case-fatality (OR 0.92 [95%CI 0.84-1.01], P=0.068), but increased major bleeding (OR 2.12 [95%CI 1.92-2.33], P<0.001) in severe PE. The benefit of CDT regarding case-fatality was age-dependent, with the largest benefit in the 8th and 9th decade of life. Conclusions Although the annual rate of CDT increased from 2005 to 2020 in Germany, only 0.2% of the PE patients were treated with CDT. Selection criteria for CDT treatment were younger age, male sex, previous surgery, and severe PE. CDT treatment was associated with reduced MACCE and case-fatality rate in PE patients with severe PE.

Deep Learning-Based ASPECTS Algorithm Enhances Reader Performance and Reduces Interpretation Time.

ASPECTS is a long-standing and well documented selection criteria for acute ischemic stroke treatment, however, the interpretation of ASPECTS is a challenging and time-consuming task for physicians with significant interobserver variabilities. We conducted a multi-reader, multi-case study in which readers assessed ASPECTS without and with the support of a deep learning (DL)-based algorithm in order to analyze the impact of the software on clinicians' performance and interpretation time. A total of 200 NCCT scans from 5 clinical sites (27 scanner models, 4 different vendors) were retrospectively collected. Reference standard was established through the consensus of three expert neuroradiologists who had access to baseline CTA and CTP data. Subsequently, eight additional clinicians (four typical ASPECTS reader and four senior neuroradiologists) analyzed the NCCT scans without and with the assistance of CINA-ASPECTS (Avicenna.AI, La Ciotat, France), a DLbased FDA-cleared and CE-marked algorithm designed to automatically compute ASPECTS. Differences were evaluated in both performance and interpretation time between the assisted and unassisted assessments. With software aid, readers demonstrated increased region-based accuracy from 72.4% to 76.5% (p<0.05), and increased ROC AUC from 0.749 to 0.788 (p<0.05). Notably, all readers exhibited an improved ROC AUC when utilizing the software. Moreover, use of the algorithm improved the score-based inter-observer reliability and correlation coefficient of ASPECTS evaluation by 0.222 and 0.087 (p<0.0001), respectively. Additionally, the readers' mean time spent analyzing a case was significantly reduced by 6% (p<0.05) when aided by the algorithm. With the assistance of the algorithm, readers' analyses were not only more accurate but also faster. Additionally, the overall ASPECTS evaluation exhibited greater consistency, less variabilities and higher precision compared to the reference standard. This novel tool has the potential to enhance patient selection for appropriate treatment by enabling physicians to deliver accurate and timely diagnosis of acute ischemic stroke. ASPECTS = Alberta Stroke Program Early Computed Tomography Score; DL = Deep Learning; EIC = Early Ischemic Changes; ICC = Intraclass Correlation Coefficient; IS = Ischemic Stroke; ROC AUC = Receiver Operating Characteristics Area Under the Curve.

Epilepsy surgery for tuberous sclerosis complex in children: literature review and clinical case

Tuberous sclerosis complex (TSC) is a multisystem, autosomal-dominant, neurocutaneous syndrome that is characterized by the presence of hamartomas involving multiple organs, including the brain. Epilepsy is the most common neurological manifestation and the main cause of disability in children. Drug-resistant epilepsy is seen in 62.5 % of cases. The challenge of surgical treatment in these patients is the multifocal nature of epilepsy. Nonetheless, there is available data to suggest that surgical intervention is most likely to achieve long-term seizure freedom.The aim of the work – to analyze current data and aspects of surgical treatment of epilepsy associated with tuberous sclerosis in children.A literature search for was done on PubMed, Google Scholar, and eLIBRARY. RU for the period from 2000 to 2022. Search phrases included: TSC-associated epilepsy in children, epilepsy surgery in children with TSC, epilepsy surgery for TSC. The tubers are not the only source of epileptic activity; the perituberal brain tissue is also a proven focus. Currently, there is a tendency towards early pre-surgical evaluation and surgical treatment, which is recommended after the failure of two antiepileptic drugs. Considering the multiple brain lesions and multifocal epilepsy, the use of invasive electroencephalography is invaluable in the preoperative assessment of these patients. The effectiveness of resection surgery is 65–75 %. Over time, the proportion of patients in complete remission from seizures decreases. Lobectomy and tuberectomy plus procedures are favorable prognostic factors. Surgical treatmentsignificantly increasesthe chances of seizure freedom. Eliminating seizures in children has been shown to improve cognitive development.There is no algorithm for pre-surgical patient evaluation or selection criteria for surgical treatment. Some methods of presurgical evaluation are not included in the compulsory health insurance system, making early diagnosis and treatment very difficult. This leads to an increase in the number of patients with disabilities and a poor quality of life.

