Lower Risk Of Adverse Events Research Articles

Role of Statins after Endovascular Repair of Abdominal Aortic Aneurysms: A Nationwide Population-Based Study.

The role of statins after endovascular abdominal aortic aneurysm repair (EVAR) has not been well established in an Asian context. In this study, the use of statins and their association with long-term health outcomes were evaluated in patients undergoing EVAR using the Korean National Health Insurance Service database. Among the 8893 patients who underwent EVAR from 2008 to 2018, 3386 (38.1%) were on statins prior to the procedure. Patients using statins had a higher prevalence of comorbidities, such as hypertension (88.4% vs. 71.5%), diabetes mellitus (24.5% vs. 14.1%), and heart failure (21.6% vs. 13.1%), compared with non-users (all p < 0.001). After propensity score matching, statin use prior to EVAR was associated with a lower risk of all-cause mortality (HR 0.85, 95% CI 0.78-0.92, p < 0.001) and cardiovascular mortality (HR 0.66, 95% CI 0.51-0.86, p = 0.002). Statin use following EVAR was associated with a lower risk of adverse events, but not significantly so. Patients on statins both preceding and following EVAR had a lower risk of all-cause mortality (HR 0.82, 95% CI 0.73-0.91, p < 0.001) and cardiovascular mortality (HR 0.62, 95% CI 0.44-0.87, p = 0.007), compared with statin non-users. Among Korean patients undergoing EVAR, the persistent use of statins prior to and after the procedure was associated with a lower risk of mortality, compared with non-statin users.

Topical growth factor preparations for facial skin rejuvenation: A systematic review.

Cosmeceutical preparations containing growth factors (GFs) are widely used for facial rejuvenation. We performed a systematic review to assess the evidence regarding their safety and effectiveness for facial rejuvenation. Electronic databases (Cochrane Library, EMBASE, MEDLINE, and Scopus) were searched from 2000 to October 2022 for prospective trials and case series assessing topical GF preparations for facial rejuvenation in 10 or more participants. Thirty-three studies, including 9 randomized controlled trials (RCTs) and 24 uncontrolled case series, representing 1180 participants receiving 23 different topical preparations containing GFs met the inclusion criteria and were included. Of the 33 studies, nine used a placebo or active control. The GF preparations were applied twice daily in all except two studies, with a mean treatment duration of 3months. Based on the investigator's assessment, preparations containing GFs induce a modest improvement in skin texture (median < 50%), fine lines/wrinkles (median < 35%), and overall facial appearance (median < 20%) versus baseline. Participant-assessed improvement was generally higher than investigator-assessed response. Three comparative RCTs showed no statistically significant differences between treatments. Studies were limited by heterogeneity with regard to the source and number of GFs used in the preparations, information about additional ingredients, and lack of standardization in the outcome measures. The preparations were associated with a low risk of adverse events. The persistence of the clinical improvements beyond 6months is not known. Administration of topical preparations containing GFs appears to be effective for facial skin rejuvenation, as demonstrated by the investigator- and participant-reported outcome measures.

Intraoperative DSA-guided minimal approach for craniocervical junction DAVFs obliteration.

Dural arteriovenous fistulas (DAVFs) are a group of diseases involving problematic shunts between dural arteries and venous structures such as sinuses, meningeal veins, or even cortical veins. To focus on craniocervical junction dural arteriovenous fistulas (DAVFs), we introduce a minimally invasive technique with midline incision combined with intraoperative digital subtraction angiography (DSA). This hybrid technique can minimize the incision wound to an average of 6 cm which leads to less destruction and lower risk of adverse events. Using this minimally invasive approach, surgical obliteration was achieved in 6 patients with craniocervical junction DAVFs. A minimal midline incision was made over the C1-2 level, measuring approximately 5 to 7 cm in length. C1 hemilaminectomy was performed for DAVF obliteration followed by intraoperative DSA for confirmation of complete obliteration. Among these 6 patients, the radiculomedullary artery was the most common feeding artery. The mean length of the operation (including DSA performance) was 6.5 ± 1.4 h. None of these cases showed cerebrospinal fluid leakage or exacerbation of neurological symptoms after the operation. Using intraoperative DSA, the minimally invasive technique offers more precise but less destructive access than conventional far lateral suboccipital craniotomy. Most importantly, intraoperative DSA provided verification of complete closure for shunts that could not be examined for indocyanine green (ICG) dye because the microscope did not have a clear line of sight. In our experience, this technique shows encouraging results of fistula obliteration.

