Gallbladder cancer (GBC) is a highly aggressive malignancy of the digestive system with a poor prognosis. Therefore, the development of effective targeted therapeutic strategies is critical for improving survival outcomes in patients with GBC. Erb-B2 receptor tyrosine kinase 2 (ERBB2) is a proto-oncogene whose overexpression or mutation has been closely linked to the initiation and progression of various cancers. Whole-exome sequencing (WES) was performed on tumor tissue from a patient with advanced GBC who underwent conversion surgery following combination therapy with the multi-targeted tyrosine kinase inhibitor anlotinib and the PD-1 immune checkpoint inhibitor camrelizumab, to identify potential genomic alterations associated with treatment response. Transcriptomic profiling was conducted in cell lines transfected with plasmids encoding either wild-type ERBB2 or the I655V mutant. Western blot analysis was used to assess activation of the downstream PI3K-AKT and MAPK-ERK signaling pathways and to measure PD-L1 expression levels. Bioinformatic analyses were employed to predict the structural and functional consequences of the ERBB2 I655V mutation. WES revealed that the ERBB2 I655V mutation may be associated with therapeutic response. Mechanistically, the I655V substitution resides within the GG4-like motif of the ERBB2 transmembrane domain and may alter the transmembrane dimerization interface, potentially promoting heterodimer formation with other ErbB family members and leading to enhanced downstream signaling. Transcriptome sequencing and in vitro experiments demonstrated that the ERBB2 I655V mutation constitutively activates ERBB2, resulting in sustained activation of the PI3K-AKT and MAPK-ERK pathways. This subsequently upregulates PD-L1 expression and contributes to an immunosuppressive tumor microenvironment, which may underline the observed clinical response to combined targeted and immunotherapy. The ERBB2 I655V mutation may be associated with improved treatment response to immunotherapy in gallbladder cancer.

Hematology patients are highly susceptible to severe bacterial infections, particularly those caused by multidrug-resistant (MDR) gram-negative pathogens, which are associated with significant morbidity and mortality. Eravacycline, a novel fluorocycline antibiotic, demonstrates broad-spectrum activity against MDR bacteria. This real-world study aimed to evaluate the effectiveness and safety of eravacycline in Chinese hematology patients. In this multicenter, retrospective study, hematology patients receiving ≥3 days of eravacycline between September 2023 and September 2024 were included. The outcomes included clinical response rate, microbiological response rate, and safety. Of 796 patients included, most had hematological diseases (94.6%) and recent chemotherapy or radiotherapy (80.2%). The most common infection was pneumonia (57.4%), and sputum (47.2%) was the most frequent specimen type for pathogen isolation. Among 481 patients with microbiological examination results, Klebsiella pneumoniae (30.5%) and Acinetobacter baumannii (17.4%) were predominant. The mean time to defervescence was 3.2 ± 2.1 days. The overall clinical response rate was 88.8%, with response rates of 84.0% in bloodstream infections and 87.5% in pulmonary infections. Microbiological response rate at the end of treatment was 90.7%. Eravacycline exhibited high susceptibility rates across A. baumannii (95.8%), K. pneumoniae (94.3%), and Staphylococcus aureus (100.0%). Only 2.5% of patients reported adverse events. Subgroup analysis showed that pulmonary diseases (P = 0.006), sepsis (P = 0.003), and duration ≤7 days (P < 0.001) of eravacycline 1 mg/kg/12 h were significantly associated with poorer clinical response rate at the end of treatment. Eravacycline demonstrated promising effectiveness and safety in treating infections of patients from the hematology department.

