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Trials Jun 2024A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of...
BACKGROUND
A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of the pandemic. Although most individuals who develop coronavirus disease 2019 (COVID-19) recover without complications, about 6% have persistent symptoms, referred to as post-COVID-19 condition (PCC). Intervention studies investigating treatments that potentially alleviate PCC-related symptoms and thus aim to mitigate the global public health burden and healthcare costs linked to PCC are desperately needed. The PYCNOVID trial investigates the effects of Pycnogenol®, a French maritime pine bark extract with anti-inflammatory and antioxidative properties, versus placebo on patient-reported health status in people with PCC.
METHODS
This is a single-center, placebo-controlled, quadruple blind, randomized trial. We aim to randomly assign 150 individuals with PCC (1:1 ratio) to receive either 200 mg Pycnogenol® or placebo daily for 12 weeks. Randomization is stratified for duration of PCC symptoms (≤ 6 months versus > 6 months) and presence of symptomatic chronic disease(s). The primary endpoint is perceived health status at 12 weeks (EuroQol-Visual Analogue Scale) adjusted for baseline values and stratification factors. Secondary endpoints include change in self-reported PCC symptoms, health-related quality of life, symptoms of depression and anxiety, cognitive function, functional exercise capacity, physical activity measured with accelerometry, and blood biomarkers for endothelial health, inflammation, coagulation, platelet function, and oxidative stress. Investigators, study participants, outcome assessors, and data analysts are blinded regarding the intervention assignment. Individuals with PCC were involved in the design of this study.
DISCUSSION
This is the first trial to investigate the effects of Pycnogenol® versus placebo on patient-reported health status in people with PCC. Should the trial proof clinical effectiveness, Pycnogenol® may serve as a therapeutic approach to mitigate symptoms associated with PCC.
TRIAL REGISTRATION
The study is registered at ClinicalTrials.gov. :NCT05890534, June 6, 2023.
Topics: Humans; Plant Extracts; Flavonoids; Randomized Controlled Trials as Topic; Quality of Life; COVID-19; Treatment Outcome; SARS-CoV-2; Health Status; COVID-19 Drug Treatment; Post-Acute COVID-19 Syndrome; Adult; Female; Male; Antioxidants; Anti-Inflammatory Agents
PubMed: 38879571
DOI: 10.1186/s13063-024-08187-6 -
BMC Cancer Jun 2024The addition of pertuzumab (P) to trastuzumab (H) and standard chemotherapy (CT) as neoadjuvant treatment (NaT) for patients with HER2 + breast cancer (BC), has...
BACKGROUND
The addition of pertuzumab (P) to trastuzumab (H) and standard chemotherapy (CT) as neoadjuvant treatment (NaT) for patients with HER2 + breast cancer (BC), has shown to increase the pathological complete response (pCR) rate, without main safety concerns. The aim of NeoPowER trial is to evaluate safety and efficacy of P + H + CT in a real-world population.
METHODS
We retrospectively reviewed the medical records of stage II-III, HER2 + BC patients treated with NaT: who received P + H + CT (neopower group) in 5 Emilia Romagna institutions were compared with an historical group who received H + CT (control group). The primary endpoint was the safety, secondary endpoints were pCR rate, DRFS and OS and their correlation to NaT and other potential variables.
RESULTS
260 patients were included, 48% received P + H + CT, of whom 44% was given anthraciclynes as part of CT, compared to 83% in the control group. The toxicity profile was similar, excluding diarrhea more frequent in the neopower group (20% vs. 9%). Three patients experienced significant reductions in left ventricular ejection fraction (LVEF), all receiving anthracyclines. The pCR rate was 46% (P + H + CT) and 40% (H + CT) (p = 0.39). The addition of P had statistically correlation with pCR only in the patients receiving anthra-free regimens (OR = 3.05,p = 0.047). Preoperative use of anthracyclines (OR = 1.81,p = 0.03) and duration of NaT (OR = 1.18,p = 0.02) were statistically related to pCR. 12/21 distant-relapse events and 14/17 deaths occurred in the control group. Patients who achieve pCR had a significant increase in DRFS (HR = 0.23,p = 0.009).
