Early Therapy Research Articles

Feasibility of Home-Based Early Infant Hybrid Therapy in Children with Unilateral Cerebral Palsy

Background: The first stage of childhood is characterized by great neuronal plasticity. In Unilateral Cerebral Palsy (UCP), it is essential to carry out early treatment, with family involvement. The aim of this study was to investigate the feasibility of Early Infant Hybrid Therapy (eI-Hybrid) applied at home with family involvement in children with UCP aged 9–18 months, and to assess its preliminary effectiveness on bimanual functional performance. Methods: A single group of 10 children (12.8 months, SD = 3.4) performed the eI-Hybrid therapy. The main outcome was measured with the mini Assisting Hand Assessment scale (mini-AHA), functional goals were measured with the Goal Attainment Scale (GAS), and satisfaction expectations on intensive therapy were also recorded. Three measures were performed (week 0, week 10, and month 6). A repeated-measures ANOVA test was performed on the mini-AHA in order to observe the statistically significant differences in pairwise comparison. Results: Ten children completed the study and the parents’ expectations were fulfilled, indicating high caregiver compliance and high adherence to the treatment. Clinically relevant changes were observed between pre- and post-intervention measurements in BFP (pre: 41.9 (SD: 7.7), post: 50.9 (SD: 6.0) and in the follow-up at 6 months (50.3 (SD:5.6); p < 0.001). Families reported a high satisfaction. Conclusions: infant hybrid treatment is feasible to be performed at home with the family’s involvement, obtaining improvements in the affected upper limb for early-age UCP.

Perceptions and Barriers to Outpatient Antiviral Therapy for COVID-19 and Influenza as Observed by Infectious Disease Specialists in North America: Results of an Emerging Infections Network (EIN) Survey, February 2024

Abstract Antiviral therapy is underutilized for outpatients at increased risk for severe COVID-19 or influenza. Results from this survey offer insights into treatment barriers from the infectious disease specialist perspective. Further education is needed about the benefits of early antiviral therapy.

Collaborative and side-by-side artmaking: reducing social isolation in refugee youth group art therapy

ABSTRACT Background Research on social isolation in refugee youth is important because it affects their sense of belonging, mental health and wellbeing; integration and acculturation into a new country; education; and future employment opportunities. There is limited art therapy research in Australia in this area, leaving a compelling gap in understanding the effectiveness of collaborative and side-by-side artmaking in group art therapy to connect refugee youth with their peers. Aims This study aimed to explore whether collaborative and side-by-side artmaking in group art therapy would connect youth more effectively; alleviate their social isolation from trauma, displacement and re-settlement experiences; provide a safe environment and platform to express themselves; and improve their mental health and wellbeing. Methods The triangular mixed-methods approach used standardised scales and semi-structured interviews to gather information from youth, teachers and art therapists. Mixed-method data analysis was applied using the Reliable Change Index, line graphs, descriptive statistics, and thematic analysis. Results Refugee youths’ self-esteem and confidence seemed to increase through collaborative and side-by-side artmaking. Results highlighted the importance of social connection, self-esteem, confidence and a sense of safety for making positive connections during artmaking. Conclusions Findings indicate potential benefits of pportunities for refugee youth to connect with their peers in the school environment and of group art therapy. Implications for practice and future research Opportunities could be achieved through collaborative and side-by-side artmaking in group art therapy. A larger study, longer programme and mixed populations in the school setting are recommended for future research. Plain-language summary The research aimed to examine if there was an effect of a six-week art therapy programme on social isolation for five 14–15-year-old female refugee youth. This research is important because social isolation affects youth’s mental health and wellbeing. Through creating art individually and next to each other (side-by-side artmaking), and creating artworks together (collaborative artmaking), the programme aimed to reduce social isolation and increase connections between youth during the sessions and in the school environment. The research was conducted in an early intervention creative therapies service onsite at a Queensland English-language transition secondary school. The service is provided by accredited art therapists and uses creative methods to support culturally diverse refugee youth in resettling, learning and recovering from trauma and stress. During the research, youth participants engaged in art activities, such as drawing and painting, while listening to music. Interventions were designed to establish group bonds, build self-esteem and resilience, and empower youth in a safe and supportive environment. Art therapists and teachers observed youth during the research period, completed standardised scales before and after the programme and participated in semi-structured interviews. The youth participants also completed standardised scales and were interviewed before and after the programme. The results showed that after the six-week programme, youths’ wellbeing and connections to each other increased. Three central themes were identified: (1) social connection is important within the school environment; (2) self-esteem and confidence are related to connecting to others and social isolation; and (3) there is a sense of safety in artmaking individually and collaboratively with peers. The study found that the art therapy programme positively affected youth mental health and wellbeing. This suggests the programme effectively reduced participants’ social isolation, potentially offering positive opportunities to connect other youth at risk of social isolation.

