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Background: Cancer is a major health problem and exploiting natural products have been one of the most successful methods to combat this disease. Verbesina encelioides is a notorious weed with various pharmacological properties. The aim of the present investigation was to screen the anticancer potential of V. encelioides extract against human lung cancer (A-549), breast cancer (MCF-7), and liver cancer (HepG2) cell lines. Methods: A-549, MCF-7, and HepG2 cells were exposed to various concentrations of (10-1000 µg/ml) of V. encelioides for 24 h. Further, cytotoxic concentrations (250, 500, and 1000 µg/ml) of V. encelioides induced oxidative stress (GSH and LPO), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest, and DNA damage in HepG2 cells were studied. Results: The exposure of cells to 10-1000 µg/ml of extract for 24 h, revealed the concentrations 250-1000 µg/ml was cytotoxic against MCF-7 and HepG2 cells, but not against A-549 cells. Moreover, the extract showed higher decrease in the cell viability against HepG2 cells than MCF-7 cells. Therefore, HepG2 cells were selected for further studies viz. oxidative stress (GSH and LPO), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest, and DNA damage. The results revealed differential anticancer activity of V. encelioides against A-549, MCF-7 and HepG2 cells. A significant induction of oxidative stress, ROS generation, and MMP levels was observed in HepG2 cells. The cell cycle analysis and comet assay showed that V. encelioides significantly induced G2/M arrests and DNA damage. Conclusion: These results indicate that V encelioides possess substantial cytotoxic potential and may warrant further investigation to develop potential anticancer agent. [ABSTRACT FROM AUTHOR]

Background: With emphasis on policy implications, the main objective of this study was to estimate the numbers of two main groups affected by FGM/C in Norway: 1) those already subjected to FGM/C and therefore potentially in need for health care and 2) those at risk of FGM/C and consequently the target of preventive and protective measures. Special attention has been paid to type III as it is associated with more severe complications.Methods: Register data from Statistics Norway (SSB) was combined with population-based survey data on FGM/C in the women/girls' countries of origin.Results: As of January 1(st) 2013, there were 44,467 first and second-generation female immigrants residing in Norway whose country of origin is one of the 29 countries where FGM/C is well documented. About 40 pct. of these women and girls are estimated to have already been subjected to FGM/C prior to immigration to Norway. Type III is estimated in around 50 pct. of those already subjected to FGM/C. Further, a total of 15,500 girls are identified as potentially at risk, out of which an approximate number of girls ranging between 3000 and 7900 are estimated to be at risk of FGM/C.Conclusion: Reliable estimates on FGM/C are important for evidence-based policies. The study findings indicate that about 17,300 women and girls in Norway can be in need of health care, in particular the 9100 who are estimated to have type III. Preventive and protective measures are also needed to protect girls at risk (3000 to 7900) from being subjected to FGM/C. Nevertheless, as there are no appropriate tools at the moment that can single these girls out of all who are potentially at risk, all girls in the potentially at risk group (15,500) should be targeted with preventive measures. [ABSTRACT FROM AUTHOR]

Introduction: The worldwide shortage of donor livers has prompted the search for alternative cell therapies. Previous data from our laboratory proved a supportive role for stem cell therapy in the treatment of end-stage liver disease patients. Therefore; this study was conducted to assess the clinical and biochemical effects of repeated stem cell infusion. Methods: Ninety patients with liver cirrhosis were randomized to receive either one session treatment (G-I) or two sessions 4 months apart (G-II) of autologous haematopoietic stem cells (HSCs) transplantation and a control group (G-III) who received regular liver treatment. G-CSF was administered to transplanted patients before infusion; HSCs were isolated from 400 cc bone marrow (BM) aspirate. CD34+/CD133+ cells were purified: 50 % of the cells were infused locally in the portal vein on the same day and the other 50 % were differentiated to MSC and infused systemically in a peripheral vein (one session treatment G-I). In G-II, the same process was repeated after 4 months from the first treatment (two session's treatment G-II). Liver function was monitored for 12 months after stem cell therapy (SCT). Results: Statistically significant improvement was reported in the transplanted patients (G-1) as regards the mean serum albumin, bilirubin and INR levels which started to improve after 2 weeks of treatment and continued to improve till the 6th month in the single infusion group. The two sessions infused group (G-II) showed sustained response which continued throughout the all follow-up period (12 month). By the end of the study, 36.7 % of the patients in G-I and 66.7 % in G-II showed improvement in the degree of ascites compared to the control group (G-III). We also reported an improvement in the hepatic functional reserve as assessed by the Child-Pugh and MELD score. Safety of the procedure was evidenced by the low incidence of complications encountered. Conclusion: In patients with end-stage liver disease, the repeated infusion with combined routes portal and peripheral veins has a beneficial effect on liver functions with minimal adverse events and more lasting clinical efficacy after repeated HSCs infusion. [ABSTRACT FROM AUTHOR]

Introduction We have assessed the utility of autologous mesenchymal stem cell (MSC) peripheral vein infusion as a possible therapeutic modality for patients with end-stage liver diseases. Methods Forty patients with post- hepatitis C virus (HCV) end-stage liver disease were randomized into two groups; Group 1 (GI): 20 patients who received granulocyte colony stimulating factor (G-CSF) for 5 days followed by autologous MSCs peripheral vein infusion and group 2 (GII): 20 patients who received regular liver supportive treatment only (control group). Results In MSC-infused patients (GI), 54% showed near normalization of liver enzymes and improvement in liver synthetic function. Significant changes were reported in albumin (P = 0.000), bilirubin (P = 0.002), increased international normalized ratio (INR) (P = 0.017), prothrombin concentration (P = 0.029) and alanine transaminase (ALT) levels (P = 0.029) with stabilization of clinical and biochemical status in 13% of cases. None of the patients in GII showed any significant improvement. Hepatic fibrosis was assessed in GI by detection of procollagen IIIC peptide level (PIIICP) and procollagen III N peptide level (PIIINP). The pre-treatment values of s-PIIICP and s-PIIINP were (9.4 ± 4.2 and 440 ± 189; respectively) with a decrease to (8.1 ± 2.6 and 388 ± 102; respectively) three months after MSC therapy. However, the difference was statistically non-significant (P = 0.7). A significant correlation coefficient was reported after three months between the s-PIIINP and prothrombin concentration (P = -0.5) and between s-PIIICP and ascites (P = 0.550). Conclusions Firstly, autologous MSC infusion into a peripheral vein is as effective as the previously reported intrahepatic infusion. Secondly, MSCs have a supportive role in the treatment of end-stage liver disease with satisfactory tolerability and beneficial effects on liver synthetic functions and hepatic fibrosis. Thirdly, IV infusion of MSCs following G-CSF mobilization improves s-albumin within the first two weeks and prothr Alanine Transaminase ombin concentration after one month. According to the data from this current study and those previously reported by our group, we recommend further studies on patients' infusion with pure CD133 and CD34 followed by IV infusion of in vitro differentiated MSCs within one week and another infusion after 3 months. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii is an increasingly worrying organism in the healthcare setting, due to its multidrug resistance and persistence. Prolonged hospitalisation, immunocompromised patients and excessive antibiotic exposure all contribute to increasing the risk of A. baumannii infections, which makes cancer patients a significant risk group. This study aims to investigate the dissemination of A. baumannii at the National Cancer Institute (NCI) in Cairo - Egypt.Methods: All bacterial isolates were typed using Multi-locus Sequence Typing (MLST) to characterise the epidemiology of isolates. The intrinsic OXA-51-like, and the acquired carbapanemases OXA-23, - 24/40, - 58, NDM, IMP, and VIM were also amplified and sequenced to genetically identify mechanisms of carbapenem resistance.Results: MLST results show a high degree of multi-clonal dissemination, with 18 different Sequence Types (STs) identified, including 5 novel. The majority of isolates belonged to International Clone (IC) 2, and carbapenem resistance was detected in 93% of isolates and mediated by blaOXA-23, blaOXA-58, blaNDM-1 and blaVIM-1. We also report the presence of a resistant ST732 (OXA-378) which has been previously identified in migratory birds. CONCLUSIONS: Multiple highly resistant clones were identified in a Cancer hospital in Cairo. It is vital that clinicians and healthcare workers are aware of the population of A. baumannii present in order to have appropriate treatment and infection control practices. [ABSTRACT FROM AUTHOR]

