Duration Of Administration Research Articles

Effect of quercetin on oxidative stress in 3T3-L1 mature and hypertrophic cells

Abstract Purpose: The process of excessive or abnormal accumulation of fat in the body is called obesity, and its prevalence is increasing globally. The imbalance between antioxidants and free radicals, or oxidative stress, can be caused by or result from obesity. Flavonoids with antioxidant potential may help lower the increased oxidative stress associated with obesity. This study aimed to determine how quercetin affected oxidative stress in hypertrophied and mature 3T3-L1 adipocytes. Materials and methods: After differentiating, 3T3-L1 adipocytes were treated with insulin and a glucose-containing medium to become mature (10 days) and hypertrophic (18 days). The cells were subsequently incubated with 80 µM quercetin for 24 and 48 hours. ELISA was used to determine the levels of total antioxidant capacity/total oxidant capacity (TAS/TOS). Using Oil Red O staining, an accumulation of triglycerides in cells was examined. Results: It was shown that the quercetin molecule had a prooxidative effect on hypertrophic adipocytes but did not impact on oxidative stress in mature adipocytes. Conclusion: It is believed that the number and kind of fat cell will determine the appropriate dose and duration of administration for quercetin's antioxidant mechanism of action, which produces numerous beneficial effects.

Association of the modified Glasgow prognostic score and prognostic nutritional index with duration of oral anamorelin administration in patients with cancer cachexia: a retrospective cohort study.

The modified Glasgow Prognostic Score (mGPS) and Prognostic Nutritional Index (PNI) are indicators of nutritional status in cancer patients; however, the effects of baseline mGPS and PNI on the duration of administration of the ghrelin receptor agonist anamorelin, which is used to treat cachexia in patients with cancer, are unclear. This study aimed to clarify the association of mGPS and PNI with the duration of oral anamorelin administration for patients who did not have beneficial effects from anamorelin. The attending physician determined the duration of oral anamorelin administration based on discontinuation due to cancer progression, poor efficacy, adverse events, or death. The 12-week continuation rate of oral anamorelin was 30.4%. Univariate analysis revealed that an Eastern Cooperative Oncology Group performance status (ECOG-PS) of ≥2 (P<.001), concurrent chemotherapy (P=.002), albumin level (P=.005), C-reactive protein level (P=.013), and a mGPS of 2 (P=.014) were statistically significant predictors of the 12-week continuation rate of oral anamorelin. In the multivariate analysis, a mGPS of 2 remained a significant risk factor, and the ECOG-PS and concurrent chemotherapy had no effect on the association between the mGPS and 12-week continuation rate of oral anamorelin. Patients with a mGPS of 2, compared with mGPS of 0 or 1, are less likely to maintain oral anamorelin therapy, regardless of the ECOG-PS or concurrent chemotherapy. Therefore, it is necessary to consider initiating anamorelin administration at mGPS 0 or 1.

Agony of Choice: Caudal Block versus Ilioinguinal/Iliohypogastric Nerve Block in Unilateral Orchidopexy.

Objective: This prospective study aimed to compare the efficacy of caudal block (CB) and ilioinguinal/iliohypogastric nerve block (IINB) for providing additional analgesia during unilateral orchidopexy. Methods: Seventy-one boys aged <48 months, classified as ASA I/II, were assigned into CB (n = 37) and IINB (n = 34) groups. Outcome measures included intra- and postoperative analgesic requirements, pain scores, and administration duration. Additional intraoperative analgesia was administered for a 10% increase in heart rate, while postoperative pain was assessed using the Children's and Infants Postoperative Pain Scale (CHIPPS), with scores >4 prompting supplementary analgesia. Monitoring was extended for 24 h post-surgery. Results: CB significantly reduced the need for intraoperative (p < 0.001) and early postoperative (p = 0.008) analgesia compared to IINB. However, the CB group exhibited a slightly higher but non-significant analgesic requirement on the ward. No clinically relevant side effects were observed in either group. Conclusions: Both CB and IINB are effective and safe methods for providing regional analgesia during orchidopexy. CB demonstrates superior efficacy intraoperatively and in the early postoperative period, while IINB may offer advantages in the later recovery phase. However, additional analgesia is often required for orchidopexy, especially in outpatient settings.

