Main Endpoint Research Articles

Outcome of percutaneous coronary intervention using ultrathin-strut biodegradable polymer sirolimus-eluting versus thin-strut durable polymer zotarolimus-eluting stents in patients with comorbid peripheral arterial disease: a post-hoc analysis from two randomized trials.

In patients with peripheral arterial disease (PADs), who underwent percutaneous coronary intervention (PCI), little is known about the potential impact of using different new-generation drug-eluting stents (DES) on outcome. In PCI all-comers, the results of most between-stent comparisons-stratified by strut thickness-suggested some advantage of coronary stents with ultrathin-struts. The current post-hoc analysis aimed to assess outcomes of PCI with ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) vs. thin-strut durable polymer zotarolimus-eluting stents (DP-ZES) in patients with PADs. We pooled 3-year patient-level data from two large-scale randomized all-comer trials to compare Orsiro ultrathin-strut BP-SES vs. Resolute-type thin-strut DP-ZES in trial participants with concomitant PADs. BIO-RESORT (December 2012 to August 2015) and BIONYX (October 2015 to December 2016) included all-comer patients who were aged 18 years or older, capable of providing informed consent, and required a PCI. The trials had web-based randomization, with block sizes of 4 and 8, performed in a 1:1:1 or 1:1 fashion. Assessors, research staff, and patients were blinded to the type of stent used. We assessed the composite main clinical endpoint target vessel failure [TVF: cardiac death, target vessel related myocardial infarction (MI), or clinically indicated target vessel revascularization (TVR)], its components, and stent thrombosis. Of 4,830 trial participants, 360 had PADs: 177 (49.2%) were treated with BP-SES and 183 (50.8%) with DP-ZES. Baseline characteristics were similar. For BP-SES, the 3-year TVF rate was 11.0% and for DP-ZES 17.9% [hazard ratio (HR): 0.59, 95% CI: 0.33-1.04; P=0.07]. For BP-SES, the TVR rate was lower than for DP-ZES (4.1% vs. 11.0%; HR: 0.36, 95% CI: 0.15-0.86; P=0.016), but this did not translate into between-group differences in cardiac death or MI. In small vessels (<2.75 mm), the TVR rate was also lower in BP-SES (5.6% vs. 13.9%; HR: 0.32, 95% CI: 0.11-0.91; P=0.024). Definite-or-probable stent thrombosis rates were 1.2% and 2.3% (P=0.43). In PCI patients with PADs, the 3-year TVF incidence was numerically lower in the ultrathin-strut BP-SES vs. the thin-strut DP-ZES group. Furthermore, TVR risk was significantly lower in ultrathin-strut BP-SES, mainly driven by a lower TVR rate in small vessels. BIO-RESORT trial: clinicaltrials.gov (NCT01674803); BIONYX trial: clinicaltrials.gov (NCT02508714).

Effectiveness of Transcatheter Closure of Patent Foramen Ovale in Clinical Practice.

Background Transcatheter closure of patent foramen ovale (PFO) has reduced the risk of recurrent stroke in patients with cryptogenic strokes in randomized clinical trials. Whether PFO closure in clinical practice is associated with similar benefit remains unknown. Methods and Results We identified patients with PFO and a history of ischemic stroke or transient ischemic attack who were treated with PFO closure or medical therapy in the OptumLabs database. The primary end point was recurrent ischemic stroke or systemic embolization. Secondary outcomes included mortality, all stroke, transient ischemic attack, and major bleeding. A total of 6668 propensity-matched patients were included (PFO closure n=4111; medical therapy n=2557). The incidence of stroke or systemic embolization per 100 person-years was 2.38 after PFO cohort and 2.99 with medical therapy (hazard ratio [HR], 0.85 [95% CI, 0.68-1.05], P=0.13). Mortality was lower in the PFO closure cohort (1.78 versus 2.59 per 100 person-years: HR, 0.69 [95% CI, 0.55-0.87], P=0.002). Falsification end points showed that this difference is unlikely to be completely explained by residual confounders. There were no significant differences between the groups in secondary end points including intracranial hemorrhage and major bleeding except for an increase in nonintracranial hemorrhage bleeding among patients treated with oral anticoagulation (1.42 versus 2.16 per 100 person-years: HR, 0.69 [95% CI, 0.48-0.99], P=0.043). The main end point was consistent in subanalyses including patients <60 years of age, patients with prior stroke, and those treated after the publication of the positive PFO trials in 2017. Conclusions In contemporary US practice, PFO closure is not associated with lower rates of recurrent ischemic stroke or systemic embolization compared with medical therapy. Potential reasons for this discrepancy warrant further investigation.