Background: Ghosting refers to the sudden cessation of communication in interpersonal relationships. Ghosting has gained attention as a phenomenon commonly encountered in the context of digital communication. Earlier studies on ghosting mostly focused on Western societies while, in Arab societies, research into this practice has yet to be initiated. The current study aimed to address this gap by translating and validating the commonly used Ghosting Questionnaire (GHOST) into Arabic., Methods: The translation process involved forward and back translation, expert review, and pilot testing to ensure linguistic and cultural equivalence. A convenience sample of 607 participants from Bahrain, Egypt, Jordan, Oman, and Tunisia completed the Arabic version of the GHOST. Statistical analyses, including reliability testing and confirmatory factor analysis, were conducted to assess the psychometric properties of the instrument., Results: The Arabic version of the GHOST demonstrated high reliability. The Cronbach's alpha (α = 0.87) and McDonald's omega (ω = 0.87) coefficients indicated strong internal consistency. Test-retest reliability coefficients confirmed the stability of the responses over time (ICC 0.89, p < 0.001). CFA supported a single-factor structure in alignment with the conceptual framework of the original English version., Conclusions: The successful translation and validation of the GHOST into Arabic provide researchers with a reliable tool for investigating ghosting behavior within Arab societies. Future research endeavors can build upon these findings to explore the psychological implications of ghosting. Researchers can now also develop culturally sensitive understanding of online dating and related practices in Arab communities., (© 2024. The Author(s).)

Background: In chronic kidney disease (CKD), the durability of patient adherence to fluid and dietary restrictions may depend on the degree to which they have hope that they will enjoy life. Previous cross-sectional studies have shown that higher hope was associated with lower distress from fluid and dietary restrictions and better adherence in the short term. In this study, we aimed to examine the long-term relationship of hope with distress from fluid and dietary restrictions., Methods: This prospective observational cohort study included 444 patients with CKD undergoing dialysis in one of five Japanese nephrology centers. Hope as a predictor was measured using an 18-item health-related hope scale. Outcomes were two-item measures of distress from fluid and dietary intake restrictions using the Japanese version of the Kidney Disease Quality of Life Short Form, Version 1.3 (higher scores indicate lower levels of distress). Multivariate linear mixed models were used to estimate the association of baseline health-related hope with distress from fluid and dietary restrictions at baseline and follow-up., Results: The mean age of the participants was 67 years, and 31.1% of them were females. In total, 124, 98, and 222 had non-dialysis CKD, peritoneal dialysis, and hemodialysis, respectively. Higher levels of baseline health-related hope were associated with lower levels of distress from fluid restriction after one year (per 10-point increase, 2.6 points (95% confidence interval, 1.0 to 4.1)); whereas the baseline score was not associated with the distress from fluid restriction at 2 years. Similarly, higher levels of baseline health-related hope were associated with lower levels of distress from dietary restriction after one year (per 10-point increase, 2.0 points (95% confidence interval, 0.3 to 3.6)); whereas the baseline score was not associated with the distress from dietary restriction at 2 years., Conclusions: Health-related hope, regardless of depression, can potentially mitigate long-term distress from fluid and dietary restrictions in patients with a wide range of CKD severities., Trial Registration: UMIN000054710., (© 2024. The Author(s).)

Background: Preoperative anxiety is commonly found in patients who are waiting for surgery and can lead to negative surgical outcomes. Understanding the sources of surgical anxiety allows healthcare providers to identify at-risk patients and implement psychosocial interventions such as counseling, relaxation techniques, and cognitive‒behavioral therapy to minimize anxiety. Few comprehensive psychiatric measures are available to assess preoperative anxiety in Arabic., Objective: Our study aimed to translate, adapt, and validate the Surgical Anxiety Questionnaire (SAQ) into the modern standard Arabic language, also known as Fusha al-Asr Arabic., Methods: To translate the questionnaire, the research team used the gold standard process of forward translation by two independent translators along with back translation evaluation by four trained medical doctors. A cross-sectional study was conducted using an online survey completed by 208 Arabic speakers (mean age 38 years, 44% women) from four countries. Psychometric analyses, which included internal consistency, test-retest reliability, convergent validity, confirmatory factor analysis, and item response analysis, were performed. Convergent validity tests were performed against the Generalized Anxiety Disorder 2-item Scale (GAD-2), Patient Health Questionnaire-4 (PHQ-2), Perceived Stress Scale 4 (PSS-4), and Arabic version of the Visual Analog Scale for anxiety (VAS-A)., Results: The mean SAQ of our sample was 19.38 ± 12.63 (possible range 0-68). The Arabic SAQ translation demonstrated excellent internal consistency, with McDonald's omega and a Cronbach's alpha of approximately 0.90. The test-retest reliability was also high, with an intraclass coefficient of 0.94. The SAQ showed strong convergent validity against the GAD-2 (r = 0.94, p < 0.01). The SAQ also showed weak-moderate correlations with the PHQ-2 (r = 0.26, p < 0.01), PSS-4 (r = 43, p < 0.01), and VAS-A (r = 0.36, p < 0.01) scores. The original three-factor structure was supported by confirmatory factor analysis, confirming the original structure reported in the original English language version. The results for fitness indices showed acceptable preliminary results (CFI/TLI approximately 0.90), and deleting some items improved the model fit (CFI/TLI > 0.90, RMSEA < 0.08). We suggest retaining the original factorial solution until further validation studies can be conducted. The item response theory (IRT) results identified no items that were excessively difficult or subject to guessing. The multidimensional IRT provided evidence that the SAQ items form a multidimensional scale assessing surgical anxiety that fits the classical model reasonably well., Conclusion: The SAQ has demonstrated acceptable reliability and validity; thus, it is a trustworthy and valid tool for evaluating preoperative anxiety in Arabic speakers. Future research could benefit from using the SAQ in both surgical and psychiatric research., (© 2024. The Author(s).)

