Prognosis Comparison Between Chronic Hepatitis B Patients Receiving a Finite Course of Tenofovir and Entecavir Treatment: A Nationwide Cohort Study in Taiwan

PurposeEntecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both recommended as first-line treatments for patients with chronic hepatitis B virus (CHB) infection according to international HBV treatment guidelines. However, recent studies reported conflicting results regarding the preferred antiviral in the prevention of hepatocellular carcinoma (HCC). This cohort study aimed to investigate this issue by using Taiwan's National Health Insurance Research Database, wherein a “finite” but not life-long treatment policy was applied.MethodsFrom January 2008 to December 2013, a total of 12,388 consecutive adult patients with CHB who received a finite course of TDF treatment (n = 1250) or ETV treatment (n = 11,138) were analyzed through screening for study eligibility followed by the 1:4 propensity score matching method.FindingsIn the entire cohort, the annual incidence and survival between the ETV and TDF groups were not significantly different regarding HCC occurrence (2.05 vs 2.74 per 100 patient-years [PY]; P = 0.055; hazard ratio [HR], 0.975; log-rank, P = 0.966), cirrhosis-related complications (1.9 vs 2.4 per 100 PY; P = 0.149; HR, 0.869; log-rank, P = 0.388), or all-cause mortality (2.16 vs 1.6 per 100 PY; P = 0.119; HR, 0.831; log-rank, P = 0.342), respectively. Propensity score matching analyses yielded similar results regarding HCC occurrence, cirrhosis-related complications, and all-cause mortality. In addition, these findings were consistently reproduced in the subgroups of patients with chronic hepatitis and cirrhosis that developed before antiviral treatment.ImplicationsETV and TDF did not significantly differ in prevention of HCC occurrence or reduction of cirrhosis-related complications and all-cause mortality in patients with CHB receiving a finite period of treatment.     

Seronegative autoimmune diseases: A challenging diagnosis

Autoimmune diseases (AID) are increasingly prevalent conditions which comprise more than 100 distinct clinical entities that are responsible for a great disease burden worldwide. The early recognition of these diseases is key for preventing their complications and for tailoring proper management. In most cases, autoantibodies, regardless of their potential pathogenetic role, can be detected in the serum of patients with AID, helping clinicians in making a definitive diagnosis and allowing screening strategies for early -and sometimes pre-clinical- diagnosis. Despite their undoubted crucial role, in a minority of cases, patients with AID may not show any autoantibody, a condition that is referred to as seronegative AID. Suboptimal accuracy of the available laboratory tests, antibody absorption, immunosuppressive therapy, immunodeficiencies, antigen exhaustion, and immunosenescence are the main possible determinants of seronegative AID. Indeed, in seronegative AID, the diagnosis is more challenging and must rely on clinical features and on other available tests, often including histopathological evaluation and radiological diagnostic tests. In this review, we critically dissect, in a narrative fashion, the possible causes of seronegativity, as well as the diagnostic and management implications, in several AID including autoimmune gastritis, celiac disease, autoimmune liver disease, rheumatoid arthritis, autoimmune encephalitis, myasthenia gravis, Sjögren’s syndrome, antiphospholipid syndrome, and autoimmune thyroid diseases.     

Effectiveness of aromatherapy with inhaled lavender essential oil and breathing exercises on ECT-related anxiety in depressed patients

Background and aims Electroconvulsive therapy (ECT) is considered a safe, effective, and significant treatment in patients suffering from a major depressive disorder. Anxiety caused by this invasive treatment may impose several side effects on patients. The purpose of this study was to evaluate the effectiveness of aromatherapy with inhaled lavender essential oil and breathing exercises on ECT-related anxiety in depressed patients.Methods In this randomized controlled clinical trial, 90 depressed patients were selected and divided into three groups: aromatherapy, breathing exercise, and routine care using a random allocation method. Before undergoing ECT, the aromatherapy group was exposed to the inhaled lavender essential oil (n = 30), the breathing exercise group performed the breathing exercises (n = 30), and the routine care group received routine care (n = 30). Before (20 min) and after the intervention (30 min later), patients' anxiety was assessed using Beck Anxiety Inventory.Results After the intervention, the results revealed that anxiety score changes were statistically significant among the three groups (p < 0.001). In addition, it was found that the patients’ mean anxiety scores significantly decreased in the aromatherapy and breathing exercise groups compared to with the pre-intervention scores (p < 0.001).Conclusion Aromatherapy with inhaled lavender essential oil and breathing exercises can be considered by clinical nurses as simple, applicable, and effective interventions to reduce ECT-related anxiety in depressed patients.     

Efficacy of Mechanical Circulatory Support Used Before Versus After Primary Percutaneous Coronary Intervention in Patients with Cardiogenic Shock From ST-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis

BackgroundOptimal timing to initiate mechanical circulatory support (MCS) in patients with ST-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS) remains unclear with studies showing conflicting results on whether to start before or after primary percutaneous coronary intervention (PPCI). This study aims to examine the association between mortality and MCS initiated before vs after PPCI in patients with STEMI complicated by CS.MethodsWe systematically searched PubMed, Embase, and Scopus for abstracts and full-text articles from inception to October 2021. Studies were included if they evaluated the association of mortality in patients who initiated MCS (specifically intra-aortic balloon pump (IABP), Impella, and venoarterial extracorporeal membrane oxygenation (VA-ECMO)) before PPCI versus after PPCI, specifically in patients with STEMI complicated by CS. Data were integrated using the random-effects models.ResultsTen studies involving 1,352 patients (956, 203, and 193 patients underwent IABP, Impella, and VA-ECMO respectively) with STEMI complicated by CS were included. There was no difference in mortality using IABP before or after PPCI ([OR] 1.77, 95% CI 0.77–1.61, I2 = 27%, p = 0.57). Nevertheless, Impella and VA-ECMO started before PPCI were significantly associated with a reduced risk of mortality compared to that started after PPCI ([OR] 0.49, 95% CI 0.26–0.92, I2 = 0%, p = 0.03 and [OR] 0.29, 95% CI 0.14–0.62, I2 = 0%, p = 0.001, respectively).ConclusionsIn patients with STEMI complicated by CS undergoing PPCI, the use of IMPELLA or VA-ECMO prior to PPCI significantly decreased mortality, in contrast to IABP, in which no difference in mortality was found between using it before or after PPCI. More rigorous studies are needed to clarify this association.     

Quantifying Lower Limb Muscle Stiffness as Ambulation Function Declines in Duchenne Muscular Dystrophy with Acoustic Radiation Force Impulse Shear Wave Elastography

Duchenne muscular dystrophy (DMD) is a progressive muscular disease, but validated imaging tools to quantify muscle microstructure alteration as mobility declines are lacking. We aimed to determine the feasibility of using acoustic radiation force impulse shear-wave elastography (ARFI/SWE) in the quantitative assessment of lower limb muscle stiffness in DMD patients. Shear wave velocities (SWVs) of lower limbs were measured in 39 DMD patients and 36 healthy controls aged 3–20 y. Mean SWV values of the controls and of the DMD patients at different ambulatory stages were compared using analysis of variance with Bonferroni correction. The DMD group had increased lower limb muscle stiffness compared with controls. Stiffness of the tibialis anterior and medial gastrocnemius muscle decreased from ambulatory to early non-ambulatory stages, whereas stiffness of the rectus femoris muscle increased from ambulatory to late non-ambulatory stages. We describe how SWV changes in lower limb muscles have the potential to predict ambulatory decline in DMD.     

Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.