This article will provide a perspective review of the most extensively investigated deep learning (DL) applications for musculoskeletal disease detection that have the best potential to translate into routine clinical practice over the next decade. Deep learning methods for detecting fractures, estimating pediatric bone age, calculating bone measurements such as lower extremity alignment and Cobb angle, and grading osteoarthritis on radiographs have been shown to have high diagnostic performance with many of these applications now commercially available for use in clinical practice. Many studies have also documented the feasibility of using DL methods for detecting joint pathology and characterizing bone tumors on magnetic resonance imaging (MRI). However, musculoskeletal disease detection on MRI is difficult as it requires multi-task, multi-class detection of complex abnormalities on multiple image slices with different tissue contrasts. The generalizability of DL methods for musculoskeletal disease detection on MRI is also challenging due to fluctuations in image quality caused by the wide variety of scanners and pulse sequences used in routine MRI protocols. The diagnostic performance of current DL methods for musculoskeletal disease detection must be further evaluated in well-designed prospective studies using large image datasets acquired at different institutions with different imaging parameters and imaging hardware before they can be fully implemented in clinical practice. Future studies must also investigate the true clinical benefits of current DL methods and determine whether they could enhance quality, reduce error rates, improve workflow, and decrease radiologist fatigue and burnout with all of this weighed against the costs.

Herbal medicines are becoming increasingly popular among patients because they are well tolerated and do not exert severe side effects. Nevertheless, they receive little consideration in therapeutic settings. The present article reviews the current state of research on the clinical benefits of herbal medicines on five indication groups, psychosomatic disorders, gynecological complaints, gastrointestinal disorders, urinary and upper respiratory tract infections. The study search was based on the database PubMed and concentrated on herbal medicines legally approved in Europe. After applying defined inclusion and exclusion criteria, 141 articles were selected: 59 for psychosomatic disorders (100% randomized controlled trials; RCTs), 20 for gynecological complaints (56% RCTs), 19 for gastrointestinal disorders (68% RCTs), 16 for urinary tract infections (UTI, 63% RCTs) and 24 for upper respiratory tract infections (URTI) (79% RCTs). For the majority of the studies, therapeutic benefits were evaluated by patient reported outcome measures (PROs). For psychosomatic disorders, gynecological complaints and URTI more than 80% of the study outcomes were positive, whereas the clinical benefit of herbal medicines for the treatment of UTI and gastrointestinal disorders was lower with 55%. The critical appraisal of the articles shows that there is a lack of high-quality studies and, with regard to gastrointestinal disorders, the clinical benefits of herbal medicines as a stand-alone form of therapy are unclear. According to the current state of knowledge, scientific evidence has still to be improved to allow integration of herbal medicines into guidelines and standard treatment regimens for the indications reviewed here. In addition to clinical data, real world data and outcome measures can add significant value to pave the way for herbal medicines into future therapeutic applications.

BACKGROUND: Most transplanted organs are obtained from brain-dead donors. Inflammation results in a higher rate of rejection. Objectives: The objective of this animal model of brain death (BD) was to evaluate the effect of the progressive institution of volume expansion, norepinephrine, and combined hormone therapy on clinical, laboratory, and histological aspects. Methods: Twenty rabbits were divided: A (control), B (induction of BD + infusion of crystalloid), C (BD + infusion of crystalloid and noradrenaline (NA)), and D (BD + infusion of crystalloid + vasopressin + levothyroxine + methylprednisolone + NA). The animals were monitored for four hours with consecutives analysis of vital signs and blood samples. The organs were evaluated by a pathologist. Results: In Group D, we observed fewer number and lesser volume of infusions (p = 0.032/0.014) when compared with groups B and C. Mean arterial pressure levels were higher in group D when compared with group B (p = 0.008). Group D had better glycemic control when compared with group C (p = 0.016). Sodium values were elevated in group B in relation to groups C and D (p = 0.021). In Group D, the organ perfusion was better. Conclusion: The optimized strategy of management of BD animals is associated with better hemodynamic, glycemic, and natremia control, besides reducing early signs of ischemia.