Background: Addressing the shortage of healthcare professionals in rural Japan poses significant challenges. At Sanmu Medical Center, incorporating resident physicians into a general medicine training program has proved effective in retaining them as supervising physicians. This study aims to identify the key factors contributing to the success of such programs., Methods: We used a qualitative research design to comprehensively understand the factors contributing to physician retention in regional community hospitals in areas with physician shortages. Interviews were conducted with four experienced physicians, including the center director, who participated in the general or family medicine training programs at Sanmu Medical Center. Using a semi-structured questionnaire, we explored the factors influencing physician retention in community-based hospitals experiencing shortages. Two physicians specializing in community medicine conducted a content analysis under the supervision of three experts in community-oriented medical education and qualitative research. This approach helped compare retention factors perceived by physicians and the center director., Results: Content analysis revealed 10 categories and 47 subcategories. The analysis revealed that "Educational activity" and "Supervising physicians and guidance system" are crucial for physician retention in rural hospitals in Japan. The study highlighted key educational factors contributing to retention: engagement in educational activities led to personal and professional growth, creating a rewarding experience for the physicians. Furthermore, a structured supervising physician system provided essential guidance and mentorship, improving the educational environment. Diverse learning opportunities and protected learning times were identified as critical for fostering a sustainable commitment among physicians to work in rural settings. These findings contribute to existing literature by detailing how structured educational activities and mentorship programs in rural hospital settings can significantly impact physician retention., Conclusions: Community-based medical education programs that focus on diverse clinical settings, mentorship, and a supportive work environment can enhance physician retention in rural areas. By fostering such educational and professional environments, healthcare institutions can address physician maldistribution and improve care quality in underserved communities. Our study offers practical insights that can be replicated or adapted by other rural hospitals facing similar challenges. It offers targeted strategies to address the unique challenges faced by female physicians in rural healthcare settings., (© 2024. The Author(s).)

Background: In light of the ongoing monkeypox (MPOX) epidemic, healthcare workers (HCWs) have been in contact with various diseases. Therefore, they should take appropriate preventive and control measures to maintain their health. This study assessed Egyptian HCWs' intentions to take MPOX vaccines., Methods: A cross-sectional survey was conducted using social media platforms between September 27 and November 4, 2022. An anonymous online survey using the 5C scale was conducted using convenience and snowball sampling methods to assess the five psychological antecedents of vaccination (i.e., confidence, constraints, complacency, calculation, and collective responsibility)., Results: A total of 399 HCWs with a mean age of 32.6 ± 5.7 participated in this study. Of them, 89.7% were female. The five C psychological antecedents of vaccination were as follows: 55.9% were confident about vaccination, 50.6% were complacent, 56.6% experienced constraints, 60.7% calculated the risk and benefit, and 58.4% had collective responsibility. Multivariate analysis showed that high income level and having information about MPOX were significant predictors of confidence in the MPOX vaccines (adjusted odds ratio ((AOR) = 4.19, 95% CI (1.12- 15.59), P = 0.032). Participants aged 31-45 years and 19-30 years showed significant association (AOR = 2.46, 95% CI (0.85-7.15), P = 0.096) and (AOR = 4.19, 95% CI (1.39-12.64), P = 0.011), respectively. Having an idea about the MPOX vaccines significantly predicted the complacency domain (AOR = 3.77, 95%CI (1.47-9.65, P = 0.006). Moreover, precollege/undergraduate education and having an idea about MPOX vaccination were significant predictors of the constraint domain (AOR = 1.81.95% CI (1.09-2.99, P = 0.020), (AOR = 2.70, 95% CI (1.05-6.95, P = 0.038), respectively). Female sex, having a diploma, postgraduate studies, and having an idea about MPOX vaccine significantly predicted calculation domain (AOR = 2.06, 95% CI (1.05-4.04, P = 0.035), (AOR = 3.98,95% CI (1.33-11.87, P = 0.013), (AOR = 2.02, 95% CI (1.25-3.26, P = 0.004) & (AOR = 2.75. 95% CI (1.05-7.18, P = 0.039), respectively. The only significant predictor of collective responsibility was having a diploma and postgraduate studies (AOR = 3.44, 95% CI (1.21-9.78, P = 0.020), (AOR = 1.90,95% CI (1.17-3.09, P = 0.009)., Conclusions: Efforts to control MPOX should focus on promoting protective measures such as the vaccination of HCWs as well as raising their awareness about the updated information regarding the virus and the approved vaccines., (© 2024. The Author(s).)

Background: The administration of antibiotic prophylaxis for clean-wound surgeries is controversial among surgeons, despite guidelines suggesting its use. This study aimed to evaluate its effectiveness in preventing surgical site infections (SSIs) in clean-wound surgeries within a regional setting with varied practices regarding prophylaxis., Materials and Methods: This retrospective cohort study included four types of common general surgeries performed from March 2021 to February 2023 at a tertiary regional hospital in Thailand. The surgeries included skin/subcutaneous excision, thyroidectomy, inguinal hernia repair, and breast surgeries, all of which required regional or general anesthesia. Antibiotic prophylaxis was administered at the discretion of the attending surgeons. SSI diagnosis followed standard diagnostic criteria, involving reviewing medical records and the records of the infection control unit. Infection risk factors were examined. The primary outcome comparison used inverse probability treatment weighting of propensity scores, with covariate balance evaluated., Results: Of the 501 surgeries identified, 84 were excluded, leaving 417 eligible for analysis. Among these patients, 233 received prophylactic antibiotics, for an SSI rate of 1.3%, while 184 did not receive antibiotics, for an SSI rate of 2.2%. A comparative analysis using propensity score weighting revealed no statistically significant difference in the incidence of SSI between the groups (risk ratio [95% confidence interval]: 0.54 (0.11, 2.50), p = 0.427)., Conclusion: In this practical setting, with the given study size, antibiotic prophylaxis in common general surgeries involving clean wounds did not significantly prevent SSIs. Routine use recommendations should be re-evaluated., Trial Registration: Not applicable as this study is a retrospective cohort study and not a clinical trial., (© 2024. The Author(s).)

