Median Difference Research Articles

Continuous Glucose Monitoring in Hospitalized Adults With Diabetic Ketoacidosis: A Prospective Open-Label Pilot Study.

Continuous glucose monitoring (CGM) devices are increasingly used in critical and non-critical care hospital units. The efficacy of CGM in assessing glucose control in adults with diabetic ketoacidosis (DKA) is unknown. This single-center pilot study compared glycemic control by real-time CGM (Dexcom G6), capillary point-of-care (POC), and basic metabolic panel (BMP) during intravenous (IV) insulin treatment and after the resolution of DKA. We compared the mean absolute relative difference (MARD), median absolute relative difference (ARD) glucose values, and Diabetes Technology Society (DTS) Error Grid analyses. We recruited 52 patients (49 ± 19 years, admission glucose: 503 ± 239.4 mg/dL) with type 1 diabetes (n = 24) and type 2 diabetes (n = 28). Compared with POC testing, the MARD was 17.4% ± 13.2%, and the median ARD was 14.2% (interquartile range [IQR]: 6.4, 28) during the initial IV insulin period and 19.8% ± 18.7% and 14.3% (7, 26.2) after DKA resolution. The DTS Error Grid analysis showed that 100% of values during the IV insulin treatment and 95% after the DKA resolution were in zones A+B. Compared with BMP glucose values, the MARD and median ARD were 18.5% ± 19.1% and 12.2% (5.4, 23.8) during the IV insulin treatment and 22.5% ± 24.7% and 15.1% (6.6, 27.6) after DKA resolution. This is the first report on the use of real-time CGM in adults with DKA. Our study indicates that CGM technology is a reliable tool for hospital use during acute insulin treatment and after the resolution of DKA. Future multicentre randomized studies are needed to determine the benefits of real-time CGM in facilitating diabetes care in hospitalized patients with hyperglycemic crises.

Adherence to delayed-release cysteamine in nephropathic cystinosis over time: data from the prospective CrYSTobs cohort study.

Adherence to cysteamine in nephropathic cystinosis (NC) remains challenging. A better adherence with delayed-release (DR) compared to immediate-release (IR) cysteamine at 1year was previously shown. This study aimed to evaluate adherence to DR cysteamine at 2years. Treatment adherence was assessed using a medication event monitoring system; adherence ranged from 0 (poor) to 2 (good). Leukocyte cystine level was measured at each 3-month visit. Long-term follow-up data (7years after the end of the study) on self-reported adherence and quality of life was also obtained in a sub-group of patients. Seventeen patients with NC under DR cysteamine from three French centers were included at a median age of 13.9 (5.4-33.0) years. The median adherence score was 1.62 (0.03-1.98) over the 2-year follow-up, with 65% of patients having good adherence and 75% having partial or good adherence. No significant difference in leukocyte cystine level between baseline and 2years was found (0.8nmol vs. 0.4nmol, respectively; difference in median of - 1.0nmol; 95% CI - 0.7, 0.4; P = 0.64). Long-term follow-up data highlighted that no patient wished to switch back to IR cysteamine, as taking the medication twice rather than four times a day was easier. This study found a fairly good adherence to DR cysteamine over time. Decreasing the number of intakes per day may improve adherence and limit the side effects of the drug, representing an additional argument in favor of its use in patients with cystinosis.

Comparison of percutaneous versus cutdown access in patients after endovascular abdominal aortic repair: a randomized controlled trial (SWEET-EVAR trial).

The optimal choice of either percutaneous or cutdown access for endovascular abdominal aortic repair (EVAR) remains uncertain due to insufficient evidence, particularly regarding patient-centered outcomes (PCOs). This study aimed at comparing both clinician-reported outcomes (ClinROs) and PCOs of percutaneous versus cutdown access in patients after EVAR. The study was a single-blind, single-center, non-inferiority, randomized controlled trial. After eligibility screening, patients diagnosed with abdominal aortic diseases were randomly assigned to either the intervention group receiving percutaneous EVAR or the control group receiving cutdown EVAR. Primary ClinRO was access-related complications, and primary PCO was time return to normal life/work. Overall, 120 patients (containing 240 accesses) were allocated to either intervention group (n =62) or control group (n =58). Percutaneous EVAR (10/124, 8.1%) was non-inferior and not superior to cutdown EVAR (17/116, 14.7%) regarding access-related complications (P =0.110; OR: 0.521, 95% CI: 0.225-1.157). As for PCOs, the recovery time back to normal life or work was superior in percutaneous EVAR compared to cutdown EVAR (16 vs. 28days, P =0.025; median difference: 7days, 95% CI: 0-13days). Moreover, percutaneous access did better in other PCOs, including a reduction in the duration of access-related pain (4 vs. 8days, P =0.001), decreased use of analgesics for access-related pain (0/61, 0% vs. 6/55, 10.9%; P =0.026), and improved quality of life scores at 2 weeks following EVAR (0.876 vs. 0.782; P =0.022). Prespecified subgroup analyses demonstrated percutaneous access significantly reduced the incidence of access-related complications compared to cutdown access in patients with thick subcutaneous tissue (1/42, 2.4% vs. 7/32, 21.9%; P =0.026). In patients without massive common femoral artery calcification, percutaneous access may accelerate postoperative recovery and enhance patient experience and quality of life following EVAR, but did not provide obvious advantages regarding access-related complications.