Long-term outcome of transcatheter repair of paravalvular leak post surgical mitral valve replacement

Objective: To explore the long-term clinical efficacy of transcatheter repair of mitral paravalvular leak (PVL) post surgical mitral valve replacement. Methods: This study is a retrospective study. Patients who completed transcatheter repair of paravalvular leak after surgical mitral valve replacement at Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine from March 2010 to December 2018 were included. Technical success was defined as the occluder being stably implanted in the paravalvular leak site without affecting the function of the mitral valve and surrounding tissues; and there were no intervention-related complications, such as new hemolysis or aggravated hemolysis, and echocardiography confirmed mitral paravalvular regurgitation reduced by more than 1 grade. Patients were followed up at 30 days, 1, and 3 years after the intervention. The main endpoints were all-cause death and re-surgery due to interventional failure or serious complications. The occurrence of occluder-mediated hemolysis and chronic renal insufficiency was recorded, and patients were monitored with echocardiography during follow up. Results: A total of 75 patients were included, aged (54.3±22.9) years old, and 38 patients were males. All patients had decreased cardiac function and/or hemolysis before intervention. Procedural success was achieved in 54 patients (72.0%). Incidence of device-mediated hemolysis was 18.7% (14/75). During the follow-up period, all-cause death occurred in 7 patients (9.3%), and 3 were cardiac deaths.The 3-year event-free survival rate was 81.3% (61/75). The need for cardiac surgery was 9.3% (7/75): 3 cases due to severe device-mediated hemolysis, 2 cases due to prosthetic valve failure and 2 cases due to moderate to severe residual regurgitation. The echocardiography follow-up results showed that the position of the occluder was stable, there was no impact on the artificial valve function and surrounding structures, and the residual regurgitation was stable without progressive increase in event-free patients. Compared with pre-intervention, the left ventricular end systolic diameter ((33.9±7.4)mm vs. (38.3±8.9) mm, P=0.036), end diastolic diameter ((53.7±8.3) mm vs. (58.4±9.1) mm, P=0.045) and left atrial diameter (59.3 (44.5, 90.7) mm vs. 64.3 (44.8, 96.6) mm, P=0.049) were significantly reduced, pulmonary artery systolic pressure was also significantly decreased ((36.5±15.8) mmHg vs. (46.3±14.9) mmHg, P=0.022, 1 mmHg=0.133 kPa). There was no significant difference between 3 years and 1 year after transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement (all P>0.05). Conclusion: Transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement is an effective treatment option in selective patients.

Substituting a randomised placebo control group with a historical placebo control in an endometriosis pain trial: a case study re-evaluating trial data using historical control data from another trial

ObjectiveThe substitution of an in-study control population with a historical control (HC) population is considered a viable option for reducing the necessary recruitment of control patients. However, it is necessary...

Comparison of efficacy of conbercept, aflibercept, and ranibizumab ophthalmic injection in the treatment of macular edema caused by retinal vein occlusion: a Meta-analysis.

To evaluate and compare the anatomical and functional outcomes and negative effects of the three anti-vascular endothelial growth factor (VEGF) drugs in the treatment of macular edema (ME) due to retinal vein occlusion (RVO) based on the evidence pooled from current clinical trials and observational studies. A systematic literature search was conducted on nine online databases from inception until April 30, 2022. The main endpoints were best corrected visual acuity (BCVA), central macular thickness (CMT), and adverse events (AEs). Cumulative Meta-analysis was conducted to synthesize the outcomes of the drugs. The retrieved data were analyzed using Stata software (version 12.0). A total of 20 studies comprising 1674 eyes met the inclusion criteria to the Meta-analysis. It was observed that conbercept and aflibercept had better visual acuity effects compared with ranibizumab at 1mo [weight mean difference (WMD)=-0.03, P=0.001; WMD=-0.05, P=0.019], but the effects were not different from that of ranibizumab at 6mo. Moreover, there was not statistically significant difference in the proportion of patients gaining ≥15 letters at 12-24mo between aflibercept and ranibizumab [odds ratio (OR)=1.16, P=0.427]. Conbercept had higher mean CMT change effects at 1mo (WMD=-14.43, P=0.014) and 6mo (WMD=-35.63, P≤0.001) compared with ranibizumab. Meanwhile, the mean CMT change effects at 1mo (WMD=-10.14, P=0.170), 6mo (WMD=-26.98, P=0.140) and 12-24mo (WMD=-12.34, P=0.071) were comparable among the groups. Similarly, AEs were not significantly different among the treatments (OR=0.75, P=0.305; OR=1.04, P=0.89). The stability of effect size of mean BCVA and CMT improved with the increase in sample size. Aflibercept and conbercept required fewer injections compared with ranibizumab. This is the first study to evaluate the efficacy and AEs of intravitreal administration of conbercept, ranibizumab, and aflibercept in the treatment of RVO-ME. Intravitreal aflibercept or conbercept results in better mean change in vision and CMT reduction compared with ranibizumab. Conbercept can be considered to be a promising and innovative drug with good anti-VEGF effects.

