Pre-operative dual-time-point [18F]FET PET differentiates CDKN2A/B loss and PIK3CA mutation status in adult-type diffuse glioma: a single-center prospective study.

PURPOSE: While [18F]FET PET plays a complementary role in glioma imaging, it needs to be more comprehensively understood for improved characterization of glioma prior to surgery given the evolving landscape of molecular neuropathology. Thus, we investigated the utility of pre-operative dual-time-point [18F]FET PET in correlation with next-generation sequencing (NGS) data in patients with adult-type diffuse glioma (ADG). METHODS: Adult patients who were suspected to have primary glioma were prospectively recruited between June 2021 and January 2024. They underwent pre-operative dual-time-point static PET/CT at 20 min (early) and 80 min (delay) after [18F]FET injection. Semi-quantitative parameters of the hottest lesion (SUVmax) of tumour and the hottest lesion-to-normal brain ratio (TBRmax) were assessed from each summed image. Furthermore, the percentage changes (△) of SUVmax and TBRmax between two images were calculated. Histopathology of glioma was determined according to the 2021 WHO classification and NGS data. RESULTS: This study investigated a dozen genes in 76 patients, of whom 51 had isocitrate dehydrogenase (IDH)-wild-type glioblastoma, 13 had IDH-mutant astrocytoma, and 12 had IDH-mutant oligodendroglioma. Every tumour was [18F]FET-avid having TBRmax more than 1.6. Patients with CDKN2A/B loss had significantly higher values of SUVmax (5.7 ± 1.6 vs. 4.7 ± 1.3, p = 0.004; 5.0 ± 1.4 vs. 4.4 ± 1.2, p = 0.026) and TBRmax (6.5 ± 1.8 vs. 5.1 ± 1.7, p = 0.001; 5.3 ± 1.5 vs. 4.3 ± 1.3, p = 0.004) in both scans than patients without CDKN2A/B loss, even after adjustment for age, MRI enhancement, tumor grade and type of pathology. Furthermore, patients with PIK3CA mutation (16.2 ± 11.8 vs. 6.7 ± 11.6, p = 0.007) had significantly higher △SUVmax than patients without PIK3CA mutation, even after adjustment for age, MRI enhancement, tumor grade, and type of pathology. CONCLUSION: Among the dozen genes investigated in this prospective study in patients with ADG, we found out that CDKN2A/B loss and PIK3CA mutation status could be differentiated by pre-operative dual-time-point [18F]FET PET/CT.

Enhancing Prognostication and Treatment Response Evaluation in Primary CNS Lymphoma with 18F-FDG PET/CT.

BACKGROUND: The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the prognostication and response evaluation of primary central nervous system lymphoma (PCNSL) remains inadequately defined. METHODS: We conducted a retrospective analysis of 268 consecutive newly diagnosed patients with PCNSL between 2006 and 2020. Of these patients, 105 and 110 patients were included to evaluate the prognostic value of baseline and post-treatment 18F-FDG-PET/CT scans, respectively. Tumor uptake was considered positive when it exceeded that of the contralateral brain upon visual assessment. Quantitative analysis of baseline 18F-FDG-PET/CT included measurement of the maximal standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG). RESULTS: The median age of the 268 patients was 62 years (range: 17-85), with 55% being male. The median progression-free survival (PFS) was 24.5 months (95% confidence interval [CI], 19.9-29.1), and the median overall survival (OS) was 34.5 months (95% CI, 22.9-46.1). The average SUVmax was 15.3 ± 5.7 and the mean TMTV and TLG were 12.6 ± 13.9 cm3 and 135.0 ± 152.7 g, respectively. Patients with a baseline TMTV ≥17.0 cm3 had significantly shorter OS (12.5 vs. 74.0 months, p=0.011). Post-treatment metabolic response by 18F-FDG-PET/CT significantly predicted PFS (median: 10.5 vs. 46.0 months, p=0.001) and OS (median: 21.0 vs. 62.0 months, p=0.002), whereas anatomic response by contrast-enhanced MRI showed no statistically significant differences in PFS (p=0.130) or OS (p=0.540). CONCLUSION: Baseline TMTV and post-treatment metabolic response, as assessed by 18F-FDG-PET/CT, are significant prognostic factors in patients with PCNSL.

