Cryptogenic HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella) CNS Abscess in an Otherwise Healthy Patient With a Patent Foramen Ovale.

Actinomyces and HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella) organisms are part of the oral microbiome and rarely affect the central nervous system (CNS). CNS infections with these agents can be caused by contiguous or hematogenous spread. We present a case of a 25-year-old immunocompetent male who presented with a one-week history of progressively worsening generalized headaches, photophobia, nausea, and vomiting. Despite a normal physical exam and the absence of leukocytosis, head imaging showed a right frontal lobe abscess. The patient was started empirically on vancomycin, ceftriaxone, and metronidazole, and surgery was performed. Surgical cultures grew organisms from the HACEK spectrum (Aggregatibacter, Eikenella), Gemella morbillorum, Streptococcus constellatus, and Actinomyces georgiae. Serial imaging studies showed a rapid increase in the size of the residual abscess, and the patient needed repeat intervention within five days. He was discharged five days after the repeat surgery on IV therapy prior to the transition to oral antibiotics. While the patient was found to have a small patent foramen ovale, there was no evidence of bacteremia or valvular vegetation, and no evidence of dental or sinus disease was seen on imaging. This case suggests that even in the absence of any clear sources of infection, cryptogenic brain abscesses can still occur sporadically in young, healthy patients.

The Impact of a Residual Atrial Communication in Patients Undergoing Complete Repair for Tetralogy of Fallot: A Propensity Score Matched Analysis.

OBJECTIVE: Surgeons may leave a residual atrial-level communication during complete repair of Tetralogy of Fallot (TOF) in anticipation of restrictive right ventricle physiology or as routine practice. We investigated the impact of closing the interatrial communication at the time of definitive TOF repair. METHODS: We retrospectively reviewed TOF patients who underwent definitive repair at <12 months of age between June 2000 and January 2023. Propensity score matching identified 82 patients with a patent interatrial communication and 50 with no interatrial communication on postoperative echocardiography (as-treated analysis). The primary endpoint was maximum vasoactive-inotropic score (VIS) as a surrogate for low cardiac output syndrome. RESULTS: A total of 132 patients (median age: 3.5[IQR,1.8-5.8] months) were matched. There was no difference in maximum VIS (patent interatrial communication: 5.0[IQR, 4.8-9.0] vs. no interatrial communication: 6.0[IQR, 5.0-8.0], P=0.78). Additionally, duration of inotrope therapy (3.0[IQR, 2.0-4.0] vs 3.0[IQR, 1.3-4.0] days, P=0.57), peak lactate (2.2[IQR, 1.9-3.0] vs. 2.3[IQR, 1.9-3.2] mmol/L, P=0.58), time to lactate clearance (0.2[IQR, 0.0-0.3] vs. 0.1[IQR, 0.0-0.3] days, P=0.57), chest tube duration (4.0[IQR,3.0-6.0] vs 4.0[IQR, 3.0-5.0] days, P=0.23), and length of intensive care stay (5.0[IQR, 3.0-7.0] vs. 5.0[IQR, 3.0-7.0] days, P=0.71) were similar. Median follow-up was 5.5[IQR, 2.7-9.9] years. Among patients with a residual communication, patency rates were 93.6% and 53.7% at discharge and latest follow-up, respectively, with most having bidirectional shunting across the defect. CONCLUSIONS: Closure of the atrial-level communication during complete TOF repair does not significantly impact the immediate postoperative course or mid-term outcomes. Further investigation is warranted to better understand how patency influences long-term outcomes.

Impact of antenatal corticosteroids-to-delivery interval on very preterm neonatal outcomes: a retrospective study in two tertiary centers in Japan.