Fatal borealpox in an immunosuppressed patient treated with antivirals and vaccinia immunoglobulin - Alaska, 2023.

Borealpox virus (BRPV, formerly known as Alaskapox virus) is a zoonotic member of the Orthopoxvirus genus first identified in a person in 2015. In the six patients with infection previously observed BRPV involved mild, self-limiting illness. We report the first fatal BRPV infection in an immunosuppressed patient. A man aged 69 years from Alaska's Kenai Peninsula was receiving anti-CD20 therapy for chronic lymphocytic leukemia. He presented to care for a tender, red papule in his right axilla with increasing induration and pain. The patient failed to respond to multiple prescribed antibiotic regimens and was hospitalized 65 days postsymptom onset for progression of presumed infectious cellulitis. BRPV was eventually detected through orthopoxvirus real-time polymerase chain reaction testing of mucosal swabs. He received combination antiviral therapy, including 21 days of intravenous tecovirimat, intravenous vaccinia immunoglobulin, and oral brincidofovir. Serial serology was conducted on specimens obtained posttreatment initiation. The patient's condition initially improved with plaque recession, reduced erythema, and epithelization around the axillary lesion beginning one-week post-therapy. He later exhibited delayed wound healing, malnutrition, acute renal failure, and respiratory failure. He died 138 days postsymptom onset. Serologic testing revealed no evidence the patient generated a humoral immune response. No secondary cases were detected. This report demonstrates that BRPV can cause overwhelming disseminated infection in certain immunocompromised patients. Based on the patient's initial response, early BRPV identification and antiviral therapies might have been beneficial. These therapies, in combination with optimized immune function, should be considered for patients at risk for manifestations of BRPV.

Undifferentiated embryonal sarcoma of the liver masquerading as a cystadenoma in a young adult: a case report

BackgroundUndifferentiated embryonal sarcoma of the liver is an infrequent hepatic malignancy, primarily observed in the pediatric population. This neoplasm is exceedingly rare among adults. Despite its scarcity in adult cases, it remains imperative to accurately discern undifferentiated embryonal sarcoma of the liver utilizing diverse imaging modalities to prevent misdiagnosis with more prevalent benign and malignant hepatic masses. In this case, a comprehensive imaging examination was conducted, encompassing ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography–computed tomography scans. Notably, the positron emission tomography–computed tomography scan revealed 18F-fluorodeoxyglucose uptake characteristics indicative of malignancy, providing a pivotal clue for prompt diagnosis of undifferentiated embryonal sarcoma of the liver.Case presentationThis report presents the diagnostic procedure employed for a 37-year-old female patient of Han ethnicity in China diagnosed with undifferentiated embryonal sarcoma of the liver. The patient was admitted with a 2-day history of mid-upper quadrant abdominal pain. The patient’s temperature and inflammatory markers, such as white blood cell count and hypersensitive reactive protein, were slightly elevated. Ultrasound showed a cystic–solid nodule in the liver. The computed tomography revealed a cystic mass in the right lobe of the liver, characterized by a low-density shadow and a lack of significant enhancement during contrast-enhanced scanning, initially suggesting cystadenoma. Enhanced magnetic resonance imaging revealed a block-like abnormal signal shadow in the right hepatic lobe, suggestive of various etiologies, including benign lesions, cystadenoma with hemorrhage, or hemangioma with hemorrhage. However, the positron emission tomography–computed tomography showed increased 18F-fluorodeoxyglucose consumption within both the cystic wall and lesion, raising suspicion of malignancy. Surgical resection of the posterior hepatic lobe was performed under general anesthesia after comprehensive preoperative preparations. During the procedure, a space-occupying lesion was identified in the right posterior hepatic lobe, adhering to the diaphragm. Surface liver parenchyma overlying the tumor exhibited rupture, with several blood clots visible. The tumor was successfully and completely excised. Pathological examination revealed a fusiform cell tumor, necrosis, hemorrhage, cystic changes, cellular atypia, mitotic images, and eosinophilic globules suggestive of undifferentiated embryonal sarcoma of the liver. Immunohistochemical staining indicated CK (+), vimentin (Vim; +), Desmin (+), actin (−), α1-AT (+), GPC-3 (+), PDGFRa (+), MDM2 (+), P16 (+), Ki-67 (+) 30–35%, and PAS (+). The patient underwent five cycles of combination chemotherapy with ifosfamide and epirubicin, administered at 21-day intervals at our hospital. Following 3 years of postoperative surveillance, the patient remained stable, with no evidence of hepatic tumor recurrence.ConclusionOn the basis of this case and a comprehensive literature review, we recommend that clinicians consider the possibility of undifferentiated embryonal sarcoma of the liver in patients presenting with non-specific clinical and serological markers, particularly when there is inconsistency between ultrasound and computed tomography imaging findings, along with elevated 18F-fluorodeoxyglucose uptake observed in both the cystic wall and lesion on positron emission tomography–computed tomography examination. Given the rarity and high-grade malignancy of undifferentiated embryonal sarcoma of the liver, heightened clinical awareness and recognition are crucial for early diagnosis and successful therapy.

