Prospective Randomised Research Articles

Endocrine Outcome and Quality of Life After Transsphenoidal Resection of Pituitary Adenoma—A Prospective Randomized Single-Blinded Study Comparing Endoscopic Versus Microscopic Resection

Background: Endoscopic pituitary surgery might yield better endocrine outcomes compared to microscopic resection. We conducted a prospective, randomized, single-blinded study to compare the endocrine outcome and quality of life (QoL) of patients with newly diagnosed pituitary adenoma who underwent either endoscopic or microscopic transsphenoidal surgery (NCT03515603). Methods: Due to slow recruitment, this study had to be stopped prematurely. Out of 170 transsphenoidal pituitary surgeries performed during the study period, 36 patients were enrolled in this study. The primary endpoint was based on the development of a new hypopituitarism. Secondary endpoints included the extent of resection, complications, and QoL. Results: Endoscopic surgery was performed in 47.2% (n = 17). A new hypopituitarism was found in 8.3% (n = 3). All these cases underwent microscopic resection. Arginine vasopressin deficiency was found in 2.7% (n = 1) after microscopic resection. Gross total resection was achieved in 94.4% (n = 34). No surgical complications or new neurological deficits were observed. QoL improved significantly after the surgery, as measured by EQ-VAS (p = 0.003). According to EQ-5D3L, QoL improved or remained unchanged in almost all patients. No significant difference was found in QoL between the endoscopic and microscopic groups. Conclusion: The endoscopic technique appears to offer benefits in the treatment of pituitary adenomas, particularly in terms of achieving a favorable endocrine outcome.

Effect of local epidural application of methylprednisolone acetate on time to ambulation in non-ambulatory dogs with thoracolumbar intervertebral disc disease: A prospective randomised, blinded control trial.

The objective of this study was to analyse the potential benefit of the epidural application of steroids on time to ambulation in non-ambulatory dogs affected by intervertebral disc disease (IVDD) treated with decompressive surgery. This prospective, randomised, blinded control trial involved 41 dogs with thoracolumbar disc extrusion, which were randomly allocated into two groups. In the control group, saline was locally applied after surgical decompression of the spinal cord (n = 23). In the treatment group (n = 18), local epidural application of methylprednisolone acetate (1mg/kg) was used. Ambulation time was the primary outcome measure, defined as the ability to take 10 independent steps. The median number of days to ambulation was 7 days (range: 1‒17 days) for the control group and 3 days (range: 1‒8 days) for the treatment group. One dog from the treatment group developed discospondylitis and abscess formation. The study's heterogeneity in dog breeds, ages and pre-existing health conditions could affect the generalisability of the findings. Epidural methylprednisolone acetate applied locally at the time of surgery may accelerate recovery in dogs following IVDD surgery.

Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study.

The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Hypomanic symptoms in major depressive disorder: Prognostic impact and treatment issues

BackgroundMixed depression (MXD), defined as (hypo)manic symptoms occurring within major depressive episodes, is common in both bipolar and unipolar disorders, but its prognostic and treatment implications remain unclear. This study aimed to examine the relationship between hypomanic symptoms, treatment response and remission of suicidal thoughts. MethodsWe analyzed 1243 adults with major depressive disorder (MDD), recruited for a naturalistic study on treatment-resistant depression. Data were gathered cross-sectionally and retrospectively through structured interviews and clinical rating scales including the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS); statistical analyses were performed using univariate and multivariate methods. ResultsHypomanic symptoms were present in 651 patients (45 %), while 307 patients (25 %) responded to treatment. Both treatment responders (p < 0.0001) and those who achieved remission from suicide ideation (p = 0.0085) showed lower hypomanic (YMRS) scores. Multivariate analysis showed that hypomanic symptoms were negatively linked to treatment response (O.R. 0.71–0.87), while bipolar spectrum markers such as age at illness onset (O.R. 1.00–1.03) and MDD recurrence (O.R. 0.47–0.89) predicted remission from suicidal thoughts. Medications commonly used to treat bipolar disorder showed some benefits, with dopamine/serotonin antagonists improving suicide ideation (p < 0.0001) and mood stabilizers being associated with reduced hypomanic symptoms (p = 0.0003). LimitationsThe study lacked prospective clinical assessments and treatment randomization. ConclusionHypomanic symptoms are common in unipolar depression; their assessment is essential to identify challenging-to-treat cases and select the best pharmacological options.