CONCLUSIONS
Adding neoadjuvant P to H and CT is safe. With the exception of diarrhea, rate of adverse events of grade > 2 did not differ between the two groups. P did not increase the cardiotoxicity when added to H + CT, nevertheless in our population all cardiac events occurred in patients who received anthracycline-containing regimens. Not statistically significant, higher pCR rate is achievable in patients receiving neoadjuvant P + H + CT. The study did not show a statistically significant correlation between the addition of P and long-term outcomes.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Neoadjuvant Therapy; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Antibodies, Monoclonal, Humanized; Retrospective Studies; Receptor, ErbB-2; Adult; Aged; Treatment Outcome; Neoplasm Staging
PubMed: 38879498
DOI: 10.1186/s12885-024-12506-0 -
European Journal of Vascular and... Jun 2024To evaluate sex based differences in ascending aorta and arch anatomy in patients with underlying proximal aortic disease and to evaluate their impact on feasibility for...
OBJECTIVE
To evaluate sex based differences in ascending aorta and arch anatomy in patients with underlying proximal aortic disease and to evaluate their impact on feasibility for total endovascular repair with custom made, arch branched devices.
METHODS
This was a retrospective cross-sectional review of all patients undergoing open and or total endovascular arch repair due to distal ascending aorta and or aortic arch pathologies in a single high volume aortic centre between 2012 and 2022. Anatomical ascending aorta and aortic arch parameters were analysed on a centreline of flow on a dedicated 3D workstation. Sex related differences of the ascending aorta, aortic arch, and supra-aortic vessels were evaluated. Subsequently, four endovascular devices were assessed for feasibility: double and triple branched devices both for the Zenith (Cook Medical) and Relay (Terumo Aortic) platforms, first in accordance with the instructions for use and then considering the possibility of adjunctive cervical debranching. The primary endpoints were sex specific differences in aortic anatomy, while secondary endpoints included sex based feasibility of branched endograft devices.
RESULTS
During the study period, 395 patients underwent total aortic arch repair, of whom 152 (51 female, 33.5%) had high quality available computed tomography angiographies and were included in the study. Female patients had a shorter proximal landing zone than male patients (22 mm vs. 47 mm; p < .001). Left subclavian artery dissection was more frequent in men (24.8% vs. 3.9%; p < .001). Other anatomical parameters showed a similar distribution between sexes. Female patients presented a lower feasibility for double branched devices (35.3% vs. 58.4%; p = .015) as well as a tendency for lower feasibility rates for triple branched devices (31.4% vs. 47.5%; p = .081).
CONCLUSION
Although most ascending aortic and arch parameters showed similar trends in both sexes, the availability of a suitable proximal landing zone was lower in female patients. Consequently, female patients had lower feasibility rates for double arch branched endografts and, to lesser extent, for triple arch branched endografts.
PubMed: 38879148
DOI: 10.1016/j.ejvs.2024.06.012 -
Radiotherapy and Oncology : Journal of... Jun 2024Preclinical research demonstrated that the exposure of microbubbles (intravascular gas microspheres) to focussed ultrasound within the targeted tumour upregulates...
BACKGROUND AND PURPOSE
Preclinical research demonstrated that the exposure of microbubbles (intravascular gas microspheres) to focussed ultrasound within the targeted tumour upregulates pro-apoptotic pathways and enhances radiation-induced tumour cell death. This study aimed to assess the safety and efficacy of magnetic resonance (MR)-guided focussed ultrasound-stimulated microbubbles (MRgFUS-MB) for head and neck cancers (HN).
MATERIALS AND METHODS
This prospective phase 1 clinical trial included patients with newly diagnosed or recurrent HN cancer (except nasopharynx malignancies) for whom locoregional radiotherapy with radical- or palliative-intent as deemed appropriate. Patients with contraindications for microbubble administration or contrast-enhanced MR were excluded. MR-coupled focussed ultrasound sonicated intravenously administered microbubbles within the MR-guided target volume. Patients receiving 5-10 and 33-35 radiation fractions were planned for 2 and 3 MRgFUS-MB treatments, respectively. Primary endpoint was toxicity per CTCAEv5.0. Secondary endpoint was tumour response at 3 months per RECIST 1.1 criteria.
