The development of a highly sensitive and quantitative SARS-CoV-2 rapid antigen test applying newly developed monoclonal antibodies to an automated chemiluminescent flow-through membrane immunoassay device.

BACKGROUND: Rapid and accurate diagnosis of individuals with SARS-CoV-2 infection is an effective way to prevent and control the spread of COVID-19. Although the detection of SARS-CoV-2 viral RNA by RT-qPCR is the gold standard for COVID-19 testing, the use of antigen-detecting rapid diagnostic tests (Ag-RDTs) is emerging as a complementary surveillance tool as Omicron case numbers skyrocket worldwide. However, the results from Ag-RDTs are less accurate in individuals with low viral loads. RESULTS: To develop a highly sensitive and accurate Ag-RDT, 90 monoclonal antibodies were raised from guinea pigs immunized with SARS CoV-2 nucleocapsid protein (CoV-2-NP). By applying a capture antibody recognizing the structural epitope of the N-terminal domain of CoV-2-NP and a detection antibody recognizing the C-terminal tail of CoV-2-NP to an automated chemiluminescence flow-through membrane immunoassay device, we developed a novel Ag-RDT, CoV-2-POCube. The CoV-2-POCube exclusively recognizes CoV-2-NP variants but not the nucleocapsid proteins of other human coronaviruses. The CoV-2-POCube achieved a limit of detection sensitivity of 0.20 ~ 0.66 pg/mL of CoV-2-NPs, demonstrating more than 100 times greater sensitivity than commercially available SARS-CoV-2 Ag-RDTs. CONCLUSIONS: CoV-2-POCube has high analytical sensitivity and can detect SARS-CoV-2 variants in 15 min without observing the high-dose hook effect, thus meeting the need for early SARS-CoV-2 diagnosis with lower viral load. CoV-2-POCube is a promising alternative to currently available diagnostic devices for faster clinical decision making in individuals with suspected COVID-19 in resource-limited settings.

[Breast and Advanced Ovarian Double Cancer with a BRCA2 Pathogenic Variant-A Case Report].

A 49-year-old woman presented with abdominal pain. A computed tomography scan revealed a left breast mass with suspected peritoneal dissemination. She had no notable family history of the disease. Following a detailed examination, she was diagnosed with ovarian cancer(Stage ⅢC)and left breast cancer(Stage Ⅰ). After confirming the diagnosis of ovarian cancer with a laparoscopic biopsy, neoadjuvant chemotherapy was scheduled. Due to its efficiency in reducing tumor burden, debulking surgery was also performed. While receiving adjuvant chemotherapy for ovarian cancer, concomitant anastrozole was administered for breast cancer. A pathogenic variant of BRCA2 was subsequently identified. Once adjuvant chemotherapy for ovarian cancer had been completed, a left mastectomy and sentinel lymph node biopsy were performed as management for breast cancer. The patient will continue treatment with anastrozole for breast cancer and olaparib for ovarian cancer and will be followed up appropriately.

Development of a novel and rapid measurement system for growth differentiation factor-15, progranulin, and osteopontin in uterine sarcoma.

Uterine sarcomas are rare and aggressive gynecologic tumors with poor prognosis; therefore, early diagnosis is crucial for therapy. However, it is very difficult to distinguish uterine sarcomas from leiomyomas which are common benign uterine tumors. Therefore, the development of a diagnostic method that utilizes reliable biomarkers to distinguish uterine sarcomas from leiomyomas is important so as to identify the rare tumors. The candidate factors as novel biomarkers were searched for in public databases and a pilot study was performed for confirmation. Growth differentiation factor-15 (GDF15), progranulin, and osteopontin were identified as candidate biomarkers for diagnosing uterine sarcoma. Thus, developing a rapid and easy method to measure these factors could help establish a screening system for uterine sarcomas. In this study, we developed a novel measurement system for these factors using a compact chemical luminescence immunological automatic analyzer POCubeTM. This assay system, which is based on the flow-through membrane immunoassay, completes the whole process and generates results within 15 min. Serum concentrations of these factors measured via POCubeTM correlated well with those measured using enzyme-linked immunosorbent assay (r = 0.994 for GDF15, r = 0.992 for progranulin, and r = 0.976 for osteopontin). The POCubeTM system provides rapid and easy measurement of these factors, thereby facilitating uterine sarcoma diagnosis.