Efficiency and Safety of Targeted Alpha Therapy in Metastatic Neuroendocrine Tumors: A Meta-analysis.

PURPOSE: Despite the effectiveness of 177Lu-based peptide receptor radionuclide therapy in treating metastatic neuroendocrine tumors (NETs), disease progression posttreatment remains a significant challenge. Targeted alpha therapy (TAT) has emerged as a promising option for patients experiencing such progression. This study aims to assess the therapeutic efficiency and toxicity of TAT in patients with metastatic NET through a meta-analysis. PATIENTS AND METHODS: We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and CINAHL using relevant keywords. The analysis focused on the pooled proportions of objective response rate (ORR) and disease control rate (DCR) to determine therapeutic efficiency. We also evaluated the incidence of serious hematologic and renal adverse events (grade 3 or 4) to assess toxicity. A subgroup analysis was performed to identify factors influencing therapeutic outcomes. RESULTS: Our meta-analysis included 7 studies comprising 162 patients. The results showed that TAT achieved ORR of 49.5% (95% confidence interval [CI]: 41.7%-57.4%) and DCR of 87.0% (95% CI: 72.1%-96.8%). The incidences of hematologic and renal toxicities were low, at 2.1% (95% CI: 0.5%-5.5%) and 3.4% (95% CI: 1.2%-7.3%), respectively. Subgroup analysis indicated consistent therapeutic efficiency across different variables, including prior 177Lu-based peptide receptor radionuclide therapy treatment, 225Ac-based TAT, absence of radiosensitizer, and methods of response evaluation, with ORR ranging from 46.6% to 57.1% and DCR from 82.0% to 91.5%. CONCLUSIONS: TAT is an effective treatment for metastatic NET, demonstrating substantial disease control and response rates with minimal toxicity. These findings suggest that TAT is a viable therapeutic alternative for patients with metastatic NET.

Heat-Processed Soybean Germ Extract and Lactobacillus gasseri NK109 Supplementation Reduce LPS-Induced Cognitive Impairment and Colitis in Mice.

Soybean alleviates cognitive impairment. In our preparatory experiment, we found that dry-heat (90 °C for 30 min)-processed soybean embryo ethanol extract (hSE) most potently suppressed lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α expression in BV2 cells among dry-heat-, steaming-, and oil exclusion-processed soybean embryo ethanol extracts (SEs). Heat processing increased the absorbable soyasaponin Bb content of SE. Therefore, we investigated whether hSE and its supplement could mitigate LPS-impaired cognitive function in mice. Among dry-heat-, steaming-, and oil exclusion-processed SEs, hSE mitigated LPS-impaired cognitive function more than parental SE. hSE potently upregulated LPS-suppressed brain-derived neurotropic factor (BDNF) expression in the hippocampus, while LPS-induced TNF-α and IL-1ß expression in the hippocampus and colon were downregulated. Lactobacillus gasseri NK109 additively increased the cognitive function-enhancing activity of hSE in mice with LPS-induced cognitive impairment as follows: the hSE and NK109 mix potently increased cognitive function and hippocampal BDNF expression and BDNF-positive neuron cell numbers and decreased TNF-α expression and NF-κB-positive cell numbers in the hippocampus and colon. These findings suggest that hSE and its supplement may decrease colitis and neuroinflammation by suppressing NF-κB activation and inducing BDNF expression, resulting in the attenuation of cognitive impairment.

Diagnostic ability of [18F]FDG PET/CT for distinguishing benign from malignant spleen lesions.