RESULTS
Twelve patients were enrolled between Jun/2020 and Nov/2023, but 1 withdrew consent. Eleven patients were included in safety analysis. Median follow-up was 7 months (range, 0.3-38). Most patients had oropharyngeal cancer (55 %) and received 20-30 Gy/5-10 fractions (63 %). No systemic toxicity or MRgFUS-MB-related adverse events occurred. The most severe acute adverse events were radiation-related grade 3 toxicities in 6 patients (55 %; dermatitis in 3, mucositis in 1, dysphagia in 6). No radiation necrosis or grade 4/5 toxicities were reported. 8 patients were included in the 3-month tumour response assessment: 4 had partial response (50 %), 3 had complete response (37.5 %), and 1 had progressive disease (12.5 %).
CONCLUSIONS
MRgFUS-MB treatment was safe and associated with high rates of tumour response at 3 months.
PubMed: 38879128
DOI: 10.1016/j.radonc.2024.110380 -
The Lancet. Microbe Jun 2024AZD2816 is a variant-adapted COVID-19 vaccine that expresses the full-length SARS-CoV-2 beta variant spike protein but is otherwise similar to AZD1222 (ChAdOx1 nCoV-19)....
Immunogenicity and safety of beta variant COVID-19 vaccine AZD2816 and AZD1222 (ChAdOx1 nCoV-19) as primary-series vaccination for previously unvaccinated adults in Brazil, South Africa, Poland, and the UK: a randomised, partly double-blinded, phase 2/3 non-inferiority immunobridging study.
BACKGROUND
AZD2816 is a variant-adapted COVID-19 vaccine that expresses the full-length SARS-CoV-2 beta variant spike protein but is otherwise similar to AZD1222 (ChAdOx1 nCoV-19). This study aimed to evaluate the safety and immunogenicity of AZD1222 or AZD2816 (or both) primary-series vaccination in a cohort of adult participants who were previously unvaccinated.
METHODS
In this phase 2/3, randomised, multinational, active-controlled, non-inferiority, immunobridging study, adult participants previously unvaccinated for COVID-19 were enrolled at 16 study sites in Brazil, South Africa, Poland, and the UK. Participants were stratified by age, sex, and comorbidity and randomly assigned 5:5:5:2 to receive a primary series of AZD1222 (AZD1222 group), AZD2816 (AZD2816 [4-week] group), or AZD1222-AZD2816 (AZD1222-AZD2816 group) at 4-week dosing intervals, or AZD2816 at a 12-week interval (AZD2816 [12-week] group) and evaluated for safety and immunogenicity through 180 days after dose 2. Primary outcomes were safety (rates of solicited adverse events occurring during 7 days and unsolicited adverse events occurring during 28 days after each dose) and immunogenicity (non-inferiority of pseudovirus neutralising antibody geometric mean titre [GMT], GMT ratio margin of 0·67, and seroresponse rate, rate difference margin of -10%, recorded 28 days after dose 2 with AZD2816 [4-week interval] against beta vs AZD1222 against ancestral SARS-CoV-2) in participants who were seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04973449, and is completed.
FINDINGS
Between July 7 and Nov 12, 2021, 1449 participants were assigned to the AZD1222 group (n=413), the AZD2816 (4-week) group (n=415), the AZD1222-AZD2816 group (n=412), and the AZD2816 (12-week) group (n=209). Ten (2·6%) of 378 participants who were seronegative at baseline in the AZD1222 group, nine (2·4%) of 379 in the AZD2816 (4-week) group, eight (2·1%) of 380 in the AZD1222-AZD2816 group, and 11 (5·8%) of 191 in the AZD2816 (12-week) group had vaccine-related unsolicited adverse events. Serious adverse events were recorded in one (0·3%) participant in the AZD1222 group, one (0·3%) in the AZD2816 (4-week) group, two (0·5%) in the AZD1222-AZD2816 group, and none in the AZD2816 (12-week) group. Co-primary immunogenicity endpoints were met: neutralising antibody GMT (ratio 1·19 [95% CI 1·08-1·32]; lower bound greater than 0·67) and seroresponse rate (difference 1·7% [-3·1 to 6·5]; lower bound greater than -10%) at 28 days after dose 2 were non-inferior in the AZD2816 (4-week) group against beta versus in the AZD1222 group against ancestral SARS-CoV-2. Seroresponse rates were highest with AZD2816 against beta (12-week interval 94·3% [95% CI 89·4-97·3]; 4-week interval 85·7% [81·5-89·2]) and with AZD1222 (84·6% [80·3-88·2]) against ancestral SARS-CoV-2.
