Effects of isochlorogenic acid A on mitochondrial dynamics imbalance and RLR damage in PAM cells induced by combined mycotoxins.

Mycotoxins have strong immunotoxicity and can induce oxidative stress and mitochondrial dynamics imbalance. Mitochondrial antiviral signaling protein (MAVS) in the RIG-I like receptor (RLR) pathway of innate immunity is located on mitochondria, and whether it is affected by mycotoxins has not been reported yet. This experiment used porcine alveolar macrophages (PAM) to evaluate the antagonism of three isomers of chlorogenic acid (chlorogenic acid, isochlorogenic acid A, and neochlorogenic acid) against combined mycotoxins (Aflatoxin B1, Deoxynivalenol, and Ochratoxin A) induced mitochondrial damage and their effects on the RLR pathway, providing assistance for further elucidating the mechanism of mycotoxin immunotoxicity. Western blotting, enzyme linked immunosorbent assay (ELISA), and flow cytometry were used to detect relevant indicators. All three types of chlorogenic acid treatment can antagonize the cytotoxicity induced by combined mycotoxins, especially isochlorogenic acid A, which can protect cells from mycotoxins damage by maintaining mitochondrial dynamic homeostasis and improving innate immune function related to the RLR pathway.

[Advances in gene therapy for inborn errors of immunity]. / åŸºå› æ²»ç–—åœ¨å ç–«å‡ºç”Ÿé”™è¯¯ä¸­çš„ç ”ç©¶è¿›å±•.

Inborn errors of immunity (IEI) are a diverse group of disorders caused by defects in immune system structure or function, involving both innate and adaptive immunity. The 2022 update of the IEI classification includes 485 distinct disorders, categorized into ten major disease groups. With the rapid development of molecular biology, the specific pathogenesis of many IEI has been revealed, making gene therapy possible in preclinical and clinical research of this type of disease. This article reviews the advancements in gene therapy for IEI, aiming to increase awareness and understanding of these disorders.

Correlation of cardiotocography with combined APGAR scores and diagnostic performance of umbilical cord parameters in predicting low combined APGAR scores - A prospective Cohort study.

Objectives: Combined Apgar score includes utilization of interventions such as Continuous positive airway pressure, Oxygen, Mask and Bag ventilation, I ntubation and ventilation, Ne onatal chest compression, Drugs, and newborn assessment. It has been proposed as a substitute for conventional Apgar score which is the gold standard for evaluating newborns right after birth but is impacted by medical interventions and preterm. Combined Apgar scores were examined to check for correlation with CTG tracing and umbilical cord blood parameters which gives an objective assessment of fetal hypoxia, in response to the demand for a more accurate tool for evaluating the neonate and to be used for medico-legal purposes. The study's objectives were to (1) determine the association of combined Apgar scores with suspicious and pathological CTG (2) the association of umbilical cord parameters with low combined Apgar scores and the diagnostic performance of these parameters in predicting low combined Apgar scores. Study design: A prospective observational cohort study was conducted in a tertiary care center in East India. 2350 consecutive laboring mothers who had completed 34 weeks of gestation underwent cardiotocography according to institutional protocol and those with suspicious and pathological CTG who delivered within 1 h of abnormal CTG were recruited. Arterial blood was analyzed and the newborn was evaluated immediately after delivery with a combined Apgar scoring system. Results: Of the 2350 women, 50.7 % and 49.3 %, respectively, exhibited suspicious and abnormal CTG tracings. CTG was reported to have low diagnostic accuracy and specificity, with a sensitivity of 66.7 % and 88.9 %, respectively, in detecting combined Apgar at 1 and 5 min. The combined Apgar score at five minutes showed a strong association with acidosis. There was a statistically significant correlation between low combined Apgar and excess lactate and base at one and five minutes. With 100 % sensitivity and 95 % specificity, high lactate levels > 4.1 mM/L were found to predict newborn encephalopathy. Conclusion: Umbilical cord blood parameters were found to be correlated with low combined Apgar scores. Combined Apgar scores may be a more useful tool for neonatal assessment and long-term morbidity of newborns. Additional research is required to determine whether it can take the role of conventional Apgar scores in clinical practice.