Pantoea agglomerans Infection in Neonates: A Systematic Review of Case Reports.

Pantoea agglomerans, a gram-negative bacterium, has emerged as an opportunistic pathogen, particularly within neonatal healthcare settings. Initially perceived as an innocuous environmental contaminant, P. agglomerans has been increasingly implicated in a spectrum of clinical infections, including neonatal sepsis and bacteremia. This systematic review conducts an in-depth analysis of the clinical cases published in 2003-2023, elucidating the multifaceted clinical presentations and therapeutic challenges associated with P. agglomerans infections in neonates. In total, 11 case reports and case series of 45 neonates from eight different countries were included. Most of the infected patients (57.8%) were reported in Asian countries (Sri Lanka, India, Kuwait) and involved preterm neonates (64.4%) with extremely low to low birth weight, and concurrent medical conditions including co-infections in a few of them (15.6%). Blood was the main culture source of the pathogen, accounting for 42 cases (91.1%) whereas clinical presentations in neonates exhibited considerable heterogeneity, encompassing common symptoms such as feeding difficulties, respiratory distress, fever, lethargy, and sepsis. Neonatal survival largely depended on the infection's origin and the timing of diagnosis. Considering antibiotic susceptibility as a criterion for treatment selection led to a 74% survival rate. Usually, a combination of antibiotics was used. There were 11 neonatal deaths reported, leading to an estimated mortality rate of 24.4%. We conclude that outbreaks within neonatal intensive care units underscore the importance of stringent infection control practices and heightened surveillance, especially considering the rapid disease progression noted in the included studies. Enhanced awareness and understanding of the clinical and microbiological characteristics of P. agglomerans infections are paramount for optimizing outcomes and reducing the burden of disease in neonatal populations.

Preoperative embolization of brain arteriovenous malformation and efficacy in intraoperative blood loss reduction: a quantitative study

BackgroundEmbolization of brain arteriovenous malformations (bAVMs) is often used as adjuvant therapy to microsurgical resection to reduce the high-risk features of bAVMs such as large size and high flow. However,...

Use of Alloplastic Total Joint Replacement of the Temporomandibular Joint of Growing Patients: A Scoping Review

Temporomandibular joint (TMJ) disorders pose unique challenges in pediatric patients undergoing craniofacial growth. Alloplastic total temporomandibular joint reconstruction (ATJR) techniques have emerged as promising solutions, offering immediate joint function and symptom relief. However, the efficacy and safety of ATJR in this population remain under scrutiny. This scoping review aims to comprehensively summarize the evolving literature on ATJR in growing patients with end-stage TMJ pathology. Our methodology adhered to PRISMA-ScR guidelines, identifying 9 relevant articles. The discussion emphasizes preoperative considerations, treatment selection criteria, and potential complications. While ATJR offers short-term benefits, concerns regarding long-term outcomes persist, necessitating further research. Collaboration among multidisciplinary teams is crucial for optimal patient care. Future research should focus on comparative efficacy and safety, refining treatment algorithms, and long-term follow-up to enhance outcomes and minimize complications in pediatric TMJ pathology.

Selection of prostate cancer therapy strategy under early androgen suppression treatment

Intermittent androgen suppression therapy is increasingly employed as an alternative method of advanced prostate cancer. However, it remains controversial whether intermittent therapy is superior to continuous therapy in controlling cancer progression. In this paper, we study the mathematical model for early treatment of prostate cancer that incorporates the individual differences and the pharmacodynamics of drugs. The mathematical criteria for selection of better treatment are established on the basis of stability of periodic solution induced by treatment. Numerical results further explore the optimal design of intermittent treatment. The results provide valuable insights for clinical practice.