Malignancy Risk Associated with Radioactive Iodine Therapy for Graves’ Disease

BackgroundRadioactive iodine therapy (RAI) is a frequently chosen therapy for Graves’ disease. The aim of this study was to determine whether RAI for Graves’ disease increases the risk of thyroid malignancy. MethodsA retrospective analysis was performed of all Graves’ disease patients who underwent thyroidectomy at a single institution between 2013-2022. Comparative analyses were performed with cohorts based on RAI therapy as the primary grouping variable. Results413 patients were identified, of which 38 received RAI prior to surgery. RAI treated patients were more likely to undergo surgery for known malignancy or indeterminate nodules. RAI patients were also more likely to have malignancies larger than 1cm. Among RAI treated patients, those who developed malignancy were older at the time of Graves’ diagnosis and received early RAI therapy. ConclusionsUse of RAI for treatment of Graves’ disease increases the progression of thyroid carcinoma, but not the prevalence. Older age and early RAI therapy may be risk factors for malignancy in RAI treated patients.

Early augmentation therapy with dextromethorphan in mild to moderate major depressive disorder: A group sequential, response adaptive randomized controlled trial

Early augmentation therapy with dextromethorphan in mild to moderate major depressive disorder: A group sequential, response adaptive randomized controlled trial

Association between differentiated HIV care delivery model and low-level viremia among people living with HIV in Rwanda

BackgroundLow-level viremia (LLV) (HIV-RNA 51–999 copies/mL) is associated with increased risk of non viral load suppression (HIV-RNA ≥ 1000 copies/mL). We assessed the association between differentiated service delivery model (DSDM) and LLV among people living with HIV (PLHIV) in Rwanda.MethodsWe conducted a retrospective cohort analysis using routinely collected data of adults living with HIV from 28-healthcare facilities in Rwanda before and after the introduction of DSDM. Under DSDM, PLHIV initiated treatment within seven days of HIV diagnosis and medication pick-up up to six months for those with sustained viral load suppression suppression. Proportions of LLV at 6,12 and 18 months were quantified. Multivariable log binomial regression models were used to assess the effect of DSDM on LLV. To handle missing data, multiple imputations was performed.ResultsOf 976 people living with HIV, 645(66.0%) were female and 463(47.4%) initiated treatment during DSDM. The median age was 37 (interquartile range: 32–43) years. LLV was 7.4%, 6.6% and 5.4%, at 6,12 and 18 months, respectively. Compared to those who initiated treatment before DSDM, starting treatment during DSDM increased six-month LLV [adjusted risk ratio (aRR) = 2.8: 95%CI (1.15–6.91)] but not at 12 [aRR = 2.3: 95%CI (0.93–5.75)] and 18 months [aRR = 0.3: 95%CI (0.09–1.20)]. Using imputed datasets, the association between DSDM and LLV persisted.ConclusionsDSDM was associated with increased risk of LLV at 6-months. possibly due to the minimal amount of time PLHIV had in pondering and accepting the HIV diagnosis. Continued support is needed among people receiving early antiretroviral therapy initiation to prevent development of LLV.

