Effect of salivary gland removal on taste preference in mice.

To evaluate the effect of decreased salivary secretion on taste preference, we investigated taste preference for five basic tastes by a 48 h two-bottle preference test using a mouse model (desalivated mice) that underwent surgical removal of three major salivary glands: the parotid, submandibular, and sublingual glands. In the desalivated mice, the avoidance behaviors for bitter and salty tastes and the attractive behaviors for sweet and umami tastes were significantly decreased. We confirmed that saliva is necessary to maintain normal taste preference. To estimate the cause of the preference changes, we investigated the effects of salivary gland removal on the expression of taste-related molecules in the taste buds. No apparent changes were observed in the expression levels or patterns of taste-related molecules after salivary gland removal. When the protein concentration and composition in the saliva were compared between the control and desalivated mice, the protein concentration decreased and its composition changed after major salivary gland removal. These results suggest that changes in protein concentration and composition in the saliva may be one of the factors responsible for the changes in taste preferences observed in the desalivated mice.

Retina as a potential biomarker in schizophrenia spectrum disorders: a systematic review and meta-analysis of optical coherence tomography and electroretinography.

INTRODUCTION: Abnormal findings on optical coherence tomography (OCT) and electroretinography (ERG) have been reported in participants with schizophrenia spectrum disorders (SSDs). This study aims to reveal the pooled standard mean difference (SMD) in retinal parameters on OCT and ERG among participants with SSDs and healthy controls and their association with demographic characteristics, clinical symptoms, smoking, diabetes mellitus, and hypertension. METHODS: Using PubMed, Scopus, Web of Science, and PSYNDEX, we searched the literature from inception to March 31, 2023, using specific search terms. This study was registered with PROSPERO (CRD4202235795) and conducted according to PRISMA 2020. RESULTS: We included 65 studies in the systematic review and 44 in the meta-analysis. Participants with SSDs showed thinning of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer- inner plexiform cell layer, and retinal thickness in all other segments of the macula. A meta-analysis of studies that excluded SSD participants with diabetes and hypertension showed no change in results, except for pRNFL inferior and nasal thickness. Furthermore, a significant difference was found in the pooled SMD of pRNFL temporal thickness between the left and right eyes. Meta-regression analysis revealed an association between retinal thinning and duration of illness, positive and negative symptoms. In OCT angiography, no differences were found in the foveal avascular zone and superficial layer foveal vessel density between SSD participants and controls. In flash ERG, the meta-analysis showed reduced amplitude of both a- and b-waves under photopic and scotopic conditions in SSD participants. Furthermore, the latency of photopic a-wave was significantly shorter in SSD participants in comparison with HCs. DISCUSSION: Considering the prior report of retinal thinning in unaffected first-degree relatives and the results of the meta-analysis, the findings suggest that retinal changes in SSDs have both trait and state aspects. Future longitudinal multimodal retinal imaging studies are needed to clarify the pathophysiological mechanisms of these changes and to clarify their utility in individual patient monitoring efforts.

Quantitative evaluation of corneal irregularity and scarring after infectious keratitis using anterior segment optical coherence tomography.

PURPOSE: Corneal scars after infectious keratitis lead to insufficient transparency and irregular astigmatism, affecting visual acuity; therefore, they should be accurately evaluated to estimate visual function. This study aimed to quantitatively evaluate corneal irregularity and scarring after infectious keratitis using anterior segment optical coherence tomography (AS-OCT). METHODS: This was an observational clinical study. We included patients who had corneal scarring after treatment of infectious keratitis between 2014 and 2021 at University of Tokyo Hospital. We retrospectively examined best spectacle-corrected visual acuity (BSCVA), average keratometric power, central corneal thickness (CCT), and four components of the Fourier harmonic analysis including spherical and asymmetry components, as well as regular astigmatism and higher-order irregularity. We included anterior and posterior corneal data and compared results with those of contralateral healthy eyes. Additionally, we quantitatively evaluated the densitometry of the cornea obtained using AS-OCT. RESULTS: A total of 122 eyes of 61 patients were examined; male predominance was observed (n = 37), and the mean patient age was 55.3 ± 19.4 years. Comparisons with contralateral healthy eyes showed that BSCVA worsened (0.30 ± 0.83 and 0.93 ± 1.36 logMAR, respectively, P = 0.003), and CCT (531.1 ± 46.2 and 591.8 ± 132.4 µm, respectively, P < 0.001) and corneal densitometry (84.4 ± 11.8 and 111.9 ± 19.2 grayscale units, respectively, P < 0.001) increased significantly in affected eyes. The asymmetry component and higher-order irregularities that were not corrected with spectacles significantly increased (both P < 0.001), and there were no significant differences in the changes among the bacterial, fungal, herpetic, and acanthamoeba types of keratitis. CONCLUSION: Corneal scarring persisted after treatment for infectious keratitis, and the asymmetry and irregularities of corneal astigmatism increased as visual acuity deteriorated. AS-OCT with the Fourier harmonic analysis was useful for evaluating corneal topographic changes in patients with corneal scarring after keratitis.