TCT-486 Ultrasound-Based Renal Denervation Reduces Blood Pressure in Patients With Chronic Kidney Disease: Results of a Multicenter Prospective Randomized Sham-Controlled Blinded Investigator Initiated Trial

TCT-486 Ultrasound-Based Renal Denervation Reduces Blood Pressure in Patients With Chronic Kidney Disease: Results of a Multicenter Prospective Randomized Sham-Controlled Blinded Investigator Initiated Trial

A comparative evaluation of ultrasound guided dual transversus abdominis plane block versus erector spinae plane block for postoperative analgesia in patients undergoing laparoscopic cholecystectomy: A randomised prospective study

: Effective pain control after laparoscopic cholecystectomy (LC) is crucial for early patient mobilization, facilitating a speedy recovery and avoiding several complications. Ultrasound (USG) guided bilateral dual transversus abdominis plane block (DTAPB) and erector spinae plane block (ESPB) are effective for providing postoperative pain relief after LC.A prospective randomised, study comprising of 100 patients posted for elective LC. To compare the effectiveness of USG-guided DTAPB and ESPB for providing postoperative pain relief in patients undergoing LC. A total of 100 patients aged 18-70 years, were included in the study and divided into two groups of 50 patients each. Group DTAPB received bilateral DTAPB and group ESPB received bilateral ESPB, using 50 ml of 0.25% ropivacaine with 8 mgs of dexamethasone. Post operative visual analogue score (VAS) score, time to first analgesia request, total number of analgesic doses required in 24 hours (hrs) and complications if any were noted. VAS score was higher in DTAPB group than ESPB group at 1,2,6,8 and 14 hrs. In DTAPB group patients requested analgesia after an average of 8 ±2.0 hrs, whereas in ESPB group they requested after 12 ± 3.16 hrs. In ESPB group 45 patients needed single analgesic dose and only 5 needed second analgesic doses. However, in DTAPB group 35 patients received single and 15 patients received second analgesic dose. Side effects were comparable in both the groups.USG-guided bilateral ESPB with 50 ml of 0.25% ropivacaine plus dexamethasone is an effective approach in reducing postoperative pain following LC.

Effects of Different Agents of the Lubrication of i-gel Airway on the Incidence of Postoperative Sore Throat: A Prospective Randomised Controlled Trial.

The aim of this study is to compare the effect of different lubricating agents used with the i-gel® laryngeal mask airwayon the incidence of postoperative sore throat. After obtaining institutional ethics approval, this prospective trial was conducted on 150 patients who were scheduled for minor surgical procedures. The study population was placed in three groups of 50 each, after randomization with computer-generated random numbers, based on the lubricant used (Group LJ: with lignocaine jelly as the lubricant, Group WJ: with water-based jelly as a lubricant, Group NS: with 0.9% normal saline as a lubricant). The time taken to secure the airway (from insertion to the first end-tidal carbon dioxide (ETCO2) tracing and five-point auscultation) and the number of attempts were noted. During extubation, blood staining was noted. In the postoperative period, sore throat was monitored with the numerical rating scale for the first 24 hours. Postoperative hoarseness of voice, cough and difficulty in swallowing were the other parameters noted. The results were entered in a standard spread sheet. Statistical analysis was done using JASP version 0.18.3.0 using the independent samples t-test and the Chi-square test for quantitative variables. All three groups were comparable in terms of demography (p > 0.05). The time taken to insertion, number of attempts and securing of the airway were also comparable amongst the three groups (p > 0.05). Blood staining during LMA removal was comparable between the three groups (p > 0.05). In the postoperative period, sore throat was comparable between the three groups (p > 0.05). The incidence of hoarseness of voice in the postoperative period however was more significant in Group LJ when compared to the other two (p < 0.05). Postoperative swallowing discomfort was also significantly higher in Group LJ than in the other two groups (p < 0.05). We conclude that lignocaine jelly, water-based jelly and normal saline used as lubricating agents on the i-gel airway did not show a difference in the incidence of postoperative sore throat. Lignocaine jelly was associated with a higher incidence of hoarseness of voice and swallowing discomfort when compared to the other lubricants.

Short Treatment of 42 Days with Oral GS-441524 Results in Equal Efficacy as the Recommended 84-Day Treatment in Cats Suffering from Feline Infectious Peritonitis with Effusion-A Prospective Randomized Controlled Study.

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective.