HTA163 Setting Treatment Selection Criteria for Breast Cancer From a Clinician Perspective: Is It a Matter of Cost?

HTA163 Setting Treatment Selection Criteria for Breast Cancer From a Clinician Perspective: Is It a Matter of Cost?

Comparison of the effect of surgical versus transcatheter aortic valve replacement on the development of postoperative acute kidney injury.

Acute kidney injury (AKI) frequently occurs after cardiac surgery. Recently, transcatheter aortic valve implantation (TAVI), a less invasive option for aortic stenosis (AS), has been increasingly performed, particularly in elderly patients. We retrospectively investigated and compared the incidence and risk factors of postoperative AKI in patients who underwent surgical aortic valve replacement (SAVR) and TAVI. This was a retrospective single-center study. Seven days postoperatively, data were obtained from medical records. Patients were classified into SAVR and TAVI groups based on age, according to the policy of the Japanese Circulation Society. A total of 155 patients underwent surgery for AS between January 2020 and December 2021. Variables included age, sex, risk score, preoperative left ventricular ejection fraction, hypertension, and renal dysfunction. AKI was defined in accordance with the Kidney Disease: Improving Global Outcomes criteria. A total of 33 SAVR and 79 TAVI procedures were included in this study. The incidences of AKI in the SAVR and TAVI groups were 45.5% and 43.0%, respectively. No significant differences existed between the two groups. Weight (p = 0.0392) and pre-renal dysfunction (p = 0.0308) affected the incidence of AKI in the SAVR group, whereas no such variables were identified in the TAVI group. Within the current age-based treatment selection criteria for AS, no significant difference in the incidence of AKI was observed between the two procedures.Although preoperative renal function may be associated with postoperative AKI, further studies are required to select the optimal surgical procedure for patients with renal dysfunction.

Stem Cell Therapy in Children with Traumatic Brain Injury.

Pediatric traumatic brain injury is a cause of major mortality, and resultant neurological sequelae areassociated with long-term morbidity. Increasing studies have revealed stem cell therapy to be a potential new treatment. However, much work is still required to clarify the mechanism of action of effective stem cell therapy, type of stem cell therapy, optimal timing of therapy initiation, combination of cocurrent medical treatment and patient selection criteria. This paper will focus on stem cell therapy in children with traumatic brain injury.

A Retrospective Study Comparing Olaparib and Bevacizumab as a Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: Impact on Recurrence-Free Survival in Japanese and Asian Populations.

The use of angiogenesis inhibitors and poly ADP-ribose polymerase inhibitors following multi-agent chemotherapy, including platinum-based agents, has become the standard treatment for platinum-sensitive recurrent ovarian cancer (PSROC). However, the optimal maintenance therapy and selection criteria for these patients remain unclear. Thus, this study aimed to optimize the treatment options and selection criteria for patients with PSROC. The clinical data of 51 patients with PSROC admitted to Nippon Medical School Chiba Hokusoh Hospital and Nippon Medical School Hospital were retrospectively collected. The log-rank test was used for the survival analysis, and Cox proportional hazard regression analysis was used for the multivariate survival analysis. Of the 51 patients, 17 received maintenance therapy with bevacizumab (Bev), and 34 received olaparib (Ola). Recurrence-free survival (RFS) was significantly prolonged in the Ola group (27 months; 95% confidence interval (CI), 19-NA months) compared with that in the Bev group (9 months; 95% CI, 5-22 months; p = 0.000103). The efficacy of Ola was independent of background factors, including response to previous chemotherapy, homologous recombination status, histological type, or laboratory data. Ola is superior to Bev as PSROC maintenance therapy, especially in Japanese and Asian populations.

Adjuvant treatments for locally advanced differentiated thyroid cancer: a nationwide survey in Japan.