Post-operative shift in pain profile following fusion surgery for adult spinal deformity: a cluster analysis.

PURPOSE: Adult spinal deformity (ASD) is associated with a combination of back and leg pain of various intensities. The objective of the present study was to investigate the diverse reaction of pain profiles following ASD surgery as well as post-operative patient satisfaction. METHODS: Multicenter surveillance collected data for patients ≥ 19 years old who underwent primary thoracolumbar fusion surgery at > 5 spinal levels for ASD. Two-step cluster analysis was performed utilizing pre-operative numeric rating scale (NRS) for back and leg pain. Radiologic parameters and patient-reported outcome (PRO) scores were also obtained. One-year post-operative outcomes and satisfaction rates were compared among clusters, and influencing factors were analyzed. RESULTS: Based on cluster analysis, 191 ASD patients were categorized into three groups: ClusterNP, mild pain only (n = 55); ClusterBP, back pain only (n = 68); and ClusterBLP, significant back and leg pain (n = 68). ClusterBLP (mean NRSback 7.6, mean NRSleg 6.9) was the oldest 73.4 years (p < 0.001) and underwent interbody fusion (88%, p < 0.001) and sacral/pelvic fixation (69%, p = 0.001) more commonly than the other groups, for the worst pelvis incidence-lumbar lordosis mismatch (mean 43.7°, p = 0.03) and the greatest sagittal vertical axis (mean 123 mm, p = 0.002). While NRSback, NRSleg and PRO scores were all improved postoperatively in ClustersBP and BLP, ClusterBLP showed the lowest satisfaction rate (80% vs. 80% vs. 63%, p = 0.11), which correlated with post-operative NRSback (rho = -0.357). CONCLUSIONS: Cluster analysis revealed three clusters of ASD patients, and the cluster with the worst pain back and leg pain had the most advanced disease and showed the lowest satisfaction rate, affected by postoperative back pain.

Proximal ligation technique prevents thrombus formation in the pulmonary vein stump after lobectomy.

PURPOSE: To assess the risk factors for thrombosis in the pulmonary vein stump (PVT) and the efficacy of proximal ligation in preventing PVT after lobectomy. METHODS: In total, 649 surgical patients with lung cancer were retrospectively reviewed. To compare the clinical effectiveness of PV proximal ligation, the simple stapler group (290 patients) and the proximal ligation group (359 patients who underwent thread ligation at the pericardial reflection with/without a stapler) were analyzed. RESULTS: In the simple stapler group, 12 of 290 patients (4.1%) developed PVT. Among these, 9 of 58 underwent left upper lobectomy (LUL). In contrast, 5 of the 359 patients (1.4%) in the proximal ligation group developed PVT. All five patients received LUL. The incidence of PVT in the proximal ligation group was significantly lower than that in the simple stapler group (p = 0.0295) as well as in the analysis by LUL alone (p = 0.0263). A logistic regression analysis indicated that higher BMI and LUL were associated with the development of PVT (p = 0.0031, p < 0.0001), and PV proximal ligation reduced PVT (p = 0.0055). CONCLUSION: Proximal ligation of the PV has the potential to prevent PVT, especially after LUL.

Continuous Monitoring of Pseudopolymorphic Transition in Ezetimibe Using T1 Relaxation with Time-Domain NMR.

