Establishing Monoclonal Gammopathy of Undetermined Significance as an Independent Pre-Disease State of Multiple Myeloma Using Raman Spectroscopy, Dynamical Network Biomarker Theory, and Energy Landscape Analysis.

Multiple myeloma (MM) is a cancer of plasma cells. Normal (NL) cells are considered to pass through a precancerous state, such as monoclonal gammopathy of undetermined significance (MGUS), before transitioning to MM. In the present study, we acquired Raman spectra at three stages-834 NL, 711 MGUS, and 970 MM spectra-and applied the dynamical network biomarker (DNB) theory to these spectra. The DNB analysis identified MGUS as the unstable pre-disease state of MM and extracted Raman shifts at 1149 and 1527-1530 cm-1 as DNB variables. The distribution of DNB scores for each patient showed a significant difference between the mean values for MGUS and MM patients. Furthermore, an energy landscape (EL) analysis showed that the NL and MM stages were likely to become stable states. Raman spectroscopy, the DNB theory, and, complementarily, the EL analysis will be applicable to the identification of the pre-disease state in clinical samples.

Effects of Hyperbaric Oxygen Therapy for Clostridioides difficile-associated Colitis: A Retrospective Study.

Objectives: Clostridioides difficile (CD) is an anaerobic spore-forming Gram-positive rod that is a major cause of antibiotic-associated diarrhea. Hyperbaric oxygen therapy (HBO) is a well-established treatment for Clostridium perfringens, but there are no reports that have examined the efficacy of HBO against CD, which is also an anaerobic bacterium. Methods: In this study, we retrospectively examined whether HBO therapy affects the prognosis following CD infections (CDI). This study included 92 inpatients diagnosed with CDI at our hospital between January 2013 and December 2022. Of these, 16 patients received HBO therapy. The indications for HBO therapy were stroke in five patients, ileus in four patients, cancer in two patients, acute peripheral circulatory disturbance in two patients, and others in three patients. The mean observation period was 5.4 years. Results: In the univariate analysis, there was no significant difference in severity, mortality, hospitalization, or overall survival between patients who did and did not receive HBO therapy. However, the HBO group had a significantly lower recurrence rate (0% vs. 22.4%, p=0.0363) and a shorter symptomatic period (6.2 vs. 13.6 days, p=0.0217). Conclusions: HBO may have beneficial effect on CDI by shortening the symptomatic period and preventing recurrence.

Perturbation theory for evolution of cooperation on networks.

Network structure is a mechanism for promoting cooperation in social dilemma games. In the present study, we explore graph surgery, i.e., to slightly perturb the given network, towards a network that better fosters cooperation. To this end, we develop a perturbation theory to assess the change in the propensity of cooperation when we add or remove a single edge to/from the given network. Our perturbation theory is for a previously proposed random-walk-based theory that provides the threshold benefit-to-cost ratio, [Formula: see text], which is the value of the benefit-to-cost ratio in the donation game above which the cooperator is more likely to fixate than in a control case, for any finite networks. We find that [Formula: see text] decreases when we remove a single edge in a majority of cases and that our perturbation theory captures at a reasonable accuracy which edge removal makes [Formula: see text] small to facilitate cooperation. In contrast, [Formula: see text] tends to increase when we add an edge, and the perturbation theory is not good at predicting the edge addition that changes [Formula: see text] by a large amount. Our perturbation theory significantly reduces the computational complexity for calculating the outcome of graph surgery.

Formation of Calcified Nodule as a Cause of Early In-Stent Restenosis in Patients Undergoing Dialysis.

