Cumulative Dose Research Articles

Definitive treatment for primary urethral cancer: A single institution's experience with organ-preserving brachytherapy

BackgroundRadical urethectomy ± cystectomy has long represented the standard of care for rare primary urethral cancer (PUC). With our analysis, we want to demonstrate the efficacy and safety of brachytherapy (BT) of urethra for organ preservation. Materials and methodsWe analyzed treatment procedures and results of three patients with PUC, which have been treated in our department between 2011 - 2020 with brachytherapy. One male patient underwent brachytherapy with chemoradiotherapy after transurethral resection (TUR). Brachytherapy has been performed as high-dose-rate (HDR) boost with a cumulative dose of 8 Gy (9.3 Gy EQD2-α/β = 10Gy). The two further female patients have been treated with sole pulsed-dose-rate (PDR) brachytherapy with a total dose of 49.9 Gy (50.3 Gy EQD2-α/β = 10Gy) and 62.2 Gy (64.6 Gy EQD2-α/β = 10Gy). ResultsMedian follow-up was 103 months (41-153). No local recurrence occurred and all patients are still alive. For the male patient we documented Grade 3 cystitis. As late side effects the pre-existing Grade 2 incontinence worsened to Grade 3. Among female patients one developed Grade 3 vaginal synechiae. There was no Grade ≥4 toxicity. ConclusionBrachytherapy in PUC is a feasible and promising option with high local control rate and tolerable toxicity. It provides a good alternative to surgery for organ preservation in selected patients.

The real-world use and effectiveness of avacopan in routine practice for the treatment of ANCA vasculitis. First experiences in Spain.

ANCA-associated vasculitis (AAV) are chronic diseases with relapses that associate organic damage because of the disease and its treatment. Avacopan is a new treatment indicated for AAV. We present the first experiences with avacopan in Spain as part of an Early Access program. Patients with AAV who started avacopan between June 2022-September 2023 were included. For comparison, a historical cohort of patients diagnosed with AAV around the same time and treated without avacopan was also included. 29 patients treated with avacopan were analyzed. Twelve patients (41.4%) were male, median age was 56 years. Most of patients were ANCA MPO positive (21/29, 72.4%). The most frequently affected organ was the kidney (23/29, 79.31%), with a mean eGFR of 23.2 ml/minMedian follow-up was 456.8 ± 181.7 days with a remission rate of 86.2%. eGFR increased from 23.2 ± 11.2-38.38 ± 18.55 ml/min after 12 months of diagnosis.2 patients had Adverse Events related to avacopan as severe neutropenia and a gastrointestinal affectation , 13 infections were reported and 1 death.Patients treated with avacopan received a significantly lower cumulative dose of prednisone at 6 and 12 months (p-values of 0.02 and <0.01, respectively) compared with historical controls. The evolution of GFR at 1 year of follow-up and the incidence of relapse were similar in both groups. The combination of avacopan in clinical practice presents a good safety profile and provides added value by contributing to the control of AAV activity, increase GFR, and removal of steroids.

More is less: image enhancement technology reduces radiation exposure during anterior lumbar interbody fusion

