Standard Of Care For Treatment Research Articles

Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression: A protocol for systematic review and meta-analysis.

Major Depressive Disorder (MDD) is a global health issue, and a significant portion of individuals with MDD experience Treatment-Resistant Depression (TRD), characterized by the lack of response to adequately trialed antidepressant medication and therapy. This systematic review aims to investigate the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) as an intervention for individuals with TRD. We will conduct a thorough search for publications of randomized clinical trials and quasi-experimental studies in MEDLINE, Embase, PsycINFO, Web of Science databases, and ClinicalTrials.gov. Furthermore, reference lists of included studies will be manually screened for additional relevant articles, with no restrictions on language or publication date. The search will be conducted from the inception of the databases until June 2024. Our PICO-guided research questions are: (1) In adults with Treatment-Resistant Depression, is MBCT more effective than standard care or other active treatments in reducing depressive symptoms? (2) In adults with Treatment-Resistant Depression, does MBCT demonstrate a comparable safety profile to standard care or other active treatments? The quality of the included studies will be assessed independently using the Cochrane Risk of Bias Tool (RoB 2). This study seeks to evaluate the effectiveness and tolerability of Mindfulness-Based Cognitive Therapy as an intervention for Treatment-Resistant Depression, and will employ the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to appraise the confidence in the evidence. Prospero registration ID: CRD42023411978. Registered on April 07, 2023.

Switching to Low Neurotoxic Antiretrovirals to Improve Neurocognition Among People Living With HIV-1-Associated Neurocognitive Disorder: The MARAND-X Randomized Clinical Trial

Background: The pathogenesis of HIV-associated neurocognitive (NC) impairment is multifactorial, and antiretroviral (ARV) neurotoxicity may contribute. However, interventional pharmacological studies are limited. Methods: Single-blind, randomized (1:1), controlled trial to assess the change of NC performance (Global Deficit Score, GDS, and domain scores) in PLWH with NC impairment randomized to continue their standard of care treatment or to switch to a less neurotoxic ARV regimen: darunavir/cobicistat, maraviroc, emtricitabine (MARAND-X). Participants had plasma and cerebrospinal fluid HIV RNA< 50 copies/mL, R5-tropic HIV, and were on ARV regimens that did not include efavirenz and darunavir. The change of resting-state electroencephalography was also evaluated. The outcomes were assessed at week 24 of the intervention through tests for longitudinal paired data and mixed-effect models. Results: Thirty-eight participants were enrolled and 28 completed the follow-up. Global Deficit Score improved over time but with no difference between arms in longitudinal adjusted models. Perceptual functions improved in the MARAND-X, while long-term memory improved only in participants within the MARAND-X for whom the central nervous system penetration-effectiveness (CNS penetration effectiveness) score increased by ≥3. No significant changes in resting-state electroencephalography were observed. Conclusions: In this small but well-controlled study, the use of less neurotoxic ARV showed no major beneficial effect over an unchanged regimen. The beneficial effects on the memory domain of increasing CNS penetration effectiveness score suggest that ARV neuropenetration may have a role in cognitive function.

High-load strength training compared with standard care treatment in young adults with joint hypermobility and knee pain: study protocol for a randomised controlled trial (the HIPEr-Knee study)

IntroductionPatients with generalised joint hypermobility, including knee hypermobility (GJHk), often experience knee pain and are typically managed with low-intensity strength training and/or proprioceptive training as part of standard care. However,...

Parenteral Buprenorphine for Opioid Withdrawal.

Buprenorphine is the standard of care for treatment of opioid withdrawal. However, when sublingual (SL) administration is not appropriate or practical, parenteral administration by the intravenous (IV) or intramuscular (IM) route may be a reasonable substitute. Although previously used intravenously for the treatment of pain, current practitioners have limited experience with parenteral use of buprenorphine. This is a case series using retrospective chart review of patients at an urban public hospital who received IV or IM buprenorphine for treatment of opioid withdrawal. A query of the electronic health record (EHR) was performed to identify patients who had received IV or IM buprenorphine from January 2020 to December 2021. Charts were reviewed for patient demographics, medical history, substance use history, urine drug screens, clinical scenario, indication for parenteral buprenorphine, dose of buprenorphine, vital sign trends, and any measure of change in withdrawal. Eight patients were identified. The most frequent initial dose of parenteral buprenorphine was 0.3 mg, and if buprenorphine needed to be re-dosed it was most commonly administered every six hours. The most common indications for use were delirium or intractable nausea and vomiting related to opioid withdrawal. Withdrawal improved in 6 of the 8 cases, and often allowed for subsequent use of SL buprenorphine. There were no adverse effects identified. Parenteral buprenorphine was successfully used to treat opioid withdrawal in a select group of patients. Further studies are needed to identify the optimal use parameters of parenteral buprenorphine.

