Treatment Approaches Research Articles

Application framework and model of Jingjin therapy in rehabilitation medicine

The Jingjin therapy and rehabilitation medicine share commonalities and complement each other. The application of Jingjin therapy from a rehabilitation perspective can broaden the development path of traditional Chinese medicine (TCM) rehabilitation. This paper, based on relevant literature and research findings, elaborates on the connection between Jingjin syndrome differentiation acupuncture and rehabilitation assessment and treatment. It discusses the application framework of Jingjin's preventive treatment theory in disease prevention and rehabilitation, and forecasts the research model of Jingjin rehabilitation medicine from an integrative perspective of Chinese and western medicine. This study aims to improve the rehabilitation application thinking of Jingjin therapy and enrich the application methods and treatment approaches of TCM rehabilitation medicine.

СИНДРОМ ДЕФИЦИТА ВНИМАНИЯ С ГИПЕРАКТИВНОСТЬЮ В ПЕДИАТРИЧЕСКОЙ ПРАКТИКЕ

Attention deficit hyperactivity disorder (ADHD) is one of the most widespread forms of neurodevelopmental disorders. Modern clinical criteria for the ADHD diagnosis, issues of differential diagnosis in the pediatric practitioner’s routine (with asthenic syndrome in somatic diseases, primary sleep disorders, fetal alcohol syndrome, thyroid diseases) are described in the Article. The data of recent studies on the ADHD pathogenesis mechanisms are discussed as well. ADHD requires comprehensive treatment approach. The results of a multicenter randomized double-blind placebo-controlled clinical trial on the efficiency and safety of the new domestically produced medication, “Prospecta,” in the treatment of ADHD in children are presented.

Evaluation of Scoring Atopic Dermatitis (SCORAD) and scratching behavior in BALB/c mice treated with house dust mite immunotherapy

Allergen specific immunotherapy controls the reaction and builds immunological tolerance by giving an allergen in escalating doses. Research on immunotherapy in atopic dermatitis (AD) mouse model offers a new perspective on the approach of treatment in AD. This was an experimental study of 33 male BALB/c mice, 6-8 weeks old, divided into 3 groups (control, AD model, and house dust mite/HDM immunotherapy). The mice received spray and patch containing allergen extract of Dermatophagoides pteronyssinus. Immunotherapy was injected subcutaneously in increasing doses. The evaluation of SCORAD and scratching behavior were observed at the end of the treatment on day 93. The SCORAD of the model group that received HDM allergen had a mean of 1.27 ± 0.467 and the immunotherapy group had a mean of 0.36 ± 0.505. There were significant differences between the groups. The model group had a mean of 5.18 ± 4.119 and the immunotherapy group had mean of 1.55 ± 1.293. The statistical analysis showed that there were significant differences between control group and model group, as well as model group and immunotherapy group. Interobserver agreement was assessed and showed substantial agreement for SCORAD (ĸ = 0.613 and p < 0.001) and scratching evaluation (ĸ = 0.714 and p < 0.001). House dust mite immunotherapy significantly reduced SCORAD and scratching behavior in BALB/c mice compared to placebo groups.

Exploring the relationship between the Emotional Literacy Support Assistant (ELSA) intervention and whole-school approaches to wellbeing – a case study

ABSTRACT The Emotional Literacy Support Assistant (ELSA) intervention was designed to build the capacity of schools to support social and emotional needs. Within the current research base, there is little focus on the relationship between the ELSA intervention and its wider school context. This study adopted a qualitative single-case-study design to explore the relationship between the ELSA intervention and whole-school approaches to wellbeing in one primary school, hearing the voices of the ELSA, school staff, parents, and an assistant educational psychologist. Reflexive thematic analysis generated five key themes: conceptualisations of whole-school approaches and the ELSA role; communication and connection facilitate wider understanding and wrap-around support; this is the way we do things – enacting relational values across the whole school; organisational and leadership support as the foundation for successful ELSA work; and the importance of increasing wider support to meet needs. Findings indicate the importance of shared relational values and practices, with understanding and support for the ELSA intervention across the school community. The ELSA intervention becoming an embedded component of a whole-school approach to wellbeing appears to facilitate addressing pupils’ needs in context and allows ELSAs to use their skills, knowledge, and ways of being to contribute towards whole-school practice. Implications for practice are discussed for both educational professionals and educational psychologists.