OBJECTIVES: [18F]Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a non-invasive imaging modality used in the differential diagnosis of splenic lesions, although ideal parameters and thresholds remain unclear. The present study evaluated the ability of [18F]FDG PET/CT, including its visual and quantitative parameters, to differentiate between benign and malignant splenic lesions. METHODS: Patients who underwent [18F]FDG PET/CT following the detection of splenic lesions on contrast-enhanced CT were retrospectively analysed. Visual parameters assessed on [18F]FDG PET/CT included whole spleen uptake intensity, lesion multiplicity, and lesion uptake, and quantitative parameters included maximum standardised uptake value (SUVmax), lesion-to-background ratio (LBR), metabolic tumour volume (MTV), total lesion glycolysis (TLG), and lesion size. Parameters differentiating between benign and malignant lesions were evaluated by Pearson's chi-square test, Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis. RESULTS: Splenic lesion uptake (p = 0.001) was the only visual parameter significantly distinguishing between benign and malignant lesions. ROC curve analysis demonstrated that SUVmax had the largest area under the ROC, 0.91 (p < 0.001), with an optimal cut-off > 5.3 having a sensitivity of 90.3% and a specificity of 80.6%. Subgroup analysis of malignant lesions showed that SUVmax (p = 0.013), LBR (p = 0.012), and TLG (p = 0.034) were significantly higher in splenic lymphomas than in splenic metastases. CONCLUSION: Of the [18F]FDG PET/CT parameters investigated, SUVmax had the highest accuracy in diagnosing malignant splenic lesions and was significantly higher in splenic lymphomas than in splenic metastases. Visual determination of [18F]FDG uptake by splenic lesions may be an easily evaluated parameter. CLINICAL RELEVANCE STATEMENT: SUVmax and visual grade of [18F]FDG PET/CT help to differentiate spleen lesions. [18F]FDG PET/CT is useful for discriminating between benign and malignant spleen lesions. KEY POINTS: Many splenic lesions are difficult to diagnose on anatomical imaging, with histopathologic analyses are required. SUVmax of PET/CT provided the diagnostic ability to differentiate between benign and malignant splenic lesions. More than normal spleen uptake can be a convenient parameter to diagnose malignant spleen lesions.

Comparison of digital and analog [68Ga]Ga-PSMA-11 PET/CT for detecting post-prostatectomy biochemical recurrence in prostate cancer patients: a prospective study.

Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [68Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [68Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.

The relationship between depression, anxiety and lower urinary tract symptoms in men.

Purpose: Patients with lower urinary tract symptoms (LUTS) often experience comorbid depression and anxiety, yet the mechanisms underlying this association remain incompletely understood. This prospective study aimed to investigate the relationship between depression, anxiety, and LUTS in men. Materials and methods: A prospective study was conducted with 350 male patients who underwent urologic examinations at our institution from January 2021 to December 2021. Of these, 131 patients meeting the inclusion criteria were included. Various questionnaires, including the International Prostate Symptom Score (IPSS) and the Hospital Anxiety and Depression Scale (HADS), as well as LUTS examinations (prostate-specific antigen test, transrectal ultrasonography, and urine flowmetry), were administered. Results: Among the 350 patients, 131 were included in the analysis, with an average age of 58.0 ± 13.69 years. The total IPSS was 18.0 ± 8.69, with the average voiding symptom score at 8.7 ± 5.19 and the average storage symptom score at 6.0 ± 3.27. Both anxiety and depression were found to be correlated with LUTS (P < 0.05). After adjusting for age, hypertension, and diabetes, anxiety (but not depression) was significantly associated with LUTS based on regression analysis. Conclusion: Men with LUTS are more likely to experience anxiety. Therefore, it is essential to assess and address anxiety when managing men with LUTS.

Evaluation of machine learning approach for surgical results of Ahmed valve implantation in patients with glaucoma.

BACKGROUND: Ahmed valve implantation demonstrated an increasing proportion in glaucoma surgery, but predicting the successful maintenance of target intraocular pressure remains a challenging task. This study aimed to evaluate the performance of machine learning (ML) in predicting surgical outcomes after Ahmed valve implantation and to assess potential risk factors associated with surgical failure to contribute to improving the success rate. METHODS: This study used preoperative data of patients who underwent Ahmed valve implantation from 2017 to 2021 at Ajou University Hospital. These datasets included demographic and ophthalmic parameters (dataset A), systemic medical records excluding psychiatric records (dataset B), and psychiatric medications (dataset C). Logistic regression, extreme gradient boosting (XGBoost), and support vector machines were first evaluated using only dataset A. The algorithm with the best performance was selected based on the area under the receiver operating characteristics curve (AUROC). Finally, three additional prediction models were developed using the best performance algorithm, incorporating combinations of multiple datasets to predict surgical outcomes at 1 year. RESULTS: Among 153 eyes of 133 patients, 131 (85.6%) and 22 (14.4%) eyes were categorized as the success and failure groups, respectively. The XGBoost was shown as the best-performance model with an AUROC value of 0.684, using only dataset A. The final three further prediction models were developed based on the combination of multiple datasets using the XGBoost model. All datasets combinations demonstrated the best performances in terms of AUROC (dataset A + B: 0.782; A + C: 0.773; A + B + C: 0.801). Furthermore, advancing age was a risk factor associated with a higher surgical failure incidence. CONCLUSIONS: ML provides some predictive value in predicting the outcomes of Ahmed valve implantation at 1 year. ML evaluation revealed advancing age as a common risk factor for surgical failure.