UNASSIGNED: Pyrotinib is a novel irreversible pan-HER tyrosine kinase inhibitor (TKI). However, real-world data of pyrotinib-containing therapy in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and developing brain metastases (BMs) are limited, and the genomic profile of this subpopulation is almost undefined.
UNASSIGNED: Patients with BM of HER2-positive MBC (n = 35) treated with pyrotinib-containing therapy were enrolled in this analysis. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity profiles were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) for disease progression were estimated using the Cox proportional hazards models. Targeted next-generation sequencing of 618 cancer-relevant genes was performed on plasma and primary breast tumors from patients with BM and without BM.
UNASSIGNED: The median PFS time was 8.00 (95% CI, 5.98-10.017) months, and the median OS time was 23 (95% CI, 10.412-35.588) months. The ORR was 45.7%, and the DCR was 74.3%. In the Cox multivariate analysis, prior exposure to brain radiotherapy (HR = 3.268), received pyrotinib as third- or higher-line treatment (HR = 4.949), subtentorial brain metastasis (HR = 6.222), and both supratentorial and subtentorial brain metastases (HR = 5.863) were independently associated with increased risk of progression. The frequent grade 3-4 adverse event was increased direct bilirubin (14.3%), and two patients suffered from grade 3-4 diarrhea. In the exploratory genomic analysis, altered frequencies of FGFR3, CD276, CDC73, and EPHX1 were higher in the BM group. The consistency of mutated profiles of plasma and primary lesion in the BM group was significantly lower (30.4% vs. 65.5%; p = 0.0038).
UNASSIGNED: Pyrotinib-containing therapy shows favorable effectiveness and tolerable safety in patients with BM of HER2-positive MBC, particularly in a population that is brain radiotherapy-naïve, received pyrotinib as first- or second-line treatment, and developed supratentorial brain metastasis. In the exploratory genomic analysis, patients with BM showed distinct genomic features from patients without BM.

Pulmonary hypertension due to left heart disease (PH-LHD) represents approximately 65%-80% of all patients with PH. The progression, prognosis, and mortality of individuals with left heart failure (LHF) are significantly influenced by PH and right ventricular (RV) dysfunction. Consequently, cardiologists should devote ample attention to the interplay between HF and PH. Patients with PH and HF may not receive optimal benefits from the therapeutic effects of prostaglandins, endothelin receptor antagonists, or phosphodiesterase inhibitors, which are specific drugs for pulmonary arterial hypertension (PAH). Sacubitril/valsartan, the angiotensin receptor II blocker-neprilysin inhibitor (ARNI), was recommended as the first-line therapy for patients with heart failure with reduced ejection fraction (HFrEF) by the 2021 European Society of Cardiology Guidelines. Although ARNI is effective in treating left ventricular (LV) enlargement and lower ejection fraction, its efficacy in treating individuals with PH and HF remains underexplored. Considering its vasodilatory effect at the pre-capillary level and a natriuretic drainage role at the post-capillary level, ARNI is believed to have a broad range of potential applications in treating PH-LHD. This review discusses the fundamental pathophysiological connections between PH and HF, emphasizing the latest research and potential benefits of ARNI in PH with various types of LHF and RV dysfunction.

In 2023, home hemodialysis (HHD) is a dialysis modality used safely and performed independently at home by patients with chronic kidney disease (CKD). HHD requires adequate training and appropriate installation which includes the management of medical devices and consumables in the environment of each patient. According to each patient, HHD can be performed daily, every other day or overnight (nocturnal). The duration of the session varies from a few hours (less than three) during the day to several hours (six to ten) during the night. Over the past 10 years, we have been part of a revival in HHD with the availability of small machines better suited to homes and patients. Few controlled interventional studies and extensive registry data support the hypothesis that increase of frequency and duration of dialysis is associated with improved patient survival, cardiovascular risk profile, and quality of life. In addition to the physiological benefits of HDD, there are clear quality of life, social and economic benefits. There are, however, some disadvantages of HHD, including the application and time required for training, the risk of burnout, and the reluctance to \"hospitalize\" at home. Overall, these limits can be anticipated and overcome by appropriate training, multidisciplinary monitoring, and a dedicated organization. This review recalls the main clinical advantages of HDD related to both physiology and lifestyle as well as the main obstacles and proposes perspectives to guarantee its development. © 2022 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

An optimally operating microbiome supports protective, metabolic, and immune functions, but disruptions produce metabolites and toxins which can be involved in many conditions. Probiotics have the potential to manage these. However, their use in vulnerable people is linked to possible safety concerns and maintaining their viability is difficult. Interest in postbiotics is therefore increasing. Postbiotics contain inactivated microbial cells or cell components, thus are more stable and exert similar health benefits to probiotics. To review the evidence for the clinical benefits of postbiotics in highly prevalent conditions and consider future potential areas of benefit. There is growing evidence revealing the diverse clinical benefits of postbiotics in many prevalent conditions. Postbiotics could offer a novel therapeutic approach and may be a safer alternative to probiotics. Establishing interaction mechanisms between postbiotics and commensal microorganisms will improve the understanding of potential clinical benefits and may lead to targeted postbiotic therapy.