A novel opioid/pramipexole combination treatment for the management of acute pain: a pilot study.

Despite their dangerous side effects, opioid drugs remain a standard of care for moderate to severe pain with few alternatives. Strategies to maintain the analgesic effects of opioids while minimizing the associated risks are needed. Pre-clinical studies have shown using a dopamine 3 receptor (D3R) agonist as an adjuvant to morphine provides superior analgesia against painful stimuli compared to morphine alone. Our objective was to test if adjunct treatment with a D3R agonist can lead to a reduction in opioid use while maintaining effective analgesia. This study was set up as a double-blinded, placebo-controlled randomized trial. Enrollment included acute renal colic patients presenting to the emergency department, from which patients were randomized to either the "control" or "study arm". The control group received standard treatment of care (morphine, 0.1 mg/kg; i.v.) and an oral placebo pill. The experimental group received half-dosed morphine and oral pramipexole pill (0.25 mg). Pain measurements including a numerical pain scale and visual analog scale were collected from enrollees at baseline and every subsequent 15 min. A total of 19 patients completed the study, 10 in the experimental arm and 9 in the control arm. During the study period, effective analgesia (50% decrease from baseline) was achieved in 80% of patients in the experimental arm vs. 33.3% in the control arm. Our pilot clinical trial demonstrated that D3R recruitment can serve as an effective adjuvant to low-dose morphine for control of renal colic pain and potentially other acute pain conditions. ClinicalTrials.gov, identifier, (NCT04160520).

Bone marrow toxicity in patients with locally advanced cervical cancer undergoing multimodal treatment with VMAT/IMRT: are there dosimetric predictors for toxicity?

PurposeFor women with locoregionally advanced cervical cancer, the standard of care treatment is the curatively intended chemoradiation therapy (CRT). A relationship between bone marrow (BM) dose–volume histograms (DVHs) and acute hematological toxicity (HT) has been debated recently. Aim of this study was the evaluation of BM dose constraints and HT in a contemporary patient cohort.MethodsRadiation treatment plans of 31 patients with cervical cancer (FIGO stage IIB–IVB) treated with intensity-modulated radiotherapy and simultaneous chemotherapy were explored retrospective. Pelvic bones (PB) and femoral heads (FH) were contoured and DVHs were correlated with white blood cells (WBC), hemoglobin levels and platelets.ResultsComparing the absolute blood levels with the dose volumes of both FH and PB the data showed a significant correlation between WBC and the median dose of the FH and the median dose, V30Gy, V40Gy and V50Gy of the PB. A correlation between the toxicity grade of anemia and mean dose, maximum dose and V5Gy of the PB was found. Counting the highest grade of HT of all three blood levels of each patient, significant correlations were found for the mean and median dose, V30Gy, V40Gy and V50Gy of the PB.ConclusionThe results show that blood levels may correlate with distinct dosimetric subvolumes of critical bone marrow compartments with a potential impact on therapeutic outcome and treatment-related toxicity. The data presented are in line with the previous findings on the relevance of dosimetric exposure of pelvic bony subvolumes.

