Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity.

Interferon regulatory factor-5 (IRF5), a transcription factor critical for the induction of innate immune responses, contributes to the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) in humans and mice. Lyn, a Src family kinase, is also implicated in human SLE, and Lyn-deficient mice develop an SLE-like disease. Here, we found that Lyn physically interacted with IRF5 to inhibit ubiquitination and phosphorylation of IRF5 in the TLR-MyD88 pathway, thereby suppressing the transcriptional activity of IRF5 in a manner independent of Lyn's kinase activity. Conversely, Lyn did not inhibit NF-κB signaling, another major branch downstream of MyD88. Monoallelic deletion of Irf5 alleviated the hyperproduction of cytokines in TLR-stimulated Lyn(-/-) dendritic cells and the development of SLE-like symptoms in Lyn(-/-) mice. Our results reveal a role for Lyn as a specific suppressor of the TLR-MyD88-IRF5 pathway and illustrate the importance of fine-tuning IRF5 activity for the maintenance of immune homeostasis.

Isolated injuries to the lateral ankle ligaments have no direct effect on syndesmotic stability.

PURPOSE: This study aim was to detect the impact of lateral ankle ligaments injury on syndesmotic laxity when evaluated arthroscopically in a cadaveric model. The null hypothesis was that lateral ankle ligament injury does not affect the stability of syndesmosis. METHODS: Sixteen fresh-frozen above-knee amputated cadaveric specimens were divided into two groups of eight specimens that underwent arthroscopic evaluation of the distal tibiofibular joint. In both the groups, the assessment was first done with all syndesmotic and ankle ligaments intact. Thereafter, Group 1 underwent sequential transection of the three lateral ankle ligaments first to identify the effects of lateral ligament injury: (1) anterior talofibular ligament (ATFL), (2) calcaneofibular ligament (CFL), (3) posterior talofibular ligament (PTFL), then followed by the syndesmotic ligaments, (4) AITFL, (5) Interosseous ligament (IOL), and (6) PITFL. Group 2 underwent sequential transection of the (1) AITFL, (2) ATFL, (3) CFL, (4) IOL, (5) PTFL, and (6) PITFL, which represent the most commonly injured pattern in ankle sprain. In all scenarios, four loading conditions were considered under 100 N of direct force: (1) unstressed, (2) a lateral fibular hook test, (3) anterior to posterior (AP) fibular translation test, and (4) posterior to anterior (PA) fibular translation test. Distal tibiofibular coronal plane diastasis at the anterior and posterior third of syndesmosis, as well as AP and PA sagittal plane translation, were arthroscopically measured. RESULTS: The distal tibiofibular joint remained stable after transection of all lateral ankle ligaments (ATFL, CFL, and PTFL) as well as the AITFL. However, after additional transection of the IOL, the syndesmosis became unstable in both the coronal and sagittal plane. Syndesmosis laxity in the coronal plane was also observed after transection of the ATFL, CFL, AITFL, and IOL. Subsequent transection of the PITFL precipitated syndesmosis laxity in the sagittal plane, as well. CONCLUSIONS: The findings from the present study suggest that lateral ankle ligament injuries itself do not directly affect the stability of syndesmosis. However, if it combines with IOL injuries, even partial injuries cause syndesmotic laxity. As a clinical relevance, accurate diagnosis is the key for surgeons to determine syndesmosis fixation whether there is only AITFL injury or combined IOL injury in concomitant acute syndesmotic and lateral ligament injury.

Identification and characterization of a novel bat polyomavirus in Japan.

A novel polyomavirus (PyV) was identified in the intestinal contents of Japanese eastern bent-wing bats (Miniopterus fuliginosus) via metagenomic analysis. We subsequently sequenced the full genome of the virus, which has been tentatively named Miniopterus fuliginosus polyomavirus (MfPyV). The nucleotide sequence identity of the genome with those of other bat PyVs was less than 80%. Phylogenetic analysis revealed that MfPyV belonged to the same cluster as PyVs detected in Miniopterus schreibersii. This study has identified the presence of a novel PyV in Japanese bats and provided genetic information about the virus.