Convalescent plasma therapy for COVID-19 – Donor selection strategies and establishment of a plasma bank

BackgroundEarly in the COVID-19 pandemic, convalescent plasma (CP) emerged as a potentially effective treatment neutralising SARS-CoV-2. Early CP therapy with high neutralising antibody (NAb) titre may benefit COVID-19 outpatients and, in sufficient quantities even some hospitalised patients. This study details the process of setting up a CP bank, containing high- and low-titre CP for a clinical trial. Study design and methodsWe identified 18–65-year-old convalescents with SARS-CoV-2 NAb titres of ≥1:40 in microneutralisation test (MNT). Following eligibility pre-screening, the Finnish Red Cross Blood Service (FRCBS) determined suitability as CP donors. ResultsOf the 6466 COVID-19 convalescents contacted, 1481 provided serum, with 851 (57.5 %) exhibiting NAb titres ≥1:40. Participation barriers included reluctance, advanced age and, for women, insufficient body size. Of the volunteers, 125 were evaluated at FRCBS, with major exclusions for HLA antibodies (42 women), interferon antibodies (five men), and NAb titres waning below 1:20 (16 participants). Finally, 70 underwent plasmapheresis, resulting in 50 suitable CP donors (0.8 % of initial contacts and 3.4 % of those tested for NAb). DiscussionThe process of setting up a CP bank proved challenging. Excessive laboratory workloads during a pandemic hamper their ability to conduct MNT, underscoring the need for rapid screening tests. Only a small proportion of our convalescents exhibited high-titre CP, this fraction declining over time because of waning immunity. Strict plasmapheresis criteria further constrained donor eligibility. Establishing a plasma bank requires meticulous planning to maximize efficiency. Detailed insights from current experiences may prove critical in future pandemics before other remedies and vaccines become available.

Vector of glycated hemoglobin in the formation of dysglycemia in postmenopause: Emphasis on early diagnosis and therapy

Introduction. The close relationship of postmenopause with insulin resistance (IR) and metabolic syndrome (MetS) marks a high cardiometabolic risk of dysglycemia, determining the need for its early diagnosis and therapy. Pathogenetically substantiated criteria for the diagnosis of prediabetes and the nature of early drug therapy for type 2 diabetes mellitus (T2DM) are debated. Information on the relationship between glucose homeostasis parameters and menopausal MetS is fragmentary.Aim. To evaluate the associations of glycated hemoglobin (HbA1c) levels with indices of IR, β-cell function and MetS character- istics in a cohort of postmenopausal women with different carbohydrate metabolic states.Materials and methods. In 94 Caucasian postmenopausal women 58.0 (53.0; 63.0) years old the following were determined: HbA1c, fasting glycemia (FG), TyG and HOMA2 indices, C-peptid, BMI, waist circumference (WC), blood pressure (BP), triglycerides (TG), HDL-C levels. When classifying women by HbA1c (ADA criteria), 15 had normoglycemia, 24 prediabetes, 55 T2DM. ME (25–75%) was assessed using SPSS (version 17); intergroup differences according to the Mann – Whitney test; Spearman and partial correlation analysis were performed.Results. HbA1c age independently correlated with IR parameters: TyG (R = 0.590; p < 0.001), HOMA2-IR (R = 0.318; p < 0.05) and beta cell function: HOMA2-B (R = -0.355; p < 0.001); with lipid markers of MetS (TG, HDL-C, respectively R = 0.382; -0.448; p < 0.001), anthropometric and blood pressure levels.Conclusion. Associations of HbA1c in postmenopausal women with a spectrum of glucose homeostasis parameters and MetS mark it as a vector of formation and progression of dysglycemia due to a close connection with the functional state of β-cells and the importance of lipoglucotoxicity in the dynamics of postmenopausal IR. The obtained data pathogenetically determine the use of HbA1c in the verification of dysglycemia and the early administration of combined antihyperglycemic therapy aimed at preserving β-cell function. The potential of dipeptidyl peptidase-4 inhibitors in slowing the progression of type 2 diabetes mellitus is considered

Peritonitis-related bacterial infections: a large-scale case-series retrospective study in 160 domestic animals (2009-2022).