Tocilizumab reduces hypercoagulation in COVID-19 – Perspectives from the coagulation and immunomodulation Covid assessment (Coag-ImmCovA) clinical trial

BackgroundDespite medical interventions, COVID-19 continues to persist at pandemic proportions. A hypercoagulation state was rapidly observed in the severely ill, and the incidence of thromboembolic events remains elevated. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality. Nevertheless, the impact of interleukin inhibitors on the coagulation system remains incompletely understood. MethodsIn this clinical trial conducted in Stockholm, Sweden, interleukin inhibitors, namely anakinra (ANA) or tocilizumab (TOCI), were randomly administered in addition to standard care (SC) to hospitalized patients with COVID-19. A control group received only SC. The primary outcome sought to measure effects on global hemostasis, as indicated by changes in functional coagulation tests, specifically Rotational Thromboelastometry (ROTEM) or Overall Hemostatic Potential (OHP), visualized through scanning electron microscopy images. Secondary outcomes included effects on conventional coagulation laboratory tests. ResultsThe study enrolled 74 patients who were randomized to receive either ANA or TOCI in addition to SC, or SC alone. In the TOCI group, ROTEM variables exhibited less hypercoagulation after 29 days compared with ANA or SC treatment groups, characterized by prolonged clot formation time and decreased clot firmness. OHP decreased, but there were no significant differences among the three treatment groups. Plasma fibrinogen levels, initially elevated, decreased significantly in TOCI recipients over time. ConclusionTocilizumab treatment demonstrated a significant reduction of hypercoagulation in hospitalized COVID-19 patients, by improvements in both global coagulation tests and conventional laboratory tests, in comparison with anakinra or SC alone. This finding underscores the significance of tocilizumab as a viable treatment option in severe COVID-19 cases, with the potential to decrease thrombosis incidence.

Randomized Controlled Trial Assessing Vitamin D's Role in Reducing BPPV Recurrence in Older Adults.

To determine if the recurrence rates of BPPV in older adults were lower in the vitamin D-treated group as compared to placebo groups. Double-blinded randomized control placebo trial. A single-centre study. Double-blinded randomized controlled trial design with 12 months follow-up. Vitamin D3 deplete participants were randomized into treatment (Group A) or placebo groups (Group B). Treatment group received 13 weeks of 2000 IU vitamin D3 followed by 1000 IU for the next 13 weeks. Patients who were replete were allocated to a control group (Group C) for observation and follow up. All groups had dietary interventions for vitamin D3 and calcium. Results showed an 87% reduction in recurrence rates of BPPV in the treatment group (Group A), with 0.75 fewer clinical episodes per 1 person-year as compared to placebo (Group B). Time to first recurrence was also significantly longer in Group A. There was no statistically significant difference between Group A and C in both recurrence rates and dizziness handicap scores. This clinical trial has laid the foundation to expand the investigation of vitamin D as standard of care treatment in BPPV patients in future phase IIb and III studies. A reduction in BPPV episodes in older adults has implications on fall risk, as dizziness from BPPV may cause falls. With fewer BPPV episodes and longer time to recurrence, seniors may have better postural stability and hence reduced risk of falls.

Sociodemographic, Health, and Lifestyle-Related Characteristics Associated With the Commencement and Completion of a Web-Based Lifestyle Educational Program for People With Multiple Sclerosis: Randomized Controlled Trial.

Digital health interventions increase access to multiple sclerosis (MS)-related knowledge for people living with MS; however, our understanding of factors associated with engagement in web-based learning is limited. This study aims to examine associations between participant sociodemographic, health, and lifestyle-related characteristics and the commencement and completion of the Multiple Sclerosis Online Course (MSOC) in a randomized controlled trial (RCT). An intervention course was developed based on the Overcoming MS Program-an evidence-based lifestyle modification program for MS, and a standard care course was developed based on international MS website information. An RCT was conducted to compare the effectiveness of the intervention course versus the standard care course in improving health outcomes in people living with MS. Participant data were collected from a baseline survey. Associations between baseline participant characteristics and MSOC commencement and completion, respectively, were assessed using multivariate log-binomial regression. Overall, 1893 participants enrolled in the RCT, and 45.27% (n=857) completed the baseline survey: 23.5% (n=444) in the intervention course and 21.8% (n=413) in the standard care course. Of these 857 participants, 631 (73.6%) commenced the standard care course or intervention course, and 49.1% (218/444) and 54.2% (224/413) completed the intervention course and standard care course, respectively. University education, partnered relationship status, and higher mental and physical quality of life were associated with 19%, 12%, 20%, and 22% higher rates of course commencement, respectively. Clinically significant fatigue was associated with a 10% reduction in the likelihood of commencement. Strongest associations with intervention course completion included middle and older adulthood, male sex, fatigue, and preexisting adherence to a diet program, with 96%, 27%, 24%, and 19% higher rates of completion observed, respectively, whereas higher self-efficacy was associated with up to 35% lower intervention course completion. Associations with standard care course completion included practicing meditation (20% higher completion), whereas employment was associated with 22% lower completion. Sociodemographic and clinical factors, as well as lifestyle-related factors, were important factors in MSOC commencement and completion. These data may help guide the design and enhancement of digital health interventions tailored for people living with MS. Australian New Zealand Clinical Trials Registry ACTRN12621001605886; https://tinyurl.com/2vyve9p9. RR2-10.1186/s12883-023-03298-0.