Accessory first lumbrical muscle within the carpal tunnel: a case report.

Carpal tunnel syndrome is the most common entrapment neuropathy in the upper extremity. Palmaris longus, flexor digitorum superficialis, and lumbricals have infrequently been reported as causes of nerve compression. During routine Korean cadaver dissection, we incidentally identified an anatomic variant of first lumbrical muscle within the carpal tunnel in both wrists. The aberrant musculature originated from the radial side of the second FDS muscle at distal forearm level, running separately across the wrist beneath the flexor retinaculum. The dissected anomalous muscle was identified as an additional muscle belly of the first lumbrical muscle. Compression of the median nerve at the wrist might rarely be caused by the presence of such a tendon or muscle anomaly found in this study. Surgeons should be aware of possible anatomic variations in the carpal tunnel, and be prepared to modify their surgical plan accordingly.

Noninvasive ROS imaging and drug delivery monitoring in the tumor microenvironment.

Reactive oxygen species (ROS) that are overproduced in certain tumors can be considered an indicator of oxidative stress levels in the tissue. Here, we report a magnetic resonance imaging (MRI)-based probe capable of detecting ROS levels in the tumor microenvironment (TME) using ROS-responsive manganese ion (Mn2+)-chelated, biotinylated bilirubin nanoparticles (Mn@bt-BRNPs). These nanoparticles are disrupted in the presence of ROS, resulting in the release of free Mn2+, which induces T1-weighted MRI signal enhancement. Mn@BRNPs show more rapid and greater MRI signal enhancement in high ROS-producing A549 lung carcinoma cells compared with low ROS-producing DU145 prostate cancer cells. A pseudo three-compartment model devised for the ROS-reactive MRI probe enables mapping of the distribution and concentration of ROS within the tumor. Furthermore, doxorubicin-loaded, cancer-targeting ligand biotin-conjugated Dox/Mn@bt-BRNPs show considerable accumulation in A549 tumors and also effectively inhibit tumor growth without causing body weight loss, suggesting their usefulness as a new theranostic agent. Collectively, these findings suggest that Mn@bt-BRNPs could be used as an imaging probe capable of detecting ROS levels and monitoring drug delivery in the TME with potential applicability to other inflammatory diseases.

Characterization of sacral chordoma and differential diagnosis from other sacral malignancy using [18F]FDG PET/CT.

2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/computed tomography (CT) is known to be a helpful imaging modality for sacral chordoma, but its detailed characteristics have not been fully described. The purpose of our study was to identify the [18F]FDG PET/CT imaging characteristics of sacral chordoma and compare them with other sacral malignancy. This retrospective study included patients who underwent [18F]FDG PET/CT because of a mass involving the sacrum. Investigated visual findings included visual score and distribution, and semiquantitative parameters measured included standardized uptake values (SUVmax, SUVpeak, SUVmean), tumor-to-liver ratio (TLR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor size. Comparison studies and receiver operating characteristics (ROC) curve analysis were performed to differentiate between sacral chordoma and other sacral malignancy. Ten patients with sacral chordoma were finally included (M:F = 6:4, median age = 67 yr). On [18F]FDG PET/CT, sacral chordomas presented as a mass with minimal-moderate uptake with a usually heterogenous distribution. Compared with 12 patients with other sacral malignancies (M:F = 4:8, median age 42 yr), sacral chordoma showed a significantly lower TLR (median value 2.1 vs 6.3, P = .021). In ROC curve analysis, TLR showed the largest area under the curve (AUC) of 0.79 (cutoff ≤ 4.0; sensitivity 100.0%, specificity 58.3%; P = .004), and SUVmax showed the second largest AUC of 0.73 (cutoff ≤ 6.9; sensitivity 80.0%, specificity 66.7%; P = .034). [18F]FDG PET/CT of sacral chordoma showed minimal-moderate uptake. The TLR of [18F]FDG PET/CT was significantly lower than that of other sacral malignancy and was the most useful parameter for differentiating sacral chordoma, with the largest AUC. SUVmax could be another helpful semiquantitative parameter.