The purpose of this study was to continuously monitor the pseudopolymorphic transition from anhydrate to monohydrate by measuring the NMR relaxation using time-domain NMR (TD-NMR). Taking advantage of the simplicity of the low-field NMR instrument configuration, which is an advantage of TD-NMR, the NMR instrument was connected to a humidity controller to monitor the pseudopolymorphic transition. First, ezetimibe (EZT) monohydrate was prepared from its anhydrate using a saturated salt solution method, and T1 relaxation of EZT monohydrate and anhydrate was measured without a humidity controller. The T1 relaxation results confirmed that EZT anhydrate and monohydrate could be distinguished using T1 relaxation measurement. Next, continuous monitoring was conducted by TD-NMR and connected to a humidity controller. Anhydrous EZT was placed in an NMR glass tube and the T1 relaxation measurement was repeated while maintaining the humidity on the side entering the NMR tube at 80% relative humidity. The T1 relaxation became gradually faster from the initial to middle monitoring phases. The final T1 relaxation was then recovered fully and these T1 relaxation times were the same as the T1 relaxation of EZT monohydrate. This study successfully monitored the pseudopolymorphic transition from EZT anhydrate to monohydrate via NMR relaxation.

NF-κB Decoy Oligodeoxynucleotide-Loaded Poly Lactic-co-glycolic Acid Nanospheres Facilitate Socket Healing in Orthodontic Tooth Movement.

Orthodontic space closure following tooth extraction is often hindered by alveolar bone deficiency. This study investigates the therapeutic use of nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides loaded with polylactic-co-glycolic acid nanospheres (PLGA-NfDs) to mitigate alveolar bone loss during orthodontic tooth movement (OTM) following the bilateral extraction of maxillary first molars in a controlled experiment involving forty rats of OTM model with ethics approved. The decreased tendency of the OTM distance and inclination angle with increased bone volume and improved trabecular bone structure indicated minimized alveolar bone destruction. Reverse transcription-quantitative polymerase chain reaction and histomorphometric analysis demonstrated the suppression of inflammation and bone resorption by downregulating the expression of tartrate-resistant acid phosphatase, tumor necrosis factor-α, interleukin-1ß, cathepsin K, NF-κB p65, and receptor activator of NF-κB ligand while provoking periodontal regeneration by upregulating the expression of alkaline phosphatase, transforming growth factor-ß1, osteopontin, and fibroblast growth factor-2. Importantly, relative gene expression over the maxillary second molar compression side in proximity to the alveolus highlighted the pharmacological effect of intra-socket PLGA-NfD administration, as evidenced by elevated osteocalcin expression, indicative of enhanced osteocytogenesis. These findings emphasize that locally administered PLGA-NfD serves as an effective inflammatory suppressor and yields periodontal regenerative responses following tooth extraction.

Unilateral nasal obstruction mediates reversible morphological and phenotypic changes in masticatory muscles of growing rats.

OBJECTIVE: Mouth breathing as a result of nasal obstruction affects craniofacial growth and development. This study aimed to investigate the effects of unilateral nasal obstruction and its recovery, along with the role of nitric oxide (NO) in masticatory muscle physiology. MATERIALS AND METHODS: Forty-eight 4-week-old male rats were divided into control and experimental groups. The five experimental groups were subjected to left-sided nasal obstruction by suturing the external nostril, and the sutures were removed after 1, 3, 5, 7, or 9 weeks to allow for varying recovery periods. We assessed morphological changes in masseter, temporalis, and digastric muscle, by examining cross-sectional area (CSA) and myosin heavy chain (MHC) isoform composition of muscle fibers. Reverse transcription-quantitative real-time polymerase chain reaction to measure messenger RNA (mRNA) levels for tumor necrosis factor-α (TNF-α), glucose transporter 4 (GLUT4), and neuronal nitric oxide synthase (nNOS) were conducted. RESULTS: The SpO2, CSA, and fibers showing MHC-2b isoforms were significantly lower, while RT-PCR showed higher mRNA levels in TNF-α and nNOS, and a decrease in GLUT4 mRNA in the jaw-closing muscles in the long-term nasal obstruction groups than that in the control group. LIMITATIONS: The study findings should be interpreted cautiously because of the functional differences between rodents and humans in terms of respiratory mechanisms. CONCLUSIONS: Unilateral nasal obstruction affects the morphology and contractile characteristics of the rat masticatory muscles during development, with possible involvement of NO in muscle hypofunction. These changes may revert to baseline levels if the nasal obstruction is eliminated before puberty in rats.