Efficacy and Safety of Pimodivir Combined with Standard-of-care in Hospitalized and Non-hospitalized High-risk Adolescents and Adults with Influenza A Infection.

An unmet need exists for effective antivirals to treat patients hospitalized with influenza. The results of 2 Phase 3 studies evaluating the efficacy and safety of pimodivir in combination with investigator-chosen standard-of-care (SoC) treatment are presented. Hospitalized patients (hospital study; NCT03376321) and high-risk outpatients (outpatient study; NCT03381196) with laboratory-confirmed influenza A infection were randomized 1:1 to 600 mg pimodivir twice daily (BID) + SoC, or placebo BID + SoC for 5 days. For most patients SoC included oseltamivir. Primary endpoints were Hospital Recovery Scale (HRS) at Day 6 (hospital study) and median time to resolution (TTR) of influenza-related symptoms (outpatient study). Pimodivir + SoC (oseltamivir) treatment showed no clinical benefit over placebo + SoC on HRS at Day 6 (common odds ratio, 0.943 [95% CI, 0.609-1.462], P = .397; hospital study). A shorter median TTR of 7 symptoms was estimated with pimodivir + SoC versus placebo (92.6 hours [95% CI, 77.6-104.2] versus 105.1 hours [95% CI, 92.7-128.6], P = .0216; outpatient study). Pimodivir + SoC showed no additional clinical benefit versus SoC treatment alone in hospitalized patients. Pimodivir + SoC demonstrated shorter TTR of influenza symptoms versus placebo + SoC in high-risk outpatients.

Cost‐Effectiveness of Prehospital Ambulance Helicopter Transportation of Patients With Presumed Stroke in the Era of Mechanical Thrombectomy

Background Mechanical thrombectomy has emerged as standard of care in treatment of patients with acute ischemic stroke attributable to large‐vessel occlusion. Efforts to reduce the time from symptom onset to treatment initiation remain critically important to improve functional outcomes in patients treated with either intravenous thrombolysis, mechanical thrombectomy, or both. The use of ambulance helicopters in prehospital acute stroke care could potentially reduce symptom onset to treatment time to mechanical thrombectomy. This study aims to optimize the use of ambulance helicopters in prehospital transportation of patients with presumed acute stroke attributable to large‐vessel occlusion given economic constraints in health care budget. Methods By means of an economic model within a decision‐analytical framework, this study evaluates the cost‐effectiveness of complementary ambulance helicopters compared with road ambulances only for prehospital acute transportation of patients with presumed stroke and potential eligibility for mechanical thrombectomy, in regard to the number and locations of ambulance helicopters in Sweden. Results A single, optimally located complementary ambulance helicopter was cost‐effective compared with road ambulances only. The most cost‐effective solution in the base‐case scenario with the current 8 thrombectomy centers comprised 13 optimally located helicopters. It reduced mean onset to treatment time with intravenous thrombolysis and onset to treatment time with mechanical thrombectomy by 7.9 and 32.1 minutes, respectively, and produced health gains equal to 91 quality‐adjusted life‐years per year. When the willingness to pay per quality‐adjusted life‐years gained was set at Euro (EUR) 80 000, the incremental net monetary benefit per patient reached EUR 2240. The solution with 13 optimally located helicopters prevailed as the most cost‐effective in the extended scenario analysis with 11 thrombectomy centers, reaching an estimated incremental net monetary benefit per patient at EUR 1754. Furthermore, mean incremental net monetary benefit per patient reached global maximum (EUR 6046) at the geodesic distance of 165.2 km between patient location and the nearest thrombectomy center in the base‐case scenario, and at 238.5 km in the extended scenario with an estimated incremental net monetary benefit per patient at EUR 7994. Conclusion This study demonstrates the cost‐effectiveness of ambulance helicopters as a complementary mode of transportation to road ambulances. The most cost‐effective solution of complementary ambulance helicopters comprises 13 optimally located heliports across Sweden.