Background: Immediate implant placement using vestibular socket therapy (VST) proved to offer a successful treatment option in compromised sockets. However, the presence of active signs infection complicates immediate implants in sockets with defective labial plates, due to the possible contamination of the implant or the bone graft with existing infected tissues or oral environment via the fistula. This study, therefore, aims to explore the success of immediate implant placement using VST in managing infected compromised sockets., Methods: We included 26 age- and sex-matched patients with 41 implants sites. Thirteen patients had 19 infected (group I) and 13 had 21 non-infected type 2 sockets (group N). Both groups were treated using vestibular socket therapy (VST) and a 6-day protocol. Implant survival, changes in facial bone thickness, and mid, mesial, and distal mucosal levels were evaluated 1 year after implant placement. The Mann-Whitney U test was used to compare both groups. Furthermore, the Wilcoxon signed-rank test was used to study changes with time within each group. The statistical significance level was set at P < 0.05., Results: All implants survived; no significant difference was found between groups N and I regarding apical, mid, and crestal bone thickness and soft tissue level, except at the mesial papilla, where the recession was significantly more in group N than in group I. Changes over time were statistically significant in the apical, mid, and crestal bone thickness in both groups. The mean bone thickness gain ranged from 0.85 to 2.4 mm and 0.26-1.63 mm in groups I and N, respectively. Additionally, the mean mucosal recession ranged from 0.29 to 0.51 mm and 0.39-1.47 mm in groups I and N, respectively., Conclusion: Within the limitations of this study immediate implant placement in type II infected sockets using the 6-day protocol and VST achieved 100% implant survival, while maintaining the regenerated facial bone thickness with minimal mucosal recession., Trial Registration: The protocol for this study was registered on clinicaltrials.gov at 3/10/2021 (registration number NCT04787224)., (© 2024. The Author(s).)

Background: The increasing incidence and prevalence of childhood overweight (OW) and obesity (OB) are major global health challenges. This study aimed to evaluate the effectiveness of a 2-year healthy lifestyle intervention program in reducing the incidence of OW and OB among schoolchildren aged 11-12 years in Vietnam., Methods: Study design: Randomized controlled trial., Participants and Interventions: In total, 733 students participated in this study. Participants were included from four schools in Hanoi based on a random cluster sampling method. Students' health outcomes were assessed at baseline and after 2 years., Main Outcomes: The primary outcomes were the incidence of OW and OB, and the secondary outcomes were the prevalence and remission of OW and OB. Generalized estimating equations (GEEs) were used to determine the outcomes and risk factors., Results: After the intervention, the prevalence of OW decreased by 9.24% in the intervention group and 3.01% in the control group. After adjustment for age and sex, the odds of overweight were 36.7% lower in the intervention group than in the control group (OR = 0.633; 95% CI: 0.434-0.925; P = 0.018). The incidence of OW was 1.31% in the intervention group compared with 5.33% in the control group. After adjustment for age and sex, the odds of incident overweight in the intervention group were 77.4% lower than in the control group (OR = 0.226; 95% CI: 0.063-0.813; P = 0.023). The proportion of patients who achieved OW remission was 41.22% in the intervention group and 28.68% in the control group. After adjustment for age and sex, the odds of OW remission of overweight were 2.219 times greater in the intervention group than in the control group (OR = 2.219; 95% CI: 1.220-4.036; P = 0.009). For most OB-related factors, there were no significant differences between the intervention and control groups., Conclusion: A multicomponent healthy lifestyle intervention was effective in reducing the incidence of OW; however, it had no significant effect on OB among children aged 11-12 years in Hanoi, Vietnam., Trial Registration: Retrospectively registered number: UMIN000014992, 20/08/2023., (© 2024. The Author(s).)

Background: Colorectal cancer is the 3rd most common cancer worldwide, representing 10% of all cancer types, and is considered the 2nd leading cause of cancer-related deaths. It usually metastasizes to the liver or lung. Para-aortic lymph node metastasis is considered a metastatic disease (stage 4) according to the AJCC and is considered a regional disease (stage 3) according to the JSCCR. Para-aortic lymph node metastases occur in about 1% of cases. Neoadjuvant CTH, followed by PALN, is the best option for metastatic para-aortic LNs in colorectal cancer patients. This study addresses the value of prophylactic para-aortic LN dissection among colon-rectal cancer patients (overtreatment protocol)., Methodology: This is a prospective study that included patients attending NCI, Cairo University, from December 2020 to December 2023 who were complaining of left colonic cancer or recto-sigmoid cancer and underwent left hemicolectomy, sigmoid colectomy, or LAR. All patients underwent formal mesenteric LN dissection and prophylactic para-aortic LN dissection., Results: Among 60 patients who underwent colorectal surgery with prophylactic para-aortic LN dissection, 21 cases (35%) were in the descending colon, 22 cases (36.7%) were in the sigmoid colon, 11 cases (18.3%) were in the recto-sigmoid, and 6 cases (10%) were in the upper rectum. 55 cases (91.7%) were in grade 2, and 5 cases (8.3%) were in grade 3. Neoadjuvant CTH was given in 3 cases (5%) while neoadjuvant RTH was given in 6 cases (10%). Regarding reported postoperative complications, lymphorrhea was reported in 2 patients (3.3%) and wound infection occurred in 6 patients (10%). A recurrence was reported among 8 cases (13.4%)., Conclusions: We aimed in this study to highlight the value of prophylactic para-aortic lymph node dissection among colorectal cancer patients (over-treatment protocol) and report its reflection on predicting the behavior of the disease and subsequently selecting the patients who will be suitable to do this procedure., (© 2024. The Author(s).)

Background: Accurate staging is necessary for predicting hepatocellular carcinoma (HCC) prognosis and guiding patient management. The Barcelona Clinic Liver Cancer (BCLC) staging system has limitations due to heterogeneity observed among patients in BCLC stages B and C. In contrast, the Hong Kong Liver Cancer (HKLC) staging system offers more aggressive treatment strategies., Aim: To compare the prognostic performance of HKLC and BCLC staging systems in Egyptian patients with HCC., Methods: We conducted a retrospective study at the National Liver Institute, Menoufia University, Egypt, on 1015 HCC patients. Data was collected from patients' medical records over 10 years (from 2008 to 2018). The BCLC and HKLC stages were identified, and Kaplan-Meier survival analysis was used to compare patients' overall survival rates within each staging system. Additionally, we evaluated the comparative prognostic performance of the two staging systems., Results: Hepatitis C was identified as the underlying etiology in 799 patients (78.7%), hepatitis B in 12 patients (1.2%), and non-viral causes in 204 patients (20.1%). The survival analysis demonstrated significant differences across the various stages within both the BCLC and HKLC systems. The receiver operating characteristic (ROC) curves indicated a marginally superior performance of the HKLC system in predicting survival at 1, 2, and 3 years compared to the BCLC system. Furthermore, the HKLC staging provided a slightly enhanced prognostic capability, particularly for patients classified under BCLC stages B and C, suggesting a potential survival benefit., Conclusion: HKLC classification had a slightly better prognostic performance than BCLC staging system and may offer a survival advantage for certain patients with HCC in BCLC stage B and C HCC cases., (© 2024. The Author(s).)

