Clinical Reports Research Articles

Weathering the storm when the end of the road is near: A qualitative analysis of supportive care needs during CAR T-cell therapy in pediatrics.

Chimeric antigen receptor (CAR) T-cell therapy provides promising outcomes in relapsed/refractory B acute lymphoblastic leukemia (ALL), yet still carries high toxicity rates and relatively poor long-term survival. Efficacy has yet to be demonstrated in other diagnoses while toxicity and risk profiles remain formidable. To date, treatment-related symptom burden is gleaned from clinical trial toxicity reports; the patient perspective remains understudied. English- or Spanish-speaking patients (ages 8-25years) undergoing CAR T-cell therapy for any malignancy and their primary caregivers were recruited from Seattle Children's Hospital (SCH), St. Jude Children's Research Hospital (SJCRH), and the Pediatric Oncology Branch of the National Cancer Institute (NCI). Both patient and caregiver completed semi-structured dyadic interviews 3months post treatment. We used directed content analysis for codebook development and thematic network analysis for inductive qualitative analysis. Twenty families completed interviews (13 patients, 15 parents). Patients were a median age 16.5years, predominantly female (65%), White (75%), and diagnosed with ALL (75%). Global themes included "A clear decision," "Coping with symptoms," and "Unforeseen psychosocial challenges." When families were asked to describe the "most challenging part of treatment," most described "the unknown." Most reported "the symptoms really weren't that bad," even among patients hospitalized for severe toxicity events. Fatigue, pain, and nausea were the most prevalent symptoms. Importantly, only one family would have chosen a different therapy, if given another opportunity. Although physical symptoms were largely tolerable, recognizing supportive care opportunities remains imperative, particularly psychosocial concerns.

Activation of pregnane X receptor sensitizes alcoholic steatohepatitis by transactivating fatty acid binding protein 4

Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR–FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.

Detection of liver metastases in patients with pancreatic adenocarcinoma: MRI versus CT

Introduction. Detection of liver metastases is important to guide therapeutic management of pancreatic cancer. Data suggest that magnetic resonance imaging (MRI) is more sensitive than computed tomography (CT) for the diagnosis of liver metastases from pancreatic cancer. However, MRI is currently not recommended in several guidelines. Purpose. To compare the performance of CT vs MRI in detection of liver metastases in patients with pancreatic adenocarcinoma. Methods. This was a retrospective single-center study over 24 months from January 2020 to December 2021 of patients suspected of having PDAC. All patients underwent contrast-enhanced triple phase CT and contrast-enhanced MRI/MRCP. The CT and MRI assessment of resectability and detection of metastases were performed according to NCCN version 1.2024 criteria by one observer based on clinical report. Composite reference standard based on decision of operability (based on multidisciplinary tumor board decision), surgical findings (delay of 2 to 3 weeks after imaging) and histopathologic findings. Results. 117 patients (M/F 52/65, mean age 62±11y) were included. The mean tumor size was 43.6±15.2mm (add range). 42/46 patients (34.2%/39.3%) were diagnosed with metastatic disease on CT/MRI, 40/36 patients (34.2%/30.8%) were resectable, 20/16 patients (17.1%/13.7%) were borderline resectable and 15/19 patients (12.8%/16.2%) were locally advanced. The detection of liver metastases on CT and MRI was compared with surgical findings in 45 patients (38.5%). The analysis showed that MRI had superior performance to CT, with sensitivity at 100% vs 60% and specificity at 97.1% vs 97.1%, PPV at 90.9% vs 85.7% and NPV 100% vs 89.5% (MRI/CT). Conclusion. MRI is more sensitive than CT in detection of liver metastases in patients with pancreatic adenocarcinoma.

Resurgence of Clinical Malaria in Ethiopia and Its Link to Anopheles stephensi Invasion.

The invasion of Anopheles stephensi into Africa poses a potential threat to malaria control and elimination on the continent. However, it is not clear if the recent malaria resurgence in Ethiopia has linked to the expansion of An. stephensi. We obtained the clinical malaria case reports and malaria intervention data from the Ethiopian Ministry of Health (MoH) for the period 2001-2022. We analyzed clinical malaria hotspots and investigated the potential role of An. stephensi in the 2022 malaria outbreaks. Clinical malaria cases in Ethiopia decreased by 80%, from 5.2 million cases in 2004 to 1.0 million cases in 2018; however, cases increased steadily to 2.6 million confirmed cases in 2022. Plasmodium vivax cases and proportion have increased significantly in the past 5 years. Clinical malaria hotspots are concentrated along the western Ethiopian border areas and have grown significantly from 2017 to 2022. Major malaria outbreaks in 2022/2023 were detected in multiple sites across Ethiopia, and An. stephensi was the predominant vector in some of these sites, however, it was absence from many of the outbreak sites. The causes of recent upsurge in malaria in Ethiopia may be multi-factorial and it is a subject of further investigation.