Factors associated with feeding behavior in the early neonatal period focusing on early skin-to-skin contact and epidural analgesia: A prospective observational study at a single hospital in Japan

BackgroundThe feeding behavior of newborns is influenced by the conditions of both the mother and newborn before and after birth. AimsThis study aimed to investigate the factors associated with newborn feeding behavior, focusing on skin-to-skin contact (SSC) as a promoting factor and epidural analgesia as an inhibiting factor, using the Japanese version of the Infant Breastfeeding Assessment Tool (IBFAT). Study DesignProspective observational study conducted in Japan. ParticipantsA total of 176 pairs of healthy mothers and their healthy full-term newborns. Outcome MeasuresThe primary outcome was newborn feeding behaviors measured using the Japanese version of IBFAT within about one day of birth. Stepwise multiple regression analysis was performed to explore the relationship between IBFAT scores and variables that might influence newborn feeding behavior. ResultsMultiple regression analysis revealed that lower IBFAT scores were associated with a higher dose of epidural fentanyl (β = −0.40), and higher IBFAT scores were associated with a longer duration of SSC (β = 0.26), even after adjusting for gestational weeks and Apgar scores. The dose and duration of synthetic oxytocin administration were not associated with IBFAT scores in the multivariate analysis. ConclusionsOur study showed a dose-dependent relationship between fentanyl and SSC, suggesting that consistently implementing SSC for the maximum duration possible may enhance newborn feeding behaviors, which are reduced by fentanyl administration.

Revision Surgery for Shoulder Infection after Arthroscopic Rotator Cuff Repair: Functional Outcomes and Eradication Rate-A Systematic Review.

The outcomes after arthroscopic rotator cuff repair (RCR) have been reported to be successful. The incidence of deep infections (defined as an infection involving any part of the anatomy other than the skin and subcutaneous tissue) after surgery ranges between 0.03% and 3.4%. This systematic review aims to investigate the outcomes of revision surgery for infection following arthroscopic RCR. Clinical outcomes and eradication rates among patients treated with different surgical and antibiotic therapies are analyzed. A total of five studies were eligible for systematic review. A total of 146 patients were treated and evaluated, of whom 71 (48%) and 75 (52%) underwent arthroscopic and open surgery to manage the infection, respectively. The most common causative bacterium was Cutibacterium acnes (50.4%). Two studies reported the pre-and postoperative ASES score and Constant-Murley score (CMS), and a statistically significant improvement was found after surgery (p < 0.001 for both). Eradication was observed in a total of 138 patients (94.5%); no difference was found between arthroscopic and open revision surgery (92.8% and 96%, respectively, p = 0.90). The frequency-weighted mean duration of the intravenous antibiotic therapy was 6.6 ± 5.4 days, while the overall mean duration of antibiotic therapy, considering intravenous and oral administration, was 43.5 ± 40 days. Patients with infection following arthroscopic RCR undergoing revision surgery experienced a high rate of eradication. A significant improvement in shoulder functionality and less residual pain can be expected.

Norepinephrine weaning guided by the Hypotension Prediction Index in vasoplegic shock after cardiac surgery: protocol for a single-centre, open-label randomised controlled trial – the NORAHPI study

IntroductionNorepinephrine (NE) is the first-line recommended vasopressor for restoring mean arterial pressure (MAP) in vasoplegic syndrome (vs) following cardiac surgery with cardiopulmonary bypass. However, solely focusing on target MAP values...

Ruxolitinib for the treatment of acute graft-versus-host disease: a retrospective analysis

Steroid-refractory acute graft-versus-host disease (aGvHD) is a serious complication after allogeneic hematopoietic stem cell transplantation, associated with significant mortality. Ruxolitinib was the first drug approved for aGvHD, based on results of the REACH2 trial; however, real-world data are limited. We retrospectively analyzed the safety and efficacy of ruxolitinib for treatment of aGvHD at our center from March 2016 to August 2022 and assessed biomarkers of risk. We identified 49 patients receiving ruxolitinib as second- (33/49), third- (11/49), fourth- (3/49), or fifth-line (2/49) treatment. Ruxolitinib was started on median day 11 (range, 7–21) after aGvHD onset; median duration of administration was 37 days (range, 20–86), with 10 patients continuing treatment at last follow-up. Median follow-up period was 501 days (range, 95–905). In the primary analysis at the 1-month assessment, overall response rate was 65%, and failure-free survival was 78%. Infectious complications ≥ CTCAE Grade III were observed in 10/49 patients within 1-month followup. Patients responding to ruxolitinib therapy required fewer steroids and exhibited lower levels of the serum biomarkers regenerating islet-derived protein 3-alpha, suppression of tumorigenicity 2, and the Mount Sinai Acute GVHD International Consortium algorithm probability. A univariate regression model revealed steroid-dependent aGvHD as a significant predictor of better response to ruxolitinib. Within 6-months follow-up, four patients experienced recurrence of underlying malignancy, and eight died due to treatment-related mortality. Overall, ruxolitinib was welltolerated and showed response in heavily pretreated patients, with results comparable to those of the REACH2 trial. Biomarkers may be useful predictors of response to ruxolitinib.