Correlation between measured and predicted mismatch with valve hemodynamics in transcatheter aortic valve replacement: A sex-based analysis.

Data regarding the reliability of predicted effective orifice area indexed (pEOAi) is scarce in transcatheter aortic valve replacement (TAVR). To assess the validity of the pEOAi in TAVR by correlating its value with echocardiography-derived hemodynamic data. A single-center retrospective cohort study of TAVR patients from 2012 to 2021 with available echocardiograms was conducted. Patient-prosthesis mismatch (PPM) was defined based on the Valve Academic Research Consortium 3 criteria. The main endpoints were the congruence of measured effective orifice area indexed(EOAi) and pEOAi with the hemodynamic data obtained by echocardiography. The secondary endpoint included a correlation of predicted PPM (pPPM) and measured PPM (mPPM) with postoperative New York Heart Association(NYHA) status. A total of 318 patients were included. pPPM was more frequent than mPPM (54 [17%]; all moderate PPM vs. 39 [12.3%]: 32 moderate and 7 severe PPM).Predicted and measured EOAi were statistically correlated with postprocedural transvalvular mean gradient and Doppler velocity index (all p < 0.001), including in both sex-based subgroups. The positive predictive value and negative predictive value (NPV) of pPPM for postprocedural transvalvular mean gradient ≥ 20 mmHg were 16% and 97%, respectively. Only pPPM was significantly more prevalent in the group in which NYHA failed to improve than in those with symptom improvement (30.1% vs. 16%, p = 0.027). Predicted PPM has an excellent NPV for postprocedural transvalvular mean gradient ≥ 20 mmHg and seems to be a good predictor of NYHA status evolution as opposed to measured PPM. Predicted EOAi can be used in procedural planning to reduce the risk of PPM in both TAVR male and female patients.

Feasibility of omitting contralateral neck irradiation in patients with node-negative sinonasal squamous cell carcinoma crossing the midline.

Identifying the lymph node target volume in patients with node-negative sinonasal squamous cell carcinoma (SNSCC) crossing the midline poses a challenge. This study aims to address this. We retrospectively reviewed clinically N0 patients with tumors crossing the midline who received elective neck irradiation (ENI) from two centers between 1999 and 2019. The main endpoint was regional relapse-free survival (RRFS). We included 104 patients: 64 received bilateral ENI, and 40 received ipsilateral-only ENI (median follow-up time was 89.99 and 95.01 months, respectively). At 5 years, the RRFS rates were comparable (57.68% vs. 55.83%, p = 0.372), as were the contralateral RRFS (57.68% vs. 61.62%, p = 0.541). Five-year OS, LRFS, and DMFS showed no significant difference between two groups. Our findings provide preliminary evidence suggesting the potential for avoiding contralateral ENI in SNSCC patients with midline crossing tumors who undergo ipsilateral ENI, covering at least level II. Validation through future prospective studies is necessary.

Impact of glycated hemoglobin on 2-year clinical outcomes in elderly patients with atrial fibrillation: sub-analysis of ANAFIE Registry, a large observational study