Impact of the Immunomodulatory Factor Soluble B7-H4 in the Progress of Preeclampsia by Inhibiting Essential Functions of Extravillous Trophoblast Cells.

A key aspect of preeclampsia pathophysiology is the reduced invasiveness of trophoblasts and the impairment of spiral artery remodelling. Understanding the causes of altered trophoblast function is critical to understand the development of preeclampsia. B7-H4, a checkpoint molecule, controls a wide range of processes, including T-cell activation, cytokine release, and tumour progression. Our previous findings indicated that B7-H4 levels are elevated in both maternal blood and placental villous tissue during the early stages of preeclampsia. Here, we investigated the function of B7-H4 in trophoblast physiology. Recombinant B7-H4 protein was used to treat human SGHPL-5 extravillous trophoblast cells. Biological functions were investigated using MTT, wound healing, and transwell assays. Signalling pathways were analysed by immunoblotting and immunofluorescence. The functionality of B7-H4 was further confirmed by immunoblotting and immunohistochemical analysis in placental tissues from control and preeclamptic patients following therapeutic plasma exchange (TPE) or standard of care treatment. This study showed that B7-H4 inhibited the proliferation, migration, and invasion capacities of SGHPL-5 extravillous cells while promoting apoptosis by downregulating the PI3K/Akt/STAT3 signalling pathway. These results were consistently confirmed in placental tissues from preterm controls compared to early-onset preeclamptic placental tissues from patients treated with standard of care or TPE treatment. B7-H4 may play a role in the development of preeclampsia by inhibiting essential functions of extravillous trophoblast cells during placental development. One possible mechanism by which TPE improves pregnancy outcomes in preeclampsia is through the elimination of B7-H4 amongst other factors.

A pilot pragmatic randomized controlled trial of a nicotine metabolite ratio-guided smoking cessation intervention in a lung health and screening program

IntroductionPatients with pulmonary nodules detected through lung cancer screening or as incidental findings are often followed in lung health and screening programs. The use of personalized pharmacotherapy for smoking cessation informed by the nicotine metabolite ratio (NMR), a measure of nicotine metabolism, has not yet been evaluated in this setting. This pilot randomized controlled trial (RCT) evaluated the feasibility of conducting a larger trial. MethodsThrough a pragmatic RCT design, participants were recruited from a Mid-Atlantic lung health and screening program. Eligible participants smoked >5 cigarettes per day and completed a blood draw to determine NMR before being randomized to standard or NMR-guided care treatment arms. Standard care participants were offered nicotine replacement therapy (NRT) or varenicline and a referral to phone-based smoking cessation counseling. NMR-guided participants received standard care except they were provided a personalized medication recommendation based on their NMR. Study outcomes included measures of feasibility, medication uptake, and treatment matching (i.e., uptake of the optimal medication). ResultsMore than 80 % of 205 screened patients were eligible. However, only 37 (22 %) of these patients enrolled in the study, with a mean age of 65 years, 43 % female, and 25 % Black. Nearly all patients who declined cited a disinterest in smoking cessation. Participants in both treatment arms had high rates of medication uptake (68 %), with NMR-guided participants showing a trend towards greater treatment matching (55 % vs. 29 %). ConclusionsThe results of this pilot study provide support for conducting a larger RCT of an NMR-guided smoking cessation intervention in a lung health and screening setting. Consideration should be given to augmenting the intervention to address barriers to study entry.

