Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial
Importance/UNASSIGNED:There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective/UNASSIGNED:To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants/UNASSIGNED:CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions/UNASSIGNED:A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures/UNASSIGNED:The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results/UNASSIGNED:Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1]â€‰=â€‰72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1]â€‰=â€‰76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1]â€‰=â€‰93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1]â€‰=â€‰97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (Pâ€‰=â€‰.57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (Pâ€‰=â€‰.06). Conclusions and Relevance/UNASSIGNED:In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04364737.
Contemporary techniques and outcomes of robotic assisted radical cystectomy with intracorporeal urinary diversion
The open approach to radical cystectomy continues to be accompanied by significant morbidity despite enhanced recovery protocols (ERP). Robotic assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) has become an increasingly popular technique for removal of aggressive bladder cancer and subsequent urinary diversion. Randomized clinical trials comparing the robotic and open techniques address the uncertainty surrounding oncological efficacy of the RARC and show that RARC is at least comparable to open radical cystectomy (ORC) in terms of oncologic adequacy and survival. Although RARC with ICUD is a technically challenging procedure, surgeons have noted ergonomic advantages while patients experience less blood loss and quicker time to recovery and to adjuvant chemotherapy (AC), if necessary. Even with these benefits, there is a paucity of data describing outcomes of ICUD. For those surgeons who have switched to ICUD, priority remains standardization of a protocol for the reconstructive component and for a safe transition from extracorporeal urinary diversion (ECUD) to ICUD. Additionally, there is a need for evidence of reduced financial toxicity for the patient, as well as more comprehensive cost-effectiveness analyses. The literature from this review represents 10 years of accumulating data on techniques and outcomes of RARC with ICUD.
Pathologic measures of quality compare favorably in patients undergoing robot-assisted radical cystectomy to open cystectomy cohorts: a National Cancer Database analysis
This study aims to assess the impact of facility characteristics on measures of surgical quality (positive surgical margin rates and lymph-node yield) in patients undergoing robot-assisted (RARC) versus open (ORC) radical cystectomy using the National Cancer Database. Patients who received RC between the years of 2010-2013 were stratified according to surgery type (ORC vs. RARC), and corresponding patient and facility-level variables (facility type and volume) were assessed. Logistic regression models for procedure type, positive surgical margins (PSMs), and LN dissection (LND) rates were estimated. Radical cystectomies (ORCâ€‰=â€‰13,236, RARCâ€‰=â€‰3687) were performed more often in academic centers (58.3%) compared to community centers (31.6%). As facility volume increased, centers performed more LNDs during ORCs (pâ€‰=â€‰0.03) and the number of nodes retrieved increased in both ORC and RARC (ORC pâ€‰<â€‰0.001; RARC pâ€‰<â€‰0.0001). Increased facility volume also resulted in significantly fewer PSMs within the RARC cohort (pâ€‰=â€‰0.01). Comparison of ORC and RARC within each facility type cohort identified improved pathological metrics for RARC with fewer PSMs (pâ€‰=â€‰0.001) as well as increased LNDs (pâ€‰<â€‰0.0001) and median number of LNs retrieved (pâ€‰<â€‰0.0001), which suggests that RARC may facilitate comparative outcomes in community centers and academic centers. Overall, higher facility volume and robot-assisted surgery resulted in more favorable pathologic metrics compared to lower facility volume and ORC.
Evaluation of a novel cystoscopic compatible cryocatheter for the treatment of bladder cancer
BACKGROUND: As the acceptance of cryoablative therapies for the treatment of non-metastatic cancers continues to grow, avenues for novel cryosurgical technologies and approaches have opened. Within the field of genitourinary tumors, cryosurgical treatments of bladder cancers remain largely investigational. Current modalities employ percutaneous needles or transurethral cryoballoons or sprays, and while results have been promising, each technology is limited to specific types and stages of cancers. OBJECTIVE: This study evaluated a new, self-contained transurethral cryocatheter, FrostBite-BC, for its potential to treat bladder cancer. METHODS: Thermal characteristics and ablative capacity were assessed using calorimetry, isothermal analyses, in vitro 3-dimensional tissue engineered models (TEMs), and a pilot in vivo porcine study. RESULTS: Isotherm assessment revealed surface temperatures below -20â—¦ C within 9 sec. In vitro TEMs studies demonstrated attainment of â‰¤-20â—¦ C at 6.1 mm and 8.2 mm in diameter following single and double 2 min freezes, respectively. Fluorescent imaging 24 hr post-thaw revealed uniform, ablative volumes of 326.2 mm3 and 397.9 mm3 following a single or double 2 min freeze. In vivo results demonstrated the consistent generation of ablative areas. Lesion depth was found to correlate with freeze time wherein 15 sec freezes resulted in ablation confined to the sub-mucosa and â‰¥30 sec full thickness ablation of the bladder wall. CONCLUSIONS: These studies demonstrate the potential of the FrostBite-BC cryocatheter as a treatment option for bladder cancer. Although preliminary, the outcomes of these studies were encouraging, and support the continued investigation into the potential of the FrostBite-BC cryocatheter as a next generation, minimally invasive cryoablative technology.