BackgroundThis ANAFIE Registry sub-analysis investigated 2-year outcomes and oral anticoagulant (OAC) use stratified by glycated hemoglobin (HbA1c) levels among Japanese patients aged ≥ 75 years with non-valvular atrial fibrillation (NVAF) with and without clinical diagnosis of diabetes mellitus (DM).MethodsThe ANAFIE Registry was a large-scale multicenter, observational study conducted in Japan; this sub-analysis included patients with baseline HbA1c data at baseline. The main endpoints evaluated (stroke/systemic embolic events [SEE], major bleeding, intracranial hemorrhage, cardiovascular death, all-cause death, and net clinical outcome [a composite of stroke/SEE, major bleeding, and all-cause death]) were stratified by HbA1c levels (< 6.0%; 6.0% to < 7.0%; 7.0% to < 8.0%; and ≥ 8.0%).ResultsOf 17,526 patients with baseline HbA1c values, 8725 (49.8%) patients had HbA1c < 6.0%, 6700 (38.2%) had 6.0% to < 7.0%, 1548 (8.8%) had 7.0% to < 8.0%, and 553 (3.2%) had ≥ 8.0%. Compared with other subgroups, patients with HbA1c ≥ 8.0% were more likely to have lower renal function, higher CHA2DS2-VASc and HAS-BLED scores, higher prevalence of non-paroxysmal AF, and lower direct OAC (DOAC) administration, but higher warfarin administration. The HbA1c ≥ 8.0% subgroup had higher event rates for all-cause death (log-rank P = 0.003) and net clinical outcome (log-rank P = 0.007). Similar trends were observed for stroke/SEE. In multivariate analysis, risk of all-cause death (adjusted hazard ratio [aHR]: 1.46 [95% confidence interval 1.11–1.93]) and net clinical outcome (aHR 1.33 [1.05–1.68]) were significantly higher in the HbA1c ≥ 8.0% subgroup. No significant differences were observed in risks of major bleeding or other outcomes in this and other subgroups. No interaction was observed between HbA1c and OACs. Use/non-use of antidiabetic drugs was not associated with risk reduction; event risks did not differ with/without injectable antidiabetic drugs.ConclusionsAmong elderly Japanese patients with NVAF, only HbA1c ≥ 8.0% was associated with increased all-cause death and net clinical outcome risks; risks of the events did not increase in other HbA1c subgroups. Relative event risks between patients treated with DOACs and warfarin were not modified by HbA1c level.Trial registrationUMIN000024006; date of registration: September 12, 2016.

Efficacy and safety of SIM0417 (SSD8432) plus ritonavir for COVID-19 treatment: a randomised, double-blind, placebo-controlled, phase 1b trial

SIM0417 (SSD8432) is an orally administered coronavirus main proteinase (3CLpro) inhibitor with potential anti-SARS-CoV-2 activity. This study aimed to evaluate the efficacy and safety of SIM0417 plus ritonavir (a pharmacokinetic enhancer) in adults with COVID-19. This was a randomised, double-blind, placebo-controlled, phase 1b study in China. Adults with asymptomatic infection, mild or moderate COVID-19 were randomly assigned (3:3:2) to receive either 750mg SIM0417 plus 100mg ritonavir, 300mg SIM0417 plus 100mg ritonavir or placebo every 12h for 10 doses. The main efficacy endpoints included SARS-CoV-2 viral load, proportion of participants with positive SARS-CoV-2 nucleic acid test and time to alleviation of COVID-19 symptoms. This trial is registered with ClinicalTrials.gov, NCT05369676. Between May 12 and August 29, 2022, 32 participants were enrolled and randomised to high dose group (n=12), low dose group (n=12) or placebo (n=8). The viral load change from baseline in high dose group was statistically lower compared with placebo, with a maximum mean difference of-2.16±0.761 log10 copies/mL (p=0.0124) on Day 4. The proportion of positive SARS-CoV-2 in both active groups were lower than the placebo. The median time to sustained alleviation of COVID-19 symptoms was 2.0 days in high dose group versus 6.0 days in the placebo group (HR=3.08, 95% CI 0.968-9.818). SIM0417 plus ritonavir were well tolerated with all adverse events in grade1. SIM0417 plus ritonavir was generally well tolerated. The efficacy of SIM0417 showed a monotonic dose-response relationship, and the 750mg SIM0417 plus 100mg ritonavir was selected as the recommended clinical dose. The study was funded by Jiangsu Simcere Pharmaceutical Co., Ltd.

Unresectable Intermediate-Size (3–5 cm) Colorectal Liver Metastases: Stereotactic Ablative Body Radiotherapy Versus Microwave Ablation (COLLISION-XL): Protocol of a Phase II/III Multicentre Randomized Controlled Trial