Accuracy of SEEG Source Localization: A Pilot Study Using Corticocortical Evoked Potentials.

EEG source localization is an established technique for localizing scalp EEG in medically refractory epilepsy but has not been adequately studied with intracranial EEG (iEEG). Differences in sensor location and spatial sampling may affect the accuracy of EEG source localization with iEEG. Corticocortical evoked potentials can be used to evaluate EEG source localization algorithms for iEEG given the known source location. We recorded 205 sets of corticocortical evoked potentials using low-frequency single-pulse electrical stimulation in four patients with iEEG. Averaged corticocortical evoked potentials were analyzed using 11 distributed source algorithms and compared using the Wilcoxon signed-rank test (P < 0.05). We measured the localization error from stimulated electrodes and the spatial dispersion of each solution. Minimum norm, standard low-resolution electromagnetic tomography (sLORETA), LP Norm, sLORETA-weighted accurate minimum norm (SWARM), exact LORETA (eLORETA), standardized weighted LORETA (swLORETA), and standardized shrinking LORETA-FOCUSS (ssLOFO) had the least localization error (13.3-15.7 mm) and were superior to focal underdetermined system solver (FOCUSS), logistic autoregressive average (LAURA, and LORETA, 17.9-21.7, P < 0.001). The FOCUSS solution had the smallest spatial dispersion (7.4 mm), followed by minimum norm, L1 norm, LP norm, and SWARM (20.8-28.3 mm). Gray matter stimulations had less localization error than white matter (median differences 3.1-6.1 mm) across all algorithms except SWARM, LORETA, and logistic autoregressive average. A multivariate linear regression showed that distance from the source to sensors and gray/white matter stimulation had a significant effect on localization error for some algorithms but not SWARM, minimum norm, focal underdetermined system solver, logistic autoregressive average, and LORETA. Our study demonstrated that minimum norm, L1 norm, LP norm, and SWARM localize iEEG corticocortical evoked potentials well with lower localization error and spatial dispersion. Larger studies are needed to confirm these findings.

Differences in Negotiated Facility Fees for Otolaryngology Procedures at Ambulatory Surgery Centers and Hospitals.

While outpatient otolaryngology procedures have been increasingly performed at ambulatory surgery centers (ASCs), the cost differences compared to hospital outpatient departments (HOPDs) remain unclear. Utilizing newly available data collected from Turquoise Health's Rate Sense as required under the Transparency in Coverage rule, we assess, in this cross-sectional analysis, the differences in negotiated facility fees between ASCs and HOPDs for 20 common otolaryngologic procedures. Analyzing data from 4613 ASCs and 2382 hospitals, we found significantly higher facility fees at HOPDs, with a median relative price difference of +146% (P < .0001). This may be explained by greater infrastructure costs and market power differences between facilities. Our findings suggest that further shifting outpatient otolaryngology procedures toward ASCs could yield substantial cost reductions across health care systems. Additional research is needed to ensure safe and cost-effective patient selection for ASCs.

Performance of MR learned pulse sequences for 3D bi-exponential, stretched-exponential, and mono-exponential T2 and T1ρ mapping of knee cartilage.

To compare the performance of a learned magnetization-prepared gradient echo (L-MPGRE) sequence against a commonly used sequence for 3D T2 and T1ρ mapping of the knee joint, the magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (MAPSS), on bi-exponential (BE), stretched-exponential (SE), and mono-exponential (ME) relaxation models. We used a combined differentiable and non-differentiable optimization to learn pulse sequence structure and its parameters for 3D T2 and T1ρ mapping of the knee joint using ME, SE, and BE models. The learned pulse sequence framework was used to improve quantitative accuracy and SNR and to reduce filtering effects. We compare the measured multi-compartment values between the two sequences (n = 8), and their repeatability (n = 4) in healthy volunteers (n = 12 total). The voxel-wise median absolute percentage difference (MAPD) between the T2 and T1ρ maps obtained with each sequence was 18.6% and 19.9%, respectively. The T2 and T1ρ repeatability tests showed a MAPD of 18.5% and 19.1% for MAPSS, and 16.8% and 15.5% for L-MPGRE. Bland-Altman region of interest (ROI)-wise analysis shows that bias is small, close to -1.5%, and the coefficient of variation is around 5.5% when comparing ROIs from both sequences. The L-MPGRE sequences can be used as a replacement for MAPSS for T2 and T1ρ mapping in the knee cartilage with advantages, achieving similar accuracy and 15% better repeatability in only half of its scan time.

