The Role of Lactobacillus plantarum in Reducing Obesity and Inflammation: A Meta-Analysis.

Recent research has underscored the efficacy of Lactobacillus plantarum (L. plantarum) in managing obesity among healthy adults. This meta-analysis reviewed randomized controlled trials (RCTs) from major databases up to May 2024, focusing on the effects of L. plantarum on body weight, body mass index (BMI), and metabolic parameters. This study has been registered in PROSPERO (number: CRD 42024531611). The analysis of nine studies revealed significant weight reduction and BMI decreases with L. plantarum supplementation compared to a placebo. Notably, using more than two strains together enhanced these effects. Improvements were also observed in abdominal fat and inflammatory markers such as interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP). This meta-analysis synthesizes evidence from nine RCTs to test the hypothesis that L. plantarum supplementation effectively reduces body weight and BMI in healthy adults compared to a placebo. However, variations in study designs, probiotic strains, and intervention durations call for more robust trials to confirm these benefits.

New-Onset Hidradenitis Suppurativa in Psoriasis Patients: A Multi-Center, Retrospective Cohort Study.

BACKGROUND: Previous research has indicated a potential correlation between hidradenitis suppurativa (HS) and psoriasis (PSO), two chronic inflammatory dermatological diseases. However, there is a lack of comprehensive evaluations that consider a variety of clinical and demographic factors, and the risk of developing HS in PSO patients remains unclear. Our study aims to examine HS risk over time among PSO patients versus matched controls while considering the influence of confounders to provide insights into the potential link between these two diseases. METHOD: In this multi-institutional cohort study using the TriNetX database, we matched 202,318 patients with PSO with an equivalent number of individuals without PSO, using propensity score matching. The study period extended from 1 January 2005 to 31 December 2018. We computed hazard ratios and their respective 95% confidence intervals (CIs) to evaluate the probability of HS manifestation over a period of 5 years in patients with PSO in comparison to those without PSO. RESULTS: PSO patients demonstrated a consistently higher risk of developing HS than matched controls across all analytic models with the hazard ratios (HR) ranging from 1.43 (95% CI 1.30-1.56) to 5.91 (95% CI 2.49-14.04). Stratified analyses showed the increased HS risk was observed in both genders but only significant in those aged 18-64 years. Kaplan-Meier analysis indicated PSO patients had a higher cumulative probability of developing HS over time (HR 1.77, 95% CI 1.49-1.89). CONCLUSIONS: PSO was associated with increased HS risk, highlighting the importance of considering HS as a potential comorbidity in PSO patients and may have implications for early detection, prevention, and management strategies for both conditions. Shared inflammatory pathways, genetic components, and skin dysbiosis may contribute. Further research should elucidate underlying mechanisms.

New-onset Fibromyalgia After Total Knee Replacement in Patients With Osteoarthritis: A Propensity-score-matched Cohort Study in the United States.

BACKGROUND/AIM: The risk of new-onset fibromyalgia after total knee replacement (TKR) in osteoarthritis patients is not well-established. This study aimed to assess the risk of developing fibromyalgia post-TKR, considering potential variations across age and sex. PATIENTS AND METHODS: Utilizing a multicenter retrospective cohort design and data from the TriNetX research network, electronic health records of osteoarthritis patients who underwent TKR and the same number of matched controls were analyzed. Propensity-score matching was performed by matching critical confounders. Hazard ratios were evaluated to assess fibromyalgia risk in the TKR cohort compared to non-TKR controls. RESULTS: The hazard ratio of future fibromyalgia for the TKR cohort was 2.08 (95% confidence interval=1.74-2.49) for 1 year after the index date, 1.81 (95% confidence interval=1.62-2.02) for 3 years, and 1.69 (95% confidence interval=1.54-1.86) for 5 years compared with non-TKR controls. The significant association remained in sensitivity models and stratification analyses in different age and sex subgroups. CONCLUSION: Clinicians should be vigilant about the potential for fibromyalgia development post-TKR and consider tailored interventions; our findings emphasize the need for further research to elucidate underlying mechanisms and identify modifiable risk factors.

Long-COVID impacts taste and olfactory in individuals with substance use disorder: A retrospective cohort study from the TriNetX US Collaborative Networks.

