Tezepelumab improved chronic rhinosinusitis with nasal polyps in a Patient with aspirin exacerbated respiratory disease.

Introduction: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) have more severe sinus disease than those without AERD. CRSwNP associated with type 2 inflammation and AERD can be difficult to control with standard medical therapy and sinus surgery. Case study: 74-year-old Japanese woman with chronic sinusitis since age 50 and asthma since age 60. At age 64, she began to experience asthma exacerbations and was started on short-term corticosteroid therapy with prednisolone. At age 70, she experienced urticaria, nasal congestion, and wheezing after taking an NSAID; based on an NSAID provocation test, we diagnosed the patient with AERD and CRSwNP. A diagnosis of severe eosinophilic chronic rhinosinusitis was also made based on the scoring system and algorithm used in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis. Results: Treatment with benralizumab (30 mg), formoterol-fluticasone combination via pressurized metered inhaler (1000 µg), and leukotriene receptor antagonist improved the asthma symptoms and exacerbations so the short-term prednisolone was stopped; however, nasal congestion and olfactory dysfunction (hyposmia) persisted, and peripheral blood eosinophil count (peak, 1500 cells/µL) and fractional exhaled nitric oxide (peak, 42 ppb) became elevated. Swapping the benralizumab for monthly tezepelumab (210 mg) improved not only the asthma symptoms but also the nasal congestion, olfactory dysfunction, eosinophil count (<300 cells/µL), and fractional exhaled nitric oxide level [8ppb]. Conclusion: Changing from benralizumab to tezepelumab improved asthma symptoms, nasal obstruction, and olfactory dysfunction in elderly, female, Japanese patient with AERD and CRSwNP.

A case report of concurrent management of acute myocardial infarction complicated by left ventricular thrombus and ischaemic stroke.

Background: Left ventricular thrombus (LVT) formation is a serious complication of acute myocardial infarction (AMI) requiring complicated management strategies and collaboration among cardiologists, cardiovascular surgeons, and neurosurgeons. Case summary: We present the case of an 83-year-old female patient with AMI. Emergency coronary angiography revealed subtotal occlusion of the proximal left anterior descending artery, and the patient was successfully treated with a drug-eluting stent. The following day, she suddenly developed loss of consciousness, global aphasia, and right hemiplegia. Brain magnetic resonance imaging revealed acute ischaemic cerebral infarction caused by multiple mobile LVT, as demonstrated by echocardiography. After a heart-brain team discussion, we decided to perform percutaneous mechanical thrombectomy. Successful recanalization was achieved with mechanical thrombectomy 2 h after presentation, which resulted in significant neurological recovery. Immediately after the thrombectomy, she was transferred to a cardiovascular surgery centre for surgical removal of multiple LV apical thrombi. Two weeks after the operation, the patient was discharged with the recovery of LV systolic function. Discussion: Although AMI complicated by acute stroke caused by LVT remains a clinical challenge, a multidisciplinary approach is critically important for optimal care. Based on an urgent team discussion, we decided to perform endovascular thrombectomy for ischaemic stroke, followed by surgical removal of the LVT, requiring patient transportation to the cardiovascular surgery centre. Given that the heart and brain team-based approach remains confined to large, specialized centres, it might be beneficial to establish a community-based integrated heart-brain team that can address the growing needs of complex patients.

A Case of Type I Food Allergy Induced by Monosodium Glutamate.

Monosodium glutamate (MSG), a salt form of a non-essential amino acid, is widely used as a food additive, particularly in Asian cuisines, due to its unique flavor-enhancing qualities. Type I allergic reactions to MSG have not previously been reported. Our patient, a 21-year-old woman, was 14 years old when she first noticed swelling of her tongue (but no oral itching, diarrhea, or abdominal pain) after eating various snack foods. Current skin prick testing elicited a weak positive reaction to MSG. We then performed an oral challenge test during which our patient ingested potato snacks. Subsequent histology showed telangiectasia of the buccal mucosa, interstitial edema in the subepithelial submucosa, and mast cell infiltration. Oral mucosal challenge tests using sodium glutamate confirmed oral swelling in this patient. This report is the first to confirm a case of type 1 allergy to MSG by combining pathology findings with the results of challenge testing.

Persistent iatrogenic muscular ventricular septal lead perforation after pacemaker implantation using delivery sheath system.