Intubation practices and outcomes for patients with suspected or confirmed COVID-19: a national observational study by the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN)

ObjectiveIntubation practices changed during the COVID-19 pandemic to protect healthcare workers from transmission of disease. Our objectives were to describe intubation characteristics and outcomes for patients tested for SARS CoV-2 infection. We compared outcomes between patients testing SARS COV-2 positive with those testing negative.MethodsWe conducted a health records review using the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) registry. We included consecutive eligible patients who presented to one of 47 EDs across Canada between March 1, 2020 and June 20, 2021, were tested for SARS-CoV-2 and intubated in the ED. The primary outcome was the proportion of patients experiencing a post-intubation adverse event during the ED stay. Secondary outcomes included first-pass success, intubation practices, and hospital mortality. We used descriptive statistics to summarize variables with subgroup differences examined using t tests, z tests, or chi-squared tests where appropriate with 95% CIs.ResultsOf 1720 patients with suspected COVID-19 who were intubated in the ED during the study period, 337 (19.6%) tested SARS-CoV-2 positive and 1383 (80.4%) SARS-CoV-2 negative. SARS-CoV-2 positive patients presented to hospital with lower oxygen levels than SARS-CoV-2 negative patients (mean pulse oximeter SaO2 86 vs 94%, p < 0.001). In total, 8.5% of patients experienced an adverse event post-intubation. More patients in the SARS-CoV-2 positive subgroup experienced post-intubation hypoxemia (4.5 vs 2.2%, p = 0.019). In-hospital mortality was greater for patients who experienced intubation-related adverse events (43.2 vs 33.2%, p = 0.018). There was no significant difference in adverse event-associated mortality by SARS-CoV-2 status. First-pass success was achieved in 92.4% of all intubations, with no difference by SARS-CoV-2 status.ConclusionsDuring the COVID-19 pandemic, we observed a low risk of adverse events associated with intubation, even though hypoxemia was common in patients with confirmed SARS-CoV-2. We observed high rates of first-pass success and low rates of inability to intubate. The limited number of adverse events precluded multivariate adjustments. Study findings should reassure emergency medicine practitioners that system modifications made to intubation processes in response to the COVID-19 pandemic do not appear to be associated with worse outcomes compared to pre-COVID-19 practices.

Regulatory approval pathway for COVID-19 vaccine in USA, Europe and India.

The coronavirus disease-2019 (COVID-19) outbreak has confused everyone, including healthcare experts, physicians and frontline workers. Monoclonal antibodies, anticoagulants and immunomodulatory therapy were initially used to treat COVID-19. However, they can only inhibit the virus from replicating, which is not enough to provide a lasting cure. As each month passes, a growing number of companies are working on vaccinations that will aid in the development of resistance against the corona virus. As a result, all regulatory bodies have stated that if a vaccine has high efficacy and low risk of adverse events, it will be approved through an emergency use application. However, there is one major hindrance: After completing phase II clinical trials with an emergency use application, the product can be released to the market. However, the firm should conduct phase III and phase IV trials at the same time, with peer review occurring after each cycle of clinical trials and also market data to be presented simultaneously to track adverse events. In this article, the author has compared the standard approval process (i.e. Standard Biological License application) with the emergency use application to describe how the COVID-19 vaccine was approved by the different regulatory bodies.

Efficacy of Fascia Iliaca Compartment Blocks in Proximal Femoral Fractures in the Prehospital Setting: A Systematic Review and Meta-Analysis.