[Clinical Significance of Palliative Esophageal Stent Placement for Esophageal Cancer].

BACKGROUND: Since the introduction of the guideline for the diagnosis and treatment of esophageal carcinoma in 2007, the indication for placing an esophageal stent has changed, especially with respect to the treatment of esophageal stricture after chemoradiotherapy(CRT). For CRT cases, irradiation after stent placement and stent placement after CRT are not recommended due to the risk of perforation. METHODS: Thirty-eight patients who underwent esophageal stenting in our department between January 2007 and December 2018 and who were diagnosed with thoracic esophageal cancer were included in this study. We retrospectively examined the safety and treatment effect of esophageal stent placement. RESULTS: Prior cancer therapy was observed in 16 cases(8 cases of chemotherapy and 8 cases of CRT). In the no prior therapy group, 13 cases were treated with BSC and 9 cases with chemotherapy. Esophageal stent placement after CRT was performed in 8 cases. Esophageal stent was placed 9(6-14)months after CRT. The stent patency period was 5(1-11)months, and the survival period after stent placement was 6(1-12)months. There was no difference in the frequency of complications and treatment outcomes of the CRT group compared with the non-CRT group. CONCLUSION: Cases undergoing esophageal stent placement after CRT can expect therapeutic effects similar to those of other cases. However, complications such as perforation can be fatal; thus, careful consideration should be given to each individual case for esophageal stent placement after CRT.

Regulation and role of the transcription factor IRF5 in innate immune responses and systemic lupus erythematosus.

The transcription factor interferon regulatory factor-5 (IRF5) plays an important role in innate immune responses via the TLR-MyD88 (Toll-like receptor - myeloid differentiation primary response 88) pathway. IRF5 is also involved in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Recent studies have identified new regulators, both positive and negative, which act on IRF5 activation events in the TLR-MyD88 pathway such as post-translational modifications, dimerization and nuclear translocation. A model of the causal relationship between IRF5 activation and SLE pathogenesis proposes that a loss of the negative regulation of IRF5 causes its hyperactivation, resulting in hyperproduction of type I interferons and other cytokines, and ultimately in the development of SLE. Importantly, to our knowledge, all murine models of SLE studied thus far have shown that IRF5 is required for the pathogenesis of SLE-like diseases. During the development of SLE-like diseases, IRF5 plays key roles in various cell types, including dendritic cells and B cells. It is noteworthy that the onset of SLE-like diseases can be inhibited by reducing the activity or amount of IRF5 by half. Therefore, IRF5 is an important therapeutic target of SLE, and selective suppression of its activity and expression may potentially lead to the development of new therapies.

Vestibular-related eye movements in the rat following selective electrical stimulation of the vestibular sensors.

Rats are the most commonly used species in the neurosciences; however, little is known about the effects of selective electrical stimulation of individual vestibular sensors, on their eye movements. This limits their use to study the effects of vestibular stimulation on the brain, and their use in further exploring novel technologies such as artificial vestibular implants. We describe the effects of electrical stimulation of each vestibular sensor on vestibular-related eye movement in rats and compared the results to other species. We demonstrated that each sensor is responsible for specific bilateral eye movements. We found that the eye movements in rats differed from other species. Although the results were similar when stimulating the horizontal canal ampulla, differences appeared when stimulating the vertical canal sensors. During utricular stimulation, the ipsilateral eye moved dorsally in most cases, while the contralateral eye usually moved either caudally, or in extorsion. Saccular stimulation usually moved the ipsilateral eye dorsally or ventrally, while the contralateral eye usually moved ventrally or caudally. This study provides the first data on the application of selective electrical vestibular stimulation in the rat to the study of vestibular-related eye movements.

[A Case of Anal Canal Adenocarcinoma Locally Controlled by Rectal Amputation after Chemoradiotherapy].

