Roadmap to safety: a single center study of evidence-informed approach to placenta accreta spectrum.

Objective: To assess the impact of an evidence-informed protocol for management of placenta accreta spectrum (PAS). Methods: This was a retrospective cohort study of patients who underwent cesarean hysterectomy (c-hyst) for suspected PAS from 2012 to 2022 at a single tertiary care center. Perioperative outcomes were compared pre- and post-implementation of a standardized Multidisciplinary Approach to the Placenta Service (MAPS) protocol, which incorporates evidence-informed perioperative interventions including preoperative imaging and group case review. Intraoperatively, the MAPS protocol includes placement of ureteral stents, possible placental mapping with ultrasound, and uterine artery embolization by interventional radiology. Patients suspected to have PAS on prenatal imaging who underwent c-hyst were included in the analysis. Primary outcomes were intraoperative complications and postoperative complications. Secondary outcomes were blood loss, need for ICU, and length of stay. Proportions were compared using Fisher's exact test, and continuous variables were compared used t-tests and Mood's Median test. Results: There were no differences in baseline demographics between the pre- (n = 38) and post-MAPS (n = 34) groups. The pre-MAPS group had more placenta previa (95% pre- vs. 74% post-MAPS, p = 0.013) and prior cesarean sections (2 prior pre- vs. 1 prior post-MAPS, p = 0.012). The post-MAPS group had more severe pathology (PAS Grade 3 8% pre- vs. 47% post-MAPS, p = 0.001). There were fewer intraoperative complications (39% pre- vs.3% post-MAPS, p < 0.001), postoperative complications (32% pre- vs.12% post-MAPS, p = 0.043), hemorrhages >1l (95% pre- vs.65% post-MAPS, p = 0.001), ICU admissions (59% pre- vs.35% post-MAPS, p = 0.04) and shorter hospital stays (10 days pre- vs.7 days post-MAPS, p = 0.02) in the post-MAPS compared to pre-MAPS patients. Neonatal length of stay was 8 days longer in the post-MAPS group (9 days pre- vs. 17 days post-MAPS, p = 0.03). Subgroup analyses demonstrated that ureteral stent placement and uterine artery embolization (UAE) may be important steps to reduce complications and ICU admissions. When comparing just those who underwent UAE, patients in the post-MAPS group experienced fewer hemorrhages greater five liters (EBL >5l 43% pre- vs.4% post-MAPS, p = 0.007). Conclusion: An evidence-informed approach to management of PAS was associated with decreased complication rate, EBL >1l, ICU admission and length of hospitalization, particularly for patients with severe pathology.

Development of obstetric anesthesia core competencies for USA residency programs through a Delphi process.

PURPOSE: The standard for anesthesia residency training in the USA mainly relies on the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project, a framework that lacks specific directives for subspecialties including obstetric anesthesia. We aimed to identify core competencies in obstetric anesthesiology that can be adapted to different residency training programs to help improve the quality of training and accountability of the institutions within the USA. METHODS: We identified a preliminary list of competencies from review of existing competency-based obstetric anesthesia training curricula and practice guidelines. We used a modified Delphi methodology to achieve expert consensus among members of the Society for Obstetric Anesthesia and Perinatology education committee. The panellists were asked to evaluate the importance of each competency using a five-point Likert scale, with consensus after two rounds defined at 80% agreement. The responders were also asked at which level of training each competency should be attained. RESULTS: The Delphi rounds had 75% response rate and derived 94 competencies that were categorized under the six ACGME domains: patient care (38), medical knowledge (45), system-based practice (two), practice-based learning and improvement (five), interpersonal communication skills (two), and professionalism (two). CONCLUSION: We generated a residency training competency list for obstetric anesthesiology through expert consensus. This list can be used by residency training programs to develop a structured competency-based curriculum with tangible milestones, thereby reducing heterogeneity in the standard of training.