Proximal femoral fractures are characterized as one of the most common and most painful injuries sustained by patients of all ages and are associated with high rates of oligoanalgesia in the prehospital setting. Current treatments include oral and parenteral opiates and sedative agents, however regional anesthesia techniques for pain relief may provide superior analgesia with lower risk of side effects during patient transportation. The fascia iliaca compartment block (FICB) is an inexpensive treatment which is performed with minimal additional equipment, ultimately making it suitable in prehospital settings. In adult patients sustaining proximal femoral fractures in the prehospital setting, what is the effect of the FICB on non-verbal pain scores (NVPS), patient satisfaction, success rate, and adverse events compared to traditional analgesic techniques? A librarian-assisted literature search was conducted of the Cochrane Database, Ovid MEDLINE, PubMed, Ovid EMBASE, Scopus, and Web of Science indexes. Additionally, reference lists for potential review articles from the British Journal of Anesthesia, the College of Anesthetists of Ireland, the Journal of Prehospital Emergency Care, Annales Francaises d'Anesthesie et Réanimation, and the Scandinavian Journal of Trauma, Resuscitation, and Emergency Medicine were reviewed. Databases and journals were searched during the period from January 1, 1980 through July 1, 2022. Each study was scrutinized for quality and validity and was assigned a level of evidence as per Oxford Center for Evidence-Based Medicine guidelines. Five studies involving 340 patients were included (ie, two randomized control trials [RCTs], two observational studies, and one prospective observational study). Pain scores decreased after prehospital FICB across all included studies by a mean of 6.65 points (5.25 - 7.5) on the NVPS. Out of the total 257 FICBs conducted, there was a success rate of 230 (89.3%). Of these, only two serious adverse events were recorded, both of which related to local analgesia toxicity. Neither resulted in long-term sequelae and only one required treatment. Use of FICBs results in a significant decrease in NVPS in the prehospital setting, and they are ultimately suitable as regional analgesic techniques for proximal femur fractures. It carries a low risk of adverse events and may be performed by health care practitioners of various backgrounds with suitable training. The results suggest that FICBs are more effective for pain management than parenteral or oral opiates and sedative agents alone and can be used as an appropriate adjunct to pain management.

Regulatory approval pathway for COVID-19 vaccine in USA, Europe and India

The coronavirus disease-2019 (COVID-19) outbreak has confused everyone, including healthcare experts, physicians and frontline workers. Monoclonal antibodies, anticoagulants and immunomodulatory therapy were initially used to treat COVID-19. However, they can only inhibit the virus from replicating, which is not enough to provide a lasting cure. As each month passes, a growing number of companies are working on vaccinations that will aid in the development of resistance against the corona virus. As a result, all regulatory bodies have stated that if a vaccine has high efficacy and low risk of adverse events, it will be approved through an emergency use application. However, there is one major hindrance: After completing phase II clinical trials with an emergency use application, the product can be released to the market. However, the firm should conduct phase III and phase IV trials at the same time, with peer review occurring after each cycle of clinical trials and also market data to be presented simultaneously to track adverse events. In this article, the author has compared the standard approval process (i.e. Standard Biological License application) with the emergency use application to describe how the COVID-19 vaccine was approved by the different regulatory bodies.

The clinical efficacy of orexin antagonists for primary insomnia- A review of the evidence

IntroductionPrimary insomnia is frequently present in the general population, with epidemiologic research reporting prevalence values from 10% to as high as 60%. Chronic insomnia is associated with a significant impact on professional, academic, and daily life functionality, and it also may be responsible for decreasing the quality of life. Multiple generations of drugs for insomnia have been launched in clinical use in the last decades, but each class of pharmacological agents has its shortcomings (i.e., low efficacy, risk of addiction, diurnal sedation, risk of falls and fractures, etc.). Initially, research on orexin receptor antagonists has been considered with enthusiasm, due to these agents’ low risk of adverse events and good safety profile in the medium and long term.ObjectivesTo assess the evidence supporting the efficiency and safety of orexin receptor antagonists in the treatment of insomnia.MethodsA literature review was performed through the main electronic databases (PubMed, Cochrane, Clarivate/Web Of Science, and EMBASE) using the search paradigm “primary insomnia” AND “orexin receptor modulators”. All papers published between January 2000 and September 2022 were included.ResultsSuvorexant is a dual antagonist of orexin 1 and 2 receptors (DORA), FDA-approved for the treatment of insomnia, both for difficulties in falling and staying asleep. Daridorexant is another DORA, approved by FDA and EMA for the same indications as suvorexant, but EMA considers „additional monitoring” necessary for this drug. Lemborexant is a DORA approved for use in US and Japan, while vornorexant, which is included in the same class, is under development for the treatment of insomnia and sleep apnea (in phase 2 and 1 clinical trials, respectively). Almorexant is a DORA that was discontinued from clinical research due to hepatic safety concerns. Seltorexant is an orexin 2 receptor antagonist (SORA2) explored in phase II trials for the treatment of insomnia. Somnolence and fatigue are the most frequently reported adverse events of DORAs, but sleepwalking and sleep driving, sleep paralysis, or hypnopompic and hypnagogic hallucinations have been described in clinical studies. Seltorexant was associated with somnolence, headache, and nausea.ConclusionsDual antagonism of orexin 1 and 2 receptors is a mechanism that produced three currently available drugs for insomnia, and other clinical applications of these agents are still under investigation. At least one other agent from this class is under investigation, therefore the potential clinical utility of DORAs is far from being exhausted. Also, the selective orexin 2 receptor antagonism could be a promising mechanism of action for the treatment of insomnia.Disclosure of InterestNone Declared