A 73-year-old man was admitted to our hospital with anal pain. The 10 cm tumor was observed externally at the 3 o' clock side of his anus. He was unable to maintain the sitting position because of pain and had fecal incontinence and erosive skin inflammation. We identified this anal stenosis as anal canal adenocarcinoma(moderately differentiated). Thereby, no distant metastasis was found; we decided to treat the patient with conventional therapy. We made a double-hole colostomy in the sigmoid colon, and then the patient received preoperative chemoradiotherapy(CRT). Radiation therapy(RT)was adminis- tered at 40 Gy/20 Fr and oral capecitabine of 825mg/m / 2/time was administered twice a day on the RT days. The tumor shrinkage was good, and then we performed a laparoscopy-assisted abdominoperineal resection of the rectum. Pathologically therapeutic effect was Grade 1b. His activity of daily living was dramatically improved, and he can now main tan the sitting position. Twelve months postoperatively, he has no sign of recurrence. In this case, we experienced an anal canal adenocarcinoma that was possibly locally controlled by preoperative CRT and rectal amputation.

[A Case of Sister Mary Joseph's Nodule from Multiple Colon Cancers].

A 94-year-old woman, who had been treated for multiple colon cancers 4 years ago, complained of umbilicus induration and had been followed up in a previous hospital with a diagnosis of periumbilical inflammation. Four years and 3 months postoperatively, the umbilical induration was enlarged, and umbilical metastasis of adenocarcinoma was diagnosed on biopsy. Umbilical resection was performed, and multiple peritoneal metastases were revealed. Umbilical metastases may worsen the patient's quality of life; thus, local resection was recommended positively.

Novel cyclovirus detected in the intestinal contents of Taiwan squirrels (Callosciurus erythraeus thaiwanensis).

A novel cyclovirus was identified in the intestinal contents of Taiwan squirrels (Callosciurus erythraeus thaiwanensis) collected in Kanagawa prefecture, Japan, by metagenomic analysis, and was named Taiwan squirrel cyclovirus-1 (TsCyV-1). Phylogenetic analysis showed that TsCyV-1 formed a branch separate from other representative cyclovirus strains. TsCyV-1 is considered to be a new species in the genus Cyclovirus because the criteria for demarcation of cyclovirus species is proposed as nucleotide identities <80 %.

Galvanic vestibular stimulation impairs cell proliferation and neurogenesis in the rat hippocampus but not spatial memory.

Galvanic vestibular stimulation (GVS) is a method of activating the peripheral vestibular system using direct current that is widely employed in clinical neurological testing. Since movement is recognized to stimulate hippocampal neurogenesis and movement is impossible without activation of the vestibular system, we speculated that activating the vestibular system in rats while minimizing movement, by delivering GVS under anesthesia, would affect hippocampal cell proliferation and neurogenesis, and spatial memory. Compared with the sham control group, the number of cells incorporating the DNA replication marker, bromodeoxyuridine (BrdU), was significantly reduced in the bilateral hippocampi in both the cathode left-anode right and cathode right-anode left stimulation groups (P ≤ 0.0001). The majority of the BrdU(+ve) cells co-expressed Ki-67, a marker for the S phase of the cell cycle, suggesting that these BrdU(+ve) cells were still in the cell cycle; however, there was no significant difference in the degree of co-labeling between the two stimulation groups. Single labeling for doublecortin (DCX), a marker of immature neurons, showed that while there was no significant difference between the different groups in the number of DCX(+ve) cells in the right dentate gryus, in the left dentate gyrus there was a significant decrease in the cathode left-anode right group compared with the sham controls (P ≤ 0.03). Nonetheless, when animals were tested in place recognition, object exploration and Morris water maze tasks, there were no significant differences between the GVS groups and the sham controls. These results suggest that GVS can have striking effects on cell proliferation and possibly neurogenesis in the hippocampus, without affecting spatial memory.

Factors influencing clinically significant delayed gastric emptying after subtotal stomach-preserving pancreatoduodenectomy.