BackgroundAlthough microwave ablation (MWA) has a low complication rate and good efficacy for small-size (≤ 3 cm) colorectal liver metastases (CRLM), local control decreases with increasing size. Stereotactic body radiotherapy (SBRT) is gaining interest as a potential means to treat intermediate-size CRLM and might be less susceptible to increasing volume. The objective of this study is to compare the efficacy of MWA to SBRT in patients with unresectable, intermediate-size (3–5 cm) CRLM.MethodsIn this two-arm, multicentre phase II/ III randomized controlled trial, 68 patients with 1–3 unresectable, intermediate-size CRLM suitable for both MWA and SBRT, will be included. Patients will be treated with MWA or SBRT as randomised. The Primary endpoint is local tumour progression-free survival (LTPFS) at 1 year (intention-to-treat analysis). Main secondary endpoints are overall survival, overall and distant progression-free survival (DPFS), local control (LC) and procedural morbidity and mortality and assessment of pain and quality of life.DiscussionCurrent guidelines lack clear recommendations for the local treatment of liver only intermediate-size, unresectable CRLM and studies comparing curative intent SBRT and thermal ablation are scarce. Although safety and feasibility to eradicate tumours ≤ 5 cm have been established, both techniques suffer from lower LTPFS and LC rates for larger-size tumours. For the treatment of unresectable intermediate-size CRLM clinical equipoise has been reached. We have designed a two-armed phase II/ III randomized controlled trial directly comparing SBRT to MWA for unresectable CRLM 3–5 cm.Level of EvidenceLevel 1, phase II/ III Randomized controlled trial.Trial Registration: NCT04081168, September 9th 2019.Graphical

The value of intraoperative dynamic liver function test ICG in predicting postoperative complications in patients undergoing staged hepatectomy: a pilot study

PurposeTo assess the predictive value of intraoperative indocyanine green (ICG) test in patients undergoing staged hepatectomy.MethodsWe analyzed intraoperative ICG measurements of future liver remnant (FLR), preoperative ICG, volumetry, and hepatobiliary scintigraphy in 15 patients undergoing associated liver partition and portal vein ligation for staged hepatectomy (ALPPS). Main endpoints were the correlation of intraoperative ICG values to postoperative complications (Comprehensive Complication Index (CCI®)) at discharge and 90 days after surgery, and to postoperative liver function.ResultsMedian intraoperative R15 (ICG retention rate at 15 min) correlated significantly with CCI® at discharge (p = 0.05) and with CCI® at 90 days (p = 0.0036). Preoperative ICG, volumetry, and scintigraphy did not correlate to postoperative outcome. ROC curve analysis revealed a cutoff value of 11.4 for the intraoperative R15 to predict major complications (Clavien-Dindo ≥ III) with 100% sensitivity and 63% specificity. No patient with R15 ≤ 11 developed major complications.ConclusionThis pilot study suggests that intraoperative ICG clearance determines the functional capacity of the future liver remnant more accurately than preoperative tests. This may further reduce the number of postoperative liver failures, even if it means intraoperative abortion of hepatectomy in individual cases.

Niveau d’anxiété et refus scolaire dans les troubles anxieux chez l’adolescent

ObjectivesThe primary objective was to compare the level of anxiety on the Multidimensional Anxiety Scale for Children in two groups of anxious secondary school children, one group out of school meeting the criteria of School Refusal and the other in school. The secondary objective was to compare these groups on other clinical, sociodemographic and therapeutic parameters. Patient and methodRetrospective observational study of 34 school-going anxious teenagers recruited at the University Hospital of Montpellier, compared with 55 out of school anxious teenagers meeting the criteria of Anxious School Refusal recruited in a multicentre study. ResultsThere was no significant intergroup difference in median scores on the Multidimensional Anxiety Scale for Children (P=0.49), but a significant intergroup difference in median scores was found on the Behavioural Anxiety and Phobia Scale with higher total scores in the School Refusal group (151.5 [130.5; 169.0] vs. 125.0 [94.0; 139.0], P<0.01). The School Refusal group was more likely to have a panel of anxiety disorders including agoraphobia, separation anxiety, depressive disorders, more impaired global functioning and more likely to receive psychotropic medication (P<0.01). There were no significant intergroup differences in sociodemographic characteristics except age. DiscussionThe absence of significant intergroup differences in the level of anxiety measured with the Multidimensional Anxiety Scale for Children could be related to a lower level of anxiety in the school refusal group due to school refusal. The higher anxiety score with the Behavioural Anxiety and Phobia Scale in the refusal group could be related to their better sensitivity. The clinical picture in the refusal group, both more severe and with co-morbidities, is comparable to what is described in the literature. ConclusionA higher level of anxiety was not associated with school refusal according to main endpoints in teenagers with anxiety disorders. However, this group had other criteria of greater clinical severity that justify early identification.

Role of Bisphosphonates in Periodontal Diseases: Systematic Review.