The Role of Omega 3 Fatty Acids on Muscle Mass: A Literature Review

Omega 3 fatty acids are known to have many benefits for human health, such as regulating lipid metabolism, treating hyperlipidemia, having anti-inflammatory function, increasing brain function and maintaining the body's immune system. Nowadays, among individuals who like to exercise, especially in the field of sports nutrition, omega 3 fatty acids are starting to become popular in their function of maintaining and increasing muscle mass because of their benefits in increasing muscle protein synthesis, reducing muscle damage (exercise-induced muscle damage) after physical exercise or during recovery after exercise so that it can maintain and increase muscle mass. This literature review deepens the benefits of omega 3 fatty acids which can potentially maintain or increase muscle mass. This literature review will discuss the mechanism by which omega 3 fatty acids influence muscle mass through cellular signaling pathways related to muscle protein synthesis which has an impact on a person's muscle mass. This literature review also discusses research results in healthy individuals, the elderly and individuals with chronic ilness. Although several studies show the benefits of omega 3 fatty acids regarding their potential to maintain and increase muscle mass. However, several research results show an insignificant effect of omega 3 fatty acids on muscle mass, causing the benefits of omega 3 fatty acids on muscle mass to continue to be a topic that will continue to be researched, some of the causes may be due to the duration of administration, different doses of administration, different type of omega 3 fatty acids given.

Efficacy and safety of ruxolitinib in the treatment of chronic graft-versus-host disease: a retrospective analysis

Steroid-refractory chronic graft-versus-host disease (cGvHD) is associated with significant morbidity and mortality, with ruxolitinib being the first drug approved for its treatment. We retrospectively analyzed the safety and efficacy of ruxolitinib for treatment of cGvHD at our center between 07/2015 and 12/2022 and identified 48 patients receiving ruxolitinib as second (18/48) or advanced (30/48) treatment line. Ruxolitinib was started on median day 340 (range 119–595) after cGvHD onset; median duration of administration was 176 (range, 79–294) days with 16/48 patients continuing treatment at last follow-up. National Institutes of Health organ grading and the intensity of immunosuppression were assessed at the start of ruxolitinib treatment and repeated after 1, 3, 6, and 12 months. Response assessment was terminated at the start of any additional new immunosuppressant treatment. The median time of follow-up was 582 (range, 104–1161) days. At the primary analysis after six months on ruxolitinib treatment, the overall response rate was 33%, and failure-free survival was 58%. Infectious adverse events ≥ CTCAE grade III were observed in 10/48 patients. The response rate was not associated with the severity of cGvHD, number of previous treatment lines, or number of additional agents combined with ruxolitinib applying a univariate regression model. At the time of the 12-month follow-up, four patients experienced recurrence of the underlying malignancy and two patients had experienced non-relapse-related mortality. Overall, ruxolitinib was relatively well-tolerated and showed outcomes comparable to the REACH3 trial in a heavily pretreated patient population.

Men's perceptions and perceived acceptability of their female partner's use of self-administered intravaginal therapies for treatment of cervical precancer in Kenya.