Radiological signs supporting idiopathic intracranial hypertension in symptomatic patients with lumbar puncture opening pressure < 250 mm.

Lumbar puncture opening pressure (LPOP) exceeding 250mmH2O is key in diagnosing idiopathic intracranial hypertension (IIH), per revised Friedman's criteria. Some patients do not meet LPOP criteria (with or without papilledema), despite having IIH-related symptoms and neuroimaging findings. This study aimed to investigate the radiological findings and clinical symptoms in patients suspected of having IIH without meeting the LPOP criteria. We retrospectively evaluated cerebral venous sinus stenosis using the conduit Farb score (CFS) and other radiological findings suggestive of IIH by computed tomography venography and magnetic resonance venography in females ≥ 18 years-old with chronic headaches, suspected IIH, and LPOP < 250 mm. Eighty-eight women (56 with LPOP < 200 mm H2O and 32 with LPOP ranging between 200 and 250mmH2O) were included. Among patients with LPOP 200-250mmH2O, 40% (12) exhibited three or more radiological findings supporting IIH, compared to 17% (8) in the LPOP < 200 mmH2O group (p = 0.048). Cerebral venous stenosis (CFS ≤ 5) was observed in 80% (24) of those with LPOP 200-250 mmH2O, contrasting with 40% (19) of those with LPOP < 200 mmH2O (p < 0.001). Cerebral venous stenosis was significantly more common in patients with LPOP 200-250 mmH2O than < 200 mmH2O, suggesting that they may benefit from IIH treatment.

Unexpected antagonism of deoxynivalenol and enniatins in intestinal toxicity through the Ras/PI3K/AKT signaling pathway.

Deoxynivalenol (DON) is a kind of widespread traditional Fusarium mycotoxins in the environment, and its intestinal toxicity has received considerable attention. Recently, the emerging Fusarium mycotoxin enniatins (ENNs) have also been shown to frequently coexist with DON in animal feed and food with large consumption. However, the mechanism of intestinal damage caused by the two mycotoxins co-exposure remains unclear. In this study, Caco-2 cell line was used to investigate the combined toxicity and potential mechanisms of four representative ENNs (ENA, ENA1, ENB, and ENB1) and DON. The results showed that almost all mixed groups showed antagonistic effects, particularly ENB at 1/4 IC50 (CI = 6.488). Co-incubation of ENNs mitigated the levels of signaling molecule levels disrupted by DON, including reactive oxygen species (ROS), calcium mobilization (Ca2+), adenosine triphosphate (ATP). The differentially expressed genes (DEGs) between the mixed and ENB groups were significantly enriched in the Ras/PI3K/Akt signaling pathway, including 28 up-regulated genes and 40 down-regulated genes. Quantitative real-time PCR further confirmed the lower expression of apoptotic gene in the mixed group, thereby reducing the cytotoxic effects caused by DON exposure. This study emphasizes that co-exposure of ENNs and DON reduces cytotoxicity by regulating the Ras/PI3K/Akt signaling pathway. Our results provide the first comprehensive evidence about the antagonistic toxicity of ENNs and DON on Caco-2 cells, and new insights into mechanisms investigated by transcriptomics.

The effect of combined application of biochar and phosphate fertilizers on phosphorus transformation in saline-alkali soil and its microbiological mechanism.