The Effects of Rational Emotive Behavior Therapy, Progressive Muscle Relaxation, Distraction, and Rumination on State Anger Using the Autobiographical Essay Memory Task

ABSTRACT Given the many negative outcomes of anger, including physical aggression and violence, there is a need to improve treatment outcomes. As such, several treatment approaches were evaluated in this study. The autobiographical essay memory task (AEMT) was given to 157 participants on Amazon’s Mturk. Using a four (intervention) by three (state anger) mixed design, participants were randomly assigned to one of four conditions: control group (a distraction task), rumination, self-help Rational Emotive Behavior Therapy (REBT), or progressive muscle relaxation (PMR). All participants were instructed to write an anger-evoking memory for ten minutes. Following this, participants were then asked to partake in their respective intervention. Using the State Anger Scale from the State-Trait Anger Expression-2, state anger was measured at baseline, after writing about the anger-evoking memory, and post-intervention. As expected, there was a significant difference across the three time points, p < .001, η2 = .30. Once the AEMT was completed, participants received an intervention. Participants indicated lower levels of state anger post-intervention compared to post-AEMT, p < .001; however, participants post-intervention still reported higher levels of state anger compared to baseline, p < .001. Using the LSD post-hoc test, participants in the rumination condition reported higher levels of state anger post-intervention compared to participants who engaged in PMR (p < .001), self-help REBT (p = .04), and the control condition (p < .001). There were no significant differences noted between PMR, self-help REBT, and the control conditions post-intervention. The AEMT was an effective tool to evoke state anger in a lab setting. Additionally, self-help REBT, PMR, and distraction are effective tools to decrease state anger.

Contemporary Management of Acute Myeloid Leukemia: A Review.

Acute myeloid leukemia (AML) is a clonal hematopoietic cancer that disrupts normal hematopoiesis, ultimately leading to bone marrow failure and death. The annual incidence rate of AML is 4.1 per 100 000 people in the US and is higher in patients older than 65 years. Acute myeloid leukemia includes numerous subgroups with heterogeneous molecular profiles, treatment response, and prognosis. This review discusses the evidence supporting frontline therapies in AML, the major principles that guide therapy, and progress with molecularly targeted therapy. Acute myeloid leukemia is a genetically complex, dynamic disease. The most commonly altered genes include FLT3, NPM1, DNMT3A, IDH1, IDH2, TET2, RUNX1, NRAS, and TP53. The incidence of these alterations varies by patient age, history of antecedent hematologic cancer, and previous exposure to chemotherapy and/or radiotherapy for any cancer. Since 2010, molecular data have been incorporated into AML prognostication, gradually leading to incorporation of targeted therapies into the initial treatment approach of induction chemotherapy and subsequent management. The first molecularly targeted inhibitor, midostaurin, was approved to treat patients with AML with FLT3 variants in 2017. Since then, the understanding of the molecular pathogenesis of AML has expanded, allowing the identification of additional potential targets for drug therapy, treatment incorporation of molecularly targeted therapies (midostaurin, gilteritinib, and quizartinib targeting FLT3 variants; ivosidenib and olutasidenib targeting IDH1 variants, and enasidenib targeting IDH2), and identification of rational combination regimens. The approval of hypomethylating agents combined with venetoclax has revolutionized the therapy of AML in older adults, extending survival over monotherapy. Additionally, patients are now referred for hematopoietic cell transplant on a more rational basis. In the era of genomic medicine, AML treatment is customized to the patient's comorbidities and AML genomic profile.

Endovascular approaches for the treatment of dural carotid-cavernous fistulas: A systematic review.

Dural carotid-cavernous fistulas (dCCFs), also known as indirect carotid-cavernous fistulas, represent abnormal connections between the arterial and venous systems within the cavernous sinus that are typically treated via endovascular approach. We aim to investigate the clinical characteristics of patients with dCCFs based on the endovascular treatment approach and assess angiographic and clinical outcomes. A systematic review of the literature was performed. Data including number of patients, demographics, presenting clinical symptoms, etiology of fistula, Barrow classification, and embolization material were collected and evaluated. Outcome measures collected included degree of fistula occlusion, postoperative symptoms, complications, and mean follow-up time. A total of 52 studies were included examining four primary endovascular approaches for treating dCCFs: transarterial, transfemoral-transvenous (transpetrosal or other), transorbital (percutaneous or via cutdown), and direct transfacial access. Overall data was collected from 736 patients with 817 dCCFs. Transarterial approaches exhibit lower dCCF occlusion rates (75.6%) compared to transvenous techniques via the inferior petrosal sinus (88.1%). The transorbital approach via direct puncture or surgical cutdown offers a more direct path to the cavernous sinus, although with greater complications including risk of orbital hematoma. The direct transfacial vein approach, though limited, shows up to 100% occlusion rates and minimal complications. We provide a comprehensive review of four main endovascular approaches for dCCFs. In summary, available endovascular treatment options for dCCFs have expanded and provide effective solutions with generally favorable outcomes. While the choice of approach depends on individual patient factors and technique availability, traditional transvenous procedures have emerged as the first-line endovascular treatment. There is growing, favorable literature on direct transorbital and transfacial approaches; however, more studies directly comparing these general transvenous options are necessary to refine treatment strategies.