[Direct Carotid Puncture for Endovascular Thrombectomy in a 96-Year-Old Patient with Acute Cerebral Infarction:A Case Report].

We report a case of direct carotid puncture for endovascular thrombectomy in a 96-year-old patient with acute cerebral infarction. Anatomical difficulties of carotid artery access, including an unfavorable aortic arch type and the tortuosity of carotids, could have resulted in a recanalization delay or failure in patients with acute ischemic stroke. A 96-year-old woman developed sudden right hemiparesis. By initiating thrombectomy, we could not access the common carotid artery;therefore, we performed a direct carotid puncture on the neck and achieved successful recanalization with improvement of hemiparesis. We discuss the limitations and technical aspects of this technique. We conclude that in case of stroke, a direct carotid artery puncture is a feasible alternative to an anatomically difficult transfemoral access.

[A Case of Carcinomatous Pericarditis of Breast Cancer Successfully Treated with Intrapericardial Mitomycin C Instillations and Systemic Chemotherapy].

A 67-year-old woman who underwent left breast mastectomy and right breast partial mastectomy under the diagnosis of left breast cancer and suspected right breast cancer 10 years earlier was admitted because of dyspnea. Chest computed tomography revealed pericardial fluid accumulation. The patient was treated with pericardial drainage; thereby, 800 mL of bloody fluid was removed. The cytological diagnosis was malignancy. After receiving mitomycin C instillation, she underwent systemic chemotherapy and endocrine therapy. At the last follow-up more than 5 years after the recurrence, no reaccumulation of the pericardial fluid was observed, and she remained alive in good condition.

[W-shaped Resection and Suture of the Posterior Mitral Leaflet in a Patient with Barlow's Disease].

A 72-year-old female presented with congestive heart failure. Ultrasound cardiogram revealed billowing mitral leaflets and severe mitral regurgitation. We diagnosed her with Barlow's disease and performed mitral valve repair. The posterior leaflet was large, and the leaflet height was more than 26 mm. Leaflet height reduction was necessary in order to prevent systolic anterior movement (SAM). The middle scallop was resected in a" W" shape, and its center vertex was designed to have a height of 18 mm, which was the final height of the posterior leaflet. SAM and major leaks were not seen by transesophageal echocardiography after weaning the patient from cardiopulmonary bypass. The use of a W-shaped resection is a simple technique that can be used to reduce the volume and height of the posterior mitral leaflet.

[Aortic regurgitation with osteogenesis imperfecta].

A 49-year-old male was referred to our hospital for cardiomegaly and severe aortic regurgitation. He had been diagnosed with osteogenesis imperfecta (OI) due to his history of multiple fractures in childhood and blue sclera. Aortic valve replacement(AVR) was performed via femoral cannulation and full sternotomy, with the opening of the sternum limited to a width of 6-7 cm in order to protect the brittle sternum and thorax. After weaning the patient off cardiopulmonary bypass, the sternum was closed using titanium plates. He subsequently recovered without excessive bleeding or other complications, and the healing of the sternum 3 months after the surgery was satisfactory. Cardiovascular surgery has been reported to be associated with high morbidity and mortality in patients with OI due to their friability of tissue and bleeding tendency. In the present case, AVR was performed successfully in a patient with OI using various surgical techniques.

[Lung Cancer Treated with Wedge Resection of the Lower Lobe of the Left Lung with the Assistance of Extracorporeal Membrane Oxygenation(ECMO) after Right Pneumonectomy].

A 59-year-old male was admitted to our hospital with an abnormal shadow on a chest X-ray. Right pneumonectomy and lymph node dissection (ND2a) were performed. A pathological examination revealed adenocarcinoma( pT3N2M0). Fourteen years later, chest computed tomography(CT) showed a tumor shadow in the lower lobe of the left lung. His pulmonary function was sufficient to allow a 2nd operation. He underwent wedge resection of the lower lobe of the left lung with the assistance of extra corporeal membrane oxygenation (ECMO). His postoperative course was uneventful. A pathological examination revealed large cell neuroendocrine carcinoma, which was 18 mm in diameter. His performance status declined slightly, but he had no problems associated with the activities of daily life. The patient is currently alive 6 months after the 2nd operation without any sign of recurrence. ECMO is a useful technique for thoracic surgery after pneumonectomy.

