Abstract
Background/aims
Despite evidence that preferential use of balanced/buffered fluids may improve outcomes compared with chloride-rich 0.9% saline, saline remains the most commonly used fluid ...for children with septic shock. We aim to determine if resuscitation with balanced/buffered fluids as part of usual care will improve outcomes, in part through reduced kidney injury and without an increase in adverse effects, compared to 0.9% saline for children with septic shock.
Methods
The Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) study is an international, open-label pragmatic interventional trial being conducted at > 40 sites in the USA, Canada, and Australia/New Zealand starting on August 25, 2020, and continuing for 5 years. Children > 6 months to < 18 years treated for suspected septic shock with abnormal perfusion in an emergency department will be randomized to receive either balanced/buffered crystalloids (intervention) or 0.9% saline (control) for initial resuscitation and maintenance fluids for up to 48 h. Eligible patients are enrolled and randomized using serially numbered, opaque envelopes concurrent with clinical care. Given the life-threatening nature of septic shock and narrow therapeutic window to start fluid resuscitation, patients may be enrolled under “exception from informed consent” in the USA or “deferred consent” in Canada and Australia/New Zealand. Other than fluid type, all decisions about timing, volume, and rate of fluid administration remain at the discretion of the treating clinicians. For pragmatic reasons, clinicians will not be blinded to study fluid type. Anticipated enrollment is 8800 patients. The primary outcome will be major adverse kidney events within 30 days (MAKE30), a composite of death, renal replacement therapy, and persistent kidney dysfunction. Additional effectiveness, safety, and biologic outcomes will also be analyzed.
Discussion
PRoMPT BOLUS will provide high-quality evidence for the comparative effectiveness of buffered/balanced crystalloids versus 0.9% saline for the initial fluid management of children with suspected septic shock in emergency settings.
Trial registration
PRoMPT BOLUS was first registered at
ClinicalTrials.gov
(
NCT04102371
) on September 25, 2019. Enrollment started on August 25, 2020.
B-cell stimulation for the purpose of evoking an effective neutralizing humoral immune response is a surface phenomenon that is exquisitely specific to antigen conformation. Consequently, successful ...delivery of antigen, such as would be desired in a vaccine, entails preservation of an antigen's apparent native surface (conformational) properties. Prior to testing the actual vaccinating efficacy of delivered antigens, the surface properties could be assessed through a variety of in vitro and in vivo assays in which the measurement standard would be the properties of the antigens in their native state (whole virus). Using surface modified nanocrystalline carbon and calcium-phosphate ceramic particulates (carbon ceramics and brushite), we evaluated the surface activity of immobilized non-nuclear material extracted from HIV-1. Physical characterization showed that the particles with immobilized antigen ("HIV decoys") measured 50 nm in diameter (HIV = 50-100 nm) and exhibited the same zeta potentials as whole (live) HIV. In vitro testing showed that the HIV decoys were recognized by both conformationally nonspecific and specific monoclonal antibodies, were recognized by human IgG from HIV antibody-positive patients, and could promote surface agglomeration among malignant T-cells similar to live HIV. Last, in vivo testing in three vaccinated animal species showed that the HIV decoys elicited humoral and cellular immune responses similar to that evoked by whole (live) HIV.
Acellular dermal matrix is frequently used in implant-based breast reconstruction to cover the inferior aspect of the breast pocket. Its performance profile remains equivocal. The authors studied ...whether adding it in implant-based immediate breast reconstruction improved outcomes when compared with non-acellular dermal matrix reconstruction.
Patients undergoing implant-based immediate breast reconstruction at a single academic medical center were evaluated. Aesthetic outcomes and postoperative complications were assessed and direct comparisons were made between acellular dermal matrix and non-acellular dermal matrix cohorts.
A total of 203 patients underwent 337 immediate expander-based breast reconstructions with acellular dermal matrix, n=208 (61.7 percent); without, n=129 (38.3 percent). Patient characteristics, including age at time of reconstruction (mean, 49±11 versus 47±10 years) and body mass index (mean, 23±5 versus 23±3 kg/m) were similar between groups (p>0.05). Complications occurred in one-third of patients (33.5 percent). In univariate analyses, acellular dermal matrix use had fewer overall complications (odds ratio, 0.61; 95 percent CI, 0.38 to 0.97). The incidences of seroma/hematoma (p=0.59), infection (p=0.31), and wound complications (p=0.26) did not differ. Aesthetic outcomes were higher in the acellular dermal matrix group. In multivariate logistic regression, acellular dermal matrix use was associated with less capsular contracture (odds ratio, 0.18; 95 percent CI, 0.08 to 0.43) and mechanical shift (odds ratio, 0.23; 95 percent CI, 0.06 to 0.78).
