Correlation Analysis Between Echinocytosis Stages and Blood Viscosity During Oxygenator Perfusion: An In Vitro Study.

The study aimed to investigate the effect of red blood cell (RBC) morphology on oxygenator perfusion, focusing on stages of echinocytosis and their correlation with blood viscosity. A test circuit with an oxygenator and human RBC mixtures was used to induce changes in RBC shape by increasing sodium salicylate concentrations (0, 10, 20, 30, 60, and 120 mmol/L), while hematocrit, blood temperature, and anticoagulation were maintained. Blood viscosity was measured using a continuous blood viscosity monitoring system based on pressure-flow characteristics. Under a scanning electron microscope, the percentages of discocytes, echinocytes I-III, spheroechinocytes, and spherocytes were determined from approximately 400 cells per RBC sample. Early echinocytes, mainly discocytes and echinocytes I and II in the range of 0-30 mmol/L were predominant, resulting in a gradual increase in blood viscosity from 1.78 ± 0.12 to 1.94 ± 0.12 mPa s. At 60 mmol/L spherocytes emerged, and at 120 mmol/L, spheroidal RBCs constituted 50% of the population, and blood viscosity sharply rose to 2.50 ± 0.15 mPa s, indicating a 40% overall increase. In conclusion, the presence of spherocytes significantly increases blood viscosity, which may affect oxygenator perfusion.

The Number of Microbubbles Generated During Cardiopulmonary Bypass Can Be Estimated Using Machine Learning From Suction Flow Rate, Venous Reservoir Level, Perfusion Flow Rate, Hematocrit Level, and Blood Temperature.

GOAL: Microbubbles (MBs) are known to occur within the circuits of cardiopulmonary bypass (CPB) systems, and higher-order dysfunction after cardiac surgery may be caused by MBs as well as atheroma dispersal associated with cannula insertion. As complete MB elimination is not possible, monitoring MB count rates is critical. We propose an online detection system with a neural network-based model to estimate MB count rate using five parameters: suction flow rate, venous reservoir level, perfusion flow rate, hematocrit level, and blood temperature. METHODS: Perfusion experiments were performed using an actual CPB circuit, and MB count rates were measured using the five varying parameters. RESULTS: Bland-Altman analysis indicated a high estimation accuracy (R2 > 0.95, p < 0.001) with no significant systematic error. In clinical practice, although the inclusion of clinical procedures slightly decreased the estimation accuracy, a high coefficient of determination for 30 clinical cases (R2 = 0.8576) was achieved between measured and estimated MB count rates. CONCLUSIONS: Our results highlight the potential of this system to improve patient outcomes and reduce MB-associated complication risk.

Total knee arthroplasty for knee osteoarthritis associated with abnormal patellar tendon deformity: a case report.

There have been no earlier reports of knee osteoarthritis with valgus knee deformity in which the patellar tendon infiltrates the tibial bone marrow instead of attaching to the tibial tubercle. This case report describes a total knee arthroplasty (TKA) performed for the treatment of a primary knee osteoarthritis resulting from a valgus knee joint position attributed to an abnormality of the patellar ligament attachment. During a TKA, the tendon tissue in the tibial medullary canal interfered with the reamer used to prepare for the stem extensions needed to improve the fixation of the component on the tibia, which had a cortical defect. The arthroplasty succeeded, and good clinical results have been maintained over the 3 years since the surgery. Surgeons should consider careful preoperative examinations by magnetic resonance imaging or CT when an abnormal bone defect is observed at the tibial tubercle on plain X-ray images.

Body positioning-related laryngeal narrowing pattern and expiratory mechanical constraints in advanced chronic obstructive pulmonary disease: A case report.

We previously reported that laryngeal widening led to improved exercise tolerance in COPD. However, it is not clear whether laryngeal narrowing occurs as a compensatory response to tracheal movement or is affected by posture. Here, we report the case of an advanced COPD patient whose more prolonged expiration in a head-forward leaning position compared with that in a neck-extended position occurred with an excessive duration of severe laryngeal narrowing without tracheal obstruction, which led to exercise intolerance with expiratory mechanical constraints. This case provided useful insights into the regulation of the upper airway with body positioning for improving exercise tolerance.