The interleukin-6 signal regulates orthodontic tooth movement and pain.

Orthodontic tooth movement (OTM) is accomplished by controlling the mechanical loading onto the bone around the roots of target teeth. The precise orthodontic force induces osteoclastic bone resorption on the compression side and osteoblastic bone formation on the tension side of the alveolar bone. Orthodontic intervention causes inflammation in the periodontal ligament (PDL), which manifests as acute pain. Because inflammation is deeply connected to bone remodeling, it has been indicated that the inflammation after orthodontic intervention affects both the movement of teeth and generation of pain. However, the precise mechanisms underlying the immune regulation of OTM and the related pain are not well elucidated. Here, we found from the search of a public database that the interleukin (IL)-6 family of cytokines are highly expressed in the PDL by mechanical loading. The IL-6 signal was activated in the PDL after orthodontic intervention. The signal promoted OTM by inducing osteoclastic bone resorption. IL-6 was found to increase the number of osteoclasts by suppressing apoptosis and increasing their responsiveness to macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). Furthermore, IL-6 signal was shown to elicit orthodontic pain by inducing neuroinflammation in the trigeminal ganglion (TG). Taken together, it was demonstrated that the IL-6 signal regulates tooth movement and pain during orthodontic treatment. It was also indicated that local blockade of the IL-6 signal is a promising therapeutic option in orthodontic treatment, targeting both tooth movement and pain.

Retinal layers and associated clinical factors in schizophrenia spectrum disorders: a systematic review and meta-analysis.

INTRODUCTION: The retina shares structural and functional similarities with the brain. Furthermore, structural changes in the retina have been observed in patients with schizophrenia spectrum disorders (SSDs). This systematic review and meta-analysis investigated retinal abnormalities and their association with clinical factors for SSD. METHODS: Studies related to retinal layers in SSD patients were retrieved from PubMed, Scopus, Web of Science, Cochrane Controlled Register of Trials, International Clinical Trials Registry Platform, and PSYNDEX databases from inception to March 31, 2021. We screened and assessed the eligibility of the identified studies. EZR ver.1.54 and the metafor package in R were used for the meta-analysis and a random-effects or fixed-effects model was used to report standardized mean differences (SMDs). RESULTS: Twenty-three studies (2079 eyes of patients and 1571 eyes of controls) were included in the systematic review and meta-analysis. The average peripapillary retinal nerve fiber layer (pRNFL) thickness, average macular thickness (MT), and macular ganglion cell layer-inner plexiform layer (GCL-IPL) thickness were significantly lower in patients than in controls (n = 14, 6, and 3, respectively; SMD = -0.33, -0.49, and -0.43, respectively). Patients also had significantly reduced macular volume (MV) compared to controls (n = 7; SMD = -0.53). The optic cup volume (OCV) was significantly larger in patients than in controls (n = 3; SMD = 0.28). The meta-regression analysis indicated an association between several clinical factors, such as duration of illness and the effect size of the pRNFL, macular GCL-IPL, MT, and MV. CONCLUSION: Thinning of the pRNFL, macular GCL-IPL, MT, and MV and enlargement of the OCV in SSD were observed. Retinal abnormalities may be applicable as state/trait markers in SSDs. The accumulated evidence was mainly cross-sectional and requires verification by longitudinal studies to characterize the relationship between OCT findings and clinical factors.

Periostin splice variants affect craniofacial growth by influencing chondrocyte hypertrophy.

