Adjuvant Therapy Research Articles

Clinical Practice Guideline: Recommendations for the Perioperative Management of Pancreatic and Colorectal Cancer Patients.

Colorectal and pancreatic carcinoma are the most common cancers of the gastrointestinal tract. Their surgical treatment carries a high morbidity: Complications arise in 25% to 30% of cases, often prolonging recovery times and delaying the initiation of adjuvant therapy, leading, in turn, to worse oncological outcomes. The goal of multimodal perioperative management (mPOM) is to lower the postoperative complication rate through a combination of perioperative measures. This guideline on the perioperative management of gastrointestinal tumors (POMGAT) meets all requirements for an S3 guideline as specified by the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). These include a systematic literature search, quality assessment of the included publications, an evaluation of the reliability of the evidence according to the GRADE approach, and a structured consensus process. Meta-analyses have shown that mPOM lowers the complication rates of both pancreatic and colorectal resections (RD 0.96 with 95% confidence interval [0.92; 0.99] and RR 0.66 [0.54; 0.80], respectively). This shortens the hospital stay after pancreatic resections by a median of 2.33 days [-2.98; -1.69] and after colorectal resections by a median of 2.59 days [-3.22; -1.97]. Adherence to the POMGAT-S3 guideline for pancreatic and colorectal cancer surgery is associated with improved recovery, which can lead to a faster return to intended oncological treatment (RIOT) and thus to better long-term outcomes. These recommendations are not restricted to gastrointestinal cancer surgery; they can also be applied to visceral surgery for benign conditions, as well as to gynecological and urological operations.

A Narrative Review on the Potential of Black Seeds (Nigella Sativa) in the Management of West Nile Virus Infection

Abstract: West Nile virus (WNV) infection is a mosquito-borne illness that is endemic to Africa, Asia, the Middle East, Australia, and Europe. WNV-infected individuals can only be managed with symptomatic therapy and supportive care at this point of time. Thus, we have analyzed the possible beneficial effects of black seeds (N. sativa) in this literature review. To find relevant articles, various online databases, such as the Web of Science, Medline, PMC, PubMed, Embase, EBSCO, Google Scholar, Science Direct, and reference lists were searched. The antiviral, analgesic, anti-inflammatory, antioxidant, and immunomodulatory effects of black seeds (N. sativa) have been established by numerous clinical, animal, in vivo, in vitro, and in silico studies. It has been found that black seeds (N. sativa) have the potential to be included as adjuvant therapy in addition to symptomatic treatment and supportive care in the early stages of WNV infection once randomized controlled clinical trials (RCTs) affirm the safety and efficacy of black seeds (N. sativa) in WNV infection management as they have been considered the gold standard of treatment in clinical studies.

Phytochemicals as Adjuvant Therapies in RND Efflux-mediated Multidrug Resistant Pseudomonas aeruginosa Infections and Evaluation Techniques of Efflux Inhibitory Activities in Bacteria

: One of the top-listed opportunistic pathogens that are frequently found in medical devices such as ventilation systems is Pseudomonas aeruginosa. These bacteria often cause infections in the lungs (pneumonia), blood after surgery, and other parts of the body. Extreme susceptibility to P. aeruginosa infection primarily exists in immunosuppressed individuals, and long-term evolution has led to the development of genetic resistance mechanisms that have high genetic flexibility against damaging antibiotics. Several lines of research evidence point to efflux as the primary reason for the organism's effectiveness against antibiotic treat-ment in infections caused by this bacterium. Drug Efflux pumps play a crucial role in medicine because they expulse a variety of unique and unrelated chemical structures with either antibi-otics or antimicrobials before they reach the concentration necessary to kill bacteria, confer-ring multiple resistance to more than one class of antibiotics. Targeting this mechanism for example by blocking the most active efflux pump MexAB-orpM would probably lead to the discovery of new ways to circumvent the bacterial system of antibiotic resistance and boost treatment effectiveness.