Rare TCF3 variants associated with pediatric B cell acute lymphoblastic leukemia.

Germline genetic variants influence development of pediatric B cell acute lymphoblastic leukemia (B-ALL). Genome-wide association studies (GWAS) have identified several pediatric B-ALL susceptibility loci. IKZF1 and PAX5, transcription factors involved in B cell development, have been reported as susceptibility genes for B-ALL development. Therefore, we hypothesized that rare variants of genes involved in B cell development would be candidate susceptibility loci for pediatric B-ALL. Thus, we sequenced TCF3, a key transcription factor gene involving in B cell development. Saliva DNA from 527 pediatric patients with pediatric B-ALL in remission who were registered with the Tokyo Children's Cancer Study Group (TCCSG) were examined. As a TCF3 gene-based evaluation, the numbers of rare deleterious germline TCF3 sequence variants in patients with pediatric B-ALL were compared with those in cancer-free individuals using data in public databases. As a TCF3 single-variant evaluation, the frequencies of rare deleterious germline TCF3 sequence variants in patients with pediatric B-ALL were also compared with those in control data. TCF3 gene-based analysis revealed significant associations between rare deleterious variants and pediatric B-ALL development. In addition, TCF3 variant-based analysis showed particularly strong association between variant rs372168347 (three in 521 TCCSG and three in the 15780 gnomAD whole genome analysis cohort, p = 0.0006) and pediatric B-ALL development. TCF3 variants are known to influence B cell maturation and may increase the risk of preleukemic clone emergence.

Hidden Bow Hunter's Syndrome Diagnosed Using Dynamic Cerebral Angiography and Successfully Treated with Spinal Surgery: A Case Report and Review of the Literature.

Hidden bow hunter's syndrome (HBHS) is a rare disease in which the vertebral artery (VA) occludes in a neutral position but recanalizes in a particular neck position. We herein report an HBHS case and assess its characteristics through a literature review. A 69-year-old man had repeated posterior-circulation infarcts with right VA occlusion. Cerebral angiography showed that the right VA was recanalized only with neck tilt. Decompression of the VA successfully prevented stroke recurrence. HBHS should be considered in patients with posterior circulation infarction with an occluded VA at its lower vertebral level. Diagnosing this syndrome correctly is important for preventing stroke recurrence.

Diagnosis and Management of Drug-Induced Interstitial Lung Disease Associated with Amikacin Liposome Inhalation Suspension in Refractory Mycobacterium Avium Complex Pulmonary Disease: A Case Report.

Amikacin liposome inhalation suspension (ALIS) is a key drug for the treatment of refractory Mycobacterium avium complex pulmonary disease (MAC-PD). Although cases of drug-induced interstitial lung disease (DIILD) by ALIS have been reported, its diagnosis is challenging due to overlapping existing pulmonary shadows, airway bleeding, exacerbation of underlying conditions, and the potential for various concurrent infections. A 72-year-old woman started treatment with ALIS for refractory MAC-PD. Three weeks later, she had a fever, cough, and appetite loss. She was hospitalized because multiple infiltrative opacities were observed on chest X-ray and chest computed tomography. Because the opacities worsened after empiric antibiotic therapy with broad-spectrum antibiotics, we initiated corticosteroid therapy, suspecting DIILD caused by ALIS, although drug lymphocyte stimulation tests for ALIS and amikacin were negative. Three days later, we found signs of improvement and quickly tapered the corticosteroids. After obtaining informed consent, we performed a drug provocation test of ALIS. Seven days later, she exhibited fever, an increased peripheral white blood cell count, and elevated serum C-reactive protein level, all of which returned to baseline 4 days after stopping ALIS, leading to a diagnosis of DIILD caused by ALIS in this patient. DIILD caused by ALIS is rare but should be carefully diagnosed to ensure that patients with refractory MAC-PD do not miss the opportunity to receive ALIS treatment.

