Therapeutic Advances in Chronic Disease最新文献

It is well established that the retina provides insights beyond the eye. Through observation of retinal microvascular changes, studies have shown that the retina contains information related to cardiovascular disease. Despite the tremendous efforts toward reducing the effects of cardiovascular diseases, they remain a global challenge and a significant public health concern. Conventionally, predicting the risk of cardiovascular disease involves the assessment of preclinical features, risk factors, or biomarkers. However, they are associated with cost implications, and tests to acquire predictive parameters are invasive. Artificial intelligence systems, particularly deep learning (DL) methods applied to fundus images have been generating significant interest as an adjunct assessment tool with the potential of enhancing efforts to prevent cardiovascular disease mortality. Risk factors such as age, gender, smoking status, hypertension, and diabetes can be predicted from fundus images using DL applications with comparable performance to human beings. A clinical change to incorporate DL systems for the analysis of fundus images as an equally good test over more expensive and invasive procedures may require conducting prospective clinical trials to mitigate all the possible ethical challenges and medicolegal implications. This review presents current evidence regarding the use of DL applications on fundus images to predict cardiovascular disease.

Background: Effective novel therapies for multiple myeloma (MM) patients who are unresponsive to conventional treatments (triple-class refractory) are an urgent need. Bispecific antibodies (BsAbs) offer a promising new approach to stimulate T cells and induce tumor cell death by targeting molecules on the surface of malignant plasma cells and CD3 on the surface of T cells.

Objectives: Addressing the issue of improving the prognosis of triple-class refractory MM patients has become a significant clinical challenge.

Design: This is a brief report.

Methods: This article summarizes the latest updates of BsAbs treatment of MM from the 2022 ASH annual meeting.

Results: BsAbs that target B-cell maturation antigen and G protein-coupled receptor family C group 5 memberD have demonstrated remarkable clinical activity and favorable safety profiles. Many potential targets for myeloma cells are currently undergoing phase I/II clinical trials, and these off-the-shelf bispecific molecules are likely to become a critical part of the MM treatment landscape.

Conclusion: This article provides an overview of the latest advances in BsAbs immunotherapy for refractory and relapsed MM and highlights significant findings from the 2022 ASH annual meeting.

The most common reasons seen for lack of asthma control include misconceptions about disease control, low controller treatment adherence, poor inhaler technique, and the resulting underuse of controllers and overuse of short-acting beta2 agonists (SABAs). Narrowing these care gaps may be achieved through well-designed patient education that considers the patient's motivation, beliefs, and capabilities regarding their asthma and its management and empowers the patient to become an active participant in treatment decisions. Digital health technologies (DHTs) and digital therapeutic (DT) devices provide new opportunities to monitor treatment behaviors, improve communication between healthcare providers and patients, and generate data that inform educational interactions. DHT and DT have been proven effective in enhancing patient self-management in other chronic conditions, particularly diabetes. Accelerated integration of DHT and DT into the management of asthma patients is facilitated by the use of digital inhalers that employ sensor technology ("smart" inhalers). These devices efficiently provide real-time feedback on controller adherence, SABA use, and inhaler technique that have the strong potential to optimize asthma control.

Background: The advantages of spleen stiffness in prediction of high-risk varices (HRV) in cirrhosis patients have been confirmed. Recently, a new device utilizing a 100 Hz probe dedicated to spleen stiffness measurement (SSM) was developed.

Objectives: To validate the clinical applicability of SSM@100 Hz in predicting HRV by comparing it with other non-invasive tests (NITs).

Design: A prospective cohort study.

Methods: A total of 171 cirrhosis patients who underwent esophagogastroduodenoscopy (EGD) examination were included in this study. SSM using a 100 Hz probe and liver stiffness measurement using a 50 Hz probe were performed. Additionally, 22 healthy controls underwent spleen stiffness evaluation using the 100 Hz probe.

Results: The failure rates of spleen stiffness examination in patients with cirrhosis and in healthy controls were 2.9% and 4.5%, respectively. The means of SSM values were 56.4 ± 21.6 and 13.8 ± 6.7 kPa in cirrhosis and controls. SSM increased proportionally with the severity of esophageal varices. The area under receiver operating characteristic (ROC) for spleen stiffness in predicting HRV was 0.881 (95% confidence interval 0.829-0.934), with a cutoff value of 43.4 kPa. The accuracy, false negative rate and EGD spare rate were 86.5%, 2.5% and 24.3%, respectively. For HRV prediction, SSM was comparable to expanded Baveno VI and VII and superior to other NITs. As to viral versus non-viral cirrhosis and compensated versus decompensated cirrhosis, the cut-off and performance of SSM were different.