Overtreatment and Undertreatment of Early-Stage Breast Cancer in Older Women: Evaluating the POWER Trial

IntroductionRadiation therapy (RT) omission is acceptable in older women with early-stage estrogen receptor + breast cancer treated with breast-conserving surgery (BCS) and adjuvant endocrine therapy (AET). However, RT rates in this population remain high, causing concern for overtreatment. Conversely, patients who omit RT and do not complete a course of AET are at risk of undertreatment. In the Pre-Operative Window of Endocrine Therapy to Inform Radiation Therapy Decisions (POWER) trial, participants receive 90 days of preoperative endocrine therapy to assess tolerance before deciding about RT. This study aimed to determine the rates of undertreatment and overtreatment institutionally and among POWER trial participants. MethodsData were retrospectively collected from medical records of women aged ≥ 65 years diagnosed with invasive, estrogen receptor +/human epidermal growth factor receptor 2- breast cancer, ≤ 3 cm, who had BCS between 2012 and 2022. Patients were categorized as undertreated (BCS alone), overtreated (BCS + RT + AET), or appropriately treated (BCS + RT or BCS + AET). ResultsThe cohort included 478 patients, of whom 62 (12.97%) were undertreated, 202 (42.26%) were overtreated, and 214 (44.77%) were appropriately treated. Appropriately treated patients were more likely to be aged 70-79 years (P < 0.0001) and have high health literacy (P = 0.0003). Of the 37 patients (7.71%) in the POWER trial, more were appropriately treated than patients not in the POWER trial (81.1% versus 44.8%) (P < 0.0001). ConclusionsDespite long-standing guideline changes, RT utilization remains high. This study highlights how a novel patient-centered approach to guide adjuvant therapy decisions may increase the number of appropriately treated patients.

The Potential of Epigallocatechin Gallate in Targeting Cancer Stem Cells: A Comprehensive Review.

The dreadful scenario of cancer prevails due to the presence of cancer stem cells (CSCs), which contribute to tumor growth, metastasis, invasion, resistance to chemo- and radiotherapy, and recurrence. CSCs are a small subpopulation of cells within the tumor that are characterized by self-renewal capability and have the potential to manifest heterogeneous lineages of cancer cells that constitute the tumor. The major bioactive green tea polyphenol (-)-epigallocatechin gallate (EGCG) has been fruitful in downgrading cancer stemness signaling and CSC biomarkers in cancer progression. EGCG has been evidenced to maneuver extrinsic and intrinsic apoptotic pathways in order to decrease the viability of CSCs. Cancer stemness is intricately related to epithelial-mesenchymal transition (EMT), metastasis and therapy resistance, and EGCG has been evidenced to regress all these CSC-related effects. By inhibiting CSC characteristics EGCG has also been evidenced to sensitize the tumor cells to radiotherapy and chemotherapy. However, the use of EGCG in in vitro and in vivo cancer models raises concern about its bioavailability, stability and efficacy against spheroids raised from parental cells. Therefore, novel nano formulations of EGCG and adjuvant therapy of EGCG with other phytochemicals or drugs or small molecules may have a better prospect in targeting CSCs. However, extensive clinical research is still awaited to elucidate a full proof impact of EGCG in cancer therapy.

The potential of EZH2 expression to facilitate treatment choice in stage II colorectal adenocarcinoma.

The current selection criteria of patients with stage II colorectal carcinoma (CRC) suitable for adjuvant therapy are not satisfactory. Enhancer of zeste homolog 2 (EZH2) has been demonstrated to be over-expressed in CRC. However, data regarding the role of EZH2 in CRC survival remains controversial, and little is known about it in stage II CRC. Thus, we conducted this study to investigate the clinical significance of EZH2 expression in stage II CRC. Cases with stage II CRC resected between 2015 and 2018 were retrospectively reviewed. EZH2 expression was analyzed by immunohistochemistry using tissue microarrays. The relationship between EZH2 expression and clinicopathological variables was analyzed. Survival curves were estimated by the Kaplan-Meier approach. We found high EZH2 expression in 134 of 221 analyzable stage II tumors (60.63%). No significant associations were observed between EZH2 expression and common clinicopathological factors. Survival analyses showed that cases receiving surgery alone had inferior overall survival (OS) than those receiving surgery and chemotherapy (P=0.0075) in stage II CRC with high EZH2 expression, however, metastasis-free survival (MFS) was similar between these two subgroups. Treatment choice had no impact on the survival of stage II CRC with low EZH2 expression. The OS of stage II CRC with high EZH2 expression improved more strikingly with surgery and adjuvant chemotherapy than with surgery alone, which suggests the potential of EZH2 expression as a biomarker to help identify a subgroup of early-stage CRC benefiting from surgery and adjuvant chemotherapy. More large-scale studies are warranted to corroborate this finding and to further evaluate the predictive nature of EZH2.

