Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses.

The intestinal immune system interacts with commensal microbiota to maintain gut homeostasis. Furthermore, stress alters the microbiome composition, leading to impaired brain function; yet how the intestinal immune system mediates these effects remains elusive. Here we report that colonic γδ T cells modulate behavioral vulnerability to chronic social stress via dectin-1 signaling. We show that reduction in specific Lactobacillus species, which are involved in T cell differentiation to protect the host immune system, contributes to stress-induced social-avoidance behavior, consistent with our observations in patients with depression. Stress-susceptible behaviors derive from increased differentiation in colonic interleukin (IL)-17-producing γδ T cells (γδ17 T cells) and their meningeal accumulation. These stress-susceptible cellular and behavioral phenotypes are causally mediated by dectin-1, an innate immune receptor expressed in γδ T cells. Our results highlight the previously unrecognized role of intestinal γδ17 T cells in the modulation of psychological stress responses and the importance of dectin-1 as a potential therapeutic target for the treatment of stress-induced behaviors.

Biological neurons act as generalization filters in reservoir computing.

Reservoir computing is a machine learning paradigm that transforms the transient dynamics of high-dimensional nonlinear systems for processing time-series data. Although the paradigm was initially proposed to model information processing in the mammalian cortex, it remains unclear how the nonrandom network architecture, such as the modular architecture, in the cortex integrates with the biophysics of living neurons to characterize the function of biological neuronal networks (BNNs). Here, we used optogenetics and calcium imaging to record the multicellular responses of cultured BNNs and employed the reservoir computing framework to decode their computational capabilities. Micropatterned substrates were used to embed the modular architecture in the BNNs. We first show that the dynamics of modular BNNs in response to static inputs can be classified with a linear decoder and that the modularity of the BNNs positively correlates with the classification accuracy. We then used a timer task to verify that BNNs possess a short-term memory of several 100 ms and finally show that this property can be exploited for spoken digit classification. Interestingly, BNN-based reservoirs allow categorical learning, wherein a network trained on one dataset can be used to classify separate datasets of the same category. Such classification was not possible when the inputs were directly decoded by a linear decoder, suggesting that BNNs act as a generalization filter to improve reservoir computing performance. Our findings pave the way toward a mechanistic understanding of information representation within BNNs and build future expectations toward the realization of physical reservoir computing systems based on BNNs.

A case of a pineal parenchymal tumor of intermediate differentiation with bifocal lesions differentiated by negative placental alkaline phosphatase in the spinal fluid.

Placental alkaline phosphatase (PLAP) in the spinal fluid is helpful for the diagnosis of intracranial germinomas. Bifocal lesions involving the pineal and pituitary regions have also been reported as characteristic findings of intracranial germinomas. We present a rare case of a 15-year-old boy with a pineal parenchymal tumor of intermediate differentiation (PPTID) with bifocal lesions negative for PLAP. Magnetic resonance imaging of the brain revealed bifocal mass lesions in the pineal and suprasellar regions and non-communicating hydrocephalus. We initially suspected a germinoma based on imaging findings, but all tumor markers, including PLAP, in the spinal fluid were negative. Based on these results, germinoma was considered less likely, and an endoscopic third ventriculostomy and endoscopic tumor biopsy were performed for diagnosis. The histopathological diagnosis was PPTID, corresponding to World Health Organization grade 3, in both pineal and suprasellar specimens. A craniotomy for tumor removal was performed, resulting in total resection. PLAP is known to have high sensitivity and extremely high negative predictive value for germinomas. Although bifocal lesions highly suggest germ cell tumors, there are exceptions, as in the present case. This case suggests that PLAP measurements are useful for differentiation, leading to appropriate treatment strategies.

Comparison of efficacy between clazosentan and fasudil hydrochloride-based management of vasospasm after subarachnoid hemorrhage focusing on older and WFNS grade V patients: a single-center experience in Japan.

