Successful autologous hematopoietic stem cell transplants using Salmonella positive products collected from asymptomatic donors.

BACKGROUND: Bacterial contamination of hematopoietic stem cell (HSC) products is most commonly due to normal skin flora. Salmonella in HSC products is rare, and to our knowledge safe administration of an autologous HSC product containing Salmonella has not been reported. STUDY DESIGN AND METHODS: We describe two patients undergoing autologous HSC transplant: peripheral blood HSC collection was performed by leukapheresis, and samples were cultured according to standard institutional protocol. Subsequent microorganism identification was performed using MALDI-TOF (Bruker Biotyper). Strain-relatedness was investigated by infrared spectroscopy using the IR Biotyper (Bruker). RESULTS: The patients were asymptomatic throughout the collection process; however, HSC products collected on two consecutive days from each patient were positive for Salmonella. Isolates from both cultures were further characterized as Salmonella enterica serovar Dublin by the local public health department. Antibiotic susceptibility testing revealed different sensitivity patterns for the two strains. IR Biotyper demonstrated significant discriminatory power among the clinically significant Salmonella enterica subspecies, serogroups B, C1, and D. The patient strains were similar as both belonged to Group D Salmonella enterica serovar Dublin but were not identical. The Salmonella positive autologous HSC products were infused to both patients following administration of empiric antibiotic therapy. Both patients successfully engrafted and did well. CONCLUSION: Salmonella is rarely seen in cellular therapy products and positivity may be the result of asymptomatic bacteremia at the time of collection. We present two instances of autologous HSC products containing Salmonella that were infused, along with prophylactic antimicrobial therapy without significant adverse clinical effects.

Assessment of adrenal function at birth using adrenal glucocorticoid precursor to product ratios to predict short-term neonatal outcomes.

BACKGROUND: Most neonatal outcomes in neonates are related to normal adrenal gland function. Assessment of adrenal function in a sick preterm neonate remains a challenge, thus we hypothesized that adrenal steroid precursors to their product ratios have a direct relationship with neonatal outcomes. METHODS: We studied demographics of pregnancy and neonatal outcomes in 99 mother-infant pairs (24-41 weeks) and assayed 7 glucocorticoid precursors in the cortisol biosynthesis/degradation pathway. We correlated antenatal factors and short-term neonatal outcomes with these precursors and their ratios to assess maturity of individual enzymes. RESULTS: We found no correlation between cortisol levels with antenatal factors and outcomes. Antenatal steroid use impacted several cortisol precursors. 17-OH pregnenolone-to-cortisol ratio at birth was the best predictor of short-term neonatal outcomes, such as hypotension, RDS, IVH and PDA. A cord blood 17-OH pregnenolone:cortisol ratio of <0.21 predicts which neonate will have a normal outcome with a high sensitivity and specificity. CONCLUSIONS: Maternal factors and antenatal steroids impact neonatal adrenal function and leads to maturation of adrenal function. 17-OH pregnenolone:cortisol ratio and not cortisol is the best predictor of adrenal function. Adrenal function can be assessed by evaluating the profile of adrenal steroids.

Vitamin D deficiency and depressive symptoms in the perinatal period.

Depression affects 1 in 7 women during the perinatal period. Women with vitamin D deficiency may be at an increased risk for depression. This study investigated the relationship between maternal and cord blood 25-hydroxyvitamin D (25OHD) and maternal depressive symptoms over the perinatal period. Study objectives were to examine variations and relationships between maternal and cord blood vitamin D levels and maternal depressive symptoms over the perinatal period. At a large medical center in southern California, pregnant women (N = 126) were recruited for this longitudinal cohort study. Depressive symptoms (Edinburgh Postnatal Depression Screen, EPDS) and vitamin D status (25OHD) were measured at three time points in the perinatal period: time 1 (T1; N = 125) EPDS and 25OHD were collected in early pregnancy; time 2 (T2; N = 96) EPDS was conducted in the third trimester with blood collected at time of delivery; and time 3 (T3; N = 88) was collected postpartum. A significant inverse relationship between vitamin D status and depressive symptoms was observed between 25OHD and EPDS scores at all time points in this sample (T1 = - 0.18, P = 0.024; T2 = - 0.27, P = 0.009; T3 = - 0.22, P = 0.019). This association remained after controlling for confounders. Low cord blood 25OHD levels were inversely associated with higher EPDS scores in the third trimester (r = - 0.22, P = 0.02). Clinicians may want to consider screening women diagnosed with vitamin D deficiency for depression and vice versa. Vitamin D may represent an important biomarker for pregnant and postpartum women diagnosed with depression. Further studies examining underlying mechanisms and supplementation are needed.