BACKGROUND: Antenatal corticosteroids (ACS) are administered to prevent neonatal complications and death in women at risk of imminent preterm birth. Internationally, the optimal interval from ACS to delivery (ACS-to-delivery interval) is within seven days; however, evidence in Asian populations specifically is limited. This study aimed to investigate the association between ACS-to-delivery interval and the incidence of neonatal complications in Japan. METHODS: This retrospective observational study enrolled singleton neonates born preterm at < 32 weeks of gestational age between 2012 and 2020 at two tertiary centers. A total of 625 neonates were divided into the following four groups according to the timing of ACS (measured in days): no ACS (n = 145), partial ACS (n = 85), ACS 1-7 (n = 307), and ACS ≥ 8 (n = 88). The following outcomes were compared between the groups: treated respiratory distress syndrome (RDS), severe intraventricular hemorrhage (IVH), treated patent ductus arteriosus (PDA), necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (ROP), periventricular leukomalacia, and death discharge. RESULTS: The ACS 1-7 group had significantly decreased adjusted odds ratios (ORs) for treated RDS (0.37 [95% confidence interval: 0.23, 0.57]), severe IVH (0.21 [0.07, 0.63]), treated PDA (0.47 [0.29, 0.75]), and treated ROP (0.50 [0.25, 0.99]) compared with the no ACS group. The ACS ≥ 8 group also showed significantly reduced adjusted ORs for RDS (0.37 [0.20, 0.66]) and treated PDA (0.48 [0.25, 0.91]) compared with the no ACS group. However, the adjusted ORs for BPD significantly increased in both the ACS 1-7 (1.86 [1.06, 3.28]) and ACS ≥ 8 groups (2.94 [1.43, 6.05]) compared to the no ACS group. CONCLUSIONS: An ACS-to-delivery interval of 1-7 days achieved the lowest incidence of several complications in preterm neonates born at < 32 weeks of gestational age. Some of the favorable effects of ACS seem to continue even beyond ≥ 8 days from administration. In contrast, ACS might be associated with an increased incidence of BPD, which was most likely to be prominent in neonates delivered ≥ 8 days after receiving ACS. Based on these findings, the duration of the effect of ACS on neonatal complications should be studied further.

Pulmonary Atresia and Ventricular Septal Defect Without Major Aortopulmonary Collateral Arteries: Diagnostic Evaluation and the Role of Ductal Stenting.

Patients with pulmonary atresia (PA) and a ventricular septal defect (VSD), similar to those with tetralogy of Fallot and PA without major aortopulmonary collateral arteries, lack antegrade pulmonary blood flow, and thus require a neonatal intervention for stabilization or augmentation of pulmonary blood flow. The role of ductal stenting in the management of these patients, and the current literature supporting it, will be reviewed.

The risk of intraoperative venous air embolism from neurosurgical procedures performed in the lounging position: an in-depth analysis of detection, management, and outcomes of 1000 consecutive cases.

OBJECTIVE: The overall benefit of employing a sitting/semisitting position for neurosurgical procedures remains under criticism due to concerns for additional risk, especially the risk of intraoperative venous air embolism (VAE). The aim of this single-center cohort study was to evaluate the frequency and severity of VAEs and associated complications in patients undergoing neurosurgery in the lounging position. METHODS: From 2010 to 2020, 1000 patients, including 172 patients with a patent foramen ovale, underwent surgery in the lounging position for different neurosurgical pathologies. All patients were monitored intraoperatively using continuous transesophageal echocardiography (TEE). The anesthesia team documented any observed incidences of VAEs and scored their severity according to the Tuebingen classification system (TCS) for VAE (TCS-VAE). The patients' clinical condition, radiological findings, and hospital course were subsequently analyzed to assess complications in a retrospective analysis of prospectively collected data. RESULTS: In the cohort of 1000 patients, 5 underwent cervical spine surgery and 995 underwent suboccipital craniotomy. VAE was detected by TEE in 51.4% (95% CI 48.4%-54.5%) of patients, with synchronous changes in end-tidal CO2 (grade 2-5 TCS-VAE) noted in 10.2% (95% CI 8.3%-12.3%). None of the patients presented with hemodynamic instability (grade 5 TCS-VAE). Patients with high-grade VAEs were significantly older (p = 0.02) and had lower BMIs (p = 0.001) than the respective mean value of the cohort. VAE grade was not associated with any of the outcome measures such as Karnofsky Performance Scale score, duration of ventilation, length of intensive care unit stay, and length of hospital stay. Postoperative acute respiratory distress syndrome (ARDS) was diagnosed in 0.3% (95% CI 0.0%-0.7%, n = 3) of all cases, and ARDS was associated with perioperative VAE grade (p = 0.001). No patient suffered a new permanent neurological deficit due to a paradoxical VAE. CONCLUSIONS: In this large cohort, the risk of an intraoperative VAE during neurosurgery in the lounging position was assessed, and contrary to the general perception in the field, no permanent sequelae or fatal adverse events attributable to VAEs were observed. Furthermore, the overall incidence of ARDS was very low. This study clearly establishes that experienced interdisciplinary teams can safely use the lounging position for neurosurgical procedures.