Ventricular septal perforation is a rare complication of pacemaker implantation. Here, we describe the case of a 69-year-old man with complete atrioventricular block and heart failure. The right ventricular pacemaker was implanted with a long pre-shaped delivery sheath. A new systolic murmur appeared after the procedure. Transthoracic echocardiography revealed a ventricular septal perforation, with a Qp/Qs of 1.09, which was a small shunt rate and required no intervention. The persistent ventricular septal perforation was observed, and the shunt rate remained at 8-month follow-up. Learning objective: Ventricular septal lead perforation (VSP) is a rare complication of pacemaker implantation. Although iatrogenic VSP generally close spontaneously without adverse clinical outcomes, clinicians should pay attention to the possibility of its persistence.

Intravenous cyclophosphamide and immunoglobulin ameliorated visual field defects in a patient with eosinophilic granulomatosis with polyangiitis.

Treating ocular involvement in eosinophilic granulomatosis with polyangiitis (EGPA) can be challenging. We present the case of a 37-year-old woman with EGPA who had severe bilateral visual field defects. Laboratory results showed leukocytosis (17,500 WBC/µL, 25.8 % eosinophils), negative MPO-ANCA titer, and elevated PR3-ANCA level (33.2 IU/mL). Diffusion-weighted MRI revealed bilateral hyperintense occipital lesions, which were more prominent on the left. Her therapy initially included a steroid pulse, followed by daily prednisolone, but her visual field defects remained refractory. The addition of intravenous cyclophosphamide (5 courses) and intravenous immunoglobulin decreased her optic neuropathy and resolved her visual field defects.

Clinical predictors of cardiac syncope in patients with unexplained syncope after the implantation of an insertable cardiac monitor.

Syncope prognosis is related to both its etiology and comorbidities, with cardiac syncope (CS) having higher risks for mortality and cardiovascular events than syncope of non-cardiac causes. Although a novel insertable cardiac monitor (ICM) is an effective diagnostic tool for unexplained syncope, decision regarding ICM implantation with a high pre-test likelihood of CS should contribute to economic cost reduction and avoidance of unnecessary complications. This study aimed to investigate clinical factors associated with CS after ICM implantation in patients with unexplained syncope. This retrospective observational study included 31 consecutive patients with ICM implantation for syncope between September 2016 and August 2021. The initial examinations for syncope included a detailed history, physical examination, blood tests, 12-lead electrocardiograms, and transthoracic echocardiography. Of the 31 patients, 13 (41.9%) experienced recurrent CS during follow-up (676 ± 469 days). Among several clinical factors, syncope-related minor injuries (p = 0.017) and higher brain natriuretic peptide (BNP; p = 0.043) levels were significantly associated with CS. Moreover, multivariable analysis showed that both syncope-related minor injuries (odds ratio, 11.2; 95% confidence interval, 1.4-88.4; p = 0.022) and BNP higher than 64.0 pg/mL (odds ratio, 7.0; 95% confidence interval, 1.1-44.2; p = 0.038) were independent predictors of CS after ICM implantation. In conclusion, a history of minor injury secondary to syncope and higher BNP levels were independent CS predictors in patients receiving ICM for syncope. These results emphasized the utility of ICM implantation early in the diagnostic journey of patients presenting with CS predictors requiring specific treatments.

Physical interaction is not necessary for the induction of housing-type social buffering of conditioned hyperthermia in male rats.

In social animals, housing with conspecific animals after a stressful event attenuates the subsequent adverse outcomes due to the event, and this has been called housing-type social buffering. We have previously found that housing-type social buffering attenuates the enhancement of hyperthermia and Fos expression in the paraventricular nucleus of the hypothalamus that occurs in response to an aversive conditioned stimulus in male rats. Here, we analyzed the role of physical interactions during social housing in the induction of housing-type social buffering. When a fear-conditioned subject was alone after the conditioning and then exposed to the conditioned stimulus, it showed behavioral, autonomic, and neural stress responses. However, social housing, during which physical interactions were prevented by wire mesh, attenuated these autonomic and neural stress responses, as has been seen in previous studies. These results suggested that physical interaction was not necessary for the induction of housing-type social buffering. With this social cohabitation model, we then found that social cohabitation increased Fos expression in the posterior complex of the anterior olfactory nucleus of the fear-conditioned subject. Social cohabitation also increased Fos expression in 11 brain regions, including the prefrontal cortex, the nucleus accumbens, the bed nucleus of the stria terminalis, and the medial, lateral, basal, and cortical amygdala. These results provide information about the neural mechanisms that induce housing-type social buffering.

Alarm pheromone is detected by the vomeronasal organ in male rats.