Conclusion: SSM@100 Hz demonstrates high accuracy in predicting HRV with a low missed HRV rate. Our findings suggest that SSM@100 Hz can be used independently due to its simplicity and effectiveness. However, further studies are needed to determine appropriate cutoff values based on the cause of cirrhosis and liver function.

Trail registration: ChiCTR2300070270.

Extraintestinal manifestations occur rather frequently in ulcerative colitis (UC) and Crohn's disease patients and are usually related to an exacerbation of the underlying intestinal bowel disease but sometimes may run a course independent of the inflammatory bowel diseases (IBD). About one-third of patients with IBD develop extraintestinal manifestations, such as pyoderma gangrenosum (PG). PG is an uncommon inflammatory skin disorder of unknown pathogenesis. There are no specific serological or histological markers, and diagnosis is predominantly clinical. Topical and systemic therapies are both vital aspects of treatment and immune modulators have been used with increasing success in recent years, although immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and comorbid patients, underlining the unmet need for safer alternative therapies. Thus, in this case report, we highlighted an adsorptive granulocyte/monocyte apheresis (GMA) as a new therapeutic possibility in IBD patients with extraintestinal manifestations. We report a case of a 60-year woman with a history of UC with a Mayo grade 3 score which was associated with a PG. Given that the patients maintained clinical remission with vedolizumab, we preferred not to perform a combined treatment with other antitumor necrosis factor-alpha or ciclosporin, thus avoiding an increased risk of serious infections in the patient. Therefore, we performed the extracorporeal leukocyte apheresis. The patient progressed favorably, with progressive improvement of skin and bowel disease. Therefore, adsorptive GMA has a very favorable safety profile and has been confirmed in numerous studies. In this study, we underlined that an intensive regimen of GMA paves the way to an ideal option for patients with severe and refractory PG complicated with UC.

Background: Infection events are a major concern for patients and physicians when making psoriasis treatment decisions.

Objective: To estimate the relative short-term risks of infection and serious infection for biologic and small molecule therapies in the treatment of moderate-to-severe plaque psoriasis (PsO) and psoriatic arthritis (PsA).

Data sources and methods: A systematic literature search of the PubMed, EMBASE, and Web of Science databases was conducted on 17 June 2022. We included phase II, III, or IV randomized controlled trials (RCTs) of biologic and small-molecule therapies that are licensed or likely to gain approval soon for PsO and PsA, as well as infection data reports. Two investigators independently extracted the data based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Network meta-analysis (NMA) was performed to estimate the pooled relative risks (RRs) and corresponding 95% confidence intervals of total infections and serious infections for treatments during placebo-controlled phases of RCTs. The surface under the cumulative ranking area (SUCRA) was calculated to rank the infection risk for each treatment.

Results: A total of 94 RCTs with a total of 19 treatment arms involving 54,369 participants were analyzed. For patients with PsO, bimekizumab, secukizumab, risankizumab, ustekinumab, apremilast, guselkumab, and adalimumab were associated with significantly higher risks of infection than placebo; SUCRA ranked infliximab, deucravacitinib, and bimekizumab with the highest risks of infection. For patients with PsA, bimekizumab, apremilast, and upadacitinib (30 mg daily) were associated with higher risks of infection; SUCRA ranked bimekizumab with the highest risk of infection. No treatments, except for upadacitinib (30 mg daily), were associated with a higher risk of serious infection than placebo in PsA.

Conclusion: This NMA provides a comprehensive assessment of the comparative short-term risks of infection, which could help physicians and patients to select individualized treatments for psoriasis.

Registration: CRD42022359873.

Sensitization of dorsal horn ganglion sensory neuron plays a crucial role in the maintenance of chronic pain disorder. Multiple interventions targeting dorsal horn ganglion can provide considerable relief of pain, including selective nerve root block, pulsed radiofrequency, and electrical nerve stimulation technique. It remains controversial about the superiority of neuromodulation mentioned above due to distinct pattern of analgesic mechanism. Here, we reported one 71-year-old male presenting at our pain clinic with severe, unilateral lower limb pain caused by postherpetic neuralgia. An implantable stimulator with dual neuromodulation mode, combining pulsed radiofrequency with electrical nerve stimulation, was then placed into the lateral epidural space adjacent to dorsal root ganglion at L4 level. Standard stimulation programing was performed with technicians to achieve satisfactory control of pain, with numerical rating scale decreasing from 8 to 2 postoperatively. This novel dual function neuromodulation strategy may provide an alternative option for pain management for those with intractable neuropathic pain.