Effectiveness and safety of acupuncture for insulin resistance in women with polycystic ovary syndrome: A systematic review and meta-analysis

ObjectiveTo perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate acupuncture's clinical effect on insulin resistance (IR) in women with polycystic ovary syndrome (PCOS). MethodsPubMed, Cochrane Library, Embase databases, and Chinese databases, including China National Knowledge Infrastructure, Technology Journal Database, and Wanfang Database, were searched without language restrictions from inception to December 20, 2021. Only RCTs in which acupuncture had been examined as the sole or adjunctive PCOS-IR treatment were included. Our primary endpoint was the homeostasis model assessment of insulin resistance (HOMA-IR). The secondary outcomes were fasting blood glucose (FBG), fasting insulin (FINS), body mass index (BMI), and adverse events. ResultsOur analysis included 17 eligible RCTs (N = 1511 participants). Compared with other treatments, acupuncture therapy yielded a greater mean reduction in HOMA-IR (MD = −0.15; 95% CI, −0.27 to −0.03; P = 0.01) and BMI (MD = −1.47; 95% CI, −2.46 to −0.47; P = 0.004). Besides acupuncture was associated with a lower risk of adverse events than other treatments (RR, 0.15; 95% CI, 0.10 to 0.22; P < 0.01). Additionally, the combination treatment of acupuncture and medicine is more effective in improving HOMA-IR (MD = −0.91; 95% CI, −1.11 to −0.71; P < 0.01), FBG (MD = −0.30; 95% CI, −0.56 to −0.04; P = 0.02), FINS (MD = −2.33; 95% CI, −2.60 to −2.06; P < 0.01) and BMI (MD = −1.63; 95% CI, −1.94 to −1.33; P < 0.01) than medicine alone. ConclusionsAcupuncture is relatively effective in improving HOMA-IR and BMI in PCOS-IR. Besides, it's safer than other treatments and could be an adjuvant strategy for improving PCOS-IR. Further large-scale, long-term RCTs with strict methodological standards are justified.

Optimizing Cancer Survivorship Care: Examination of Factors Associated with Transition to Primary Care.

Healthcare systems in Canada and elsewhere have identified the need to develop methods to effectively and safely transition appropriate cancer survivors to primary care. It is generally accepted that survivors with a low risk of adverse events, including recurrence and toxicity, should be more systematically identified and offered transition. There remains a lack of clarity about what constitutes an appropriate profile that would assist greater application in practice. To address this gap, we examined the clinical profiles of patients that were transitioned from a large regional cancer centre to the community. The factors examined included disease site, clinical stage, time since diagnosis/first consult, cancer treatments, and Edmonton Symptom Assessment System (ESAS) scores. In total, 2604 patients were identified as transitioned between 2013 and 2020. These patients tended to have common cancers (e.g., breast, endometrium, colorectal) that were generally of lower stage. Half of the patients had received chemotherapy and/or radiation treatment. Nearly one-third of survivors were transitioned within a year of first consult and a third after five years. Most patients reported minimal symptoms based on ESAS scores prior to being transitioned. This study represents one of the first to analyze the types of cancer patients that are being selected for transition to primary care.