The chief aim in managing periodontal diseases is the elimination of causative factors that may vary from pathogens to physical parameters. In the current systematic review, the effectiveness of "Bisphosphonate Therapy" as a supplement to "Scaling and Root Planing (SRP)" in the management of periodontitis is calibrated from the previous studies. An extensive online search in the various databanks of EMBASE, Medline, Pubmed, and Scopus was conducted. The keywords searched were "Probing depth (PD)" which was the main endpoint, and variations in "Clinical Attachment Level (CAL)" and/or "Bone Defect (BD) fill" were the secondary variants that were searched for in the current study. The data collected were tabulated and compared using the means and the standard deviations. Using the random effect method the mean variations and the confidence intervals (95%) of the parameters were assessed. Eight studies were finalized. Alendronate was utilized as a supplement to SRP in seven studies, four of which employed topical administration and three of which used oral alendronate. A substantial grade of heterogeneity for Probing depth (P < 0.0001), Clinical Attachment Level (P = 0.007), and Bone Defect fill (P < 0.0001) was observed amongst groups when comparing the properties of adjunctive BT to SRP alone. In comparison to SRP alone, SRP with bisphosphonate treatment significantly reduced PD (P = 0.002), increased CAL (P = 0.008), and filled BD (P < 0.001). Although BT as an adjunct appears to be successful in treating periodontitis, its practical applicability is questionable due to the possibility of developing jaw osteonecrosis and the short-range follow-up of the research.

Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study

BackgroundThe leading cause of acute bacterial meningitis in adults is Streptococcus pneumoniae. This infection is associated with high rates of mortality and morbidity related, among other factors, to the excessive...

Endoscopic submucosal dissection of appendicular lesions is feasible and safe: a retrospective multicenter study (with video)

Endoscopic submucosal dissection (ESD) is challenging for appendicular lesions. We report the outcomes of ESD in this context. We collected data of ESD procedures for appendiceal neoplasia in a multicenter prospective registry. Main study endpoints were R0, en-bloc, and curative resection rates and adverse event rate. One hundred twelve patients were included, 47 (42%) with previous appendectomy. Fifty-six (50%) were Toyonaga type 3 lesions (15 [13.4%] postappendectomy). En-bloc and R0 resection rates were 86.6% and 80.4%, respectively, with no significant difference associated with different grades of appendiceal invasion (P= .9 and P= .4, respectively) or previous appendectomy (P= .3 for both). The curative resection rate was 78.6%. Additional surgery was performed in 16 cases (14.3%), including 10 (62.5%) Toyonaga type 3 lesions (P= .04). This included the treatment of 5 cases (4.5%) of delayed perforation and 1 acute appendicitis. ESD for appendicular lesions is a potentially safer and effective alternative to surgery for a significant proportion of patients.

The effect of neoadjuvant treatment on postoperative morbidity in upper rectal cancer

Background. The need of neoadjuvant treatment for upper rectal cancer remains the object of discussion, which makes further study of this topic important.Аim. To estimate the postoperative complications rate depending on the type of neoajuvant treatment.Materials and methods. A retrospective cohort multicenter study, that analyzed data of medical records of patients with upper rectal cancer from the archive of N.N. Blokhin Cancer Research Center of the ministry of Health of Russia, Ryzhikh national medical Research Center of Coloproctology of the ministry of Health of Russia and Stavropol Regional Clinical Oncology Center for 2007–2020. Patients were devided into 3 groups: the group of radiotherapy (5*5 gy), the group of neoadjuvant chemotherapy (4 courses of XELOX before surgery) and the group of surgery. The main endpoint was the study of anastomotic leak rate. Also we estimated the postoperative complications rate III–Iv degree (Clavien– Dindo), the sphincter-preserving surgery rate, the stoma creation rate, the postoperative mortality.Results. we included 110 patients in radiotherapy group, 188 patients in neoadjuvant chemotherapy group, 103 patients in surgery group. Study groups were comparable by sex, ASA status and histological grade. Postoperative grade III– Iv complications (in all cases were associated with anastomotic leak) developed in 8 (6.8 %) patients in neoadjuvant chemotherapy group versus 11 (10.0 %) patients in radiotherapy group (p = 0.379) and 12 (11.7 %) patients in surgery group (p = 0.208). There weren»t any significant differences in this parameter between the radiotherapy and the surgery group (p = 0.698). R0-resection was performed in 117 (99.2 %) patients in neoadjuvant chemotherapy group versus 107 (97.3 %) patients in radiotherapy group (p = 0.280) and 103 patients (100 %) in surgery group (p = 0.349). Radiotherapy and surgery groups didn’t differ significantly in R0-resection rate (p = 0.091). 1 patient (0.84 %) in neoadjuvant chemotherapy died before surgery, in other groups there weren’t any lethal outcomes (p = 0.283). Only the male sex, had a statistically significant effect on the anastomotic leak rate (risk ratio (HR) 2.875; 95 % confidence interval (CI) 1.24–6.63; p = 0.003).Conclusions. A study of these case histories of patients with cancer of the upper ampullary rectum, conducted by us, showed that neoadjuvant treatment didn»t affect the postoperative complications rate.