A protein-based blood panel test for the early detection of colorectal cancer and advanced neoplasia.

46 Background: Early detection of colorectal cancer (CRC) is key to survival. CRC screening compliance is still low because of either the invasive procedure (colonoscopy) or the so-called "ick factor" (stool-based tests). Stool-based tests also lack ability to detect advanced adenoma (CRC precursor). A blood-based test could improve adherence to screening guidelines, but no one has so far been recommended due to a lack of sufficient sensitivity and specificity. Here we report the potential clinical utility of a blood-based biomarker panel providing high sensitivity (SE) and specificity (SP) for CRC and advanced adenomas (AA) as a screening triage option addressing positive patients to colonoscopy. Methods: A total of 241 retrospective serum samples (179 CRC, 22 adenoma, 40 healthy controls) were obtained from the Cooperative Human Tissue Network (CHTN) biobank and tested with a proprietary sandwich ELISA that detects dual CRC specific biomarkers (BF7 and CC3). A standard curve was generated and biomarkers concentration in the samples were calculated using a 4-parameter logistic method. The median biomarker concentration values in each patient group were compared to determine whether differences were statistically significant (p&lt; 0.05). Statistical analysis of two-group and multi-group comparisons was carried out using the non-parametric Mann-Whitney U test and the Kruskal-Wallis test, respectively. Receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic performance, by determining sensitivity (SE), specificity (SP), area under the curve (AUC), and confidence interval (CI). Statistical analysis, ROC curves and scatter plots were performed with GraphPad Prism 7.0. Results: Both biomarker's median concentration difference between CRC versus healthy samples groups were found to be statistically significant (p&lt;0.05). Both biomarkers were also elevated in AA as compared to healthy samples, but difference in median concentration was only statistically significant for CC3 (p&lt;0.0001). BF7 serum levels in cancer patients were significantly associated with TMN stage (p=0.019), N stage (p=0.039) and M stage (p=0.0006). No significant associations were found between this biomarker levels and other clinical characteristics of the CRC patients including age. Our test discriminated CRC (all stages) from healthy individuals with a SE of 80% and a SP of 90%. Sensitivity for early (n=95) and late-stage CRC (n=80) was 79% and 84%, respectively. Our test was also able to detect 81% of serum from advanced adenoma patients who are at increased risk of CRC. Conclusions: This study illustrates the potential clinical utility of our blood-based assay for the early detection of CRC which has a better sensitivity for advanced adenoma than tests in current clinical use. A large prospective cohort study is planned to further validate the clinical performance of this test.

Individualized blood pressure regulation and acute kidney injury in older patients having major abdominal surgery: a pilot randomized trial.

Acute kidney injury (AKI) is a common postoperative complication, and hypotension may contribute. We therefore tested the primary hypothesis that individualized intraoperative blood pressure regulation reduces postoperative AKI in older surgical patients. We enrolled patients ≥60years old scheduled for elective major abdominal surgery with invasive arterial pressure monitoring. All had goal-directed fluid management based on stroke volume variation and cardiac output, and administration of a starch. Participants were randomly assigned to: 1) individualized blood pressure management targeting a systolic blood pressure (SBP) within -20% and+10% if baseline SBP was ≥ 130mmHg or diastolic blood pressure was ≥ 80mmHg, or otherwise, to target SBP within±10% of the baseline value; 2) maintenance of SBP ≥ 90mmHg and MAP ≥ 65mmHg. Metaraminol was used to achieve the blood pressure target. AKI incidence was assessed by Kidney Disease Improving Global Outcomes criteria during the initial 7 postoperative days. 192 patients were assigned to individualized (n=96) or routine (n=96) pressure management. 179 patients were included in the intention-to-treat analysis. Age averaged 68±5 (SD) yr and 64% were male. Randomization to the individualized management reduced the area under MAP <65mmHg [median difference:-37 (-47 to -25) mmHg-min, P < 0.001]. The incidence of the AKI was 11% in patients assigned to individualized management versus 16 % in those assigned to routine management: relative risk 0.72 [95% CI 0.34 to 1.54], P=0.396. Patients assigned to individualized pressure management had more urine output, a shorter postoperative mechanical ventilation duration, and faster recovery of bowel function. Individualized blood pressure management markedly reduced hypotension. As expected in a pilot trial, the 28% reduction in AKI was not statistically significant. However, the reduction was clinically meaningful and suggests that a full trial is warranted.