Implementation of a low-titer stored whole blood transfusion program for civilian trauma patients: Early experience and logistical challenges.

INTRODUCTION: Cold-stored low titer group O whole blood (LTOWB) is increasingly utilized in the initial resuscitation of exsanguinating trauma patients. We report on our early experience with LTOWB, focusing on logistics, implementation challenges, and outcomes. METHODS: In February, 2019, LTOWB was incorporated into the massive transfusion protocol (MTP) activated for trauma patients in the emergency department (ED.) Up to 4 units of LTOWB were included in the MTP cooler, depending on availability, and were transfused prior to transfusion of any other blood products from the MTP cooler. Demographics, injury characteristics, and outcomes were obtained, and the logistics of LTOWB availability were reviewed. RESULTS: Over a 12-month period, MTP was activated for 74 trauma patients. Of those, 38 (51%) MTP included at least one unit of LTOWB, with 19/38 (50%) including 4 LTOWB units. A total of 177 units of LTOWB were purchased during the study period, and of those, 74 (42%) expired before use. Patients who received LTOWB had a similar mortality compared to those who received component therapy (39% vs. 47%; Odds Ratio [95% CI]: 0.7 [0.3, 2.0]; p = 0.72,) however, they were able to achieve a significantly higher plasma:pRBC ratio during the duration of MTP activation (mean [SD] 0.8 [0.2] vs. 0.4 [0.4]; mean difference [95% CI]: 0.4 [0.2, 0.5]; p < 0.01.) CONCLUSIONS: Our early experience with LTOWB transfusion demonstrates feasibility, but also highlights challenges with inventory management. These findings triggered changes to our protocol aiming at minimizing wastage. The use of LTOWB may yield a higher plasma:pRBC ratio early during the resuscitation period. Further investigation is required to explore whether this may yield a survival advantage. LEVEL OF EVIDENCE: III (Therapeutic/Care Management).

Overtransfusion of packed red blood cells during massive transfusion activation: a potential quality metric for trauma resuscitation.

Objectives: The goal of this study was to explore the incidence of overtransfusion in trauma patients requiring massive transfusion protocol (MTP) activation and identify modifiable risk factors. We hypothesized that overtransfusion is common after MTP activation. Methods: Patients admitted to a level I trauma center from July 2016 to December 2019 and who required MTP activation were selected. The primary outcome was overtransfusion, defined as a hemoglobin (Hg) ≥11 g/dL at 24 hours (±2 hours). A Cox regression model was used to identify independent risk factors for overtransfusion. Results: 140 patients met inclusion criteria. The median age was 39.0 years, with the majority (74.3%) being male. The median (IQR) Injury Severity Score (ISS) was 24.0 (58.0) and 38.4% had a penetrating mechanism. The median (IQR) admission Hg was 12.6 (11.7) g/dL. Overall, 71.4% of patients were overtransfused by the conclusion of MTP, 43.6% 24 hours later, and 29.5% at discharge. Overtransfusion did not correlate with the number of units of blood transfused nor with the duration of MTP. Overtransfused patients at 24 hours after the conclusion of MTP were significantly more likely to present with a penetrating injury (52.5% vs. 27.3%, p=0.003) and have a significantly lower ISS (median (IQR) 18.5 (44.0) vs. 26.0 (58.0), p=0.035.) In a Cox regression model, penetrating mechanism (adjusted HR (AHR): 2.93; adjusted p=0.004) and admission base excess (BE) (AHR: 1.15; adjusted p=0.001) were the only variables independently associated with overtransfusion. Conclusions: Overtransfusion of trauma patients requiring MTP activation is highly common, leading to overutilization of a limited resource. Penetrating trauma and BE may be modifiable risk factors that can help limit overtransfusion. Overtransfusion should be tracked as a data point by blood banks and trauma centers and be further studied as a potential quality metric for the resuscitation of massively transfused trauma patients. Level of evidence: III.

Platelet-rich plasma for the replenishment of bone.

This review examines the use of platelet-rich plasma (PRP) in the treatment of bone injuries and to stimulate bone formation. Studies examining both in vivo bone healing and in vitro actions of PRP on osteoblasts are reviewed. Overall, the available literature suggests that PRP does not appreciably impact bone healing or induce bone formation. However, there is some evidence to suggest that PRP might augment recruitment of osteoblast progenitors to injection sites or in sites expected to experience delayed healing. In this capacity PRP might be utilized to initiate repair of an otherwise poorly healing skeletal lesion. The demonstration that PRP is a viable therapy is hindered by a lack of standardized criteria for what constitutes PRP, and more studies are needed to compare the efficacy of PRP to that of transforming growth factor-ß or platelet-derived growth factor used as sole agents.