Mechanism of norcantharidin intervention in gastric cancer: analysis based on antitumor proprietary Chinese medicine database, network pharmacology, and transcriptomics.

BACKGROUND: Combining antitumor proprietary Chinese medicine (pCm) with radiotherapy and chemotherapy can effectively improve tumor cure rates and enhance patients' quality of life. Gastric cancer (GC) severely endangers public health. Despite satisfactory therapeutic effects achieved by using antitumor pCm to treat GC, its underlying mechanism remains unclear. OBJECTIVE: To integrate existing research data, construct a database of antitumor pCm, and study the intervention mechanisms in GC by focusing on their monomer components. METHODS: We constructed an antitumor pCm database based on China's medical insurance catalog, and employed network pharmacology, molecular docking methods, cell experiments, transcriptomics, and bioinformatics to investigate the intervention mechanisms of effective pCm components for GC. RESULTS: The study built an antitumor pCm database including 55 pCms, 171 Chinese herbal medicines, 1955 chemical components, 2104 targets, and 32 disease information. Network pharmacology and molecular docking technology identified norcantharidin as an effective component of antitumor pCm. In vitro experiments showed that norcantharidin effectively inhibited GC cell proliferation, migration, and invasion; blocked the G2/M cell cycle phase; and induced GC cell apoptosis. Transcriptomic results revealed that norcantharidin affected biological processes, such as cell adhesion, migration, and inflammatory responses by influencing PI3K-AKT, NF-κB, JAK-STAT, TNF-α signaling pathways, and EMT-related pathways. Core molecules of norcantharidin involved in GC intervention include SERPINE1, SHOX2, SOX4, PRDM1, TGFR3, TOX, PAX9, IL2RB, LAG3, and IL15RA. Additionally, the key target SERPINE1 was identified using bioinformatics methods. CONCLUSION: Norcantharidin, as an effective component of anti-tumor pCm, exerts its therapeutic effects on GC by influencing biological processes such as cell adhesion, migration, and inflammation. This study provides a foundation and research strategy for the post-marketing re-evaluation of antitumor pCms.

The Potential of Ambroxol as a Panacea for Neonatal Diseases: A Scoping Review.

Ambroxol, a commonly used mucolytic agent, has been extensively studied for its clinical effectiveness in managing respiratory conditions in pediatric and adult patients. The existing body of research on ambroxol demonstrates its safety and efficacy. However, its potential role in preventing and treating neonatal diseases still needs to be explored. This scoping review aims to shed light on the unexplored potential of ambroxol, particularly its applications in perinatal and neonatal care. We aim to offer valuable insights for healthcare professionals, researchers, and academics, thus presenting a positive perspective. Key scientific databases such as Google Scholar, PubMed, Cochrane Library, and Europe PMC were meticulously searched for relevant literature on ambroxol in perinatal and neonatal medicine. Gray literature was also surveyed, and the search encompassed all study designs and languages up to June 2024. Furthermore, citations and reference lists of relevant articles were scrutinized to identify additional pertinent literature. Ambroxol has demonstrated promising effects in preventing and managing respiratory distress syndrome (RDS). It can enter the placental circulation and rapidly build up in human lung tissue to a much greater extent than in plasma. It promotes fetal lung maturation, surfactant production, and alveolar expansion. Numerous studies have demonstrated the efficacy of antenatal and postnatal ambroxol in the prevention and treatment of RDS. Ambroxol has the potential to be administered intravenously or through nebulization, offering the hopeful possibility of reducing the high failure rate typically associated with non-invasive ventilation in extremely preterm infants, instilling a sense of hope and optimism about the potential of ambroxol. It also shows potential in treating bronchopulmonary dysplasia, meconium aspiration syndrome, and neonatal infections. Ambroxol has been observed to assist in the closure of patent ductus arteriosus in preterm infants by inhibiting vasodilator agents such as nitric oxide and exerting vasoconstrictive properties. However, these biological actions may raise concerns regarding the potential induction of pulmonary hypertension and an increased risk of necrotizing enterocolitis. The present scoping review also examines the clinical evidence and the potential of ambroxol in reducing the incidence of intraventricular hemorrhage in preterm infants. Ambroxol may have potential analgesic properties in managing neonatal pain, and as it can penetrate the blood-brain barrier, it suggests potential neuroprotective properties. These properties may encompass the modulation of microglial activation and the antagonistic impact on glutamate receptors. Ambroxol's attributes could contribute to a decreased susceptibility to neurological complications and have demonstrated anticonvulsant effects in preclinical studies. While low-to-moderate-quality evidence indicates potential applications of ambroxol in neonatal care, further research is needed to determine the drug's optimal dosing, timing, and safety profiles in this patient population. We need to investigate ambroxol's potential synergistic effects with antenatal steroids. Exploration is required to assess ambroxol's potential in reducing the high failure rate associated with non-invasive respiratory support for RDS. Lastly, comprehensive studies on the long-term neurodevelopmental outcomes of neonates exposed to ambroxol are essential.