Cervical cancer continues to be a major health issue in low- and middle-income countries (LMICs). Despite increasing access to screening, access to precancer treatment remains a significant challenge in LMICs, highlighting a need for innovative, accessible and resource-appropriate treatment approaches, including self-administered therapies. A cross-sectional mixed-methods study was conducted among men aged 25-65 with a current female partner in Kisumu County, Kenya. Participants were sequentially recruited and surveyed to evaluate their understanding of human papillomavirus and cervical cancer, their views on screening and treatment and their attitudes toward self-administered therapies. Focus group discussions (FGDs) with a subset of the survey participants further explored their treatment preferences and perceptions. Two hundred fourteen men participated in the survey, and 39 men participated in FGDs. The median age was 39 years, and 51% had a primary school education or less. Most (96%) were in a committed relationship, and 74% earned $10 or less daily. There was strong support for self-administered topical therapies, with 98% willing to support their partners using such treatments if available. Additionally, most participants were open to supporting necessary abstinence or condom use, though 76% believed their partners might hesitate to request condom use. When given an option, most preferred their partner to self-administer such therapies at home compared to provider administration at a health facility, citing convenience, cost-effectiveness and privacy. Preferences varied between two potential therapies, 5-Fluorouracil and Artesunate, based on their administration frequency, duration and abstinence requirements. Qualitative findings largely supported the quantitative analysis. The study demonstrates strong support for self-administered topical therapies for cervical precancer among Kenyan men. Additional research on acceptability, feasibility and efficacy in different LMICs could pave the way for these therapies to help bridge current cervical precancer treatment gaps in these settings.

Evaluation of antimicrobial stewardship implementation in elective surgery in dr Cipto Mangunkusumo General Hospital using Gyssens Method

Introduction. Nowadays, surgical site infections (SSI) remain the most common complication of surgical procedures. In prevention, prophylactic antibiotics are the first option, which leads to the high use of antibiotics. However, antibiotic administration should be based on strategies such as stewardship. Thus, the study aimed to assess the situation using Gyssens' method. Method. A retrospective cohort study analyzed the antibiotic administration of most major elective surgeries, including thyroidectomy, mastectomy, and cholecystectomy, proceeded in Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, from January to July 2023. Indication, type, dosage, timing, interval, duration, and route of administration were the variables of interest. Results. Of 191 subjects who underwent the most common elective surgery procedures, 30 used combination antibiotics. Gyssens category 0 consists of 165 subjects (86.5%), and 11 subjects (5.8%) were classified as category IIA, indicating inappropriate dose (inadequate, insufficient). Inaccuracies were identified as mistimed administration (5.8%), less effective antibiotic selection (3.1%), incorrect dosage (2.6%), and inappropriate timing (2.1%). The association of Gyssens categories with SSIs showed a p-value of &gt; 0.05 with an odds ratio of 1, indicating that both appropriate and inappropriate antibiotics of the Gyssens category showed no impact on SSIs or non–SSIs. Conclusion. The adherence to antimicrobial stewardship in the most common elective surgery in the Department of Surgery, dr. Cipto Mangunkusumo General Hospital was 86.4 and subjected to improvement.

Fluid resuscitation with balanced electrolyte solutions results in faster resolution of diabetic ketoacidosis than with 0.9% saline in adults – A systematic review and meta‐analysis

AbstractFluid resuscitation during diabetic ketoacidosis (DKA) is most frequently performed with 0.9% saline despite its high chloride and sodium concentration. Balanced Electrolyte Solutions (BES) may prove a more physiological alternative, but convincing evidence is missing. We aimed to compare the efficacy of 0.9% saline to BES in DKA management. MEDLINE, Cochrane Library, and Embase databases were searched for relevant studies using predefined keywords (from inception to 27 November 2021). Relevant studies were those in which 0.9% saline (Saline‐group) was compared to BES (BES‐group) in adults admitted with DKA. Two reviewers independently extracted data and assessed the risk of bias. The primary outcome was time to DKA resolution (defined by each study individually), while the main secondary outcomes were changes in laboratory values, duration of insulin infusion, and mortality. We included seven randomized controlled trials and three observational studies with 1006 participants. The primary outcome was reported for 316 patients, and we found that BES resolves DKA faster than 0.9% saline with a mean difference (MD) of −5.36 [95% CI: −10.46, −0.26] hours. Post‐resuscitation chloride (MD: −4.26 [−6.97, −1.54] mmoL/L) and sodium (MD: −1.38 [−2.14, −0.62] mmoL/L) levels were significantly lower. In contrast, levels of post‐resuscitation bicarbonate (MD: 1.82 [0.75, 2.89] mmoL/L) were significantly elevated in the BES‐group compared to the Saline‐group. There was no statistically significant difference between the groups regarding the duration of parenteral insulin administration (MD: 0.16 [−3.03, 3.35] hours) or mortality (OR: −0.67 [0.12, 3.68]). Studies showed some concern or a high risk of bias, and the level of evidence for most outcomes was low. This meta‐analysis indicates that the use of BES resolves DKA faster than 0.9% saline. Therefore, DKA guidelines should consider BES instead of 0.9% saline as the first choice during fluid resuscitation.