Reducing 30-Day Readmissions in Patients With Alcohol Use Disorder

The 30-day hospital readmission rate for alcohol use disorder (AUD) at a Veteran’s Affairs hospital is 2% higher than the national benchmark. This quality improvement project aimed to implement a holistic approach to care of veterans with AUD through optimization of the Clinical Institute Withdrawal Assessment for Alcohol Scale-Revised protocol and development of a revised and evidence-based alcohol withdrawal syndrome order set. After implementation, there was a statistically significant decrease in 30-day readmissions and an increase in prescription of adjuvant therapies such as gabapentin and hydroxyzine. This quality improvement project improved the processes of care related to treatment of veterans with AUD admitted with alcohol withdrawal syndrome.

Abstract C053: Racial differences in adverse sexual symptoms and implications for quality of life and adjuvant endocrine therapy adherence among women with early-stage breast cancer

Abstract C053: Racial differences in adverse sexual symptoms and implications for quality of life and adjuvant endocrine therapy adherence among women with early-stage breast cancer

Comparative Efficacy of 21 Treatment Strategies for Resectable Pancreatic Cancer: A Network Meta-Analysis

The primary treatment for operable pancreatic cancer (PC) involves surgery followed by adjuvant therapy. Nevertheless, perioperative or neoadjuvant chemotherapy (CT) may be used to mitigate the likelihood of recurrence and mortality. This network meta-analysis (NMA) assesses the comparative efficacy of various treatment approaches for resectable PC. A thorough search was carried out on January 31, 2023, encompassing PubMed/MEDLINE, Cochrane Library, and Embase databases. We incorporated randomized clinical trials (RCTs) that compared surgical interventions with or without (neo)adjuvant or perioperative therapies for operable PC. We conducted a fixed-effects Bayesian NMA. We presented the effect sizes in terms of hazard ratios (HRs) for overall survival (OS) along with 95% credible intervals (95% CrIs). The treatment was deemed statistically superior when the 95% credible interval (CrI) did not encompass a null value (hazard ratio &lt; 1). Treatment rankings were established based on the surface under the cumulative ranking curve (SUCRA). A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone, with HRs ranging from 0.38 for perioperative treatments to 0.73 for adjuvant 5-fluorouracil. After the exclusion of studies conducted in Asia, it was found that the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen (SUCRA, p = 0.99). The findings endorse the utilization of perioperative CT, especially multi-agent CT, as the favored intervention for operable PC in Western nations.

Metaplastic Carcinoma Breast in Polycythemic Octogenarian – Lessons Learnt: Case Report

An 80-year-old lady presented with lump Left breast of 8 months duration. Clinically was aT4b lesion, sonomammogram showed BIRADS V lesion and core needle breast biopsy features were suggestive of metaplastic carcinoma breast of adenosquamous type, ER, PR-Positive, Her2Neu-Negative. Patient received preoperative hormonal therapy followed by modified radical mastectomy and postoperative adjuvant chemotherapy and hormonal therapy. Post operative patient showed good clinical recovery and was recurrence free at 6 months follow up although patient had all the poor prognostic factors with large size, LN involvement and high Ki 67. This article is a rare example of metaplastic breast carcinoma presenting in geriatric age group and showing good recovery despite presence of all poor prognostic factors. Hence this report is to enlighten the medical caregivers about the existence of this rare entity and challenges involved in management of this entity.