Subarachnoid hemorrhage often leads to poor outcomes owing to vasospasm, even after successful aneurysm treatment. Clazosentan, an endothelin receptor inhibitor, has been proven to be an effective treatment for vasospasms in a Japanese randomized controlled trial. However, its efficacy in older patients (≥ 75 years old) and those with World Federation of Neurosurgical Societies (WFNS) grade V has not been demonstrated. We retrospectively evaluated the efficacy of clazosentan in older patients and those with WFNS grade V, using real-world data. Patients with subarachnoid hemorrhage treated before and after the introduction of clazosentan were retrospectively evaluated. The patients were categorized into two groups (clazosentan era versus pre-clazosentan era), in which vasospasm management and outcomes were compared. Vasospasms were managed with fasudil hydrochloride-based (pre-clazosentan era) or clazosentan-based treatment (clazosentan era). Seventy-eight patients were included in this study: the clazosentan era (n = 32) and pre-clazosentan era (n = 46). Overall, clazosentan significantly reduced clinical vasospasms (clazosentan era: 31.3% versus pre-clazosentan era: 60.9%, p = 0.01), delayed cerebral ischemia (DCI) (9.4% versus 39.1%, p = 0.004), and vasospasm-related morbidity and mortality (M/M) (3.1% versus 19.6%, p = 0.03). In subgroup analysis of older patients or those with WFNS grade V, no significant difference was observed in clinical outcomes, although both DCI and vasospasm-related M/M were lower in the clazosentan era. Clazosentan was more effective than fasudil-based management in preventing DCI and reducing vasospasm-related M/M. Clazosentan could be used safely in older patients and those with WFNS grade V, although clinical outcomes in these patients were comparable to those of conventional treatment.

Development of intravascular large B-cell lymphoma during prophylactic antibiotic treatment for anti-interferon-gamma autoantibody syndrome: A case report.

Anti-interferon (IFN)-γ autoantibody-positive syndrome is one of the acquired non-HIV cellular immunodeficiencies, caused by abnormalities in the IFN-γ/interleukin (IL)-12 pathways. It is often diagnosed alongside the onset of disseminated mycobacterium infection, and requires continuous antimycobacterial chemotherapy; however, the detailed pathological mechanisms underlying this syndrome, including its prognosis, are not known. To the best of our knowledge, this is the first reported case of intravascular large B-cell lymphoma complicated by anti-IFN-γ autoantibody syndrome, presented in an 82-year-old woman. The patient had been diagnosed with anti-IFN-γ autoantibody immunodeficiency ten years ago. She had repeated subacute fever of undetermined origin for 13 months that made us suspect infections, such as disseminated mycobacterium disease and other viral and fungal infections, despite receiving prophylactic antimycobacterial chemotherapy with rifampicin and clarithromycin. However, all the screenings performed showed no evidence of infectious diseases; thus, she was finally diagnosed with intravascular large B-cell lymphoma via a random skin biopsy. Unfortunately, the patient debilitated rapidly and died. Evidence supporting a correlation between anti-IFN-γ autoantibody syndrome and carcinogenesis is still lacking, although it is known that patients with anti-IFN-γ autoantibody syndrome are at risk of persistent viral infection-related and T-cell lineage-related carcinogenesis. This case demonstrated that patients with anti-IFN-γ autoantibody syndrome are also at risk of developing B-cell lymphoma, such as intravascular lymphoma. This emphasizes that caution should be paid to increased risk of developing malignancy during the long-term management of anti-IFN-γ autoantibody syndrome with cellular immunodeficiency.

A case series describing the risk of periodontal disease in Marfan syndrome patients harboring a possible aortic aneurysm or dissection.