BACKGROUND CONTEXTFluoroscopy and radiation exposure occur during anterior lumbar interbody fusion (ALIF). Image enhancement technology is available that can potentially reduce radiation exposure. PURPOSEThe purpose of this study is to evaluate radiation exposure and fluoroscopy times comparing standard fluoroscopy (FL) with a low dose image enhancement platform (LD). STUDY DESIGNRetrospective review of prospectively maintained database. PATIENT SAMPLEConsecutive patients undergoing ALIF with either standard fluoroscopy or low dose image enhancement technology. OUTCOME MEASURESRadiation dispersion and fluoroscopy times in ALIF patients with standard fluoroscopy and low dose image enhancement technology. METHODSA retrospective review of a prospective database on consecutive patients who have undergone ALIF, stratified into 2 groups: subjects with standard fluoroscopy (FL), and low dose fluoroscopy with image enhancement technology (LD). RESULTSA total of 487 ALIF patients were included (FL: 372 vs. LD: 115). LD patients were significantly older (66 vs. 60 years), with more deformity cases (28% vs. 12%), and less degenerative cases (71% vs. 87%), all p<.05; no differences in sex, BMI, or the number of levels operated on between groups. Fluoroscopy time (sec) was significantly higher in LD (51.4 vs. 45.5), with a statistically significant reduction in radiation (mGy) compared to FL (23.3 vs. 48.2), both p<.05. Furthermore, the results showed that radiation dispersion is increasingly reduced as fluoroscopy time increases in LD compared to FL (12%, 56%, and 65% reduction in radiation dispersion for fluoroscopy time <30 sec, between 30 to 60 sec, and >60 sec, respectively). CONCLUSIONSThe use of low dose fluoroscopy with image enhancement technology significantly reduces the cumulative dose of radiation during ALIF compared to standard dose fluoroscopy. Also, radiation dispersion increasingly decreases as fluoroscopy time increases using low dose image enhancement technology. Low dose image enhancement technology improves the safety profile of ALIF for patients and operating room staff.

Epidural Steroid Injections and Fracture Incidence Among Older Individuals with Radiculopathy.

Epidural steroid injections (ESIs) are a common and often effective treatment for radicular back pain. While oral glucocorticoids increase fracture incidence, little is known regarding fracture risk after ESI. This study investigated the incidence of fractures among individuals who received ESI and those who did not. We hypothesized that ESI exposure would be associated with an increased incidence of osteoporotic fracture and specifically vertebral fractures. Using 2005-2018 5% Medicare data, individuals with radicular pain who had ≥1 ESI and those who did not (non-ESI) were matched 1:10 by age, sex, and month of radicular pain diagnosis using exposure density sampling (EDS). Using a high-dimensional propensity score (HDPS) calculated based on the top 500 covariates across multiple data dimensions, ESI and non-ESI individuals were matched 1:1. Fractures were identified using validated ICD-9/10 diagnosis codes. Fracture incidence rate (IR) was calculated by group, and hazard ratios (HR) compared using Cox regression. 25 062 ESI patients and 221 735 non-ESI patients who met eligibility criteria were identified using EDS. Mean age was 76years (74% female). Among ESI-treated individuals, there were 2296 fractures, IR 49.1 (95% CI: 47.2-51.2) per 1000 person years. For non-ESI individuals, there were 11 917 fractures, IR 35.2 (95% CI: 34.5-35.8). Individuals who received ESI had a greater hazard of fracture at typical osteoporotic sites, HR 1.39 (95% CI 1.33-1.46) by EDS and 1.32 (1.12-1.54) by HDPS, and greater hazard of vertebral fracture, 1.54 (1.45-1.64) by EDS and 1.69 (1.38-2.07) by HDPS. Patients who received greater cumulative ESI doses (≥3 in 1year) had a higher risk of fractures within the first six months of follow-up. ESI exposure in older individuals is associated with an increased risk of fracture, suggesting there may be lasting detrimental skeletal effects of ESI. Further research into strategies to reduce fracture risk in this population is warranted.

Mitochondrial Dysfunction Plays a Relevant Role in Heart Toxicity Caused by MeHg.