Altered type 1 interferon responses in alloimmunized and nonalloimmunized patients with sickle cell disease.

Patients with sickle cell disease (SCD) have a high prevalence of RBC alloimmunization. However, underlying mechanisms are poorly understood. Given that proinflammatory type 1 interferons (IFNα/ß) and interferon stimulated genes (ISGs) promote alloimmunization in mice, we hypothesized that IFNα/ß may contribute to the increased frequency of alloimmunization in patients with SCD. To investigate this, expression of ISGs in blood leukocytes and peripheral blood mononuclear cells (PBMCs) of previously transfused SCD patients with or without alloimmunization and race-matched healthy controls were quantified, and IFNα/ß gene scores were calculated. IFNα/ß gene scores of SCD leukocytes and plasma cytokines were elevated, compared to controls (gene score, p < 0.01). Upon stimulation with IFNß, isolated PBMCs from patients with SCD had elevated ISGs and IFNα/ß gene scores (p < 0.05), compared to stimulated PBMCs from controls. However, IFNß-stimulated and unstimulated ISG expression did not significantly differ between alloimmunized and non-alloimmunized patients. These findings indicate that patients with SCD express an IFNα/ß gene signature, and larger studies are needed to fully determine its role in alloimmunization. Further, illustration of altered IFNα/ß responses in SCD has potential implications for IFNα/ß-mediated viral immunity, responses to IFNα/ß-based therapies, and other sequelae of SCD.

Management of familial hypertriglyceridemia during pregnancy with plasma exchange.

Hypertriglyceridemia-induced pancreatitis is a serious complication of familial dyslipidemias. Hormonal influences during pregnancy can compromise otherwise controlled lipid levels in women with familial hypertriglyceridemia and predispose to pancreatitis leading to increased morbidity in both mother and fetus. We report the successful use of therapeutic plasma exchange (TPE) in the management of hypertriglyceridemia during pregnancy resulting in avoidance of pancreatitis and delivery of a healthy term infant. Thirteen TPEs were performed from 19 to 36 weeks gestation to maintain tight control of triglyceride levels.

Therapeutic plasma exchange for desensitization prior to transplantation in ABO-incompatible renal allografts.

BACKGROUND: Although there have been desensitization protocols used for ABO-incompatible (ABOi) renal transplants, there are a lack of studied protocols. Our center developed a preconditioning protocol that involved mycophenolic acid, therapeutic plasma exchange (TPE), anti-CD20 monoclonal antibody (rituximab), and intravenous immunoglobulin (IVIG) that allowed for ABOi renal transplantation. METHODS: Ten patients in our institution with end-stage renal disease who were unable to procure ABO-compatible donor kidneys underwent treatment with this protocol (which included a uniform 5 TPE sessions) prior to an ABOi renal transplant. A retrospective chart review was performed on these patients and clinical endpoints including ABO antibody titers, serum creatinine, clinical complications, and graft performance were analyzed. RESULTS: The median ABO antibody titers at presentation, after completion of the protocol, and after transplant for the patients were 32 (range, 2-128), 8 (range, 1-64), and 4 (range, 2-32), respectively. The mean serum creatinine at study conclusion was 1.45 +/- 1.04 mg/dl at an average of 262.20 days from transplant. There were four incidents of antibody-mediated rejection (AMR) and two incidents of delayed graft function (DGF). There was one incident of graft failure and no patient deaths. CONCLUSIONS: The desensitization protocol used by our institution allowed for successful ABOi renal transplantation. Although there were incidents of AMR and DGF, the majority of the transplants resulted in viable grafts. A larger patient study group may be needed to fully evaluate the efficacy and safety of this protocol.

Therapeutic plasma exchange: an underutilized therapeutic modality?

Since its clinical availability approximately 25 years ago, therapeutic plasma exchange (TPE) has become recognized as appropriate primary therapy for many diverse medical conditions. In some aspects TPE has been constrained in its use according to schedules of efficacy. Expansion of TPE to other indications is likely once attention is focused on its ability to enable patients to avoid potentially toxic pharmacologic interventions if employed as a chronic therapy, and especially when it is accepted that adjunctive use, not only a curative role, is a valuable use of this therapeutic modality.

Disseminated coccidioidomycosis in pregnancy.

Coccidioidomycosis is a fungal infection contracted through the inhalation of airborne spores, which are most frequently present in desert areas of the southwestern United States and Mexico. Primary immune response to infection is by T(H)1, a subset of helper T cells. Although pulmonary symptoms are most common, hematogenous systemic spread can also occur. Pregnancy is a well-noted risk factor for disseminated Coccidioides infection. The objective of this review is to provide an overview of coccidioidomycosis and to review immunologic and hormonal factors that increase risk of dissemination in pregnancy. Dissemination may occur more frequently in pregnant patients than in nonpregnant women because of shifts in T-cell immunity, changes in cytokine production, and increased hormone levels. There is disagreement regarding the precise incidence of systemic spread in pregnancy, but most sources agree that risk is substantially increased and vigilance must be high in patients with exposures in endemic areas.