RéSUMé: OBJECTIF: La norme pour la formation en résidence en anesthésie aux États-Unis repose principalement sur le Projet de résultats (Outcome Project) de l'Accreditation Council for Graduate Medical Education (ACGME), un cadre qui ne dispose pas de directives spécifiques pour les surspécialités, notamment pour l'anesthésie obstétricale. Notre objectif était d'identifier les compétences de base en anesthésiologie obstétricale qui pourraient être adaptées aux différents programmes de formation en résidence afin d'améliorer la qualité de la formation et la responsabilisation des établissements aux États-Unis. MéTHODE: Nous avons dressé une liste préliminaire de compétences en passant en revue les programmes de formation axés sur les compétences et les lignes directrices de pratique existants en anesthésie obstétricale. Nous avons utilisé une méthodologie Delphi modifiée pour parvenir à un consensus d'expert·es parmi les membres du comité d'éducation de la Society for Obstetric Anesthesia and Perinatology. Les panélistes ont été invité·es à évaluer l'importance de chaque compétence à l'aide d'une échelle de Likert à cinq points, le consensus étant défini à 80 % d'accord après deux tours. On a également demandé aux répondant·es à quel niveau de formation chaque compétence devrait être atteinte. RéSULTATS: Les étapes du processus Delphi ont eu un taux de réponse de 75 % et ont permis de déterminer 94 compétences qui ont été classées dans les six domaines ACGME : soins aux patient·es (38), connaissances médicales (45), pratique systémique (deux), apprentissage et amélioration basés sur la pratique (cinq), compétences en communication interpersonnelle (deux) et professionnalisme (deux). CONCLUSION: Nous avons généré une liste de compétences pour la formation de résidence en anesthésiologie obstétricale grâce à un consensus d'expert·es. Cette liste peut être utilisée par les programmes de formation en résidence pour élaborer un programme structuré axé sur les compétences avec des jalons tangibles, réduisant ainsi l'hétérogénéité dans la norme de formation.

Anesthesia Considerations for Placenta Accreta Spectrum.

Anesthesiologists are critical members of the multidisciplinary team managing patients with suspected placenta accreta spectrum (PAS). Preoperatively, anesthesiologists provide predelivery consultation for patients with suspected PAS where anesthetic modality and invasive monitor placement is discussed. Additionally, anesthesiologists carefully assess patient and surgical risk factors to choose an anesthetic plan and to prepare for massive intraoperative hemorrhage. Postoperatively, the obstetric anesthesiologist hold unique skills to assist with postoperative pain management for cesarean hysterectomy. We review the unique aspects of peripartum care for patients with PAS who undergo cesarean hysterectomy and explain why these responsibilities are critical for achieving successful outcomes for patients with PAS. KEY POINTS: · Anesthesiologists are critical members of the multidisciplinary team planning for patients with suspected placenta accreta spectrum.. · Intraoperative preparation for massive hemorrhage is a key component of anesthetic care for patients with PAS.. · Obstetric anesthesiologists have a unique skill set to manage postpartum pain and postoperative disposition for patients with PAS who undergo cesarean hysterectomy..

Placenta Accreta Spectrum Disorders: Knowledge Gaps in Anesthesia Care.

Placenta accreta spectrum (PAS) disorder is a potentially life-threatening condition that can occur during pregnancy. PAS puts pregnant individuals at a very high risk of major blood loss, hysterectomy, and intensive care unit admission. These patients should receive care in a center with multidisciplinary experience and expertise in managing PAS disorder. Obstetric anesthesiologists play vital roles in the peripartum care of pregnant patients with suspected PAS. As well as providing high-quality anesthesia care, obstetric anesthesiologists coordinate peridelivery care, drive transfusion-related decision making, and oversee postpartum analgesia. However, there are a number of key knowledge gaps related to the anesthesia care of these patients. For example, limited data are available describing optimal anesthesia staffing models for scheduled and unscheduled delivery. Evidence and consensus are lacking on the ideal surgical location for delivery; primary mode of anesthesia for cesarean delivery; preoperative blood ordering; use of pharmacological adjuncts for hemorrhage management, such as tranexamic acid and fibrinogen concentrate; neuraxial blocks and abdominal wall blocks for postoperative analgesia; and the preferred location for postpartum care. It is also unclear how anesthesia-related decision making and interventions impact physical and mental health outcomes. High-quality international multicenter studies are needed to fill these knowledge gaps and advance the anesthesia care of patients with PAS.

Performance assessment of intravenous catheters for massive transfusion: A pragmatic in vitro study.