The effects of methylmercury (MeHg) on exposed populations are a public health problem. In contrast to widely studied neurological damage, few cardiovascular changes have been described. Our group evaluated the cardiotoxicity of a cumulative dose of 70 mg.kg-1 fractioned over a 14-day exposure period in mice (MeHg70 group). The effects of MeHg on proteins relevant to cardiac mitochondrial function were also investigated. The results obtained showed a reduction in oxygen consumption in the two settings. In cardiac tissue samples in oxygraphy studies, this reduction was related to a lower efficiency of complexes II and V, which belong to the oxidative phosphorylation system. In vivo, mice in the MeHg70 group presented lower oxygen consumption and running tolerance, as shown by ergometric analyses. Cardiac stress was evident in the MeHg70 group, as indicated by a marked increase in the level of the mRNA encoding atrial natriuretic peptide. Electrocardiogram studies revealed a lower heart rate at rest in the animals from the MeHg70 group, as well as prolonged left ventricular depolarisation and repolarisation. Through echocardiographic analysis, reductions in the left ventricular ejection fraction and left ventricular wall thickness of approximately 10% and 20%, respectively, were detected. These results indicate that the oral intake of MeHg can decrease cardiac function and oxidative metabolism. This finding highlights the importance of monitoring MeHg levels in humans and animals in contaminated areas, as well as periodically carrying out cardiac function tests.

SYNCHRONIZE: Real-World Retrospective Safety Analysis of Patients Treated with OnabotulinumtoxinA for More than One Therapeutic Indication.

OnabotulinumtoxinA (onabotA) is approved in the US for 12 therapeutic indications. Real-world data on onabotA multi-indication use are limited, often leading to delayed or reduced treatment. This study provides real-world evidence on the safety of onabotA when treating multiple indications concomitantly. SYNCHRONIZE was a multicenter, retrospective, chart-review study evaluating onabotA's safety for adults treated for ≥2 therapeutic indications within a 3-month period. The primary outcome was treatment-emergent adverse events (TEAEs) within 6 months post-treatment. A total of 279 patients were included. The most common concomitant indications treated were cervical dystonia and chronic migraine (43.4%). The average 3-month cumulative dose for multiple indications was 282.2 U. The treatment interval for multiple indications was ≤24 h for most patients (62.4%). Overall, 28.7% of patients reported ≥1 TEAE with no apparent trends in TEAEs and dose interval or cumulative dose. Reported TEAEs included UTI (5.7%), neck pain (5.0%), and headache (4.3%). No patient had a lack of effect according to clinical objective measurements. SYNCHRONIZE described the real-world safety of onabotA for patients treated concomitantly for ≥2 indications within a 3-month period. TEAEs were generally consistent with the known safety profiles of individual indications. No new safety signals were identified).

Association between hydroxychloroquine intake and damage to the outer nuclear layer in eyes without manifest retinal toxicity

BackgroundHydroxychloroquine (HCQ) is widely used to treat various autoimmune diseases but carries a risk of retinal toxicity, particularly with prolonged use. Despite advancements, uncertainty persists regarding optimal screening methods. Recent advances in OCT have enabled early detection of retinal damage, with studies suggesting that thinning of specific retinal layers may be an early indicator of toxicity. However, there is a gap in research on outer nuclear layer (ONL) thinning in HCQ users without apparent retinal toxicity. This information is crucial for improving screening and identifying the ONL as a reliable biomarker for screening. Therefore, this study aimed to investigate the association between HCQ intake and ONL damage in eyes without manifest retinal toxicity.MethodsA case‒control study was conducted at the ophthalmology department of Eye and Ear Hospital International from July 2022 to June 2023. The study included 20 individuals on HCQ and 20 age-matched controls. The data were obtained through chart reviews, and participants underwent comprehensive ophthalmic assessments.ResultsA total of 80 eyes were analyzed. Patients on HCQ exhibited significantly thinner perifoveal, parafoveal, and overall ONL compared to controls (P < .001, P < .012, and P < .004, respectively). Similarly, this association was found in the nasal, inferior, and temporal quadrants of both the inner (region 3: P < .01, region 4: P < .001, and region 5: P < .03) and outer zones (region 7: P < .04, region 8: P < .001, region 9: P < .02), most pronounced in the inferior regions. The cumulative dose was weakly associated with decreased ONL thickness only in the nasal quadrant of the inner zone (region 3: P < .047). Correlation analysis of the initial and most recent OCT scans in the same individuals revealed a weak association with ONL thinning in the central zone (region 1: P < .0048).ConclusionThe thickness of the ONL can significantly decrease in patients taking HCQ, even in the absence of of manifest retinal toxicity. This study is the first to evaluate this association in eyes with negative screening and diagnostic tests for HCQ retinopathy. The findings suggest that ONL thickness could serve as an early diagnostic indicator for HCQ retinal toxicity.