Pausing propofol during neurosurgery to record intraoperative electrocorticography is feasible;10 years of clinical experience

ObjectiveIntraoperative electrocorticography (ioECoG) during neurosurgery is influenced by anesthetics. In our center we stop the propofol to enable interpretation of ioECoG. We reported our clinical experience and evaluated awareness and hemodynamic changes during the propofol-free periods (PFP). MethodsWe retrospectively included surgeries with paused propofol administration to record ioECoG (period: 2008–2019). Clinical reports were screened for symptoms of awareness. We compared mean arterial blood pressure (MAP; mmHg) and heart rate (HR;bpm) during PFP to baseline (ten minutes preceding PFP). An increase > 15% was defined as clinically relevant. The association between hemodynamic changes and clinical characteristics was analyzed using logistic regression models. ResultsPropofol administration was paused 742 times in 352 surgeries (mean PFP duration 9 ± 5 min). No signs of awareness were reported. MAP and HR increased > 15% in 54 and six PFPs. Five PFPs showed both MAP and HR increases. Prolonged PFP was associated with having MAP and HR increase during surgery (OR=1.18, 95%CI [1.12–1.26]). ConclusionsSigns of inadequate sedation depth were rare. MAP and HR increases were related to the length of PFP. SignificanceWe summarize 10 years of clinical experience with pausing propofol administration during epilepsy surgery to record ioECoG without evidence of awareness.

3102: NSCLC Electronic Health Records Analysis by Named Entity Recognition in Italian Clinical Reports

3102: NSCLC Electronic Health Records Analysis by Named Entity Recognition in Italian Clinical Reports

A new and simplified extraoral approach for inferior alveolar nerve block: a cadaveric study and clinical case reports.

Inferior alveolar nerve (IAN) and lingual nerve (LN) blocks are commonly performed using the intraoral landmark techniques. However, these methods have a risk of unanticipated nerve and arterial injury or a higher failure rate. We developed a novel extraoral approach for the IAN and LN blocks, the "inferior alveolar nerve block mandibular angle approach (IANB-MA)," using ultrasound guidance. The mechanism of action of this nerve block was examined anatomically, and its clinical feasibility was reported. We performed the IANB-MA on four cadavers using different dye volumes (2, 4, 6 and 8mL). The ultrasound probe was placed on the lower edge of the mandibula of each cadaver, and the needle was advanced to the mandibular inner surface. Blue acrylic paint solution was injected, and its spread was evaluated by dissection. Our study showed that the medial pterygoid muscle fascia was stained in all cadavers. The dye reached the LN consistently, and the IAN was stained with higher volumes (6mL and 8mL). The pterygomandibular space was filled with 6mL and 8mL of the dye. The IANB-MA successfully reduced pain in three patients with trigeminal neuralgia, tongue or jaw pain. The IANB-MA is a novel ultrasound-guided approach to the IAN and the LN. The clinical feasibility and effectiveness of this technique were confirmed in our patients. It may be a good alternative analgesic approach to other conventional approaches.

Comparative analysis of GPT-4-based ChatGPT's diagnostic performance with radiologists using real-world radiology reports of brain tumors.