Optimizing the inframammary fold with acellular dermal matrix creates a superior aesthetic result. Its use appears safe and is associated with less capsular contracture and mechanical shift and improvement in the inframammary fold appearance, without increasing postoperative complications.
Therapeutic, III.
This Editorial discusses the recent overturning of a proposed Centers for Medicare & Medicaid Services policy that reduced reimbursement for deep inferior epigastric perforator flap breast ...reconstruction. The authors highlight the importance of advocacy efforts in sustaining access to complex microsurgical procedures, even those under investigation such as breast reinnervation and lymphatic reconstruction.
Patients undergoing immediate breast reconstruction with tissue expanders are frequently admitted after surgery for monitoring and pain control, which introduces additional costs and risks of ...nosocomial infection. Same-day discharge could conserve resources, mitigate risk, and return patients home for faster recovery. The authors used large data sets to investigate the safety of same-day discharge after mastectomy with immediate postoperative expander placement.
A retrospective review was performed of patients in the National Surgical Quality Improvement Program database who underwent breast reconstruction using tissue expanders between 2005 and 2019. Patients were grouped based on date of discharge. Demographic information, medical comorbidities, and outcomes were recorded. Statistical analysis was performed to determine efficacy of same-day discharge and identify factors that predict safety.
Of the 14,387 included patients, 10% were discharged the same day, 70% on postoperative day 1, and 20% later than postoperative day 1. The most common complications were infection, reoperation, and readmission, which trended upward with length of stay (6.4% versus 9.3% versus 16.8%), but were statistically equivalent between same-day and next-day discharge. The complication rate for later-day discharge was statistically higher. Patients discharged later had significantly more comorbidities than same or next-day discharge counterparts. Predictors of complications included hypertension, smoking, diabetes, and obesity.
Patients undergoing mastectomy with immediate tissue expander reconstruction are usually admitted overnight. However, same-day discharge was demonstrated to have an equivalent risk of perioperative complications as next-day discharge. For the otherwise healthy patient, going home the day of surgery is a safe and cost-effective option, although the decision should be made based on the individual patient.
Therapeutic, III.
In the past decade, surgeons have increasingly advocated for a return to prepectoral breast reconstruction with claims that surgical mesh (including acellular dermal matrix) can reduce complication ...rates. However, numerous surgical and implant advancements have occurred in the decades since the initial prepectoral studies, and it is unclear whether mesh is solely responsible for the touted benefits.
The authors conducted a systematic review of all English language articles reporting original data for prepectoral implant-based breast reconstruction. Articles presenting duplicate data were excluded. Complications were recorded and calculated on a per-breast basis and separated as mesh-assisted, no-mesh prior to 2006, and no-mesh after 2006 (date of first silicone gel-filled breast implant approval). Capsular contracture comparisons were adjusted for duration of follow-up.
A total of 58 articles were included encompassing 3120 patients from 1966 to 2019. The majority of the included studies were retrospective case series. Reported complication outcomes were variable, with no significant difference between groups in hematoma, infection, or explantation rates. Capsular contracture rates were higher in historical no-mesh cohorts, whereas seroma rates were higher in contemporary no-mesh cohorts.
Limited data exist to understand the benefits of surgical mesh devices in prepectoral breast reconstruction. Level I studies with an appropriate control group are needed to better understand the specific role of mesh for these procedures. Existing data are inconclusive but suggest that prepectoral breast reconstruction can be safely performed without surgical mesh.
Use of acellular dermal matrices (ADMs) for tissue expander breast reconstruction remains controversial with an uncertain safety and efficacy profile. This study analyzes the rates and factors for ...reoperation and postoperative infection in patients who underwent tissue expander breast reconstruction with and without ADM.
Patients who underwent breast reconstruction with and without ADM were identified from the National Surgical Quality Improvement Program database utilizing CPT codes. Covariates included patient demographics, preoperative comorbidities, and operative characteristics, while outcomes of interest were postoperative infection and reoperation. Univariate and multivariate analyses were performed to identify predictors of adverse outcomes.