Background Dialysis is an independent risk factor for in-stent restenosis (ISR) after stent implantation in coronary arteries. However, the characteristics of ISR in patients undergoing dialysis remain unclear, as there are no histological studies evaluating the causes of this condition. The aim of the present study was to investigate the causes of ISR between patients who are undergoing dialysis and those who are not by evaluating tissues obtained from ISR lesions using directional coronary atherectomy. Methods and Results A total of 29 ISR lesions from 29 patients included in a multicenter directional coronary atherectomy registry of 128 patients were selected for analysis and divided into a dialysis group (n=8) and a nondialysis group (n=21). Histopathological evaluation demonstrated that an in-stent calcified nodule was a major histological characteristic of ISR lesions in the dialysis group and the prevalence of an in-stent calcified nodule was significantly higher in the dialysis group compared with the nondialysis group (75% versus 5%, respectively; P<0.01). On the other hand, the prevalence of an in-stent lipid-rich plaque was significantly lower in the dialysis group compared with the nondialysis group (0% versus 43%, respectively; P=0.03). In all cases with an in-stent calcified nodule, the underlying calcification before stent implantation was moderate to severe. When tissue characteristics were stratified according to duration post-stent implantation, an in-stent calcified nodule in the dialysis group was mainly observed within 1 year after stent implantation. Conclusions In-stent calcified nodules are a common cause of ISR in patients undergoing dialysis and are observed within 1 year after stent implantation, suggesting different causes of ISR between patients undergoing dialysis and those who are not.

Anti-TIF1-γ antibody and cancer-associated myositis: A clinicohistopathologic study.

OBJECTIVE: We aimed to analyze the clinical and histopathologic features of cancer-associated myositis (CAM) in relation to anti-transcriptional intermediary factor 1 γ antibody (anti-TIF1-γ-Ab), a marker of cancer association. METHODS: We retrospectively studied 349 patients with idiopathic inflammatory myopathies (IIMs), including 284 patients with pretreatment biopsy samples available. For the classification of IIMs, the European Neuromuscular Center criteria were applied. Patients with CAM with (anti-TIF1-γ-Ab[+] CAM) and without anti-TIF1-γ-Ab (anti-TIF1-γ-Ab[-] CAM) were compared with patients with IIM without cancers within and beyond 3 years of myositis diagnosis. RESULTS: Cancer was detected in 75 patients, of whom 36 (48%) were positive for anti-TIF1-γ-Ab. In anti-TIF1-γ-Ab(+) patients with CAM, cancers were detected within 1 year of myositis diagnosis in 35 (97%) and before 1 year of myositis diagnosis in 1. All the anti-TIF1-γ-Ab(+) patients with CAM satisfied the dermatomyositis (DM) criteria, including 2 possible DM sine dermatitis cases, and were characterized histologically by the presence of perifascicular atrophy, vacuolated fibers (VFs), and dense C5b-9 deposits on capillaries (dC5b-9). In contrast, 39 anti-TIF1-γ-Ab(-) patients with CAM were classified into various subgroups, and characterized by a higher frequency of necrotizing autoimmune myopathy (NAM). Notably, all 7 patients with CAM classified into the NAM subgroup were anti-TIF1-γ-Ab(-) and exhibited no dC5b-9 or VFs. CONCLUSIONS: CAM includes clinicohistopathologically heterogeneous disease entities. Among CAM entities, anti-TIF1-γ-Ab(+) CAM has characteristically shown a close temporal association with cancer detection and the histopathologic findings of dC5b-9 and VFs, and CAM with NAM is a subset of anti-TIF1-γ-Ab(-) CAM.

Intravascular ultrasound-guided percutaneous coronary interventions with minimum contrast volume for prevention of the radiocontrast-induced nephropathy: report of two cases.

Radiocontrast-induced nephropathy (CIN) is one of the most serious complications of percutaneous coronary interventions (PCI). The prevention of PCI-related CIN for chronic kidney disease (CKD) patients has not been established yet. The intravascular ultrasound (IVUS) is commonly used as an imaging device during PCI. We performed IVUS-guided PCI while only using fluoroscopic imaging and without administering any routine contrast dye injection during the procedures. All patients underwent a baseline coronary angiography prior to the elective PCI. During the PCI, all the following procedures were done with X-ray fluoroscopic imaging without or with a minimized contrast dye injection: the engagement of the guiding catheter, insertion of the coronary guidewire, insertion of the IVUS catheter, the stent deployment and the post-dilatation. The diameter and the length of the balloon and the stent were determined according to the pre-procedural IVUS findings, and the end point of the stent dilatation was also judged according to the acquired minimal cross-sectional area of the stent. Here we report our findings from two cases representative of IVUS-guided minimum contrast PCI in which the volumes of contrast dye during the procedure were 5 and 4 ml, respectively. No CIN occurred after either procedure. The IVUS-guided minimum contrast PCI could be a promising option for the prevention of CIN after PCI.