INTRODUCTION: Periostin, an extracellular matrix protein, plays an important role in osteogenesis and is also known to activate several signals that contribute to chondrogenesis. The absence of periostin in periostin knockout mice leads to several disorders such as craniosynostosis and periostitis. There are several splice variants with different roles in heart disease and myocardial infarction. However, little is known about each variant's role in chondrogenesis, followed by bone formation. Therefore, the aim of this study is to investigate the role of several variants in chondrogenesis differentiation and bone formation in the craniofacial region. Periostin splice variants included a full-length variant (Control), a variant lacking exon 17 (ΔEx17), a variant lacking exon 21 (ΔEx21), and another variant lacking both exon 17 and 21 ***(ΔEx17&21). MATERIALS AND METHODS: We used C56BL6/N mice (n = 6) for the wild type (Control)*** and the three variant type mice (n = 6 each) to identify the effect of each variant morphologically and histologically. Micro-computed tomography demonstrated a smaller craniofacial skeleton in ΔEx17s, ΔEx21s, and ΔEx17&21s compared to Controls, especially the mandibular bone. We, thus, focused on the mandibular condyle. RESULTS: The most distinctive histological observation was that each defected mouse appeared to have more hypertrophic chondrocytes than Controls. Real-time PCR demonstrated the differences among the group. Moreover, the lack of exon 17 or exon 21 in periostin leads to inadequate chondrocyte differentiation and presents in a diminutive craniofacial skeleton. DISCUSSION: Therefore, these findings suggested that each variant has a significant role in chondrocyte hypertrophy, leading to suppression of bone formation.

Tobacco Exposure During Pregnancy and Infections in Infants up to 1 Year of Age: The Japan Environment and Children's Study.

BACKGROUND: Tobacco exposure during pregnancy is associated with several adverse outcomes in infants. We investigated the association between tobacco exposure during pregnancy (both active and second-hand) and various infections in infants up to 1 year. METHODS: This prospective cohort study used a fixed dataset (jecs-an-20180131) from the Japan Environment and Children's Study of registered births in Japan during 2011-2014 that included 104,065 fetal records from enrolled pregnant women. Based on the participants' responses to the questionnaire on smoking status, mothers were first divided into "never smoked," "quit smoking," and "current smoker" groups and then into "no second-hand smoking (SHS)" and "SHS" groups. Infectious diseases included central nervous system infection, otitis media (OM), upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), gastroenteritis (GI), and urinary tract infection. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis and adjusted for maternal, socioeconomic, and postnatal confounding factors. RESULTS: Among the 73,205 newborns enrolled, multivariable analysis revealed that the aOR of LRTI and GI was 1.20 (95% CI, 1.07-1.33) and 1.18 (95% CI, 1.04-1.35), respectively, for the "current smoker with/without SHS" group compared with the "never smoked without SHS" group. "Quit smoking without SHS" was not associated with the risk of LRTI. SHS was associated with an increased risk of OM, URTI, LRTI, and GI, especially with LRTI and GI. CONCLUSION: Exposure to tobacco smoke during pregnancy was associated with an increased risk of OM, URTI, LRTI, and GI in infants during their first year of life.

N-methyl-2-pyridone-5-carboxamide (N-Me-2PY) has potent anti-fibrotic and anti-inflammatory activity in a fibrotic kidney model: is it an old uremic toxin?

BACKGROUND: Uremic toxins accumulate in renal tissues and cells due to chronic kidney disease (CKD). Abnormalities in nicotinamide adenine dinucleotide (NAD +) metabolism lead to the progression of CKD. NAD + metabolites, such as N-methyl-2-pyridone-5-carboxamide (N-Me-2PY) and N-methyl-4-pyridone-5-carboxamide (N-Me-4PY), have been recognized as uremic toxins. However, no reports have validated whether they are actually harmful to the body. Therefore, we focused on the structural similarity of these metabolites to the anti-fibrotic drug pirfenidone and evaluated their effects on renal fibrosis. METHODS: Each NAD + metabolite was treated with TGFß1 to kidney fibroblasts or tubular epithelial cells, and quantitative RT-PCR and Western blot analysis were conducted. N-Me-2PY was orally administered to a ligated murine kidney fibrosis model (UUO) to evaluate its anti-fibrotic and toxic effects on the body. RESULTS: N-Me-2PY, N-Me-4PY, and nicotinamide N-oxide (NNO) inhibited TGFß1-induced fibrosis and inflammatory gene expression in kidney fibroblasts. N-Me-2PY strongly suppressed the expression of types I and III collagen, αSMA, and IL-6. N-Me-2PY also suppressed TGFß1-induced type I collagen and IL-6 expression in renal tubular epithelial cells. No toxic effect was observed with N-Me-2PY treatment, while attenuating renal fibrosis and tubular dilation in UUO mice. Suppression of various fibrosis- and inflammation-related genes was also observed. N-Me-2PY did not inhibit TGFß1-induced Smad3 phosphorylation but inhibited Akt phosphorylation, suggesting that N-Me-2PY exerts anti-fibrotic and anti-inflammatory effects through Akt inhibition, similar to pirfenidone. CONCLUSIONS: NAD + metabolites, such as N-Me-2PY, are not uremic toxins but are potential therapeutic agents that have anti-fibrotic effects in CKD.