Trifluridine/tipiracil + oxaliplatin ± nivolumab vs FOLFOX ± nivolumab in HER2 negative advanced oesogastric adenocarcinoma: The PRODIGE73-UCGI40-LOGICAN trial

BackgroundTrifluridine/tipiracil (FTD/TPI) is approved in third-line treatment of patients with advanced/metastatic gastric and gastroesophageal junction adenocarcinomas (aGA/GEJA). The association of oxaliplatin with FTD/TPI is promising and the combination of FTD/TPI + oxaliplatin + nivolumab has shown a predictable and manageable safety profile. AimsThe aim is to evaluate the efficacy and safety of FTD/TPI plus oxaliplatin with or without nivolumab in patients, with HER2 negative aGA/GEJA, unfit for triplet chemotherapy (TFOX/mFLOT regimen), in the first-line metastatic setting in comparison with the standard of care FOLFOX with or without nivolumab. MethodsThis study is a prospective randomised, open label, comparative, multicentre, phase II trial designed to include 118 patients. The primary objective is to evaluate the superiority of FTD/TPI plus oxaliplatin with or without nivolumab over FOLFOX regimen with or without nivolumab in terms of PFS in a population of patients non candidate for triplet chemotherapy. Nivolumab will be used for patients whose tumour express PD-L1 with a CPS score ≥5. DiscussionPRODIGE73-UCGI40-LOGICAN study will provide efficacy and safety data on the association of FTD/TPI plus oxaliplatin with or without nivolumab versus FOLFOX regimen with or without nivolumab in first-line palliative setting, in patients with aGA/GEJA (NCT05476796).

Association between lung function and risk of microvascular diseases in patients with diabetes: A prospective cohort and Mendelian randomization study

Background and aimsTo investigate causal relationships of lung function with risks microvascular diseases among participants with diabetes, type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM), respectively, in prospective and Mendelian randomization (MR) study. Methods and results14,617 participants with diabetes and without microvascular diseases at baseline from the UK Biobank were included in the prospective analysis. Of these, 13,421 had T2DM and 1196 had T1DM. The linear MR analyses were conducted in the UK Biobank with 6838 cases of microvascular diseases and 10,755 controls. Lung function measurements included forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The study outcome was microvascular diseases, a composite outcome including chronic kidney diseases, retinopathy and peripheral neuropathy. During a median follow-up of 12.1 years, 2668 new-onset microvascular diseases were recorded. FVC (%predicted) was inversely associated with the risk of new-onset microvascular diseases in participants with diabetes (Per SD increment, adjusted HR = 0.86; 95%CI:0.83–0.89), T2DM (Per SD increment, adjusted HR = 0.86; 95%CI:0.82–0.90) and T1DM (Per SD increment, adjusted HR = 0.87; 95%CI: 0.79–0.97), respectively. Similar results were found for FEV1 (%predicted). In MR analyses, genetically predicted FVC (adjusted RR = 0.55, 95%CI:0.39–0.77) and FEV1 (adjusted RR = 0.48, 95%CI:0.28–0.83) were both inversely associated with microvascular diseases in participants with T1DM. No significant association was found in those with T2DM. Similar findings were found for each component of microvascular diseases. ConclusionThere was a causal inverse association between lung function and risks of microvascular diseases in participants with T1DM, but not in those with T2DM.

A Multicenter Prospective Randomized Controlled Trial Comparing Cxbladder Triage to Cystoscopy in Patients With Microhematuria: The Safe Testing of Risk for Asymptomatic Microhematuria Trial.

AUA guidelines for patients with microhematuria (≥3 red blood cells [RBC]/high-power field [hpf]) include cystoscopy for most over age 40 due to risk of urothelial cancer (UC). Cxbladder Triage (CxbT) is a urinary genomic test with UC negative predictive value of 99%. In this prospective randomized controlled trial, we compared cystoscopy use in a standard of care (SOC) arm vs a marker-based approach. All patients with hematuria provided urine for a CxbT. Those categorized as lower risk (LR), defined as 3 to 29 RBC/hpf and minimal smoking history (<10 pack-years) were randomized between the test group provided with the CxbT result vs the SOC control group. Negative CxbT patients were offered omission of cystoscopy with surveillance. "Not lower risk" (NLR) patients (>30 RBC/hpf or >10 pack-year smoking history) had a CxbT but otherwise SOC. Patient decision and outcomes were recorded. Of 390 eligible patients, 255 were NLR and 135 were LR randomized to CxbT informed decision or SOC. The median age was 62 years (range 18-94) and 54% were male. Overall, 63% of CxbT tests were negative. For NLR patients, 82% had cystoscopy. In the LR control group, cystoscopy was performed in 67% of SOC and 27% in the test group (relative risk 0.41 [95% CI 0.27-0.61]). Compared to cystoscopy, CxbT had 90% sensitivity, 56% specificity, and 99% negative predictive value for UC. In this prospective randomized controlled trial, use of CxbT in patients with LR hematuria resulted in 59% reduction of cystoscopy use. This clinical utility of CxbT can reduce the burden of unnecessary cystoscopies.