Asthma is a prevalent chronic inflammatory disease in childhood, associated with high morbidity and impact on quality of life. The clinical variability of symptoms can make diagnosis difficult, making a detailed analysis of the clinical profile essential for proper management. The clinical and epidemiological profile of children diagnosed with asthma who were followed in an immunoallergology outpatient clinic of a university hospital was obtained. This was an observational, retrospective, and descriptive study, conducted through the analysis of 30 medical records of pediatric patients diagnosed with asthma. Demographic variables, initial symptoms, allergic comorbidities, family history, hospitalizations, laboratory tests (total and specific IgE, immediate reading skin test), spirometry, and instituted treatment were evaluated. The data was organized in spreadsheets and analyzed using descriptive statistics. The average age of the patients was 7.6 years, with a predominance of illnesses. The most frequent symptoms were recurrent dry cough, wheezing, and exertional dyspnea, with functional impact such as school absenteeism. A family history of allergic diseases was present in 76.6% of cases. A high prevalence of allergic comorbidities was observed, suggesting atopic march. Patients with positive allergy tests showed greater clinical severity and a higher number of hospitalizations. Spirometry revealed mild to moderate obstructive ventilatory disorder in part of the sample. Treatment with inhaled corticosteroids showed good clinical response and satisfactory adherence. The findings demonstrate the predominance of asthma with an allergic component, highlighting the importance of specialized follow-up, environmental control, and appropriate treatment for disease management and quality of life improvement.

Paediatric Cardiopulmonary resuscitation (CPR) is critical for saving children who experience cardiac arrest, but traditional teaching is often ineffective at improving clinical competence and teamwork. This study evaluates an innovative, understudied model: integrated simulation combined with Team-Based Learning (TBL) in CPR training among paediatric postgraduates. This multi-methods observational study involved twenty-four paediatric postgraduates. The teaching method consisted of integrated simulation combined with TBL. Learning performance was measured before and after the course. Semi-structured interviews were conducted and recorded to collect data until data saturation was achieved, with the resulting data analyzed using inductive thematic analysis within a constructivist paradigm. Two researchers independently coded transcripts using NVivo 12.0, identified themes iteratively, and ensured rigour through member checking. The integrated simulation with TBL approach produced significant improvements in clinical operation scores: hands-on CPR (80.95 ± 5.81 vs. 88.46 ± 7.35), endotracheal intubation (76.03 ± 6.51 vs. 81.89 ± 9.72), defibrillation (79.96 ± 4.37 vs. 89.84 ± 3.98), and teamwork (28.33 ± 2.46 vs. 32.99 ± 2.85) (P < 0.05). For the qualitative component, semi-structured interviews were conducted with 11 participants, and analysis identified 10 core themes grouped into four clusters: "reflection and feedback," "highly simulated clinical scenario," "improving clinical thinking," and "teamwork and communication." The integrated simulation with TBL improves instructional effectiveness and overall clinical emergency response capabilities among paediatric postgraduates, thereby offering an innovative structured small-group learning method for paediatric CPR training.

The development of endometrial cancer is a gradual malignant transformation process driven by multiple factors, and the immune microenvironment is closely related to clinical outcomes and immunotherapy responses. Under physiological conditions, the immune microenvironment of the normal endometrium undergoes periodic reshaping under the regulation of estrogen and progesterone, maintaining the balance between immune defense and reproductive capacity. However, continuous exposure to risk factors, such as non-antagonistic estrogen, may trigger endometrial intraepithelial neoplasia. During this period, the immune microenvironment becomes dysregulated, supporting malignant progression. For example, estrogen-stimulated interactions between endothelial cells and macrophages, elevated neutrophil/lymphocyte ratios, and the accumulation of regulatory T cells all combine to cause dysregulation of immune microenvironment. The abnormal immune microenvironment that occurs in the precancerous lesion stage interacts with systemic and genetic carcinogenic factors, ultimately shaping the unique immune microenvironment of each molecular subtype of endometrial cancer. POLE-mutated and MSI-H subtype endometrial cancer are immune-infiltrated tumors, whereas the copy-number high subtype is immune-suppressive tumor and the copy-number low subtype is immune-desert tumor. However, still little is known about the immune dysregulation that occurs during the precancerous stage and its impact on subsequent malignant progression. This review systematically describes the changes in the immune microenvironment during the process from normal endometrium to endometrial cancer, emphasizing that endometrial intraepithelial neoplasia is a key stage of immune imbalance, thus paving the way for early immune intervention and precise immunotherapy.

Efficacy and safety of mirikizumab in paediatric participants with moderately-to-severely active ulcerative colitis (SHINE-1): a multicentre, open-label, non-randomised phase 2 trial.

Management of antineutrophil cytoplasmic antibody vasculitis-associated orbital inflammatory disease: A systematic literature review.

Outcomes from a combined cognitive behavioral therapy for insomnia (CBT-I) and sleep-related medication and substance use reduction treatment.