Impact of vascular remodeling on the coronary plaque compositions: an investigation with in vivo tissue characterization using integrated backscatter-intravascular ultrasound.

Recent studies have indicated that positive remodeling is strongly associated with development of acute coronary syndrome (ACS). The aim of this study was to compare plaque composition of vascular remodeling patterns by an established in vivo tissue characterization method using integrated backscatter (IB)-intravascular ultrasound (IVUS). The study population consisted of 41 consecutive patients who received IVUS prior to percutaneous coronary intervention. Remodeling index (RI) was calculated as the external elastic membrane (EEM) area at the minimal lumen area (MLA) site divided by average EEM area at the proximal and distal reference sites. The patients were divided into two groups based on RI: positive remodeling (PR) defined as RI>1 and non-PR as RI

Tiagabine is neuroprotective in the N171-82Q and R6/2 mouse models of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by chorea, incoordination, and shortened life-span, and by huntingtin inclusions and neurodegeneration. We previously screened the 1040 FDA-approved compounds from the NINDS compound library and found that a compound, nipecotic acid, significantly reduced mutant huntingtin aggregations and blocked cell toxicity in an inducible cell model of HD. Because nipecotic acid does not cross the blood-brain barrier (BBB), we studied its analogue, tiagabine, which is able to cross the BBB, in both N171-82Q and R6/2 transgenic mouse models of HD. Tiagabine was administered intraperitoneally at 2 and 5 mg/kg daily in HD mice. We found that tiagabine extended survival, improved motor performance, and attenuated brain atrophy and neurodegeneration in N171-82Q HD mice. These beneficial effects were further confirmed in R6/2 HD mice. The levels of tiagabine at effective doses in mouse serum are comparable to the levels in human patients treated with tiagabine. These results suggest that tiagabine may have beneficial effects in the treatment of HD. Because tiagabine is an FDA-approved drug, it may be a promising candidate for future clinical trials for the treatment of HD.

Predictive factors of TIMI-3 flow before percutaneous coronary intervention in facilitated percutaneous coronary intervention for acute myocardial infarction.

The outcome for facilitated percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is known to be more favorable in cases in which TIMI-3 flow is obtained before PCI. We investigated factors that affect the acquisition of TIMI-3 flow before PCI. Facilitated PCI was performed on 178 patients divided into two groups, a group in which TIMI-3 flow was acquired before conducting PCI and another in which it was not, and their background factors and short-term outcomes were investigated. The hemoglobin concentrations, white blood cell (WBC) counts, and HbA1c values were significantly lower in the group in which TIMI-3 flow was acquired before PCI and significantly more had a history of past smoking. According to the results of logistic analysis, WBC count (odds ratio [OR], 0.865, P = 0.0077), hemoglobin concentration (OR, 0.77, P = 0.0257), and smoking history (OR, 0.266, P = 0.0021) were independent factors that predicted acquisition of TIMI-3 flow. The WBC count and hemoglobin value on arrival at the emergency room and history of smoking were shown to be independent factors for acquisition of TIMI-3 flow before PCI in facilitated PCI.

[Spinal anesthesia with bupivacaine for a patient with a history of severe leg pain after intrathecal dibucaine].

An 87-year-old man was scheduled for the 11th transurethral bladder tumor resection (TURBT). He had a history of non-active syphilis for 21 years, diabetes mellitus for 7 years, and severe emphysema. Preoperative physical examination of the lower extremities, revealed loss of knee-jerk reflex, and loss of vibratory and proprioceptive perception. Four years previously, he underwent TURBT twice under spinal anesthesia with dibucaine, which caused severe leg pain during anesthesia. Therefore, subsequent TURBTs (eight times) were performed under general anesthesia with tracheal intubation, which frequently caused postoperative respiratory distress. Recently, bupivacaine, less neurotoxic than dibucaine, was on the market in Japan for use in spinal anesthesia. Therefore we planned spinal anesthesia using 0.5% bupivacaine, 2.0 ml. This time, he did not complain of leg pain during anesthesia, and postoperative conditions were satisfactory. We can conclude that bupivacaine is very useful for spinal anesthesia especially in patients with a history of leg pain by spinal anesthesia with dibucaine.