Assessment of occupational dose during abdominal fluoroscopic-guided procedures in Thailand using nanoDot OSL dosimeters

Interventional radiology is one of the most widely used treatment options for abdominal abnormality. Due to new dose limitations, radiation is a hazard that needs to be considered when choosing the international treatment technique. The aim of this study was to measure the effective/equivalent doses and to investigate the associated factors correlating with the doses during Transarterial Chemoembolization (TACE) and Percutaneous Transhepatic Biliary Drainage (PTBD) for radiologists, technologists and nurses involved with the treatment. This prospective study reports occupational dose per procedure of 57 cases (TACE = 42, PTBD = 15) in a Thailand hospital spanning one year. All staff included in this study wore 30 nanoDot Optically Stimulated Luminescence Dosimeter for measuring doses at 7 bodily locations. The average dose area product and cumulative doses was 151.3 Gy·cm2, 1,185.1 mGy during TACE and 21.3 Gy·cm2, 212.2 mGy during PTBD. The radiation exposure of the radiologists was significantly higher than technologists and nurses (p-value < 0.05). The lead protection equipment was a dose-reducing factor which decreased the dose up to 93%. The present study also contributes to the establishment of an individual dose location report and identifies significant correlations between associated factors and dose values. The left hand (1.2 mSv) and the left eye (1.1 mSv) showed maximum doses during the PTBD procedure. The exceeded dose over the limitation was observed in the left eye. We concluded that the dose feedback was able to increase awareness of the occupation staff. So, dose monitoring, updating education and regular training could be applied simply and effectively to improve skills, while reducing the occupational dose.

Immunogenicity of Botulinum Toxin Type A in Different Clinical and Cosmetic Treatment, a Literature Review.

Botulinum toxin type A is widely utilized for both therapeutic and aesthetic purposes, yet concerns regarding its immunogenicity have raised issues related to treatment failure and adverse reactions. This review aims to evaluate the immunogenicity of commercially available botulinum toxin type A products across various clinical indications and identify the risk factors associated with antibody formation. A comprehensive search of electronic databases was conducted to find studies that investigated the immunogenicity of botulinum toxin type A in patients treated for different conditions. The studies were classified based on the Oxford Center for Evidence-Based Medicine's evidence hierarchy. The overall incidence of neutralizing antibody formation with botulinum toxin type A treatment is relatively low. However, it varies depending on the indication and is influenced by factors such as the frequency of injections and the cumulative dose. The total cumulative dose and the number of treatment cycles are critical factors in determining the risk of developing antibodies against botulinum toxin type A. This literature review highlights that the immunogenicity of botulinum toxin type A products differs across indications, with repeated injections posing a significant risk for the formation of neutralizing antibodies. The findings underscore the need for further research to better understand antibody formation mechanisms and to develop strategies that minimize their impact on treatment efficacy.

Real-world treatment patterns in patients with systemic lupus erythematosus: associations with comorbidities and damage

ObjectiveTo assess treatment patterns and the association between long-term glucocorticoid (GC) and hydroxychloroquine (HCQ) use and damage accrual in patients with systemic lupus erythematosus (SLE).MethodsA retrospective study including patients with...

α-Arbutin ameliorates UVA-induced photoaging through regulation of the SIRT3/PGC-1α pathway.