Efficacy of vitamin D supplementation in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials

Context: Coronavirus disease 2019 (COVID-19) has substantial effects on respiratory health and overall well-being. Recent studies suggest vitamin D as a potential treatment, but the results are inconclusive. Objective: We conducted a systematic review of randomized controlled trials (RCTs) to examine the link between vitamin D and patients with COVID-19. Data Sources: We searched electronic databases PubMed, Cochrane, CINAHL, EMBASE and Google Scholar from their inception till August 2023. Study Selection: Inclusion criteria used in our systematic review include: 1) patients who tested positive for COVID-19 2) intervention was vitamin D supplementation 3) the comparator was either a placebo, standard care of treatment, or, no treatment, 4) at least one of the clinical outcomes of interest were investigated 5) study design being RCTs. Data Extraction: Two independent reviewers manually extracted information from selected articles, including study characteristics, patient characteristics, and the primary outcomes: all-cause mortality, ICU and hospital stay length and secondary outcomes: mechanical ventilation, supplemental oxygen, ICU admission, and adverse events. Risk Ratios or Mean Differences and 95% confidence intervals were calculated using a random-effects model. Data Synthesis: Our analysis included 14 RCTs with 2165 patients. Vitamin D significantly reduced ICU admissions and lowered the need for mechanical ventilation compared to placebo. However, it did not significantly affect hospital stay length, ICU stay length, mechanical ventilation duration, mortality, or the need for supplemental oxygen. Conclusion: Vitamin D does not significantly improve certain clinical outcomes, such as hospital and ICU stay length, for patients with COVID-19. However, it still may be significantly beneficial in decreasing the burden on intensive care services.

SUNRAY-01, a pivotal, global study of olomorasib (LY3537982) in combination with pembrolizumab with or without chemotherapy for 1L treatment in KRAS G12C-mutant advanced NSCLC.

TPS218 Background: Mutations in KRAS are among the most frequent oncogenic drivers with the G12C variant found in ~13% of NSCLC. Outcomes for KRAS G12C-mutant NSCLC may be improved by combining KRAS G12C inhibitors with current 1L standard of care (SOC). Olomorasib is a potent and highly selective second-generation inhibitor of KRAS G12C, which delivers >90% sustained target occupancy in preclinical models. In the LOXO-RAS-20001 phase 1/2 study, olomorasib in combination with pembrolizumab demonstrated preliminary efficacy and a favorable safety profile.1 Methods: SUNRAY-01 (NCT06119581) is a pivotal, global, phase 3 study in 1L advanced KRAS G12C-mutated NSCLC designed to seamlessly 1) optimize the dosing of olomorasib in combination with 1L SOC, and then 2) compare efficacy and safety of olomorasib plus SOC with placebo plus SOC. In the open-label randomized dose optimization (pembrolizumab plus olomorasib 50 mg vs 100 mg BID) and single arm safety lead-in (olomorasib plus pembrolizumab, pemetrexed, platinum), the optimal dose of olomorasib for combination therapy will be determined before the phase 3 study (parts A and B) is opened for enrollment. In part A, 384 participants with PD-L1 expression ≥50% are randomized (1:1) to pembrolizumab plus olomorasib or placebo. In part B, 552 participants are randomized (1:1) to pembrolizumab, pemetrexed, platinum plus olomorasib or placebo regardless of PD-L1 expression. Allocation of participants with PD-L1 expression ≥50% to either part A or part B will be at the discretion of the investigator. The primary objective is to compare efficacy based on PFS per RECIST v1.1 by blinded independent central review. Secondary endpoints include OS, ORR, DOR, DCR, TTR, PFS2, safety and tolerability, and patient-reported outcomes. Eligible participants (≥18 years) must have a KRAS G12C mutation in tumor or blood and known PD-L1 expression (0-100%), stage IIIB, IIIC, or IV NSCLC not suitable for curative intent radical surgery or radiation therapy, measurable disease per RECIST v1.1, and an ECOG PS 0-1. Participants can be enrolled based on local KRAS and PD-L1 testing results. Participants should not have received prior systemic therapy for advanced or metastatic NSCLC, however 1 cycle of SOC treatment prior to enrollment is allowed if immediate treatment is clinically indicated. Participants with asymptomatic (lesions ≤1.5 cm) or previously treated radiographically stable brain metastases are eligible. Key exclusion criteria include history of pneumonitis/interstitial lung disease and clinically significant active cardiovascular disease or malabsorption syndrome. The study opened for enrollment in December 2023. Reference: 1. Murciano-Goroff et al. 2023 Cancer Res 83 (8 Suppl): CT028. Clinical trial information: NCT06119581 .