A simple and robust parametric shared frailty model for recurrent events with the competing risk of death: An application to the Carvedilol Prospective Randomized Cumulative Survival trial.

Many non-fatal events can be considered recurrent in that they can occur repeatedly over time, and some researchers may be interested in the trajectory and relative risk of non-fatal events. With the competing risk of death, the treatment effect on the mean number of recurrent events is non-identifiable since the observed mean is a function of both the recurrent event and terminal event processes. In this paper, we assume independence between the non-fatal and the terminal event process, conditional on the shared frailty, to fit a parametric model that recovers the trajectory of, and identifies the effect of treatment on, the non-fatal event process in the presence of the competing risk of death. Simulation studies are conducted to verify the reliability of our estimators. We illustrate the method and perform model diagnostics using the Carvedilol Prospective Randomized Cumulative Survival trial which involves heart-failure events.

Multicenter prospective randomized controlled clinical trial comparing the pocket-creation method with and without single-clip traction of colonic endoscopic submucosal dissection.

The pocket-creation method (PCM) was developed to overcome the technical difficulties of endoscopic submucosal dissection (ESD), although opening the pocket remains challenging. We developed a novel technique of PCM with single-clip traction (PCM-CT), which uses a reopenable clip as a traction device to maintain stability during the procedure. No prospective study has compared the efficacy of PCM-CT and PCM. This study aimed to investigate the effectiveness of PCM-CT vs. PCM in a randomized controlled trial. This randomized controlled clinical trial was conducted at four Japanese institutions. Patients with superficial colorectal neoplastic lesions were included following Japanese guidelines for colorectal cancer. Seven moderately experienced endoscopists performed the ESD procedures using either PCM-CT or PCM. 100 patients were enrolled in the study. Compared with PCM, PCM-CT achieved significantly faster mean (SD) dissection speed (21.4 [10.8] vs. 27.0 [14.5] mm2/min [95%CI 0.5 to 10.7], P = 0.03), and reduced the mean procedure time (81.8 [57.9] vs. 64.8 [47.6] minutes [95%CI -38.2 to 4.3], P = 0.12) and pocket-opening time (37.8 [33.0] vs. 30.0 [28.9] minutes [95%CI -20.2 to 4.6], P = 0.22). En bloc and R0 resection rates were not significantly different between the two groups (100% vs. 100%, P >0.99; 100% vs. 96%, P = 0.50, respectively). No significant differences were observed in adverse events between the two groups. ESD facilitated by the novel PCM-CT method appeared to be significantly faster than PCM. Both methods achieved high R0 resection rates.

Efficacy of Octyl-Cyanoacrylate Dermabond Adhesive Glue versus Polyglactin 3/0 Suture for Closure of Caesarean Section Skin Incision - A Prospective Randomised Controlled Trial

This was a prospective randomised controlled trial conducted at a tertiary hospital on 82 women who underwent caesarean section aiming to assess the efficacy of octyl-cyanoacrylate tissue adhesive glue versus polyglactin 3/0 suture for the closure of caesarean sections skin incision. The study group consisted of 41 women who underwent skin closure using octyl-cyanoacrylate tissue adhesive glue, whereas 41 women in the control group had subcuticular skin closure using polyglactin 3/0 sutures. The choice of anaesthesia, prophylactic antibiotic, operative technique, and immediate post-operative oral analgesia was standardised between the two groups. Time taken for skin closure, pain score at day 2 and 14, the total analgesia dose needed and duration (day two onwards), and any adverse events were recorded. The time required for skin closure was significantly less in the study group, with a mean difference of 97.7 seconds (170.8 seconds vs 268.5 seconds, p&lt;0.001). Pain scores on day 2 were similar between the two groups (4.0 vs 5.0, p=0.09), whereas pain score on day 14 was significantly lower in the study group (2.0 vs 4.0, p&lt;0.001). The median duration (day two onward) of oral analgesia use was four days in the study group and six days in the control group. The difference was statistically significant (p=&lt;0.001). The median amount of additional analgesia required was a third less in the tissue adhesive group than in the control group. On day 14, surgical site infection was similar in both groups. In conclusion, octyl-cyanoacrylate tissue adhesive glue may safely close a caesarean section skin incision. It was associated with faster application, lesser pain score, and lesser need for analgesia without additional adverse events compared to the conventional suturing method.