BACKGROUND: Subtotal stomach-preserving pancreatoduodenectomy (SSPPD), in which the pylorus ring is resected and most of the stomach is preserved, has been performed recently in Japan. This study was undertaken to clarify the incidence of delayed gastric emptying (DGE) after SSPPD at a high-volume hospital and to determine the independent factors that influence the development of DGE after SSPPD. METHODS: Between 2002 and 2011, 201 consecutive patients underwent standardized SSPPD. After SSPPD, DGE (defined according to the International Study Group of Pancreatic Surgery) was analyzed, and associated variables were assessed by univariate and multivariate analyses, retrospectively. RESULTS: Clinically significant DGE (grades B and C) occurred in 35 (17 %) of the 201 patients; 26 patients had other accompanying abdominal complications (secondary DGE), and pancreatic leakage was the sole risk factor for DGE (odds ratio 6.63, 95 % CI 2.86-15.74; p < 0.001). Only nine (4 % of all patients) of the 35 patients with clinically significant DGE were classified as having DGE that had arisen without any obvious etiology (primary DGE). CONCLUSIONS: DGE after SSPPD is strongly linked to the occurrence of other postoperative intra-abdominal complications such as pancreatic fistula. The incidence rate of primary DGE after SSPPD was 4 %. Although the ISGPS classification of DGE is clearly applicable, the grades do not explain why DGE occurs. Primary and secondary DGE should therefore be defined separately.

Geometric-based approach for linking various building measurement data to a 3D city model.

Currently, the Ministry of Land, Infrastructure, Transport, and Tourism (Japan) is in the process of developing an open 3D city model known as PLATEAU. Abundant measurement data related to buildings, including maps produced by private companies and mobile mapping system point clouds, have been collected to enhance the value of the 3D city model. To achieve this, it is necessary to identify the buildings for which measurement data is available. In this study, we propose and evaluate an efficient matching method for various building measurement data, primarily using geometric properties. In Numazu city, PLATEAU IDs were assigned to 88,525 Zenrin buildings as part of a private map. The results indicate that 90.6% of the polygons were matched. For aerial images, 93.6% of the extracted buildings matched the PLATEAU buildings, although only 70.9% of the PLATEAU data was extracted from the images. Using the level of detail 1 and 2 models, 46 textured building files were created from the mobile mapping system point cloud. In addition, the cover ratio for the laser profiling point cloud was mostly greater than 40%, which was higher than that of the mobile mapping system.

Effects of sodium bicarbonate solution on hypergravity-induced Fos expression in neurons of the amygdala in rats: Implication of sodium bicarbonate therapy for vertigo.

OBJECTIVE: In Japan, intravenous injection of a 7 % solution of sodium bicarbonate (NaHCO3) had been originally developed to inhibit motion sickness and then have long been used to treat vertigo. Previously, we reported that Fos-positive neurons appear in the amygdala after hypergravity stimulation in rats. In the present study, we examined whether injection of 7 % NaHCO3 inhibits hypergravity-induced Fos expression in the neurons in the central nucleus of the amygdala in rats. METHODS: Rats were exposed to 2 G hypergravity in an animal centrifuge device for 3 h. A solution of 7 % NaHCO3 at a dose of 4 mM/kg was injected intraperitoneally before 2 G hypergraviy. Fos-positive neurons in the amygdala were stained immunohistochemically. RESULTS: The number of Fos-positive neurons in the central nucleus of the amygdala was significantly increased after 2 G hypergravity in rats that received no drugs or saline, compared to that in rats exposed only to the noise of the centrifuge and received 7 % NaHCO3 solution. The number of Fos-positive neurons in the central nucleus of the amygdala after 2 G hypergravity was significantly decreased in rats that received 7 % NaHCO3 solution, compared to that in rats that received no drugs or saline. CONCLUSION: Since Fos expression is a marker of activated neurons, the present findings suggest that hypergravity activates the amygdala and that administration of 7 % NaHCO3 suppresses hypergravity-induced activation of the amygdala. Hypergravity disturbs spatial orientation to produce motion sickness and the amygdala is involved in fear response. Recently, Ziemann et al. suggested that fear-evoking stimuli reduce the pH in the amygdala to activate it, leading to induction of fear behavior and that administering HCO3- attenuates fear behavior [Cell 2009; 139: 1012-1021]. Therefore, it is possible that hypergravity reduces the pH in the amygdala to activate it, thereby inducing the fear associated with motion sickness and that administration of 7 % NaHCO3 increases the brain pH thereby suppressing hypergravity-induced activation of the amygdala and inhibiting the fear associated with motion sickness. In patients with vertigo, 7 % NaHCO3 therapy may increase the brain pH thereby suppressing the activation of the amygdala and inhibiting the fear associated with vertigo to elicit a beneficial clinical effect.

