Takahiro Ushida

Objectives: The objectives were to investigate the clinical characteristics and course of long COVID, defined as the persistence of symptoms at least one month after the onset of COVID-19, in outpatients and to clarify differences in symptoms between SARS CoV-2 mutant strains. Methods: Our observational study in a primary care institution in Japan included 1053 patients with long COVID who visited our outpatient clinic between April 2021 and March 2023. Symptom distribution, performance status, and patient background at the time of the first outpatient visit were compared between infectious strains (Delta and before group and Omicron group). Background factors and symptoms related to time to remission were also analyzed. Results: The severity of COVID-19 in the acute phase was mild, moderate, and severe in 82.2%, 14.9%, and 2.9% in the Delta and before group; and in 97.6%, 1.7%, and 0.4% in the Omicron group, respectively. Vaccination coverage was significantly different between the Delta and before (37.1%) and Omicron groups (73.1%) (p < 0.001), probably due to the period of vaccine unavailability in the former group. Symptoms of fatigue and headache occurred most frequently, irrespective of infectious strain. The mean number of symptoms per patient was significantly higher in the Delta and before group than the Omicron group (3.4 vs. 2.7, p < 0.0001). The median time overall to remission of long COVID was 169 days. Cox hazard model analysis identified female sex, high body mass index, and dyspnea (but not infectious strain) as significant factors prolonging the time to remission (p < 0.05). Conclusions: Differences in the number of symptoms between infectious strains may be related to differences in viral virulence and/or vaccination coverage. However, the clinical course was found to be minimally influenced by the infectious strain. The present results should improve the understanding of prognosis in patients with long COVID from both the clinical and social perspectives.

Background: Numbness is a term commonly used in clinical practice to describe an abnormal sensory experience that is produced by a stimulus or is present even without a stimulus. However, there is still much that remains obscure in this field, and also, few reports have focused on its symptoms. In addition, while pain itself is known to have a significant impact on quality of life (QOL), the relationship between numbness and QOL is often unclear. Therefore, we conducted an epidemiological survey and analyzed the relationship between painless numbness and QOL, using type, location, and age as influencing factors, respectively. Methods: A nationwide epidemiological survey was conducted by mail using a survey panel designed by the Nippon Research Center. Questionnaires were sent to 10,000 randomly selected people aged 18 and over from all over Japan. Out of the 5682 people who responded, the relationship between numbness and QOL was analyzed using the EuroQol 5 Dimension-3L (EQ5D-3L) for patients who are currently experiencing painless numbness. Findings: The results suggest that painless numbness affects QOL and that QOL decreases as its intensity increases. Furthermore, the two factors of numbness of feet and numbness among the young may be less likely to affect QOL. This study may be of great significance in the field of numbness research.

: The gut microbiota (GM) plays an important role in gut-brain communication, and the ‘gut-brain axis’ has attracted much attention as a factor influencing human host health. We previously reported that pain perception may be associated with GM composition in males. The aim of this study was to investigate the relationship between GM composition and pain perception among 42 healthy female university students in Japan. Pain perception was evaluated by pressure pain threshold (PPT), current perception threshold (CPT), temporal summation of pain (TSP), conditioned pain modulation (CPM), and a questionnaire on psychological state. CPT was stimulated at 5, 250, and 2,000 Hz, which reflected the thresholds of the C, Aδ, and Aβ fibers, respectively. Also, GM composition was estimated using 16S rRNA analysis. The lower alpha diversity was associated with, the lower PPT (rs = 0.330, P < 0.05) and CPT of 2000 Hz (re = 0.339, P < 0.05). Furthermore, alpha diversity was identified as an explanatory variable for PPT (β = 0.424, P < 0.01) and TSP (β = -0.317, P < 0.05), alpha diversity and state anxiety for CPT of 2000 Hz (β = 0.321, P < 0.05), and state anxiety for CPT of 250 Hz (β = 0.320, P < 0.05). However, there was no relationship between the rate of major phylum and pain perception.