INTERPRETATION
Primary series of AZD1222 and AZD2816 were well tolerated, with no emergent safety concerns. Both vaccines elicited robust immunogenicity against beta and ancestral SARS-CoV-2 with greater responses demonstrated when testing against SARS-CoV-2 strains that matched those targeted by the respective vaccine. These findings demonstrate the continued importance of ancestral COVID-19 vaccines in protecting against severe COVID-19 and highlight the feasibility of using the ChAdOx1 platform to develop COVID-19 vaccines against future SARS-CoV-2 variants.
FUNDING
AstraZeneca.
PubMed: 38878794
DOI: 10.1016/S2666-5247(24)00078-8 -
BMC Surgery Jun 2024Obstructive defecation syndrome (ODS) defines a disturbed defecation process frequently associated with pelvic organ prolapse (POP) in women that substantially...
Early safety and efficiency outcomes of a novel interdisciplinary laparoscopic resection rectopexy combined with sacrocolpopexy for women with obstructive defecation syndrome and pelvic organ prolapse: a single center study.
BACKGROUND
Obstructive defecation syndrome (ODS) defines a disturbed defecation process frequently associated with pelvic organ prolapse (POP) in women that substantially compromises quality of life. Conservative management offers limited relief and a surgical intervention may be required. This is characterized by individual approaches. AIM OF THE STUDY: This retrospective single center study evaluated the surgical and clinical short-term outcome of a novel interdisciplinary laparoscopic resection rectopexy (L-RRP) with mesh- sacrocolpopexy (L-SCP) for women suffering from ODS and POP.
METHODS
The study participants underwent surgery in an interdisciplinary laparoscopic approach. Safety was the primary endpoint, assessed via postoperative morbidity classified by Clavien-Dindo scale. Secondary outcomes included evaluation of bowel function, fecal and urinary incontinence and pelvic organ prolapse status at 12 months follow-up. Additionally, a biological mesh (BM) was offered to women, who asked for an alternative to synthetic mesh material (SM).
RESULTS
Of the 44 consecutive patients requiring surgery for ODS and POP, 36 patients underwent the interdisciplinary surgical approach; 28 patients with SM and 8 patients with BM. In total 5 complications occurred, four of them were classified as minor. One minor complication was observed in the BM group. One anastomotic leakage occurred in the SM group. The two ODS scores, the bowel dysfunction score, and the incontinence score improved significantly (p = 0.006, p = 0.003, p < 0.001, and p = 0.0035, respectively). Pelvic floor anatomy was fully restored (POP-Q 0) for 29 (80%) patients after surgery. 17 patients (47%) suffered from urinary incontinence before surgery, which was restored in 13 patients (76.5%).
CONCLUSIONS
The interdisciplinary approach with L-RRP and L-SCP and the use of a BM in a small subgroup were technically feasible, safe, and effective in this single center setting. The study's retrospective design, the small sample size and the lack of comparators limit the generalizability of the findings requiring future randomized trials.
TRIAL REGISTRATION
Retrospectively registered at clinicaltrials.gov, trial number NCT05910021, date of registration 06/10/2023.
Topics: Humans; Female; Retrospective Studies; Pelvic Organ Prolapse; Laparoscopy; Middle Aged; Aged; Surgical Mesh; Treatment Outcome; Vagina; Rectum; Defecation; Postoperative Complications; Gynecologic Surgical Procedures; Syndrome; Constipation
PubMed: 38877450
DOI: 10.1186/s12893-024-02474-4 -
NPJ Vaccines Jun 2024The safety, reactogenicity, and immunogenicity of 3 doses of ExPEC10V (VAC52416), a vaccine candidate to prevent invasive Escherichia coli disease, were assessed in a...