Development of a sensitive novel diagnostic kit for the highly pathogenic avian influenza A (H5N1) virus.

BACKGROUND: Sporadic emergence of the highly pathogenic avian influenza (HPAI) H5N1 virus infection in humans is a serious concern because of the potential for a pandemic. Conventional or quantitative RT-PCR is the standard laboratory test to detect viral influenza infections. However, this technology requires well-equipped laboratories and highly trained personnel. A rapid, sensitive, and specific alternative screening method is needed. METHODS: By a luminescence-linked enzyme immunoassay, we have developed a H5N1 HPAI virus detection kit using anti-H5 hemagglutinin monoclonal antibodies in combination with the detection of a universal NP antigen of the type A influenza virus. The process takes 15 minutes by use of the fully automated luminescence analyzer, POCube. RESUTLS: We tested this H5/A kit using 19 clinical specimens from 13 patients stored in Vietnam who were infected with clade 1.1 or clade 2.3.4 H5N1 HPAI virus. Approximately 80% of clinical specimens were H5-positive using the POCube system, whereas only 10% of the H5-positive samples were detected as influenza A-positive by an immunochromatography-based rapid diagnostic kit. CONCLUSIONS: This novel H5/A kit using POCube is served as a rapid and sensitive screening test for H5N1 HPAI virus infection in humans.

A Case of Isolated Superior Mesenteric Artery Dissection Resulting in Recurrent Necrosis of the Small Intestine.

Isolated superior mesenteric artery dissection (ISMAD) is a rare cause of acute abdominal conditions. Most cases of ISMAD have a favorable prognosis, and only a few cases of ISMAD-associated intestinal necrosis have been reported. A 75-year-old male was referred to our department because of abdominal pain and portal venous gas detected on imaging. Computed tomography suggested ileal necrosis, necessitating emergency surgery. Indocyanine green was used for blood flow assessment; however, no fluorescence was observed in the ileum proximal to the Bauhin valve, leading to the decision for ileocecal resection. On postoperative day 6, abdominal pain recurred when meals were resumed. As a surgical intervention for ISMAD, a bypass was created using the left great saphenous vein as a graft between the superior mesenteric artery and the right external iliac artery. This case highlights a rare occurrence where intestinal necrosis recurred due to ISMAD. We propose that in cases of ISMAD with concomitant intestinal necrosis, a more aggressive revascularization strategy for the dissected segment of the superior mesenteric artery may be required.

Beneficial Effects of Human Schwann Cell-Derived Exosomes in Mitigating Secondary Damage After Penetrating Ballistic-Like Brain Injury.

There is a growing body of evidence that the delivery of cell-derived exosomes normally involved in intracellular communication can reduce secondary injury mechanisms after brain and spinal cord injury and improve outcomes. Exosomes are nanometer-sized vesicles that are released by Schwann cells and may have neuroprotective effects by reducing post-traumatic inflammatory processes as well as promoting tissue healing and functional recovery. The purpose of this study was to evaluate the beneficial effects of human Schwann-cell exosomes (hSC-Exos) in a severe model of penetrating ballistic-like brain injury (PBBI) in rats and investigate effects on multiple outcomes. Human Schwann cell processing protocols followed Current Good Manufacturing Practices (cGMP) with exosome extraction and purification steps approved by the Food and Drug Administration for an expanded access single ALS patient Investigational New Drug. Anesthetized male Sprague-Dawley rats (280-350g) underwent PBBI surgery or Sham procedures and, starting 30 min after injury, received either a dose of hSC-Exos or phosphate-buffered saline through the jugular vein. At 48h after PBBI, flow cytometry analysis of cortical tissue revealed that hSC-Exos administration reduced the number of activated microglia and levels of caspase-1, a marker of inflammasome activation. Neuropathological analysis at 21 days showed that hSC-Exos treatment after PBBI significantly reduced overall contusion volume and decreased the frequency of Iba-1 positive activated and amoeboid microglia by immunocytochemical analysis. This study revealed that the systemic administration of hSC-Exos is neuroprotective in a model of severe TBI and reduces secondary inflammatory injury mechanisms and histopathological damage. The administration of hSC-Exos represents a clinically relevant cell-based therapy to limit the detrimental effects of neurotrauma or other progressive neurological injuries by impacting multiple pathophysiological events and promoting neurological recovery.