P-2178. Can serum ferritin be used as a marker of severity in dengue fever?: a prospective observational study from North India

Abstract Background Dengue has a variable clinical course and there is no standardised marker for predicting dengue severity. Studies have shown higher ferritin levels in dengue compared to other febrile illnesses. Prospective studies to show correlation of ferritin with dengue severity are lacking. Demographic profile and workflow From 134 patients 99 were selected for the study , 35 were excluded as per the exclusion criteria (figure 1 flowchart). Majority of the patients were young (figure 3) with male predominance (figure 2), the male female percentages and age did not vary significantly across different grades of severity (table1 and figure 4). Methods Single centre prospective observational study conducted over 2 years. Patients of chronic inflammatory diseases, thalassemia, haematological malignancy or severe anemia (Hb &amp;lt; 7gm/dl) were excluded. Two ferritin samples 3 days apart measured by automated BECKMAN COULTER DxI.800 immunoassay analyzer. Clinical features and median ferritin value across different dengue severties In Figure 5 the pie chart shows that majority of the patients were dengue without warning signs , approximately 1/5th were severe dengue. Figure 6 shows that initial clinical features were more or less similar in the three groups of severities , however bleeding, pain abdomen , vomiting were more common in severe dengue group. Table 2 showing median ferritin values of day 0 and day 3 ferritin in different severity groups and whether their differences are statistically significant between each groups or not. The Box and whisker plots in figure 7, 8 and 9 shows the same with corresponding p values and Median ferritin level annotated. Results Total study population was 99 patients with median age of 28 years (24.5-34.5) and male predominance (68%). 2009 WHO classification wise 43% were dengue without warning signs 36% dengue with warning signs and 21% were severe dengue patients. Both day 0 and day 3 ferritin median value were higher across all three groups and the difference were statistically significant (p=0.00002 and p=0.045 respectively). Day 0 ferritin median value difference was statistically significant between severe dengue and dengue without warning sign (0.00001) and warning sign group (p=0.0003). In case of early ferritin sample (within day 7 of illness) it was significantly different between all groups. Serum ferritin also showed strong positive correlation with AST, ALT and negative correlation with Albumin levels. ROC curve analysis showed that a ferritin cut off of 9185 ng/ml with AUC 0.811, standard error 0.06 and 95% CI of 0.69-0.92 could differentiate severe from non severe dengue with 52.4% sensitivity and 97.4% specificity. For early ferritin sample cut off becomes 2132 ng/ml with a 70% sensitivity and 82.4% specificity with AUC 0.821, standard error 0.085 and 95% CI of 0.65-0.98. Multivariate logistic regression shows baseline platelet counts &amp;lt; 50000 cells/uL [OR 4.7, p=0.02, 95% CI 1.19-18.54] and Albumin &amp;lt; 3.5 gm/dL [OR 6.33 p=0.007 95% CI 1.67-24.06] to be independent predictors of severe dengue. Day 0 ferritin level &amp;gt; 9185ng/mL gave an Odd’s ratio of 10.47 with p=0.052 and 95% CI [0.98-112]. Correlation of ferritin with various biochemical parameters and Ferritin cutoff value to differentiate Severe from Non severe dengue by ROC curve Table 3 and Figure 10 Scatter plot showing strong positive correlation between serum ferritin and SGOT/ SGPT levels, and negative correlation with serum albumin level .Figure 11 ROC curve analysis showing the ferritin cutoff being 9185ng/ml to differentiate between severe and non severe dengue. If sample taken within day 7 of illness the cut off becomes 2132 ng/ml (Figure 12) Conclusion Ferritin can be a useful biomarker for differentiating different grades of dengue severity especially if sample taken in the 1st week of illness. Serum ferritin cut off values can be used to predict severe dengue. Multivariate Logistic regression to find independant predictor of severe Dengue Table 4 showing Multivariate logistic regression result, which reveals baseline platelet count &amp;lt;50000 and Albumin level &amp;lt;3.5gm/dL to be independent predictor of severe dengue.Day 0 Ferritin cutoff of 9185 ng/dL as per the ROC curve analysis shows that the Odds of prediction of severe dengue is 10.47 (p=0.052 and 95% CI 0.98-112). Disclosures All Authors: No reported disclosures

Changes in Coagulation Factor XI Activity Levels in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI.

Background - Although Factor XI (FXI) inhibitors are currently tested for the prevention of thrombotic events, their early treatment could prevent thrombus consolidation in ST-segment elevation myocardial infarction (STEMI). This study aims to characterize coagulation FXI levels and their variations in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Methods - Patients with STEMI were prospectively enrolled between December 2023 and May 2024. FXI activity (FXIa) levels were measured at admission and after PCI (i.e., before discharge). Variations in FXIa levels were evaluated. Differences in indicators of thrombotic risk between groups with high and low FXIa variability were analyzed, and predictors of high FXIa variability were identified. Results - After screening, 54 patients with STEMI were included. The median FXIa level was 0.865 IU/mL (interquartile range [IQR] 0.554-0.978) at admission and 1.161 IU/mL (IQR 0.982-1.317) before discharge, with a median difference of +34.2% (p-value < 0.001). No significant differences were found in indicators of thrombotic risk between groups at high and low FXIa variability, except for the days intercurred between the essays (p-value = 0.016). Neither this nor other variables emerged as independent predictors of high FXIa variability. Conclusions - This study firstly reported an increase in FXIa levels from admission to discharge in STEMI patients undergoing PCI. Common indicators of thrombotic risk were not associated with FXIa levels or their variability. These findings aim to stimulate further research into anticoagulant therapies tailored to the patient's coagulative state and disease.

