Enhanced tumor control and survival in preclinical models with adoptive cell therapy preceded by low-dose radiotherapy.

Introduction: Effective infiltration of chimeric antigen receptor T (CAR-T) cells into solid tumors is critical for achieving a robust antitumor response and improving therapeutic outcomes. While CAR-T cell therapies have succeeded in hematologic malignancies, their efficacy in solid tumors remains limited due to poor tumor penetration and an immunosuppressive tumor microenvironment. This study aimed to evaluate the potential of low-dose radiotherapy (LDRT) administered before T-cell therapy to enhance the antitumor effect by promoting CAR-T cell infiltration.

Multidevice spinal cord stimulation trials: shared decision making in the era of multiple neuromodulation paradigms.

There is a lack of evidence-based standards for matching spinal cord stimulation (SCS) paradigm to individual patients. We aim to determine the feasibility and safety of a new alternative trial strategy, a sequential multidevice trial. A retrospective analysis was performed on 116 patients who underwent SCS trials, single device or sequential multidevice (tonic and high-frequency), for chronic low back pain to assess feasibility and compare trial-to-implantation rate and explantation rate.

Newer Treatments for Mood and Anxiety Disorders.

For more than 20 years, the mainstay of pharmacologic treatment for depression and anxiety disorders has been serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors. There are newer medications, many with novel mechanisms of action, that have come to market; however, first-line treatments remain the same. There are now more robust data on the use of various augmentation agents in the treatment of major depressive disorder providing better recommendations for use by the primary care provider.

Experience and impact of inappropriate patient sexual behaviors within a large VA healthcare system.

Inappropriate patient sexual behaviors (IPSBs) can negatively impact work performance, job satisfaction, and the psychological well-being of clinicians and staff. Although the Veterans Health Administration (VHA) is the largest integrated healthcare system in the United States, the rate of IPSBs in VHA hospitals is unknown. The unique demographic and cultural characteristics of military populations may be associated with IPSBs.

Lymphodepletion - an essential but undervalued part of the chimeric antigen receptor T-cell therapy cycle.

Lymphodepletion (LD) or conditioning is an essential step in the application of currently used autologous and allogeneic chimeric antigen receptor T-cell (CAR-T) therapies as it maximizes engraftment, efficacy and long-term survival of CAR-T. Its main modes of action are the depletion and modulation of endogenous lymphocytes, conditioning of the microenvironment for improved CAR-T expansion and persistence, and reduction of tumor load. However, most LD regimens provide a broad and fairly unspecific suppression of T-cells as well as other hematopoietic cells, which can also lead to severe side effects, particularly infections.

Evaluating the balance of benefits and harms in chronic pain clinical trials: prioritizing individual participants over individual outcomes.

Background: Randomized clinical trials (RCTs) generally assess efficacy and safety separately, with the conclusion of whether a treatment is beneficial based solely on the efficacy endpoint. However, assessing and combining efficacy and safety domains, using a single composite outcome measure, can provide a more comprehensive assessment of the overall effect of a treatment. Furthermore, composite outcomes can incorporate information regarding the relationship between the individual outcomes.

Recommendations for terminology and the identification of neuropathic pain in people with spine-related leg pain. Outcomes from the NeuPSIG working group.

Pain radiating from the spine into the leg is commonly referred to as "sciatica," "Sciatica" may include various conditions such as radicular pain or painful radiculopathy. It may be associated with significant consequences for the person living with the condition, imposing a reduced quality of life and substantial direct and indirect costs. The main challenges associated with a diagnosis of "sciatica" include those related to the inconsistent use of terminology for the diagnostic labels and the identification of neuropathic pain.

Research objectives and general considerations for pragmatic clinical trials of pain treatments: IMMPACT statement.

Many questions regarding the clinical management of people experiencing pain and related health policy decision-making may best be answered by pragmatic controlled trials. To generate clinically relevant and widely applicable findings, such trials aim to reproduce elements of routine clinical care or are embedded within clinical workflows. In contrast with traditional efficacy trials, pragmatic trials are intended to address a broader set of external validity questions critical for stakeholders (clinicians, healthcare leaders, policymakers, insurers, and patients) in considering the adoption and use of evidence-based treatments in daily clinical care.