Aetiology and outcome in hospitalized cardiac arrest patients.

To study aetiologies of in-hospital cardiac arrests (IHCAs) and their association with 30-day survival. Observational study with data from national registries. Specific aetiologies (n = 22) of IHCA patients between April 2018 and December 2020 were categorized into cardiac vs. non-cardiac and six main aetiology categories: myocardial ischemia, other cardiac causes, pulmonary causes, infection, haemorrhage, and other non-cardiac causes. Main endpoints were proportions in each aetiology, 30-day survival, and favourable neurological outcome (Cerebral Performance Category scale 1-2) at discharge. Among, 4320 included IHCA patients (median age 74 years, 63.1% were men), approximate 50% had cardiac causes with a 30-day survival of 48.4% compared to 18.7% among non-cardiac causes (P < 0.001). The proportion in each category were: myocardial ischemia 29.9%, pulmonary 21.4%, other cardiac causes 19.6%, other non-cardiac causes 11.6%, infection 9%, and haemorrhage 8.5%. The odds ratio (OR) for 30-day survival compared to myocardial ischemia for each category were: other cardiac causes OR 1.48 (CI 1.24-1.76); pulmonary causes OR 0.36 (CI 0.3-0.44); infection OR 0.25 (CI 0.18-0.33); haemorrhage OR 0.22 (CI 0.16-0.3); and other non-cardiac causes OR 0.56 (CI 0.45-0.69). IHCA caused by myocardial ischemia had the best favourable neurological outcome while those caused by infection had the lowest OR 0.06 (CI 0.03-0.13). In this nationwide observational study, aetiologies with cardiac and non-cardiac causes of IHCA were evenly distributed. IHCA caused by myocardial ischemia and other cardiac causes had the strongest associations with 30-day survival and neurological outcome.

Efficacy and safety of inetetamab-containing regimens in patients with HER2-positive metastatic breast cancer: a real-world retrospective study in China.

Inetetamab (cipterbin) is an innovative anti-HER2 humanized monoclonal antibody. The efficacy and safety of a combination of inetetamab and vinorelbine in the first-line treatment of human epidermal receptor positive (HER2+) metastatic breast cancer (MBC) have been confirmed. We aimed to investigate real-world data of inetetamab in complex clinical practice. We retrospectively reviewed the medical records of patients who received inetetamab as a salvage treatment at any line setting from July 2020 to June 2022. The main endpoint was progression-free survival (PFS). A total of 64 patients were included in this analysis. The median progression-free survival (mPFS) was 5.6 (4.6-6.6) months. Of the patients, 62.5% received two or more lines of therapy before treatment with inetetamab. The most common chemotherapy and anti-HER2 regimens combined with inetetamab were vinorelbine (60.9%) and pyrotinib (62.5%), respectively. Patients treated with inetetamab plus pyrotinib plus vinorelbine benefited the most (p=0.048), with the mPFS of 9.3 (3.1-15.5) months and an objective response rate of 35.5%. For patients with pyrotinib pretreatment, inetetamab plus vinorelbine plus pyrotinib agents resulted in mPFS of 10.3 (5.2-15.4) months. Regimens (inetetamab plus vinorelbine plus pyrotinib vs. other therapeutic agents) and visceral metastases (yes vs. no) were independent predictors of PFS. Patients with visceral metastases treated with inetetamab plus vinorelbine plus pyrotinib had a mPFS of 6.1(5.1-7.1) months. The toxicity of inetetamab was tolerable, with the most common grade 3/4 adverse event being leukopenia (4.7%). HER2+ MBC patients pretreated with multiple-line therapies still respond to inetetamab-based treatment. Inetetamab combined with vinorelbine and pyrotinib may be the most effective treatment regimen, with a controllable and tolerable safety profile.

