Background In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months ...postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss. Study Design 36-month follow-up of the intention-to-treat population. Setting & Participants CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate eGFR, 35-75 mL/min/1.73 m2 ). Interventions At 6 to 36 months posttransplantation, patients were randomly assigned to switch to belatacept-based immunosuppression (n = 84) or continue CNI-based therapy (n = 89). Outcomes Safety was the primary outcome. eGFR, acute rejection, transplant loss, and death were also assessed. Measurements Treatment exposure−adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan-Meier analyses for efficacy. Results Serious adverse events occurred in 33 (39%) belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment exposure−adjusted incidence rates for serious infections (belatacept vs CNI, 10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person-years) were similar. More patients in the belatacept versus CNI group had any-grade viral infections (14.60 vs 11.00 per 100 person-years). No posttransplantation lymphoproliferative disorder was reported. Belatacept-treated patients had a significantly greater estimated gain in mean eGFR (1.90 vs 0.07 mL/min/1.73 m2 per year; P for time-by-treatment interaction effect = 0.01). The probability of acute rejection was not significantly different for belatacept (8.38% vs 3.60%; HR, 2.50 95% CI, 0.65-9.65; P = 0.2). HR for the comparison of belatacept to the CNI group for time to death or transplant loss was 1.00 (95% CI, 0.14-7.07; P = 0.9). Limitations Exploratory post hoc analysis with a small sample size. Conclusions Switching patients from a CNI to belatacept may represent a safe approach to immunosuppression and is being further explored in an ongoing phase 3b trial.
Wound care is a major healthcare expenditure. Treatment of burns, surgical and trauma wounds, diabetic lower limb ulcers and skin wounds is a major medical challenge with current therapies largely ...focused on supportive care measures. Successful wound repair requires a series of tightly coordinated steps including coagulation, inflammation, angiogenesis, new tissue formation and extracellular matrix remodelling. Zinc is an essential trace element (micronutrient) which plays important roles in human physiology. Zinc is a cofactor for many metalloenzymes required for cell membrane repair, cell proliferation, growth and immune system function. The pathological effects of zinc deficiency include the occurrence of skin lesions, growth retardation, impaired immune function and compromised would healing. Here, we discuss investigations on the cellular and molecular mechanisms of zinc in modulating the wound healing process. Knowledge gained from this body of research will help to translate these findings into future clinical management of wound healing.
Abstract Background Retained surgical items (RSI) are designated as completely preventable “never events”. Despite numerous case reports, clinical series, and expert opinions few studies provide ...quantitative insight into RSI risk factors and their relative contributions to the overall RSI risk profile. Existing case-control studies lack the ability to reliably detect clinically important differences within the long list of proposed risks. This meta-analysis examines the best available data for RSI risk factors, seeking to provide a clinically relevant risk stratification system. Methods Nineteen candidate studies were considered for this meta-analysis. Three retrospective, case-control studies of RSI-related risk factors contained suitable group comparisons between patients with and without RSI, thus qualifying for further analysis. Comprehensive Meta-Analysis 2.0 (BioStat, Inc, Englewood, NJ) software was used to analyze the following “common factor” variables compiled from the above studies: body-mass index, emergency procedure, estimated operative blood loss >500 mL, incorrect surgical count, lack of surgical count, >1 subprocedure, >1 surgical team, nursing staff shift change, operation “afterhours” (i.e., between 5 PM and 7 AM), operative time, trainee presence, and unexpected intraoperative factors. We further stratified resulting RSI risk factors into low, intermediate, and high risk. Results Despite the fact that only between three and six risk factors were associated with increased RSI risk across the three studies, our analysis of pooled data demonstrates that seven risk factors are significantly associated with increased RSI risk. Variables found to elevate the RSI risk include intraoperative blood loss >500 mL (odds ratio OR 1.6); duration of operation (OR 1.7); >1 subprocedure (OR 2.1); lack of surgical counts (OR 2.5); >1 surgical team (OR 3.0); unexpected intraoperative factors (OR 3.4); and incorrect surgical count (OR 6.1). Changes in nursing staff, emergency surgery, body-mass index, and operation “afterhours” were not significantly associated with increased RSI risk. Conclusions Among the “common risk factors” reported by all three case-control studies, seven synergistically show elevated RSI risk across the pooled data. Based on these results, we propose a risk stratification scheme and issue a call to arms for large, prospective, and multicenter studies evaluating effects of specific changes at the institutional level (i.e., universal surgical counts, radiographic verification of the absence of RSI, and radiofrequency labeling of surgical instruments and sponges) on the risk of RSI. Overall, our findings provide a meaningful foundation for future patient safety initiatives and clinical studies of RSI occurrence and prevention.