It is widely known that a stressed animal releases specific pheromones, possibly for alarming nearby conspecifics. We previously investigated an alarm pheromone in male rats and found that this alarm pheromone evokes several responses, including increases in the defensive and risk assessment behaviors in a modified open-field test, and enhancement of the acoustic startle reflex. However, the role of the vomeronasal organ in these pheromone effects remains unclear. To clarify this point, vomeronasal organ-excising or sham surgeries were performed in male rats for use in 2 experimental models, after which they were exposed to alarm pheromone. We found that the vomeronasal organ-excising surgery blocked the effects of this alarm pheromone in both the modified open-field test and acoustic startle reflex test. In addition, the results of habituation/dishabituation test and soybean agglutinin binding to the accessory olfactory bulb suggested that the vomeronasal organ-excising surgery completely ablated the vomeronasal organ while preserving the functioning of the main olfactory system. From the above results, we showed that the vomeronasal organ plays an important role in alarm pheromone effects in the modified open-field test and acoustic startle reflex test.

Olfactory signals mediate social buffering of conditioned fear responses in male rats.

In social animals, the presence of an affiliative conspecific alleviates acute stress responses, and this is called social buffering. We previously reported that social buffering mitigates the fear responses of male rats to auditory conditioned stimuli that had been paired with foot shocks. Subsequent studies revealed that signals that are perceived by the main olfactory epithelium are important for social buffering. Because olfactory signals are the signal perceived by the main olfactory epithelium, we hypothesized that we could induce the social buffering of conditioned fear responses by presenting olfactory signals that were derived from a conspecific. In order to test this hypothesis, we exposed fear-conditioned subjects to a conditioned stimulus either in a clean test box or in a test box that was odorized by keeping a conspecific in it as an odor donor beforehand. When the subjects were tested in the clean test box, they showed behavioral fear responses and enhanced Fos expression in the paraventricular nucleus. In contrast, the presence of conspecific olfactory signals blocked these fear responses and Fos expression. These results suggested that olfactory signals suppress conditioned fear responses. Fos expression in the posteromedial region of the olfactory peduncle and amygdala suggested that this suppression involves the same neural mechanisms as those of social buffering. Taken together, we concluded that olfactory signals mediate the social buffering of conditioned fear responses.

Twelve hours is sufficient for social buffering of conditioned hyperthermia.

We previously reported that in male rats, 24 h of social housing with an associate male rat immediately following fear conditioning attenuated conditioned hyperthermia in response to an auditory conditioned stimulus. In this study, we investigated the time window and threshold of social housing where "social buffering" mitigates conditioned hyperthermia. When 6 h of social housing immediately followed the conditioning procedure, attenuation of conditioned hyperthermia did not occur. However, an 18-h social housing period that started 6h after the conditioning procedure successfully blocked the subsequent hyperthermia, as was observed in our previous study. We also shortened the duration of social housing and found that a 12-h, but not a 6-h, period of social housing mitigated the subsequent hyperthermia. In addition, a 24-h social housing period that started 24 h after the conditioning procedure mitigated the hyperthermia. These results suggest that 12 h is sufficient for social buffering of conditioned hyperthermia.

Effects of early weaning on anxiety and prefrontal cortical and hippocampal myelination in male and female Wistar rats.

We investigated developmental changes in myelin formation in the prefrontal cortex and the hippocampus, and behavioral effects of early weaning in Wistar rats. Early-weaned rats showed decreased numbers of open-arm entries in an elevated plus-maze in both sexes at 4 weeks old; this effect persisted in males, but ceased in females after this age. Expression of myelin basic protein (MBP) showed both age-dependent increases and sex differences; 4-week-old males exhibited higher MBP levels in the hippocampus, whereas 7-week-old males showed lower MBP levels in the prefrontal cortex compared to females of the same age. There was a tendency for group differences from weaning for the 21.5-kDa isoform in the prefrontal cortex. Although these results suggest that male rats are more vulnerable than females to early-weaning effects on anxiety-related behaviors, further detailed analysis is needed to clarify the functional relationship between myelination and anxiety-related behaviors.

Early weaning decreases play-fighting behavior during the postweaning developmental period of Wistar rats.

We examined the influence of early weaning on the development of play-fighting behaviors and anxiety status in Wistar rats. Pups were divided into two groups, those weaned at postnatal day (PD) 16 (early-weaned group) and those weaned at PD30 (normally weaned group), and were housed in pairs of the same sex. Playful interactions were measured for each pair once a week from 4 to 7 weeks of age. Thereafter, during early adulthood, all the rats were subjected to the elevated plus-maze test. The frequencies of pinning and playful attack were less in the early-weaned group than in the normally weaned group. In the elevated plus-maze test, rat pups in the early-weaned group had higher anxiety levels. The results showed that deprivation of mother-pup interactions during the preweaning period decreases affiliative interactions between cage mates, including play-fighting behaviors during the postweaning developmental period, and increases anxiety levels during early adulthood.