Consensus statement addressing controversies and guidelines on pediatric urolithiasis.

We aimed to investigate controversial pediatric urolithiasis issues systematically, integrating expert consensus and comprehensive guidelines reviews. Two semi-structured online focus group meetings were conducted to discuss the study's need and content, review current literature, and prepare the initial survey. Data were collected through surveys and focus group discussions. Existing guidelines were reviewed, and a second survey was conducted using the Delphi method to validate findings and facilitate consensus. The primary outcome measures investigated controversial issues, integrating expert consensus and guideline reviews. Experts from 15 countries participated, including 20 with 16+ years of experience, 2 with 11-15years, and 4 with 6-10years. The initial survey identified nine main themes, emphasizing the need for standardized diagnostic and treatment protocols and tailored treatments. Inter-rater reliability was high, with controversies in treatment approaches (score 4.6, 92% agreement), follow-up protocols (score 4.8, 100% agreement), and diagnostic criteria (score 4.6, 92% agreement). The second survey underscored the critical need for consensus on identification, diagnostic criteria (score 4.6, 92% agreement), and standardized follow-up protocols (score 4.8, 100% agreement). The importance of personalized treatment in pediatric urolithiasis is clear. Prioritizing low-radiation diagnostic tools, effectively managing residual stone fragments, and standardized follow-up protocols are crucial for improving patient outcomes. Integrating new technologies while ensuring safety and reliability is also essential. Harmonizing guidelines across regions can provide consistent and effective management. Future efforts should focus on collaborative research, specialized training, and the integration of new technologies in treatment protocols.

Clinical features, surgical management and outcome of squamous and basal cell carcinoma in squamates and chelonians.

Squamous cell carcinoma (SCC) is one of the most commonly diagnosed neoplastic disorders in reptiles. Recently, however, it has been demonstrated that basal cell carcinomas (BCCs) are frequently misclassified as SCCs. Several histological SCC and BCC variants have been characterised and their classification may allow the establishment of appropriate prognosis estimation and treatment approaches. To describe the clinical features and surgical outcomes of SCCs and BCCs diagnosed between 2010 and 2022 in reptiles. Thirty-three captive reptiles (21 squamates and 12 chelonians). Detailed clinical history, including staging and surgical outcomes, were performed. Statistical analysis assessed significant factors using Prism (v8.2.1). While SCC was predominantly diagnosed in lizards, BCC was most commonly diagnosed in chelonians, and both neoplasms mainly occurred in adult to aged, male individuals. Although the gross pathological findings were highly comparable between SCC and BCC, considerable variation could be seen according to the primary location (oral, cutaneous or epidermis of the shell). Humane euthanasia or noncurative intent surgeries were performed in a minority of the cases. Curative intent surgeries were successful in 19 of 27 cases during a 1- to 7-year follow-up period, yet recurrence was seen in 8 cases. The results of this study allowed the identification of significant high-risk prognostic factors for SCC and BCC in reptiles. This study contributes to predicting the clinical behaviour and prognosis of distinct SCC and BCC histological variants, and selecting the most appropriate treatment protocol.