Bacterial peritonitis infections comprise a life-threatening clinical condition in domestic animals that commonly lead to sepsis and high mortality. A set of bacterial pathogens have been identified in septic peritonitis in livestock and companion animals. Nonetheless, most descriptions are restricted to case reports or limited to only one domestic species, and a restrict number of comprehensive studies involving this infection has focused on a great number of domestic animals. Here, we retrospectively investigated selected epidemiological data (with an emphasis in outcome), clinical signs, bacteriological culturing, and in vitro antimicrobial susceptibility patterns of microorganisms isolated of peritoneal fluid from 160 domestic animals (2009-2023) compatible with septic peritonitis. Bacteria were isolated from 71.9% (115/160) of the peritoneal fluid from 75 dogs (75/115 = 65.2%), 22 cats (22/115 = 19.1%), 14 horses (14/115 = 12.2%), and 4 cattle (4/115 = 3.5%). Among animals with bacterial isolation, Escherichia coli (34/115 = 29.6%), alfa-hemolytic Streptococcus (12/115 = 10.4%), Staphylococcus aureus (8/115 = 6.9%), beta-hemolytic Streptococcus (7/115 = 6.1%), and Pasteurella multocida (6/115 = 5.2%) were predominant in pure culture, in addition to a miscellaneous of other bacteria isolated in minor frequency, e.g., Pseudomonas sp., Trueperella pyogenes, Klebsiella pneumoniae, and Salmonella sp. In general, in vitro susceptibility tests of isolates revealed that florfenicol, chloramphenicol, and amoxicillin/clavulanic acid showed moderate effectivity (≥ 60%). Conversely, most of isolates exhibited resistance mainly to trimethoprim/sulfamethoxazole, enrofloxacin, and penicillin (> 60%). Additionally, multidrug resistance was found in 42.6% (49/115) of the isolates. Data related to the outcome were available in 37.4% (43/115) of animals that had bacterial isolation and, from these, the mortality rate was 79.1% (34/43), with a significant association (p < 0.036) between mortality and septic peritonitis by gram-negative bacteria. Neoplasia (7/43 = 16.3%), pneumonia/pulmonary abscess (5/43 = 11.6%), hepatitis (5/43 = 11.6%), metritis/pyometra (4/43 = 9.3%), and gall bladder rupture (3/43 = 7%) represented the probable main sources of septic peritonitis. Anorexia (34/115 = 29.6%), emesis (29/115 = 25.2%), lethargy (26/115 = 22.6%), respiratory distress (25/115 = 21.7%), ascites (20/115 = 17.4%), and fever (19/115 = 16.5%) were the most frequent clinical signs among animals with bacterial isolation. A variety of bacteria were isolated in the peritoneal fluid of animals, with a predominance of Enterobacteriaceae, streptococci, and staphylococci, highlighting the opportunistic nature of the pathogens in septic peritonitis. High in vitro multidrug resistance of isolates and high mortality of animals reinforce the need for early diagnosis and therapy based on the in vitro antimicrobial profile of the pathogens involved in septic peritonitis. Our results contribute to the etiological characterization, clinical-epidemiological findings, and vigilance of multidrug-resistant bacteria in septic peritonitis among livestock and companion animals.

Early Conservative Physical Therapy Management of Babies With Obstetric Brachial Plexus Injury to Facilitate Spontaneous Recovery.

To evaluate the effect of early immobilization and proper handling techniques in infants with Obstetric Brachial Plexus Injury (OBPI) in the first 2weeks of life. Six 1-day-old infants (2 males and 4 females) with OBPI were included. The assessments were done at baseline, post-intervention, and 3-month follow-up, which involved a physical exam, Narakas classification, Active Movement Scale, and gross and fine motor skills evaluation. All infants had upper Erb's palsy. They had statistically significant improvement in the Active Movement Scale scores post-intervention with a large effect size. These improvements were maintained at follow-up. All infants achieved age-appropriate gross and fine motor skills with the affected upper limb at 3months of age. Early conservative physical therapy management had a statistically significant effect on enhancing spontaneous recovery and preventing further nerve injury in OBPI infants.

Resilience, Mental Health, Sleep, and Smoking Mediate Pathways Between Lifetime Stressors and Multiple Sclerosis Severity

Introduction: Lifetime stressors (e.g., poverty, violence, discrimination) have been linked to features of multiple sclerosis (MS); yet mechanistic pathways and relationships with cumulative disease severity remain nebulous. Further, protective factors like resilience, that may attenuate the effects of stressors on outcomes, are seldom evaluated. Aim: To deconstruct pathways between lifetime stressors and cumulative severity on MS outcomes, accounting for resilience. Methods: Adults with MS (N = 924) participated in an online survey through the National MS Society listserv. Structural equation modeling was used to examine the direct and indirect effects of lifetime stressors (count/severity) on MS severity (self-reported disability, relapse burden, fatigue, pain intensity, and interference) via resilience, mental health (anxiety and depression), sleep disturbance, and smoking. Results: The final analytic model had an excellent fit (GFI = 0.998). Lifetime stressors had a direct relationship with MS severity (β = 0.27, p &lt; 0.001). Resilience, mental health, sleep disturbance, and smoking significantly mediated the relationship between lifetime stressors and MS severity. The total effect of the mediation was significant (β = 0.45). Conclusions: This work provides foundational evidence to inform the conceptualization of pathways by which stress could influence MS disease burden. Resilience may attenuate the effects of stressors, while poor mental health, smoking, and sleep disturbances may exacerbate their impact. Parallel with usual care, these mediators could be targets for early multimodal therapies to improve the disease course.