Association between sarcopenia-related markers and cholelithiasis: A prospective and Mendelian randomization study.

Cholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia-related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia-related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two-sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow-up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis.

GCISAVE: A non-comparative randomized phase II study of combination of gemcitabine cisplatin (GCis) +/- avelumab (A) in 1st line treatment for locally advanced or metastatic urothelial bladder carcinoma (MUBC)—GETUG AFU V07.

GCISAVE: A non-comparative randomized phase II study of combination of gemcitabine cisplatin (GCis) +/- avelumab (A) in 1st line treatment for locally advanced or metastatic urothelial bladder carcinoma (MUBC)—GETUG AFU V07.

OP20 Postoperative endoscopic recurrence after resection of Crohn’s terminal ileitis with Kono-S or side-to-side functional end anastomosis: results of a Multicenter Prospective Randomized Trial

Abstract Background A novel anastomosis (Kono-S) was described in 2003 in Crohn’s disease. Subsequent observations have suggested that this anastomosis is associated with lower endoscopic and surgical recurrence rates. The purpose of this study was to compare the endoscopic recurrence between the Kono-S and the side-to-side functional end anastomosis at 3-6 months after resection of Crohn’s terminal ileitis. Methods This was a prospective multi-center randomized trial conducted at eight international centers. Patients with Crohn’s terminal ileitis requiring elective ileocecal resection were randomized to a Kono-S (Group1) or a side-to-side functional end (Group2) anastomosis (Image1). Patients were discharged on no biologicals. Exclusion criteria included age (&amp;lt;18), pregnancy, recurrent or multisite Crohn’s disease, and need of postoperative treatment with biologicals. Data were collected prior to and during surgery, daily after surgery until discharge, at 30 days post-op, and at 3-6 months colonoscopy. Participating surgeons were instructed in the Kono-S technique through videos. Disease clinical activity was measured by Harvey Bradshaw Index (HBI). Endoscopic remission/recurrence was graded with the modified Rutgeerts score: endoscopic remission was defined as a Rutgeerts score of 0, 1, or 2a, and a Rutgeerts score of 2b or higher was considered a recurrence. All study sites had Institutional Review Board approval, ClinicalTrial.gov # NCT03256240. Results We enrolled 288 Crohn’s patients (50.7% female) with a median age of 34 (18-81). 154 patients were randomized to Group 1 (Kono-S) and 134 to Group 2 (Side-to-Side). 30 days follow-up was completed on 278 (96.9%) patients. The Kono-S group had a higher percentage of past smokers (57 vs.30, p = 0.007) and current smokers (33 vs.12, p = 0.004). The mean operative time was 22 minutes longer in the Kono-S group (154 vs.132 minutes; p = 0.386). There was no mortality. 233 (81%) patients underwent a colonoscopy at 3-6 months. There was no significant difference between the two groups in terms of endoscopic recurrence (p = 0.883) and HBI (p = 0.109) or in recurrence-free survival (Log Rank Mantel-Cox test p = 0.256) (Table 1). On multivariable analysis, current smokers had significantly higher odds for endoscopic recurrence at 3-6 months (OR= 2.80, [95% CI =1.10 - 6.92], p = 0.029). Conclusion Kono-S and Side-to-side anastomoses have similar endoscopic recurrence rates at 3-6 months. Independently of surgical techniques, smokers had a significantly higher rate of endoscopic recurrence at 3-6 months after surgery.

Comparison of Ultrasound Versus Non Ultrasound based Techniques for Internal Jugular Venous Cannulation in Cardiac Surgical Patients: A Prospective Randomised Controlled Trial

Comparison of Ultrasound Versus Non Ultrasound based Techniques for Internal Jugular Venous Cannulation in Cardiac Surgical Patients: A Prospective Randomised Controlled Trial

364. Novel Polygalacturonic and Caprylic Acid (PG+CAP) Antimicrobial Wound Ointment is Effective in Managing Microbially Contaminated Chronic Wounds in a Pilot Prospective Randomized Clinical Study