Owing to its tyrosinase inhibitory activity, α-arbutin has been added to several skin care products as a skin-lightening agent. However, the protective effect of α-arbutin against ultraviolet A (UVA)-induced photoaging has not been well investigated. The present study was designed to investigate the photoprotective effect and mechanism of α-arbutin against UVA-induced photoaging. In vitro experiments, HaCaT cells were treated with UVA at a dose of 3J/cm2 to evaluate the anti-photoaging effect of α-arbutin. α-Arbutin was found to exhibit a strong antioxidant effect by increasing glutathione (GSH) level and inhibiting reactive oxygen species (ROS) production. Meanwhile, α-arbutin markedly improved the expression of sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) proteins, initiating downstream signaling to increase mitochondrial membrane potential and mediate mitochondrial biogenesis, and improve mitochondrial structure significantly. In vivo analysis, the mice with shaved back hair were irradiated with a cumulative UVA dose of 10J/cm2 and a cumulative ultraviolet B (UVB) dose of 0.63J/cm2. The animal experiments demonstrated that α-arbutin increased the expression of SIRT3 and PGC-1α proteins in the back skin of mice, thereby reducing UV-induced skin damage. In conclusion, α-arbutin protects HaCaT cells and mice from UVA damage by regulating SIRT3/PGC-1α signaling pathway.

Predictive factors for treatment response in active thyroid eye disease

Introduction/objectiveActive moderate-to-severe thyroid eye disease (TED) is a major therapeutic challenge. Pulse therapy with intravenous glucocorticoids is the standard treatment, with variable response. Radioactive iodine therapy (RAI) was reported as a risk factor for onset or worsening of TED. We evaluated putative predictive factors for response to intravenous methylprednisolone in patients with active TED. MethodsData were collected for 64 consecutive patients (45 women) with active moderate-to-severe TED treated with a minimum cumulative dose of 4.5g methylprednisolone. Patients were classified as responders (R) or non-responders (NR) on Clinical Activity Score (CAS), and clinical features were compared between groups. ResultsSixty-two patients had Graves’ disease (GD), and 2 had Hashimoto's thyroiditis (HT). Median age at thyroid dysfunction diagnosis, TED manifestation and pulse therapy was 46, 48 and 51 years, respectively; 56.2% were euthyroid when TED manifested. Among them, 73.4% were responders. R and NR were comparable for gender, age, thyroid function, serum antibodies, disease duration, pre-treatment CAS, smoking, lipid profile, and adverse events. Forty-nine patients were treated with RAI for GD: 15 before the active phase of TED (before pulse therapy), 16 during, 17 after, and 1 both before and after pulse therapy. Response rate was higher in patients who received RAI during than after pulse therapy (P=0.032) and similar to those not treated with RAI at all (P=0,599). ConclusionPulse therapy was effective in the majority of patients. The only factor associated with response to pulse therapy was the timing of RAI, suggesting that it seems to be safe when used concomitantly with pulse therapy.

An Enhanced LPRAFF with Tri-State Inverter Embedded Non-Clock Gating via the CT-GWO Algorithm

Since a long time ago, it has been understood how radiation affects digital circuits, particularly those using the Complementary Metal Oxide Semiconductor (CMOS) model. Total Ionisation Dose (TID) and Single Event Effects (SEE) are the two most significant radiation effects. Depending on the gate input count, the complexity of the circuit will rise, which will worsen the radiation and raise the cumulative dose levels. The incremental dose level affects the circuit parameter failure, which affects how well the logic design functions. Many authors concentrate on minimising the effects of radiation while preventing function loss, but these extra efforts use excess energy. To improve the efficiency of the Low Power Radiation Aware (LPRA) circuit, this paper introduces optimisation concepts in a Flip Flop (FF) architecture named Chaos Theory-based Grey Wolf Optimised FF (CT-GWOFF). First, compute each component's radiation response using a physics-based modelling strategy. To minimise undesirable latches and disable the inverter chain when the input data remain constant, a tri-state inverter, incorporating a non-clocked gating mechanism, is provided. This prevents repeated transitions of delayed clock signals. Moreover, the proposed model is implemented in FFs for simulation purposes, making it more cognizant of radiation effects and power consumption. Using the HSPICE tool, the performance of the suggested circuit design is evaluated at the 16 nm CMOS Predictive Technology Model (PTM).