Community-Associated MRSA—Not So Innocent Sibling per Se: A Case Report

Background: Methicillin-resistant S. aureus (MRSA) is a major healthcare burden and is classified as healthcare-associated (HA-MRSA) and community-associated (CA-MRSA). While HA-MRSA is clinically feared, CA-MRSA is often considered less pathogenic. This case report highlights the serious course of illness due to CA-MRSA infection and provides a treatment strategy for the management of such cases. Case description: A 41-year-old male presented with fever and breathlessness for five days. Upon admission, he was provided empirical treatment for atypical infections and vasopressor support for hypotension. His condition deteriorated, necessitating ventilator support. Although the initial tracheal Bio Fire test indicated MRSA, his clinical manifestations did not match MRSA pneumonia symptoms; however, CA-MRSA was confirmed within 12 h. Skin legions developed within 16 h and progressed gradually from ecchymosis, petechial, and palpable purpura to bullous lesions over 72 h. The antibiotic regimen was modified and optimized with the addition of Clindamycin, Vancomycin, and Meropenem–Colistin. Owing to high IL-6 levels, dual vasopressor support, and acute kidney failure, he was started on early (within 12 h) continuous renal replacement therapy (CRRT) with CytoSorb filter (for 3 days) for cytokine removal. IL-6 levels decreased after two days of CytoSorb use. Subsequently, the patient stabilized with reduced dependence on vasopressor and ventilator assistance. Discussion: Early diagnosis of CA-MRSA and management with CRRT using CytoSorb may help improve patient outcomes. To our knowledge, this is the first report of clinical management of CA-MRSA with CytoSorb therapy in India that resulted in positive outcomes.

Sympathetic Ophthalmia: A Comprehensive Update

Introduction: Although sympathetic ophthalmia (SO) rarely occurs, it is still considered as a harmful condition that requires early recognition and aggressive therapy to maintain or improve visual outcome. Objective: This review aims to provide recent information regarding etiopathogenesis, clinical manifestation, diagnosis, and SO treatment as well. Methodology: Articles were identified from databases using keywords combination of (“Sympathetic Ophthalmia” AND “Clinical Features” AND “Diagnosis” AND “Treatment”). Conclusion: SO is an underdiagnosed vision-injuring disease. Therefore, early detection and adequate treament of SO are needed as the main principle for successful SO management. Keywords: Sympathetic ophthalmia, Clinical features, Diagnosis, Treatment

Early antiplatelet therapy after intravenous thrombolysis for acute ischemic stroke: a systematic review and meta-analysis.

Early neurological deterioration (END) and recurrence of vessel blockage frequently complicate intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). Several studies have indicated the potential effectiveness of the early initiation (within < 24 h) of antiplatelet therapy (APT) after IVT. However, conflicting results have been reported by other studies. We aimed to offer a thorough overview of the current literature through a systematic review and meta-analysis. Our systematic review and meta-analysis were prospectively registered on PROSPERO (ID: CRD42023488173) following the PRISMA guidelines. We systematically searched Web of Science, SCOPUS, PubMed, and Cochrane Library until May 5, 2024. Rayyan. ai facilitated the screening process. The R statistical programming language was used to calculate the odds ratios and conduct a meta-analysis. Our primary outcomes were excellent functional recovery (modified Rankin Scale score 0-1), symptomatic intracranial hemorrhage (sICH), and mortality. Eight studies involving 2,134 participants were included in the meta-analysis. Early APT showed statistically significant increased odds of excellent functional recovery (mRS 0-1) compared to the standard APT group (OR, 1.81; [95% CI: 1.10, 2.98], p = 0.02). However, we found no differences between the early and standard APT groups regarding sICH (OR, 1.74; [95% CI: 0.91, 3.33], p = 0.10) and mortality (OR, 0.88; [95% CI: 0.62, 1.24]; p = 0.47). Early APT within 24 h of IVT in stroke patients is safe, with no increase in bleeding risk, and has a positive effect on excellent functional recovery. However, there was a statistically insignificant trend of increased sICH with early APT, and the current evidence is based on highly heterogeneous studies. Further large-scale RCTs are warranted.