This study investigated the effects of combining Phragmites australis-based biochar, prepared at 400 °C, with various types of phosphate fertilizers-soluble, insoluble, and organic-on the content and transformation of phosphorus fractions in saline-alkali soil. Additionally, we explored microbiological mechanisms driving these transformations. The results showed that this combination significantly increased the concentrations of dicalcium phosphate (Ca2P), octacalcium phosphate (Ca8P), aluminum phosphate (AlP), moderately labile organic phosphorus (MLOP), and resistant organic phosphorus (MROP) in soil. Conversely, the levels of hydroxyapatite (Ca10P) and highly resistant organic phosphorus (HROP) decreased. The increase in labile organic phosphorus (LOP) content or decrease in iron phosphate (FeP) was found to effectively enhance the availability of Olsen phosphorus (Olsen-P) in soil. Furthermore, the study revealed that biochar mixed with organic phosphate fertilizers increased the activity of soil acid phosphatase (ACP) and neutral phosphatase (NEP), while reducing alkaline phosphatase (ALP) activity. In contrast, biochar combined with soluble and insoluble phosphate fertilizers decreased the activity of ACP (22.59 % and 28.57 %, respectively) and NEP (62.50 % and 11.11 %, respectively), with the combination with insoluble fertilizers also reducing ALP activity by 55.84 %, whereas the soluble combination increased it by 190.34 %. Additionally, the co-application of biochar and phosphate fertilizers altered the composition and abundance of the gene phoD-harboring microbial community, enhancing the abundance of Proteobacteria and reducing that of Actinobacteria. Correlation analysis between phoD-functional microbial species and various phosphorus fractions showed that Rhodopseudomonas was significantly associated with several phosphorus components, exhibiting a positive correlation with Ca2P, Ca8P, AlP, LOP, MLOP, and MROP, but a negative relationship with Ca10P. These findings suggest that the combined application of biochar and phosphate fertilizers could change the abundance of Rhodopseudomonas, potentially influencing phosphorus cycling in the soil. This research provides a strong scientific foundation for the efficient combined use of biochar and phosphate fertilizers in managing saline-alkali soil.

Comprehensive exploration of FCHO1 mutations: Clinical manifestations and implications across disorders.

FCH domain only 1 (FCHO1) is a key player in clathrin-mediated endocytosis, vital for various cellular processes, including immune regulation and cancer progression. However, the clinical implications of FCHO1 mutations, particularly in combined immunodeficiency, remain unclear. This systematic review aims to provide an objective analysis of the molecular genetics, clinical manifestations, and potential therapeutic targets associated with FCHO1 mutations. A systematic search following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted across electronic databases up to March 25, 2024, to identify studies investigating the relationship between FCHO1 and different clinical manifestations. Eligibility criteria were applied to screen studies, and data extraction included study characteristics, reported symptoms, genetic variants, and primary outcomes. In silico analyses were performed to assess protein-protein interactions and gene expression patterns. Five studies were included, offering insights into the molecular genetics, T-cell deficiency mechanisms, clinical manifestations, and potential therapeutic targets associated with FCHO1 mutations. Molecular analyses identified specific mutations disrupting FCHO1 function, leading to impaired T-cell proliferation, cytokine production, and susceptibility to infections. Clinically, patients exhibited recurrent infections, lymphopenia, and malignancies, with allogeneic hematopoietic stem cell transplantation emerging as a therapeutic option. In silico analyses revealed potential interactions and co-expression between FCHO1 and genes involved in cancer progression and immune signaling pathways. This systematic review objectively elucidates the multifaceted role of FCHO1 in immune regulation and disease pathogenesis. Understanding the molecular mechanisms underlying FCHO1 mutations and their impact on disease manifestations is crucial for guiding clinical management and developing targeted therapeutic strategies.

A 27-Year-Old Female With JAK2 Mutation: A Case of Budd-Chiari Syndrome Secondary to Prolonged Oral Contraceptive Pill Use.

Individuals with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) such as polycythemia vera and essential thrombocythemia (ET) demonstrate an increased thrombotic risk associated with JAK2 mutations. Physicians must take heed when treating these patients, to mitigate this pro-thrombotic state as much as possible. Failure to do so, or exacerbating the state, can lead to dire consequences. We present the case of a 27-year-old female with a history of ulcerative colitis (UC) and ET, currently taking estrogen-containing oral contraceptive pills (OCPs). She presented to the emergency department with rapid weight gain, jaundice, nausea, and diarrhea and was found to have obstructive jaundice and thrombotic burden that extended into the portal, mesenteric, splenic, and hepatic veins. On the second attempt, a successful transjugular intrahepatic portosystemic shunt procedure was performed, resulting in improved venous flow. This case underscores the importance of cautious medication use, especially OCPs, in patients with hypercoagulable states due to JAK2 mutations, for example, the V617F mutation in JAK2. It emphasizes the need for vigilant monitoring, individualized management, and a multidisciplinary approach to mitigate thrombotic complications. Increased awareness and continued research are crucial for optimizing treatment strategies for patients with MPNs and associated genetic mutations.