Summary
GATA2 deficiency was described in 2011, and shortly thereafter allogeneic hematopoietic stem cell transplantation (HSCT) was shown to reverse the hematologic disease phenotype. However, there ...remain major unanswered questions regarding the type of conditioning regimen, type of donors, and graft‐versus‐host disease (GVHD) prophylaxis. We report 59 patients with GATA2 mutations undergoing HSCT at National Institutes of Health between 2013 and 2020. Primary endpoints were engraftment, reverse of the clinical phenotype, secondary endpoints were overall survival (OS), event‐free survival (EFS), and the incidence of acute and chronic GVHD. The OS and EFS at 4 years were 85·1% and 82·1% respectively. Ninety‐six percent of surviving patients had reversal of the hematologic disease phenotype by one‐year post‐transplant. Incidence of grade III‐IV aGVHD in matched related donor (MRD) and matched unrelated donor recipients (URD) patients receiving Tacrolimus/Methotrexate for GVHD prophylaxis was 32%. In contrast, in the MRD and URD who received post‐transplant cyclophosphamide (PT/Cy), no patient developed grade III‐IV aGVHD. Six percent of haploidentical related donor (HRD) recipients developed grade III‐IV aGVHD. In summary, a busulfan‐based HSCT regimen in GATA2 deficiency reverses the hematologic disease phenotype, and the use of PT/Cy reduced the risk of both aGVHD and cGVHD.
Background All hospitals are required to perform quality assurance activities. Many risk adjustment methodologies have been developed, and many medical centers use 1 or more than 1 risk adjustment ...program in an attempt to characterize their outcomes better rather than simply assessing unadjusted outcome statistics. The University HealthSystem Consortium (UHC) and American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) both produce risk-adjusted outcome data. Our institution recognized a large disparity between our UHC and NSQIP risk-adjusted mortality. The purpose of this study was to attempt to discover the cause of that disparity. Methods One hundred twenty consecutive NSQIP records were matched with their UHC submissions during 2006. All patients' comorbidities and outcomes were reviewed, and the 2 systems, UHC and NSQIP, were compared for degree of discordance. Results Approximately twice the number of comorbidities per patient were documented in UHC (2.85±2.52) submissions compared with NSQIP (1.38±1.52, P < .001). The reporting of the comorbidities of hypertension, cardiac disease, pulmonary disease, and diabetes between UHC and NSQIP were similar in the percentage of patients reported as having each of those disease states, but the discordance between the 2 systems was 12%, 13%, 15%, and 5%, respectively ( P < .001 in all 4). A total of 28% of patients were reported as suffering complications in NSQIP but only 11% in UHC, with a 26% rate of discordance ( P < .01). Overall, 13% of patients were reported as having a surgical site infection in NSQIP, but only 1% in UHC. Conclusions We found significant differences in the reporting of both comorbidities and outcomes between our medical center's submissions to UHC and NSQIP in a consecutive series of patients. This may be at least partially responsible for the difference in the risk-adjusted mortality for our institution, as reported by UHC and NSQIP.
Retained Surgical Items: A Problem Yet to Be Solved Stawicki, Stanislaw P.A., MD, FACS; Moffatt-Bruce, Susan D., MD, PhD, FACS; Ahmed, Hesham M., MD ...