Characteristics and Clinical Management Strategy of Petrous Apex Cholesterol Granulomas

Purpose: To evaluate the clinical characteristics of petrous apex cholesterol granulomas (PACG) and assess outcomes after different treatment strategies. Method: A consecutive case series of 34 patients with a PACG. Main outcomes were PACG growth, symptoms, and the outcomes of different treatment strategies: wait-and-scan (WS) and surgical drainage. Results: Thirty-four patients were analyzed; mean follow-up time was 7.1 years. Twenty-one patients (61.7%) showed symptoms, mostly more than one. Most symptoms reported were cranial nerve palsy (58.8%) and headache (35.3%). Twenty-one patients (61.8%) received solely wait-and-scan (WS), and thirteen patients (38.2%) underwent surgery, five of whom (38.5%) after an initial WS period. In the solely WS group, one (4.8%) developed new symptoms, and two (9.5%) reported symptom progression despite a stable granuloma size. Two (9.5%) showed granuloma growth on follow-up scans without symptom progression. Surgery consisted of drainage. Eleven (84.6%) of these thirteen patients reported partial recovery; one (7.7%) reported no recovery; and one (7.7%) reported full recovery of reported symptoms related to PACG. Among the patients with cranial nerve involvement, 7.7% showed full recovery after surgery; 84.6% showed partial recovery; and 7.7% did not recover. Adverse events occurred in five out of 13 patients who underwent surgery, all with full recovery. Conclusions: This study confirms that PACG are slow-growing lesions with a low risk of adverse events. Solely using wait-and-scan strategy is a safe option for patients without symptoms, with acceptable symptoms without symptom progression, and with asymptomatic growth. Surgical treatment can be considered in patients with symptom progression or symptomatic growth.

The Use of Eculizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in an Academic Hematology Center.

Introduction Eculizumab is a complement inhibitor used in treating atypical hemolytic uremic syndrome (aHUS). This study showcases patient demographics, clinical and laboratory results of these patients, and overall outcomes of patients with aHUS treated with eculizumab. Methods The authors conducted a retrospective case study including 9 patients who received at least 1 dose of eculizumab for treating aHUS. A linear mixed effects model was used with random effects for each patient and fixed effects for eculizumab and time since admission. A p value < 0.05 was significant. Results Nine patients were treated with eculizumab for aHUS. Most patients were Black (n = 5) with either Medicare or Medicaid (n = 5). Genetic mutations were tested for in 5 patients. There were significant decreases in lactate dehydrogenase (LD, p = 0.029) and creatinine (Cr, p = 0.012) when on treatment. No significance was found in hemoglobin (p = 0.258) or platelets (p = 0.569). Treatment was stopped in 7 patients, of which 3 had no evidence of disease relapse. The only adverse event was severe thrombocytopenia (n = 1). Discussion This multicase study is the first of its kind in which most patients are Black, showing that there is a lack of research of this kind, especially on genetic mutations. Most of our patients did not have private insurance or had Medicaid/Medicare. There was a 246.5-day median duration of treatment. There was low risk of adverse events. Conclusion This case series elucidates the effective use of eculizumab for atypical hemolytic uremic syndromein a diverse patient population and emphasizes the need for more research in this area.

Exercise in patients with repaired tetralogy of Fallot: a systematic review and meta-analysis

ObjectiveChildren and adults with repaired tetralogy of Fallot (rTOF) have an impaired exercise capacity, a less active lifestyle and an increased long-term risk of adverse outcomes compared with healthy peers....

LB1531. Administration of Abatacept or Infliximab Reduces Mortality in Hospitalized Patients with COVID-19 Pneumonia: Results from the ACTIV-1 IM Master Protocol