Development, implementation, and evaluation of an innovative clinical trial operations training program for Africa (ClinOps)

BackgroundAfrica’s involvement in clinical trials remains very low. Although the crucial role of training initiatives in building clinical trial capacity in Africa has been documented, current efforts fall short as they lack alignment with local contexts. This study aimed to design, develop, implement, and evaluate an innovative clinical trial operations training program for Africa.MethodsWe developed ClinOps, a novel 10-week clinical trial operations training program for study coordinators in Africa to enhance their expertise in four fundamental areas: designing, conducting, managing, and reporting clinical trials. To streamline the learning process, we used cloud-based applications that minimize the need for software installations while maximizing student engagement. VoiceThread facilitated interactive content that could be accessed offline. Moodle, an open-source learning management system, offered a platform for sharing learning tools, mentorship, and rubric-driven competency assessments, including quizzes, forums, tutorials, and group assignments. We utilized Zoom for live tutorials and mentoring as required. Effectiveness of the program was evaluated through quantitative pre- and post-surveys, qualitative end-course evaluations, and a comprehensive monitoring and evaluation framework. The pre- and post-surveys measured changes in trainees’ confidence in clinical trial domains and leadership and coordination skills. End-course evaluations gathered feedback on the course content, organization, technology, and instructional methods. We used Wilcoxon rank test to analyze pre- and post-survey scores and thematic analysis to analyze the qualitative data.ResultsIn the initial cohort, 88 study coordinators from 19 countries participated, including 56 (64%) females, with 57 (65%) actively employed as study coordinators during the training, and 85 (97%) possessing prior experience in clinical trial roles. Among these, 71 (81%) successfully completed the course, with 69 (97%) also completing the post-course assessment. Post-training scores demonstrated substantial improvement compared to pre-training scores in each competency area, including in designing (pre-post training median score = 3.6 vs. 4.6, median difference = 1.0, 95% CI 0.8–1.1, p < 0.001), managing (pre-posttest median score = 3.4 vs. 4.2, median difference = 0.6, 95% CI 0.4–0.8, p < 0.001), conducting (pre-post training median score = 3.9 vs. 4.7, median difference = 0.9, 95% CI 0.6-1.0, p < 0.001), and reporting (pre-posttest median score = 3.0 vs. 4.5, median difference = 1.0, 95% CI 0.9–1.5, p < 0.001) clinical trials. The monitoring and evaluation data confirm the program’s adherence to training best practices, including alignment with local priorities, country ownership, pedagogic innovation, institutional capacity building, sustainability, and ongoing partnerships. The end-course evaluation reflects participants’ positive feedback on the program’s structure, content, relevance to their current roles, and overall delivery methods.ConclusionThe ClinOps program, designed by experts from academia and product development partners, enhanced participants’ clinical trial competencies. To effectively build clinical trials capacity on the continent, training programs should provide thorough competency development in designing, conducting, managing, and reporting trials.

Patient-specific implants combined with 3D-printed drilling guides for corrective osteotomies of multiplanar tibial and femoral shaft malunions leads to more accurate corrections

PurposeThe aim of this study was to evaluate the feasibility of using patient-specific implants (PSI) for complex shaft corrective osteotomies in multiplanar deformities of long bones in the lower extremities. Additionally, it aimed to investigate the added value of these implants by quantifying surgical accuracy on postoperative CT, comparing their outcomes to two commonly used techniques: 3D virtual visualizations and 3D-printed surgical guides.MethodsSix tibial and femoral shaft corrective osteotomies were planned and performed on three Thiel embalmed human specimen. Depending on the specimen a different respective technique was used; 1) ‘3D Visualization’ using 3D virtual plan preoperatively and free-hand corrective osteotomy techniques with standard manually contoured plates; 2) ‘3D guided’ utilizing 3D surgical guides and manually contouring of conventional implant; and 3)‘3D PSI’ utilizing a 3D surgical guide with a patient-specific implant. Accuracy of the corrections was assessed through measurements for varus/valgus angulation, ante/recurvation, rotation and osteotomy plane error as quantified on postoperative CT-scans.ResultsTwelve corrective osteotomies were performed. For, the median difference between the surgical plan and postoperative CT assessment was 3.4°, 4.6°, and 2.2° for the ‘3D visualization’, ‘3D guided’, and ‘3D PSI’ methods respectively. Regarding ante/recurvation, the differences were 3.8°, 43.8°, and 1.2°, respectively. For rotation, the differences were 11.9°, 18.7°, and 3.5°, respectively. Discrepancies between planned and executed levels of osteotomy plane were 6.2 mm, 3.2 mm, and 1.4 mm, respectively.ConclusionPSIs with 3D-printed drilling guides for complex multiplanar corrective osteotomies of femoral and tibial shaft malunions is feasible and achieves accurate corrections. This technique enables precise determination of the osteotomy plane, guides correction in all three planes, and ensures satisfactory implant fitting; thus accurately translating the virtual surgical plan into clinical practice. The 3D PSI method is beneficial for complex cases with significant multiplanar deformities in bone anatomy, particularly with rotational malalignment.