BACKGROUND: Rapid infusion of warmed blood products is the cornerstone of trauma resuscitation and treatment of surgical and obstetric massive hemorrhage. Integral to optimizing this delivery is selection of an intravenous (IV) catheter and use of a rapid infusion device (RID). We investigated which IV catheter and RID system enabled the greatest infusion rate of blood products and the governing catheter characteristics. STUDY DESIGN AND METHODS: The maximum flow rates of nine IV catheters were measured while infusing a mixture of packed red blood cells and fresh frozen plasma at a 1:1 ratio using a RID with and without a patient line extension. To account for IV catheters that achieved the RID's maximum 1000 ml/min, the conductance of each infusion circuit configuration was calculated. RESULTS: IV catheters of 7-Fr caliber or higher reached the maximum pressurized flow rate. The 9-Fr multi-lumen access catheter (MAC) achieved the greatest conductance, over sevenfold greater than the 18 g peripheral catheter (4.6 vs. 0.6 ml/min/mmHg, p < .001). Conductance was positively correlated with internal radius (ß = 1.098, 95% CI 4.286-5.025, p < .001) and negatively correlated with length (ß= - 0.495, 95% CI -0.007 to 0.005, p < .001). Use of an extension line (ß= - 0.094, 95% CI -0.505 to -0.095, p = .005) was independently associated with reduced conductance in large caliber catheters. CONCLUSION: Short, large-diameter catheters provided the greatest infusion rates of massive transfusion blood products for the least pressure. For patients requiring the highest transfusion flow rates, extension tubing should be avoided when possible.

Neuraxial Anesthesia During Cesarean Delivery for Placenta Previa With Suspected Morbidly Adherent Placenta: A Retrospective Analysis.

BACKGROUND: General anesthesia (GA) is often selected for cesarean deliveries (CD) with placenta previa and suspected morbidly adherent placenta (MAP) due to increased risk of hemorrhage and hysterectomy. We reviewed maternal outcomes and risk factors for conversion to GA in a cohort of patients undergoing CD and hysterectomy under neuraxial anesthesia (NA). METHODS: We performed a single-center, retrospective cohort study of parturients undergoing nonemergent CD for placenta previa with suspected MAP from 1997 to 2015. Patients were classified according to whether they received GA, NA, or intraoperative conversion from NA to GA. The primary outcome measure was postoperative acuity, defined as the need for intensive care unit admission, arterial embolization, reoperation, or ongoing transfusion with ≥3 units packed red blood cells. We additionally identified variables positively associated with intraoperative conversion from NA to GA during hysterectomy. Confounding was controlled with logistic regression models. RESULTS: Of 129 patients undergoing nonemergent CD for placenta previa with suspected MAP, 122 (95%) received NA as the primary anesthetic. NA was selected in the majority of patients with a body mass index ≥40 kg/m (9 of 10, 90%), a history of ≥3 prior CDs (18 of 20, 90%), suspected placenta increta or percreta (29 of 35, 83%), and Mallampati classification ≥3 (19 of 21, 90%). Of 72 patients with NA at the time of delivery who required hysterectomy, 15 (21%) required conversion to GA intraoperatively. Converted patients had a higher rate of major packed red blood cell transfusion (60% vs 25%; P = .01), with similar rates of massive transfusion (9% vs 7%; P = 1.0). Converted patients also had a higher incidence of postoperative acuity (47% vs 4%; P < .0001), including 5 intensive care unit admissions for airway management after large-volume resuscitation. After adjusting for multiple confounders, the only independent predictors of conversion among hysterectomy patients were longer surgical duration (adjusted odds ratio 1.54, 95% CI, 1.01-2.42) and a history of ≥3 prior CDs (adjusted odds ratio, 6.45; 95% CI, 1.12-45.03). CONCLUSIONS: NA was applied to and successfully used in the majority of patients with suspected MAP. Our findings support selective conversion to GA during hysterectomy in these patients, focusing on those with the highest levels of surgical complexity.

Non-Neuraxial Labor Analgesia: Options.

Although it is the most effective method to treat labor pain, neuraxial analgesia may be undesired, contraindicated, unsuccessful, or unavailable. Providing safe choices for labor pain relief is a central goal of health care providers alike. Consequently, knowledge of the efficacy, clinical implementation, and side effects of various non-neuraxial strategies is needed to provide appropriate options for laboring patients. In addition to nonpharmacologic alternatives, inhaled nitrous oxide and systemic opioids represent two broad classes of non-neuraxial pharmacologic labor analgesia most commonly available. This review summarizes the current published literature for these non-neuraxial labor analgesic options.

Concurrent visualization of trafficking, expansion, and activation of T lymphocytes and T-cell precursors in vivo.