BACKGROUND: Marfan syndrome (MFS) is a systemic disorder of connective tissues caused by insufficient elastic fiber formation that leads to structural weakness and results in various tissue disorders, including cardiovascular and periodontal disease. Notably however, the risk of periodontal disease in MFS patients affected by an aortic aneurysm or dissection has not yet been clarified. METHODS: We investigated the periodontal condition in the following three groups: MFS patients diagnosed with an aortic aneurysm or dissection with a planned aortic surgery (MFS surgery), MFS patients who had already undergone aortic surgery (MFS post-surgery) and healthy control patients (Healthy). The periodontal condition of all of these patients was evaluated at their first visit, reassessed again at two-month after the first visit, and evaluated again at a six-month follow-up after the reassessment. RESULTS: A total of 14 participants, 3 MFS surgery patients, 4 MFS post-surgery patients and 7 healthy control volunteers were examined. Saliva examinations revealed no significant differences between any of the groups at the first visit, reassessment, or follow-up. Interestingly, the MFS surgery cases showed a higher BOP and PISA at the first visit and follow-up compared with the other groups. In contrast, the MFS surgery patients showed an improvement in their LVDd and EF values, both markers of cardiac function, at the reassessment and follow-up compared with the first visit. CONCLUSIONS: MFS associated with an aortic aneurysm or dissection leads to a higher risk of periodontal disease, indicating the need for more frequent oral hygiene maintenance in these patients. In addition, MFS patients who undergo frequent professional cleaning of their teeth show a lower onset of cardiovascular disease, suggesting that professional oral hygiene in these cases contributes to a healthier condition.

New hemostatic technique with combined use of Hydrofit® and Surgicel®: an in vitro and in vivo study.

We developed an effective hemostatic technique using Hydrofit® and Surgicel® simultaneously. The aim of this study was to demonstrate the hemostatic efficacy of the Hydrofit® and Surgicel® combination technique through an in vitro experiment and to elucidate mid-term consequences of the combined components through an in vivo experiment. For the in vitro experiment, a closed circuit using a heparin-coated cardiopulmonary bypass circuit and a prosthetic graft was created. The amount of bleeding from the prosthetic graft was measured, and the following three hemostatic methods were applied: only gauze compression in control group, Hydrofit® application in Hydrofit group, Surgicel® spread Hydrofit® application in Hydrofit and Surgicel (HS) group, respectively. In the in vivo experiment, Hydrofit® and/or Surgicel® were implanted under skin on the back of rats (n = 10) at 4 points. In the control group, only an incision was made; in the Hydrofit, Surgicel, and HS groups, Hydrofit® and/or Surgicel® was implanted. One and three months later, each of the five rats were killed and in each section histopathologic examination was carried out. In the in vitro experiment, the amount of bleeding was 7.84 ± 1.08, 2.26 ± 1.02, and 0.87 ± 0.38 ml in the control, Hydrofit, and HS groups, respectively. The amount of bleeding in the HS group was more suppressed than in the Hydrofit group (p = 0.012). In the in vivo experiment, the maximal depth diameter of each remaining hemostatic sealant was measured. After 3 months, the diameter was 0, 2289.0 ± 768.2, 3850.3 ± 935.8 µm in Surgicel, Hydrofit and HS groups, respectively. The diameter was significantly increased in the HS group compared with the Surgicel and Hydrofit groups (p < 0.001, respectively,). In conclusion, the combination of Hydrofit® and Surgicel® was effective in achieving hemostasis. The remnants of Hydrofit® and Surgicel® were present for a long time in the tissues which could compress the surrounding tissue.

Aortic Insufficiency Causes Symptomatic Heart Failure during Left Ventricular Assist Device Support.

De novo aortic insufficiency is often documented during long-term left ventricular assist device (LVAD) support, despite the absence of aortic insufficiency at the time of LVAD implantation. However, whether aortic insufficiency affects long-term mortality and symptomatic heart failure in LVAD-supported patients remains controversial. We aimed to examine whether aortic insufficiency development influenced mortality and symptomatic heart failure following LVAD implantation. Fifty-three patients who underwent durable LVAD implantation between January 1, 2008 and April 31, 2017 were retrospectively examined in a single center institute. After discharge, we performed the echocardiographic examination in accordance with the Japanese registry for the mechanically assisted circulatory support protocol. Aortic insufficiency was graded on an interval scale (severe = 4, moderate = 3, mild = 2, trivial or none = 1). Kaplan-Meier estimates for long-term mortality at the follow-up were generated. We used a logistic regression model to identify risk factors for symptomatic heart failure. The overall median duration of LVAD support was 856.3 ± 430.8 days (range, 12-1,744 days). We did not observe a significant difference in long-term mortality in patients with aortic insufficiency ≥ 3 grade compared with patients with aortic insufficiency < 3 grade (P = 0.767; log-rank). Aortic insufficiency was associated with an increased risk for heart failure event after discharge (odds ratio, 4.12; confidence interval, 1.48-16.93; P = 0.005). Aortic insufficiency was an independent risk factor for symptomatic heart failure and was not associated with long-term mortality. Aortic insufficiency progression was associated with symptomatic heart failure.