Abstract Background The use of antibiotics and antiseptics in the management of biofilm colonized chronic wounds is not fully effective in eradicating multidrug-resistant organisms. We developed PG+CAP ointment combining naturally derived agents commonly used in skin care and showed in our in vitro study that PG-+CAP combination ointment could rapidly eradicate gram positive, gram negative and fungal organisms embedded in biofilm within 1 hour. Furthermore, in a full thickness, microbially contaminated swine wound model study we found that with daily ointment application, PG+CAP ointment was significantly better at healing wounds at 2 weeks compared to MediHoney and was also significantly better at eradicating microbes colonizing wound tissues. In this current pilot human study, we compared PG+CAP ointment to MediHoney at three international centers. Methods This is a multicenter prospective randomized open label comparative study where patients with chronic full-thickness wounds at three academic international medical centers (American University of Beirut and Lebanese American University, Lebanon and Albert Einstein Medical Center, Brazil) were randomized to a daily treatment with either PG+CAP ointment or MediHoney. Clinical and wound assessments were obtained weekly up to 6 weeks. Full improvement was defined as 50% or greater decrease in wound size and/or a 75% or greater re-epithelialization and granulation of the wound with no necrosis or related adverse events (AEs) or sepsis. The validated Pressure Ulcer Scale for Healing (PUSH) score was used to track wound healing. Results A total of 20 patients with chronic wounds were included (10 patients in each arm). Age and clinical characteristics were comparable in both groups. Diabetes mellitus tended to occur more frequently in the PG+CAP arm (See Table 1-P=0.06). Full improvement/healing occurred in all patients (100%) randomized to PG+CAP with no AEs vs 70% full improvement in the MediHoney arm. Patients who received PG+CAP had more than two-fold wound improvement in terms of their PUSH scores compared to MediHoney:Table 1.Characteristics &amp; Outcomes Conclusion Based on preliminary data from this prospective randomized multicenter trial, PG+CAP is safe and possibly more effective in achieving full improvement of chronic contaminated wounds when compared to MediHoney. Disclosures Joel Rosenblatt, PhD, Novel Anti-Infective Technologies, LLC: Licensed Technology Issam I. Raad, Distinguished Professor, Novel Anti-Infective Technologies, LLC: Technology License

Investigating linear and nonlinear associations of LDL cholesterol with incident chronic kidney disease, atherosclerotic cardiovascular disease and all-cause mortality: A prospective and Mendelian randomization study

Background and aimsObservational studies suggest potential nonlinear associations of low-density lipoprotein cholesterol (LDL-C) with cardio-renal diseases and mortality, but the causal nature of these associations is unclear. We aimed to determine the shape of causal relationships of LDL-C with incident chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality, and to evaluate the absolute risk of adverse outcomes contributed by LDL-C itself. MethodsObservational analysis and one-sample Mendelian randomization (MR) with linear and nonlinear assumptions were performed using the UK Biobank of >0.3 million participants with no reported prescription of lipid-lowering drugs. Two-sample MR on summary-level data from the Global Lipid Genetics Consortium (N = 296,680) and the CKDGen (N = 625,219) was employed to replicate the relationship for kidney traits. The 10-year probabilities of the outcomes was estimated by integrating the MR and Cox models. ResultsObservationally, participants with low LDL-C were significantly associated with a decreased risk of ASCVD, but an increased risk of CKD and all-cause mortality. Univariable MR showed an inverse total effect of LDL-C on incident CKD (HR [95% CI]:0.84 [0.73–0.96]; p = 0.011), a positive effect on ASCVD (1.41 [1.29–1.53]; p<0.001), and no significant causal effect on all-cause mortality. Multivariable MR, controlling for high-density lipoprotein cholesterol (HDL-C) and triglycerides, identified a positive direct effect on ASCVD (1.32 [1.18–1.47]; p<0.001), but not on CKD and all-cause mortality. These results indicated that genetically predicted low LDL-C had an inverse indirect effect on CKD mediated by HDL-C and triglycerides, which was validated by a two-sample MR analysis using summary-level data from the Global Lipid Genetics Consortium (N = 296,680) and the CKDGen consortium (N = 625,219). Suggestive evidence of a nonlinear causal association between LDL-C and CKD was found. The 10-year probability curve showed that LDL-C concentrations below 3.5 mmol/L were associated with an increased risk of CKD. ConclusionsIn the general population, lower LDL-C was causally associated with lower risk of ASCVD, but appeared to have a trade-off for an increased risk of CKD, with not much effect on all-cause mortality. LDL-C concentration below 3.5 mmol/L may increase the risk of CKD.