Clinical Features and Survival Analysis of Lupus Nephritis among Patients with Systemic Lupus Erythematosus: A Three-Decade-Long Retrospective Cohort Study.

Background/Objectives: Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). The aim of our retrospective cohort study was to compare the clinical characteristics, therapy, survival, causes of death, and prognostic factors of LN and non-LN lupus patients. Moreover, we compared a wide spectrum of clinical data of LN patients diagnosed before and since 2005 to determine any changes in disease course and outcomes. Methods: We assessed the clinical and laboratory data of 384 SLE patients, out of whom, 127 patients were diagnosed with LN between 1990 and 2020. Results: Based on our observations, discoid LE, subacute cutaneous LE, antiphospholipid syndrome, Sjögren's syndrome, and rheumatoid arthritis were more common in non-LN patients, while anemia and anti-RNP positivity were more frequent in LN patients. Development of LN did not affect survival rates; male sex and presence of APS were negative prognostic parameters in the non-LN group while achieving remission was a positive prognostic factor in both groups. Death caused by sepsis was more prevalent in the LN group. Serositis and neurological manifestations occurred less frequently in LN patients diagnosed after 2005. The use of mycophenolate mofetil became more common, and the cumulative corticosteroid dose decreased. The SLICC Damage Index score also decreased. Conclusions: Our study demonstrated that the disease course has changed in recent years, and the main therapeutic goal in both SLE and lupus nephritis should be to achieve remission because this significantly improves long-term prognosis and patient survival.

Opioid Use and Outcomes in Patients Hospitalized With Acute Severe Ulcerative Colitis.

Opioid use has not been shown to improve hospitalized inflammatory bowel disease patient pain scores and may prolong the length of stay (LOS). Additional clinical implications of opioid use, particularly high amounts, in the hospital setting have not yet been explored. We sought to determine how high opioid use impacts clinical outcomes in acute severe ulcerative colitis (ASUC). In this single-center study, we identified all patients hospitalized with ASUC who received intravenous corticosteroids from July 1, 2014 to December 31, 2021. Clinical outcomes including opioid exposure, cumulative intravenous corticosteroid dose, biologic rescue therapy initiation date, colectomy rate, opioid prescription at discharge, LOS, and hospitalization cost were collected. High opioid use was defined as ≥40 oral morphine equivalents (OMEs) per day. A univariable logistic regression was performed to evaluate the association of high opioid use with ASUC outcomes. 185 eligible hospitalizations for ASUC were evaluated. 75 patients (41%) received opioids during hospitalization, and 20 patients (11%) received ≥40 OMEs/day. High opioid use was associated with a median 3-day delay in biologic rescue therapy initiation when compared with low/no opioid use (P = .02). 70% of patients with high opioid use received an opioid prescription at discharge compared with 10% of those with low/no use (P < .001). Opioid use was not associated with LOS, duration of corticosteroid therapy, colectomy rate, or hospitalization cost. Among ASUC hospitalizations, high opioid use was associated with delayed biologic rescue therapy initiation and higher rates of opioid prescriptions at discharge.

THE ANALYSIS STUDY OF SAFETY AND LONG-TERM EFFECTS OF GLUCOCORTICOIDS IN TREATMENT OF INFLAMMATORY RHEUMATIC DISEASE: A COMPREHENSIVE SYSTEMATIC REVIEW

Background: Glucocorticoids (GCs) are often the first-line therapy for autoimmune diseases including many neurological conditions. Their use is commonly associated with complications and comorbidities. These include both immediate and long-term complications that are often related to the dose and cumulative dose of GCs. The aim: The aim of this study to show about safety and long term effects of glucocorticoids in treatment of inflammatory rheumatic disease. Methods: By the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. This search approach, publications that came out between 2014 and 2024 were taken into account. Several different online reference sources, like Pubmed, SagePub, and Sciencedirect were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: Eight publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. Conclusion: Glucocorticoids are effective drugs for many rheumatic diseases. However, there are serious adverse effects that can ensue. These are often dose related and related to the duration of therapy. Several of the complications occur in patients already at risk for these adverse events. The adverse effects, such as weight gain, osteoporosis, fracture, osteonecrosis, infections, ocular complications, cardiovascular effects, hyperglycemia, etc.