Early intervention for perioperative hypertension in cataract surgery.

PURPOSE: Although perioperative blood-pressure control is important, especially for high-risk patients, no previous report has examined early monitoring of perioperative blood-pressure changes before cataract surgery. In this single-center, retrospective, observational study, we evaluated the early intervention for perioperative hypertension in cataract surgery with topical anesthesia. METHODS: Hospitalized patients who underwent phacoemulsification and intraocular-lens insertion and whose blood pressure was controlled using standardized management to start early monitoring and control (standardized group; 134 eyes of 134 patients) were compared to age- and sex-matched patients who underwent the same cataract surgery and whose blood pressure was controlled using conventional means (control group; 134 eyes of 134 patients). The perioperative blood pressure, pulse pressure, and heart rate were compared preoperatively, upon entering the operation room, and at the beginning, end, and after the operation. RESULTS: Although there was no difference before the operation, the changes in systolic pressure in the standardized group were significantly lower at the point of entering the operation room, at the beginning of the operation, and at the end of the operation (P = 0.003, < 0.001, and < 0.001, respectively). No significant difference was observed between etizolam and nicardipine use. CONCLUSION: Early monitoring and control of blood pressure in cataract surgery could effectively control perioperative hypertension without additional drug use and could be widely applied in the clinical setting.

Changes in the preoperative ocular surface flora with an increase in patient age: A surveillance analysis of bacterial diversity and resistance to fluoroquinolone.

PURPOSE: This study analyzed the relationship between patient age and the prevalence and fluoroquinolone susceptibility of gram-positive cocci from the ocular surface flora before ophthalmic surgery. METHODS: This surveillance study included scraped samples from the conjunctival sac of 8923 eyes of 5490 patients (70.0 ± 13.7 years) without ocular infection before ophthalmologic surgery between August 2018 and December 2020. A review of microbiological records regarding patient age was used to determine the number of isolates and gram-positive species obtained, as well as their fluoroquinolone susceptibility. Fluoroquinolone susceptibility was determined using the Clinical and Laboratory Standards Institute protocols of broth microdilution. Statistical analysis was performed using a generalized additive model and a log-linear model. RESULTS: In total, 9,894 bacterial isolates obtained from scraped samples from the patients were analyzed. The detected species were Staphylococcus epidermidis (31.0%), Staphylococcus aureus (6.1%), Staphylococcus lugdunensis (3.9%), Enterococcus faecalis (5.8%), Corynebacterium species (31.7%), and Cutibacterium acnes (7.5%) and others. The number of species isolated from the ocular surface was increased at the rate of 1.018 per 10 years of age (p < 0.0001). S. epidermidis, S. lugdunensis, E. faecalis, and Corynebacterium species were isolated more often with an increase in patient age. The levofloxacin resistance ratio of methicillin-sensitive S. epidermidis and Corynebacterium species increased at the rate of 1.204 and 1.087 respectively with a 10-year increase in age (both p < 0.0001). CONCLUSION: Gram-positive bacteria in the ocular surface flora (OSF) exhibited gradual changes in diversity and fluoroquinolone resistance with an increase in patient age. It is important to monitor the OSF of the patients before ophthalmologic surgery to prevent refractory ocular postoperative infection.

Predictors for hemostatic thrombin-gelatin matrix usage in spine surgery: a multicenter observational study.