Examining the Relationships Among Treatment, Pain, and Physical Function in Patients With Osteoarthritis: A Mediation-Modeling Approach.

Objectives: To better understand the relationships among treatment, pain, and physical function (PF).

Methods: Data were collected from 2 published randomized clinical trials of osteoarthritis patients who received tanezumab or a placebo. PF was measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) PF domain.

Resection of NAFLD/NASH-related Hepatocellular Carcinoma (HCC): Clinical Features and Outcomes Compared with HCC Due to Other Etiologies.

Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the leading causes of hepatocellular carcinoma (HCC) worldwide. Limited data exist on surgical outcomes for NAFLD/NASH-related HCC compared with other HCC etiologies. We evaluated differences in clinicopathological characteristics and outcomes of patients undergoing surgical resection for NAFLD/NASH-associated HCC compared with other HCC etiologies.

Optimizing and Accelerating the Development of Precision Pain Treatments for Chronic Pain: IMMPACT Review and Recommendations.

Large variability in the individual response to even the most-efficacious pain treatments is observed clinically, which has led to calls for a more personalized, tailored approach to treating patients with pain (ie, "precision pain medicine"). Precision pain medicine, currently an aspirational goal, would consist of empirically based algorithms that determine the optimal treatments, or treatment combinations, for specific patients (ie, targeting the right treatment, in the right dose, to the right patient, at the right time). Answering this question of "what works for whom" will certainly improve the clinical care of patients with pain.

Predicting Treatment Response with Sensory Phenotyping in Post-Traumatic Neuropathic Pain.

Objective: Currently available treatments for neuropathic pain are only modestly efficacious when assessed in randomized clinical trials and work for only some patients in the clinic. Induced-pain or gain-of-function phenotypes have been shown to predict response to analgesics (vs placebos) in patients with neuropathic pain. However, the predictive value of these phenotypes has never been studied in post-traumatic neuropathic pain.

Multimethod quantitative benefit-risk assessment of treatments for moderate-to-severe osteoarthritis.

Objective: Demonstrate how benefit-risk profiles of systemic treatments for moderate-to-severe osteoarthritis (OA) can be compared using a quantitative approach accounting for patient preference.

Study Design And Setting: This study used a multimethod benefit-risk modelling approach to quantifiably compare treatments of moderate-to-severe OA. In total four treatments and placebo were compared.

Prospective, randomized, multicenter study of intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: 24-Month treatment arm results.

Background: Vertebral endplates, innervated by the basivertebral nerve, can be a source of vertebrogenic low back pain when damaged with inflammation, visible as types 1 or 2 Modic changes. A randomized controlled trial (RCT) compared basivertebral nerve ablation (BVNA) to standard care (SC) showed significant differences between arms at 3 and 6-months. At 12-months, significant improvements were sustained for BVNA.

Evaluation of Basic Life Support First Responder Naloxone Administration Protocol Adherence.

Objectives: Opioid overdoses have become a significant problem across the United States resulting in respiratory depression and risk of death. Basic Life Support (BLS) first responders have had the option to treat respiratory depression using a bag-valve-mask device, however naloxone, an opioid antagonist, has been shown to quickly restore normal respiration. Since the introduction of naloxone and recent mandates across many states for BLS personnel to carry and administer naloxone, investigation into the adherence of naloxone use standing protocols is warranted.

Tanezumab for chronic low back pain: a long-term, randomized, celecoxib-controlled Japanese Phase III safety study.

This trial investigated long-term (56-week treatment/24-week follow-up) use of subcutaneous tanezumab (5 or 10 mg every 8 weeks) or oral celecoxib (200 mg/day) in Japanese patients with chronic low back pain. Tanezumab safety was consistent with previous studies, except overall adverse events (tanezumab 5 mg = 63.0%, tanezumab 10 mg = 54.

Benefit-risk assessment and reporting in clinical trials of chronic pain treatments: IMMPACT recommendations.

Chronic pain clinical trials have historically assessed benefit and risk outcomes separately. However, a growing body of research suggests that a composite metric that accounts for benefit and risk in relation to each other can provide valuable insights into the effects of different treatments. Researchers and regulators have developed a variety of benefit-risk composite metrics, although the extent to which these methods apply to randomized clinical trials (RCTs) of chronic pain has not been evaluated in the published literature.

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain.