Adjuvant Medications Research Articles

Quality of pain management in patients with cancer in the outpatient setting.

12106 Background: Pain represents a common health issue among patients with cancer. Uncontrolled pain significantly impairs the quality of life, resulting in increased healthcare utilization and costs. We examined the patterns of pain medication prescriptions among patients with cancer pain in the outpatient setting. Methods: We used the National Ambulatory Medical Care Survey (NAMCS), an annually administered survey designed to collect data regarding the use of ambulatory medical services from office-based physicians in the United States. We analyzed NAMCS data from 2005 to 2019 for all types of cancers visits. The primary outcome was prescription of pain medications among patients with cancer pain. We performed multivariate logistic regression to identify factors associated with opioid and non-opioid prescription among patients with cancer pain. Results: We captured a total of 520.8 million outpatient visits from 2005-2019. Breast cancer (18.7%) followed by cancer of the male genital tract (11.0%) represented the highest proportion of patient visits. 4.8% of cancer patients reported pain. Majority (60%) complaining of pain did not receive any pain medications. 14.9% received opioids and 25.1% received nonsteroidal anti-inflammatory drugs, acetaminophen, or adjuvant pain medications. The odds of receiving opioids were 3.4 times higher among 45-65 years vs patients over 75 years. African-Americans had 84% higher odds of receiving opioid prescription compared to white patients. The odds of receiving opioids were 61% lower for privately insured vs patients on Medicare. Patients visiting oncologic care had 2.1 times higher odds of receiving opioids compared to primary care (Table). Conclusions: This is one of the largest drug utilization studies among patients with cancer in outpatient setting, covering half a billion patient visits. A significant proportion of outpatients with cancer who reported pain did not receive a prescription for analgesics suggesting a possibility of undertreatment of pain. Within the limitation of this dataset, undertreatment of pain in outpatients with cancer remains a major unmet patient need. [Table: see text]

A158 Efficacy of Adjuvant Weight Loss Medications in Post-Bariatric Surgery Patients Regarding Weight, Insulin Resistance, & Hyperlipidemia

A158 Efficacy of Adjuvant Weight Loss Medications in Post-Bariatric Surgery Patients Regarding Weight, Insulin Resistance, & Hyperlipidemia

To assess the efficacy of injection nalbuphine as an adjuvant to intrathecal bupivacaine in endoscopic urological surgeries for prolongation of postoperative analgesia

Spinal anesthesia has a quicker onset of action and completely blocks all motor functions. It requires less local anesthetic and has a reduced rate of failed blocks hence the preferred anesthetic method for lower abdomen procedures is spinal anesthesia. Intrathecal local anesthetics benefit from adjuvant medications by extending postoperative analgesia and thus improving the sensory blockade's duration and quality. Intrathecal opioids and local anesthetics work together synergistically to increase the sensory block while decreasing the sympathetic block. Adjuvants to local anesthetics for intrathecal administration have certain benefits, including lowered local anesthetic medication dose, improved hemodynamic stability, and fewer adverse effects. The opioid medication nalbuphine has a kappa agonist and mu antagonist action that reduces pain without having many negative side effects. It acts on opoid receptor as both an agonist and an antagonist to offer visceral nociception with a moderately powerful analgesic. Almost all general anesthesia and regional anesthesia treatments employ it. To cause analgesia, nalbuphine adheres to k receptors. Perioperative analgesia is also improved when administered as an adjuvant to bupivacaine. It is a hybrid which has both agonist and antagonist actions that increases and attenuates the effects of -opioids. Numerous researchers have investigated the properties of intrathecal nalbuphine. This study's objective to determine the efficacy of injectable nalbuphine as an augmentation to intrathecal bupivacaine in endoscopic urological surgeries to extend post operative analgesia.

Evaluation of Gabapentin and Baclofen Combination for Inpatient Management of Alcohol Withdrawal Syndrome.

Benzodiazepines are considered the gold standard for treatment of alcohol withdrawal syndrome (AWS), a group of symptoms that occur after abrupt cessation of alcohol use, but may be associated with serious adverse effects. Given the safety concerns, alternative treatment options for AWS management have been investigated, including gabapentin and baclofen. Because no available studies have investigated the inpatient use of the gabapentin and baclofen combination for alcohol detoxification, this study aims to evaluate their efficacy and safety in the inpatient hospital setting. This retrospective cohort study at the Captain James A. Lovell Federal Health Care Center in North Chicago, Illinois, included patients who were aged ≥ 18 years and who were admitted to the general acute medicine floor for the primary indication of AWS from January 1, 2014, to July 31, 2021. The primary outcome was the length of stay, defined as hours from admission to either discharge or 36 hours with a Clinical Institute Withdrawal Assessment of Alcohol (CIWA) score ≤ 8. Electronic health records were reviewed to collect CIWA scores, alcohol withdrawal seizure and delirium tremens incidence, rates of conversions from gabapentin/baclofen to lorazepam, rates of transitions to a higher level of care, and readmission for AWS within 30 days. Mean length of stay in the gabapentin/baclofen group was statistically significantly shorter compared with the benzodiazepine group (42.6 vs 82.5 hours, P < .001). The study found no significant difference between the gabapentin/baclofen and benzodiazepine groups in AWS readmission, adjuvant medications for AWS management, and number of patients who transitioned to a higher level of care. Overall, the safety of gabapentin/baclofen vs benzodiazepine were comparable; however, 1 patient experienced a seizure, and 1 patient experienced delirium tremens during admission in the benzodiazepine group. Gabapentin/baclofen combination seems to be an effective and safe alternative to benzodiazepines and may be considered for managing mild AWS in hospitalized patients, but additional research is needed to examine this regimen.

Impact of in utero drug exposure on neonates requiring ECMO: A retrospective cohort study

The incidence of in utero drug exposure (IUDE) and neonatal extracorporeal membrane oxygenation (ECMO) utilization have both increased over the past decade. However, there are no studies to date that examine the impact that IUDE has on neonates requiring ECMO. In this retrospective cohort study, we compared the clinic course and outcomes of neonates who were placed on ECMO with IUDE vs. neonates without IUDE. Analysis included data extracted from medical records from all neonatal ECMO runs between January 2014 and January 2021 at the University of Kentucky Children's Hospital. A total of 56 neonatal patients were placed on ECMO during this time period and there were a total of 57 ECMO runs. Nearly one-third of neonates (16) had documented IUDE. There were no differences in gestational age, length of ECMO run, survival to discharge, or number of major complications while on ECMO in the neonates with IUDE compared to those without. In contrast, greater use of sedative and analgesic adjuvant medications during ECMO was required for IUDE-ECMO cases (p < 0.01). Trending results indicated that post-ECMO feeding complications and total hospitalization length were also greater in the IUDE-ECMO group. These findings illustrate the complex influence of prenatal drug exposures on neonatal patient care and warrant the development of clinical care strategies optimized for this unique patient group.

Therapeutic effects of herbal medicines in different types of retinopathies: A systematic review.

Retinopathy is an ocular manifestation of systemic diseases such as diabetes and vascular diseases. Herbal drugs have been considered as an effective therapeutic option with minimal side effects for the treatment of retinopathy by reducing the symptoms and improving visual acuity. The purpose of this systematic review was to collect studies on the effectiveness of medicinal plants in the treatment or prevention of retinopathy. A systematic literature search was performed in PubMed, Scopus, Google Scholar, and other databases in April 2021 using "herbal products" and "Retinopathy" with all their equivalent and similar terms. For this purpose, human clinical trials with the English language were included and articles with subject irrelevancy were excluded from further evaluation. Overall, 30 articles with 2324 patients were studied for possible effects of herbal therapy on retinopathy. From 30 included articles, different herbal products had been evaluated. Out of 30 selected articles, 11 articles were for the treatment of age-related macular degeneration (AMD), 14 articles covered patients with diabetic retinopathy, and the other five studies were for other retinal disorders. The outcomes in majority of the studies include changes in visual acuity (VA), fundus performance, best-corrected visual acuity (BCVA), central macular thickness (CMT), focal electroretinogram (fERG), supplements and adjuvant medications appeared to be more beneficial in patients with AMD and diabetic maculopathy. Herbal therapy can be considered as a potential candidate in the adjuvant and complementary therapies of retinopathy. However, further studies are required to verify such efficiency.

Possible immuno-modulatory effects of tocilizumab in patients with refractory status epilepticus.

Refractory Status Epilepticus (RSE) is a neurologic emergency that carries a high risk of mortality and morbidity. Every year, there are about 200,000 cases in the United States, affecting people of all ages. This study aimed to investigate the possible immuno-modulatory effect of tocilizumab in RSE patients receiving conventional anti-epileptic drugs. 50 outpatients who fulfilled the inclusion requirements for RSE were recruited in this randomized, controlled, and prospective study. The patients were divided into two groups randomly (n=25); the control group received standard RSE treatment, consisting of propofol, pentobarbital, and midazolam, and the tocilizumab group received standard RSE treatment plus tocilizumab. A neurologist evaluated each patient at the beginning of the therapy and after 3 months. Before and after treatment, serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and serum electrolytes were assessed. The tocilizumab group showed a statistically significant reduction in the level of assessed parameters in comparison with the control group. Tocilizumab might be a novel adjuvant anti-inflammatory medication in managing RSE.

Abstract TMP6: Association Of Tirofiban With Outcomes After Thrombectomy In Stroke Due To Atherosclerosis: An Exploratory Analysis Of The RESCUE BT Placebo-controlled Randomized Trial

Background: The efficacy and safety of tirofiban, as an adjuvant medication of endovascular therapy (EVT), in patients with large vessel occlusion due to atherosclerotic thrombosis was still unclear. Methods: The Endovascular Treatment With versus Without Tirofiban in Stroke (RESCUE BT) trial was a randomized, double-blinded, placebo-controlled trial that was performed at 55 centers in China from October 10, 2018 to October 31, 2021. This was a post hoc exploratory analysis of the RESCUE BT trial and 435 patients were included in the intention-to-treat analysis. The primary outcome was the proportion of functional independence (defined as modified Rankin Scale 0-2) at 90 days. We estimated the efficacy and safety of EVT plus placebo versus EVT plus tirofiban using binary logistic regression analysis. A causal mediation analysis was also performed to assess the potential mediators of tirofiban on functional outcome. Results: This study included 435 patients, including 197 patients assigned to the tirofiban group and 238 patients assigned to the placebo group. The median age was 65 [IQR, 56-72] years, and 311 (71.5%) patients were men. Tirofiban was associated with higher rates of functional independence at 90 days compared with the placebo (adjusted odds ratio with 95% CI, 1.68 [1.11–2.56], P = 0.014). There was no significant difference in mortality and symptomatic intracranial hemorrhage between the two groups, thought the rate of intracranial hemorrhage was numerically higher in the tirofiban group (29.1% versus 23.2%, P = 0.165). Tirofiban was also associated with fewer number of thrombectomy passes (beta, -0.48; 95% CI, -0.62 to -0.34; P &lt; 0.001). Treatment-reduced passes explains 20.0% (95% CI, 4-76) of the beneficial effect of tirofiban on functional independence. Conclusion: Tirofiban plus EVT might be an effective and well-tolerated option for patients with anterior large vessel occlusion due to atherosclerosis. These findings are needed to be confirmed in future trials.

Neuropathic pain: Mechanisms and therapeutic strategies.

The physiopathology and neurotransmission of pain are of an owe inspiring complexity. Our ability to satisfactorily suppress neuropathic or other forms of chronic pain is limited. The number of pharmacodynamically distinct and clinically available medications is low and the successes achieved modest. Pain Medicine practitioners are confronted with the ethical dichotomy imposed by Hippocrates: On one hand the mandate of primum non nocere, on the other hand, the promise of heavenly joys if successful divinum est opus sedare dolorem. We briefly summarize the concepts associated with nociceptive pain from nociceptive input (afferents from periphery), modulatory output [descending noradrenergic (NE) and serotoninergic (5-HT) fibers] to local control. The local control is comprised of the "inflammatory soup" at the site of pain origin and synaptic relay stations, with an ATP-rich environment promoting inflammation and nociception while an adenosine-rich environment having the opposite effect. Subsequently, we address the transition from nociceptor pain to neuropathic pain (independent of nociceptor activation) and the process of sensitization and pain chronification (transient pain progressing into persistent pain). Having sketched a model of pain perception and processing we attempt to identify the sites and modes of action of clinically available drugs used in chronic pain treatment, focusing on adjuvant (co-analgesic) medication.

Liujunzi decoction exerts potent antitumor activity in oesophageal squamous cell carcinoma by inhibiting miR-34a/STAT3/IL-6R feedback loop, and modifies antitumor immunity

BackgroundLiujunzi decoction (LJZD), a traditional herbal formula and one of the most commonly used adjuvant medications for the treatment of oesophageal squamous cell carcinoma (ESCC), exerts good antitumor and immunomodulatory activity. However, its specific mechanism of action remains largely unclear. PurposeIn order to examine the potential primary and adjuvant antitumor mechanisms of LJZD, both in vitro and in vivo. MethodsIL-6 and miR-34a inhibitors were used to activate the miR-34a/STAT3/IL-6R feedback loop to observe the effects of LJZD. A humanised mouse model with a functional human immune system was constructed to evaluate the antitumor efficacy of LJZD in vivo on xenograft tumours, which was compared to that of the positive control drug anti-PD-1 monoclonal antibodies (mAb). Finally, a co-culture system of peripheral blood mononuclear and tumour cells in vitro was used to analyse the cytotoxic activity of LJZD on T cells. ResultsLJZD significantly interfered with IL-6-induced activation of the miR-34a/STAT3/IL-6R feedback loop in ESCC by restoring the expression of the tumour suppressor miR-34a, and inhibited the proliferation of EC109 oesophageal cancer cells in a dose-dependant manner. Furthermore, LJZD effectively suppressed oesophageal tumour growth in vivo and alleviated organ injury and visceral index. Furthermore, LJZD boosted antitumor immunity by increasing IFN-γ expression and CD8+tumour-infiltrating lymphocytes (TILs) infiltration in the peripheral blood and tumour tissues, respectively, which may be related to a decrease in PD-1, but not PD-L1 expression. Finally, we confirmed that LJZD strengthens the killing ability of T cells by suppressing PD-1 expression in a co-culture system in vitro. ConclusionLJZD exerts excellent antitumor effect by interfering with the miR-34a/STAT3/IL-6R feedback loop and augmenting antitumor immune responses. Which provides new insights into mechanisms for LJZD and sheds light on the multifaceted role of phytomedicine in cancer.

Efficacy and Safety of Dual Anti-HER2 Blockade and Docetaxel With or Without Carboplatin as Neoadjuvant Regimen for Treatment of HER2-Positive Breast Cancer.

Introduction: This study aimed to compare the efficacy and safety of docetaxel + trastuzumab + pertuzumab and docetaxel + carboplatin + trastuzumab + pertuzumab for treating HER2-positive breast cancer. Method: HER2-positive breast cancer from patients diagnosed between January 2020 and September 2022 were included in this retrospective study. Docetaxel + trastuzumab + pertuzumab or docetaxel + carboplatin + trastuzumab + pertuzumab was selected as the neoadjuvant regimen. The primary endpoint was a complete pathological remission rate. Secondary endpoints were toxicity during neoadjuvant treatment, adjustment of the neoadjuvant therapy scheme, and adjuvant medication. Result: A total of 81 patients were included in this study (38 in the docetaxel + carboplatin + trastuzumab + pertuzumab treatment group and 43 in the docetaxel + trastuzumab + pertuzumab group). The complete pathological remission rates in the docetaxel + carboplatin + trastuzumab + pertuzumab and docetaxel + trastuzumab + pertuzumab groups were 44.7% (95% confidence interval: 30.2%-60.3%) and 51.2% (95% confidence interval: 36.8%-65.4%), respectively. The incidence of grade 3 or higher toxicity in the docetaxel + carboplatin + trastuzumab + pertuzumab group was significantly higher than that in the docetaxel + trastuzumab + pertuzumab group (68.4% vs 39.5%, P = .009). Neutropenia and asthenia were the most common grade 3 or higher toxicities. The incidence of neoadjuvant scheme adjustment was significantly higher in the docetaxel + carboplatin + trastuzumab + pertuzumab group than in the docetaxel + trastuzumab + pertuzumab group (26.3% vs 7.0%, P = .039). The proportion of patients who received <6 cycles of neoadjuvant therapy was significantly higher in the docetaxel + carboplatin + trastuzumab + pertuzumab group than in the docetaxel + trastuzumab + pertuzumab group (31.6% vs 4.7%, P = .004). Patients in the docetaxel + carboplatin + trastuzumab + pertuzumab group received higher doses of granulocyte-macrophage colony-stimulating factor. Conclusion: In the neoadjuvant treatment of HER2-positive breast cancer, the docetaxel + trastuzumab + pertuzumab regimen might be more tolerated than the docetaxel + carboplatin + trastuzumab + pertuzumab regimen and did not show a lower complete pathological remission rate. However, our findings require further validation through prospective studies.

Pain Treatment and Cancer Patients: Are we Heeding Quality of Life?

The use of opioid analgesics remains the primary therapy for pain control in cancer patients. However, ample evidence persists showing that treatment is still inadequate. This cross-sectional study was carried out during one year in a Brazilian Cancer Hospital to evaluate the impact of opioid use on analgesia and patients’ quality of life. The Pain Management Index (PMI), EORTC QLQ.C30 (Quality of Life of Cancer Patients), Karnofsky Performance Status (KPS), Douleur Neuropathique 4 (DN4), and Brief Pain Inventory-Short Form (BPI-SF) were used. A hundred patients with advanced solid tumors and using opioids were included, with 82% of them reporting daily pain with 58% having intense pain. Morphine with a mean dose of 49 Morphine Milligram Equivalent were used by 57% of them, and PMI was negative in 34% of the sample. Neuropathic pain was found in 72% of patients. The pain was related to all BPI variables. Despite the substantial negative impact of pain on QOL, no association was found between the clinical factors assessed and QOL itself. This gap can be related to the persistence of high levels of sub-treatment, depression, and neuropathic pain associated with the use of low doses of opiates and adjuvant medications in the sample.

The Women’s Health Initiative cancer survivorship clinic incorporating electronic patient-reported outcomes: a study protocol for the Linking You to Support and Advice (LYSA) randomized controlled trial

BackgroundThe improved survival rate for many cancers in high-income countries demands a coordinated multidisciplinary approach to survivorship care and service provision to ensure optimal patient outcomes and quality of life. This study assesses the feasibility of introducing a Women’s Health Initiative cancer survivorship clinic in Ireland.MethodsThe trial comprises an intervention and control arm. Two hundred participants will be recruited. Key eligibility (1) women with early-stage hormone receptor-positive breast or gynecologic cancer (cervix or endometrial), within 12 months of completion of primary curative therapy, and (2) access to the Internet.The complex intervention comprises a nurse-led clinic targeting symptom management through a trigger alert system, utilizing electronic patient-reported outcome (ePRO) assessments at baseline, and 2, 4, 6, 8, 10, and 12 months. It also includes input from a dietitian monitoring diet and nutritional status.The control group will receive their usual care pathway standard of care and attend the cancer survivorship clinic and complete ePRO assessments at the start and end of the study.The primary endpoint (feasibility) includes the proportion of enrolled participants who complete baseline and follow-up ePRO surveys and partake in health professional consultations after ePRO data triggers. Secondary endpoints include changes in cancer-related symptom scores assessed by ePROs, health-related Quality of Life Questionnaire (QLQ) scores, Appraisal Self-Care Agency-R scores, and adjuvant endocrine therapy medication adherence. A process evaluation will capture the experiences of participation in the study, and the healthcare costs will be examined as part of the economic analysis.Ethical approval was granted in December 2020, with accrual commencing in March 2021.DiscussionThis protocol describes the implementation of a parallel arm randomized controlled trial (RCT) which examines the feasibility of delivering a Cancer Survivorship Clinic. The ePRO is an innovative symptom monitoring system which detects the treatment-related effects and provides individualized support for cancer survivors. The findings will provide direction for the implementation of future survivorship care.Trial registrationClinicalTrials.gov, NCT05035173. Retrospectively registered on September 5, 2021

Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein.

The in silico method has provided a versatile process of developing lead compounds from a large database in a short duration. Therefore, it is imperative to look for vaccinations and medications that can stop the havoc caused by SARS-CoV-2. The spike protein of SARS-CoV-2 is required for the viral entry into the host cells, hence inhibiting the virus from fusing and infecting the host. This study determined the binding interactions of 36 flavonoids along with two FDA-approved drugs against the spike protein receptor-binding domain of SARS-CoV-2 through molecular docking and molecular dynamics (MD) simulations. In addition, the molecular mechanics generalized Born surface area (MM/GBSA) approach was used to calculate the binding-free energy (BFE). Flavonoids were selected based on their in vitro assays on SARS-CoV and SARS-CoV-2. Our pharmacokinetics study revealed that cyanidin showed good drug-likeness, fulfilled Lipinski's rule of five, and conferred favorable toxicity parameters. Furthermore, MD simulations showed that cyanidin interacts with spike protein and alters the conformation and binding-free energy suited. Finally, an in vitro assay indicated that about 50% reduction in the binding of hACE2 with S1-RBD in the presence of cyanidin-containing red grapes crude extract was achieved at approximately 1.25 mg/mL. Hence, cyanidin may be a promising adjuvant medication for the SARS-CoV-2 spike protein based on in silico and in vitro research.

DO AROMATASE INHIBITORS AND TAMOXIFEN IMPACT THE NUMBER OF OOCYTES RETRIEVED IN OOCYTE OR EMBRYO BANKING CYCLES?

To compare the number of oocytes retrieved in oocyte/embryo banking cycles using Tamoxifen with traditional gonadotropins (Tam) vs. Aromatase Inhibitors with traditional gonadotropins (AI) vs. cycles with no adjuvant medications utilizing only traditional gonadotropins (NAM).

The natural medicinal fungus Huaier promotes the anti-hepatoma efficacy of sorafenib through the mammalian target of rapamycin-mediated autophagic cell death.