Journal of the American College of Surgeons,
2013, January 2013, 2013-Jan, 2013-01-00, 20130101, Letnik:
216, Številka:
1
Journal Article
Recenzirano
Background Retained surgical items (RSI) continue to occur. Large RSI studies are few due to low RSI frequency in single institutions and the medicolegal implications. Consequently, RSI risks are not ...fully defined, with discrepancies persisting among published studies. The goals of this study were to better define risk factors for RSI, to clarify previously discrepant risk factors, and to evaluate other potential contributors to RSI occurrence, such as trainee presence during an operation. Study Design Multicenter case-match study of RSI risk factors was conducted between January 2003 and December 2009. Cases complicated by RSI were identified at participating centers using clinical quality improvement and adverse event reporting data. Case match controls (non-RSI) were selected from same or similar-type cases performed at each respective institution. Retained surgical item risk factors were evaluated by univariate and multivariate conditional logistic regression. Results Fifty-nine RSIs and 118 matched controls were analyzed (RSI incidence 1 in 6,975 or 59 in 411,526). Retained surgical items occurred despite use of confirmatory x-rays (13 of 27 instances) and/or radiofrequency tagging (2 of 32 instances). Among previously discrepant results, we confirmed that body mass index, unexpected intraoperative events, and procedure duration were associated with increased RSI risk. The occurrence of any safety variance, and specifically an incorrect count at any time during the procedure, was associated with elevated RSI risk. Trainee presence was associated with 70% lower RSI risk compared with trainee absence. Conclusions Longer duration of surgery, safety variances, and incorrect counts during the procedure result in elevated RSI risk. The possible positive influence of trainee presence on RSI risk deserves additional study. Our findings highlight the need for zero tolerance for safety omissions, continued study and development of novel approaches to RSI reduction, and establishing anonymous RSI reporting systems to better track both the incidence and risks associated with this problem, which has yet to be solved.
Background Surgical site infections (SSI) continue to be a significant problem in surgery. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) Best Practices ...Initiative compared process and structural characteristics among 117 private sector hospitals in an effort to define best practices aimed at preventing SSI. Study Design Using standard NSQIP methodologies, we identified 20 low outlier and 13 high outlier hospitals for SSI using data from the ACS-NSQIP in 2006. Each hospital was administered a process of care survey, and site visits were conducted to five hospitals. Comparisons between the low and high outlier hospitals were made with regard to patient characteristics, operative variables, structural variables, and processes of care. Result Hospitals that were high outliers for SSI had higher trainee-to-bed ratios (0.61 versus 0.25, p < 0.0001), and the operations took significantly longer (128.3 ± 104.3 minutes versus 102.7 ± 83.9 minutes, p < 0.001). Patients operated on at low outlier hospitals were less likely to present to the operating room anemic (4.9% versus 9.7%, p = 0.007) or to receive a transfusion (5.1% versus 8.0%, p = 0.03). In general, perioperative policies and practices were very similar between the low and high outlier hospitals, although low outlier hospitals were readily identified by site visitors. Overall, low outlier hospitals were smaller, efficient in the delivery of care, and experienced little operative staff turnover. Conclusions Our findings suggest that evidence-based SSI prevention practices do not easily distinguish well from poorly performing hospitals. But structural and process of care characteristics of hospitals were found to have a significant association with good results.
Study Type – Therapy (case series)
Level of Evidence 4
What’s known on the subject? and What does the study add?
Accurate preoperative staging for upper‐tract urothelial carcinoma (UTUC) lesions is ...presently limited. Urinary cytology has shown promise for characterizing pathological features of bladder cancer. The role of cytology for UTUC is at present poorly defined.
In this large multi‐institutional cohort of patients, urinary cytology was limited in its ability to accurately predict the grade and stage of upper‐tract lesions. Selective ureteral sampling improved the diagnostic accuracy of cytology when compared to bladder specimens. Improved preoperative surrogate markers for staging UTUC remain necessary.
OBJECTIVE
• To evaluate the diagnostic accuracy of urine cytology for detecting aggressive disease in a multi‐institutional cohort of patients undergoing extirpative surgery for upper‐tract urothelial carcinoma (UTUC).
METHODS
• We reviewed the records of 326 patients with urinary cytology data who underwent a radical nephroureterectomy or distal ureterectomy without concurrent or previous bladder cancer.
• We assessed the association of cytology (positive, negative and atypical) with final pathology. Sensitivity and positive predictive value (PPV) of a positive (± atypical) cytology for high‐grade and muscle‐invasive UTUC was calculated.
RESULTS
• On final pathology, 53% of patients had non‐muscle invasive disease (pTa, pTis, pT1) and 47% had invasive disease (≥pT2). Low‐grade and high‐grade cancers were present in 33% and 67% of patients, respectively.