Long-term outcomes and adaptive behavior in adult patients with Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy characterized by difficult-to-control seizures and cognitive dysfunction. Previous studies mainly focused on pediatric populations, and little is known about the long-term cognitive outcome in adult patients with LGS. The objective of this study was to investigate the long-term functional and adaptive behavior in adult patients with LGS. This cross-sectional study enrolled adult patients diagnosed with LGS according to the recently published International League Against Epilepsy (ILAE) diagnostic criteria. The adaptive behavior of participants was assessed using the Vineland Adaptive Behavior Scales, Survey Interview, Second Edition (VABS-II). Demographic, clinical, electroencephalography (EEG), and antiseizure medication (ASM) data were also collected at different timepoints, to investigate their association with VABS-II scores. The study included 38 adult patients with LGS. A low score on the Adaptive Behavior Composite Scale was found in all patients. When considering single VABS-II domains, particularly low scores were found in daily living skills and socialization, whereas slightly higher performances were observed in communication. An earlier age at LGS diagnosis was identified as the most significant predictor of worse adaptive outcomes in adult life. At the time of study evaluation, high seizure frequency, higher EEG background slowing, and multifocal EEG epileptiform abnormalities were significantly associated with lower VABS-II raw scores. Furthermore, in an exploratory correlation analysis with ASM regimen at the study visit, treatment with cannabidiol was associated with higher adaptive behavior scores, whereas benzodiazepine intake correlated with lower scores. This study provides relevant insights into the long-term challenges faced by adults with Lennox-Gastaut syndrome (LGS), highlighting significant impairments in adaptive behavior as well as the associated clinical and electroencephalography features. Additionally, this study provides a more specific neuropsychological profile in adults with LGS and underscores the importance of comprehensive care approaches that go beyond seizure control in this population. This study examined adults with Lennox-Gastaut syndrome (LGS), a severe type of epilepsy, to understand their long-term abilities to perform daily tasks and adapt socially. We found that these adults have significant difficulties with daily living and social skills, although not all areas were equally affected. They performed somewhat better in communication, particularly in understanding others (receptive communication). Importantly, the younger the age at which LGS was diagnosed, the worse their outcomes were as adults. This study highlights the need for research and treatment approaches that focus not only on controlling seizures but also on improving daily life skills.

IPSC-derived lung and lung cancer organoid model to evaluate cisplatin encapsulated autologous iPSC-derived mesenchymal stromal cell-isolated extracellular vesicles

BackgroundLung cancer remains a leading cause of cancer-related mortality globally. Although recent therapeutic advancements have provided targeted treatment approaches, the development of resistance and systemic toxicity remain primary concerns. Extracellular vesicles (EVs), especially those derived from mesenchymal stromal cells (MSC), have gained attention as promising drug delivery systems, offering biocompatibility and minimal immune responses. Recognizing the limitations of conventional 2D cell culture systems in mimicking the tumor microenvironment, this study aims to describe a proof-of-principle approach for using patient-specific organoid models for both lung cancer and normal lung tissue and the feasibility of employing autologous EVs derived from induced pluripotent stem cell (iPSC)-MSC in personalized medicine approaches.MethodsFirst, we reprogrammed healthy fibroblasts into iPSC. Next, we differentiated patient-derived iPSC into branching lung organoids (BLO) and generated patient-matched lung cancer organoids (LCO) from patient-derived tumor tissue. We show a streamlined process of MSC differentiation from iPSC and EV isolation from iPSC-MSC, encapsulated with 0.07 µg/mL of cytotoxic agent cisplatin and applied to both organoid models. Cytotoxicity of cisplatin and cisplatin-loaded EVs was recorded with LDH and CCK8 tests.ResultsFibroblast-derived iPSC showed a normal karyotype, pluripotency staining, and trilineage differentiation. iPSC-derived BLO showed expression of lung markers, like TMPRSS2 and MUC5A while patient-matched LCO showed expression of Napsin and CK5. Next, we compared the effects of iPSC-MSC derived EVs loaded with cisplatin against empty EVs and cisplatin alone in lung cancer organoid and healthy lung organoid models. As expected, we found a cytotoxic effect when LCO were treated with 20 µg/mL cisplatin. Treatment of LCO and BLO with empty EVs resulted in a cytotoxic effect after 24 h. However, EVs loaded with 0.07 µg/mL cisplatin failed to induce any cytotoxic effect in both organoid models.ConclusionWe report on a proof-of-principle pipeline towards using autologous or allogeneic iPSC-MSC EVs as drug delivery tests for lung cancer in future. However, due to the time and labor-intensive processes, we conclude that this pipeline might not be feasible for personalized approaches at the moment.

RTMS as a Next Step in Antidepressant Nonresponders: A Randomized Comparison With Current Antidepressant Treatment Approaches.