Sorafenib (SOR) is currently the first line molecular targeting agent for advanced liver cancer therapy. Unfortunately, the insensitivity of liver cancer patients to SOR relatively limits its effectiveness. Huaier (HUA), a natural medicinal parasitic fungus found on the Sophora japonica Linn., has been widely employed as an adjuvant medication for numerous malignancies due to its potent anti-tumoral properties. This studyaims to elucidate the enhancing therapeutic efficacy of HUA on SOR treatment in hepatocellular carcinoma (HCC) cells and mouse models. The CCK-8, clone formation, flow cytometry, immunofluorescence, transmission electron microscopy, western blot, bioinformaticanalysis, and xenografttumorassays were performed to evaluate the synergistic anti-hepatoma efficacy and mechanisms of HUA-SOR combination treatment on HCC cells. The results revealed combination treatment further inhibited proliferation, promoted apoptosis, enhanced autophagy of HCC cells, and suppressed the growth of transplanted tumors in mice, compared with either HUA or SOR treatment alone. For Hep3B and Huh7 cells, the optimal synergistic doses of HUA in combination with SOR were 8 mg/mL + 4 μM and 4 mg/mL + 2 μM, with combination index values of 0.646 and 0.588, respectively. Additionally, the underlying mechanisms might be related to biological processes that are mediated by mammalian target of rapamycin (mTOR). The combination treatment downregulated the protein expression levels of p-mTOR, p-p70S6K, p62, and upregulated the protein expression levels of Beclin-1 and LC3B-II. The mTOR activator MHY1485 attenuated the effect of HUA-SOR combination by inhibiting autophagy, suggesting HUA may potentiate the sensitivity of HCC cells to SOR by partially inducing mTOR-mediated autophagic cell death. These findings might provide a rationale experimental foundation for clinical applications of HUA with SOR.

Spironolactone alleviates schizophrenia-related reversal learning in Tcf4 transgenic mice subjected to social defeat

Cognitive deficits are a hallmark of schizophrenia, for which no convincing pharmacological treatment option is currently available. Here, we tested spironolactone as a repurposed compound in Tcf4 transgenic mice subjected to psychosocial stress. In this ‘2-hit’ gene by environment mouse (GxE) model, the animals showed schizophrenia-related cognitive deficits. We had previously shown that spironolactone ameliorates working memory deficits and hyperactivity in a mouse model of cortical excitatory/inhibitory (E/I) dysbalance caused by an overactive NRG1-ERBB4 signaling pathway. In an add-on clinical study design, we used spironolactone as adjuvant medication to the standard antipsychotic drug aripiprazole. We characterized the compound effects using our previously established Platform for Systematic Semi-Automated Behavioral and Cognitive Profiling (PsyCoP). PsyCoP is a widely applicable analysis pipeline based on the Research Domain Criteria (RDoC) framework aiming at facilitating translation into the clinic. In addition, we use dimensional reduction to analyze and visualize overall treatment effect profiles. We found that spironolactone and aripiprazole improve deficits of several cognitive domains in Tcf4tg x SD mice but partially interfere with each other’s effect in the combination therapy. A similar interaction was detected for the modulation of novelty-induced activity. In addition to its strong activity-dampening effects, we found an increase in negative valence measures as a side effect of aripiprazole treatment in mice. We suggest that repurposed drug candidates should first be tested in an adequate preclinical setting before initiating clinical trials. In addition, a more specific and effective NRG1-ERBB4 pathway inhibitor or more potent E/I balancing drug might enhance the ameliorating effect on cognition even further.

Prognostic value of programmed cell death ligand-1 expression in patients with bladder urothelial carcinoma undergoing radical cystectomy: A meta-analysis.

BackgroundRadical cystectomy and removal of pelvic lymph nodes (RC-PLND) is a recommended treatment for high-risk non-muscle-invasive and muscle-invasive non-metastatic bladder cancer (BC). However, 50% of patients relapse after RC-PLND. This study aimed to evaluate the effect of programmed cell death ligand-1 (PD-L1) on the prognosis of bladder urothelial carcinoma (BUC) after RC-PLND.MethodsWe present this meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Guidelines. The main outcomes were overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) of 3 and 5 years after RC-PLND.ResultsOverall, 11 studies and 1393 BUC cases were included in our meta-analysis. In tumor cells (TCs), the PD-L1 negative group had statistically significant advantage in 5-year OS (risk ratio [RR]: 0.85, 95% confidence interval [CI]: 0.74–0.97, P = 0.02), RFS (RR: 0.76, 95% CI: 0.58–0.99, P = 0.04), and CSS (RR: 0.73, 95% CI: 0.58–0.92, P = 0.009) compared with the PD-L1 positive group. But, no statistically significant difference in 5-year OS and RFS was observed between the PD-L1 negative and positive groups in tumor-infiltrating immune cells.ConclusionsOur study found that patients with BUC who tested positive for PD-L1 in TCs had a poor prognosis after RC-PLND. PD-1 or PD-L1 inhibitors could be used as a adjuvant medication for patients with BUC after RC-PLND who exhibit PD-L1 overexpression in TCs.Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42022301424.