Neglected posterior interosseous nerve injury.

Posterior interosseous nerve (PIN) injury is uncommon due to its anatomically deep location. We report a neglected, rare case of PIN injury presenting the loss of extension of thumb, index, and small fingers with weakness of thumb abduction in a 49-year-old male patient. The patient sustained a penetrating injury to his right forearm caused by a kitchen knife that was repaired primarily through an emergency surgery under general anesthesia. During the regular follow-up on the 52nd postoperative day, the patient presented 20° of extension lags in the right thumb and index finger and 30° in the small finger. Wrist extension was intact, and there was no sensory deficit. We explored the wound and traced the PIN completely, identifying a club-shaped neuroma formation at the proximal cut end of the PIN. Delayed nerve repair was performed with a double-strip cable graft. Hand surgeons should be aware of the probable PIN injury in certain situations of forearm-penetrating injury and perform proper preoperative physical examination to rule out neurovascular deficits. Careful exploration and immediate repair of severe PIN are mandatory, even in emergency situations.

Security Comparison of Various Surgical Knots Using Nylon Suture.

OBJECTIVE: To evaluate the strengths of various surgical knot techniques, including square knot, surgeon's knot, granny knot, and random knot with the same three throws. METHODS: The authors tested each of the four knot techniques using four different gauges of nylon (polyamide [Ethicon]): 4-0, 5-0, 6-0, and 7-0. Each knot type was tested 20 times per nylon gauge, for a total of 320 knots tested. The authors used a static pull machine to measure elongation at yield and maximal force to break. RESULTS: A comparison of elongation at yield revealed that the surgeon's knot was superior to the square knot, granny knot, and random knots across all gauges of nylons. Further, a comparison of maximal force to break revealed that the surgeon's knot was superior to the square knot, granny knot, and random knots when using 4-0, 5-0, and 6-0 nylon but not when using 7-0 nylon. CONCLUSIONS: The surgeon's knot was the strongest, and random knot was the weakest when the authors used nylon 4-0, 5-0, and 6-0. While handling fine suture materials such as 7-0 nylon, knot failure appears to be unrelated to the knot technique used. This study provides not only fundamental guidance for tying surgical knots using nylon, but also a rational basis for an adequately strong knot choice in various fields of surgery.

Clinical characteristics of endometrioma with and without dysmenorrhea diagnosed by laparoscopy: A retrospective cohort study in a tertiary center.

OBJECTIVE: Clinical characteristics of patients with endometrioma without dysmenorrhea have not been well delineated; our goal was to remedy this issue by performing a retrospective cohort study. METHODS: A total of 379 patients who underwent laparoscopic surgery for endometrioma ≥4 cm at a tertiary hospital were included in this retrospective study. Patients were divided into two groups based on the presence of dysmenorrhea at the time of hospital visit; with dysmenorrhea group and without dysmenorrhea group. RESULTS: Patients without dysmenorrhea comprised 9.5% of all surgically confirmed endometriomas. Significant differences were found in the revised American Society for Reproductive Medicine (rASRM) stage, age at surgery, and bilaterality. Patients with rASRM stage IV were more likely to have dysmenorrhea than were subjects with rASRM stage III (odds ratio (OR), 10.58; 95% confidence interval (CI), 4.63-24.21; P < 0.001). Older patients were less likely to have dysmenorrhea (OR, 0.94; 95% CI, 0.88-1.00; P = 0.045), as were patients with bilateral rather than unilateral endometrioma (OR, 0.36; 95% CI, 0.15-0.82; P = 0.015). No significant differences in cyst size, age at menarche, body mass index (BMI), parity, or history of previous ovarian surgery were found between the two groups. CONCLUSION: Patients without dysmenorrhea comprised 9.5% of endometrioma cases and had less advanced rASRM stage, were older at surgery, and had a higher probability of bilateral than unilateral endometrioma than patients with dysmenorrhea.