The role of adjuvant external-beam radiotherapy (EBRT) for locally advanced differentiated thyroid cancer (DTC) is controversial because of the lack of prospective data. To prepare for a clinical trial, this study investigated the current clinical practice of adjuvant treatments for locally advanced DTC. A survey on treatment selection criteria for hypothetical locally advanced DTC was administered to representative thyroid surgeons of facilities participating in the Japan Clinical Oncology Group Radiation Therapy Study Group. Of the 43 invited facilities, surgeons from 39 (91%) completed the survey. For R1 resection or suspected residual disease, 26 (67%) facilities administered high-dose (100-200 mCi) radioactive iodine (RAI), but none performed EBRT. For R2 resection or unresectable primary disease, 26 (67%) facilities administered high-dose RAI and 7 (18%) performed adjuvant treatments, including EBRT. For complete resection with nodal extra-capsular extension, 13 (34%) facilities administered high-dose RAI and 1 (3%) performed EBRT. For unresectable mediastinal lymph node metastasis, 31 (79%) facilities administered high-dose RAI and 5 (13%) performed adjuvant treatments, including EBRT. Adjuvant EBRT was not routinely performed mainly because of the lack of evidence for efficacy (74%). Approximately 15% of the facilities routinely considered adjuvant EBRT for DTC with R2 resection or unresectable primary or lymph node metastasis disease. Future clinical trials will need to optimize EBRT for these patients.

Predictive Value of Staging PET/CT to Detect Bone Marrow Involvement in Marginal Zone Lymphoma (MZL): An Analysis from LEO MZL Working Group

Introduction: Bone marrow (BM) involvement impacts stage and prognosis in lymphoma, remaining an important factor in risk-stratification scores, including the MALT-IPI. PET/CT is routinely implemented in the staging and response assessment of patients with lymphoma. However, FDG avidity to detect marginal zone lymphoma (MZL) remains debatable. In this study we aimed to assess the predictive value of PET/CT to detect BM involvement and survival implications in MZL using prospectively collected data from the Lymphoma Epidemiology of Outcomes (LEO) cohort. Methods: The LEO cohort is a prospective cohort from 8 academic cancer centers in which patients are enrolled within 6 months of lymphoma diagnosis and followed. We extracted baseline data of MZL patients enrolled in the LEO cohort between 5/2015 and 2/2020. BM biopsy was used as a gold standard for BM involvement. In addition, radiology reports were reviewed for PET/CT-suggested BM involvement. Event-free survival (EFS) defined as time from diagnosis to relapse/progression, retreatment, or death due to any cause and overall survival (OS) defined as time from diagnosis to death due to any cause were estimated by Kaplan-Meier. Results: Of 706 MZL patients enrolled in LEO, 311 (44%) with data on BM status by both biopsy and PET/CT were included in the analysis. Patients’ characteristics were median age 64 (range 24-89) years with most <70 years (n=217, 69.8%), non-Hispanic (n=264, 84.9%) white (n=276, 88.7%), without B symptoms (n=246, 79.1%), and normal LDH (n=185, 59.5%). The most common MZL subtype was extranodal (EMZL, n=208, 66.9%) followed by nodal (NMZL, n=61, 19.6%) and splenic (SMZL, n=42, 13.5%). Stage distribution was as follows: early-stage (I-II; n=134, 43.1%), advanced-stage (III-IV; n=159, 51.1%), and unknown (n=18, 5.8%). BM biopsy was positive in 99 (31.8%) and negative in 212 (68.2%) patients. Across all MZL subtypes, biopsy-proven and PET/CT-suggested BM involvement was present in 11.6% (n=36/311), and positive BM biopsy with negative PET/CT was observed in 20.3% (n=63/311) (EMZL=9.6%, n=20/208; NMZL=31.1%, n=19/61; and SMZL=57.1%, n=24/42). For EMZL, 15.9% (n=33) demonstrated pathologically confirmed BM involvement, and among those patients PET/CT was positive in 39.4% (n=13) and negative in 60.6% (n=20). For NMZL, 50.8% (n=31) demonstrated pathologically confirmed BM involvement, and among those patients PET/CT was positive in 38.7% (n=12) and negative in 61.3% (n=19). Most patients (83.3%, n=35) with SMZL demonstrated pathologically confirmed BM involvement, with positive PET/CT in 31.4% (n=11) and negative in 68.6% (n=24). Considering BM result from biopsy as the standard, PET/CT-based sensitivity and specificity in EMZL, NMZL, and SMZL were 39.4% & 98.9%, 38.7% & 100%, and 31.4% & 100%, respectively. PET/CT-based positive and negative predictive values in EMZL, NMZL, and SMZL were 86.7% & 89.6%; 100% & 61.2%; and 100% & 22.6%, respectively. With a median follow up of 35.4 months there were 70 EFS events and 18 OS events across all MZL subtypes. The 2-year EFS and OS were 81.7% (95%CI 76.8-85.7%) and 96.8% (95%CI 93.9-98.3%), respectively. The 2-year EFS and OS by histology were EMZL= 84.7% (95%CI 78.7-89.1%) & 97.2% (95%CI 93.5-98.8%); NMZL= 69.6% (95%CI 56.1-79.6%) & 96.5% (95%CI 86.9-99.1%); and SMZL= 85.6% (95%CI 70.7-93.3%) & 95.2% (95%CI 82.3-98.8%), respectively. Acknowledging the low number of events and unspecific criteria for treatment selection, those patients exhibiting pathological BM involvement (n= 99) did not show significantly different EFS (p=0.097) (EMZL p=0.48; NMZL p=0.68; and SMZL p=0.75, respectively) or OS (p=0.978) (EMZL p=0.46; NMZL=0.53; and SMZL=0.21, respectively) compared to those without BM disease. Conclusions: While PET/CT may be positive in nodal and some extranodal locations, assessment of BM involvement by PET/CT is characterized by a low sensitivity across all MZL subtypes and low negative predictive value in SMZL, underscoring the limitations of current Lugano criteria in staging MZL. With currently relatively limited follow-up, we did not observe significantly different survival based on BM status.