Although repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, little is known about the comparative effectiveness of rTMS and other treatment options, such as antidepressants. In this multicenter randomized controlled trial, rTMS was compared with the next pharmacological treatment step in patients with treatment-resistant depression. Patients with unipolar nonpsychotic depression (N=89) with an inadequate response to at least two treatment trials were randomized to treatment with rTMS or to a switch of antidepressants, both in combination with psychotherapy. Treatment duration was 8 weeks and consisted of either 25 high-frequency rTMS sessions to the left dorsolateral prefrontal cortex or a switch of antidepressant medication following the Dutch treatment algorithm. The primary outcome was change in depression severity based on the Hamilton Depression Rating Scale (HAM-D). Secondary outcomes were response and remission rates as well as change in symptom dimensions (anhedonia, anxiety, sleep, rumination, and cognitive reactivity). Finally, expectations regarding treatment were assessed. rTMS resulted in a significantly larger reduction in depressive symptoms than medication, which was also reflected in higher response (37.5% vs. 14.6%) and remission (27.1% vs. 4.9%) rates. A larger decrease in symptoms of anxiety and anhedonia was observed after rTMS compared with a switch in antidepressants, and no difference from the medication group was seen for symptom reductions in rumination, cognitive reactivity, and sleep disorders. Expectations regarding treatment correlated with changes in HAM-D scores. In a sample of patients with moderately treatment-resistant depression, rTMS was more effective in reducing depressive symptoms than a switch of antidepressant medication. In addition, the findings suggest that the choice of treatment may be guided by specific symptom dimensions.

Clinical characteristics and treatment approach of established New-Onset status epilepticus (eNOSE): A Real-World multicenter experience

IntroductionStatus Epilepticus (SE) can occur in patients without a previous epilepsy diagnosis, a condition identified as “new-onset status epilepticus” (NOSE). Treatment with benzodiazepine may fail in NOSE termination, requiring anti-seizure medication (ASM) employment. The term “established NOSE” (eNOSE) is generally employed in this context. This study aims to describe the main clinical characteristics of a large sample of patients suffering from eNOSE, compare the ASM efficacy, and explore the risk factors associated with ASM treatment unresponsiveness and eNOSE-associated mortality. MethodsAdult patients diagnosed with eNOSE were retrospectively selected between January 2016 and December 2022. We reviewed demographics, clinical data, diagnostic work-up, and treatment. We considered the last ASM introduced before the eNOSE termination as effective. Results123 patients were included (age: 67.9 ± 17.3). eNOSE acute etiology was mostly reported. In the overall cohort, phenytoin showed the highest response rate (p = 0.01). In the pairwise comparisons, valproate was superior to levetiracetam (p = 0.02) but not to lacosamide (p = 0.50). Phenytoin had a significantly higher resolution rate than levetiracetam (p = 0.001) but not lacosamide (p = 0.14). Thirty patients were refractory to ASM treatment. No predictors of refractoriness were identified. Thirty-nine patients died. Age and GCS were identified as eNOSE-related mortality risk factors. ConclusioneNOSE frequently has an acute etiology with several associated syndromes. Phenytoin is more effective in managing eNOSE, even though lacosamide, valproate, and levetiracetam can represent further therapeutic options. Age and GCS are the main risk factors for eNOSE-associated mortality.

Clinical Features, Psychiatric Comorbidities and Treatments in Childhood OCD in terms of OCD Severity, Age and Gender

Objective: The aim of this study was to investigate the clinical features, psychiatric comorbidities, and treatments of childhood obsessive-compulsive disorder (OCD), with consideration given to OCD severity, gender and age. Method: The study included 104 children and adolescents between the ages of 6 and 17 who were diagnosed with OCD and followed up in Child and Adolescent Psychiatry outpatient clinics between 2016 and 2023. The study examined the sociodemographic characteristics, clinical features, comorbid psychiatric disorders, and treatment approaches of children and adolescents with OCD. Results: The sample had a mean age of 13.1 ± 2.7 years, and the mean age at onset of OCD was 11.9 ± 2.7 years (range: 5-17 years). Those with mild OCD had a significantly lower mean age at presentation and onset of OCD compared to those with moderate and severe OCD (p=0.012, p=0.02, respectively). Patients with severe OCD had longer illness duration (p=0.009) and outpatient follow-up (p=0.004) compared to those with moderate OCD. Boys had significantly higher rates of family history of psychiatric disorders (p=0.006), attention-deficit/hyperactivity disorder/oppositional defiant disorder (p=0.003), and tic disorder (p=0.035) comorbidity rates than girls, while girls had higher rates of anxiety disorders (p=0.022) comorbidity. The study found that repeating and counting compulsions were more common in adolescents than in preadolescents (p=0.003, all). Conclusion: These results suggest that clinical presentation and comorbidity may vary with disease severity, gender and age, in children and adolescents with OCD. Early intervention is crucial to prevent clinical progression, worsening, and mental health sequelae.