Comparison between the Efficacy of Sacral Erector Spina Plane Block and Pudendal Block on Catheter-Related Bladder Discomfort: A Prospective Randomized Study.

Objective: Catheter-related bladder discomfort (CRBD) due to indwelling urinary catheterization in patients undergoing transurethral resection of the prostate (TURP) is difficult to tolerate and needs to be treated. This randomized prospective study aimed to compare the efficacy of sacral erector spinae plane block (SESPB) and pudendal nerve block (PNB) in reducing the incidence and score of CRBD. Methods: This study was conducted between November and December 2023. ASA I-III, fifty-four TURP patients were divided into two groups: Group 1 received SESPB (n = 27) and Group 2 received PNB (n = 27) under ultrasound guidance at the end of surgery. The incidence of CRBD, CRBD score, numerical rating scale (NRS) score, use of rescue analgesics, block performance time, first call for analgesics, patient satisfaction, and side effects were recorded for 24 h. Results: The incidence of CRBD was lowest at 33.3% and highest at 48.1% in Group 1 and lowest at 25.9% and highest at 48.1% in Group 2, with no significant difference between the groups at all measurement times. CRBD scores and NRS scores were low and similar between the two groups. Block performance times were 9 ± 1.7 min in SESPB and 20 ± 2.5 min in PNB, and there was a significant difference between the mean times (p < 0.001). Patient satisfaction was adequate and similar in both groups. Conclusions: SESPB demonstrated a similar decreasing effect to PNB on the incidence and scores of CRBD in the first 24 h following TURP operations. The duration of SESPB administration was shorter than PNB.

Real-World Experience with Isavuconazole in Allogeneic Stem Cell Transplantation in Spain

Invasive fungal infections (IFI) pose a significant complication after hematopoietic stem cell transplantation (HSCT). Isavuconazole (ISV) is a new generation azole with a favourable adverse effect and interaction profile approved for the treatment of invasive aspergillosis and mucormycosis. We analyzed the indications, effectiveness, adverse event profile and drug interaction management of ISV in the real-world setting in adults who received allogeneic-HSCT (allo-HSCT) within the Spanish Group of HSCT and Cell Therapy (GETH-TC). We conducted a multicenter retrospective study of all consecutive adult allo-HSCT recipients (≥18 years) who received ISV either for IFI treatment or prophylaxis, from December 2017 to August 2021, in 20 centers within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cell Therapy (GETH-TC). A total of 166 adult allografted patients who received ISV from 2017 to 2021 were included. Median age was 48 years with 43% females. In 81 (49%) patients, ISV was used for treatment of IFI, and in 85 (51%) for prophylaxis. Median duration of ISV administration for IFI treatment was 57 days (range 31-126) and 86 days (range 33-196) for prophylaxis. Most frequent indication for treatment was invasive aspergillosis (78%), followed by mucormycosis (6%). Therapeutic success (45%) was the most frequent reason for ISV withdrawal. In the prophylaxis group, the resolution of IFI risk factors was the most frequent reason for withdrawal (62%). Six (7%) breakthrough IFI were reported. The majority of patients (80%) presented pharmacologic interactions. Twenty-one patients (13%) reported adverse events related to ISV, mainly liver biochemistry abnormalities, which led to ISV withdrawal in 7 patients (4%). ISV was effective and well tolerated for IFI treatment and prophylaxis, with a manageable interaction profile.