The impact of virtual reality on patient experience during wide-awake surgery: a randomized controlled trial.

This study aimed to establish whether virtual reality can reduce patient anxiety and improve surgical satisfaction during wide-awake local anaesthetic no tourniquet hand procedures. Previously validated questionnaires were used to assess subjective anxiety and patient satisfaction. Objective anxiety was determined using patient blood pressure and heart rate measured four times during the procedure. The median difference in intra-operative minus pre-operative diastolic blood pressure was significantly lower in the virtual reality group compared with the control group (p = 0.003). There was a significant decrease in heart rate from pre-operative to post-operative within the virtual reality group (p < 0.001). No differences were observed in subjective anxiety or surgical satisfaction between the groups. Virtual reality can benefit wide-awake patients during hand procedures, particularly where patient preference exists.Level of evidence: Level I, Randomized Controlled Trial.

Association between frailty and specific comorbidities on oncological outcomes in metastatic hormone-sensitive and castration resistant prostate cancer.

Demographic changes will lead to higher proportions of metastatic hormone-sensitive (mHSPC) and castration resistant metastatic prostate cancer (mCRPC) patients with higher frailty index and multiple comorbidities. We relied on an institutional tertiary-care database to explore the effect of frailty (Eastern Cooperative Oncology Group [ECOG]), as well as cardiovascular (CVD) and secondary malignancy (SecCa) comorbidities on overall survival (OS) and time to mCRPC in mHSPC and OS in mCRPC patients with Kaplan-Meyer estimates and Cox regression models. Of 802 mHSPC patients, 61% were ECOG0 vs. 32% ECOG1 vs. 6.5% ECOG≥2. Significant differences in baseline patient and baseline mHSPC characteristics were observed for all three groups (all P ≤ 0.05). In time to mCRPC analyses and OS analyses of mHSPC and mCRPC patients, significant disadvantages were observed for ECOG 1/≥2 patients, relative to ECOG0, even after multivariable adjustment. Moreover, 31% of included patients had history/active CVD, which yielded significant median OS differences in mHSPC patients (95 vs. 63 months, multivariable hazard ratio: HR: 1.77, P < 0.01), but not in mCRPC patients (P = 0.085). After stratification according to SecCa, 14% had a SecCa which led to significant median OS differences in mCRPC patients (50 vs. 37 months, P < 0.01) but not in mHSPC patients (76 vs. 64 months, P = 0.089). Patients with higher frailty index and comorbidities showed significant differences in therapy lines. Frailty and specific comorbidities significantly influence cancer-control outcomes in mHSPC, as well as mCRPC patients, even after controlling for adverse tumor characteristics.

Comparison of radiation exposure for interventional radiology vs urology-guided renal access for percutaneous nephrolithotomy.

Radiation exposure during percutaneous nephrolithotomy (PCNL) can vary depending on the method used for renal access. This study aimed to compare fluoroscopy time and dose during PCNL when renal access is achieved via interventional radiology (IR) versus urology. A retrospective review of patients who underwent unilateral PCNL between January 2020 and February 2023 was conducted. Patients were categorized by renal access method: endoscopic combined intrarenal surgery performed by a urologist (ECIRS) or IR-assisted. A Wilcoxon rank-sum test and multivariate analyses were done to compare several parameters of the two groups. 66 patients underwent ECIRS (group 1), and 31 underwent IR-assisted access (group 2). The groups were similar in age, BMI, sex, and stone size. The difference in medians for fluoroscopy dose, fluoroscopy time, operative time and length of stay were statistically significant (p < 0.001). Average fluoroscopy dose (39.6 vs. 327mGy) and time (1.46 vs. 10.9min), along with average operative time (1.97 vs. 3.00h) and length of stay (1.26 vs 3.06days) were all lower in group 1. In the IR group, a positive correlation was noted between BMI and fluoroscopy dose (p < 0.001), though this correlation was absent with ECIRS. PCNL with ECIRS access significantly reduces radiation exposure and operative time compared to IR-assisted access. Additionally, BMI influenced radiation exposure and operative time in the IR group, but not in the ECIRS group. Endoscopic renal access may lower overall radiation exposure and postoperative complications.