Stereotactic Ablative Radiation for Oligoprogressive Cancers: Results of the Randomized Phase 2 STOP Trial

This trial examined if patients with ≤5 sites of oligoprogression benefit from the addition of stereotactic ablative radiotherapy (SABR) to standard of care (SOC) systemic therapy. We enrolled patients with 1-5 metastases progressing on systemic therapy, and after stratifying by type of systemic therapy (cytotoxic vs. non-cytotoxic), randomized 1:2 between continued SOC treatment vs. SABR to all progressing lesions plus SOC. The trial was initially limited to non-small cell lung cancer but was expanded to include all non-hematologic malignancies to meet accrual goals. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), lesional control, quality of life, adverse events (AEs), and duration of systemic therapy post-randomization. Ninety patients with 127 oligoprogressive metastases were enrolled across 8 Canadian institutions, with 59 randomized to SABR and 31 to SOC. Median age was 67 years and 39 (43%) were female. The most common primary sites were lung (44%), genitourinary (23%) and breast (13%). Protocol adherence in the SOC arm was suboptimal, with 11 patients (35%) either receiving high-dose/ablative therapies (conflicting with trial protocol) or withdrawing from the study. Median follow-up was 31 months. There was no difference in PFS between arms (median PFS 8.4 months in the SABR arm vs. 4.3 months in the SOC arm but curves cross and 2-year PFS was 9% vs. 24% respectively, p=0.91). Median OS was 31.2 months vs. 27.4 months, respectively (p=0.22). Lesional control was superior with SABR (70% vs. 38% respectively, p=0.0015). There were 2 (3.4%) grade 3 and no grade 4/5 AEs attributable to SABR. SABR was well-tolerated with superior lesional control but did not improve PFS or OS. Accrual to this study was difficult, and the results may have been impacted by an unwillingness to forgo ablative treatments on the SOC arm. (NCT02756793).

Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer.

Ovarian cancer is the most fatal of all the reproductive cancers within the female population, mainly due to its late diagnosis that limits surgery and medical treatment. Classically, ovarian cancer therapy has included conventional chemotherapy, and other therapeutic approaches are now being used to treat these patients, but the outcomes of the disease are still poor. Therefore, new strategies are needed to improve life expectancy and life quality of ovarian cancer patients. Considering that, we investigated the effect of the nutritional supplement Ocoxin Oral Solution (OOS) in ovarian cancer models. OOS contains several nutritional supplements, some of them with demonstrated antitumoral action. In vitro studies showed that OOS inhibited the proliferation of several ovarian cancer cell lines, especially of those representative of the endometrioid subtype, in a time- and dose-dependent manner. A fast cell death induction after OOS treatment was observed, and when the molecular mechanisms leading to this effect were investigated, an activation of the DNA damage checkpoint was detected, as shown by activation (phosphorylation) of CHK1 and CHK2 kinases that was followed by the phosphorylation of the target protein histone H2AX. When tested in animal models of ovarian cancer, OOS reduced tumor growth without any observed secondary effects. Moreover, such reduction in tumor proliferation was caused by the induction of DNA damage as corroborated by the in vivo phosphorylation of CHK2 and Histone H2AX. Finally, OOS potentiated the action of carboplatin or olaparib, the standard of care treatments used in ovarian clinics, opening the possibility of including OOS in combination with those standard of care agents in patients with ovarian cancer.

Trial Protocol of a Phase II Study of mFOLFOXIRI after Metastasectomy in Patients with Oligometastatic Colorectal Cancer (FANTASTIC Study).