A randomized phase II trial on the addition of dutasteride to combined androgen blockade therapy versus combined androgen blockade therapy alone in patients with advanced or metastatic salivary duct carcinoma – the DUCT study protocol

BackgroundSalivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer, frequently associated with incurable recurrences and distant metastases (R/M). Proliferation of SDC relies on androgen receptor (AR) signalling, prompting the use of combined androgen blockade (CAB, i.e., luteinizing hormone-releasing hormone agonist and/or AR antagonists) to R/M SDC patients. However, only a subset of patients benefits from such treatments. We have shown that response to CAB is associated with steroid 5α-reductase 1 (SRD5A1) mRNA expression. SRD5A1 catalyses the intracellular conversion of testosterone into the more potent AR-agonist dihydrotestosterone. This conversion can be inhibited by dutasteride, a potent SRD5A1-inhibitor, which is currently prescribed for benign prostatic hyperplasia. We hypothesize that repurposing dutasteride to target AR signalling in SDC could enhance therapeutic response and clinical outcome in SDC patients.MethodsThis prospective, open-label, randomized controlled phase II clinical trial, is designed to investigate whether dutasteride as an adjunct drug to CAB improves response rate and clinical outcome in patients with AR-positive R/M SDC. Patients are divided in two cohorts based on their prior systemic treatments. In cohort A, CAB-naïve patients (n = 74) will be randomly assigned to either a control arm (Arm 1) receiving CAB (goserelin 10.8 mg/3m and bicalutamide 50 mg/OD) or an experimental arm (Arm 2) where dutasteride (0.5 mg/OD) is added to the CAB regimen. In cohort B, patients with disease progression after adjuvant or first-line palliative CAB therapy (max. n = 24) will receive goserelin, bicalutamide, and dutasteride to assess whether the addition of dutasteride can overcome therapy resistance. The primary endpoints are the objective response rate and duration of response. Secondary endpoints are progression-free survival, overall survival, clinical benefit rate, quality of life, and safety. Translational research will be performed to explore molecular target expression differences and their correlation with clinical outcome.DiscussionThe DUCT study addresses an unmet medical need by investigating the repurposing of dutasteride to enhance treatment response and improve clinical outcome for patients with R/M SDC, especially those with limited alternative treatment options, such as HER2-negative cases. By repurposing a registered low-cost drug, this trial’s findings could be readily applied into clinical practice.Trial registrationClinicaltrials.gov Identifier: NCT05513365. Date of registration: August 24, 2022.Protocol versionCurrent protocol version 4.0, February 21, 2024.

Add-on multidrug treatment based on quadruple therapy successfully treated worsening heart failure caused by anthracycline-induced cardiomyopathy in a survivor of cancer as a young adult: a case report

BackgroundThe overall mortality and morbidity benefit in patients with heart failure with a reduced ejection fraction is greatest with a treatment combination of sacubitril/valsartan, beta-blockers, mineralocorticoid-receptor antagonists, and sodium-glucose transporter-2 inhibitors, termed the “fantastic four” or “quadruple therapy.” The addition of vericiguat (an oral soluble guanylate cyclase stimulator) is believed to aid in managing worsening heart failure after quadruple therapy. Among childhood and young adult cancer survivors, cardiovascular complications that develop more than 10 years after anthracycline-based chemotherapy have a poor prognosis. Therefore, this study reports the efficacy of multidrug regimen based on quadruple therapy for worsening heart failure in cancer survivors with anthracycline-induced cardiomyopathy.Case presentationA survivor of cancer as a young adult who received high-dose anthracycline chemotherapy presented with acute decompensated heart failure 20 years post-chemotherapy and worsening heart failure 1.5 years after discharge. The patient showed signs of improvement after a step-wise introduction of carvedilol, empagliflozin, sacubitril/valsartan, ivabradine, and spironolactone for worsening heart failure. Vericiguat was accelerated owing to the risk of more severe cardiovascular events associated with ongoing aortic stenosis and the poor prognosis of anthracycline-induced cardiomyopathy. Heart failure symptoms continued to improve, with significant cardiac reverse remodeling, and the patient successfully underwent aortic valve replacement for severe aortic stenosis.ConclusionsOur case highlighted that multidrug treatment with add-on vericiguat and ivabradine based on quadruple therapy can potentially treat worsening heart failure in young adult cancer survivors with severe anthracycline-induced cardiomyopathy.