Influence of humic substances on growth performance and blood serum parameters in fattening turkeys

The present study was conducted to evaluate the effect of humic substances on performance and selected blood biochemical parameters in turkeys. A total of twenty 6-week-old turkey hybrids (Big 6) were divided into two groups. The first group of turkeys was fed the basal diet without any supplementation of humic substances as a control group. The second group was fed the basal diet supplemented with 5 g of humic substances per kg of diet. The study lasted 35 days, until the 11th week of age of the turkeys. The addition of humic substances had no effect on the live body weight, body weight gain, feed intake, feed conversion ratio, or growth rate of turkeys. Similarly, the monitored blood biochemical parameters, except for the levels of P, Mg, and Na, were not significantly affected by the addition of humic substances. The addition of humic substances led to a significant decrease in the concentration of P (p˂0.05), Mg (p˂0.05), and Na (p˂0.01) in the blood serum of turkeys. It was concluded that the addition of humic substances may lead to a reduction of some mineral substances in the blood of animals, which may be due to their chelating effects. This may indicate a reduced availability of some biologically important minerals for the body, which could subsequently manifest itself in some health issues and a decrease in animal production. During the duration of our study, there were no signs of disturbance in the health of the animals. In view of the achieved results, further studies will be necessary to determine the appropriate concentration and duration of administration of the monitored preparation and to evaluate its influence on the availability of nutrients and feed conversion and its possible use as a safe non-antibiotic growth stimulator in turkey nutrition.

Clinical applications and perspectives of immune checkpoint inhibitors in oral squamous cell carcinoma

Abstract Immune checkpoint inhibitors (ICIs) promote antitumour immune responses by blocking inhibitory signals expressed by T cells and have significant clinical benefits in the treatment of oral squamous cell carcinoma (OSCC). With the advancement of immunotherapy, an increasing number of ICIs have been developed or are in clinical trial stages. However, drug resistance and immune-related adverse events (irAEs) associated with ICIs have limited the clinical application of immunotherapy in OSCC, and the optimal drug regimen for ICIs and the optimal duration of ICIs administration also deserves to be further discussed. New therapeutic regimens and drug delivery technologies are key to promoting the further development of ICIs. This article elucidates the mechanism of ICIs’ action and presents a review of their clinical applications and current development status in OSCC. Additionally, it summarizes the current challenges and outlines future research directions for ICIs therapy, with the aim of offering fresh insights to researchers.

Development of a Compartment Model to Study the Pharmacokinetics of Medical THC after Oral Administration

The therapeutic potential of delta9-tetrahydrocannabinol (THC), a primary cannabinoid in the cannabis plant, has led to its development into oral medical products for treating various conditions. However, THC, being a psychoactive substance, can lead to addiction if taken in inappropriate amounts. Thus, studying the pharmacokinetics of THC is crucial for understanding how the drug behaves in the body after administration. This study aims to develop a multi-compartmental model to investigate the pharmacokinetics of medical THC and its metabolites after oral administration. Using the law of mass action, the model was converted into ordinary differential equations (ODEs) to describe the rate of concentration changes of THC and its metabolites in each compartment. The nonstandard finite difference (NSFD) method was then applied to construct numerical solution schemes, which were implemented in MATLAB along with estimated pharmacokinetic rate constants. The results demonstrate that the simulation curves depicting the plasma concentration–time profiles of THC and 11-hydroxy-THC (THC-OH) closely resemble actual data samples, indicating the model’s accuracy. Moreover, the model predicts the pharmacokinetics of THC and its metabolites in various tissues. Consequently, this model serves as a valuable tool for enhancing our understanding of the pharmacokinetics of THC and its metabolites, guiding dosage adjustments, and determining administration durations for oral medical THC.

Clinicopathological characteristics of methotrexate-related lymphoproliferative disorder of the thyroid: A study of 11 patients

Methotrexate (MTX) is a well-known agent that can potentially cause lymphoproliferative disorder (LPD), known as MTX-related LPD (MTX-LPD). Only two cases of thyroid MTX-LPD have been reported to date. This study aimed to report 11 cases of MTX-LPDs arising in the thyroid gland and discuss their clinicopathological characteristics. Of the 747 patients with cytologically suspected lymphoma, 11 had received MTX. The mean age of the patients with MTX-LPD was 70.2 years (range: 51–82 years), and all were female. The duration of MTX administration ranged from 5 to 31 years (mean: 19.5 years). Nine patients (81.8 %) tested positive for anti-thyroglobulin antibody and/or anti-thyroid peroxidase antibody. In three patients, the tumor decreased in size or disappeared without surgery or chemotherapy after withdrawal of MTX therapy. Histologically, all eight nodules examined were B-cell lymphomas, and seven were mucosa-associated lymphoid tissue (MALT) lymphomas. Epstein-Barr virus-encoded small RNA in situ hybridization showed negative results for all six nodules examined. All five patients who were followed-up at our hospital exhibited progression-free survival for >3 years without chemotherapy. Six patients were transferred to other hospitals, and their follow-up details are unknown. MTX-LPDs occurring in the thyroid are characterized by a high female predominance, positivity for anti-thyroid autoantibodies, high prevalence of MALT lymphomas, negativity for Epstein-Barr virus, and good outcomes without chemotherapy. We recommend that patients with thyroid lymphoma should be checked for a history of MTX.