Large language models like GPT-4 have demonstrated potential for diagnosis in radiology. Previous studies investigating this potential primarily utilized quizzes from academic journals. This study aimed to assess the diagnostic capabilities of GPT-4-based Chat Generative Pre-trained Transformer (ChatGPT) using actual clinical radiology reports of brain tumors and compare its performance with that of neuroradiologists and general radiologists. We collected brain MRI reports written in Japanese from preoperative brain tumor patients at two institutions from January 2017 to December 2021. The MRI reports were translated into English by radiologists. GPT-4 and five radiologists were presented with the same textual findings from the reports and asked to suggest differential and final diagnoses. The pathological diagnosis of the excised tumor served as the ground truth. McNemar's test and Fisher's exact test were used for statistical analysis. In a study analyzing 150 radiological reports, GPT-4 achieved a final diagnostic accuracy of 73%, while radiologists' accuracy ranged from 65 to 79%. GPT-4's final diagnostic accuracy using reports from neuroradiologists was higher at 80%, compared to 60% using those from general radiologists. In the realm of differential diagnoses, GPT-4's accuracy was 94%, while radiologists' fell between 73 and 89%. Notably, for these differential diagnoses, GPT-4's accuracy remained consistent whether reports were from neuroradiologists or general radiologists. GPT-4 exhibited good diagnostic capability, comparable to neuroradiologists in differentiating brain tumors from MRI reports. GPT-4 can be a second opinion for neuroradiologists on final diagnoses and a guidance tool for general radiologists and residents. This study evaluated GPT-4-based ChatGPT's diagnostic capabilities using real-world clinical MRI reports from brain tumor cases, revealing that its accuracy in interpreting brain tumors from MRI findings is competitive with radiologists. We investigated the diagnostic accuracy of GPT-4 using real-world clinical MRI reports of brain tumors. GPT-4 achieved final and differential diagnostic accuracy that is comparable with neuroradiologists. GPT-4 has the potential to improve the diagnostic process in clinical radiology.

Lung adenocarcinoma concurrent with pulmonary cryptococcosis: a case report and literature review

Pulmonary cryptococcosis (PC) is a common opportunistic fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. PC primarily invades the respiratory system, followed by the central nervous system. Few clinical reports have examined the coexistence of PC and lung cancer. This study reports the case of a 54-year-old immunocompetent PC patient with lung adenocarcinoma. Chest CT revealed multiple nodules in the right lung, with the largest nodule located in the dorsal segment of the right lower lobe. 18 F‑FDG positron emission tomography-computed tomography (PET-CT) revealed elevated glucose metabolism in the dorsal segment of the right lower lobe, which suggested lung cancer. The metabolism level of the nodule in the basal segment of the right lower lobe and the anterior segment of the right upper lobe was not abnormally increased, but the possibility of a malignant tumour could not be excluded. The pulmonary nodules in the dorsal segment and the basal segment of the right lower lobe were simultaneously resected via video-assisted thoracic surgery (VATS), and the final histopathology revealed primary lung adenocarcinoma and pulmonary cryptococcal infection, respectively. After surgery, antifungal treatment was administered for 3 months. Over the 3-year follow-up, contrast-enhanced computed tomography (CT) revealed no recurrence of either disease. This case study highlights the possibility of dualism in the diagnosis of multiple pulmonary nodules on chest CT, such as the coexistence of lung cancer and PC. Surgical resection is recommended for micronodules that are not easy to diagnose via needle biopsy; in addition, early diagnosis and treatment are helpful for ensuring a good prognosis. This paper reports the clinical diagnosis and treatment of one patient with pulmonary cryptococcal infection of the right lung complicated with lung adenocarcinoma, including 3 years of follow-up, providing a reference for clinical practice.

Cardiac Findings Following Cerebrovascular Disease.

Accumulating evidence suggests that cardiac findings after stroke are an important, yet understudied, manifestation of brain-heart interactions. Our aim was to investigate and compare cardiac findings after different cerebrovascular events (acute ischemic stroke, transient ischemic attack, and hemorrhagic stroke). There were 7113 patients screened who were treated between December 2013 and December 2020 at the University Hospital Zurich for ischemic stroke, transient ischemic attack, and hemorrhagic stroke. Seven hundred twenty-one patients without evidence of previous cardiac disease or presumed cardioembolic origin of their cerebrovascular disease and with at least 1 cardiac checkup were included. Clinical reports from the year following disease onset were screened for new cardiac findings, which were categorized as arrhythmia/electrocardiographic changes, myocardial alterations, valvular abnormalities, and coronary perfusion insufficiency. Differences in proportions of findings among groups were analyzed using the Pearson χ2 test or Fisher exact test. ECG changes were observed in 81.7% (n=474) of patients with ischemic stroke, 71.4% (n=70) of patients with transient ischemic attack, and 55.8% (n=24) of patients with hemorrhagic stroke (P<0.001). Myocardial alterations occurred often in all 3 groups (60.9% ischemic stroke [n=353], 59.2% transient ischemic attack [n=58], 44.2% hemorrhagic stroke [n=19]; P=0.396). Cardiac findings are frequent in patients with cerebrovascular disease, even without prior cardiac problems or suspected cardiac cause. Similarities, especially between patients with ischemic stroke and transient ischemic attack, were observed. Our data suggest that all patients with acute cerebrovascular events should receive thorough workup searching for cardiac manifestations.