[Total Aortic Arch Replacement after a Prior Ascending Aortic Replacement].

Surgeries for non-dissected aortic arch diseases have been performed with increasing frequency in recent years. Accordingly, the awareness of the pitfalls in reoperation after a previous ascending aortic replacement is needed. Indications for redo total aortic arch replacement after a prior ascending aortic replacement include pseudoaneurysm formation at the distal anastomosis site and newly developed aortic arch aneurysms. At reoperation, we should take the assurance of safety during re-sternotomy into consideration. Cannulation sites should be strategically selected. The radiologic features of the high-risk re-sternotomy include a close approximation( <5 mm) between the sternum and the aorta or the previously placed vascular prosthesis and a presence of pseudoaneurysm underneath the sternum. In such cases, it is reasonable to establish partial cardiopulmonary bypass and selective cerebral perfusion via bilateral carotid artery cannulation prior to sternotomy to avoid disastrous neurological complications. Adhesions around a previously placed vascular prosthesis with innominate vein or main pulmonary artery can be troublesome;thus, care must be taken so as not to injure the surrounding vital organs. Liberal employment of hypothermia can be life-saving by preserving brain, heart and other vital end-organs at the expense of prolonged procedure time.

[Anomalous Origin of the Right Coronary Artery from the Pulmonary Artery Treated with Fistula Closure and Coronary Artery Bypass Grafting:Report of a Case].

An anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital disease, and it sometimes remains unnoticed until cardiac symptoms appear in adulthood. We report an adult case of surgically treated ARCAPA. A 72-year-old male was diagnosed with ARCAPA by examination for heart failure. The origin of the right coronary artery (RCA) was dilated, and ischemic change was found in the RCA area by myocardial scintigraphy. Therefore, coronary artery bypass grafting to distal RCA was performed at first, then the fistula was closed using an autologous pericardial patch, and the dilated origin of RCA was resected. Postoperative scintigraphy showed disappearance of the ischemic pattern, and the patient was discharged without any symptom of heart failure.

Spindle pole body movement is affected by glucose and ammonium chloride in fission yeast.

The complexity of chromatin dynamics is orchestrated by several active processes. In fission yeast, the centromeres are clustered around the spindle pole body (SPB) and oscillate in a microtubule- and adenosine triphosphate (ATP)-dependent manner. However, whether and how SPB oscillation are affected by different environmental conditions remain poorly understood. In this study, we quantitated movements of the SPB component, which colocalizes with the centromere in fission yeast. We found that SPB movement was significantly reduced at low glucose concentrations. Movement of the SPB was also affected by the presence of ammonium chloride. Power spectral analysis revealed that periodic movement of the SPB is disrupted by low glucose concentrations. Measurement of ATP levels in living cells by quantitative single-cell imaging suggests that ATP levels are not the only determinant of SPB movement. Our results provide novel insight into how SPB movement is regulated by cellular energy status and additional factors such as the medium nutritional composition.

The exercise-glucocorticoid paradox: How exercise is beneficial to cognition, mood, and the brain while increasing glucocorticoid levels.

Exercise is known to have beneficial effects on cognition, mood, and the brain. However, exercise also activates the hypothalamic-pituitary-adrenal axis and increases levels of the glucocorticoid cortisol (CORT). CORT, also known as the "stress hormone," is considered a mediator between chronic stress and depression and to link various cognitive deficits. Here, we review the evidence that shows that while both chronic stress and exercise elevate basal CORT levels leading to increased secretion of CORT, the former is detrimental to cognition/memory, mood/stress coping, and brain plasticity, while the latter is beneficial. We propose three preliminary answers to the exercise-CORT paradox. Importantly, the elevated CORT, through glucocorticoid receptors, functions to elevate dopamine in the medial prefrontal cortex under chronic exercise but not chronic stress, and the medial prefrontal dopamine is essential for active coping. Future inquiries may provide further insights to promote our understanding of this paradox.