Risk factors and management of intraprocedural rupture during coil embolization of unruptured intracranial aneurysms: role of balloon guiding catheter.

Introduction: Intraprocedural rupture (IPR) is a serious complication of endovascular coil embolization of unruptured intracranial aneurysms (UIAs). Although outcomes after IPR are poor, methods to prevent subsequent neurological deterioration have not yet been investigated. We evaluated the risk factors and management strategies for IPR, particularly the role of balloon guiding catheters (BGCs) in rapid hemostasis. Methods: We retrospectively reviewed all UIA cases treated with coil embolization at three institutions between 2003 and 2021, focusing on preoperative radiological data, operative details, and outcomes. Results: In total, 2,172 aneurysms were treated in 2026 patients. Of these, 19 aneurysms in 19 patients (0.8%) ruptured during the procedure. Multivariate analysis revealed that aneurysms with a bleb (OR: 3.03, 95% CI: 1.21 to 7.57, p = 0.017), small neck size (OR: 0.56, 95% CI: 0.37 to 0.85, p = 0.007), and aneurysms in the posterior communicating artery (PcomA) (OR: 4.92, 95% CI: 1.19 to 20.18, p = 0.027) and anterior communicating artery (AcomA) (OR: 12.08, 95% CI: 2.99 to 48.79, p < 0.001) compared with the internal carotid artery without PcomA were significantly associated with IPR. The incidence of IPR was similar between the non-BGC and BGC groups (0.9% vs. 0.8%, p = 0.822); however, leveraging BGC was significantly associated with lower morbidity and mortality rates after IPR (0% vs. 44%, p = 0.033). Discussion: The incidence of IPR was relatively low. A bleb, small aneurysm neck, and location on PcomA and AcomA are independent risk factors for IPR. The use of BGC may prevent fatal clinical deterioration and achieve better clinical outcomes in patients with IPR.

[Circulatory disturbance of middle lobe by bending of lobar pedicle after right upper lobectomy].

A 66-year-old man was diagnosed as lung cancer. We performed right upper lobectomy and lymphnode dissection. On the 1st postoperative day, a chest radiograph showed an opacification in the right upper lung field. Computed tomography (CT) showed a stenosis of the middle lobe bronchus and infiltrative shadow of the middle lobe on the 3rd postoperative day. Fiber optic bronchoscopic examination also revealed a bend and stenosis of the middle lobe bronchus, but tortion was not demonstrated. On the 6th postoperative day, chest radiographic findings was worsened. Torsion of the middle lobe was suspected, and rethoracotomy was performed on the 7th postoperative day. The right middle lobe was not rotated, but the lobar pedicle bend toward cranial. The middle lobe was highly congested necessitating lobectomy.

Advances in Traumatic Brain Injury Biomarkers.

Traumatic brain injury (TBI) is increasingly a major cause of disability across the globe. The current methods of diagnosis are inadequate at classifying patients and prognosis. TBI is a diagnostic and therapeutic challenge. There is no Food and Drug Administration (FDA)-approved treatment for TBI yet. It took about 16 years of preclinical research to develop accurate and objective diagnostic measures for TBI. Two brain-specific protein biomarkers, namely, ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein, have been extensively characterized. Recently, the two biomarkers were approved by the FDA as the first blood-based biomarker, Brain Trauma Indicator™ (BTI™), via the Breakthrough Devices Program. This scoping review presents (i) TBI diagnosis challenges, (ii) the process behind the FDA approval of biomarkers, and (iii) known unknowns in TBI biomarker biology. The current lag in TBI incidence and hospitalization can be reduced if digital biomarkers such as hard fall detection are standardized and used as a mechanism to alert paramedics to an unresponsive trauma patient.

Reinforcement of pericranium as a dural substitute by fibrin sealant.