Strike early-strike strong lipid-lowering strategy with PCSK9i in ACS patients. Real-world evidence from AT-TARGET-IT registry

Abstract Background/Introduction No data are available on early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with acute coronary syndrome (ACS) in real-world. Purpose This study investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. Methods The lipid control outcome was the percentage of patients reaching the LDL-C target of &amp;lt; 55 mg/dL at first lipid control. The clinical outcome was the incidence of composite major CV events (all cause death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization) during follow-up in relation to quartiles of LDL-C at first lipid control. Results We included 771 patients with ACS from AT-TARGET-IT registry, receiving PCSK9i prescription during hospitalization or at discharge. Median LDL-C was 137 mg/dL and decreased to 43 mg/dL at first lipid control. 527 (68.3%) patients achieved LDL-C target at the first lipid control at a median time of 37 days from hospitalization; of them, 404 (76.8%) were discharged on statin plus ezetimibe background therapy. Event curves through a median follow-up of 11 months across quartiles of LDL-C showed a stepwise lower risk of 4P-MACE, 3P-MACE, all-cause mortality, and ischemia-driven revascularization in lower quartile of LDL-C values at first lipid control (&amp;lt;23 mg/dL) and in patients reaching LDL-C &amp;lt;55 mg/dL. Conclusions Intensive and early lipid-lowering therapy using PCSK9i in patients with ACS (strike early strike strong strategy) is safe and effective in clinical practice and associated with a reduction of residual CV risk.

Association between hs-CRP/HDL-C ratio and three-month unfavorable outcomes in patients with acute ischemic stroke: a second analysis based on a prospective cohort study

ObjectiveThe associations between the ratio of blood high-sensitivity C-reactive protein (hs-CRP) to high-density lipoprotein cholesterol (HDL-C) (hs-CRP/HDL-C ratio) and outcomes in patients with acute ischemic stroke (AIS) have yet to be established. This study is the first to examine the relationship between the hs-CRP/HDL-C ratio and three-month unfavorable outcomes in patients with AIS.MethodsThis secondary analysis utilized data from a prospective cohort study involving 1559 AIS patients recruited at a South Korean hospital between January 2010 and December 2016. We constructed a binary logistic regression model to explore the association between the hs-CRP/HDL-C ratio and unfavorable outcomes in patients with AIS. An attempt was made to use a generalized additive model (GAM) with smooth curve fitting to elucidate potential nonlinear interactions. Furthermore, inflection points were identified via a recursive method, and binary logistic regression models were developed for each side of these inflection points. Ultimately, a log-likelihood ratio test was used to identify the most appropriate model for explaining the connection between the hs-CRP/HDL-C ratio and unfavorable outcomes in patients with AIS.ResultsThe incidence of unfavorable outcomes was 24.5%, with a median hs-CRP/HDL-C ratio of 3.64. After accounting for other factors, the binary logistic regression model revealed a statistically significant positive association between the hs-CRP/HDL-C ratio and the likelihood of poor outcomes in AIS patients (OR = 1.013, 95% CI: 1.005–1.022; P = 0.002). A nonlinear relationship was observed, with the first inflection point of the hs-CRP/HDL-C ratio at 42.74. Each 1-unit increase in the hs-CRP/HDL-C ratio was associated with a 2.4% greater risk of unfavorable outcomes (OR = 1.024, 95% CI: 1.011–1.038, P < 0.001).ConclusionThis study provides evidence of a positive and nonlinear correlation between the hs-CRP/HDL-C ratio and poor three-month functional outcomes in AIS patients. When the hs-CRP/HDL-C ratio was less than 42.74, a positive association was observed with the risk of unfavorable outcomes. This finding offers a reference for optimizing early individualized therapy and aids in clinical counseling for patients with AIS.

Guideline-directed medical therapy and in-hospital mortality in acute coronary syndrome patients with advanced renal dysfunction