KIAA1199 has a strong hyaluronidase activity in inflammatory arthritis. This study aimed to identify a drug that could reduce KIAA1199 activity and clarify its effects on inflammatory arthritis. Rat chondrosarcoma (RCS) cells were strongly stained with Alcian blue (AB). Its stainability was reduced in RCS cells, which were over-expressed with the KIAA1199 gene (RCS-KIAA). We screened the drugs that restore the AB stainability in RCS-KIAA. The effects of the drug were evaluated by particle exclusion assay, HA ELISA, RT-PCR, and Western blotting. We further evaluated the HA accumulation and the MMP1 and three expressions in fibroblast-like synoviocytes (FLS). In vivo, the effects of the drug on symptoms and serum concentration of HA in a collagen-induced arthritis mouse were evaluated. Ipriflavone was identified to restore AB stainability at 23%. Extracellular matrix formation was significantly increased in a dose-dependent manner (p = 0.006). Ipriflavone increased the HA accumulation and suppressed the MMP1 and MMP3 expression on TNF-α stimulated FLS. In vivo, Ipriflavone significantly improved the symptoms and reduced the serum concentrations of HA. Conclusions: We identified Ipriflavone, which has inhibitory effects on KIAA1199 activity. Ipriflavone may be a therapeutic candidate based on its reduction of KIAA1199 activity in inflammatory arthritis.

Background: We aimed to determine a cut-off value for physical activity (PA), measured using an accelerometer, between patients with knee osteoarthritis (OA) who decided to undergo total knee arthroplasty (TKA) and those who continued conservative treatment. Methods: Forty-two participants were assigned to either a TKA group or a non-TKA group (21 per group). They were instructed to wear an accelerometer throughout the day. Average daily steps (steps/day), average daily time of light PA (LPA) (min/day), and average daily time of moderate-to-vigorous PA (MVPA) (min/day) were measured for seven days. Variables between the two groups were compared using univariate analyses, and then a stepwise logistic regression was conducted to determine which variables best correlated with undergoing TKA. The PA cut-offs were analysed using the receiver operating characteristic curve. Results: Pain severity (p = 0.002), KL grade (p = 0.001), and MVPA (p = 0.012) differed significantly between the groups. The most useful cut-off value was 5.84 (min/day) for MVPA (AUC = 0.773), although only pain severity and KL grade were found to be significant contributors to undergoing TKA. Conclusions: Our results revealed there was a significant decrease in PA levels (MVPA cut-off, 5–6 min/day) in the TKA group compared with the non-TKA group.

Purpose: The purpose of the present study was to investigate the visual attentional behavior towards a pain-affected area and face/body images using eye tracking in complex regional pain syndrome (CRPS) patients. Moreover, we investigated the relationship between visual attentional behavior and clinical symptoms. Patients and methods: Eight female patients with CRPS type 1 in their upper limbs and 8 healthy adult women participated in this study. First, the participants were asked to watch videoclips in a relaxed manner (Videoclip 1 featured young adults who introduced themselves; Videoclip 2 featured young adults touching the hand of the other person sitting across from them with their hand.) Eye movement data were tracked with eye-tracking glasses. Results: In video clip 1, the fixation duration (FD) and fixation count (FC) on faces tended to be lower in CRPS patients than in healthy controls. This tendency was found in patients with low body cognitive distortions. In video clip 2, CRPS patients displayed significantly lower FD and FC on the unaffected hand while watching a video of the unaffected hand being touched compared with healthy controls. Moreover, patients with low body cognitive distortion displayed significantly longer FD on the affected hand. Conclusion: Some CRPS patients differed in visual attentional behavior toward the face and body compared with healthy controls. In addition, our findings suggest that patients with lower body cognitive distortion may have a high visual attention for the affected hand, while patients with higher distortion may be neglecting the affected hand.