Substance use disorder (SUD) exacerbates the impact of Long-COVID, particularly increasing the risk of taste and olfactory disorders. Analyzing retrospective cohort data from TriNetX and over 33 million records (Jan 2020-Dec 2022), this study focused on 1,512,358 participants, revealing that SUD significantly heightens the likelihood of experiencing taste disturbances and anosmia in Long-COVID sufferers. Results indicated that individuals with SUD face a higher incidence of sensory impairments compared to controls, with older adults and women being particularly vulnerable. Smokers with SUD were found to have an increased risk of olfactory and taste dysfunctions. The findings underscore the importance of early screening, diagnosis, and interventions for Long-COVID patients with a history of SUD, suggesting a need for clinicians to monitor for depression and anxiety linked to sensory dysfunction for comprehensive care.

Risk of Keratitis and Keratopathy in Hidradenitis Suppurativa Patients: A Global Federated Health Network Analysis.

BACKGROUND/AIM: Hidradenitis suppurativa (HS) is linked to immune dysregulation and systemic inflammation. While previous studies indicate a higher prevalence of ocular manifestations in HS, the specific risk of keratopathy and keratitis remains unclear. The primary aim of this study was to assess the risk of keratitis and keratopathy in individuals with HS. PATIENTS AND METHODS: In this retrospective cohort study conducted with data from the TriNetX database, 53,716 patients with HS were matched to an equivalent number of non-HS controls using propensity score matching. The study covered the period from January 1st, 2005, to December 31st, 2017. Hazard ratios and their respective 95% confidence intervals (CIs), were computed to evaluate the occurrences of keratitis and keratopathy over a 5-year duration in patients with HS, compared to non-HS controls. RESULTS: HS was associated with a 1.52 times higher risk of keratitis over a 5-year period (95%CI=1.24-1.86) and a 1.47 times higher risk of keratopathy (95%CI=1.18-1.84). These risks remained consistent in sensitivity analyses. The elevated risk of keratitis was observed across both sexes. However, the risk of keratopathy was significantly higher in women with HS (HR=1.61, 95%CI=1.24-2.10) and individuals aged 18-64 years (HR=1.32, 95%CI=1.04-1.68). CONCLUSION: HS was linked to an elevated risk of both keratitis and keratopathy over a 5-year period. Ophthalmologic manifestations are recommended to be considered in HS standard care.

Honey in Alleviating Severe Oral Mucositis Among Head and Neck Cancer Patients Undergoing Radiation Therapy.

BACKGROUND/AIM: Aiming to resolve debates on honey's efficacy for radiotherapy-induced severe oral mucositis in head and neck cancer, we conducted a meta-analysis focused on randomized trials, primarily assessing severe mucositis incidence. Secondary outcomes included weight loss, pain management, and honey types. MATERIALS AND METHODS: A comprehensive literature search was conducted in PubMed, Embase, WOS, and the Cochrane Library up to December 2023. The analysis concentrated on randomized controlled trials that assessed the efficacy of honey, targeting the incidence of mucositis as the main outcome. Additional outcomes explored were weight loss, intolerable pain, and the specific types of honey used in interventions. Data analysis was performed using CMA software, and a funnel plot was employed to identify publication bias. RESULTS: The analysis of 176 records resulted in the inclusion of 10 studies with 599 patients receiving radiotherapy. The research showed that honey significantly reduced the occurrence of grade 3-4 mucositis (severe mucositis), provided significant pain relief, and had a positive effect on reducing weight loss. Regarding the type of honey used, no significant differences were found in their effectiveness in alleviating severe mucositis. CONCLUSION: Honey serves as an effective intervention for individuals with oral mucositis. It can be considered as an adjuvant in the management of clinical radiotherapy-associated oral mucositis, particularly for patients requiring prolonged use of anti-analgesic or antifungal medications.

Hidradenitis suppurativa as a potential risk factor of periodontitis: a multi-center, propensity-score-matched cohort study.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with systemic symptoms. Periodontitis, a prevalent dental disease, shares immune-mediated inflammatory characteristics with HS. This cohort study aims to evaluate the association between HS and periodontitis. Methods: Using the TriNetX research network, a global-federated database of electronic health records, we conducted a retrospective cohort study. People being diagnosed of HS were identified and propensity score matching was performed to identify proper control group, via balancing critical covariates Within the follow-up time of 1 year, 3 year and 5 years, hazard ratios were calculated to assess the risk of periodontitis in HS patients compared to controls. Results: Within the 53,968 HS patients and the same number of matched controls, the HS patients exhibited a significantly increased risk of developing periodontitis compared to controls after 3 years of follow-up (HR: 1.64, 95% CI: 1.11, 2.44) and 5 years of follow-up (HR: 1.64, 95% CI: 1.21, 2.24) of follow-up. Sensitivity analyses supported these findings under various matching models and washout periods. While comparing with patients with psoriasis, the association between HS and periodontitis remained significant (HR: 1.73, 95% CI: 1.23, 2.44). Conclusion: The observed increased risk suggests the need for heightened awareness and potential interdisciplinary care for individuals with HS to address periodontal health.