Impact of hemoadsorption with CytoSorb® on meropenem and piperacillin exposure in critically ill patients in a post-CKRT setup: a single-center, retrospective data analysis

PurposeCytoSorb® (CS) adsorbent is a hemoadsorption filter for extracorporeal blood purification often integrated into continuous kidney replacement therapy (CKRT). It is primarily used in critically ill patients with sepsis and related conditions, including cytokine storms and systemic inflammatory responses. Up to now, there is no evidence nor recommendation for the use of CS filters in sepsis (22). There is limited clinical data on the effect of CS on the plasma concentrations of beta-lactams. We aimed to evaluate the statistical and clinical impact of CS in a post-filter CKRT-CS setting on the plasma concentrations of the antibiotics meropenem and piperacillin in critically ill patients.MethodsPatients admitted to the intensive care unit (ICU) who received a prolonged infusion of piperacillin or meropenem with CS-combined CKRT were included in this retrospective analysis. TDM (therapeutic drug monitoring) plasma blood samples were collected at three different points. The differences in antibiotic concentrations between Pre, Intra, and Post were statistically compared to evaluate the total and isolated contributions of CKRT and CS to antibiotic removal. CS, CKRT and combined clearance (CL) values were calculated. The hypothesis was that the CS filter would have no clinically relevant impact on antibiotic levels.Results207 TDM samples were taken from 24 critically ill patients requiring beta-lactam antibiotics. Among these, 129 were meropenem samples, and 78 were piperacillin samples. A decrease in both antibiotic levels was observed between Pre and Intra, and Pre and Post, and the median relative difference between was >15% (meropenem: Pre–Intra 34.8%, Pre–Post 35.8%; piperacillin: Pre–Intra 41.1%, Pre–Post 34.7%), indicating a statistically and clinically significant effect of CKRT on both antibiotic exposures. No significant difference was observed between Intra and Post indicating no clinically relevant drug removal via the CS filter. Changes in CL attributed to CS were minimal, with combined CL differing by ≤8.60% compared to CKRT clearance.ConclusionThe application of CS does not appear to significantly affect plasma concentrations of meropenem and piperacillin in critically ill patients.

Analysis of IL10 gene promoter haplotypes and changes in mRNA expression and soluble levels in patients with basal cell carcinoma.

Interleukin-10 (IL-10) is an immunomodulatory molecule that may play an immunosuppressive role in nonmelanoma skin cancer (NMSC), specifically basal cell carcinoma (BCC). We analyzed the role of IL10 promoter variants in genetic determinants of BCC susceptibility and their association with IL10 mRNA and IL-10 serum levels. Three promoter variants (-1082 A > G, -819T > C, and -592 A > C) were examined in 250 BCC patients and 250 reference group (RG) individuals. IL10 relative gene expression was evaluated in total leucocytes in peripheral blood, and IL-10 levels were quantified in serum. The allelic and genotypic frequencies did not show significant differences between the groups. However, haplotype analysis revealed that the ATA haplotype was associated with a decreased risk of BCC (OR: 0.73, 95% CI 0.56-0.95, p = 0.02), whereas the ATC and ACA haplotypes were associated with an increased risk for the neoplasia (OR: 4.15, 95% CI 1.56-11.04, p < 0.01, and OR: 3.51, 95% CI 1.33-9.29, p < 0.01, respectively). BCC patients showed a 0.09-fold reduction in IL10 mRNA expression compared to the RG. Significant differences were in IL-10 median serum levels between the RG and BCC patients (0.4 vs 0.64pg/mL, p = 0.02). Significant median serum differences were also observed between low- and high-grade histopathological BCC (0.34 vs 1.35pg/mL, p = 0.02). The ATA, ATC, and ACA haplotypes, and serum IL-10 levels, could be markers of susceptibility to BCC in Western Mexican individuals. BCC patients had higher serum IL-10 levels than the RG, with levels increasing with the severity of lesions, confirming the role of IL-10 in immunosuppression in neoplasia.

Discordance and Performance of the ARC-HBR and PRECISE-DAPT High Bleeding Risk Definitions After CoronaryStenting.

The aim of the ARC-HBR (Academic Research Consortium for High Bleeding Risk) and PRECISE-DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) score definitions for high bleeding risk is to identify patients who would benefit from shorter or less intensive antiplatelet therapy after coronary stenting. The aim of this study was to assess the performance of the ARC-HBR and PRECISE-DAPT score definitions for high bleeding risk in routine clinical practice. Using nationwide registers, all patients in Stockholm, Sweden, who were discharged after coronary stenting with dual antiplatelet therapy (January 1, 2013, to July 1, 2018) were included. Patients were categorized as high bleeding risk according to the 2 risk tools, and risk for bleeding (BARC [Bleeding Academic Research Consortium] types 3-5 or TIMI major or minor) and ischemic events (myocardial infarction or ischemic stroke) within 1 year after discharge was assessed. Of 7,562 patients, the proportions categorized as high bleeding risk were 27% (2,004 of 7,562) using the ARC-HBR definition and 38% (2,894 of 7,562) using the PRECISE-DAPT score; 22% (1,696 of 7,562) had discordant categorization of high bleeding risk comparing the 2 risk tools. Patients with vs without high bleeding risk according to the ARC-HBR definition had higher risk for BARC type 3 to 5 bleeding (1-year risk 7.1% vs 2.3%; HR: 3.21; 95%CI: 2.47-4.17) andischemic events (7.8% vs 2.8%; HR: 2.96; 95%CI: 2.31-3.79). Patients with vs without high bleeding risk according to the PRECISE-DAPT score had higher risk for TIMI major or minor bleeding (4.4% vs 2.1%; HR: 2.17; 95%CI: 1.63-2.89) and ischemic events (6.2% vs 2.7%; HR: 2.38; 95%CI: 1.85-3.05). The PRECISE-DAPT score underestimated bleeding risk across almost all score levels (median absolute difference between observed and predicted 1-year risk 1.1%; Q1-Q3: 0.8%-1.4%). There was substantial discordance in the categorization of high bleeding risk between the ARC-HBR definition and the PRECISE-DAPT score. Both tools identified patients at increased bleeding risk, but those patients also had increased ischemic risk. The PRECISE-DAPT score underestimated bleeding risk. Guideline-recommended high bleeding risk definitions may not be generalizable across patient populations, and refined scoring systems are needed.