BACKGROUND: For dural plasty, several kinds of substitute materials are used clinically. Among these materials, pericranium is often used as a dural substitute since it is autologous and easy to harvest. However, it is rather thin and fragile, which makes it difficult to suture onto peripheral dura mater, especially when the defect is large. OBJECTIVE: We present a simple method of reinforcing the pericranium with fibrin sealant, which facilitates easier handling and suturing of the pericranium. METHODS: Fifteen patients who underwent surgical removal of meningioma, metastatic brain tumor and glioma attached to the dura mater were included in this analysis. To close the defects, we use 'fibrin-sealed pericranium'. Herein we describe the method we employed in these cases. First, a standard skin flap is made by dissecting the subgaleal layer, leaving the periosteum on the bone. Second, fibrin sealant is evenly applied to the pericranium. Finally, the pericranium is cut along the reinforced area and dissected from the bone. The harvested pericranium is then used for closure of the dural defect. Some of these patients received further treatment as needed according to each pathology. The fibrin-sealed pericranium was examined histopathologically. RESULTS: Fibrin-sealing of pericranium made it durable enough to be handled and sutured easily. There were no significant complications or treatment failures, such as infection or CSF leakage. CONCLUSIONS: Reinforcement of the pericranium with fibrin sealant is a simple and easy method to reduce the stress of dural plasty.

[Successful repair of penetrating cardiac injury with chopstick; report of a case].

We used percutaneous cardiopulmonary support (PCPS) to resuscitate a 54-year-old man who had stabbed himself in the left anterior chest with a chopstick. Chest computed tomography showed that the chopstick had penetrated the heart. As he was in shock due to the development of tamponade while waiting for emergency surgery, we immediately decided to initiate PCPS. After cardiopulmonary bypass was established through a median sternotomy replacing PCPS, the chopstick was removed and the stab wounds were closed by mattress sutures. The postoperative course was uneventful.

Visualization of extracranial-intracranial bypass in moyamoya patients using intraoperative three-dimensional digital subtraction angiography with intravenous contrast injection and robotic C-arm: patient series.

BACKGROUND: The authors describe a noninvasive intraoperative imaging strategy of three-dimensional (3D) digital subtraction angiography (DSA) with intravenous (IV) contrast injection, using indocyanine green (ICG) as a test bolus, during extracranial-intracranial (EC-IC) bypass surgery for moyamoya disease. OBSERVATIONS: Four patients underwent EC-IC bypass surgery in a hybrid operating room. During the surgery, bypass patency was verified using ICG videoangiography and Doppler ultrasonography. After skin closure, the patients under anesthesia underwent IV 3D-DSA with a robotic C-arm in which the scan delay time for the 3D-DSA scan was estimated from the arrival time of ICG during the ICG videoangiography. One day after the surgery, the patients underwent magnetic resonance angiography (MRA). The IV 3D-DSA images were retrospectively compared with those obtained with other modalities. Good bypass patency was confirmed on IV 3D-DSA, ICG videoangiography, Doppler ultrasonography, and postoperative MRA in all cases. The delay time determined using ICG videoangiography as a test bolus resulted in IV 3D-DSA with adequate image quality, allowing assessment of the spatial relationships between the vessels and anastomoses from all directions. LESSONS: To evaluate bypass patency and anatomical relationships immediately after EC-IC bypass surgery, IV 3D-DSA may be a useful modality. ICG videoangiography can be used to determine the scan delay time.

Visual complications after coil embolization of internal carotid artery aneurysms at the ophthalmic segment.

BACKGROUND: Coil embolization of aneurysms of the ophthalmic segment of the internal carotid artery (ICA-OphA ANs) has potential risks of visual complications. We analyzed this risk and focused on the relationship of the ophthalmic artery (OphA) origin with the aneurysm neck. METHODS: From January 2003 to April 2018, 179 unruptured ICA-OphA ANs were treated with endovascular surgery in our institution. Two ruptured and four aneurysms with missing data were excluded. Finally, 173 unruptured aneurysms were included in this study. The aneurysms were classified into three groups according to the location of the OphA origin: Separate, Shared, and Dome type. We retrospectively assessed visual complications based on the relationship between types of aneurysm and postoperative angiographic findings for the OphA. RESULTS: Visual deficits remained permanent in eleven cases (6.4%). In the Dome type, visual complications were significantly more frequent compared to the Separate type. Change in the OphA flow was significantly associated with a higher complication rate of 2.9%, but patients with changed OphA flow had a significant rate of 7.5% (p = 0.020). We found no significant difference in the incidence of visual complications concerning the use of perioperative antithrombotic therapy. CONCLUSIONS: The location of OphA origin regarding the aneurysmal neck and postoperative OphA flow were significantly correlated with the visual outcome after coil embolization for ICA-OphA ANs. Post-procedural flow in the OphA was an important factor affecting the rate of ischemic retinal complications. Retinal embolic events occurred with preserved flow in the OphA, albeit at a lower rate.