STUDY DESIGN: A prospective cohort study. OBJECTIVES: Thrombin-gelatin matrix (TGM) is a rapid and potent hemostatic agent, but it has some limitations, including the cost and its preparation time. The purpose of this study was to investigate the current trend in the use of TGM and to identify the predictors for TGM usage in order to ensure its proper use and optimized resource allocation. METHODS: A total of 5520 patients who underwent spine surgery in a multicenter study group within a year were included in the study. The demographic factors and the surgical factors including spinal levels operated, emergency surgery, reoperation, approach, durotomy, instrumented fixation, interbody fusion, osteotomy, and microendoscopy-assistance were investigated. TGM usage and whether it was routine or unplanned use for uncontrolled bleeding were also checked. A multivariate logistic regression analysis was used to identify predictors for unplanned use of TGM. RESULTS: Intraoperative TGM was used in 1934 cases (35.0%), among which 714 were unplanned (12.9%). Predictors of unplanned TGM use were female gender (adjusted odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.02-1.43, p = 0.03), ASA grade ≥ 2 (OR: 1.34, 95% CI: 1.04-1.72, p = 0.02), cervical spine (OR: 1.55, 95% CI: 1.24-1.94, p < 0.001), tumor (OR: 2.02, 95% CI: 1.34-3.03, p < 0.001), posterior approach (OR: 1.66, 95% CI: 1.26-2.18, p < 0.001), durotomy (OR: 1.65, 95% CI: 1.24-2.20, p < 0.001), instrumentation (OR: 1.30, 1.03-1.63, p = 0.02), osteotomy (OR: 5.00, 2.76-9.05, p < 0.001), and microendoscopy (OR: 2.24, 1.84-2.73, p < 0.001). CONCLUSIONS: Many of the predictors for unplanned TGM use have been previously reported as risk factors for intraoperative massive hemorrhaging and blood transfusion. However, other newly revealed factors can be predictors of bleeding that is technically challenging to control. While routine usage of TGM in these cases will require further justification, these novel findings are valuable for implementing preoperative precautions and optimizing resource allocation.

Continuous Monitoring of the Agglomeration and Sedimentation of Indomethacin Nanosuspensions Using T2 Relaxation Time with Time-Domain NMR.

The time-domain NMR technique was utilized to monitor precisely the physicochemical stability of indomethacin (IMC) nanosuspensions using T2 relaxation time (T2). We investigated whether T2 values can distinguish between agglomeration and sedimentation. Nanosuspensions of IMC were prepared using aqueous wet bead milling with polyvinylpyrrolidone as a stabilizer. Prepared nanosuspensions were divided into two fractions: one was stored in the NMR equipment for continuous T2 measurements and the other was stored in the dispersion analyzer. Measurements of both nanosuspensions were carried out, without dilution, over a period of 24 h at 10-min intervals. Transmission profiles based on multilight scattering technology showed that agglomeration predominantly occurred at 25 and 35 °C immediately after wet bead milling up to 4 h, followed by sedimentation from 4 to 24 h. Upon measuring the T2 relaxation, T2 values at both 25 and 35 °C showed a two-step change-there was a significant prolongation in T2 values immediately after preparation of nanosuspensions up to approx. 4 h and a gradual prolongation in T2 values from approx. 4 to 24 h. Considering the results of transmission profiles, these two-step T2 changes correspond to agglomeration and sedimentation. In other words, this study established that monitoring the T2 values of nanosuspensions could be used to evaluate the agglomeration and sedimentation of contained drug particles. This technique does not directly observe the nanoparticles themselves, but the water molecules. Thus, measurement of T2 relaxation is considered to be a general-purpose technique, independent of the type of drug or polymer.

Determination of the Solid Content of Active Pharmaceutical Ingredient Powders in Suspension-Type Pharmaceutical Oral Jelly Using Time-Domain NMR.