SWI/SNF-Related Matrix-Associated Actin-Dependent Regulator of Chromatin Subfamily B Member 1 (SMARCB1)-Deficient Tumor in the Parapharyngeal Space: A Case Report.

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) is a tumor suppressor gene, and SMARCB1 deficits have been associated with numerous malignant tumors. Carcinomas with a SMARCB1 deficit generally have a poor prognosis. In the head and neck region, there have been many recent cases of SMARCB1-deficient sinonasal carcinoma, but reports of extrasinonasal sites are extremely rare. This study reports a case of SMARCB1-deficient tumor in the right parapharyngeal space. A 64-year-old woman with right neck swelling was presented to our hospital, and imaging revealed a tumor in the right parapharyngeal space. After four years of follow-up, the tumor had increased in size, and a biopsy revealed deficits in SMARCB1 in the tumor cells. No definitive histological diagnoses were made. Radiation reduced the size of the tumor, and the patient survived without progression, three years after completion of treatment.

Vestibular compensation: Neural mechanisms and clinical implications for the treatment of vertigo.

After unilateral peripheral vestibular lesions, the neural activity of neurons in the ipsi-lesional medial vestibular nucleus (ipsi-MVe) are markedly decreased, resulting in static and dynamic asymmetries of the vestibulo-ocular and vestibulo-spinal reflexes. Consequently, static vestibular symptoms such as spontaneous nystagmus and postural deviation and dynamic vestibular symptoms such as oscillopsia and swaying gait are induced. However, these behavioral asymmetries gradually recover after the lesion. Progressive balance restoration is termed vestibular compensation, which is divided into two phases: static and dynamic. Static vestibular compensation is further divided into initial and late processes. In the initial process of static vestibular compensation after unilateral labyrinthectomy (UL) in rats, plastic changes in the cerebello-vestibular and vestibular commissural inhibitory pathways suppress neurons in the contra-lesional MVe (contra-MVe), resulting in the restoration of symmetrical resting activity of MVe neurons on both sides at low levels. The declining frequency of spontaneous nystagmus after UL is an index of the initial process, and short-term administration of diazepam, a GABAA receptor agonist, has been shown to accelerate the initial process in rats. Accordingly, short-term administration of diazepam is recommended for the treatment of acute vertigo in patients with unilateral vestibular dysfunction. In the late process of static vestibular compensation after UL in rats, the resting activity of ipsi-MVe neurons gradually recovers due to changes in cell membrane properties, resulting in the reinforcement of balanced intervestibular nuclear activities to nearly normal levels without the suppression of contra-MVe neurons. The declining number of MK801-induced Fos-positive neurons in contra-MVe after UL is an index of the late process, and long-term administration of betahistine, a histamine H3 receptor antagonist, has been shown to accelerate the late process in rats. Accordingly, long-term administration of betahistine is recommended for the treatment of subacute vertigo in patients who were not compensated for unilateral vestibular dysfunction. In the process of dynamic vestibular compensation after UL, the sensitivity of ipsi-MVe neurons to head velocity and acceleration is restored due to synaptic changes such as long-term potentiation and sprouting of commissures, resulting in the restoration of the dynamic vestibulo-ocular and vestibulo-spinal reflexes. To facilitate dynamic vestibular compensation, early ambulation and subsequent vestibular rehabilitation exercise are recommended for the treatment of chronic vertigo in patients with uncompensated unilateral vestibular dysfunction. Although vestibular compensation after bilateral vestibular loss is not expected, vestibular rehabilitation with a sensory-substitution strategy can improve imbalance in patients with bilateral vestibular lesions.