Comparison of Clinical Outcomes After Stent-Assisted Coiling with 3 Types of Self-Expanding Laser-Cut Stents in Patients with Wide-Necked Intracranial Aneurysms.

OBJECTIVE: We report the clinical outcomes of stent-assisted coiling for wide-necked intracranial aneurysms using 3 low-profile laser-cut stents and compare the results according to stent type. METHODS: All patients treated with stent-assisted coiling for their intracranial aneurysms at our hospital between July 2010 and September 2019 were reviewed. We selected patients with Enterprise, Neuroform EZ, or Neuroform Atlas stents who underwent imaging follow-up and investigated aneurysm and stent features, stent-related complications, recanalization, and retreatment rates. We compared the retreatment risk among the patients treated with the 3 stent types using Kaplan-Meier survival analysis and Cox regression analysis. RESULTS: We evaluated 364 consecutive cases (103 Enterprise, 105 Neuroform EZ, and 156 Neuroform Atlas stents). Neuroform Atlas was more frequently used in distal vessels: 8 (7.8%) Enterprise, 2 (1.9%) Neuroform EZ, and 41 (26.3%) Neuroform Atlas cases, respectively. The median follow-up durations were 6.49, 4.91, and 1.24 years for the Enterprise, Neuroform EZ, and Neuroform Atlas cases, respectively, and retreatment was performed in 11 (10.1%), 9 (8.6%), and 6 (3.8%) cases. In the first 2 years of follow-up, the estimated retreatment risk ratios for Neuroform EZ and Neuroform Atlas with Enterprise as reference were 0.63 (95% confidence interval, 0.24-1.65; P = 0.35) and 0.54 (95% confidence interval, 0.18-1.59; P = 0.26), respectively. CONCLUSIONS: Neuroform Atlas stents were more frequently deployed in small-caliber vessels compared with the other 2 types of stents. The complication rate and retreatment risk until at least 1 year after the aneurysm treatment appeared to be similar for the 3 stent types.

Complete Obliteration of a Foramen Magnum Dural Arteriovenous Fistula by Microsurgery After Failed Endovascular Treatment Using Onyx: Case Report and Literature Review.

BACKGROUND: Foramen magnum dural arteriovenous fistula (DAVF) is a rare disease, with some reported cases of successful treatment. We achieved complete obliteration of the foramen magnum DAVF through microsurgery after complications of endovascular embolization. We reviewed the treatment modalities and outcomes, focusing on pathologic and anatomic features from the literature. CASE DESCRIPTION: A 65-year-old man was admitted to our hospital with sudden diplopia. Magnetic resonance imaging revealed a subarachnoid hemorrhage around the right side of the prepontine cistern, and a foramen magnum DAVF was diagnosed by angiography. Subsequent angiography revealed that the fistula was supplied by the right neuromeningeal trunk of the ascending pharyngeal artery and the right posterior meningeal artery of the vertebral artery (VA), and the veins of the pouch via the fistula were retrogradely draining into the intracranial veins. We aimed to treat complete occlusion endovascularly with balloon-augmented transarterial Onyx injection via the posterior meningeal artery, but Onyx was refluxed to the VA through the anastomosis between the VA and posterior meningeal artery. Onyx subsequently migrated to the top of the basilar artery, causing occlusion, so we urgently removed the Onyx with a stent retriever (Trevo). Several weeks later, we performed complete obliteration of the foramen magnum DAVF via a lateral suboccipital approach with a C1 laminectomy. CONCLUSIONS: Most foramen magnum DAVFs were obliterated completely with only endovascular treatment. Microsurgery is an effective and reliable treatment for incomplete occlusion and complications.