Navigating precision: the crucial role of next-generation sequencing recurrence risk assessment in tailoring adjuvant therapy for hormone receptor-positive, human epidermal growth factor Receptor2-negative early breast cancer

Navigating precision: the crucial role of next-generation sequencing recurrence risk assessment in tailoring adjuvant therapy for hormone receptor-positive, human epidermal growth factor Receptor2-negative early breast cancer

Surgical outcomes following neoadjuvant chemotherapy with and without immunotherapy in patients with triple-negative breast cancer

PurposeAdding pembrolizumab to neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) improves pathologic complete response (pCR) rates and event-free survival. The impact of adding immunotherapy to NAC on surgical outcomes is unknown. This study compares 90-day post-surgical complications (PSCs) and time to adjuvant treatment among patients undergoing NAC for TNBC with and without immunotherapy.MethodsPatients treated with NAC alone or with immunotherapy (NAC-I) for stage I–III TNBC between 2018 and 2022 were retrospectively identified at a single academic institution. Kruskal–Wallis rank sum and Fisher's exact tests compared patient sociodemographic and clinical characteristics. Multivariable logistic regression determined odds ratios (OR) predicting PSCs.ResultsOf 54 patients, 29 received NAC alone and 25 received NAC-I. Compared to NAC patients, NAC-I patients had more advanced stage tumors (p = 0.038), and had slightly higher rates of mastectomy with reconstruction (p = 0.193). 72.0% of NAC-I patients experienced a pCR, compared with 44.8% of NAC patients (p = 0.193). There were 10 PSCs (34.5%) in NAC patients compared to 9 PSCs (36.0%) in NAC-I patients (p > 0.99). Regression analysis demonstrated no association of PSCs with NAC-I (OR 0.83, 95% CI 0.19–3.60). Time to adjuvant therapy was shorter for NAC-I patients (28 days vs 36 days, p = 0.013).ConclusionsPatients with TNBC receiving NAC-I have higher pCR rates and do not appear to have added 90-day PSCs or delays to adjuvant therapy despite trending toward more extensive surgical procedures compared to NAC alone. Larger studies are needed to further evaluate the surgical safety of immunotherapy.

Efficacy of chemotherapy for patients with gastric cancer with early recurrence during or after adjuvant chemotherapy with S-1 alone: a multicenter retrospective study

This study aimed to survey the efficacy of chemotherapy regimens in the real world setting and explore the most promising regimen for patients experiencing early recurrence for gastric cancer. We retrospectively reviewed the clinical course of 207 patients with gastric cancer, who developed early recurrence during or within 6 months after completing S-1 adjuvant therapy at 19 Japanese institutions between 2012 and 2016. The treatment regimens after recurrence were fluoropyrimidines plus platinum-based regimens (FP) in 91 (44%) patients, paclitaxel-based regimens (PTX) in 102 (49%), and irinotecan-based regimens (IRI) in 14 (7%). The overall response and disease control rates were 28.7% and 54.1%. Median progression-free survival (PFS) and overall survival (OS) were 5.1 and 12.9 months, respectively. In the FP, PTX, and IRI regimens, the median PFS and OS were 5.9, 4.1, 4.1 months and 12.8, 12.9, and 11.8 months, respectively. The combination of PTX and ramucirumab showed survival comparable to capecitabine plus platinum. Multivariate analyses for OS showed that recurrence during adjuvant chemotherapy and undifferentiated histological type were independent poor prognostic factors. Although the prognosis of patients with early recurrence even with adjuvant S-1 was poor, PTX plus ramucirumab therapy could be a potential treatment option.

High expression of PAX8-AS1 correlates with poor prognosis and response to fluorouracil-based chemotherapy in stage II colon cancer

Decisions regarding adjuvant therapy in patients with stage II colon cancer remains controversial and challenging. We aimed to determine novel biomarkers that help to predict relapse free survival (RFS) and identify a subset of patients with stage II colon cancer who could gain survival benefits from adjuvant chemotherapy. Public microarray datasets of stage II colon cancer samples were extracted from Gene Expression Omnibus database. Global gene expression changes were then analyzed between the paired early relapse and long-term survival group to identify the differentially expressed mRNAs and lncRNAs. Based on Lasso Cox regression modeling analysis, a total of 30 mRNAs and 2 lncRNAs were finally identified. With specific formula, stage II patients in training and validation sets were divided into low and risk groups with significantly different RFS. PAX8-AS1 is the novel lncRNA which showed the highest upregulation in early relapse group. Patients with high PAX8-AS1 expression level showed notably poorer RFS in both meta GEO cohort (P = 0.04, Figure 4B) and FUSCC cohort (P < 0.001, Figure 4C). Among the stage II patients with high PAX8-AS1 level, administration of fluorouracil-based adjuvant chemotherapy provided a substantial improvement in RFS (P = 0.002, Figure 3C). Further mechanistic study unveiled that PAX8-AS1 increases the response of CRC cells to chemotherapy in vitro and in vivo by maintaining the mRNA stability of PAX8. In conclusion, PAX8-AS1 as a novel and reliable biomarker for predicting prognosis and identification of patients with stage II disease who could gain survival benefit from fluorouracil-based adjuvant chemotherapy.

Evaluating Treatment Modalities for Reducing Recurrence in Central Giant Cell Granuloma: A Narrative Review

Treating central giant cell granuloma (CGCG) is challenging due to high recurrence rates and variable therapy responses. This study examines the efficacy of various treatments in reducing CGCG recurrence. A literature review explored outcomes of surgical excision, curettage, intralesional corticosteroid injection, and adjuvant therapy, considering factors like lesion location, size, and histological features. Aggressive surgical techniques such as en bloc resection were found to potentially lower recurrence rates compared to conservative approaches. However, treatment should be tailored to individual patient needs. Further research is needed to confirm these findings and improve treatment strategies. A concise literature review was conducted using PubMed, MEDLINE, and Google Scholar, focusing on papers published from 1986 to 2024. Search terms included “central giant cell granuloma”, “recurrence”, “treatment modalities”, and “surgical excision”. Studies reporting recurrence rates and treatment outcomes for CGCG were analyzed. Twenty-nine studies were reviewed, including six studies on surgical excision and curettage, eight studies on intralesional corticosteroid injections, six studies on calcitonin therapy, five studies on interferon-alpha therapy, and four studies on the therapy with denosumab. Analysis indicated that aggressive surgical treatments like en bloc resection were associated with lower recurrence rates compared to conservative methods. Predictors of recurrence included lesion size (&gt;3 cm), location (mandible), and aggressive histopathological features. Aggressive surgical excision combined with nonsurgical methods may lower recurrence rates, while conservative techniques remain viable in some cases. Further prospective research is needed to validate these findings and enhance CGCG treatment options.

Radiological Assessment of Different Retroperitoneal Lymph Node Measurements in Stage 1 Testicular Cancer Patients: Impact on Clinical Stage and Treatment

Background: In staging for testicular germ cell tumor (GCT), current guidelines lack consensus regarding the measurement of retroperitoneal lymph node metastasis, concerning the recommended plane and dimension. This exploratory study aimed to assess its impact on clinical stage (cS) and therapy. Methods: We retrospectively examined 154 cSI (retroperitoneal lymph nodes &lt; 10 mm in axial short-axis diameter (SAD)) GCT patients, without adjuvant therapy and a follow-up ≥ 24 months. Retroperitoneal lymph nodes were measured in staging images in different dimensions (SAD and long-axis diameter (LAD)) and planes (axial, sagittal and coronal). Results: Overall survival was 100%, with 82% free of recurrence after a median follow-up of 83 months. All patients were classified as cSI, based on axial SAD (RECIST 1.1). However, significantly more patients would have been classified as cSIIA (0% vs. 38% vs. 52%) or even cSIIB (0% vs. 1% vs. 25%) according to axial LAD (SWENOTECA, German S3 guideline) or maximum LAD in any plane (EAU, ESMO, AJCC and onkopedia) (p &lt; 0.001). Overtreatment was predicted in 0%, 31% and 61% of patients based on axial SAD, axial LAD and maximum LAD, while undertreatment was estimated at 18%, 10% and 2%, respectively, (p &lt; 0.001). Conclusions: These findings indicate considerable variability in cS based on current lymph node staging recommendations, suggesting that axial SAD (RECIST 1.1) could be the most appropriate parameter for standardized guideline recommendations.