Pain Decrement Using Radiofrequency Therapy After Knee Platelet-Rich Plasma Injections Within First 72 h in Active Populations with Patellar Chondropathy.

Objective: To determine whether 448 kHz capacitive-resistive monopolar radiofrequency (CRMR) after platelet-rich-plasma (PRP) injections can further reduce pain sensation within the first 72 h in an active population with patellar chondropathy. Methods: One-hundred fifty-three active patients with patellar chondropathy grade II-III were followed for three days after PRP injections with and without CRMR under a control-placebo study. They were clinically evaluated for pain sensation using a visual analog scale ranging from zero (no pain sensation) to ten (highest pain sensation). Pain sensation was described using medians and analyzed through the Friedman and Conover test for within-group comparison (pre-intervention, and 24, 48, and 72 h post-intervention) and the Mann-Whitney test for between-group comparisons (Intervention vs. Placebo) with α = 5% and 1-β = 80%. Results: The placebo group showed statistical significance between pre-intervention and 24 h (Δ = -2.0 pts, p < 0.001), baseline and 48 h (Δ = -2.0 pts, p < 0.001), baseline and 72 h (Δ = -3.0 pts, p < 0.001), 24 h and 48 h (Δ = 0.0 pts, p < 0.016), and 24 h and 72 h (Δ = -1.0 pts, p < 0.001). The radiofrequency group showed statistical significance between baseline and 24 h (Δ = -7.0 pts, p < 0.001), baseline and 48 h (Δ = -7.0 pts, p < 0.001), baseline and 72 h (Δ = -8.0 pts, p < 0.001), 24 h and 72 h (Δ = -1.0 pts, p < 0.001), and 48 h and 72 h (Δ = -1.0 pts, p < 0.001). The placebo and radiofrequency groups were significantly different at 24 h (Δ = 4.0 pts, p < 0.001), 48 h (Δ = 4.0 pts, p < 0.001), and 72 h (Δ = 4.0 pts, p < 0.001). Conclusions: CRMR therapy administered after knee intra-articular injections of PRP within the first 72 h in active populations with patellar chondropathy reduces pain sensation with a median difference of 8.0 pts compared to baseline and 4.0 pts compared to placebo group.

Effects of Tesamorelin on Neurocognitive Impairment in Abdominally Obese Persons with HIV.

In people with HIV (PWH) who are virally suppressed (VS) on antiretroviral therapy (ART), abdominal obesity (AO) is linked to neurocognitive impairment (NCI), potentially due to visceral adiposity, inflammation, and reduced insulin-like growth factor 1 (IGF-1). Tesamorelin, a growth hormone-releasing hormone, reduces AO and increases IGF-1, suggesting it might mitigate NCI in VS PWH. This 6-month, Phase II randomized, open-label clinical trial compared Tesamorelin versus standard-of-care (SOC) for NCI in abdominally obese PWH. Participants had VS, NCI, and AO (elevated waist circumference [WC]). Exclusions included conditions other than HIV causing NCI, active substance use disorder, and malignancy. Seventy-three participants were randomized 3:2 to Tesamorelin or SOC (2mg subcutaneously daily). The primary outcome was the change in neurocognitive performance at 6 months, with secondary outcomes including WC, mood, and daily functioning. The groups were well-matched at baseline. The Tesamorelin group showed a trend toward improved neurocognitive performance after 6 months (mean change: 0.146, 95% CI: -0.002 to 0.294, p=0.060), while the SOC group did not (0.103, 95% CI: -0.095 to 0.301, p=0.295), but the between-group difference was not significant (p=0.673). IGF-1 levels increased, but changes did not correlate with sRCS or WC. The Tesamorelin group had a greater reduction in WC than the SOC group (median difference -2.7 cm, p=0.015). While tesamorelin reduced WC, the cognitive benefits did not significantly differ between groups. Recognizing the limitations of insufficient power and no placebo arm, this study suggests no clear benefit of short-term AO reduction with tesamorelin on NCI.