Background: A decline in cognitive function is associated with inflammatory processes. However, the association between high-sensitivity C-reactive protein (hs-CRP) levels and cognitive decline in the Japanese population remains inconclusive. Thus, this study aimed to determine whether hs-CRP is associated with low cognitive function in 70- and 80-year-old community-dwelling Japanese individuals., Methods: The participants in this cross-sectional study were 872 Japanese residents aged 70 and 80 years who voluntarily participated in the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study between 2010 and 2011. Blood sample collection, cognitive assessment, and other measurements were performed at the venue. Low cognitive function was defined as a score of 25 points or lower on the Japanese version of the Montreal Cognitive Assessment. The odds ratio (OR) and 95% confidence interval (95% CI) for each hs-CRP quartile were calculated using logistic regression analysis., Results: A total of 288 (69.9%) parsons in the 70-year-old group and 372 (80.9%) in the 80-year-old group exhibited low cognitive function. The association between hs-CRP levels and low cognitive function was significant among 70- and 80-year-old Japanese community-dwelling adults. In particular, the fourth quartile of hs-CRP (0.727-7.420 mg/L) in the 70-year-old group and the second and fourth quartiles (0.214-0.404 and 0.911-9.890 mg/L) in the 80-year-old group were associated with low cognitive function. Furthermore, the third quartile (0.409-0.892 mg/L) in the 80-year-old group was closely associated with low cognitive function., Conclusions: High hs-CRP levels were associated with lower cognitive function in 70- and 80-year-old Japanese community-dwelling individuals, suggesting that high hs-CRP levels may influence cognitive function., (© 2024. The Author(s).)

Introduction: MicroRNAs (miRNAs) are single RNA molecules that act as global regulators of gene expression in mammalian cells and thus constitute attractive targets in treating cancer. Here we aimed to investigate the possible involvement of miRNA-141 (miR-141) in cervical cancer and to identify its potential targets in cervical cancer cell lines., Methods: The level of miR-141 in HeLa and C-33A cells has been assessed using the quantitative real-time PCR (qRT-PCR). A new miR-141 construct has been performed in a CMV promoter vector tagged with GFP. Using microarray analysis, we identified the potentially regulated genes by miR-141 in transfected HeLa cells. The protein profile of killer-like receptor C1 (KLRC1), KLRC3, carcinoembryonic antigen-related cell adhesion molecule 3 (CAM3), and CAM6 was investigated in HeLa cells transfected with either an inhibitor, antagonist miR-141, or miR-141 overexpression vector using immunoblotting and flow cytometry assay. Finally, ELISA assay has been used to monitor the produced cytokines from transfected HeLa cells., Results: The expression of miR-141 significantly increased in HeLa and C-33A cells compared to the normal cervical HCK1T cell line. Transfection of HeLa cells with an inhibitor, antagonist miR-141, showed a potent effect on cancer cell viability, unlike the transfection of miR-141 overexpression vector. The microarray data of HeLa cells overexpressed miR-141 provided a hundred of downregulated genes, including KLRC1, KLRC3, CAM3, and CAM6. KLRC1 and KLRC3 expression profiles markedly depleted in HeLa cells transfected with miR-141 overexpression accompanied by decreasing interleukin 8 (IL-8), indicating the role of miR-141 in avoiding programmed cells death in HeLa cells. Likewise, CAM3 and CAM6 expression reduced markedly in miR-141 transduced cells accompanied by an increasing level of transforming growth factor beta (TGF-β), indicating the impact of miR-141 in cancer cell migration. The IntaRNA program and miRWalk were used to check the direct interaction and potential binding sites between miR-141 and identified genes. Based on this, the seeding regions of each potential target was cloned upstream of the luciferase reporter gene in the pGL3 control vector. Interestingly, the luciferase activities of constructed vectors were significantly decreased in HeLa cells pre-transfected with miR-141 overexpression vector, while increasing enormously in cells pre-transfected with miR-141 specific inhibitor., Conclusion: Together, these data uncover an efficient miR-141-based mechanism that supports cervical cancer progression and identifies miR-141 as a credible therapeutic target., (© 2024. The Author(s).)

Background: To compare the operative effect and clinical efficacy of the Moses laser mode and the Raykeen holmium laser energy platform powder mode under flexible ureteroscopic lithotripsy in patients with impacted upper ureteral stones., Methods: From March 2022 to September 2022, 72 patients were divided into a Moses laser group and a Raykeen laser group according to surgical method, with 36 patients in each group. CT and ureteroscopy confirmed that all patients had isolated impacted upper ureteral stones. The stone volume (mm 3 ), stone density (Hu) and severity of hydronephrosis were measured by CT. Postoperative complications were evaluated using the Clavien-Dindo score., Results: There were no complications of ureteral stenosis related to the laser treatment. The operative time and lithotripsy time were lower in the Moses laser group than in the Raykeen laser group (P < 0.05). The stone-free survival rate did not differ significantly between the two groups (P = 0.722). Stone volume was found to be positively correlated with laser energy and lithotripsy time in both groups (P < 0.01). There was no significant correlation between laser energy and lithotripsy time or ureteral stone density (Hu) in the Moses laser group (P > 0.05) or the Raykeen laser group (P > 0.05)., Conclusions: The contact mode of Moses technology and the powder mode of Raykeen laser lithotripsy can be used for the ablation of a single impacted upper ureteral stone. The ablation speed was related to the stone volume and the severity of polyp hyperplasia, not the stone density. We recommend the use of the powdered mode as a therapeutic measure for the treatment of impacted upper ureteral stones in flexible ureteroscopic lithotripsy., (© 2024. The Author(s).)

Background: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a cancer stem cell (CSC) marker of colorectal cancer and may be a CSC marker of other cancer types. Few studies have been conducted on LGR5 expression in extrahepatic cholangiocarcinoma (ECC)., Methods: We analyzed LGR5 expression using RNAscope, a highly sensitive RNA in situ hybridization technique. Fifty-three ECCs were selected from the medical archives at Shinshu University Hospital and analyzed using a tissue microarray. LGR5 expression levels were divided into expression and no expression groups. LGR5 expression and clinicopathological characteristics were analyzed., Results: Among 25 cases, no LGR5-positive dots were identified. Among 28 cases, some LGR5-positive dots were observed in carcinoma cells, together with a wide range of LGR5-positive cells. LGR5 expression was conspicuous in glandular duct formations. Well- to moderately differentiated types showed significantly higher LGR5 expression than the poorly differentiated type (p = 0.0268). LGR5 expression was associated with good overall survival (p = 0.0219) and good disease-free survival (DFS) (p = 0.0228). High LGR5 expression was associated with well- to moderately-differentiated types, indicating a favorable prognosis. In terms of DFS, multivariate analysis showed that high LGR5 expression was an independent favorable prognostic factor (p = 0.0397)., Conclusions: These findings suggest that LGR5 is a promising, novel prognostic marker., (© 2024. The Author(s).)