Lipopolysaccharide-producing Veillonella infantium and Escherichia fergusonii cause vagus nerve-mediated cognitive impairment in mice.

Gut microbiota communicates bidirectionally with the brain through the nervous, immune, and endocrine systems of the gut. In our preliminary study, the fecal microbiota of volunteers with mild cognitive impairment (Fmci) exhibited a higher abundance of Escherichia fergusonii (NK2001), Veillonella infantium (NK2002), and Enterococcus faecium (NK2003) populations compared with those of healthy volunteers. Therefore, we examined the effects of Fmci, NK2001 (gram-negative), NK2002 (gram-negative-like), and NK2003 (gram-positive) on cognitive impairment-like behavior, neuroinflammation, and colitis in mice with or without antibiotics. Fmci transplantation increased cognitive impairment-like behavior, hippocampal tumor necrosis factor (TNF)-α expression, and the size of toll-like receptor (TLR)4+Iba1+, TLR2+Iba1+, and NF-κB+Iba1+ cell populations independent of antibiotic treatment. Oral gavage of NK2001, NK2002, or NK2003, which induced TNF-α expression in Caco-2 cells, significantly increased cognitive impairment-like behavior and hippocampal TNF-α expression and Iba1-positive cell populations and decreased brain-derived neurotrophic factor (BDNF) expression in mice. Celiac vagotomy significantly decreased NK2001- or NK2002-induced cognitive impairment-like behavior and hippocampal Iba1+ cell population and TNF-α expression and increased NK2001- or NK2002-suppressed hippocampal BDNF expression. However, NK2003-induced cognitive impairment-like behavior and hippocampal Iba1+ cell population and TNF-α expression were partially, but not significantly, attenuated by celiac vagotomy. Furthermore, celiac vagotomy did not affect NK2001-, NK2002-, or NK2003-induced lipopolysaccharide (LPS) levels in the blood and feces and TNF-α expression and NF-κB-positive cell population in the colon. In conclusion, LPS-producing NK2001 and NK2002 and LPS-nonproducing NK2003 may induce NF-κB-mediated neuroinflammation through the translocation of byproducts such as LPS and peptidoglycan into the brain through gut-blood/vagus nerve-brain and gut-blood-brain pathways, respectively, resulting in cognitive impairment.

Immunotherapy targeting the obese white adipose tissue microenvironment: Focus on non-communicable diseases.

Obesity triggers inflammatory responses in the microenvironment of white adipose tissue, resulting in chronic systemic inflammation and the subsequent development of non-communicable diseases, including type 2 diabetes, coronary heart disease, and breast cancer. Current therapy approaches for obesity-induced non-communicable diseases persist in prioritizing symptom remission while frequently overlooking the criticality of targeting and alleviating inflammation at its source. Accordingly, this review highlights the importance of the microenvironment of obese white adipose tissue and the promising potential of employing immunotherapy to target it as an effective therapeutic approach for non-communicable diseases induced by obesity. Additionally, this review discusses the challenges and offers perspective about the immunotherapy targeting the microenvironment of obese white adipose tissue.

Dienogest attenuates STAT3 activation in ovarian endometriotic cysts.

OBJECTIVE: Recent studies have suggested that endometriosis could be the result of excessive activation of signal transducer and activator of transcription 3 (STAT3), which is associated with the regulation of essential cellular mechanisms such as proliferation, invasion, and apoptosis. That finding implies that regulating STAT3 activation could play a key role in treating endometriosis. In the present study, we aimed to evaluate whether the anti-endometriotic effects of dienogest is mediated by the regulation of STAT3 activation. STUDY DESIGN: STAT3 activation was evaluated in normal endometrial and ovarian endometriotic tissues obtained from patients with/without preoperative dienogest treatment. A subsequent in vitro analysis with endometriotic cyst stromal cells (ECSCs) was used to confirm the direct influence of dienogest in STAT3 activation. RESULT: STAT3 activation is significantly higher in endometriotic tissues from non-treated patients than in normal endometrial tissues, and that difference is reversed by preoperative administration of dienogest. Similarly, the inhibitory effects of dienogest on STAT3 activation are demonstrated by in vitro results showing that dienogest treatment significantly inhibits IL-6-stimulated STAT3 activation in cultured ECSCs. That inhibition was accompanied by decreased expression of proliferative (PCNA), invasive (MMP-2), and anti-apoptotic (BCL-2) proteins. Furthermore, downregulating STAT3 activity with siRNA decreased PCNA, MMP-2, and BCL-2 expression in IL-6-treated ECSCs. CONCLUSION: Dienogest inhibits STAT3 activation in ECSCs, which affects their proliferation, invasiveness, and apoptosis.