A Systematic Review and Comparative Analysis of Botox Treatment in Aesthetic and Therapeutic Applications: Advantages, Disadvantages, and Patient Outcomes.

The objective of this review article is to comprehensively analyze Botox treatment, emphasizing its aesthetic and therapeutic applications, along with the associated advantages, disadvantages, and patient outcomes. By reviewing current literature, the article evaluates Botox's efficacy and safety in various clinical settings, including cosmetic procedures and medical treatments for conditions such as chronic migraines and excessive sweating, while also exploring patient satisfaction and potential risks. This review article provides a comprehensive analysis of Botox treatment, focusing on its aesthetic and therapeutic applications, as well as the associated advantages, disadvantages, and patient outcomes. Botulinum toxin, derived from Clostridium botulinum, is widely recognized for its ability to induce temporary muscle paralysis, leading to significant improvements in both cosmetic and medical conditions. The article reviews findings from recent clinical trials, case reports, and observational studies, highlighting the efficacy and safety of Botox in treating various conditions such as chronic migraines, excessive sweating, and muscle spasticity, alongside its cosmetic use in wrinkle reduction. While the benefits of Botox are substantial, including its minimally invasive nature and high patient satisfaction rates, potential risks and complications, including rare adverse events, are also discussed.

Methods to incorporate patient preferences into medical decision algorithms and models and their quantification, balancing and evaluation: a scoping review protocol.

The objective of this scoping review is to identify and map methods used to incorporate patient preferences into medical algorithms and models as well report on their quantification, balancing, and evaluation in the literature. It will focus on computational methods used for incorporating patient preferences into algorithms and models at an individual level as well as the types of medical algorithms and models where these methods have been applied. Medical algorithms and models are increasingly being used to support clinical and shared decision-making; however, their effectiveness, accuracy, acceptance, and comprehension may be limited if patients' preferences are not considered. To address this issue, it is important to explore methods integrating patient preferences. This review will investigate patient preferences and their integration into medical algorithms and models for individual-level clinical decision-making. The scoping review will include diverse sources, such as peer-reviewed articles, clinical practice guidelines, gray literature, government reports, guidelines, and expert opinions for a comprehensive investigation of the subject. This scoping review will follow JBI methodology. A comprehensive search will be conducted in PubMed, Web of Science, ACM Digital Library, IEEE Xplore, the Cochrane Library, OpenGrey, the National Technical Reports Library, and the first 20 pages of Google Scholar. The search strategy will include keywords related to patient preferences, medical algorithms and models, decision-making, and software tools and frameworks. Data extraction and analysis will be guided by the JBI framework, which includes an explorative and qualitative analysis. Open Science Framework https://osf.io/qg3b5.

Influence of humanistic care-based operating room nursing on safety, recovery, and satisfaction after radical surgery for colorectal carcinoma

BACKGROUND Radical surgery is a preferred treatment for colorectal carcinoma, wherein nursing intervention is essential for postoperative recovery and prevention of complications. Recently, the application of humanistic care in medical care has attracted attention. Humanistic care emphasizes comprehensive care, with importance attached to patients’ physical needs as well as psychological and emotional support to provide more humane and personalized care services. However, no clinical reports have examined the use of humanistic care in patients undergoing radical surgery for colorectal carcinoma. AIM To investigate the influence of humanistic care-based operating room nursing on the safety, postoperative recovery, and nursing satisfaction of patients who have undergone radical surgery for colorectal carcinoma. METHODS In total, 120 patients with rectal cancer who underwent surgery in Zhongnan Hospital of Wuhan University between August 2023 and March 2024 were selected and grouped based on the nursing methods employed. Of these patients, 55 were treated with routine nursing intervention (control group) and 65 were provided humanistic care-based operating room nursing (research group). The patients’ vital signs were recorded, including systolic/diastolic blood pressure (SBP/DBP) and heart beats per minute (BPM), as well as serum stress indices, including norepinephrine (NE), adrenal hormone (AD), and cortisol (Cor). Postoperative recovery and complications were also recorded. Patients’ negative emotions, life hope, and nursing satisfaction were evaluated using the Self-rating Depression/Anxiety Scale (SDS/SAS), Herth Hope Index (HHI), and self-developed nursing satisfaction questionnaire, respectively. RESULTS During emergence from anesthesia, SBP, DBP, and BPM levels were found to be lower in the research group than those in the control group, also serum Cor, AD, and NE levels were lower. In addition, the research group had shorter operative, awakening, anal exhaust, first postoperative ambulation, drainage tube removal, intestinal recovery, and hospital times. The total complication rate and the SDS and SAS scores were lower in the research group than those in the control group. The HHI and nursing satisfaction scores were higher in the research group. CONCLUSION Humanistic care-based operating room nursing can mitigate physiological stress responses, reduce postoperative complications, promote postoperative recovery, relieve adverse psychological emotions, and enhance life hope and nursing satisfaction in patients undergoing radical surgery for colorectal carcinoma, which can be popularized in clinical practice.