The safety, reactogenicity, and immunogenicity of 3 doses of ExPEC10V (VAC52416), a vaccine candidate to prevent invasive Escherichia coli disease, were assessed in a phase 1/2a study (NCT03819049). In Cohort 1, ExPEC10V was well tolerated; the high dose was selected as optimal and further characterized in Cohort 2. Cohort 2 comprised a maximum 28-day screening, vaccination (Day 1), double-blind 181-day follow-up, and open-label long-term follow-up until Year 1. Healthy participants (≥60 years) with a history of urinary tract infection (UTI) within 5 years were randomized to receive ExPEC10V or placebo. The primary endpoint evaluated the safety and reactogenicity of ExPEC10V (solicited local and systemic AEs [until Day 15]; unsolicited AEs [until Day 30], SAEs [until Day 181], and immunogenicity [Day 30]) via multiplex electrochemiluminescent (ECL) and multiplex opsonophagocytic assay (MOPA). 416 participants (ExPEC10V, n = 278; placebo, n = 138) were included (mean age [SD], 68.8 [6.52] years; female, 79.6%; White, 96.1%). The incidence of solicited AEs was higher with ExPEC10V (local, 50.0% [n = 139]; systemic, 50.0% [n = 139]) than placebo (15.9% [n = 22]; 38.4% [n = 53]); rates of unsolicited AEs were comparable (ExPEC10V, 28.4% [n = 79]; placebo, 26.1% [n = 36]). No vaccine-related SAEs or deaths were reported. ExPEC10V elicited a robust antibody-mediated immunogenic response across all serotypes with ECL (Day 30 geometric mean fold increase, 2.33-8.18) and demonstrated functional opsonophagocytic killing activity across all measured serotypes (Day 30 geometric mean fold increase, 1.81-9.68). ExPEC10V exhibited an acceptable safety profile and a robust vaccine-induced functional immunogenic response in participants with a history of UTI. Clinical trial registration details: https://clinicaltrials.gov/study/NCT03819049 .
PubMed: 38877036
DOI: 10.1038/s41541-024-00885-1 -
Endocrine Practice : Official Journal... Jun 2024Studies are needed to examine the effects of testosterone replacement therapy (TRT) on ambulatory blood pressure (BP) parameters. This study assessed a testosterone...
OBJECTIVE
Studies are needed to examine the effects of testosterone replacement therapy (TRT) on ambulatory blood pressure (BP) parameters. This study assessed a testosterone transdermal system (TTS) using 24-hour ambulatory BP monitoring (ABPM).
METHODS
In a single-arm, noninferiority trial conducted at 41 US sites, 168 men (mean age: 56.2 years) with hypogonadism not receiving TRT in the past 6 months were enrolled and received ≥1 study drug dose. Nightly TTS treatment was administered for 16 weeks (starting dose: 4 mg/d; min, max dose: 2, 6 mg/d) to achieve testosterone concentration of 400-930 ng/dL. The primary endpoint was mean change from baseline to week 16 in 24-hour systolic BP (SBP). Noninferiority was determined based on the upper bound of the 2-sided 95% CI <3.0 mmHg.
RESULTS
62 men had ≥85% study drug compliance and a valid week 16 ABPM session. Mean change from baseline to week 16 in 24-hour average SBP was 3.5 mmHg (95% CI, 1.2-5.8 mmHg; n=62). Since the upper limit of the CI was >3 mmHg, an effect of TTS could not be ruled out. Mean changes were larger at daytime vs nighttime and in subgroups of men with vs without hypertension. Cardiovascular adverse events (AEs) were rare (<2%) and nonserious; no major cardiovascular AEs were reported.
CONCLUSION
A meaningful effect of 16-week TTS treatment on 24-hour average SBP among men with hypogonadism could not be ruled out based on the study's noninferiority criterion. The magnitude of mean changes observed may not be clinically meaningful regarding cardiovascular events.