Frequent Unrecognized Vertebral Fractures Associated with Increased Body Fat Mass in Children and Adolescents with Duchenne Muscular Dystrophy.

Patients with Duchenne muscular dystrophy (DMD) have an increased risk of vertebral fractures (VFs). Ethnic variations may partly contribute to the fracture risk. This study aimed to demonstrate the VFs and body fat mass in Asian patients with DMD. Demographic data and DMD-related parameters of the enrolled patients were collected. Lateral thoracolumbar spine radiographs were performed for VF assessment. Genant classification was applied for VF severity grading (mild, moderate and severe). Body composition analysis using dual-energy X-ray absorptiometry was performed. Serum calcium, phosphate, intact parathyroid hormone and 25-hydroxyvitamin D concentrations were determined. There were 25 children and adolescents with DMD enrolled. Median (IQR) age was 12.9 (9.6, 19.3) years. Nine patients (36%) had VFs with a total of 31 sites of VFs (mild, N=10; moderate, N=3 and severe, N=18). These VFs had never been recognized prior to this study. Comparing with the non-VF group, the VF group received a significantly greater cumulative prednisolone equivalent dose (1,258 (948, 1,664) vs. 291 (17, 823) mg/kg, p=0.003). Body fat mass, represented by fat mass index and body fat percentage Z-scores was greater in the VF group [2.46 (2.21, 2.51) vs. 1.63 (0.36, 2.07), p=0.011 and 4.4 (3.1, 5.5) vs. 1.8 (0.6, 3.5), p=0.008, respectively]. No differences in serum calciotropic hormones and vitamin D status were demonstrated between patients with and without VFs. VFs were frequent in patients with DMD. Patients with VFs had greater cumulative glucocorticoid dose and body fat mass than those without VFs.

The Effect of Perioperative Cimetidine on the Outcomes of Stage 2 Melanoma

Objectives The use of immunotherapies in the treatment of melanoma has significantly improved the survival of patients with advanced disease. Historically, histamine has been implicated in the pathogenesis of several cancers. Cimetidine does play a role in modulating the immune system and was advocated as an immunotherapeutic agent since the 1970s. Cimetidine has been showing promise in conjunction with standard care in many cancers in vitro and in vivo. However, its effects in melanoma have not been explored yet. Our study was designed to determine if cimetidine taken in the perioperative period improves the disease-free survival (DFS) or overall survival in patients with the American Joint Committee on Cancer, seventh edition (AJCC 7) stage 2 melanoma. Materials and Methods We have reviewed all the patients with stage 2 melanoma in our center in a retrospective cohort to assess the difference in survival between patients who received H2 blockers in the perioperative period and those who did not. Statistical Analysis and Results Thirty-two patients were included in the analysis. Nine of 32 patients received H2 blockers in the perioperative period. All the patients were males except for one female in the control group (4.3%). The age in the analyzed population ranged between 51 and 92 years; the median age was 70 years (mean: 71; standard deviation: 10). The median overall survival of the patients who received H2 blockers was 112.7 months and it was 77.2 months for those who did not receive H2 blockers. There was no difference in DFS between the two groups (p = 0.5395), and there was no difference in the overall survival (p = 0.4770). The cumulative dose was strongly correlated with the overall survival in the patients who received H2 blockers (r = 0.8341, p = 0.0196). Conclusion Despite having a small treatment group, we were able to detect a strong correlation between the cumulative dose of H2 blockers received and the overall survival.

Ultrasound-Guided Lumbar Plexus-Sciatic Nerve Blocks Versus Epidurals for Orthopaedic Surgeries: A Study to Compare the Competency of Novice Anaesthesiology Residents in a High-Volume Level 1 Trauma Centre.