Abstract Background It is unclear whether early (initiated within 24 hours of admission) guideline-directed medical therapy [GDMT, i.e., the combined use of β-blocker, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, dual antiplatelet drugs and statin] could benefit acute coronary syndrome (ACS) patients with advanced renal dysfunction [estimated glomerular filtration rate (eGFR) &amp;lt; 30 mL/min/1.73 m2]. Objectives The purpose of this study was to verify whether GDMT could improve in-hospital mortality in ACS patients with advanced renal dysfunction. Methods This study included 3,288 and 3,520 ACS patients with admission with advanced renal dysfunction from the CNEDSSP and CCC-ACS cohorts, respectively. Multivariable-adjusted analysis and propensity score matching (PSM) were employed to assess the impact of GDMT on in-hospital mortality. Results In a pooled analysis of the CNEDSSP and CCC-ACS cohorts, early GDMT was associated with significantly lower in-hospital mortality (relative ratio [RR]: 0.62, 95% CI: 0.47 to 0.81). PSM revealed an attenuation of the association of in-hospital mortality with early GDMT in ACS patients, with statistically significant associated reductions observed only in myocardial infarction (MI) patients (hazard ratio [HR]: 0.45, 95% CI: 0.27 to 0.75 in CNEDSSP cohort; HR: 0.48, 95% CI: 0.27 to 0.84 in CCC-ACS cohort). A random-effect pooled analysis for MI patients with admission advanced renal dysfunction demonstrated a 56% lower in-hospital mortality among GDMT users (RR: 0.44, 95% CI: 0.31 to 0.65). Conclusions This nationwide study highlights that early GDMT is associated with a reduced risk of in-hospital mortality in ACS patients (particularly in MI patients) with advanced renal dysfunction.

Management of children with heterozygous familial hypercholesterolemia worldwide: a meta-analysis

Abstract Background HeFH is one of the most frequent monogenic disorders in the world, leading to premature ASCVD. Purpose The aim of this meta-analysis was to evaluate the efficacy and safety of lipid lowering therapy (LLT) and achievement of LDL-C goal in heFH children. Methods The main endpoint was efficacy of goal achievement for LDL-C and other lipid parameters: total cholesterol [TC], triglycerides [TG], high density lipoprotein cholesterol [HDL-C], apolipoprotein B [apo B] and lipoprotein(a) [Lp(a)]), and the LLT safety (adverse events [AEs], including endocrine function, and growth indices). The secondary endpoint was an effect of LLT on attainment of LDL-C goal treatment (&amp;lt;3.5 mmol/L/130 mg/dL). Results A total of 41 studies with 4667 pediatric patients at mean age 12.08±2.4 years were included. At median follow-up of 18.8 months, the group on LLT had significantly higher mean reductions of TC, LDL-C, TG, and increased HDL-C compared to control (-1.75 [-67,7 mg/dl], -1.84 [-71.2 mg/dl], -0.11 [-9.74 mg/dl], 0.08 mmol/L [3.1 mg/dl], respectively, p&amp;lt;0.001 for all). In the subgroup analysis according to different types of LLT we observed a significantly higher mean reduction of LDL-C by statin combined with ezetimibe treatment, followed by PCSK9 inhibitors, statins in monotherapy, and monotherapy with ezetimibe (-2.48 [-95.9 mg/dl], -2.16 [-83.5 mg/dl], -2.03 [-78.5 mg/dl], and -1.50 mmol/L [-58 mg/dl], respectively, test for overall effect: p&amp;lt;0.001). The pooled LDL-C was reduced by 33.44% (-2.14 mmol/L [-82.8 mg/dl], p&amp;lt;0.001) and failed to reach the goal treatment (&amp;lt;3.5 mmol/L) by 12.6% (95%CI, 12.4 – 12.9%). 38.7% of children achieved the LDL-C goal, 23.9% fell short by up to 10%, 10.7% experienced moderate failure (were over the LDL-C target between &amp;gt;10-20%), and 26.7% failed by more than 20% to reach the LDL-C target. When comparing different regions, only Sweden and Greece achieved the LDL-C goal &amp;lt;3.5 mmol/L in the follow-up, followed by the Netherlands, Norway, Poland, USA, UK, France, Spain, Belgium, and Austria (with the following additional required LDL-C reduction to be on the goal: 2.2%, 3.4%, 3.5%, 8.9%, 10.2%, 11.2%, 11.2%, 15%, 19.4%, respectively). For other investigated countries over 20% mean LDL-C reduction was required. All parameters related to endocrine function and demographic indices were unaffected by LLT therapy (p&amp;gt;0.05). The adverse events were not reported significantly higher when compared to the control and the prevalence of therapy discontinuation was only 0.8%. Conclusions Despite the efficacy of LLT in children with HeFH and the low occurrence of discontinuation-related adverse events, achieving LDL-C treatment goals was relatively rare, with large differences between the investigated countries. These results underscore the importance of considering early combination therapy of statins and ezetimibe, and PCSK9 inhibitors (if available) to attain LDL-C goals effectively.Lipoproteins reduction with LLT.Goal achievement and therapy safety.