Clinical criteria for treatment selection in metastatic pancreatic adenocarcinoma: a real-world retrospective analysis

Clinical criteria for treatment selection in metastatic pancreatic adenocarcinoma: a real-world retrospective analysis

The Role of Knee Flexors Hypertonia in the Decision-Making of Hamstring Lengthening Surgery for Individuals with Cerebral Palsy

Popliteal angle (PA) and the knee position at the end of the swing phase during walking (Kts) are considered criteria for treatment selection and outcome prediction of hamstring lengthening surgery in individuals with cerebral palsy (CP). However, the relationships among Kts, PA, and hypertonia are not clear. This study aimed to determine whether hamstrings hypertonia affects the values of PA and Kts, and how it may affect the hamstring lengthening decision for CP. One hundred and twenty-six subjects with CP (male = 72, female = 54; age = 11.1 ± 3.9 years) underwent gait analysis and examination of hamstrings hypertonia (Tardieu scale) and length (PA). We found that Kts increased with PA (Kts = 5.00 + 0.31 × PA (r = 0.39; p &lt; 0.001)). Every 10° change of PA leads to 3° improvement of knee position in walking. Kts were larger (p &lt; 0.001) in the limbs with (20.40 ± 11.27°) than without (15.60 ± 9.99°) knee flexors hypertonia (Tardieu slow); and were larger (p &lt; 0.001) in the limbs with (20.39 ± 11.01°) than without (14.85 ± 9.89°) knee flexors hypertonia (Tardieu fast). PAs were larger (p &lt; 0.05) in the limbs with (42.81 ± 12.66°) than without (38.96 ± 14.38°) hypertonia (Tardieu fast). Kts = 13.93° and PA = 30° were cutoff values of the presence of hypertonia with sensitivities of 75.0% and 89.1%, respectively. Kts increased with the PA in ambulatory CP. It is estimated that pathological increase of Kts occurs at PA ≥ 40°. The hypertonia of knee flexors affected Kts and PA. The presence of knee flexors hypertonia should be considered in the decision-making of hamstring lengthening for individuals with CP if Kts ≥ 13.93° and PA ≥ 30°.