We have developed a dual bioluminescent reporter system allowing noninvasive, concomitant imaging of T-cell trafficking, expansion, and activation of nuclear factor of activated T cells (NFAT) in vivo. NFAT activation plays an important role in T-cell activation and T-cell development. Therefore we used this system to determine spatial-temporal activation patterns of (1) proliferating T lymphocytes during graft-versus-host disease (GVHD) and (2) T-cell precursors during T-cell development after allogeneic hematopoietic stem cell transplantation (HSCT). In the first days after HSCT, donor T cells migrated to the peripheral lymph nodes and the intestines, whereas the NFAT activation was dominant in the intestines, suggesting an important role for the intestines in the early stages of alloactivation during development of GVHD. After adoptive transfer of in vitro-derived T-cell receptor (TCR) H-Y transgenic T-cell precursors into B6 (H-2(b)) hosts of both sexes, NFAT signaling and development into CD4(+) or CD8(+) single-positive cells could only be detected in the thymus of female recipients indicating either absence of positive selection or prompt depletion of double-positive thymocytes in the male recipients. Because NFAT plays an important role in a wide range of cell types, our system could provide new insights into a variety of biologic processes.

IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell-mediated rejection of systemic lymphoma in immunodeficient mice.

The gamma(c)-cytokines are critical regulators of immunity and possess both overlapping and distinctive functions. However, comparative studies of their pleiotropic effects on human T cell-mediated tumor rejection are lacking. In a xenogeneic adoptive transfer model, we have compared the therapeutic potency of CD19-specific human primary T cells that constitutively express interleukin-2 (IL-2), IL-7, IL-15, or IL-21. We demonstrate that each cytokine enhanced the eradication of systemic CD19(+) B-cell malignancies in nonobese diabetic/severe combined immunodeficient (NOD/SCID)/gamma(c)(null) mice with markedly different efficacies and through singularly distinct mechanisms. IL-7- and IL-21-transduced T cells were most efficacious in vivo, although their effector functions were not as enhanced as IL-2- and IL-15-transduced T cells. IL-7 best sustained in vitro T-cell accumulation in response to repeated antigenic stimulation, but did not promote long-term T-cell persistence in vivo. Both IL-15 and IL-21 overexpression supported long-term T-cell persistence in treated mice, however, the memory T cells found 100 days after adoptive transfer were phenotypically dissimilar, resembling central memory and effector memory T cells, respectively. These results support the use of gamma(c)-cytokines in cancer immunotherapy, and establish that there exists more than 1 human T-cell memory phenotype associated with long-term tumor immunity.

Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors.

We present a strategy for adoptive immunotherapy using T-lineage committed lymphoid precursor cells generated by Notch1-based culture. We found that allogeneic T-cell precursors can be transferred to irradiated individuals irrespective of major histocompatibility complex (MHC) disparities and give rise to host-MHC restricted and host-tolerant functional allogeneic T cells, improving survival in irradiated recipients as well as enhancing anti-tumor responses. T-cell precursors transduced to express a chimeric receptor targeting hCD19 resulted in significant additional anti-tumor activity, demonstrating the feasibility of genetic engineering of these cells. We conclude that ex vivo generated MHC-disparate T-cell precursors from any donor can be used universally for 'off-the-shelf' immunotherapy, and can be further enhanced by genetic engineering for targeted immunotherapy.

Zinc-dependent cleavage in the catalytic core of the hammerhead ribozyme: evidence for a pH-dependent conformational change.

We have characterized a novel Zn2+-catalyzed cleavage site between nucleotides C3 and U4 in the catalytic core of the hammerhead ribozyme. In contrast to previously described divalent metal-ion-dependent cleavage of RNA, U4 cleavage is only observed in the presence of Zn2+. This new cleavage site has an unusual pH dependence, in that U4 cleavage products are only observed above pH 7.9 and reach a maximum yield at about pH 8.5. These data, together with the fact that no metal ion-binding site is observed in proximity to the U4 cleavage site in either of the crystal structures, point toward a pH-dependent conformational change in the hammerhead ribozyme. We have described previously Zn2+-dependent cleavage between G8 and A9 in the hammerhead ribozyme and have discovered that U4 cleavage occurs only after A9 cleavage. To our knowledge, this is the first example of sequential cleavage events as a possible regulatory mechanism in ribozymes.