Simultaneous Control of Venous Reservoir Level and Arterial Flow Rate in Cardiopulmonary Bypass With a Centrifugal Pump.

Cardiopulmonary bypass (CPB) is an indispensable technique in cardiac surgery, providing the ability to temporarily replace cardiopulmonary function and create a bloodless surgical field. Traditionally, the operation of CPB systems has depended on the expertise and experience of skilled perfusionists. In particular, simultaneously controlling the arterial and venous occluders is difficult because the blood flow rate and reservoir level both change, and failure may put the patient's life at risk. This study proposes an automatic control system with a two-degree-of-freedom model matching controller nested in an I-PD feedback controller to simultaneously regulate the blood flow rate and reservoir level. CPB operations were performed using glycerin and bovine blood as perfusate to simulate flow-up and flow-down phases. The results confirmed that the arterial blood flow rate followed the manually adjusted target venous blood flow rate, with an error of less than 5.32%, and the reservoir level was maintained, with an error of less than 3.44% from the target reservoir level. Then, we assessed the robustness of the control system against disturbances caused by venting/suction of blood. The resulting flow rate error was 5.95%, and the reservoir level error 2.02%. The accuracy of the proposed system is clinically satisfactory and within the allowable error range of 10% or less, meeting the standards set for perfusionists. Moreover, because of the system's simple configuration, consisting of a camera and notebook PC, the system can easily be integrated with general CPB equipment. This practical design enables seamless adoption in clinical settings. With these advancements, the proposed system represents a significant step towards the automation of CPB.

Acute cerebral hemorrhage mimicking glioblastoma on intraoperative magnetic resonance imaging: A case report.

Intraoperative magnetic resonance imaging (iMRI) is important in neurosurgical practice, especially for glioma surgery. However, the well-reported possibility to mistake lesions for brain tumors (tumor mimics) with MRI also exists for iMRI. Here, we first report a case of glioblastoma with acute cerebral hemorrhage that mimicked a newly emerged brain tumor on iMRI. A 53-year-old man underwent a second surgery for recurrent glioblastoma. Intraoperatively, iMRI revealed a new, enhanced lesion near the resected area that was absent on preoperative MRI and difficult to differentiate from newly emerged tumors. Here, a recent preoperative MRI was helpful and the new lesion was actually a hematoma. Neurosurgeons must understand that, as acute intracerebral hemorrhaging can mimic brain tumors on iMRI, preoperative MRI should be conducted just before surgery to place iMRI findings in proper context and avoid unnecessary resections.

Senso-immunology: the past, present, and future.

Pain and mechanical stimulation are thought to be alarm systems that alert the brain to physical abnormalities. When we experience unpleasant feelings in infected or traumatized tissues, our awareness is directed to the afflicted region, prompting activities such as resting or licking the tissue. Despite extensive research into the molecular biology of nociceptors, it was unclear whether their role was limited to the generation and transmission of unpleasant feelings or whether they actively modulate the pathogenesis of infected or traumatized tissues. Recently, it has become clear how the sensory and immune systems interact with one another and share similar receptors and ligands to modify the pathogenesis of various diseases. In this paper, we summarize the mechanisms of crosstalk between the sensory and immune systems and the impact of this new interdisciplinary field, which should be dubbed 'senso-immunology,' on medical science.

Clinical utility of markerless motion capture for kinematic evaluation of sit-to-stand during 30 s-CST at one year post total knee arthroplasty: a retrospective study.