Preventing recurrence of focal segmental glomerulosclerosis following renal transplantation: a case report.

While the recurrence of FSGS in a primary renal transplant has been well studied, strategies to prevent subsequent recurrence in later transplants, has not been well formulated. This is important considering that one center's experience with adults reported an initial recurrence rate of 57% with reoccurrence of 37% in subsequent transplants. However, renal function was maintained in 62% (1). In pediatrics, data from a single-center reported 100% recurrence of FSGS in the second allograft after an initial recurrence of 52% (2). Two commentaries reviewing such data, one each in adults and pediatrics, suggested that the benefits of living-related donation might not be realized in patients with FSGS because of this frequent recurrence (3, 4). Here, we report a patient who was considered to be at very high risk for post-transplant recurrence of FSGS, because of the established risk factors, who was successfully retransplanted after a course of pretransplant plasmapheresis, followed by post-transplant plasmapheresis and the use of cyclosporine. Eighteen months post-transplant, he has no proteinuria and his serum creatinine is 1.2 mg/dL.

Combination vincristine and plasma exchange as initial therapy in patients with thrombotic thrombocytopenic purpura: one institution's experience and review of the literature.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) was once a highly fatal disease with mortality reaching nearly 95 percent; however, application of therapeutic plasma exchange (TPE) has dramatically increased survival. Nevertheless, mortality remains substantial (10%-30% in many published reports), requiring the search for more efficacious treatments. Vincristine (VCR) has been generally reserved for refractory TTP. Despite its effectiveness in a salvage mode, VCR has not been widely advocated as first-line therapy in conjunction with TPE. We previously reported improved survival when VCR and TPE were administered at presentation in patients treated from 1979 to 1994. Utilizing this standardized approach, outcomes of an additional group of patients and the results of a literature review of VCR therapy for TTP are reported. STUDY DESIGN AND METHODS: Medical records of all patients with a diagnosis of TTP treated between 1995 and 2002 at Cedars-Sinai Medical Center were reviewed. TPE was performed daily, exchanging 1.25 plasma volumes, until the platelet count normalized. Patients received VCR 1.4 mg/m2, (up to 2.0 mg total dose) after the first TPE. A literature review of all publications utilizing VCR in the management of TTP was performed with MEDLINE. RESULTS: Twelve consecutive patients meeting the diagnostic criteria received treatment with VCR and TPE. All patients achieved durable remission. Patients tolerated VCR without significant complications. CONCLUSION: Our 100 percent survival rate, as well as evidence garnered from the literature review, suggests that combination therapy with VCR and TPE at presentation might be more effective than TPE alone and therefore warrants consideration as first-line therapy for TTP patients.

A case-control study of the impact of WBC reduction on the cost of hospital care for patients undergoing coronary artery bypass graft surgery.

BACKGROUND: WBC reduction of blood components may reduce the incidence of transfusion reactions. The cost of this intervention might be offset by a reduction in the incidence of postoperative infection, thereby reducing the length of hospital stay and thus the cost of care for patients receiving transfusion. Cedars-Sinai Medical Center provided WBC-reduced blood components to all patients for a period of 2 years, creating an opportunity to compare the incidence of postoperative infection, length of hospital stay, and total hospital costs for patients undergoing coronary artery bypass graft surgery, before, during, and after WBC reduction. STUDY DESIGN AND METHODS: Data were obtained by examining hospital records of patients who received transfusion and control patients who did not receive transfusion for the years 1991 (before WBC reduction), 1992 to 1993 (during WBC reduction), and 1994 (following discontinuation of WBC reduction). Comparisons were made by use of ANOVA following log or square root transformation of the data. RESULTS: Length of hospital stay for patients who received transfusion decreased over time. Mean hospital stays were 15.9, 14.1, and 12.1 days before, during, and after WBC reduction, respectively. A similar trend was seen in the patients who did not receive transfusion. There was no indication that WBC reduction functioned as an independent variable that was responsible for the observed decrease. The rate of postoperative infection stayed constant during WBC reduction and only dropped when WBC reduction was stopped. Mean hospital cost showed no significant change over time for either the transfusion group or the nontransfusion group. CONCLUSION: The cost of providing a totally WBC-reduced blood supply may not be offset by immediate savings related to decreased postoperative infections, reduced length of hospital stay, and cost of hospital care.