Abstract Background Severe COVID-19 infection is characterized by a dysregulated hyperinflammatory state that contributes to morbidity and mortality. Immunomodulatory therapy has been shown to improve outcomes. We investigated if abatacept, CTLA-4-Ig, a selective costimulation modulator, provides additional benefit when added to standard of care. Methods We conducted a double-blind, randomized, placebo-controlled trial evaluating abatacept (given as a single infusion of 10mg/kg, to a maximum of 1000 mg) compared to standard of care (including remdesivir and dexamethasone) in patients hospitalized with COVID-19 pneumonia. The primary outcome was median time to recovery by day 29. Key secondary endpoints included 28-day mortality. Results A total of 1019 patients received an infusion (509 assigned to abatacept and 510 to placebo), constituting the analyzed modified intention-to-treat cohort. The mean age 54.9 years (SD 14.65), 60.5% were male, 44.2% Hispanic or Latino and 13.7% black. Patients were evenly matched in terms of severity of illness, and comorbidities. Participants randomized to abatacept did not show a statistically significant difference in the primary endpoint with a recovery rate ratio of 1.135 (95% CI 0.996-1.294, p=0.057) compared to placebo. The median (IQR) time to recovery was 9 days (8, 10) for both groups. The 28-day mortality in the abatacept arm was 11.0% and in control arm 15.0% (OR 0.62 (95% CI 0.41, 0.94)), with a 37.8% lower odds of dying in patients receiving abatacept. The improvement in mortality was demonstrated for patients requiring low or high flow O2 at baseline but was not seen in patients who required mechanical ventilation or ECMO at time of randomization. Subgroup analysis identified the strongest effect in those with baseline CRP &amp;gt;75mg/L, age &amp;gt;65 and diabetics. Safety data demonstrated slightly lower risk of adverse events. Rates of secondary infections were similar (abatacept 16.1% and placebo 14.3%). Conclusion Although single-dose IV abatacept did not demonstrate statistically significant improvement in time to recovery, it did show a substantial reduction in 28-day mortality compared to standard of care. Disclosures All Authors: No reported disclosures.

LB1531A. Administration of abatacept, reduces mortality in hospitalized patients with COVID pneumonia. Results of a randomized controlled trial.

Abstract Background Severe COVID-19 infection is characterized by a dysregulated hyperinflammatory state that contributes to morbidity and mortality. Immunomodulatory therapy has been shown to improve outcomes. We investigated if abatacept, CTLA-4-Ig, a selective costimulation modulator, provides additional benefit when added to standard of care. Methods We conducted a double-blind, randomized, placebo-controlled trial evaluating abatacept (given as a single infusion of 10mg/kg, to a maximum of 1000 mg) compared to standard of care (including remdesivir and dexamethasone) in patients hospitalized with COVID-19 pneumonia. The primary outcome was median time to recovery by day 29. Key secondary endpoints included 28-day mortality. Results A total of 1019 patients received an infusion (509 assigned to abatacept and 510 to placebo), constituting the analyzed modified intention-to-treat cohort. The mean age 54.9 years (SD 14.65), 60.5% were male, 44.2% Hispanic or Latino and 13.7% black. Patients were evenly matched in terms of severity of illness, and comorbidities. Participants randomized to abatacept did not show a statistically significant difference in the primary endpoint with a recovery rate ratio of 1.135 (95% CI 0.996-1.294, p=0.057) compared to placebo. The median (IQR) time to recovery was 9 days (8, 10) for both groups. The 28-day mortality in the abatacept arm was 11.0% and in control arm 15.0% (OR 0.62 (95% CI 0.41, 0.94)), with a 37.8% lower odds of dying in patients receiving abatacept. The improvement in mortality was demonstrated for patients requiring low or high flow O2 at baseline but was not seen in patients who required mechanical ventilation or ECMO at time of randomization. Subgroup analysis identified the strongest effect in those with baseline CRP &amp;gt;75mg/L, age &amp;gt;65 and diabetics. Safety data demonstrated slightly lower risk of adverse events. Rates of secondary infections were similar (abatacept 16.1% and placebo 14.3%). Conclusion Although single-dose IV abatacept did not demonstrate statistically significant improvement in time to recovery, it did show a substantial reduction in 28-day mortality compared to standard of care. Disclosures Reynold Panettieri, Jr., MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|AstraZeneca: Honoraria|Equillium: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|Janssen: Grant/Research Support|MedImmune: Grant/Research Support|Merck: Honoraria|Novartis: Grant/Research Support|Origo: Grant/Research Support|RIFM: Advisor/Consultant|RIFM: Grant/Research Support|Sanofi: Honoraria|Vault Health: Grant/Research Support Jane A. O'Halloran, MD PhD, Janssen Scientific Affairs, LLC: Grant/Research Support Michael A. Maldonado, MD, Bristol Myers Squibb: Employee|Bristol Myers Squibb: Stocks/Bonds William G. Powderly, MD, Merck: Advisor/Consultant.