Developmental Alcohol Exposure Impairs Activity-Dependent S-Nitrosylation of NDEL1 for Neuronal Maturation.

Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.

[Unroofing Technique on Anomalous Aortic Origin of a Left Coronary Artery;Report of a Case].

An anomalous aortic origin of coronary artery is a cause of sudden death in young people. We report a surgical case of an anomalous aortic origin of the left coronary artery. A 16-year-old man with chest pain, which occurred while playing football, was taken in an ambulance. Electrocardiogram (ECG) revealed an ST-segment elevation in V1-V5. We performed coronary angiogram (CAG) and detected the anomalous aortic origin of left anterior descending artery. The computer tomography( CT) angiography revealed the intramural pathway of the left coronary artery. Surgery performed as an unroofing procedure for releasing the intramural portion of the left coronary artery. We confirmed a dilation of the left coronary artery ostia in postoperative coronary CT angiography. He did not have chest pain and other symptoms while cardiopulmonary exercise testing. He was discharged on the 18th postoperative day. He is seen as an outpatient without any symptoms.

Poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit can reduce transfusion of platelet products compared to heparin-coated circuit during aortic arch surgery.

Several coating techniques for extracorporeal circulation have been developed to reduce the systemic inflammatory response during cardiopulmonary bypass (CPB). We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethylacrylate (PMEA)- and heparin-coated CPB circuits in total aortic arch replacement (TAR) with the prolonged use of the bypass technique. Twenty patients who underwent elective TAR were divided randomly into two equal groups: group P (n = 10) to use PMEA-coated circuits and group H (n = 10) to use heparin-coated circuits. Clinical outcomes, hematological variables, and acute phase inflammatory response were analyzed perioperatively. Demographic, CPB, and clinical outcome data were similar for both groups. Hemoglobin and platelet count showed similar time-course curves. However, the amount of platelet products transfused intraoperatively was significantly larger in group H (group P 26.0 ± 7.0 units; group H 33.0 ± 6.7 units, p = 0.04). Total protein, and albumin levels were significantly higher in group P during and after the operation (total protein, p = 0.04; albumin, p = 0.02). The use of PMEA-coated circuit is associated with retainment of perioperative plasma proteins levels and may help to reduce transfusion of platelet products in TAR in comparison with the heparin-coated circuit.

Adolescent cannabis exposure interacts with mutant DISC1 to produce impaired adult emotional memory.

Cannabis is an increasingly popular and controversial drug used worldwide. Cannabis use often begins during adolescence, a highly susceptible period for environmental stimuli to alter functional and structural organization of the developing brain. Given that adolescence is a critical time for the emergence of mental illnesses before full-onset in early adulthood, it is particularly important to investigate how genetic insults and adolescent cannabis exposure interact to affect brain development and function. Here we show for the first time that a perturbation in disrupted in schizophrenia 1 (DISC1) exacerbates the response to adolescent exposure to delta-9-tetrahydrocannabinol (Δ(9)-THC), a major psychoactive ingredient of cannabis, consistent with the concept that gene-environment interaction may contribute to the pathophysiology of psychiatric conditions. We found that chronic adolescent treatment with Δ(9)-THC exacerbates deficits in fear-associated memory in adult mice that express a putative dominant-negative mutant of DISC1 (DN-DISC1). Synaptic expression of cannabinoid receptor 1 (CB1R) is down-regulated in the prefrontal cortex, hippocampus, and amygdala, critical brain regions for fear-associated memory, by either expression of DN-DISC1 or adolescent Δ(9)-THC treatment. Notably, elevation of c-Fos expression evoked by context-dependent fear memory retrieval is impaired in these brain regions in DN-DISC1 mice. We also found a synergistic reduction of c-Fos expression induced by cue-dependent fear memory retrieval in DN-DISC1 with adolescent Δ(9)-THC exposure. These results suggest that alteration of CB1R-mediated signaling in DN-DISC1 mice may underlie susceptibility to detrimental effects of adolescent cannabis exposure on adult behaviors.