Orbital apex syndrome secondary to acute invasive fungal rhinosinusitis diagnosed by transnasal endoscopic biopsy of the optic canal:A case report.

Orbital apex syndrome (OAS) is a complex condition characterized by visual loss, diplopia, and eye pain that occurs secondary to several pathological processes involving the orbital apex. We report a case of acute invasive fungal rhinosinusitis (AIFRS) associated with OAS. A 76-year-old man with left-sided visual loss, diplopia, palpebral ptosis, and headache was diagnosed with OAS secondary to Tolosa-Hunt syndrome and received systemic corticosteroid therapy from his neurologist. Owing to persistent symptoms, we opened the optic canal using a transnasal endoscopic approach for a surgical biopsy of the orbital apex lesions. Histopathological evaluation revealed numerous Aspergillus organisms in the biopsied granuloma. After surgical debridement, he received a 12-month course of voriconazole, and no recurrence of AIFRS occurred during 8-year follow-up. Patients with OAS may occasionally be prescribed corticosteroids because the clinical manifestations of AIFRS-induced OAS are similar to those observed in OAS secondary to Tolosa-Hunt syndrome, especially no nasal symptoms which is known to respond to corticosteroid therapy. Because both AIFRS-induced OAS and OAS secondary to Tolosa-Hunt syndrome induce ophthalmoplegia, proptosis, eye pain, it is sometimes difficult to differentiate these two diseases in early stage. However, corticosteroid therapy causes exacerbation of fungal infection in patients with AIFRS-induced OAS resulting in delayed accurate diagnosis and poor prognosis. AIFRS is associated with a high mortality rate ; therefore, transnasal endoscopic biopsy of orbital apex lesions before corticosteroid administration is recommended in patients with OAS. J. Med. Invest. 71 : 310-313, August, 2024.

Long-term effect of posterior nasal neurectomy for perennial allergic rhinitis.

BACKGROUND: Surgical treatment is recommended for patients with severe allergic rhinitis (AR) refractory to medical treatment. Endoscopic posterior nasal neurectomy (PNN) is primarily performed to improve rhinorrhea in severe perennial AR, however studies on its long-term prognosis are lacking. AIMS/OBJECTIVES: This study aimed to investigate the long-term prognosis of PNN. MATERIALS AND METHODS: A questionnaire survey was administered to 17 patients (12 men and 5 women) at least 1 year after PNN. Nasal symptoms and medications, as well as patient satisfaction with surgery at the time of survey, were scored. Furthermore, scores were compared between patients with postoperative periods of >5 years and <5 years. RESULTS: Nasal symptoms and medication scores significantly improved after surgery. There was no significant difference between patients with a postoperative period of >5 years and <5 years in both preoperative and postoperative nasal symptoms and medication scores. No correlation was found between patient satisfaction with surgery and postoperative period. CONCLUSIONS AND SIGNIFICANCE: PNN improved nasal symptoms and medication scores in patients with severe perennial AR. Furthermore, the study results suggest that the long-term effect of PNN for perennial AR lasts for >5 years. J. Med. Invest. 71 : 62-65, February, 2024.

Location of ethmoidal arteries in relation to ethmoid cells and the anterior skull base.

BACKGROUND: Ethmoidal arteries are at risk of accidental injury during endoscopic sinus surgery (ESS). AIMS/OBJECTIVES: We aimed to examine the location of ethmoidal arteries in relation to ethmoid cells and the anterior skull base (ASB) in Japanese patients. MATERIAL AND METHODS: CT images of 100 sides of 50 patients were retrospectively reviewed. The location of anterior ethmoidal arteries (AEAs), middle ethmoidal arteries (MEAs) and posterior ethmoidal arteries (PEAs) in relation to ethmoidal cells and their distance from the ASB were evaluated. RESULTS: AEAs and PEAs were present in all sides. 60% of AEAs and 9% of PEAs ran below the level of ASB. MEAs were present in 21 sides and ran below the ASB in 23.8% (5/21) of these sides. The incidence of AEAs running below the level of ASB was significantly higher in the sides with supraorbital ethmoid cells (SOECs) than in those without SOECs. CONCLUSION AND SIGNIFICANCE: This study revealed the position and the distance from ASB of AEAs, PEAs, and MEAs in relation to ethmoid cells in Japanese patients. In cases with SOECs, surgeons should be careful not to injure the AEAs running below the level of ASB. J. Med. Invest. 71 : 273-278, August, 2024.