Efficacy and safety of iliofemoral bypass using arm veins as an alternative conduit for chronic limb-threatening ischemia

ObjectiveThe use of basilic vein in iliofemoral revascularizations was previously described in the literature as an autologous option for the treatment of vascular prosthesis infection and as a primary conduit in patients at high risk of infectious surgical complications. However, the publications available include several different indications and are limited to case reports. Therefore, the aim of this study was to evaluate the outcomes of the use of arm veins as a safe and effective autologous alternative for iliofemoral reconstruction in patients with chronic limb-threatening ischemia (CLTI) and at high risk of prosthesis infection. MethodsWe performed a multicenter, retrospective cohort study with 53 consecutive iliofemoral bypasses using arm veins as an alternative conduit. The procedures were performed between November 2013 and November 2021, exclusively for patients with CLTI classified as TASC aortoiliac C or D with increased risk of postoperative surgical infection. Demographic, clinical variables, and outcomes were collected from a prospective database. Main endpoints were amputation-free survival (AFS) and major adverse cardiovascular events. Secondary endpoints included primary and secondary patencies and overall survival. Cox regression analysis was used to identify the predictors of AFS. Postoperative surgical complications and 30-day mortality were also assessed. ResultsThe mean age was 64.2 ± 8.4 years, with a predominance of male gender. The median follow-up period was 615 days. All patients had CLTI, with a predominance of tissue loss (n = 51; 96.2%) and a median ankle-brachial index of 0.28. The basilic vein was utilized in most procedures (69.8%). Thirty-day major adverse cardiovascular events occurred in five cases (9.4%), and the 30-day mortality rate was 3.8%. The AFS, primary patency, secondary patency, and overall survival in 720 days were 71%, 72%, 89%, and 75%, respectively. Cox regression analysis revealed no association between the variables analyzed for AFS. There was no graft late infection nor pseudoaneurysmal degeneration. ConclusionsIliofemoral bypass using arm veins as an autologous conduit proved to be an effective and safe procedure with low incidence of postoperative cardiovascular complications and high rates of AFS in patients with CLTI. Also, this suggests that arm veins can be an interesting and suitable autologous alternative conduit for iliofemoral reconstructions, especially in cases in which a prosthesis should be avoided or when it is not available.

#5393 INFLUENCE OF CELLULAR INFLAMMATION ON THE OUTCOME OF KIDNEY TRANSPLANTATION AFTER RECURRENCE OF IGA NEPHROPATHY

Abstract Background and Aims The recurrence of IgA nephropathy (rIgAN) worsens the prognosis of renal transplantation, representing the third cause of loss in these recipients. Several variables at the time of recurrence, such as worse renal function, greater proteinuria, previous steroid withdrawal, and MEST-C histological findings have been associated with a higher risk of graft loss after recurrence. The presence of clinical or subclinical inflammation has been associated with a higher risk of kidney graft loss, but it is not precisely known how it influences the outcome of patients with rIgAN. Method A multicenter retrospective study was carried out including renal transplant recipients with biopsy-proven IgA nephropathy as the underlying disease in which the recurrence of the primary disease had been verified by means of graft biopsy and in which the Banff criteria were available or could be reviewed. Cellular inflammation was defined according to Banff scores as “t” or “i” ≥2. The main endpoint was progression to CKD stage 5 or death censored-graft loss (DCGL). Results 118 kidney transplant recipients were included with an age of 47 ± 14 years at recurrence, 80% male, with a mean time to biopsy of 65 ± 69 months and a post-transplant follow-up of 118 ± 70 months. After recurrence, 34 (28.8%) transplants were lost after 35 ± 28 months, excluding death. Using univariate Cox regression, the factors related to CKD stage 5 or graft loss were systolic blood pressure (HR 1.039, 95%CI 1.016-1.064, p = 0.001), glomerular filtration rate (HR 0.948, 95%CI 0.922-0.974, p &amp;lt;0.001), the logarithm of proteinuria (HR 15.836, 95% CI 5.504-45.565, p &amp;lt; 0.001), Oxford-C score (HR 3.490, 95% CI 2.137-5.699, p &amp;lt;0.001), interstitial fibrosis (HR 2.173, 95% CI 1.362-3.468, p = 0.001) and cellular inflammation (HR 2.458, 95% CI 1.237-4.884, p = 0.010). After multivariate analysis, cellular inflammation remained significantly related to CKD stage 5 or DCGL (HR 2.338, 95% CI 1.077-5.075, p = 0.032). independently of systolic blood pressure, glomerular filtration rate, the logarithm of proteinuria and Oxford-C score. Conclusion In addition to the previously described factors usually related to worse evolution of IgA nephropathy in the native kidney and after post-transplant recurrence, we observed that cellular inflammation influences worse evolution after rIgAN. We suggest to considering the Banff criteria for acute cellular inflammation to better understand the subsequent evolution of patients with rIgAN.