Prolonged prophylactic antibiotic use following megaprosthesis surgery may reduce periprosthetic infection

IntroductionMegaprostheses provide a reconstructive option for patients with bone loss after musculoskeletal tumor resection. However, the postoperative surgical site infection (SSI) risk is significant. This study aims to evaluate outcomes of extended postoperative antibiotic regimens in patients after megaprosthesis surgery and gather insight into strategies to minimize SSI. MethodsThis retrospective cohort study evaluated patients who underwent megaprosthesis surgery by a single surgeon at a single center from 2014 to 2022. Patient demographics, comorbidities, cancer treatment details, and antibiotic regimens were collected. Excluded were patients with less than 1 year of follow-up, active infection at time of surgery, non-healing wounds unrelated to SSI, and preoperative antibiotic regimens secondary to being immunocompromised. Measures of interest included the development of SSI within 1 year of surgery and development of antibiotic-related complications. ResultsIncluded were 49 patients, with a mean age of 61.2 ± 2.0 years and a mean BMI of 29.4 ± 7.0. The mean drain duration was 6.5 days (standard deviation [SD], 6.9 days), and the mean intravenous antibiotic administration duration was 6.4 days (SD, 6.9 days). The median time to drain removal was five days, and the median time for intravenous antibiotic cessation was five days. The mean total antibiotic administration duration (intravenous and oral) was 25.4 days (SD, 13.4 days). Only 1 patient in the included cohort (2.04 %) developed an SSI requiring operative intervention. No other patient within the cohort experienced an antibiotic-related complication. DiscussionThis study suggests that the site's current protocol for managing post-megaprosthesis antibiotic prophylaxis based on drain duration and incision healing status has resulted in a low rate of SSI and antibiotic-related complications. Further research is needed to validate these findings and gain additional insights into managing antibiotic prophylaxis after megaprosthesis surgery.

Geniposide dosage and administration time: Balancing therapeutic benefits and adverse reactions in liver disease treatment

Gardenia jasminoides Ellis, a staple in herbal medicine, has long been esteemed for its purported hepatoprotective properties. Its primary bioactive constituent, geniposide, has attracted considerable scientific interest owing to its multifaceted therapeutic benefits across various health conditions. However, recent investigations have unveiled potential adverse effects associated with its metabolite, genipin, particularly at higher doses and prolonged durations of administration, leading to hepatic injury. Determining the optimal dosage and duration of geniposide administration while elucidating its pharmacological and toxicological mechanisms is imperative for safe and effective clinical application.This study aimed to evaluate the safe dosage and administration duration of geniposide in mice and investigate its toxicological mechanisms within a comprehensive dosage-duration-efficacy/toxicity model. Four distinct mouse models were employed, including wild-type mice, cholestasis-induced mice, globally farnesoid X-activated receptor (FXR) knock out mice, and high-fat diet-induced (HFD) NAFLD mice. Various administration protocols, spanning one or four weeks and comprising two or three oral doses, were tailored to each model's requirements. Geniposide has positive effects on bile acid and lipid metabolism at doses below 220 mg/kg/day without causing liver injury in normal mice. However, in mice with NAFLD, this dosage is less effective in improving liver function, lipid profiles, and bile acid metabolism compared to lower doses. In cholestasis-induced mice, prolonged use of geniposide at 220 mg/kg/day worsened liver damage. Additionally, in NAFLD mice, this dosage of geniposide for four weeks led to intestinal pyroptosis and liver inflammation. These results highlight the lipid-lowering and bile acid regulatory effects of geniposide, but also warn of potential negative impacts on intestinal epithelial cells, particularly with higher doses and longer treatment durations. Therefore, achieving optimal therapeutic results requires a decrease in treatment duration as the dosage increases, in order to maintain a balanced approach to the use of geniposide in clinical settings.