A Pilot Study of Radiculopathy Following Osteoporotic Vertebral Fracture in Elderly Patients: An Algorithmic Approach to Surgical Management.

Background: Osteoporotic vertebral compression fractures (OVCF) due to severe and refractory back pain or neurological complications require surgical treatment. In this study, patients with radiculopathy due to foraminal stenosis following OVCF were surgically managed by performing transforaminal full-endoscopic lumbar foraminoplasty and/or discectomy (FELFD). Methods: From May 2015 to November 2019, fifteen patients underwent transforaminal FELFD. Patient data, Charlson comorbidity index (CCI), and American Society of Anesthesiologists (ASA) score were collected. Clinical outcomes, including pre- and postoperative Visual Analog Scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI), and MacNab criteria of response to surgical treatment, were evaluated. Results: Mean of age, bone mineral density (T-score), CCI, ASA, and follow-up duration were 69.5 ± 6.6 years, -2.6 ± 0.8, 5.2 ± 2.3, 2.4 ± 0.5, and 24.5 ± 8.8 months, respectively. Mean VAS for leg pain significantly decreased from 6.9 ± 0.8 preoperatively to 2.9 ± 1.1 (P < .05). Mean ODI decreased from 39.9 ± 3.2 preoperatively to 19.3 ± 4.6 postoperatively (P < .05). The satisfaction rate is 86.7% (based on Macnab criteria), showed six patients had excellent outcomes and seven had good outcomes. Conclusions: Transforaminal FELFD is an effective treatment option for patients with radiculopathy due to lumbar OVCF, including those with severe osteoporosis and elderly patients.

Effect of ethanol extracts of Hericium erinaceus mycelium on morphine­induced microglial migration.

Microglia serve important roles in chronic pain signal transduction pathways. Glia cells, especially microglia, seem to share mechanisms that lead to chronic pain and morphine­induced tolerance. Evidence has suggested that downregulating cytoskeleton activity in microglia provides pain relief in chronic pain and morphine tolerance. The purpose of the present study was to evaluate the effect of ethanol extracts of Hericium erinaceus (EHE) mycelium on morphine­induced BV2 microglial cell activation. BV2 cells were starved for 4 h in DMEM before being incubated with 100 ng/ml EHE for 30 min, followed by 1 µM morphine for 2 h. Subsequently, the cells were harvested and used for migration experiments and western blotting. The results showed that 1 µM morphine enhanced BV2 cell activation and chemotactic reaction, and it increased histone deacetylase 6 (HDAC6) expression and heat shock protein 90 (HSP90) deacetylation as well as HSP90 cleavage. Pretreatment with 100 ng/ml EHE significantly inhibited the morphine­stimulated effects on BV2 cells. The present study demonstrated that EHE inhibited morphine­induced BV2 activations by regulating the HDAC6/HSP90 deacetylation signal transduction pathway.

Melatonin regulation of transcription in the reversal of morphine tolerance: Microarray analysis of differential gene expression.

Tolerance and associated hyperalgesia induced by long­term morphine administration substantially restrict the clinical use of morphine in pain treatment. Melatonin, a neurohormone released by the pineal gland, has been demonstrated to attenuate anti­nociceptive morphine tolerance. The present study investigates differentially expressed genes in the process of morphine tolerance and altered gene expression subsequent to melatonin treatment in chronic morphine­infused ratspinal cords. Morphine tolerance was induced in male Wistar rats by intrathecal morphine infusion (the MO group). Melatonin (the MOMa group) was administered to overcome the effects derived by morphine. The mRNA collected from L5­S3 of the spinal cord was extracted and analysed by rat expression microarray. Principal component analysis and clustering analysis revealed that the overall gene profiles were different in morphine and melatonin treatments. Subsequent to Gene Ontology analysis, the biological processes of differentially expressed genes of MO and MOMa compared with the control group were constructed. Furthermore, a panel of genes exclusively expressed following melatonin treatment and another panel of genes with inverse expression between the MO and MOMa group were also established. Subsequent to PANTHER pathway analysis, a group of genes with inverse expression following melatonin administrated compared with morphine alone were identified. The expression levels of genes of interest were also confirmed using a reverse transcription­quantitative polymerase chain reaction. The gene panel that was constructed suggests a potential signaling pathway in morphine tolerance development and is valuable for investigating the mechanism of morphine tolerance and the regulatory gene profiles of melatonin treatment. These results may contribute to the discovery of potential drug targets in morphine tolerance treatments in the future.