Could a ring treatment approach be proposed to control Taenia solium transmission in a post elimination setting? A pilot study in Zambia.

Geographically targeted Taenia solium ring approaches consisting of treating individuals within a radius of 100-meter of a cysticercosis positive pig have been trialled in Peru. This study explored if a similar approach could be proposed to control T. solium transmission in a post elimination setting in Zambia, focussing on community members' willingness to be sampled and treated. The study was conducted in a community where elimination of active T. solium transmission was achieved. All eligible pigs and people were sampled, at 4- to 6-monthly intervals, followed by implementation of the ring treatment approach. This implied that whenever a pig was seropositive for cysticercosis during sampling, every human and pig residing in a radius of 50-meters of the seropositive pig would be treated. The results of the positive human stool samples were used to create the rings, whenever no pigs were positive. From June 2018 to October 2019, four samplings, followed by ring treatments were conducted. Between 84% and 91% of the willing people provided a stool sample, covering 46% to 59% of the total population living in the study area. Between 78% and 100% of the eligible pigs got sampled. Three ring treatments were based on porcine seropositivity and one on taeniosis results. Two to four rings were opened per sampling. During the ring treatments, between 89% and 100% of the eligible human and pig population living within a ring was treated. Participants were willing to participate and get treatment, once the rings were opened. However, the utility of ring treatment approaches in a post elimination setting needs further evaluation, given the lack of highly accurate diagnostic tools for porcine cysticercosis and the challenges in obtaining stool samples. The ring treatment approach adopted should be further improved before recommendations to public health authorities can be given.

The efficacy of Salvia-ligustrazine and Ligustrazine in treating gestational hypertension: A systematic review and meta-analysis.

Pregnancy-induced hypertension syndrome (PIH), a prevalent and critical condition, has garnered increasing attention due to its significant impact on maternal and fetal health outcomes. The conventional treatment approaches rely on magnesium sulfate and various antihypertensive drugs; however, the clinical efficacy of these treatments is limited, highlighting the need to explore alternative avenues for improvement. Recently, a growing number of clinical studies have investigated the use of Salvia-ligustrazine or Ligustrazine in combination with conventional therapy. A comprehensive synthesis and critical analysis of these studies is necessary to evaluate the efficacy and safety of Salvia-ligustrazine or Ligustrazine in treating PIH. We sought all articles published prior to December 2, 2023, from seven databases to identify randomized controlled trials (RCTs) that involved traditional Chinese medicine Salvia-ligustrazine or Ligustrazine in combination with Western medicines for the conventional treatment of PIH, according to predefined inclusion criteria. The studies were assessed using the Cochrane Risk of Bias tool (ROB2.0), and meta-analyses were conducted using Stata 15.0 statistical software. We analyzed 47 RCTs encompassing 4,517 patients. The results demonstrated that combining Salvia-ligustrazine or Ligustrazine with Western medications was more efficacious than using Western medications alone. This combination improved the overall response rate, reduced the incidence of adverse pregnancy outcomes for mothers and infants, and decreased the occurrence of side effects associated with PIH treatment. While we evaluated the efficacy of traditional Chinese medicine injections of Salvia-ligustrazine or Ligustrazine alongside conventional Western treatments, our conclusions must be considered provisional due to potential bias and the limited availability of RCTs.

Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections.

The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant (AMR) infections. This guidance document focuses on infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), AmpC β- lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa with difficult-to-treat resistance (DTR P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. This updated document replaces previous versions of the guidance document. A panel of six infectious diseases specialists with expertise in managing antimicrobial- resistant infections formulated questions about the treatment of infections caused by ESBL-E, AmpC-E, CRE, DTR P. aeruginosa, CRAB, and S. maltophilia. Because of differences in the epidemiology of AMR and availability of specific anti-infectives internationally, this document focuses on the treatment of AMR infections in the United States. Preferred and alternative suggested treatment approaches are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, transitioning to oral therapy, duration of therapy, and other management considerations are discussed briefly. Suggested approaches apply for both adult and pediatric populations, although suggested antibiotic dosages are provided only for adults. The field of AMR is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of AMR infections. This document is current as of December 31, 2023 and will be updated periodically. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance/.