Overview and Future Direction of Embolic Stroke of Undetermined Source from the Insights of CHALLENGE ESUS/CS Registry.

Cryptogenic stroke (CS) accounts for approximately one-fourth of acute ischemic strokes, with most cases derived from embolic etiologies. In 2014, embolic stroke of undetermined source (ESUS) was advocated and the efficacy of anticoagulant therapy was anticipated. However, 3 large-scale clinical trials failed to demonstrate the superiority of direct oral anticoagulants (DOACs) over aspirin, potentially due to the heterogeneous and diverse pathologies of ESUS, including paroxysmal atrial fibrillation (AF), arteriogenic sources such as nonstenotic carotid plaque and aortic complicated lesion (ACL), patent foramen oval (PFO), and nonbacterial thrombotic endocarditis (NBTE) related to active cancer.Transesophageal echocardiography (TEE) is one of the most effective imaging modalities for assessing embolic sources in ESUS and CS. The Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for Embolic Stroke of Undetermined Source/Cryptogenic Stroke (CHALLENGE ESUS/CS) registry is a multicenter registry that enrolled consecutive patients with CS who underwent TEE at 8 hospitals in Japan between April 2014 and December 2016. Their mean age was 68.7±12.8 years, and 455 patients (67.2%) were male. The median National Institutes of Health Stroke Scale (NIHSS) score was 2. Since 7 analyses have been conducted from each institution to date, novel and significant insights regarding embolic origins and pathophysiologies of ESUS and CS were elucidated from this multicenter registry. This review discusses the diagnosis and treatment of ESUS and CS, tracing their past and future directions. Meaningful insights from the CHALLENGE ESUS/CS registry are also referenced and analyzed.

MEK inhibitors in oncology: a patent review and update (2016 - present).

INTRODUCTION: Mitogen-activated protein kinase (MEK) is one of the important components of Ras/Raf/MEK/ERK signaling pathway, transduces signal for cell growth, differentiation, and development. Deregulation of MEK leads to a wide variety of cancer; hence, MEK is considered as potential therapeutic targets for the treatment of cancer. The MEK1/2 inhibitors in combination with other inhibitors showed better therapeutic outcomes in various malignancies including resistant or relapsed or refractory cancer. AREAS COVERED: A comprehensive patent literature from the year 2016 to May 2024 on MEK inhibitors in oncology, their combination products and structural insights have been reviewed through searching relevant information in PubMed, Scopus, Espacenet, Web of Science, World Intellectual Property Organization and Google Patent databases. EXPERT OPINION: Overexpression and mutation of MEK have been reported to cause a wide variety of cancers especially resistant cancers. The MEK1/2 inhibitors in combination with other kinase (BRaf/KRas/PI3K) inhibitors showed significant anti-proliferative activity. Other combination of MEK inhibitor with PD-1, DYRK1, EGFR, BTK and/or VEGF inhibitors, etc. showed promising results in many cancers including colorectal, pancreatic, gastrointestinal, solid tumor, breast cancer, melanoma and multiple myeloma, etc. The dual or multi-targeted approaches of these combinations showed better and precise treatment of patients with resistant cancer.