For stage IVB gastric cancer, recently, systemic cancer therapy (including cytotoxic chemotherapy, immune checkpoint inhibitors, and molecular targeted agents) is the standard treatment based on biomarker testing. If these treatments are successful and the tumor becomes resectable, conversion surgery may be considered, though its significance remains unclear. In cases showing clinical complete response (cCR), the necessity of surgery is further debated. This retrospective single-center study included patients with cStage IVB gastric cancer who received chemotherapy or systemic cancer therapy, regardless of undergoing conversion surgery, between 2013 and 2023. Patients were stratified by objective tumor response on imaging (cCR or others). Those achieving cCR were further divided into two groups: non-OP (follow-up without surgery) and OP (underwent conversion surgery) for survival comparison. Among 1591 patients treated with systemic chemotherapy, 51 (3.2%) achieved cCR (33 non-OP; 18 OP). In the cCR cohort, the median follow-up was 57 months. The 3-year overall survival (OS) was 97% in the non-OP group and 86% in the OP group (P = 0.44), respectively. Among the entire population, conversion surgery was performed in 121 patients (7.6%), in whom pathological CR (pCR) was seen in 17 (14%). This included 10 patients with cCR and seven without cCR. Three-year OS of pCR patients was 93%. The results suggested the potential for long-term survival without surgery in patients showing cCR. However, further investigation is needed regarding accurate methods to assess tumor disappearance.

Visceral Leishmaniasis is a systemic vector-borne infection with a poor prognosis if not treated. Classical antiparasitic therapy with liposomal amphotericin B (LAmB) is effective, but occasionally not well-tolerated. An 11-month-old male infant was admitted to our hospital due to prolonged fever, following an RSV infection. The patient had pale skin and splenomegaly, but was hemodynamically stable. An infectious cause was investigated through serology for Leishmania species , Brucella melitensis , Toxoplasma gondii , EBV, CMV, PB19 and Salmonella species . After admission, the infant developed Hemophagocytic lymphohistiocytosis (HLH, with pancytopenia, triglycerides: 346 U/L, ferritin: 1071 ng/mL; γ-globulin was administered without clinical response). On the second hospitalization day, the Leishmania rapid test was positive, while blood polymerase chain reaction identified Leishmania Infantum as the cause of infection, and LAmB was initiated. After the 4th dose, the patient developed hypokalemia, bradycardia and premature supraventricular complexes. The arrhythmia persisted despite electrolyte replacement; amphotericin-induced cardiotoxicity was suspected, and LAmB was discontinued. Oral miltefosine was started after approval by the National Public Health Organization, since the medicine was given in Greece for the first time to a pediatric patient. Miltefosine therapy lasted 1 month, with remission. Hepatotoxicity occurred at the end of the treatment and gradually resolved over the following 4 months with complete normalization of hepatic markers. The child remained asymptomatic at the 1-year follow-up. Leishmaniasis should always be investigated in pediatric patients with secondary HLH, especially in endemic countries. Cardiotoxicity of LAmB is extremely rare; in this case, however, miltefosine is an effective and safe alternative.

Longitudinal characterization of inflammatory plasma protein signatures in ECT response.

Circulating T cells Mirror Bone Marrow T cell Clonal Dynamics and Correlate with Clinical Response in Multiple Myeloma Post-Autologous HCT

Risky decision-making under stress in individuals with suicidal history: emotion regulation strategies and a potential pharmacological interaction.

ASO Visual Abstract: Is Surgery Necessary for Stage IVB Gastric Cancer Showing Clinical Complete Response to Chemotherapy or Systemic Cancer Therapy?

Belumosudil Achieves Clinical Responses in Sclerotic Skin and Fascial Chronic Graft-Versus-Host Disease: Analysis from 2 Prospective Trials

Pulmonary macrophage-targeted RNAi and mRNA co-delivery via SORT lipid nanoparticles enhances immunotherapy in lung cancer.

Humoral correlates of clinical response to thymectomy in myasthenia gravis.

Hypnosis as therapy for non-REM parasomnia: A literature review.

Microbiome-modulated immunotherapy in oncology: Current applications and future prospects.

The role of frontal EEG in predicting clinical response of major depressive disorder to intranasal ketamine and esketamine.