BACKGROUND: Although the importance of kinematic evaluation of the sit-to-stand (STS) test of total knee arthroplasty (TKA) patients is clear, there have been no reports analyzing STS during the 30-s chair sit-up test (30 s-CST) with a focus on kinematic characteristics. This study aimed to demonstrate the clinical utility of kinematic analysis of STS during the 30 s-CST by classifying STS into subgroups based on kinematic parameters, and to determine whether differences in movement strategies are expressed as differences in clinical outcomes. METHODS: The subjects were all patients who underwent unilateral TKA due to osteoarthritis of the knee and were followed up for one year postoperatively. Forty-eight kinematic parameters were calculated using markerless motion capture by cutting STS in the 30 s-CST. The principal components of the kinematic parameters were extracted and grouped by kinematic characteristics based on the principal component scores. Clinical significance was examined by testing whether differences in patient-reported outcome measures (PROMs) were observed. RESULTS: Five principal components were extracted from the 48 kinematic parameters of STS and classified into three subgroups (SGs) according to their kinematic characteristics. It was suggested that SG2, using a kinematic strategy similar to the momentum transfer strategy shown in previous studies, performed better in PROMs and, in particular, may be associated with achieving a "forgotten joint", which is considered the ultimate goal after TKA. CONCLUSIONS: Clinical outcomes differed according to kinematic strategies used STS, suggesting that kinematic analysis of STS in 30 s-CST may be useful in clinical practice. TRIAL REGISTRATION: This study was approved by the Medical Ethical Committee of the Tokyo Women's Medical University (approval number: 5628 on May 21, 2021).

Spontaneous Middle Meningeal Arteriovenous Fistula Caused by Aneurysm Rupture: A Case Report.

Middle meningeal arteriovenous fistula (MMAVF) is a shunt between the middle meningeal artery and the vein surrounding the artery. We report an extremely rare case of spontaneous MMAVF; then, we evaluated the effectiveness of trans-arterial embolization for spontaneous MMAVF and the possible cause of spontaneous MMAVF. A 42-year-old man with tinnitus, a left temporal headache, and pain surrounding the left mandibular joint was diagnosed with MMAVF on digital subtraction angiography. Trans-arterial embolization with detachable coils was conducted, which resulted in a fistula closure and symptoms' diminishment. The cause of MMAVF was thought to be the rupture of the middle meningeal artery aneurysm. A middle meningeal artery aneurysm can be a cause of spontaneous MMAVF, and trans-arterial embolization might be an optimal treatment.

Decrease in current perception thresholds of A-beta fibers by subthreshold noise stimulation using transcutaneous electrical nerve stimulation.

Developing effective supplements and rehabilitation of the impaired tactile and proprioception sensation is a significant challenge. One potential method for improving these sensations in clinical practice is using stochastic resonance with white noise. While transcutaneous electrical nerve stimulation (TENS) is a simple method, the effect of subthreshold noise stimulation via TENS on sensory nerve thresholds is currently unknown. This study aimed to investigate whether subthreshold TENS can alter afferent nerve thresholds. The electric current perception thresholds (CPT) of A-beta, A-delta, and C fibers were assessed in 21 healthy volunteers during both subthreshold TENS and control conditions. Subthreshold TENS was found to have lower CPT values compared to the control condition for A-beta fibers. No significant differences were observed between subthreshold TENS and control for A-delta and C fibers. Our findings indicated that subthreshold TENS might selectively enhance the function of A-beta fibers.

Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK-Ay mice.

AIMS/INTRODUCTION: Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes produce IL-18 upon being activated by various stimuli via the P2 receptors. Previously, we showed that serum and urine IL-18 levels are positively associated with albuminuria in patients with type 2 diabetes, indicating the involvement of inflammasome activation in the pathogenesis of diabetic kidney disease (DKD). In the present study, we investigated whether the administration of suramin, a nonselective antagonist of the P2 receptors, protects diabetic KK.Cg-Ay /TaJcl (KK-Ay) mice against DKD progression. MATERIALS AND METHODS: Suramin or saline was administered i.p. to KK-Ay and C57BL/6J mice once every 2 weeks for a period of 8 weeks. Mouse mesangial cells (MMCs) were stimulated with ATP in the presence or absence of suramin. RESULTS: Suramin treatment significantly suppressed the increase in the urinary albumin-to-creatinine ratio, glomerular hypertrophy, mesangial matrix expansion, and glomerular fibrosis in KK-Ay mice. Suramin also suppressed the upregulation of NLRP3 inflammasome-related genes and proteins in the renal cortex of KK-Ay mice. P2X4 and P2X7 receptors were significantly upregulated in the isolated glomeruli of KK-Ay mice and mainly distributed in the glomerular mesangial cells of KK-Ay mice. Although neither ATP nor suramin affected NLRP3 expression in MMCs, suramin inhibited ATP-induced NLRP3 complex formation and the downstream expression of caspase-1 and IL-18 in MMCs. CONCLUSIONS: These results suggest that the NLRP3 inflammasome is activated in a diabetic kidney and that inhibition of the NLRP3 inflammasome with suramin protects against the progression of early stage DKD.