Concurrent Undisplaced Patellar Fracture and Posterior Cruciate Ligament Avulsion Fracture Managed With Surgical Fixation and Rehabilitation: A Case Report.

This case report explains the successful management of a rare, combined injury: an undisplaced patellar fracture and a posterior cruciate ligament (PCL) avulsion fracture at the tibial attachment in a 44-year-old male patient following a motorbike accident. While both injuries are frequently seen in orthopedic practice, their concurrent occurrence is uncommon. The patient presented with significant knee swelling, limited range of motion, and pain following the accident. An X-ray revealed a patellar fracture and magnetic resonance imaging (MRI) confirmed an undisplaced fracture, a PCL tear, and a medial meniscus injury. The patient underwent surgical intervention for PCL fixation with a cannulated cancellous (CC) screw under spinal anesthesia. Following surgery, a comprehensive rehabilitation program was implemented, focusing on pain management, reducing swelling, regaining range of motion, and strengthening the surrounding musculature. The program progressed through three phases, steadily increasing the intensity and complexity of exercises. The patient exhibited significant improvement in pain, swelling, range of motion, and muscle strength throughout the rehabilitation program. By week 12, he had achieved near-normal knee function and was able to resume most daily activities.

Immunotherapy for small cell lung cancer: the current state and future trajectories.

Small cell lung cancer (SCLC) constitutes approximately 10% to 15% of all lung cancer diagnoses and represents a pressing global public health challenge due to its high mortality rates. The efficacy of conventional treatments for SCLC is suboptimal, characterized by limited anti-tumoral effects and frequent relapses. In this context, emerging research has pivoted towards immunotherapy combined with chemotherapy, a rapidly advancing field that has shown promise in ameliorating the clinical outcomes of SCLC patients. Through originally developed for non-small cell lung cancer (NSCLC), these therapies have extended new treatment avenues for SCLC. Currently, a nexus of emerging hot-spot treatments has demonstrated significant therapeutic efficacy. Based on the amalgamation of chemotherapy and immunotherapy, and the development of new immunotherapy agents, the treatment of SCLC has seen the hoping future. Progress has been achieved in enhancing the tumor immune microenvironment through the concomitant use of chemotherapy, immunotherapy, and tyrosine kinase inhibitors (TKI), as evinced by emerging clinical trial data. Moreover, a tripartite approach involving immunotherapy, targeted therapy, and chemotherapy appears auspicious for future clinical applications. Overcoming resistance to post-immunotherapy regimens remains an urgent area of exploration. Finally, bispecific antibodies, adoptive cell transfer (ACT), oncolytic virus, monotherapy, including Delta-like ligand 3 (DLL3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), as well as precision medicine, may present a prospective route towards achieving curative outcomes in SCLC. This review aims to synthesize extant literature and highlight future directions in SCLC treatment, acknowledging the persistent challenges in the field. Furthermore, the continual development of novel therapeutic agents and technologies renders the future of SCLC treatment increasingly optimistic.

Quantitative imaging methods in combined pulmonary fibrosis and emphysema.

TOPIC IMPORTANCE: Combined pulmonary fibrosis and emphysema (CPFE) is an underdiagnosed syndrome in which individuals have variable degrees of pulmonary fibrosis and emphysema. Patients with CPFE have high morbidity, including poor exercise tolerance and increased development of co-morbidities. CPFE mortality also appears to outpace lone emphysema and pulmonary fibrosis. A major limitation to rigorous, large-scale studies of CPFE has been the lack of a precise definition for this syndrome. A 2022 ATS/ERJ/JRS/ALAT Research Statement called attention to fundamental gaps in our understanding of CPFE and highlighted the potential use of quantitative imaging techniques to better define CPFE. REVIEW FINDINGS: Broadly, CPFE has been defined using visual interpretation of chest computed tomography (CT) documenting the presence of both emphysema and fibrosis, with varying distributions. When quantitative approaches were employed, varying thresholds of emphysema and fibrosis on imaging have been used across different studies. SUMMARY: This review is structured into three primary themes, starting with early imaging studies, then evaluating the use of quantitative methods and imaging-based thresholds both in large population studies and single center cohorts to define CPFE and assess patient outcomes, and concludes by discussing current challenges and how to focus our efforts so quantitative imaging methods can effectively address the most pressing clinical dilemmas in CPFE.