There were 8334 patients in the ADM cohort and 12,451 patients who underwent tissue expander breast reconstruction without ADM. There were significantly fewer reoperations in the non-ADM cohort (5.4%) compared to the ADM cohort (7.7%) (
< 0.0001), with infection and hematoma as the most common etiologies in both cohorts. Surgical infections were also more prevalent in the ADM cohort (4.7%) compared with the non-ADM cohort (3.6%) (
< 0.0001). Univariate and multivariate analysis of the tissue expander breast reconstruction cohort revealed race, obesity, hypertension, smoking status, albumin, and operative time as predictive for infection risk, while race, obesity, hypertension, smoking, albumin, operative time, and age were significant for reoperation.
Our study of 20,817 patients revealed significantly higher risk of infection and reoperation in patients who underwent breast reconstruction utilizing ADM versus without ADM. Patients considering ADM for breast reconstruction should engage in discussion with their surgeon about complications, aesthetics, and cost.
Adjuvant radiation therapy for locally advanced breast cancer decreases local recurrence and improves survival. Immediate autologous breast reconstruction before postmastectomy irradiation is highly ...controversial. However, it is presently unknown whether there exist differences in the durability of various autologous flaps (myocutaneous or fasciocutaneous) to the effects of radiation.
All patients who underwent autologous breast reconstruction at the authors' institution between July of 2002 and July of 2005 were evaluated retrospectively. Patients who did not complete all stages of their reconstruction at the authors' institution were excluded. Free flap types were analyzed based on postoperative radiation exposure versus no radiation exposure. The authors also analyzed patients who underwent reconstruction in a delayed fashion with prior radiation exposure and assessed overall outcomes for early and late complications and secondary breast procedures.
Three hundred sixty-three of 446 flaps (81 percent) were included in the analysis, with the three most common flaps being the free transverse rectus abdominis myocutaneous (TRAM) flap (7.4 percent), the muscle-sparing free TRAM flap (44 percent), and the deep inferior epigastric perforator flap (41 percent). There were no significant differences in early or late complications among the different flap types or radiation categories. Flaps with prior radiation exposure were associated with higher percentages of contralateral symmetry procedures, whereas flaps with postoperative radiation exposure had a lower incidence of ipsilateral revisions.
Autologous breast reconstruction can be performed safely regardless of preoperative or postoperative radiation therapy. There are no significant differences in complication rates or number of revisions based on the type of free flap.
Therapeutic, III.
Deep inferior epigastric artery perforator flaps are increasingly utilized over other autologous methods of breast reconstruction. We evaluated the relationship between annual hospital volume and ...costs after breast reconstruction with the deep inferior epigastric artery perforator flap.
All female patients undergoing elective implant or autologous tissue breast reconstruction were identified using the 2016–2019 Nationwide Readmission Database. Annual hospital volume of deep inferior epigastric artery perforator reconstructions was tabulated and modeled using restricted cubic splines. Institutions were categorized into high- and low-volume based on the inflection point of the spline between annual caseload and costs. The association between high volume status and costs, complications, length of stay, and 30-day nonelective readmission was assessed using multivariable regression.
Of an estimated 94,524 patients meeting inclusion criteria, 33,046 (34.6%) underwent deep inferior epigastric artery perforator flap reconstruction. Deep inferior epigastric artery perforator flap utilization increased from 31% in 2016 to 40% in 2019 (P < .001) among inpatient breast reconstructions. High-volume hospitals more frequently performed bilateral reconstructions (43.3 vs 37.7%, P = .021) but had similar rates of concurrent mastectomy (28.7 vs 30.6%, P = .46), relative to low-volume hospitals. The median cost of deep inferior epigastric artery perforator reconstruction was lower ($29,900 interquartile range: 22,400–37,400 vs $31,600 interquartile range: 22,500–44,900, P = .036) at high-volume hospitals compared to low-volume. On adjusted analysis, high-volume status was associated a $3,800 (95% confidence interval: -6,200 to -1,400) decrement in hospitalization costs, and reduced odds of perioperative complications (adjusted odd ratio: 0.68 95% confidence interval: 0.54–0.86). High-volume status was not associated with length of stay or likelihood of unplanned readmission.
The present study demonstrated an inverse cost–volume relationship in deep inferior epigastric artery perforator flap breast reconstruction. In line with goals of value-based health care delivery, our findings may inform referral patterns to suitable centers for deep inferior epigastric artery perforator breast reconstruction.
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