Trends in covalent drug discovery: a 2020-23 patent landscape analysis focused on select covalent reacting groups (CRGs) found in FDA-approved drugs.

INTRODUCTION: Covalent drugs contain electrophilic groups that can react with nucleophilic amino acids located in the active sites of proteins, particularly enzymes. Recently, there has been considerable interest in using covalent drugs to target non-catalytic amino acids in proteins to modulate difficult targets (i.e. targeted covalent inhibitors). Covalent compounds contain a wide variety of covalent reacting groups (CRGs), but only a few of these CRGs are present in FDA-approved covalent drugs. AREAS COVERED: This review summarizes a 2020-23 patent landscape analysis that examined trends in the field of covalent drug discovery around targets and organizations. The analysis focused on patent applications that were submitted to the World International Patent Organization and selected using a combination of keywords and structural searches based on CRGs present in FDA-approved drugs. EXPERT OPINION: A total of 707 patent applications from >300 organizations were identified, disclosing compounds that acted at 71 targets. Patent application counts for five targets accounted for ~63% of the total counts (i.e. BTK, EGFR, FGFR, KRAS, and SARS-CoV-2 Mpro). The organization with the largest number of patent counts was an academic institution (Dana-Farber Cancer Institute). For one target, KRAS G12C, the discovery of new drugs was highly competitive (>100 organizations, 186 patent applications).

Pulmonary artery in situ thrombosis due to patent ductus arteriosus: a case report.

Background: Pulmonary Artery in situ Thrombosis (PAIST) refers to a thrombus forming within the pulmonary arterial system, distinct from an embolus originating from elsewhere in the body (e.g., the deep veins of the lower extremities) and traveling to the lungs where it lodges and forms. Case presentation: We present a case of PAIST caused by the arterial ductus arteriosus. The patient primarily presented with dyspnea, and the chest pain dichotomy Computed Tomography Angiography(CTA) suggested that a nodular low-density filling defect was seen in the lumen of the left pulmonary artery trunk. Initially, pulmonary embolism (PE) was suspected. However, upon reevaluation of the imaging, it became apparent that the patient's pulmonary artery obstruction was closely associated with the ductus arteriosus. After admission, the patient was treated with sodium ampicillin (2.0 g Q12H) for infection, heparin sodium (5,000 IU Q12H) for anticoagulation, and metoprolol succinate extended-release tablets (23.75 mg QD) to correct cardiac remodeling, among other treatments. Subsequently, the patient underwent a cardiac surgery involving the ligation of the arterial duct, resection of pulmonary artery lesions, and open-heart surgery with extracorporeal circulation support. Postoperative examination of the pulmonary artery mass indicated coagulation tissue. The final diagnosis was "PAIST". Conclusion: Both PAIST and PE manifest as low-density filling defects in the pulmonary arteries. However, due to the relative unfamiliarity with PAIST, such findings are often initially attributed to PE.

Striving for healthy lungs: Enhancing respiratory outcomes of prematurity.

Infants born prematurely are born in a critical developmental time period and because of arrest of lung maturation at that period their pulmonary functions are below the normal for their age. Early lung development has a lifelong effect on respiratory health and disease. Can we affect that sequence of events and change the outcome of chronic lung disease of prematurity?

Top 50 Spine Surgery Publications Most Cited by Patents: A Bibliometric Analysis Focused on Research Driving Innovation.