Gait apraxia evaluation in normal pressure hydrocephalus using inertial sensors. Clinical correlates, ventriculoperitoneal shunt outcomes, and tap-test predictive capacity

BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is a neurological condition with gait apraxia signs from its early manifestation. Ventriculoperitoneal shunt (VPS) is a surgical procedure available for treatment. The Cerebrospinal fluid Tap Test (CSF-TT) is a quick test used as selection criterion for VPS treatment. Its predictive capacity for VPS outcomes is still sub judice. This study is aimed to test the hypothesis that wearable motion sensors provide valid measures to manage iNPH patients with gait apraxia.MethodsForty-two participants of the Bologna PRO-Hydro observational cohort study were included in the analyses. The participants performed the Timed Up and Go (TUG) and the 18 m walking test (18mW) with inertial sensors at baseline, three days after the CSF-TT, and six months after VPS. 21 instrumental variables described gait and postural transitions from TUG and 18mW recordings. Furthermore, participants were clinically assessed with scales (clinical variables). We tested the hypothesis by analysing the concurrent validity of instrumental and clinical variables, their individual- and group-level responsiveness to VPS, and their predictive validity for VPS outcomes after CSF-TT.ResultsThe instrumental variables showed moderate to high correlation with the clinical variables. After VPS, most clinical and instrumental variables showed statistically significant improvements that reflect a reduction of apraxic features of gait. Most instrumental variables, but only one clinical variable (i.e., Tinetti POMA), had predictive value for VPS outcomes (significant adjusted R2 in the range 0.12–0.70).ConclusionsThese results confirm that wearable inertial sensors may represent a valid tool to complement clinical evaluation for iNPH assessment and prognosis.

Abstract 1774: Circulating IL-6, an early biomarker in HR-positive, HER2-negative metastatic breast cancer patients progressing on CDK4/6 inhibitors

Abstract Background: CDK4/6 inhibitors (CDK4/6i, e.g. palbociclib) in combination with endocrine therapy (ET) have proven successful in delaying progression in hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer patients; however, 60-70% will progress within 1-2 years of treatment. Thus, understanding the mechanisms of resistance and identifying novel treatment strategies are needed to improve survival. Our previously published data shows that palbociclib resistance is marked by significant upregulation of the IL6-STAT3 signaling pathway in HR+, HER2- breast cancer cells and treatment with TTI-101, a small-molecule STAT3 inhibitor completing Phase I studies in solid tumor patients, significantly decreased cell viability. Additionally, matched biopsies from advanced HR+, HER2- breast cancer patients who progressed on palbociclib plus ET had an upregulation in activated STAT3 (STAT3 phosphorylated on Y705, pY-STAT3) as compared to their pre-treatment biopsy. Collectively, these data suggest that targeting the IL-6/STAT3 pathway is a viable therapeutic strategy. Our ongoing studies are directed at delineating the role of IL-6 and pY-STAT3 as predictive biomarkers to provide preclinical rationale for targeting STAT3 in patients who develop CDK4/6i resistance. Methods: We downregulated IL-6 using shRNA in MCF7 and T47D palbociclib sensitive and resistant cells. We tested the efficacy of TTI-101 in patient-derived xenograft (PDX) models from patients with metastatic HR+, HER2- breast cancer who progressed on treatment with palbociclib + ET. We also collected plasma samples from patients with metastatic HR+, HER2- breast cancer just prior to CDK4/6i treatment and at disease progression. Results: Downregulation of IL-6 in palbociclib resistant cells reduced pY-STAT3 levels and re-sensitized cells to ET and palbociclib. Induction of IL-6 is an early event by treating sensitive cells with 1uM palbociclib for 21 days during which the cells adapted and eventually developed resistance. Suppression of IL-6 in sensitive cells revealed that it is needed for cells to overcome growth inhibition by palbociclib. Targeting STAT3 in palbociclib resistant PDX mouse models using TTI-101 (50mg/kg twice daily by oral gavage), resulted in significantly reduced tumor volume; a synergistic effect was observed when TTI-101 was combined with palbociclib. Lastly, IL-6 levels in plasma samples from metastatic HR+, HER2- breast cancer patients were significantly higher at disease progression compared to pre-treatment with CDK4/6i. Conclusion: Collectively, these studies suggest that IL-6 signaling through STAT3 is a key mediator of resistance to palbociclib. We provide the rationale for using circulating IL-6 as a biomarker of disease progression and tumor pY-STAT3 as a selection criterion for treatment with TTI-101 to prevent or reverse resistance. Citation Format: Nicole M. Kettner, Tuyen N. Bui, Juliana Navarro-Yepes, T Kris Eckols, Akshara S. Raghavendra, David J. Tweardy, Kelly K. Hunt, Debu Tripathy, Khandan Keyomarsi. Circulating IL-6, an early biomarker in HR-positive, HER2-negative metastatic breast cancer patients progressing on CDK4/6 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1774.