ESCMID/EUCIC clinical guidelines on preoperative decolonization and targeted prophylaxis in patients colonized by multidrug-resistant Gram-positive bacteria before surgery.

SCOPE: The aim of these guidelines is to provide recommendations on decolonization and perioperative antibiotic prophylaxis (PAP) in multidrug-resistant Gram-positive bacteria (MDR-GPB) adult carriers before inpatient surgery. METHODS: These European Society of Clinical Microbiology and Infectious Diseases (ESCMID)/European Committee on Infection Control (EUCIC) guidelines were developed following the systematic review of published studies targeting methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), methicillin-resistant coagulase-negative staphylococci (MR-CoNS) and pan-drug-resistant (PDR)-GPB. Critical outcomes were the occurrence of surgical site infections (SSIs) caused by the colonizing MDR-GPB and SSIs-attributable mortality. Important outcomes included the occurrence of SSIs caused by any pathogen, hospital-acquired infections, all-cause mortality, and adverse events associated with the interventions, including resistance development to the agents used and incidence of Clostridioides difficile infections. The last search of all databases was performed on November 1st, 2023. The level of evidence and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included. RECOMMENDATIONS: The guideline panel reviewed the impact of decolonization, targeted PAP, and combined interventions (e.g., decolonization and targeted PAP) on the risk of SSIs and other outcomes in MDR-GPB carriers, according to the type of bacteria and type of surgery. We recommend screening for S. aureus (SA) before high-risk operations, such as cardiothoracic and orthopedic surgery. Decolonization with intranasal mupirocin with or without chlorhexidine bathing is recommended in patients colonized with SA before cardiothoracic and orthopedic surgery and suggested in other surgeries. Addition of vancomycin to standard prophylaxis is suggested for MRSA carriers in cardiothoracic surgery, orthopedic surgery, and neurosurgery. Combined interventions (e.g., decolonization and targeted prophylaxis) are suggested in MRSA carriers undergoing cardiothoracic and orthopedic surgery. No recommendation could be made regarding screening, decolonization, and targeted prophylaxis for VRE due to the lack of data. No evidence was retrieved for MR-CoNS and PDR-GPB. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship as well as infection control teams are warranted before implementing screening procedures or performing changes in PAP policy. Future research should focus on novel decolonizing techniques, on the monitoring of resistance to decolonizing agents and PAP regimens, and on standardized combined interventions in high-quality studies.

Comparative analysis of internal limiting membrane peeling versus internal limiting membrane flap insertion for treating idiopathic macular holes.

OBJECTIVE: To evaluate the clinical efficacy of internal limiting membrane (ILM) peeling combined with perimacular hole massage versus ILM flap insertion in the management of patients with idiopathic macular holes was conducted. METHODS: 35 patients (total of 35 eyes) with idiopathic macular holes (with hole diameters ranging from 366 to 1430 µm) were divided into two groups-Group A consisted of 20 eyes that underwent pars plana vitrectomy (PPV) combined with ILM peeling and perimacular hole massage, while Group B comprised 15 eyes that underwent PPV combined with ILM flap insertion. Subsequent follow-up examinations were performed at 1 week, 1 month, and 3 months post-surgery. The study also involved a comparison of best corrected visual acuity (BCVA) and optical coherence tomography (OCT) classifications between both the patient groups. RESULTS: The macular hole closure rates in Group A were 60%, while in Group B, the closure rate was 93%. There was significant difference in hiatus healing rate between the two groups (t = 4.843, p = 0.048). The difference in BCVA at 3 months post-operation between the two groups was statistically significant (t = 3.221, p = 0.003). Three months post-operatively, the BCVA in Group B demonstrated improvement compared to the pre-operative BCVA, with a statistically significant difference (p > 0.05). Three months post-operatively, the BCVA in Group A demonstrated improvement compared to the pre-operative BCVA, but this difference was not statistically significant (p > 0.05). CONCLUSION: The combination of PPV with ILM flap insertion demonstrates favorable therapeutic efficacy in the treatment of idiopathic macular holes, leading to improved visual acuity.

The Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group: outstanding contribution and entering a new phase.

The Lung Cancer Surgical Study Group (LCSSG) of the Japan Clinical Oncology Group (JCOG) was organized in 1986 and initially included 26 collaborative institutions, which has increased to 52 institutions currently. JCOG-LCSSG includes thoracic surgeons, medical oncologists, pathologists, and radiotherapists. In the early period, the JCOG-LCSSG mainly focused on combined modality therapies for lung cancer. Since the 2000s, the JCOG-LCSSG has investigated adequate modes of surgical resection for small-sized and peripheral non-small cell lung cancer and based on the radiological findings of whole tumor size and ground-glass opacity. Trials, such as JCOG0802, JCOG0804, and JCOG1211, have shown the appropriateness of sublobar resection, which has significantly influenced routine clinical practice. With the introduction of targeted therapy and immunotherapy, treatment strategies for lung cancer have changed significantly. Additionally, with the increasing aging population and medical costs, tailored medicine is strongly recommended to address medical issues. To ensure comprehensive treatment, strategies, including surgical and nonsurgical approaches, should be developed. Currently, the JCOG-LCSSG has conducted numerous clinical trials to adjust the diversity of lung cancer treatment strategies. This review highlights recent advancements in the surgical field, current status, and future direction of the JCOG-LCSSG.

Development and Validation of a Novel Multiplex Real-Time PCR Assay for Rapid Detection of Carbapenemase Genes in Carbapenem-Resistant Enterobacterales Isolates and Clinical Samples.

Purpose: Carbapenem-resistant Enterobacterales (CRE) infection is an urgent threat to human health. This study aimed to develop and validate a novel multiplex real-time PCR (multi-qPCR) assay for the detection of the blaKPC, blaNDM, blaIMP, blaOXA-48-like, and blaVIM genes in CRE isolates and clinical samples, as well as to compare it with three phenotypic methods. Methods: The reliability and limit of detection (LOD) of the multi-qPCR assay were evaluated. PCR and DNA sequencing were used as the reference methods to identify carbapenemase genes in CRE isolates and clinical samples. The accuracy of the multi-qPCR assay, modified carbapenem inactivation and EDTA-modified carbapenem inactivation method (mCIMandeCIM), carbapenemase inhibitor-based combined disk test (CDT), and colloidal gold-based immunochromatographic test was compared with the reference methods with 182 isolates of CRE. Furthermore, 112 clinical samples were collected to validate the efficacy of this multi-qPCR assay. Results: The standard deviations (CVs) of intra-assay and inter-assay of the multi-qPCR assay were ≤ 0.53% and ≤ 2.04% for detecting the five major carbapenemase genes, respectively; while the LOD ranged from 2×102 copies/mL to 8×102 copies/mL. PCR and DNA sequencing confirmed 168 out of 182 CRE isolates producing carbapenemase(s): KPC (n = 93), NDM (n = 46), IMP (n = 8), OXA-48-like (n = 14), VIM (n = 1), KPC&NDM (n = 5), and KPC&NDM&IMP (n = 1). The accuracy of mCIMandeCIM, CDT, Colloidal Gold, and the multi-qPCR assay was 96.2%, 89.6%, 100%, and 100% respectively for detecting carbapenemase(s) producers. Moreover, the sensitivity and specificity of the multi-qPCR assay were all 100% for the detection of each carbapenemase gene in clinical samples, compared with PCR and sequencing. Conclusion: For clinical isolate detection, the multi-qPCR assay is comparable to Colloidal Gold, and superior to mCIMandeCIM and CDT; while for clinical samples detection, it also shows excellent performance. Therefore, the multi-qPCR assay has great potential for clinical diagnosis.