This study determined the content of solid active pharmaceutical ingredient (API) powders dispersed in suspension-type pharmaceutical oral jellies using a low-field time-domain NMR (TD-NMR). The suspended jellies containing a designated API content were prepared and tested. Acetaminophen (APAP), indomethacin (IMC) and L-valine were used as test APIs. First, this study measured the T2 relaxation rate (the reciprocal of T2 relaxation time) by the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence, and then evaluated whether the API content could be determined by the acquired T2 relaxation rate. The T2 relaxation rate negatively correlated with API content to a certain extent, but their correlation was not sufficient for achieving a precise determination. Subsequently, the solid-echo pulse sequence measurement was adopted for this study. We found that NMR signals corresponding to solid components strongly correlated with API content. Thus, this method achieved a precise determination of API contents in suspended jellies. In addition, this study confirmed the effect of API particle size on the T2 relaxation rate by using an L-valine-containing jelly: the T2 relaxation rate became faster when a smaller API size was incorporated into the suspended jelly, while there was no difference in terms of the NMR signals measured by solid-echo pulse sequence. From these findings, TD-NMR could be a powerful tool for evaluating the API dispersion state in suspended oral jellies.

Continuous Monitoring of the Hydration Behavior of Hydrophilic Matrix Tablets Using Time-Domain NMR.

Time-domain NMR (TD-NMR) was used for continuous monitoring of the hydration behavior of hydrophilic matrix tablets. The model matrix tablets comprised high molecular weight polyethylene oxide (PEO), hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG). The model tablets were immersed in water. Their T2 relaxation curves were acquired by TD-NMR with solid-echo sequence. A curve-fitting analysis was conducted on the acquired T2 relaxation curves to identify the NMR signals corresponding to the nongelated core remaining in the samples. The amount of nongelated core was estimated from the NMR signal intensity. The estimated values were consistent with the experiment measurement values. Next, the model tablets immersed in water were monitored continuously using TD-NMR. The difference in hydration behaviors of the HPMC and PEO matrix tablets was then characterized fully. The nongelated core of the HPMC matrix tablets disappeared more slowly than that of the PEO matrix tablets. The behavior of HPMC was significantly affected by the PEG content in the tablets. It is suggested that the TD-NMR method has potential to be utilized to evaluate the gel layer properties, upon replacement of the immersion medium: purified (nondeuterated) water is replaced with heavy (deuterated) water. Finally, drug-containing matrix tablets were tested. Diltiazem hydrochloride (a highly water-soluble drug) was employed for this experiment. Reasonable in vitro drug dissolution profiles, which were in accordance with the results from TD-NMR experiments, were observed. We concluded that TD-NMR is a powerful tool to evaluate the hydration properties of hydrophilic matrix tablets.

Does surgical site infection affect patient-reported outcomes after spinal surgery? A multicenter cohort study.

BACKGROUND: Surgical site infections are common in spinal surgeries. It is uncertain whether outcomes in spine surgery patients with vs. without surgical site infection are equivalent. Therefore, we assessed the effects of surgical site infection on postoperative patient-reported outcomes. METHODS: We enrolled patients who underwent elective spine surgery at 12 hospitals between April 2017 and February 2020. We collected data regarding the patients' backgrounds, operative factors, and incidence of surgical site infection. Data for patient-reported outcomes, namely numerical rating scale, Neck Disability Index/Oswestry Disability Index, EuroQol Five-Dimensional questionnaire, and 12-Item Short-Form Health Survey scores, were obtained preoperatively and 1 year postoperatively. We divided the patients into with and without surgical site infection groups. Multivariate logistic regression analyses were performed to identify the risk factors for surgical site infection. Using propensity score matching, we obtained matched surgical site infection-negative and -positive groups. Student's t-test was used for comparisons of continuous variables, and Pearson's chi-square test was used to compare categorical variables between the two matched groups and two unmatched groups. RESULTS: We enrolled 8861 patients in this study; 74 (0.8 %) developed surgical site infections. Cervical spine surgery and American Society of Anesthesiologists physical status classification ≥3 were identified as risk factors; microendoscopy was identified as a protective factor. Using propensity score matching, we compared surgical site infection-positive and -negative groups (74 in each group). No significant difference was found in postoperative pain or dysesthesia of the lower back, buttock, leg, and plantar area between the groups. When comparing preoperative with postoperative pain and dysesthesia, statistically significant improvement was observed for both variables in both groups (p < 0.01 for all variables). No significant differences were observed in postoperative outcomes between the matched surgical site infection-positive and -negative groups. CONCLUSIONS: Patients with surgical site infections had comparable postoperative outcomes to those without surgical site infections.