Endoscopic ablation therapy for the pancreatic neoplasms.

Recently, endoscopic ultrasound (EUS)-guided ablation therapy has been reported as a less invasive therapy for patients with pancreatic neoplasms. Some ablation techniques, including injective ablation (using ethanol or other ablative agents), radiofrequency ablation (RFA), photodynamic therapy, and laser ablation, have been described in the literature. Among these, injective ablation and RFA are more frequently used for treating pancreatic neoplasms. Few studies have evaluated the effectiveness of EUS-guided ethanol ablation (EUS-EA) for potentially malignant solid neoplasms (neuroendocrine neoplasms or solid pseudopapillary neoplasms) and have reported a complete response (CR) rate of 60-80%. In addition, the CR rate after EUS-RFA for these lesions has been reported to be 55-100%, with no additional procedure-related adverse events (AEs). Regarding the amelioration of the symptoms of an insulinoma, the success rates of both the therapies were found to be excellent. Regarding complete tumor ablation, EUS-RFA appeared to be superior to EUS-EA. Although EUS-RFA has been reported as a safe treatment for pancreatic cancers, its effectiveness remains inadequate. Some studies have examined the effectiveness of EUS-guided injection ablation therapy for pancreatic cystic neoplasms (PCNs) and have reported CR rates that range from 35% to 79%. Alcohol-free chemotherapeutic agent ablation appears to be effective, with a low risk of AEs. However, studies on the effectiveness of EUS-RFA for PCNs are limited. In the future, EUS-guided ablation therapy could become a more widely used approach for potentially malignant and malignant pancreatic lesions.

Rituximab, a Safer Option for Rheumatoid Arthritis: A Comparison of the Reported Adverse Events of Approved Monoclonal Antibodies

Monoclonal antibodies (mAbs), which are commonly used to treat rheumatoid arthritis (RA), have been linked to a variety of adverse events (AEs). The objective of the study was to compare the safety profiles of six FDA approved mAbs (sarilumab, tocilizumab, adalimumab, golimumab, infliximab, and rituximab) marketed for the treatment of RA. A systematic review of the literature was conducted using the databases PubMed, Cochrane Library, and Science Direct. The manuscript comprised a total of 23 clinical studies. The percentage of patients who had AEs was calculated and presented using box-whisker and forest plots. Infections and infestations were found to be the most common AEs in RA patients treated with mAbs. Raised alanine aminotransferase (ALT), aspartate aminotransferase (AST), upper respiratory tract infection (URTI), and nasopharyngitis were frequently reported. The most common AEs were reported with adalimumab. The highest percentage of patients reporting AEs was associated with golimumab (52%), while rituximab had the fewest AEs (4.9%). In conclusion, rituximab appears to be a safer treatment option for RA as it is found to be associated with a lower risk of AEs, particularly respiratory infections.

Mucosal Injury During Per-oral Endoscopic Myotomy: A Single-Center Experience.

Peroral endoscopic myotomy is associated with a low risk of adverse events. Mucosal injury is the most common intraprocedural adverse event of peroral endoscopic myotomy. Severe mucosal injury may cause serious consequences, such as esophageal leak and mediastinitis, which affect the outcome of the procedure and prolong hospital stay. The aim of the present study was to determine the characteristics, predictors, and management approaches for unintended mucosal injury during peroral endoscopic myotomy. A total of 211 patients who underwent peroral endoscopic myotomy between November 2014 and June 2019 were enrolled in this study. Mucosal injury was defined according to a previous study and maintained in the endoscopy database. Patient-related and procedure-related factors were compared between patients with and without mucosal injury. Multivariate analysis was performed after adjusting for confounding factors. A total of 206 patients were eligible for study enrollment. Of these, 44 experienced mucosal injury, with an overall frequency of 21.4% (44/206). On multivariable analysis, mucosal injury was associated with submucosal fibrosis (odds ratio, 8.33; P = .024), intraprocedural bleeding (OR, 14.29; P < .001), endoscopic diameter of 9.9 mm (OR, 4.389; P = .006), and procedure duration over 60 minutes (OR, 1.016; P = .034). Mucosal injury is a significant event encountered during peroral endoscopic myotomy, affecting its short- and long-term outcomes. Intra-procedural bleeding, endoscopic submucosal fibrosis, and use of an endoscope with a large outer diameter have been found to be significant predictors of mucosal injury. Endoscopists should pay more attention to risk factors associated with mucosal injury to avoid adverse events.