Conformational change in transfer RNA is an early indicator of acute cellular damage.

Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases, including AKI and CKD. Thus, early detection of oxidative tissue damage is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we show that oxidative stress induces a direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation and occurs much earlier than DNA damage. In various models of tissue damage (ischemic reperfusion, toxic injury, and irradiation), the levels of circulating tRNA derivatives increased rapidly. In humans, the levels of circulating tRNA derivatives also increased under conditions of acute renal ischemia, even before levels of other known tissue damage markers increased. Notably, the level of circulating free m1A correlated with mortality in the general population (n=1033) over a mean follow-up of 6.7 years. Compared with healthy controls, patients with CKD had higher levels of circulating free m1A, which were reduced by treatment with pitavastatin (2 mg/d; n=29). Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis.

"GO" to move toward dementia-friendly communities: A pilot study.

BACKGROUND: To the creation of mutual aid relationships among people with cognitive decline is important in aging societies. This study aimed to develop and examine the feasibility of a GO Program in which older adults, with experience in playing GO, support the learning of GO by older adults with cognitive decline and other barriers to social participation, which in turn reduces social isolation and creates opportunities for older adults to use their role. METHODS: This single-arm intervention study was conducted in Tokyo, Japan. Introductory GO classes were held for 10 participants who had never played GO (beginners) and 10 participants who had (supporters) once a week for an hour, for a total of 12 sessions. Supporters and beginners were paired to solve problems and play games. We assessed the feasibility of the program and its effects on mental health social network, and cognitive function. RESULTS: Cognitive test scores were at the mild cognitive Impairment level for beginners as well as for supporters. Satisfaction with the program was high, with an overall class attendance rate of 99.1% and none leaving the program. No significant changes were observed over time for beginners in each measurement; however, there was a significant improvement in the Mini Mental State Examination-Japanese scores for supporters (p < .05). CONCLUSIONS: The results suggest that this program could contribute to the creation of mutual aid relationships among older adults with cognitive decline; even if they have mildly declined cognitive function, they can still play an active role in society. Moreover, creating such opportunities may positively impact cognitive function.

Therapeutic Resistance in G-CSF Producing Lung Cancer With EGFR Mutation.

Background/Aim: Granulocyte colony-stimulating factor (G-CSF)-producing neoplasms are relatively rare; however, little is known on the clinical features of G-CSF-producing lung cancer harboring activating epidermal growth factor receptor (EGFR) mutations. Case Report: A 66-year-old female was definitively diagnosed with G-CSF-producing lung cancer that was positive for EGFR mutations. She repeatedly received epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as osimertinib and afatinib. However, she developed resistance to these molecular-targeting drugs within 2 to 3 months after immediate shrinkage. Thus, the patient was treated with chemoimmunotherapy including bevacizumab, and demonstrated a slight survival benefit. Conclusion: Overall, G-CSF-producing lung cancers positive for EGFR mutations were resistant to different treatment modalities. Clinicians should be attentive to the potential resistance of G-CSF-producing EGFR mutant lung cancer to EGFR-TKI therapy.

Severe Atelectasis due to Aspirated Valproic Acid Tablet.

A 60-year-old man treated with valproic acid (VPA) for epilepsy developed atelectasis and respiratory failure after an accidentally aspirated VPA tablet-induced mucus hypersecretion. Following bronchoscopic removal of the aspirated tablet, his respiratory status improved and massive sputum production did not recur. We hypothesized that the aspirated VPA tablet increased the expression of mucin-related genes, thereby increasing mucus production. Our in vitro experiments using a human respiratory epithelial cell line revealed that VPA directly upregulates the airway mucin-related genes. We believe that this is the first case report of aspirated VPA-induced severe atelectasis and respiratory failure, which were successfully treated with the bronchoscopic removal of the VPA tablet.