Background: Mutual learning and shared decision-making are key elements of Participatory Action Research (PAR), highlighting the important role of the facilitator to support this. This study aims to illustrate how a facilitator can contribute to successful PAR sessions based on the reflection of three PAR projects., Methods: Participatory sessions took place with adolescents for 3-4 school years. After each session (n = 252 sessions across three projects), facilitators filled in a reflection form that assessed the group process and their facilitating role. Facilitators independently coded a selection of 135 reflection forms partly deductive and partly inductive based on core PAR principles derived from a pragmatic literature search., Results: A well-prepared session - for example, including active and creative participatory methods and a clearly stated goal - contributed to efficiency and the necessary flexibility. Making agreements, making sure everyone is heard and taking 'fun-time' appeared important for creating and maintaining a safe, functional and positive atmosphere. Finally, facilitators needed to encourage co-researchers to take the lead and adapt to the group dynamics, to ensure ownership and shared decision-making., Conclusion: In-depth qualitative analyses of a standardized reflection form used in three different PAR projects resulted in various lessons to support facilitators in collaborating with co-researchers in PAR projects., (© 2024. The Author(s).)

Background: We aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course., Methods: Serum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment., Results: Serum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients (n = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group., Conclusions: Vitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course., (© 2024. The Author(s).)

Background: Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent-offspring trios and proband only analysis., Methods: We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation., Results: Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications., Conclusion: CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities., (© 2024. The Author(s).)

Introduction: It is unclear how dietary intake changes after sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment is started in patients with type 2 diabetes., Methods: We performed a non-controlled, open-label study that enrolled 51 patients with type 2 diabetes. The patients were newly administered empagliflozin, and their dietary habits were examined using a self-administered diet history questionnaire at the beginning of the study and after 24 weeks. We investigated the association of changes in HbA1c and body weight with changes in energy, nutrient, and food group intakes., Results: At 24 weeks after the start of the study, HbA1c improved significantly and body weight decreased. In the food group, only the intake of confectionery increased, and there were no significant differences in the association between changes in HbA1c and body weight and changes in energy, nutrient, and food group intakes after 24 weeks. However, a significant negative correlation was found between change in HbA1c after 4 weeks and change in energy intake after 24 weeks, and principal component analysis showed an association between change in HbA1c levels after 4 weeks and change in energy intake and some food group intakes including confectionery after 24 weeks., Conclusion: In this study, after 24 weeks of treatment with empagliflozin, only intake of confectionery increased. Early assessment by dietitians after initiation of SGLT2i treatment might be important because our data suggested that the reduction in blood glucose levels after the start of empagliflozin was associated with a subsequent increase in energy intake., Trial Registration: University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on September 5, 2016 (registration ID, UMIN000002309|| http://www.umin.ac.jp/ctr/ )., (© 2024. The Author(s).)

Background: Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose level. Some GK activators (GKAs) disrupt GK-GKRP interaction which increases hepatic cytoplasmic GK level. Excess hepatic GK activity may exceed the capacity of glycogen synthesis with excess triglyceride formation. It remains uncertain whether hypertriglyceridemia associated with some GKAs in previous clinical trials was due to direct GK activation or impaired GK-GKRP interaction., Methods: Using publicly available genome-wide association study summary statistics, we selected independent genetic variants of GCKR and GCK associated with fasting plasma glucose (FPG) as instrumental variables, to mimic the effects of impaired GK-GKRP interaction and direct GK activation, respectively. We applied two-sample Mendelian Randomization (MR) framework to assess their causal associations with lipid-related traits, risks of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular diseases. We verified these findings in one-sample MR analysis using individual-level statistics from the Hong Kong Diabetes Register (HKDR)., Results: Genetically-proxied impaired GK-GKRP interaction increased plasma triglycerides, low-density lipoprotein cholesterol and apolipoprotein B levels with increased odds ratio (OR) of 14.6 (95% CI 4.57-46.4) per 1 mmol/L lower FPG for MASLD and OR of 2.92 (95% CI 1.78-4.81) for coronary artery disease (CAD). Genetically-proxied GK activation was associated with decreased risk of CAD (OR 0.69, 95% CI 0.54-0.88) and not with dyslipidemia. One-sample MR validation in HKDR showed consistent results., Conclusions: Impaired GK-GKRP interaction, rather than direct GK activation, may worsen lipid profiles and increase risks of MASLD and CAD. Development of future GKAs should avoid interfering with GK-GKRP interaction., (© 2024. The Author(s).)

Background: Sarcoidosis is a systemic disease that can affect multiple organs. While pulmonary sarcoidosis is most commonly observed, renal sarcoidosis occurs less frequently. We herein report a case of sarcoidosis with an exceptionally rare distribution including renal lesions., Case Presentation: A 51-year-old Japanese female was referred because of bilateral parotid swelling and renal dysfunction. Computed tomography scan showed the swelling of bilateral kidneys, parotid glands, and uterus. Ga scintigraphy also showed remarkable accumulation in these organs. Renal biopsy and cytological evaluations of parotid gland and uterus were performed and she was diagnosed as sarcoidosis of these organs. Treatment was initiated with prednisolone 40 mg/day and then renal dysfunction subsequently improved. In addition, the swelling of parotid glands and uterus improved and Ga accumulation in each organ had disappeared., Conclusion: This is a first case of renal sarcoidosis complicated by parotid glands and uterus lesions. Pathological findings and the reactivity observed in Ga scintigraphy indicated the presence of lesions in these organs., (© 2024. The Author(s).)

Background: In the context of persistent wars and conflicts worldwide, the impact of acute, excessive and constant exposure to media coverage of such events on mental health outcomes becomes a serious problem for public health, and requires therefore urgent investigation to inform an effective prevention and management response. The objective of the present study was to test the hypothesis that war-related media exposure is directly and indirectly associated with insomnia through depression and perceived stress among adults from the general population of different Arab countries., Methods: A cross-sectional study was carried-out two weeks after the beginning of Israel-Gaza war on the 7th of October 2023. An anonymous online survey and a snowball sampling method were adopted to collect data. A sample of 2635 general population adults (mean age of 23.98 ± 7.55 years, 73.1% females) took part of this study., Results: The results of the mediation analysis showed that, after adjusting over potential confounders, depression and perceived stress fully mediated the association between war media exposure and insomnia; higher war media exposure was significantly associated with higher depression (Beta = 0.13; p < .001) and perceived stress (Beta = 0.07; p < .001), whereas higher depression (Beta = 0.43; p < .001) and perceived stress (Beta = 0.31; p < .001) were significantly associated with higher insomnia. It is of note that war media exposure was not significantly and directly associated with insomnia (Beta = - 0.01; p = .178 and Beta = 0.02; p = .098 respectively)., Conclusion: The present study is the first to provide evidence that more time spent viewing the horrors of war is significantly associated with insomnia. In addition, symptoms of stress and depression were present as early as two weeks following the beginning of the war, and played a significant role in mediating the association between war media coverage and insomnia. These findings suggest that timely screening for, and management of depression and stress symptoms in clinical and preventive programs might be beneficial for community adults who have been heavily and indirectly exposed to war through media, and present with insomnia., (© 2024. The Author(s).)