BACKGROUND: The use of bibliometric analysis studies allows for the precise assessment of high impact contributions to various fields of study. A bibliometric assessment of academic works cited in filed patents enables tracking the academic studies which have been most influential in the development of new technologies in spine surgery. METHODS: The Lens database was utilized to retrieve scholarly articles related to the field of spine surgery, with special focus on spinal fusion and biologics. Scholarly works cited in patents were organized by publishing journal, article topic, study type, publishing institution, and authors information. Such publications were also categorized by country of origin and, for U.S. patents, region of origin. RESULTS: The employed search criteria yielded 37,005 scholarly works related to spine surgery published between 1889 and 2022 and a total of 947 scholarly works cited in patents from 1968 to 2022. Many of the top contributing authors were orthopedic surgeons while the top 3 authors were biomedical engineers. The region in the U.S. with the most citations in patents and the most scholarly work overall was the middle-Atlantic region. CONCLUSIONS: This patent bibliometric analysis provides a general overview of trends in publications impacting spine surgery innovation over time. Our results highlight top instutions and regional contributions to spine surgery innovation within the United States and worldwide. As the first patent bibliometric study providing data on the most technologically impactful scholarly work in spine surgery, this study has not only historical value in terms of documenting the scientific and intellectual property developments in spine surgery in the past 50 years, but also practical relevance insofar as the identified trends and research hotspots that may provide researchers valuable insights regarding future decisions involving research efforts and resources allocation.

Feasibility and Success of Muscular Ventricular Septal Defect Occluders and Mushroom-Shaped Occluders in Transcatheter Patent Ductus Arteriosus Closure in Low-Weight Children: A Propensity Score-Matched Retrospective Analysis from a Chinese National Regional Health Center.

INTRODUCTION: Muscular ventricular septal defect occluders (MVSDOs) have been attempted as an option in low-weight patients with patent ductus arteriosus (PDA). However, few studies have assessed the safety of transcatheter patent ductus arteriosus closure (TCPC) using MVSDO. Therefore, we compared the outcomes in low-weight patients who used MVSDO and mushroom-shaped occluder (MSO). METHODS: Medical records of children under 10 kg (n = 417) who underwent TCPC from 2015 to 2021 at a Chinese health center were reviewed. They were divided into MSO (n = 372) and MVSDO (n = 45) groups. A 1:1 propensity score matching (PSM) was done considering gender, height, weight, body surface area (BSA), PDA diameter, and BSA-corrected PDA diameter. RESULTS: All 45 children in the MVSDO group (mean weight: 5.92 ± 1.32 kg) achieved successful immediate occlusion. One case in the MVSDO group experienced device migration within 24 h requiring unplanned surgery. MVSDO significantly ameliorated pulmonary artery hypertension. After PSM, each group comprised 41 children. The MVSDO group had a smaller effect on platelet counts (MVSDO vs. MSO = 259.85 ± 114.82 vs. 356.12 ± 134.37, p < 0.001), a reduced incidence of thrombocytopenia (MVSDO vs. MSO = 2/41 vs. 7/41, p = 0.001), and a higher rate of residual shunting (MVSDO vs. MSO = 16/41 vs. 5/41, p = 0.005), compared with the MSO group. Thrombocytopenia resolved during hospitalization and micro-shunts disappeared by 6 months. No pulmonary artery or descending aortic secondary stenosis was observed in 1-year follow-up. CONCLUSIONS: MVSDO used in low-weight children is feasible, with high success and satisfactory postoperative and short-term follow-up outcomes, including lower thrombocytopenia incidence, compared to MSO. Further long-term studies with larger samples are recommended.

Platypnea-orthodeoxia syndrome in a patient with poor activity of daily living: Struggling with a definitive diagnosis.