Biofeedback-Assisted pelvic floor muscle training combined with a short-duration drug regimen is safe and effective in women with overactive bladder: A randomized controlled trial.

OBJECTIVE: We hypothesized that combination therapy would provide a synergistic effect to improve treatment outcomes for overactive bladder (OAB), thus enhancing the motivation for continuous exercise, and that it would be associated with fewer adverse events than monotherapy. Therefore, we investigated whether biofeedback-assisted pelvic floor muscle training (PFMT), drug therapy, or a combination of both would be more effective in improving the symptoms of OAB. STUDY DESIGN: This randomized controlled trial included women diagnosed with OAB. Group 1 received biofeedback-assisted pelvic muscle floor training (PFMT) for 12 weeks; group 2 took 5 mg of solifenacin/day for 12 weeks; and group 3 received 5 mg of solifenacin/day in combination with biofeedback-assisted PFMT during the first 4 weeks and biofeedback-assisted PFMT for another 8 weeks. All participants had 5 follow-up visits. The primary outcomes were objective improvement of OAB symptoms and quality of life. The secondary outcomes were treatment-related adverse events, subjective improvement of OAB symptoms, and electromyographic activity of pelvic floor muscle (PFM) contraction. RESULTS: All participants reported significant improvement of OAB symptoms and quality of life. Participants in group 2 experienced more pronounced adverse events than those in group 3. Intervention duration was positively associated with subjective improvement in OAB symptoms in groups 2 and 3. Drug-related adverse events, including dry mouth, myalgia, and restlessness, had a negative impact on the subjective improvement of OAB symptoms in group 2. In group 1, exercise adherence was positively correlated with subjective improvement of OAB symptoms, whereas in group 3, PFM contraction and biofeedback effect were positively correlated with symptom improvement. CONCLUSION: Combination therapy is efficacious in treating women with OAB.

Uniportal Thoracoscopic Complex Combined Seg-Sub-subsegmentectomy of RS9+10bii: Dual-Display Method and Combined Approaches (Trans-fissure and Trans-ligament).

BACKGROUND: Uniportal thoracoscopic lateral basal segmentectomy is the most technically challenging anatomic segmentectomy,1-3 especially when it involves combined subsegmentectomy or sub-subsegmentectomy. Therefore, there are very few reports detailing its technical aspect. PATIENT AND METHOD: In this multimedia article, we describe a very complex uniportal thoracoscopic combined seg-sub-subsegmentectomy of RS9+10bii through the oblique fissure approach and the inferior pulmonary ligament approach, following a single-direction strategy4,5 to advance the procedure, utilizing the stem-branch method3,6 for segmental/subsegmental/sub-subsegmental structure tracking, and employing dual-display method, which comprises the intravenous ICG injection method and the inflation/deflation method, to identify intersegmental and inter-seg-sub-subsegmental planes. RESULTS: The operation lasted 169 min, with approximately 20 mL of blood loss. The patient experienced an active hemothorax and two spontaneous pneumothoraxes on postoperative days 1, 4, and 19, respectively, all of which resolved promptly after treatment. Histopathological examination of the specimen documented invasive non-mucinous adenocarcinoma with negative surgical margins and lymph nodes. The staging was determined as pT1bN0M0, stage IA2. During the 14-month follow-up period, there were no signs of tumor recurrence or metastasis observed. The FVC, FEV1, and FEV1%pred decreased by 11.9%, 12.5%, and 12.8%, respectively, at postoperative month 6. CONCLUSIONS: Complex basal segmentectomies, which necessitate combined subsegmental or sub-subsegmental resections, such as RS9+10bii, are feasible using the dual-display and combined approaches method. This method simplifies the steps of the very complex combined subsegmentectomy, averting the need for extensive lung resection. In addition, when performing these combined segmentectomies, precise anatomical dissection is crucial to prevent complications such as minor bronchopleural fistulas.

Reconstitution of norovirus-specific T cell responses following hematopoietic stem cell transplantation in patients with inborn errors of immunity and chronic norovirus infection.