Oral lichenoid lesion in association with chemotherapy treatment for non-Hodgkin lymphoma or lichen planus? Review of the literature and report of two challenging cases

BackgroundThe diagnosis of oral lichenoid lesions (OLL) remains a challenge for clinicians and pathologists. Although, in many cases, OLL cannot be clinically and histopathologically distinguishable from oral lichen planus (OLP), one important difference between these lesions is that OLL has an identifiable etiological factor, e.g. medication, restorative material, and food allergy. The list of drugs that can cause OLL is extensive and includes anti-inflammatory drugs, anticonvulsants, antihypertensives, antivirals, antibiotics, chemotherapeutics, among others. This work aimed to perform a literature review of OLL related to chemotherapy drugs and to report two cases of possible OLL in patients with B-cell and T-cell non-Hodgkin lymphomas in use of chemotherapy and adjuvant medications. We also discuss the challenge to clinically and histopathologically differentiate OLL and OLP.Case presentationIn both cases, oral lesions presented reticular, atrophic, erosive/ulcerated, and plaque patterns. The diagnosis of OLL was initially established in both cases by the association of histopathology and history of onset of lesions after the use of medications. Although the patients have presented a significant improvement in the oral clinical picture for more than 2 years of follow-up, they still have some lesions.ConclusionA well-detailed anamnesis associated with the drug history, temporal relationship of the appearance of the lesions, and follow-up of patients are fundamental for the diagnosis of OLL related to drugs. Nevertheless, its differentiation from OLP is still a challenge.

Analgesic Efficacy of Adjuvant Medications in the Pediatric Caudal Block for Infraumbilical Surgery: A Network Meta-Analysis of Randomized Controlled Trials.

Various adjuvants are added to local anesthetics in caudal block to improve analgesia. The comparative analgesic effectiveness and relative rankings of these adjuvants are unknown.This network meta-analysis (NMA) sought to evaluate the comparative analgesic efficacy and relative ranking of caudal adjuvants added to local anesthetics (versus local anesthetics alone) in pediatric infra-umbilical surgery. We searched the United States National Library of Medicine database (MEDLINE), PubMed, and Excerpta Medica database (Embase) for randomized controlled trials (RCTs) comparing caudal adjuvants (clonidine, dexmedetomidine, ketamine, magnesium, morphine, fentanyl, tramadol, dexamethasone, and neostigmine) among themselves, or to no adjuvant (control). We performed a frequentist NMA and employed Cochrane’s ‘Risk of Bias’ tool to evaluate study quality. We chose the duration of analgesia (defined as 'the time from caudal injection to the time of rescue analgesia') as our primary outcome. We also assessed the number of analgesic dose administrations and total dose of acetaminophen within 24 h.The duration of analgesia [87 randomized control trials (RCTs), 5285 patients] was most prolonged by neostigmine [mean difference: 513 min, (95% confidence interval, CI: 402, 625)]. Dexmedetomidine reduced the frequency of analgesic dose administrations within 24 h [29 RCTs, 1765 patients; -1.2 dose (95% CI: -1.6, -0.9)] and the total dose of acetaminophen within 24 h [18 RCTs, 1156 patients; -350 mg (95% CI: -467, -232)] the most. Among caudal adjuvants, neostigmine (moderate certainty), tramadol (low certainty), and dexmedetomidine (low certainty) prolonged the duration of analgesia the most. Dexmedetomidine also reduced the analgesic frequency and consumption more than other caudal adjuvants (moderate certainty).