Metabolomic characterization of human glioblastomas and patient plasma: a pilot study

Background Glioblastoma (GBM) is a clinically challenging primary brain tumor with poor survival outcome despite surgical resection and intensive chemoradiation. The metabolic heterogeneity of GBM can become biomarkers for treatment response, resistance, and outcome prediction. The aim of the study is to investigate metabolic distinctions between primary and recurrent GBM tissue and patient plasma to establish feasibility for metabolic profiling. Methods A single-center cohort study analyzed tissue and blood samples from 15 patients with GBM using untargeted metabolomic/lipidomic assays. Metabolomic, lipidomic, and biogenic amine analyses were conducted on GBM tissue and patient plasma at diagnosis and recurrence using untargeted mass spectrometry. The study utilized a small but longitudinally collected cohort to evaluate alteration in metabolites, lipids, and biogenic amines between specimens at diagnosis and recurrence. Results Exploratory analysis revealed significant alteration in metabolites, lipids, and biogenic amines between diagnostic and recurrent states in both tumor and plasma specimens. Notable metabolites differed at recurrence, including N-alpha-methylhistamine, glycerol-3-phosphate, phosphocholine, and succinic acid in tissue, and indole-3-acetate, and urea in plasma. Principal component analysis revealed distinct metabolomic profiles between tumor tissue and patient plasma. Distinct metabolic profiles were observed in GBM tissue and patient plasma at recurrence, demonstrating the feasibility of using metabolomic methodologies for longitudinal studies. One patient exhibited a unique tumor resistance signature at diagnosis, possibly indicating a high-risk metabolomic phenotype. Conclusions In this small cohort, the findings suggest the potential of metabolomic signatures of GBM tissue and patient plasma for risk stratification, outcome prediction, and the development of novel adjuvant metabolic-targeting therapies. The findings suggest metabolic discrepancies at diagnosis and recurrence in tissue and plasma, highlighting potential implications for evaluation of clinical response. The identification of significant changes in metabolite abundance emphasizes the need for larger studies using targeted metabolomics to validate and further explore these profiles.

Effects of intermittent theta burst stimulation add-on to dialectical behavioral therapy in borderline personality disorder: results of a randomized, sham-controlled pilot trial

AbstractDialectical behavioral therapy (DBT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in borderline personality disorder (BPD). We hypothesized that intermittent theta burst stimulation (iTBS), a modified rTMS protocol that provides unilateral stimulation to the left dorsolateral prefrontal cortex, would enhance the effects of DBT and reduce BPD-specific symptoms more than sham stimulation. We performed a single-blind, randomized, sham-controlled pilot study to evaluate iTBS as an add-on to 8-week DBT for BPD in routine inpatient treatment. A total of 53 BPD patients were randomly assigned to either iTBS (n = 25) or sham stimulation (n = 28) in weeks 4–8 of DBT; 40 patients were eligible for inclusion in the analyses according to pre-specified criteria (≥ 16 of 20 iTBS sessions). The primary endpoint was change on the 23-item Borderline Symptom List; secondary endpoints were changes in depressive symptoms and general level of functioning. A mixed model repeated measures analysis with a 2 × 2 factorial between-subjects design showed no significant effect of add-on iTBS treatment, but a distinct trend was observed in favor of iTBS (Cohen’s d = 0.23 for group difference). We found a main effect of DBT with and without iTBS over time, indicating efficacy of 8 weeks’ DBT (d = 0.89–1.12). iTBS may be beneficial as an add-on to DBT in the long term and warrants further evaluation in larger studies. Trial registration Registered at drks.de (no. DRKS00020413) on January 13, 2020.