BACKGROUND: Chronic norovirus infection (CNI) causes significant morbidity in immunocompromised patients. No effective prevention or treatment currently exists. METHODS: Two patients with inborn errors of immunity, X- linked severe combined immunodeficiency (X-SCID) and DOCK8 deficiency, were followed longitudinally for clinical course, immune reconstitution, norovirus-specific T cell (NST) response, B cell reconstitution, and norovirus-specific antibody production. Samples were obtained in the peri-hematopoietic stem cell transplant setting (HSCT) before and after CNI clearance. The norovirus strain causing CNI was followed longitudinally for norovirus stool viral loads and sequencing. RESULTS: The noroviruses were identified as GII.4 Sydney[P4 New Orleans] in one patient and GII.17[P17] in the other. An exacerbation of diarrhea post-HSCT in the patient with X-SCID was consistent with norovirus infection but not with graft-vs-host-disease on pathologic samples. Both patients recovered polyfunctional NSTs in the CD4 and CD8 T cell compartments which recognized multiple norovirus structural and non-structural viral antigens. T cell responses were minimal during active CNI but detectable after resolution. Mapping of norovirus-specific T cell responses between the patient with DOCK8 and his matched sibling donor were nearly identical. B cell reconstitution or new endogenous antibody production for IgA or IgG were not observed. CONCLUSION: This report is the first to demonstrate reconstitution of norovirus-specific T cell immunity after HSCT closely temporally aligned with clearance of CNI suggesting that cellular immunity is sufficient for norovirus clearance.

[Traumatic gallbladder rupture in a 9-year-old child]. / Travmaticheskii razryv zhelchnogo puzyrya pri sochetannoi travme u rebenka 9 let.

We present gallbladder rupture following trauma. A 9-year-old boy admitted in 1.5 hours after injury. Considering clinical and ultrasound data, we diagnosed traumatic damage to the spleen and hemoperitoneum, biliary dyskinesia, cholestasis, sludge. Hemostatic therapy was carried out. After 3 days, signs of peritonitis appeared. Follow-up ultrasound revealed gallbladder enlargement with heterogeneous content, fluid in all parts of abdominal cavity. Intraoperatively, the gallbladder was enveloped in omentum soaked in bile. After mobilization of the gallbladder, we found longitudinal linear tear up to 3 cm clogged with omentum. Cholecystectomy was performed. Thus, we present a patient with combined injury and damage to the spleen. However, gallbladder wall thickening and heterogeneous content were interpreted as concomitant pathology. Delayed manifestation of peritonitis was due to gallbladder enveloped in omentum. The last one soaked in bile partially entered the gallbladder through perforation and prevented bile leakage into abdominal cavity. Timely diagnosis of gallbladder damage presents certain difficulties, especially in case of combined injury. Ultrasound signs of traumatic gallbladder rupture in this case were wall thickening, heterogeneous content and gradual gallbladder enlargement. It is necessary to analyze all organs at the damage site including computed tomography in patients with combined trauma.

[The Koblenz algorithm for thoracoabdominal wounds in a military hospital]. / Pervoe primenenie «koblentsskogo algoritma¼ v lechenii patsientov s torakoabdominal'nymi raneniyami v usloviyakh voennogo gospitalya. Klinicheskii sluchai.

Despite available armored personal protection in troops, the incidence of abdominal wounds in modern wars is 6.6-9.0%. Of these, penetrating abdominal injuries comprise 75-80%. Thoracoabdominal injuries occupy a special place with incidence up to 88%. We present the first case of the "Koblenz algorithm" in the treatment of a patient with mine explosion wound, combined injury of the head, limbs, thoracoabdominal trauma, widespread peritonitis, small intestinal obstruction and septic shock in a military hospital. This algorithm was implemented under import substitution considering the peculiarities of abdominal adhesive process in a patient with thoracoabdominal wound. This case demonstrates the advantage of this algorithm for patients with severe combined wounds of the chest and abdomen complicated by diffuse purulent peritonitis. Clinical status of these patients does not allow not only open laparostomy, but also "classical" redo laparotomies.