Effects of high-dose betahistine on intractable dizziness in patients with uncompensated unilateral vestibulopathy.

OBJECTIVE: In the present study, we examined the effects of high-dose betahistine on dizziness handicap inventory (DHI) scores in patients with unilateral vestibulopathy. METHODS: An uncontrolled, open-label, multicenter clinical trial was conducted. Fifteen patients with unilateral vestibulopathy, such as vestibular neuritis, who complained of intractable dizziness for more than three months were enrolled. Initially, all patients were orally administered betahistine at a dose of 36 mg/day for four weeks, which is the standard dose and dosing period for the treatment of dizziness in Japan. The patients were then administered betahistine at a double dose of 72 mg/day for four weeks. Six patients who became aware of the benefits of high-dose betahistine were further administered betahistine at 72 mg/day for an additional 12 weeks (a total of 16 weeks). Perceived disability due to dizziness was assessed by DHI scores. RESULTS: In all 15 patients, short-term administration with high-dose (72 mg/day) betahistine for four weeks, but not low-dose betahistine (36 mg/day) for four weeks significantly decreased DHI scores. In particular, in six responding patients with self-reported benefits after short-term administration with high-dose betahistine, long-term administration with high-dose betahistine for 16 weeks further significantly decreased DHI scores. However, DHI scores of the remaining nine non-responding patients were not changed after short-term administration with high-dose betahistine for four weeks. CONCLUSION: Short-term administration with the standard dose and dosing period of betahistine did not improve DHI scores in the enrolled patients, indicating that they were not compensated for unilateral vestibulopathy with intractable dizziness. The present findings suggest that long-term administration with high-dose betahistine facilitates vestibular compensation to improve intractable dizziness in some, but not all patients with uncompensated unilateral vestibulopathy.

Oxygen delivery-guided perfusion for the prevention of acute kidney injury: A randomized controlled trial.

OBJECTIVES: The reduction of postoperative acute kidney injury in patients undergoing cardiopulmonary bypass surgery using an oxygen delivery-guided perfusion strategy (oxygen delivery strategy) for cardiopulmonary bypass management compared with a fixed flow perfusion (conventional strategy) remains controversial. The purpose of this study was to determine whether a oxygen delivery strategy would reduce the incidence of postoperative acute kidney injury in patients undergoing cardiopulmonary bypass surgery. METHODS: We randomly enrolled 300 patients undergoing cardiopulmonary bypass surgery. Patients were randomly assigned to a oxygen delivery strategy (maintaining a oxygen delivery index value >300 mL/min/m2 through pump flow adjustments during cardiopulmonary bypass) or a conventional strategy (a target pump flow was determined on the basis of the body surface area). The primary end point was the development of acute kidney injury. Secondary end points were the red blood cell transfusion rate and number of red blood cell units, intubation time, postoperative length of stay in the intensive care unit and the hospital, predischarge estimated glomerular filtration rate, and hospital mortality. RESULTS: Acute kidney injury occurred in 20 patients (14.6%) receiving the oxygen delivery strategy and in 42 patients (30.4%) receiving the conventional strategy (relative risk, 0.48; 95% confidence interval, 0.30-0.77; P = .002). The secondary end points were not significantly different between strategies. In a prespecified subgroup analysis of patients who had nadir hematocrit less than 23% or body surface area less than 1.40 m2, the oxygen delivery strategy seemed to be superior to the conventional strategy and the existence of quantitative interactions was suggested. CONCLUSIONS: An oxygen delivery strategy for cardiopulmonary bypass management was superior to a conventional strategy with respect to preventing the development of acute kidney injury.