The place of phytotherapy in the treatment of acute upper respiratory tract infections

Phytotherapy is based on the use of herbal medicines. Treatment with phytopreparations is characterized by efficiency, low risk of adverse events and the ability to enhance the effect of complex therapy. Herbal preparations are subject to standard requirements for quality control, safety and effectiveness. Inflammatory diseases of the respiratory tract are characterized by numerous symptoms that significantly reduce the quality of life of the patient. Along with pathogenetic therapy, symptomatic treatment is used. For the treatment of respiratory diseases, phytopreparations with antipyretic, immunomodulatory, anti-inflammatory, antitussive, mucolytic, bronchodilator and other clinically proven effects are used. The most common symptom of inflammatory diseases of the respiratory tract is cough. Many medicinal plants have antitussive effects. Ivy leaf extract has pronounced antitussive and mucolytic properties. The therapeutic effects of ivy are primarily due to the presence of saponins in its composition. Numerous randomized controlled trials have proven the efficacy and safety of H. Helix-based drugs in the treatment of cough in adults. A meta-analysis conducted by Barnes LA et al revealed that monopreparations and combined phytopreparations, including H. Helix, reduce the frequency and intensity of cough caused by viral respiratory infection. In a study involving 5,162 children, efficacy in the treatment of productive cough in children was proven. Currently, there are several medicines based on ivy leaves in liquid and solid forms on the pharmaceutical market of Russia. It leading position in sales of mucolytic agents of plant origin in Russia, due to its high efficiency and low frequency of adverse events.

CTNI-40. PHASE I TRIAL OF SULFASALAZINE COMBINED WITH STEREOTACTIC RADIOSURGERY FOR RECURRENT GLIOBLASTOMA: STUDY PROTOCOL FOR NCT04205357

Abstract Glioblastoma (GBM) is one of the most aggressive, radioresistant types of cancer with a dismal prognosis. Sulfasalazine (SAS) has shown tumor selective radiosensitizing properties in preclinical studies. The antioxidant glutathione (GSH) produced at high levels in glioma cells normally protects against radiation injury by scavenging reactive oxygen species produced during radiation therapy (RT). SAS blocks cysteine uptake through the xCT-channel, a rate-limiting step for GSH production. We have previously shown slowing of tumor growth and prolonged survival when SAS was combined with stereotactic radiosurgery (SRS) in vivo compared to either treatment alone. Our hypothesis is that SAS potentiates the efficacy of SRS for recurrent GBM with a low risk of adverse events (AE). The primary end-point is to establish the recommended dose for efficacy testing in phase II/III trials. This phase 1 dose-escalation trial utilizes a standard 3 + 3 design with 3-6 patients per cohort. Patients will be treated with oral SAS (1.5, 3.0, 4.5 or 6.0 g/day) 3 days prior to single session SRS. The SAS-dose will be escalated depending on the absence/presence of toxicity in the previous cohort of treated patients. If more than 1 of 3-6 patients ( ≥ 33 %) is experiencing grade 3 or higher toxicity levels, the study will be terminated. The dose below will be the recommended dose. Toxicity is graded using the Common Toxicity Criteria for Adverse Events (CTCAE) v5.0 recorded the first 30 days. Secondary end-points are assessments of 1) intratumoral GSH production (GSH-spectroscopy), 2) late AE utilizing 11C-MET-MRI-PET 3) changes in KPS/quality of life (FACT-Br), 4) need for steroidal treatment, 5) progression free and overall survival. Novel treatment modalities are urgently needed. This trial will establish the recommended dose for SAS repurposed as a radiosensitizer for a future phase 2/3 trial and may ultimately lead to improvement of current GBM treatment.