The relative merits of peripheral nerve blocks (PNB) over central neuraxial anaesthesia and the advantages of the above two techniques over general anaesthesia for surgical interventions of the lower limb are well established. The competency of anaesthetic trainees in a high-volume level 1 trauma centre in administering dual ultrasound and nerve stimulator-guided lumbar plexus-sciatic nerve block(DUNLuPS) vs. epidural anaesthesia (EA) was compared by reporting the adequacy of anaesthesia with the two techniques, time taken for the performance of block, time of onset of sensoryblock (TOSB), and time of onset of motor block (TOMB). This prospective, randomized, study enrolled 92 patients aged 18-80 years with lower limb fractures admitted in trauma triage and scheduled for surgery. Thepatients were randomly allocated equally into the EA group and the DUNLuPS group. A total of 20 anaesthesia trainees in the third year of residencywith clinical experience of more than 15 independent lumbar plexus-sciatic nerve blocks were included in the study.A volume of 20 ml of 0.5% ropivacaine was administered in the lumbar plexus (Shamrock technique) but the volume used for sciatic nerve (subgluteal approach) was varied so that the cumulative dose did not exceed 3 mg/kg. For each block, the onset of nerve blockade was assessed every five minutes, and the assessments continued for an additional 30 minutes after the nerve blocks were finished. Clinical characteristics and adequacy of anaesthesia were comparable, i.e., 95.65% and93.47% success in the EA (n = 46) and DUNLuPS (n = 46) groups, respectively. Performance time was significantly more in the DUNLuPS group but followed by significantly less TOSB and TOMB. The time for the first analgesic request was 351.63 ± 148.70 minutes in the DUNLuPS group and 147.60 ± 52.65 minutes in the EAgroup (p < 0.0001). Both EA and DUNLuPS provide effective and comparable intra-operative anaesthesia for orthopaedic lower limb surgeries (OLLS) when administered by residents with more than two years of experience (third year of residency)in ultrasound-guided regional nerve blocks in a high-volume level 1 trauma centre. Statistically significant differences in the block performance characteristicshad no clinical advantage as it was compensated by the faster onset time in the DUNLuPS group. Post-operative pain management was better in the DUNLuPS group, sothe practice and conduct of anaesthesia for trauma patients should focus on the establishment of "block rooms" and timely training of residents in the former so that the advantages can be extended to the patient population.

Oxaliplatin-induced peripheral neuropathy with hepatic arterial versus intravenous infusion in metastatic colorectal cancer.

Oxaliplatin, a major drug in metastatic colorectal cancer (mCRC), is responsible for cumulative, dose-limiting peripheral neuropathy (PN). Whether the hepatic arterial infusion (HAI) route can limit oxaliplatin-induced PN in comparison with the intravenous (IV) route has not been specifically explored so far. We compared the frequency and severity of PN in oxaliplatin-naive patients with mCRC included in trials that evaluated treatment with oxaliplatin administered either by HAI (ACCORD 04, CHOICE, OSCAR, and PACHA-01 trials) or by IV route (FFCD 2000-05 trial). We retrieved anonymized, prospectively collected data from trial databases for the ACCORD 04, CHOICE, and FFCD 2000-05 trials and through a review of Gustave Roussy patients' electronic medical records for PACHA-01 and OSCAR trials. The primary endpoint was the incidence of clinically significant PN (grades 2 to 4) according to the cumulative dose of oxaliplatin received. Secondary endpoints were time to onset of neuropathy as a function of the cumulative dose of oxaliplatin, discontinuation of oxaliplatin for neurotoxicity, and safety. A total of 363 patients were included (IV, 300; HAI, 63). In total, 180 patients in the IV group (60%) and 30 patients in the HAI group (48%) developed clinically significant PN, with no significant difference between the two groups (p = 0.23). No difference was shown in the time to onset of PN either (p = 0.23). The administration of oxaliplatin HAI rather than IV in the treatment of mCRC does not reduce the incidence, precocity, and severity of PN.