Optimal Treatment Strategies for cT2 Staged Adenocarcinoma of the Esophagus and the Gastroesophageal Junction: A Multinational, High-volume Center Retrospective Cohort Analysis.

A multi-national high-volume center study was undertaken to evaluate outcomes after primary surgery (PS) or neoadjuvant treatment followed by surgery (NAT/S) in cT2 staged adenocarcinomas of the esophagus (EAC) and gastroesophageal junction (GEJ). Optimal treatment approach with either NAT/S or PS for clinically staged cT2cNany or cT2N0 EAC and GEJ remains unknown due to the lack of randomized controlled trials. Retrospective analysis of prospectively maintained databases from ten centers was performed. Between 01/2012-08/2023 645 patients who fulfilled inclusion criteria of GEJ Siewert type I, II or EAC with cT2 status at diagnosis underwent PS or NAT/S with curative intent. Primary endpoint was overall survival (OS). In the cT2cNany cohort 192 patients (29.8%) underwent PS and 453 (70.2%) underwent NAT/S. In all cT2cN0 patients (n=333), NAT/s remained the more frequent treatment (56.2%). Patients undergoing PS were in both cT2 cohorts older (P<0.001) and had a higher ASA classification (P<0.05). R0 resection showed no differences between NAT/S and PS in both cT2 cohorts (P>0.4).Median OS was 51.0 months in the PS group (95% CI 31.6-70.4) versus 114.0 months (95% CI 53.9-174.1) in the NAT/S group (P=0.003) of cT2cNany patients. For cT2cN0 patients NAT/S was associated with longer OS (P=0.002) and disease-free survival (DFS) (P=0.001). After propensity score matching of cT2N0 patients, survival benefit for NAT/S remained (P=0.004). Histopathology showed that 38.1% of cT2cNany and 34.2% of cT2cN0 patients were understaged. Due to unreliable identification of cT2N0 disease, all patients should be offered a multimodal therapeutic approach.

Laboratory-based measures of executive function and daily living skills in young children with Down syndrome: informing future interventions.

Adaptive behaviour refers to the practical skills necessary for independence and is considered a high-priority intervention target for children with neurogenetic conditions associated with intellectual disability, like Down syndrome (DS). Daily living skills (DLS) are a critical aspect of adaptive behaviour, but they have received little intervention attention, possibly because they involve a wide variety of skills across many settings. The present study aimed to advance DLS intervention science by examining the concurrent and longitudinal association between DLS performances and a cognitive skillset hypothesised to support DLS skill acquisition, executive function (EF). Participants were 71 children with DS between the ages of 2.5 and 8.7years (M=5.23years; standard deviation=1.65) who completed a battery of adapted EF tasks and a primary caregiver who completed the Vineland Adaptive Behavior Scales 3rd Edition Parent/Caregiver Comprehensive Report Form. A subset of caregivers also provided 6- and 12-month follow-up adaptive behaviour information. Results demonstrated a positive association between EF task performance and DLS standard scores and v-scores both concurrently and longitudinally. The findings have implications for potential future intervention approaches that aim to strengthen DLS performances by advancing EF skills in this population.

Molecular Features and Treatment Paradigms of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a common hematologic malignancy that is considered to be a disease of aging, and traditionally has been treated with induction chemotherapy, followed by consolidation chemotherapy and/or allogenic hematopoietic stem cell transplantation. More recently, with the use of next-generation sequencing and access to molecular information, targeted molecular approaches to the treatment of AML have been adopted. Molecular targeting is gaining prominence, as AML mostly afflicts the elderly population, who often cannot tolerate traditional chemotherapy. Understanding molecular changes at the gene level is also important for accurate disease classification, risk stratification, and prognosis, allowing for more personalized medicine. Some mutations are well studied and have an established gene-specific therapy, including FLT3 and IDH1/2, while others are being investigated in clinical trials. However, data on most known mutations in AML are still minimal and therapeutic studies are in pre-clinical stages, highlighting the importance of further research and elucidation of the pathophysiology involving these genes. In this review, we aim to highlight the key molecular alterations and chromosomal changes that characterize AML, with a focus on pathophysiology, presently available treatment approaches, and future therapeutic options.