Comprehensive Review on Effectiveness of Single and Multiple Visit Regenerative Endodontics and Comparative Evaluation of Patient Reported Outcomes in Single Visit and Multiple Visit Regenerative Endodontics in Permanent Teeth: A Systematic Review and Meta-Analysis

This systematic review aimed to investigate the efficacy of single visit and multiple visit regenerative endodontics and compare the patient based clinical outcome of permanent teeth treated with single visit &amp; multiple visit regenerative endodontic therapy. The protocol was registered with Prospero registration code CRD42024505225. A comprehensive search strategy was performed in different databases—PubMed, CENTRAL, ScienceDirect, CINAHL, ERIC and PsycINFO using searching keywords and was limited to studies published till January 2024 in English. The Inclusion criteria for the study were randomized clinical trial, prospective clinical studies, case Reports and case Series. The search found 20 eligible articles, which were included in the study. Risk of bias of clinical studies was conducted using ROBINS-I tool and JBL tool was used for quality assessment of case reports and case series included. The conclusions of our study concluded that in terms of clinical outcome both the approaches presented success of treatment with odds were greater with multiple visits as compared to single visit REP but statistically there was no difference between both the group. Radiographically outcome - In terms of root width diameter post treatment, single visit REPs were more successful as compared to multiple visits but statistical difference was not present. However, further research and emphasis should be given on undertaking more clinical trials regeneration in endodontics to provide proper results.

Drug-resistant tuberculosis care and treatment outcomes over the last 15 years in Ethiopia: Results from a mixed-method review of trends.

Drug resistant tuberculosis (DR-TB) remains a global challenge with about a third of the cases are not detected. With the recent advances in the diagnosis and treatment follow-up of DR-TB, there have been improvements with treatment success rates. However, there is limited evidence on the successful models of care that have consistently registered good outcomes. Our aim was to assess Ethiopia's experience in scaling up an ambulatory, decentralized model of care while managing multiple regimen transition processes and external shocks. This was a cross-sectional, mixed-method study. For the quantitative data, we reviewed routine surveillance data for the period 2009-2022 and collected additional data from publicly available reports. We then analyzed the data descriptively. Qualitative data were collected from program reports, quarterly presentations, minutes of technical working group meetings, and clinical review committee reports and analyzed thematically. The number of DR-TB treatment initiating centers increased from 1 to 67, and enrollment increased from 88 in 2010 to 741 in 2019, but declined to 518 in 2022. A treatment success rate (TSR) of over 70% was sustained. The decentralized and ambulatory service delivery remained the core service delivery model. The country successfully navigated multiple regimen transitions, including the recently introduced six-month short oral regimen. Several challenges remain, including the lack of strong and sustainable specimen transportation system, lack of established systems for timely tracing and linking of missed DR-TB cases, and data quality issues. Ethiopia scaled up a decentralized ambulatory model of care, kept up to date with recent developments in treatment regimens, and maintained a high TSR, despite the influence of multiple external challenges. The recent decline in case notification requires a deeper look into the underlying reasons. The feasibility of fully integrating DR-TB treatment and follow up at community level should be explored further.

When Type 1 von Willebrand Disease Lives Together with Hashimoto Thyroiditis, Hypothyroidism, Hypoparathyroidism, Morbid Obesity, and Bariatric Surgery: A Case Report

Von Willebrand disease (vWD) is the most common bleeding disorder with type 1 being the more prevalent, although underdiagnosis is an actual concern. This case is the first clinical report of a type 1 vWD with several comorbidities submitted to bariatric surgery. The authors demonstrate the importance of a diagnosis and the consideration of other diseases or disturbances in vWD patients’ perioperative management. A multidisciplinary approach is crucial for minimizing and preventing bleeding risk.

Spontaneous Intracranial Hypotension Associated With Vascular Malformations.