The survival benefit of adjuvant chemotherapy after surgical resection of oligometastases from colorectal cancer (CRC) remains unclear. The prognostic role of circulating-tumor DNA (ctDNA) was reported recently and a risk stratification strategy based on monitoring minimal/molecular residual disease (MRD) has been proposed, however, which drug regimen is most effective for ctDNA-positive patients is unknown. Oligometastatic CRC patients planning to undergo surgery were registered in this study. After metastasectomy, the registered patients were enrolled in the treatment arm, in which 8 courses of modified-FOLFOXIRI (mFOLFOXIRI; irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, l-leucovorin (l-LV) 200 mg/m2, and 46-h continuous infusion of 5-fluorouracil (5-FU) 2400 mg/m2 every 2 weeks) followed by 4 courses of 5-FU/l-LV are administered. The patients who did not meet the eligibility criteria for the treatment arm or did not consent to mFOLFOXIRI enrolled in the observation arm in which standard of care treatment is provided. Prospective blood collections for retrospective ctDNA analysis are scheduled pre-surgery, and at 28 days, 4 and 7 months after surgery. The primary endpoint is treatment compliance at 8 courses of mFOLFOXIRI and the key secondary endpoints are the ctDNA-positivity rate and survival outcomes in ctDNA-positive and -negative groups. A total of 85 patients will be enrolled from 11 institutions. First patient-in was on July 2020. Accrual completed in February 2024. This study will potentially identify a better treatment strategy for patients with resectable oligometastatic CRC having postsurgical ctDNA positivity, compared to the current standard of care approaches.

MINT Registry: Rationale and Study Design

Background Mechanical thrombectomy has become the standard of care for treatment of acute ischemic stroke secondary to large‐vessel occlusion up to 24 hours from last known normal time. Multiple different techniques for mechanical thrombectomy have been described, including a direct aspiration first‐pass technique and stent retriever thrombectomy. With a direct aspiration first‐pass technique, classically, a large‐bore aspiration catheter is delivered over a microcatheter and microwire to the clot. Recently, a novel macrowire has been introduced as a potential alternative to the use of microwire–microcatheter to allow the delivery of the aspiration catheter. The aim of this study is to develop a multicenter registry comparing delivery of an aspiration catheter for intracranial thrombectomy for acute ischemic stroke secondary to emergent large‐vessel occlusion over a macrowire in comparison with traditional use of microcatheter and microwire. Methods MINT (Macrowire for Intracranial Thrombectomy) is a multicenter, observational study currently enrolling patients with large‐vessel occlusion who underwent mechanical thrombectomy using a macrowire to deliver the aspiration catheter to the intracranial occlusion. All the participating sites will screen and report cases on a monthly basis. The decision to use the macrowire and various aspiration catheters is at the discretion of the interventionalist. Results We will collect patient's clinical, demographic, and radiographic data. In addition, we plan to collect procedure variables and postprocedure clinical and imaging data. Outcomes include successful delivery of the reperfusion catheter to the clot interface, time taken from groin access to first pass, and a bailout strategy for thrombectomy in cases where this is not feasible. Conclusion The MINT registry will add to our understanding of safety and efficacy of this novel macrowire in intracranial thrombectomy. This registry will also highlight and allow for understanding in workflow improvements from simplifying setup and possibly cost effectiveness of this technique.

Effect of High Dose Atorvastatin and Allopurinol Preloading on No-Reflow in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction

Abstract Background No reflow is linked to worse prognosis post revascularization, so preventing no reflow is better than treating it. Objective this study aims to evaluate the effect of adding high-dose allopurinol and atorvastatin in preventing NRP when given before undergoing primary PCI in patients presenting with STEMI. Patients and Methods This study recruited 300 patients who were classified into 3 groups (100 each), Group A: patients were preloaded with high dose Allopurinol and Atorvastatin on top of the standard of care treatment according to the European society of cardiology guidelines. Group B: patients were preloaded with high dose Atorvastatin only on top of the standard of care treatment, Group C: were only preloaded with the standard care treatment according to the European society of cardiology guidelines, each group was subjected to the same pre procedural laboratory tests, primary percutaneous coronary intervention was done by the most experienced operator available according to the European society of cardiology guidelines. Results Percentage of post procedural no reflow was significantly lower in patients who were preloaded with high dose Allopurinol and Atorvastatin compared to the other 2 groups (highest with group C) (Group A: 11%, Group B: 23%, Group C: 39%). Conclusion preloading patients before primary percutaneous coronary intervention in patients presenting with ST elevation myocardial infarction with high dose Allopurinol and Atorvastatin significantly decreases incidence of post procedural no reflow.