Recently approved migraine preventive therapies facilitate rapid control of migraine activity, potentially improving patients\' lives and minimizing the societal burden of migraine. This review synthesizes available evidence on rates and timing of early onset of migraine prevention and identifies patient-level outcomes related to early onset prevention. This evidence-based scoping review identified all available clinical trial evidence regarding the early onset of prevention of migraine, under the hypothesis \'Patients with migraine (episodic or chronic) report additional benefits when receiving an approved migraine preventive treatment that demonstrates an early onset of prevention\'. Early onset of prevention was defined as migraine preventive benefits within 30 days post-administration. PubMed, EMBASE, and CINAHL were searched for publications between 1988 and 2020. Overall, 16 publications described 18 studies. All studies were conducted in approved treatments [four anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies and one chemodenervation agent] in patients with episodic/chronic migraine; no publications were identified for traditional oral agents for early migraine prevention. Compared to placebo, erenumab (three studies) reduced weekly migraine days within 1 week; fremanezumab (six studies) increased reports of no headache of at least moderate severity on Day 1 and significantly reduced migraine frequency within 1 week; galcanezumab (three studies) significantly reduced the mean number of patients with migraine beginning Day 1 and each day of the first week; eptinezumab (four studies) significantly reduced migraine attack likelihood on Day 1 by > 50% versus baseline; and onabotulinumtoxinA (two studies) reduced headache and migraine days within 1 week. Four publications described function, disability, and quality of life improvements as early as Week 4; none reported cost-benefit. Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) and a chemodenervation agent (onabotulinumtoxinA) provide clinically relevant benefits during the first treatment week. Literature describing clinically relevant benefits regarding early onset of prevention in patients with migraine is limited.

OBJECTIVE: To compare the clinical benefits of rivaroxaban and warfarin in patients with non-valvular atrial fibrillation (NVAF) with high bleeding risk.
METHODS: A retrospective study was conducted on patients with high bleeding risk NVAF who were hospitalized at the First Affiliated Hospital of Zhengzhou University between May 31, 2016 and May 31, 2019 and took at least rivaroxaban and warfarin. The clinical benefits of both drugs were assessed by efficacy benefit and safety risk. The primary efficacy benefit was a composite end point for stroke (both ischemic and hemorrhagic) and systemic embolism. The secondary efficacy end points were death and myocardial infarction (MI). The principal safety end point was the composite end point of fatal bleeding and critical organ bleeding.
RESULTS: A total of 1,246 patients with high bleeding risk were enrolled, including 787 patients in the rivaroxaban group and 459 patients in the warfarin group. Results of the primary efficacy benefit endpoint were obtained from 104 patients (13.2%) in the rivaroxaban group and 88 (19.2%) patients in the warfarin group (hazard ratio [HR]: 0.681; 95% confidence interval [CI]: 0.512-0.906; P < 0.001 for non-inferiority). The principal safety end points were observed in 49 (6.23%) patients in the rivaroxaban group and in 55 (11.98%) patients in the warfarin group (HR: 0.469 in the rivaroxaban group; 95% CI: 0.314-0.702; P < 0.001). With respect to secondary efficacy and benefit endpoints, 28 (3.56%) patients in the rivaroxaban group and 22 (4.79%) patients in the warfarin group died, with an HR of 0.760 (95% CI: 0.435-1.329; P = 0.336); 32 (4.07%) patients in the rivaroxaban group; and 26 (5.66%) patients in the warfarin group had MI, with an HR of 1.940 (95% CI: 0.495-1.069, P = 0.254) in the rivaroxaban group.
CONCLUSIONS: Rivaroxaban is non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with high blood NVAF. Rivaroxaban is superior to warfarin in reducing fatal bleeding and bleeding in critical organs.
BACKGROUND: Chinese Clinical Trials Registry, identifier ChiCTR2100052454.

UNASSIGNED: This umbrella review aimed to understand the clinical benefits and adverse events associated with different modalities of intradialytic exercise in patients with end-stage renal disease undergoing hemodialysis.
UNASSIGNED: The search was performed until September 10th, 2020 on Scopus, Web of Science, the Cochrane Database, CINAHL, and PubMed.
UNASSIGNED: This umbrella review was conducted following the PRISMA guideline statement. The methodological quality of the reviews was assessed with the AMSTAR-2. Standardized mean differences with 95% confidence intervals were estimated. The I-squared statistic was used to assess heterogeneity and the Eggers\' test was performed to test asymmetry/small-study effects.
UNASSIGNED: Eleven reviews were included and 48 unique meta-analyses were examined. Nine were supported by suggestive evidence (P < 0.05, small heterogeneity, absence of small-study effects, and excess significance bias). Clinical benefits were found for functional capacity associated with aerobic exercise (d = 0.81; k = 6), resistance training (d = 0.58; k = 6), neuromuscular electrical stimulation (d = 0.70; k = 5), and inspiratory muscle training (d = 1.13; k = 2), measured by the distance covered in the 6-minutes walking test. This outcome was also associated with aerobic exercise (d = 0.28; k = 7) and combined exercise, measured by VO2peak (d = 1.01; k = 5) and by the duration of the cardiopulmonary test (d = 1.07; k = 4). Isometric quadriceps muscle strength improved with neuromuscular electrical stimulation (d = 1.19; k = 7) while patients\' perception of vitality improved with combined exercise (d = 0.60; k = 3).
UNASSIGNED: Suggestive evidence was found for the associations between various modalities of intradialytic exercise and functional capacity. Combined exercise was associated with improvements in physical and psychosocial variables. Few or no adverse events were reported.