Spinal CSF leaks from dural tears or CSF-venous fistulas are the most common causes of spontaneous intracranial hypotension. Rarely, CSF leaks have also been associated with vascular malformations, which have primarily been discussed in case reports or small series. In this clinical report, we report the clinical features, imaging findings, and treatment of 6 children and adults with CSF leaks associated with vascular malformations in the spine and skull base depicted on CT myelography and cisternography.ABBREVIATIONS: SIH = spontaneous intracranial hypotension.

The Use of 3D Printing in Fetal Surgery for Surgical Planning: A Scoping Review.

Objectives: We sought to identify in which clinical scenarios 3D printed models are used to plan for fetal surgeries as well as the main purpose and the imaging method utilized for the models. In addition, we describe benefits and shortcomings of the models, as well as potential future improvements. Methods: In this scoping review, data were collected retrospectively from scientific databases (PubMed, Embase, Cochrane CENTRAL, CINAHL, Scopus, and the Web of Science platform) and screened by title, abstract, and full text against strict criteria. The inclusion criteria required the study be performed on a live fetus and involve 3D models used for fetal surgery. The models must have been designed from diagnostic imaging modalities such as CT, MRI, or ultrasound. The articles considered include clinical trials, review articles, cohort studies, case series, case reports, and conference abstracts. Results: Of the initial 742 articles collected, six met the inclusion criteria. Spina bifida and EXIT procedures were the most frequent use cases that inspired surgeons to print models for surgical planning. The ability to view patient-specific anatomy in a 3D handheld model was often touted as providing a great benefit to the surgical team's ability to anticipate intraoperative challenges. Conclusions: Three-dimensional printing models have been applied to plan for fetal surgeries, more specifically, for EXIT procedures and fetoscopic surgical repair of spina bifida. The potential benefits of 3D printing in fetal surgery are enormous.

Carrying both the heterozygous Myh6-R453C and Tnnt2-R92W mutations aggravate the hypertrophic cardiomyopathy phenotype in mice

Hypertrophic cardiomyopathy (HCM) is an inherited disease of the heart muscle that is dominated by variations in eight genes encoding sarcomere proteins. Although there are clinical or basic research reports that carrying double mutations can lead to more severe HCM phenotypes, there are also research reports that after reanalyzing the reported mutations, the severity of clinical symptoms in patients with double mutations did not significantly increase compared to patients with only one mutation. To determine whether double pathogenic mutations can aggravate the phenotype of hypertrophic cardiomyopathy in mice, we constructed mice carrying single pathogenic heterozygous mutation Myh6-R453C or Tnnt2-R92W and mice carrying both pathogenic heterozygous mutations. Our results showed that mice with double heterozygous mutations exhibited significant hypertrophic cardiomyopathy phenotypes at 4 weeks of age, and the degree of hypertrophy was significantly higher than that of single heterozygous mutant mice of the same age. Our study suggests that carrying the two pathogenic heterozygous mutations simultaneously can aggravate the phenotype of HCM in mice, which provides experimental evidence for the genotype-phenotype relationship of double pathogenic mutations and provides reference significance for clinical risk stratification of HCM patients.

Novel Challenges and Therapeutic Options for Pulmonary Embolism and Deep Vein Thrombosis.

Acute pulmonary embolism (PE), often resulting from deep vein thrombosis (DVT), is the third most frequent cause of cardiovascular death and is associated with increasing incidence, causing considerable morbidity and mortality. This review aims to evaluate the efficacy, safety, and outcomes of treatment options in the management of acute PE and DVT, encompassing both established and emerging technologies, such as catheter-directed thrombolysis, aspiration thrombectomy, and other endovascular techniques. A comprehensive literature review was conducted, assessing clinical studies, trials, and case reports that detail the use of percutaneous interventions for PE and DVT and analyzing the advantages and disadvantages of each percutaneous system. Several percutaneous treatments have shown promising results, especially in cases where rapid thrombus resolution is critical, such as in high- and intermediate-high-risk patients. The incidence of major complications, such as bleeding, remains a consideration, though it is generally manageable with proper patient selection and technique. It is fundamentally important to tailor the specific treatment strategy to the clinical and anatomical characteristics of each patient. Percutaneous treatments for acute PE and DVT represent valuable options in the therapeutic arsenal, offering enhanced outcomes in appropriately selected patients. Ongoing advancements in technology and technique, along with comprehensive clinical trials, are essential to further define the role and optimize the use of these interventions.