Ganoderma microsporum immunomodulatory protein induces apoptosis and potentiates mitomycin C-induced apoptosis in urinary bladder urothelial carcinoma cells.

Current chemotherapy and immunotherapy treatments followed by transurethral resection for urinary bladder urothelial carcinoma (UC) usually suffer from poor prognosis and high recurrence rate. Design and modification of current formulation with the novel adjuvants are needed. A recombinant protein derived from Ganoderma microsporum named as Ganoderma microsporum immunomodulatory protein (GMIP) was used to treat UC cells. We found GMIP elicits a dose-dependent and time-dependent anti-UC cell proliferation effect, with a half-maximal inhibition concentration (IC50 ) comparable to mitomycin C (MMC), a commonly used chemotherapy agent. After GMIP treatment, UC cells showed apoptotic phenomenon including cell cycle arrest in the G1 phase, elevated sub-G1 population, mitochondrial membrane potential loss, up-regulated p21 expression, p21 nuclear translocation, caspase activation, and PARP cleavage in a p53-independent but p21-mediated pathways. Unlike lung cancer cells, GMIP treated UC cells showed no autophagic scheme including Beclin-1, an autophagy to apoptosis switch marker, was not cleaved by caspase 3 and slight LC3B-II accumulation. Also, the classic autophagic inhibitor, chloroquine had no effect in GMIP-mediated cell death made us conclude that GMIP induced apoptosis through caspase activation but not autophagy in UC cells. Additionally, GMIP showed synergistic effects with MMC in killing UC cells and thus decreased the concentration of MMC usage to reach the comparable apoptotic effects. Our results delineate novel strategies for treatment of UC by GMIP alone or in combination with MMC application and provide a promising therapeutic cocktail for better treatment of urinary bladder urothelial carcinoma.

Association of anterior cruciate ligament injury with knee osteoarthritis and total knee replacement: A retrospective cohort study from the Taiwan National Health Insurance Database.

OBJECTIVE: This study aimed to support the potential protective role of anterior cruciate ligament (ACL) reconstruction against the development of osteoarthritis (OA). METHODS: In this retrospective cohort study, the long-term results of ACL reconstruction in Taiwan were evaluated based on data from the National Health Insurance Research Database (NHIRD). In total, 8,769 eligible cases were included from 11,921 ACL-injured patients. The cumulative incidence rates of OA and total knee replacement (TKR) were analyzed using the Kaplan-Meier estimator. Cox proportional hazards models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of OA. RESULTS: There was a lower cumulative incidence of OA among ACL-reconstructed patients (271, 33.1%) than among non-reconstructed patients (1,874, 40.3%; p < 0.001). Patients who underwent ACL reconstruction had a lower cumulative incidence of TKR during the follow-up period (0.6%) than the non-reconstructed patients (4.6%, p < 0.001). After adjusting for covariates, ACL-injured patients who underwent reconstruction within one month after ACL injury showed a significantly lower risk of OA than those who never underwent reconstruction (adjusted HR = 0.83, 95% CI = 0.69-0.99). CONCLUSIONS: These results indicate that ACL reconstruction might not provide complete protection from OA development after traumatic knee injury but does yield a lower cumulative incidence of OA development and TKR. Moreover, based on the present study, ACL-injured patients should undergo reconstruction as early as possible (within one month) to lower the risk of OA.

Melatonin reverses morphine tolerance by inhibiting microglia activation and HSP27 expression.

AIMS: Melatonin has been reported to attenuate opioid tolerance. In this study, we explored the possible mechanism of melatonin in diminishing morphine tolerance. MAIN METHODS: Two intrathecal (i.t.) catheters were implanted in male Wistar rats for drug delivery. One was linked to a mini-osmotic pump for morphine or saline infusion. On the seventh day, 50µg of melatonin or vehicle was injected through the other catheter instantly after discontinuation of morphine or saline infusion; 3h later, 15µg of morphine or saline was injected. The antinociceptive response was then measured using the tail-flick test every 30min for 120min. KEY FINDINGS: The results showed that chronic morphine infusion elicited antinociceptive tolerance and upregulated heat shock protein 27 (HSP27) expression in the dorsal horn of the rat spinal cord. Melatonin pretreatment partially restored morphine's antinociceptive effect in morphine-tolerant rats and reversed morphine-induced HSP27 upregulation. In addition, chronic morphine infusion induced microglial cell activation and was reversed by melatonin treatment. SIGNIFICANCE: The present study provides evidence that melatonin, acting via inhibiting morphine-induced neuroinflammation, can be useful as a therapeutic adjuvant for patients under long-term opioid treatment for pain relief.