Background: Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking.

Objective: This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review.

Design: Systematic review of randomized controlled trials (RCTs).

Methods: A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane 'risk of bias' tool. A qualitative analysis was conducted due to heterogeneity of included studies.

Results: A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program.

Conclusion: CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.

Background: Numerous first-line immune checkpoint inhibitors (ICI) were developed for patients with advanced non-small cell lung cancer (NSCLC) lacking driver gene mutations. However, this group consists of a heterogeneous patient population, for whom the optimal therapeutic choice is yet to be confirmed.

Objective: To identify the best first-line immunotherapy regimen for overall advanced NSCLC patients and different subgroups.

Design: Systematic review and Bayesian network meta-analysis (NMA).

Methods: We searched several databases to retrieve relevant literature. We performed Bayesian NMA for the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (tr-AEs) with a grade equal or more than 3 (grade ⩾ 3 tr-AEs). Subgroup analysis was conducted according to programed death ligand 1 (PD-L1) levels, histologic type, central nervous system (CNS) metastases and tobacco use history.

Results: For the PD-L1 non-selective patients, sintilimab plus chemotherapy (sinti-chemo) provided the best OS [hazard ratio (HR) = 0.59, 95% confidence interval (CI):0.42-0.83]. Nivolumab plus bevacizumab plus chemotherapy (nivo-bev-chemo) was comparable to atezolizumab plus bevacizumab plus chemotherapy (atezo-bev-chemo) in prolonging PFS (HR = 0.99, 95% CI: 0.51-1.91). Atezo-bev-chemo remarkably elevated the ORR than chemotherapy (OR = 3.13, 95% CI: 1.51-6.59). Subgroup analysis showed pembrolizumab plus chemotherapy (pembro-chemo) ranked first in OS in subgroups of PD-L1 < 1%, non-squamous, no CNS metastases, with or without smoking history, and ranked second in OS in subgroups of PD-L1 ⩾ 1% and PD-L1 1-49%. Cemiplimab and sugemalimab plus chemotherapy ranked first in OS and PFS for squamous subgroup, respectively. For patients with CNS metastases, nivolumab plus ipilimumab plus chemotherapy (nivo-ipili-chemo) and camrelizumab plus chemotherapy provided the best OS and PFS, respectively.

Conclusions: Sinti-chemo and nivo-bev-chemo were two effective first-line regimens ranked first in OS and PFS for overall patients, respectively. Pembro-chemo was favorable for patients in subgroups of PD-L1 < 1%, PD-L1 ⩾ 1%, PD-L1 1-49%, non-squamous, no CNS metastases, with or without smoking history. Addition of bevacizumab consistently provided with favorable PFS results in patients of all PD-L1 levels. Cemiplimab was the best option in squamous subgroup and nivo-ipili-chemo in CNS metastases subgroup due to their advantages in OS.

Background: Medication adherence in Medicare-enrolled older adults with asthma and chronic obstructive pulmonary disease (COPD) before and during the coronavirus disease 2019 (COVID-19) pandemic is unknown.

Objectives: To evaluate medication adherence and determinants of high adherence before and during the COVID-19 pandemic in this population.

Design: Retrospective cohort study.

Methods: The proportion of days covered (PDC) reflected medication adherence from January to July 2019 and from January to July 2020. Patients <65 years of age, with COPD or asthma alone, or with cystic fibrosis were excluded. Paired t tests were used to assess adherence changes. Logistic regression explored association of age, sex, diagnosis of depression, number of medications, medication-related problems, prescribers, pharmacies, controller medication classes, albuterol rescue inhaler fills, oral corticosteroid fills, and having a 90-day supply with high adherence (PDC ⩾ 80%).

Results: This analysis included 989 patients. In this cohort, 61.2% of patients received oral corticosteroids. Over 60% of patients had ⩾3 rescue fills in both 2019 and 2020. Medication adherence to controller medications significantly decreased for all controller medications (p < 0.001) in 2020. In 2019 and 2020, number of controller medication classes and having a 90-day supply were associated with high adherence (p < 0.001). In 2019, variables associated with high adherence also included number of medication-related problems and having ⩾3 albuterol rescue inhalers (p < 0.001).

Conclusion: Medication adherence to controllers significantly decreased during the pandemic among older adults with asthma and COPD. Patients with multiple controller classes and a 90-day supply were more likely to be highly adherent. A 90-day supply of medications should be used to facilitate access to medication during the pandemic. Healthcare professionals should assess medication adherence, resolve the barriers of adherence and medication-related problems to achieve desired clinical outcomes among older adults with both asthma and COPD.