Association between Preoperative Glucose Dysregulation and Delirium after Non-Cardiac Surgery.

This study aimed to investigate the association between glucose dysregulation and delirium after non-cardiac surgery. Among a total of 203,787 patients who underwent non-cardiac surgery between January 2011 and June 2019 at our institution, we selected 61,805 with available preoperative blood glucose levels within 24 h before surgery. Patients experiencing glucose dysregulation were divided into three groups: hyperglycemia, hypoglycemia, and both. We compared the incidence of postoperative delirium within 30 days after surgery between exposed and unexposed patients according to the type of glucose dysregulation. The overall incidence of hyperglycemia, hypoglycemia, and both was 5851 (9.5%), 1452 (2.3%), and 145 (0.2%), respectively. The rate of delirium per 100 person-months of the exposed group was higher than that of the unexposed group in all types of glucose dysregulation. After adjustment, the hazard ratios of glucose dysregulation in the development of delirium were 1.35 (95% CI, 1.18-1.56) in hyperglycemia, 1.36 (95% CI, 1.06-1.75) in hypoglycemia, and 3.14 (95% CI, 1.27-7.77) in both. The subgroup analysis showed that exposure to hypoglycemia or both to hypo- and hyperglycemia was not associated with delirium in diabetic patients, but hyperglycemia was consistently associated with postoperative delirium regardless of the presence of diabetes. Preoperative glucose dysregulation was associated with increased risk of delirium after non-cardiac surgery. Our findings may be helpful for preventing postoperative delirium, and further investigations are required to verify the association and mechanisms for the effect we observed.

RHEA: Real-World Observational Health Data Exploration Application.

We developed a standardized framework named RHEA to represent longitudinal status of patient with cancer. RHEA generates a dashboard to visualize patients' data in the Observational Medical Outcomes Partnership-Common Data Model format. The generated dashboard consists of three main parts for providing the macroscopic characteristics of the patient: 1) cohort-level visualization, 2) individual-level visualization and 3) cohort generation.

Perioperative adverse cardiac events and mortality after non-cardiac surgery: a multicenter study.

BACKGROUND: Perioperative adverse cardiac events (PACE), a composite of myocardial infarction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, and stroke during 30-day postoperative period, is associated with long-term mortality, but with limited clinical evidence. We compared long-term mortality with PACE using data from nationwide multicenter electronic health records. METHODS: Data from 7 hospitals, converted to Observational Medical Outcomes Partnership Common Data Model, were used. We extracted records of 277,787 adult patients over 18 years old undergoing non-cardiac surgery for the first time at the hospital and had medical records for more than 180 days before surgery. We performed propensity score matching and then an aggregated meta­analysis. RESULTS: After 1:4 propensity score matching, 7,970 patients with PACE and 28,807 patients without PACE were matched. The meta­analysis showed that PACE was associated with higher one-year mortality risk (hazard ratio [HR]: 1.33, 95% CI [1.10, 1.60], P = 0.005) and higher three-year mortality (HR: 1.18, 95% CI [1.01, 1.38], P = 0.038). In subgroup analysis, the risk of one-year mortality by PACE became greater with higher-risk surgical procedures (HR: 1.20, 95% CI [1.04, 1.39], P = 0.020 for low-risk surgery; HR: 1.69, 95% CI [1.45, 1.96], P < 0.001 for intermediate-risk; and HR: 2.38, 95% CI [1.47, 3.86], P = 0.034 for high-risk). CONCLUSIONS: A nationwide multicenter study showed that PACE was significantly associated with increased one-year mortality. This association was stronger in high-risk surgery, older, male, and chronic kidney disease subgroups. Further studies to improve mortality associated with PACE are needed.