Background: Tuberculosis (TB) represents a major global health challenge. Drug resistance in Mycobacterium tuberculosis (MTB) poses a substantial obstacle to effective TB treatment. Identifying genomic mutations in MTB isolates holds promise for unraveling the underlying mechanisms of drug resistance in this bacterium., Methods: In this study, we investigated the roles of single nucleotide variants (SNVs) in MTB isolates resistant to four antibiotics (moxifloxacin, ofloxacin, amikacin, and capreomycin) through whole-genome analysis. We identified the drug-resistance-associated SNVs by comparing the genomes of MTB isolates with reference genomes using the MuMmer4 tool., Results: We observed a strikingly high proportion (94.2%) of MTB isolates resistant to ofloxacin, underscoring the current prevalence of drug resistance in MTB. An average of 3529 SNVs were detected in a single ofloxacin-resistant isolate, indicating a mutation rate of approximately 0.08% under the selective pressure of ofloxacin exposure. We identified a set of 60 SNVs associated with extensively drug-resistant tuberculosis (XDR-TB), among which 42 SNVs were non-synonymous mutations located in the coding regions of nine key genes (ctpI, desA3, mce1R, moeB1, ndhA, PE&#95;PGRS4, PPE18, rpsA, secF). Protein structure modeling revealed that SNVs of three genes (PE&#95;PGRS4, desA3, secF) are close to the critical catalytic active sites in the three-dimensional structure of the coding proteins., Conclusion: This comprehensive study elucidates novel resistance mechanisms in MTB against antibiotics, paving the way for future design and development of anti-tuberculosis drugs., (© 2024. The Author(s).)

Background: As co-design and community-based participatory research gain traction in health and disability, the challenges and benefits of collaboratively conducting research need to be considered. Current literature supports using co-design to improve service quality and create more satisfactory services. However, while the 'why' of using co-design is well understood, there is limited literature on 'how' to co-design. We aimed to describe the application of co-design from start to finish within a specific case study and to reflect on the challenges and benefits created by specific process design choices., Methods: A telepractice re-design project has been a case study example of co-design. The co-design was co-facilitated by an embedded researcher and a peer researcher with lived experience of disability. Embedded in a Western Australian disability organisation, the co-design process included five workshops and a reflection session with a team of 10 lived experience and staff participants (referred to as co-designers) to produce a prototype telepractice model for testing., Results: The findings are divided into two components. The first describes the process design choices made throughout the co-design implementation case study. This is followed by a reflection on the benefits and challenges resulting from specific process design choices. The reflective process describes the co-designers' perspective and the researcher's and organisational experiences. Reflections of the co-designers include balancing idealism and realism, the value of small groups, ensuring accessibility and choice, and learning new skills and gaining new insights. The organisational and research-focused reflections included challenges between time for building relationships and the schedules of academic and organisational decision-making, the messiness of co-design juxtaposed with the processes of ethics applications, and the need for inclusive dissemination of findings., Conclusions: The authors advocate that co-design is a useful and outcome-generating methodology that proactively enables the inclusion of people with disability and service providers through community-based participatory research and action. Through our experiences, we recommend community-based participatory research, specifically co-design, to generate creative thinking and service design., (© 2024. The Author(s).)

Background: Healthcare staff deliver patient care in emotionally charged settings and experience a wide range of emotions as part of their work. These emotions and emotional contexts can impact the quality and safety of care. Despite the growing acknowledgement of the important role of emotion, we know very little about what triggers emotion within healthcare environments or the impact this has on patient safety., Objective: To systematically review studies to explore the workplace triggers of emotions within the healthcare environment, the emotions experienced in response to these triggers, and the impact of triggers and emotions on patient safety., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, four electronic databases were searched (MEDLINE, PsychInfo, Scopus, and CINAHL) to identify relevant literature. Studies were then selected and data synthesized in two stages. A quality assessment of the included studies at stage 2 was undertaken., Results: In stage 1, 90 studies were included from which seven categories of triggers of emotions in the healthcare work environment were identified, namely: patient and family factors, patient safety events and their repercussions, workplace toxicity, traumatic events, work overload, team working and lack of supervisory support. Specific emotions experienced in response to these triggers (e.g., frustration, guilt, anxiety) were then categorised into four types: immediate, feeling states, reflective, and longer-term emotional sequelae. In stage 2, 13 studies that explored the impact of triggers or emotions on patient safety processes/outcomes were included., Conclusion: The various triggers of emotion and the types of emotion experienced that have been identified in this review can be used as a framework for further work examining the role of emotion in patient safety. The findings from this review suggest that certain types of emotions (including fear, anger, and guilt) were more frequently experienced in response to particular categories of triggers and that healthcare staff's experiences of negative emotions can have negative effects on patient care, and ultimately, patient safety. This provides a basis for developing and tailoring strategies, interventions, and support mechanisms for dealing with and regulating emotions in the healthcare work environment., (© 2024. The Author(s).)

Background: Various factors can cause vascular endothelial damage during cardiovascular surgery (CVS) with cardiopulmonary bypass (CPB), which has been suggested to be associated with postoperative complications. However, few studies have specifically investigated the relationship between the degree of vascular endothelial damage and postoperative acute kidney injury (pAKI). The objectives of this study were to measure perioperative serum syndecan-1 concentrations in patients who underwent CVS with CPB, evaluate their trends, and determine their association with pAKI., Methods: This was a descriptive and case‒control study conducted at the National University Hospital. Adult patients who underwent CVS with CPB at a national university hospital between March 15, 2016, and August 31, 2020, were included. Patients who were undergoing preoperative dialysis, had preoperative serum creatinine concentrations greater than 2.0 mg dl -1 , who were undergoing surgery involving the descending aorta were excluded. The perioperative serum syndecan-1 concentration was measured, and its association with pAKI was investigated., Results: Fifty-two patients were included. pAKI occurred in 18 (34.6%) of those patients. The serum syndecan-1 concentration increased after CPB initiation and exhibited bimodal peak values. The serum syndecan-1 concentration at all time points was significantly elevated compared to that after the induction of anesthesia. The serum syndecan-1 concentration at 30 min after weaning from CPB and on postoperative day 1 was associated with the occurrence of pAKI (OR = 1.10 [1.01 to 1.21], P = 0.03]; OR = 1.16 [1.01 to 1.34], P = 0.04]; and the cutoff values of the serum syndecan-1 concentration that resulted in pAKI were 101.0 ng ml -1 (sensitivity = 0.71, specificity = 0.62, area under the curve (AUC) = 0.67 (0.51 to 0.83)) and 57.1 ng ml -1 (sensitivity = 0.82, specificity = 0.56, AUC = 0.71 (0.57 to 0.86)). Multivariate logistic regression analysis revealed that the serum syndecan-1 concentration on postoperative day 1 was associated with the occurrence of pAKI (OR = 1.02 [1.00 to 1.03]; P = 0.03)., Conclusion: The serum syndecan-1 concentration at all time points was significantly greater than that after the induction of anesthesia. The serum syndecan-1 concentration on postoperative day 1 was significantly associated with the occurrence of pAKI., Trial Registration: This study is not a clinical trial and is not registered with the registry., (© 2024. The Author(s).)