A 73-year-old female patient was diagnosed with lumbar spinal stenosis by an orthopedic surgeon. During admission for further evaluation, she was found to have hypoxemia. Contrast-enhanced computed tomography revealed a 43-mm ascending aortic aneurysm, but there were no signs of pulmonary embolism, and no abnormalities were detected in the lung fields. Upon initiating rehabilitation in the standing position, respiratory distress and hypoxemia worsened. Careful observation revealed that hypoxemia worsened in the seated position but normalized while lying down. We considered the possibility of platypnea-orthodeoxia syndrome (POS), in which hypoxemia worsens in the seated position. Transesophageal echocardiography revealed that a patent foramen ovale (PFO), which was hardly noticeable while lying down, worsened in the seated position. A pulmonary perfusion scan showed a 27 % right-to-left shunt. Cardiac catheterization confirmed the presence of right-to-left shunting during right atrial injection. Consequently, it was diagnosed that the ascending aortic aneurysm aggravated the PFO in the seated position, leading to POS. The PFO was unsuitable for transcatheter treatment. Consequently, the patient underwent direct closure surgery in the cardiac surgery department. Postoperatively, the patient's hypoxemia and respiratory distress in the seated position improved, and subsequent progress has been favorable. Learning objective: Diagnosing platypnea-orthodeoxia syndrome in patients with poor activities of daily living (ADL) is challenging. Careful observation of the percutaneous oxygen saturation in both supine and seated positions is crucial, and a transesophageal echocardiogram in the supine and seated positions is inevitable. Lung perfusion scintigraphy is often used to evaluate the cause of hypoxemia; however, whole-body scans are important for detecting the presence and number of right-left shunts. This case report highlights the pitfalls of diagnosis in patients with poor ADL.

Platypnea-Orthodeoxia Syndrome After the Bentall Procedure.

Platypnea-orthodoxia syndrome (POS) is a clinical condition that causes dyspnea and hypoxia in the sitting and standing positions. In this case, a 67-year-old man showed hypoxemia after undergoing the Bentall procedure that worsened in the standing position during rehabilitation. Contrast-enhanced computed tomography of the thorax and abdomen revealed no cause of respiratory failure. POS was suspected as the cause of the positional exacerbation of oxygen saturation. A bubble study showed a positive grade IV within three heartbeats on transthoracic echocardiography, which also confirmed an intracardiac shunt caused by a patent foramen ovale (PFO). Percutaneous PFO closure was performed, and hypoxemia was immediately resolved. Various factors were considered to cause the POS, including right heart failure, constrictive pericarditis, and postoperative adhesions, and each of these factors was discussed. POS after open-heart surgery is very rare. This is the first reported case of POS treated with a closure device following the Bentall procedure.

International treatment outcomes of neonates on extracorporeal membrane oxygenation (ECMO) with persistent pulmonary hypertension of the newborn (PPHN): a systematic review.

BACKGROUND: PPHN is a common cause of neonatal respiratory failure and is still a serious condition and associated with high mortality. OBJECTIVES: To compare the demographic variables, clinical characteristics, and treatment outcomes in neonates with PHHN who underwent ECMO and survived compared to neonates with PHHN who underwent ECMO and died. METHODS: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature for studies on the development of PPHN in neonates who underwent ECMO, published from January 1, 2010 to May 31, 2023, with English language restriction. RESULTS: Of the 5689 papers that were identified, 134 articles were included in the systematic review. Studies involving 1814 neonates with PPHN who were placed on ECMO were analyzed (1218 survived and 594 died). Neonates in the PPHN group who died had lower proportion of normal spontaneous vaginal delivery (6.4% vs 1.8%; p value > 0.05) and lower Apgar scores at 1 min and 5 min [i.e., low Apgar score: 1.5% vs 0.5%, moderately abnormal Apgar score: 10.3% vs 1.2% and reassuring Apgar score: 4% vs 2.3%; p value = 0.039] compared to those who survived. Neonates who had PPHN and died had higher proportion of medical comorbidities such as omphalocele (0.7% vs 4.7%), systemic hypotension (1% vs 2.5%), infection with Herpes simplex virus (0.4% vs 2.2%) or Bordetella pertussis (0.7% vs 2%); p = 0.042. Neonates with PPHN in the death group were more likely to present due to congenital diaphragmatic hernia (25.5% vs 47.3%), neonatal respiratory distress syndrome (4.2% vs 13.5%), meconium aspiration syndrome (8% vs 12.1%), pneumonia (1.6% vs 8.4%), sepsis (1.5% vs 8.2%) and alveolar capillary dysplasia with misalignment of pulmonary veins (0.1% vs 4.4%); p = 0.019. Neonates with PPHN who died needed a longer median time of mechanical ventilation (15 days, IQR 10 to 27 vs. 10 days, IQR 7 to 28; p = 0.024) and ECMO use (9.2 days, IQR 3.9 to 13.5 vs. 6 days, IQR 3 to 12.5; p = 0.033), and a shorter median duration of hospital stay (23 days, IQR 12.5 to 46 vs. 58.5 days, IQR 28.2 to 60.7; p = 0.000) compared to the neonates with PPHN who survived. ECMO-related complications such as chylothorax (1% vs 2.7%), intracranial bleeding (1.2% vs 1.7%) and catheter-related infections (0% vs 0.3%) were more frequent in the group of neonates with PPHN who died (p = 0.031). CONCLUSION: ECMO in the neonates with PPHN who failed supportive cardiorespiratory care and conventional therapies has been successfully utilized with a neonatal survival rate of 67.1%. Mortality in neonates with PPHN who underwent ECMO was highest in cases born via the caesarean delivery mode or neonates who had lower Apgar scores at birth. Fatality rate in neonates with PPHN who underwent ECMO was the highest in patients with higher rate of specific medical comorbidities (omphalocele, systemic hypotension and infection with Herpes simplex virus or Bordetella pertussis) or cases who had PPHN due to higher rate of specific etiologies (congenital diaphragmatic hernia, neonatal respiratory distress syndrome and meconium aspiration syndrome). Neonates with PPHN who died may need a longer time of mechanical ventilation and ECMO use and a shorter duration of hospital stay; and may experience higher frequency of ECMO-related complications (chylothorax, intracranial bleeding and catheter-related infections) in comparison with the neonates with PPHN who survived.