Surgical methods in management of metastatic spinal cord lesions

Malignant neoplasms remain the leading cause of death worldwide. The spine is a target for metastasis more often than other skeletal bones. This article details the principles of diagnosis, treatment, and the clinical picture of secondarylesions of the spinal column. The causes of pain syndrome in cancerous lesions of the spine are reviewed: compression of nerve structures, pathological fractures, spinal instability, lytic foci and paraneoplastic pain syndrome. The causes and patterns of each type of pain syndrome are described in detail. The article presents the scales used to predict the life expectancy of these patients: Tokuhashi, Tomita and Bauer. The effectiveness of these scales is compared. The selection criteria for surgical treatment of patients with metastatic lesions of the spine are described in detail. Modern methods of surgical treatment of secondary lesions of the spinal column are presented: palliative, subtotal, total (enblock resections). The indications and contraindications for each type of surgical treatment are described. Methods of intraoperative hemostasis are described, with the special attention given to preoperative tumor embolization. The errors and complications of this technique are described in detail. The correlation dependence of intraoperative blood loss volume on the embolization terms is presented. Modern trends in the development of surgical methods in metastatic spinal tumors are described in conclusion.

Efficacy and safety of outpatient parenteral antibiotic therapy in patients with infective endocarditis: a meta-analysis.

BackgroundTo investigate the clinical outcome of patients with infective endocarditis (IE) during and after outpatient parenteral antimicrobial treatment (OPAT), and to further clarify the safety and efficacy of OPAT for IE patients.MethodsThrough December 20, 2021, a total of 331 articles were preliminarily searched in Pubmed, Web of Science, Cochrane Library and Embase, and 9 articles were eventually included in this study.ResultsA total of 9 articles comprising 1,116 patients were included in this study. The overall mortality rate of patients treated with OPAT was 0.04 (95% CI, 0.02-0.07), that means 4 deaths per 100 patients treated with OPAT. Separately, mortality was low during the follow-up period after OPAT treatment, with an effect size (ES) of 0.03 (95%CI, 0.02-0.07) and the mortality of patients during OPAT treatment was 0.04 (95% CI, 0.01-0.12). In addition, the readmission rate was found to be 0.14 (95% CI, 0.09-0.22) during the follow-up and 0.18 (95% CI, 0.08-0.39) during treatment, and 0.16 (95% CI, 0.10-0.24) for patients treated with OPAT in general. Regarding the relapse of IE in patients, our results showed a low overall relapse rate, with an ES of 0.03 (95% CI, 0.01-0.05). In addition, we found that the incidence of adverse events was low, with an ES of 0.26 (95% CI, 0.19-0.33).ConclusionIn general, the incidence of adverse events and mortality, readmission, and relapse rates in IE patients treated with OPAT are low both during treatment and follow-up period after discharge, indicating that OPAT is safe and effective for IE patients. However, our study did not compare routine hospitalization as a control group, so conclusions should be drawn with caution. In order to obtain more scientific and rigorous conclusions and reduce clinical risks, it is still necessary to conduct more research in this field and improve the patient selection criteria for OPAT treatment, especially for IE patients. Finally, clinical monitoring and follow-up of OPAT-treated patients should be strengthened.