Clinical and Genetic Characterization of Patients with Artemis Deficiency in Japan.

PURPOSE: Artemis is an exonuclease essential for V(D)J recombination and repair of DNA double-stranded breaks. Pathogenic variants in DCLRE1C encoding Artemis cause T-B-NK+ severe combined immunodeficiency (SCID), and patients with Artemis-deficient SCID (ART-SCID) require definitive therapy with allogeneic hematopoietic cell transplantation (HCT). Here we describe the clinical and genetic characteristics of patients with ART-SCID who were diagnosed in Japan from 2003 to 2022. METHODS: Clinical data of ART-SCID patients who were diagnosed between 2003 and 2022 in Japan were collected from their physicians using a questionnaire. RESULTS: ART-SCID diagnosis was made in eight patients from seven families with severe infections within 6 months of life. Two patients had missense variants, five patients had large genomic deletions, and one patient was compound heterozygous for a missense variant and large genomic deletion. All eight underwent allogeneic HCT within 4 months after the diagnosis, 7 receiving a conditioning regimen containing alkylating agents, and one patient without conditioning due to uncontrolled infection. Two patients with poor performance status (PS) died of complications 410 days and 32 days post-HCT, respectively. Of the six surviving patients with a median follow-up time of 8.3 (0.5-17.9) years, three patients had growth retardation. The patients with PS of 0-2 showed a tendency for better overall survival than those with PS 3-4. CONCLUSION: Large deletions were the most common genetic cause of ART-SCID in Japan. To improve HCT outcome, early diagnosis with newborn screening for SCID is urgently needed.

Direct Carotid-Cavernous Fistula Caused by Internal Carotid Artery Perforation by a Microcatheter Body during Mechanical Thrombectomy.

Rapid advances in emergent mechanical thrombectomy have resulted in a higher occurrence of arterial perforations during neurointerventions. Here, we report a case of internal carotid artery (ICA) perforation during mechanical thrombectomy in a 78-year-old man with a left middle cerebral artery occlusion. The ICA was perforated by a microcatheter during thrombectomy, forming a direct carotid-cavernous fistula. A two-stage drainer occlusion was conducted because of cortical venous reflex aggravation and ocular symptoms. Here, we report the perforation details and treatment, adding to evidence that ICA perforation with the microcatheter body is a concern during mechanical thrombectomy.

Neural Network-based Estimation of Microbubbles Generated in Cardiopulmonary Bypass Circuit: A Clinical Application Study.

The cardiopulmonary bypass system used in cardiac surgery can generate microbubbles (MBs) that may cause complications, such as neurocognitive dysfunction, when delivered into the blood vessel. Estimating the number of MBs generated, thus, is necessary to enable the surgeons to deal with it. To this end, we previously proposed a neural network-based model for estimating the number of MBs from four factors measurable from the cardiopulmonary bypass system: suction flow rate, venous reservoir level, blood viscosity, and perfusion flow rate. However, the model has not been adapted to the data collected from actual surgery cases. In this study, the accuracy of MBs estimated by the proposed model was examined in four clinical cases. The results showed that the coefficient of determination between estimated MBs and the measured MBs throughout the surgeries was R2=0.558 (p<0.001). We found that the surgical treatments, such as administration of drugs, fluids and blood transfusions, increased the number of measured MBs. The coefficient of determination increased to R2= 0.8762 (p<0.001) by excluding the duration of these treatments. This result indicates that the model can estimate the number of MBs with high accuracy under the clinical environment.