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The Natural History and Composition of Urinary Catheter Biofilms: Early Uropathogen Colonization with Intraluminal and Distal Predominance
PURPOSE/OBJECTIVE:To determine the composition and site of initiation of bacterial biofilm location on indwelling urinary catheters, and to track biofilm progression over time. MATERIALS & METHODS/METHODS:Indwelling urinary catheters were collected from two tertiary care centers following removal from patients. Indwelling time was noted, and catheters were de-identified. Catheters were sectioned, stained for biofilms, and analyzed using spectrophotometry and visualization. Biofilm colonization patterns were analyzed using descriptive statistical analyses and bacterial composition was determined using next-generation sequencing. RESULTS:33 catheters from 26 males and 7 females were collected with indwelling times ranging from 15 minutes to 43 days and analyzed. Biofilm colonization was consistently high on the region of the balloon throughout indwelling times. After week 1, the distal third of the catheter had higher biofilm colonization than the proximal third (week 2: p=0.034). At all indwelling times, the intraluminal surface of the catheter had greater biofilm colonization than the outer surface. Next-generation sequencing detected potential uropathogenic bacteria in 10 of 10 analyzed samples. CONCLUSIONS:The catheter balloon, its distal aspect, and its lumen were the predominant locations of biofilms, comprised of uropathogenic bacteria. Strategies to prevent or treat biofilms should be targeted to these areas.
Patient-reported quality of life progression in men with prostate cancer following primary cryotherapy, cyberknife, or active holistic surveillance
BACKGROUND:Technological advancements have led to the success of minimally invasive treatment modalities for prostate cancer such as CyberKnife and Cryotherapy. Here, we investigate patient-reported urinary function, bowel habits, and sexual function in patients following CyberKnife (CK) or Cryotherapy treatment, and compare them with active holistic surveillance (AHS) patients. METHODS:An IRB-approved institutional database was retrospectively reviewed for patients who underwent CK, Cryotherapy, or AHS. Quality of life (QoL) survey responses were collected every three months and the mean function scores were analyzed in yearly intervals over the 4 years post-treatment. RESULTS:279 patients (767 survey sets) were included in the study. There was no difference among groups in urinary function scores. The CyberKnife group had significantly lower bowel habit scores in the early years following treatment (year 2 mean difference: -5.4, Pâ€‰<â€‰0.01) but returned to AHS level scores by year 4. Cryotherapy patients exhibited initially lower, but not statistically significant, bowel function scores, which then improved and approached those of AHS. Both CyberKnife (year 1 mean difference: -26.7, Pâ€‰<â€‰0.001) and Cryotherapy groups (-35.4, Pâ€‰<â€‰0.001) had early lower sexual function scores relative to AHS, but then gradually improved and were not significantly different from AHS by the third year post-treatment. A history of hormonal therapy was associated with a lower sexual function scores relative to those patients who did not receive hormones in both CyberKnife (-18.45, Pâ€‰<â€‰0.01) and Cryotherapy patients (-14.6, Pâ€‰<â€‰0.05). CONCLUSIONS:After initial lower bowel habits and sexual function scores, CyberKnife or Cryotherapy-treated patients had no significant difference in QoL relative to AHS patients. These results highlight the benefit of CyberKnife and Cryotherapy in the management of organ-confined prostate cancer.
MODERATE MINIMUM TUMOR TEMPERATURE IN CRYOTHERAPY IS ASSOCIATED WITH SUPERIOR QUALITY OF LIFE AND NO DIFFERENCE IN DISEASE CONTROL IN PROSTATE CANCER PATIENTS [Meeting Abstract]
PRIMARY TREATMENT MODALITY FOR PROSTATE CANCER IS ASSOCIATED WITH RISK OF BIOCHEMICAL RECURRENCE FOLLOWING SALVAGE CRYOTHERAPY [Meeting Abstract]
COMBINATION OF PSA DENSITY, PROSTATE CANCER ANTIGEN 3 AND PI-RADS IN THE PREDICTION OF PROSTATE CANCER IN INITIAL BIOPSY [Meeting Abstract]