• Positive, atypical and negative urine cytology was noted in 40%, 40% and 20% of cases. Positive urinary cytology had sensitivity and PPV of 56% and 54% for high‐grade and 62% and 44% for muscle‐invasive UTUC.
• Inclusion of atypical cytology with positive cytology improved the sensitivity and PPV for high‐grade (74% and 63%) and muscle‐invasive (77% and 45%) UTUC. Restricting analysis to patients with selective ureteral cytologies further improved the diagnostic accuracy when compared with bladder specimens (PPV > 85% for high‐grade and muscle‐invasive UTUC).
CONCLUSIONS
• In this cohort of patients with UTUC treated with radical surgery, urine cytology in isolation lacked performance characteristics to accurately predict muscle‐invasive or high‐grade disease.
• Improved surrogate markers for pathological grade and stage are necessary, particularly when considering endoscopic modalities for UTUC.
Ras-related C3 botulinum toxin substrate 2 (RAC2), through interactions with reduced NAD phosphate oxidase component p67phox, activates neutrophil superoxide production, whereas interactions with ...p21-activated kinase are necessary for fMLF-induced actin remodeling. We identified 3 patients with de novo RAC2E62K mutations resulting in severe T- and B-cell lymphopenia, myeloid dysfunction, and recurrent respiratory infections. Neutrophils from RAC2E62K patients exhibited excessive superoxide production, impaired fMLF-directed chemotaxis, and abnormal macropinocytosis. Cell lines transfected with RAC2E62K displayed characteristics of active guanosine triphosphate (GTP)–bound RAC2 including enhanced superoxide production and increased membrane ruffling. Biochemical studies demonstrated that RAC2E62K retains intrinsic GTP hydrolysis; however, GTPase-activating protein failed to accelerate hydrolysis resulting in prolonged active GTP-bound RAC2. Rac2+/E62K mice phenocopy the T- and B-cell lymphopenia, increased neutrophil F-actin, and excessive superoxide production seen in patients. This gain-of-function mutation highlights a specific, nonredundant role for RAC2 in hematopoietic cells that discriminates RAC2 from the related, ubiquitous RAC1.
•E62K is a dominant activating mutation of the small GTPase, RAC2; patients with RAC2E62K have lymphoid and myeloid defects.•Rac2+/E62K mice phenocopy the T- and B-cell lymphopenia, increased neutrophil F-actin, and excessive superoxide production seen in patients.
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Hypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT.
To ...evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT.
This randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up. Adult patients with biopsy-proven, T1 to T2 prostate cancer with a Gleason score 7 or less and prostate-specific antigen level of 20 ng/mL or less (to convert to μg/L, multiply by 1) were blinded to the treatment arms. Of the 260 consented patients, 201 patients (77.3%) were randomized (2:1) to the presence or absence of the spacer. Patients were stratified by intended 4-month androgen deprivation therapy use and erectile quality.
For the primary outcome, we hypothesized that more than 70% of patients in the spacer group would achieve a 25% or greater reduction in the rectal volume receiving 54 Gy (V54). For the secondary outcome, we hypothesized that the spacer group would have noninferior acute (within 3 months) grade 2 or higher GI toxic effects compared with the control group, with a margin of 10%.
Of the 201 randomized patients, 8 (4.0%) were Asian, 26 (12.9%) Black, 42 (20.9%) Hispanic or Latino, and 153 (76.1%) White; the mean (SD) age for the spacer group was 68.6 (7.2) years and 68.4 (7.3) years for the control group. For the primary outcome, 131 of 133 (98.5%; 95% CI, 94.7%-99.8%) patients in the spacer group experienced a 25% or greater reduction in rectum V54, which was greater than the minimally acceptable 70% (P < .001). The mean (SD) reduction was 85.0% (20.9%). For the secondary outcome, 4 of 136 patients (2.9%) in the spacer group and 9 of 65 patients (13.8%) in the control group experienced acute grade 2 or higher GI toxic effects (difference, -10.9%; 95% 1-sided upper confidence limit, -3.5; P = .01).
The trial results suggest that rectal spacing with hyaluronic acid improved rectal dosimetry and reduced acute grade 2 or higher GI toxic effects. Rectal spacing should potentially be considered for minimizing the risk of acute grade 2 or higher toxic effects for hypofractionated RT.
ClinicalTrials.gov Identifier: NCT04189913.
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