Background: Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks., Methods: In this study, we conducted an in-depth genomic analysis on a large-scale collection of 328 multidrug-resistant (MDR) K. pneumoniae strains recovered from 239 patients from a single major hospital in the western coastal city of Jeddah in Saudi Arabia from 2014 through 2022. We employed a broad range of phylogenetic and phylodynamic methods to understand the evolution of the predominant clones on epidemiological time scales, virulence and resistance determinants, and their dynamics. We also integrated the genomic data with detailed electronic health record (EHR) data for the patients to understand the clinical implications of the resistance and virulence of different strains., Results: We discovered a diverse population underlying the infections, with most strains belonging to Clonal Complex 14 (CC14) exhibiting dominance. Specifically, we observed the emergence and continuous expansion of strains belonging to the dominant ST2096 in the CC14 clade across hospital wards in recent years. These strains acquired resistance mutations against colistin and extended spectrum β-lactamase (ESBL) and carbapenemase genes, namely bla OXA-48 and bla OXA-232 , located on three distinct plasmids, on epidemiological time scales. Strains of ST2096 exhibited a high virulence level with the presence of the siderophore aerobactin (iuc) locus situated on the same mosaic plasmid as the ESBL gene. Integration of ST2096 with EHR data confirmed the significant link between colonization by ST2096 and the diagnosis of sepsis and elevated in-hospital mortality (p-value < 0.05)., Conclusions: Overall, these results demonstrate the clinical significance of ST2096 clones and illustrate the rapid evolution of an emerging hypervirulent and MDR K. pneumoniae in a clinical setting., (© 2024. The Author(s).)

Background: We aimed to reveal the effect of abatacept (ABT) on atherosclerosis in rheumatoid arthritis (RA) patients, 3-year efficacy for arthritis, and safety in a population of older vs. younger patients., Methods: In this open-label, prospective, observational study, patients were stratified into four groups: younger (20-64 years old) and older (≥ 65 years) patients taking ABT (AY and AO) and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (CY and CO). Primary endpoints were change from baseline in mean intima-media thickness (IMT) of the common carotid artery, IMT max (bulbus, bifurcation, and internal and common carotid artery), and plaque score at Week 156. Disease activity, retention rate, and adverse effects were also evaluated., Results: The ABT group (AY + AO) tended to have smaller increases in mean IMT, max IMT, and plaque score than the csDMARD group (CY + CO) at Week 156, although the differences between groups were not statistically significant. Multivariate analysis showed significantly lower increases in plaque score with ABT than with csDMARDs, only when considering disease activity at 156 weeks (p = 0.0303). Proportions of patients with good or good/moderate European League Against Rheumatism response were higher in the ABT group, without significant difference between older and younger patients. No significant differences were observed in ABT retention rates between older and younger patients. Serious adverse effects, especially infection, tended to be more frequent with ABT than with csDMARDs, although no significant differences were found., Conclusions: ABT may decelerate atherosclerosis progression and may be useful for patients with high risk of cardiovascular disease, such as older patients., Trial Registration Number: UMIN000014913., (© 2024. The Author(s).)

Background: The activity level of alkaline phosphatase, a zinc-requiring enzyme in the serum, is used to indicate zinc nutritional status; however, it does not correlate with serum zinc levels or subjective symptoms of taste disorder in many cases. Hence, this study focused on the total activity of alkaline phosphatase, a zinc-requiring enzyme. The total alkaline phosphatasa activity level in the saliva was measured before and after zinc supplementation, and the results were compared with serum zinc levels., Case Presentation: This study included patients with hypozincemia, specifically a patient with zinc-deficient taste disorder (patient 1: a 69-year-old Japanese woman) and a patient with glossodynia with zinc deficiency (patient 2: an 82-year-old Japanese woman). Saliva samples were collected, and blood tests were performed before and after zinc supplementation. Subjective symptoms and serum zinc levels were simultaneously evaluated. Zinc supplementation was performed using zinc acetate hydrate or Polaprezinc., Conclusions: Total alkaline phosphatase activity levels were found to be associated with serum zinc levels and subjective symptoms. A further study with a higher number of patients is necessary to confirm whether total alkaline phosphatase activity levels more accurately reflect the amounts of zinc in the body than serum zinc levels., (© 2024. The Author(s).)

Background: Hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH) was considered rare but is increasing with prolonged prognosis. Its impact on the overall prognosis of AIH is unknown, and treatment has not been established., Aim: To investigate the risk factors and prognosis of HCC in patients with AIH and identify appropriate management strategies., Methods: We studied patients with AIH including background liver disease, sex, age, complications, treatment, response to treatment, liver fibrosis, prognosis, and treatment., Results: In 131 patients, deaths due to liver failure were more common early after the onset of AIH; however, deaths due to HCC increased gradually. HCC was observed in 12 patients (median age, 70 years; male/female, 4/8; cirrhosis at onset, 11; median time to carcinogenesis, 7 years). Cirrhosis at diagnosis was identified as a risk factor for carcinogenesis in the multivariate analysis (odds ratio, 41.36; p < 0.0001) and cumulative cancer rates were high. Multidisciplinary therapy other than immune checkpoint inhibitors was administered as treatment for HCC. Two of the three patients who used molecular-targeted drugs discontinued the treatment because of adverse events., Conclusion: HCC is an important cause of death in patients with AIH. Currently available drug therapies are limited and early detection is desirable., Trial Registration: This trial was retrospectively registered in the Ethics Committee of Kagawa University School of Medicine under the identifier 2019 - 238, registered on 4 Feb 2020., (© 2024. The Author(s).)

Background: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements., Case Report: We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases. Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole + lapatinib, trastuzumab emtansine, and lapatinib + capecitabine., Conclusions: We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes., (© 2024. The Author(s).)

Background: IgG4, which plays a pivotal role in the progression of phenotypically diverse tumors, serves as a prognostic marker because of its influence on cancer immunity. Nevertheless, the functions of IgG4 in tongue squamous cell carcinoma (TSCC) remained to be identified., Methods: To evaluate the significance of IgG4 expression in TSCC, we performed immunohistochemical analysis of patients with TSCC (n = 50) to evaluate the correlation of IgG4 expression with patients' clinicopathological features and prognoses., Results: Higher IgG4 expression detected in TSCC tissues was associated with the less advanced mode of invasion (Yamamoto-Kohama [YK] 1-3) (P = 0.031) and with well-differentiated TSCC (P = 0.077). Kaplan-Meier analyses revealed that the higher IgG4 expression group exhibited better prognosis indicated by overall survival (OS) (P = 0.04) and recurrence-free survival (RFS) (P = 0.016). Univariate analysis of OS indicated that IgG4 expression was associated with longer OS (P = 0.061), and multivariate analysis of RFS revealed that IgG4 expression served as an independent prognostic factor for longer RFS (P = 0.005)., Conclusion: These results indicate that relatively higher IgG4 levels serve as a favorable prognostic factor for TSCC., (© 2024. The Author(s).)