PubMed: 38876182
DOI: 10.1016/j.eprac.2024.05.015 -
Medicine Jun 2024The present study aims to determine the impact of different cuff diameters on the cuff pressure of endotracheal tubes (ETTs) when the trachea is adequately sealed.
BACKGROUND
The present study aims to determine the impact of different cuff diameters on the cuff pressure of endotracheal tubes (ETTs) when the trachea is adequately sealed.
METHODS
In the present single-center clinical trial, adult patients who underwent cardiothoracic surgery were assigned to use ETTs from 2 brands (GME and GZW). The primary endpoint comprised of the following: cuff diameter, inner diameter of the ETT, manufacturer, and the number of subjects with tracheal leakage when the cuff pressure was 30 cm H2O.
RESULTS
A total of 298 patients were assigned into 2 groups, based on the 2 distinct brands of ETTs: experimental group (n = 122, GME brand) and control group (n = 176, GZW brand). There were no significant differences in baseline characteristics. However, the cuff diameter was significantly smaller in the control group, when compared to the experimental group (P = .001), and the incidence of tracheal leakage was significantly higher in the control group (P = .001). Furthermore, the GME brand ETT had a significantly larger cuff diameter, when compared to the GZW brand ETT.
CONCLUSION
The cuff size would mismatch the tracheal area in clinical practice. Therefore, chest computed tomography is recommended to routinely evaluate the tracheal cross-sectional area during anesthesia, in order to ensure the appropriate cuff size selection.
Topics: Humans; Intubation, Intratracheal; Male; Female; Middle Aged; Critical Illness; Aged; Trachea; Equipment Design; Adult
PubMed: 38875381
DOI: 10.1097/MD.0000000000038326 -
PloS One 2024Renal dysfunction is associated with poor outcomes in patients with coronavirus disease 2019 (COVID-19). In an effort to improve outcomes, intravenous remdesivir has... (Observational Study)
Observational Study
BACKGROUND AND AIM
Renal dysfunction is associated with poor outcomes in patients with coronavirus disease 2019 (COVID-19). In an effort to improve outcomes, intravenous remdesivir has been broadly used for the treatment of COVID-19 even in patients with low estimated glomerular filtration rate (eGFR). Our study assessed the residual risk of outcomes of patients with low eGFR despite treatment with remdesivir for COVID-19, during a timeframe prior to the expanded label across all levels of renal function.
METHODS
We conducted an observational, retrospective, multi-site cohort study of adults hospitalized with COVID-19 treated with at least one dose of remdesivir between November 6, 2020, and November 5, 2021. Electronic medical records were reviewed to obtain patient characteristics, related laboratory data, and outcomes. The primary endpoint was all-cause mortality by day 28. Multivariable logistic regression was used to evaluate association between groups.
RESULTS
The study population consisted of 3024 patients hospitalized with COVID-19 and treated with remdesivir. The median age was 67 [IQR 55, 77] years; 42.7% were women, and 88.6% were white. The median eGFR was 76.6 mL/min/1.73 m2 [IQR 52.5, 95.2]; the majority (67.2%) of patients had an eGFR ≥ 60, while 9% had an eGFR <30. All-cause mortality by day 28 was 8.7%. All-cause mortality rates were significantly higher among patients with impaired renal function (Odds Ratio [OR] 1.63 for patients with eGFR 30-59; OR 1.46 for eGFR 15-29; OR 2.42 for eGFR <15 and OR 5.44 for patients on dialysis) compared to patients with eGFR ≥60 mL/min/1.73m2.
CONCLUSIONS
Lower eGFR remains an independent risk factor for mortality in COVID-19 even in patients treated with remdesivir.
Topics: Humans; Alanine; Adenosine Monophosphate; Female; Male; Middle Aged; Aged; COVID-19 Drug Treatment; Glomerular Filtration Rate; Retrospective Studies; COVID-19; Antiviral Agents; Hospitalization; SARS-CoV-2; Kidney
PubMed: 38875257
DOI: 10.1371/journal.pone.0303896