Deep vein thrombosis in patients with stroke or transient ischemic attack presenting with patent foramen ovale: a retrospective observational study.

OBJECTIVE: Deep vein thrombosis (DVT) is discussed as a source of embolism for cerebral ischemia in the presence of patent foramen ovale (PFO). However, previous studies reported varying rates of DVT in stroke patients, and recommendations for screening are lacking. This study aimed to characterize patients with stroke or transient ischemic attack (TIA) and concomitant PFO and explore the rate of DVT and associated parameters. METHODS: Medical records were screened for patients with stroke or TIA and echocardiographic evidence of PFO. Concomitant DVT was identified according to compression ultrasonography of the lower limbs. A variety of demographic, clinical, and laboratory parameters, the RoPE and Wells scores were compared between patients with and without DVT. RESULTS: Three-hundred-thirty-nine patients (mean age 61.2 ± 15.4 years, 61.1% male) with stroke or TIA and PFO, treated between 01/2015 and 12/2020, were identified. Stroke and TIA patients did not differ for demographic and vascular risk factors. DVT was found in 17 cases out of 217 (7.8%) with compression ultrasonography. DVT was associated with a history of DVT, cancer, previous immobilization, calf compression pain, calf circumference difference, and a few laboratory abnormalities, e.g., increased D-dimer. A multivariate regression model with stepwise backward selection identified the Wells score (odds ratio 35.46, 95%-confidence interval 4.71-519.92) as a significant predictor for DVT. CONCLUSION: DVT is present in a relevant proportion of patients with cerebral ischemia and PFO, which needs to be considered for the individual diagnostic workup. The Wells score seems suitable for guiding additional examinations, i.e., compression ultrasonography.

Case Report: Patent ductus arteriosus with tuberous sclerosis complex.

A 33-year-old patient presented with a chief complaint of patent ductus arteriosus (PDA) persisting for over 30 years. Physical examination revealed bilateral facial angiofibromas, multiple nail fibromas, intraoral fibromas, and a 'shagreen patch' on the left lumbar region. Genetic testing was performed using a peripheral venous blood sample, which confirmed the diagnosis of Tuberous Sclerosis Type 2 (TSC2). Subsequently, the patient underwent cardiac color Doppler ultrasound and chest computed tomography angiography, which confirmed the presence of PDA. Tuberous sclerosis complex (TSC) is associated with cardiovascular diseases. The initial clinical manifestation of TSC is usually cardiac rhabdomyoma in children, and it is rarely reported in adults with PDA. In this case, the patient was diagnosed with PDA when he was young, and the genetic test showed heterozygous variation of TSC2 gene. The purpose of this article is to explore the correlation between TSC and PDA at the gene level through literature review.