Search

Combined rearrangements of MYC and BCL2 are rare in precursor B-cell acute lymphoblastic leukemia (B-ALL). A 14-year-old boy presented with swelling of the knee and face. Imaging revealed diffuse infiltration of lacrimal glands, parotid glands along with the extensive epidural disease. Morphology and immunophenotype of knee joint aspirate were consistent with precursor B-ALL. Fluorescent in situ hybridization identified rearrangements of MYC and BCL2 genes. The disease was refractory to intensive treatment. The patient died of progressive disease. Precursor B-ALL with combined MYC and BCL2 rearrangements is rare, characterized by an aggressive clinical course, and has an inadequate response to standard therapeutic approaches., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A glass ceiling effect exists for women in male-dominated professions. Recent studies also show a glass-cliff effect where senior women can more easily fall from positions of leadership. Transplantation remains a male-dominated specialty. This study investigated gender and the perception of adverse clinical incidents in transplantation., Methods: Prospective randomised web-based survey involving five clinical scenarios presenting two versions of episodes with errors or mistakes, with either a male or female as a randomly named protagonist (Set1 and Set2). To address unconscious bias, the study was described as examining actions following clinical adverse incidents in transplantation. Each scenario was followed by 2 closed questions: (1) clinical performance rating and (2) selection of action required. Reasoning was invited (open-text comments). Responses were analyzed using quantitative and qualitative methods., Results: One hundred ninety-one invitees responded; 134 completed questionnaires. There were no statistically significant differences (P > 0.05) in responses between sets for performance ratings or recommended actions. However, for "first solo laparoscopic surgery" scenario, there was some indication that "No Action" was more likely if surgeon was male (P = 0.056). Male responses rated female performance as significantly worse (P = 0.035) for the laboratory-based scenario. One hundred two participants provided open-text comments. Thematic analysis identified 7 themes. Acceptable levels of risk theme demonstrated engendered leadership beliefs, that is, when clinical judgment proved incorrect, males described as forceful but females as needing support. In cases where things went wrong, respondents were more likely to comment females should not have decided to proceed., Conclusions: While gender may no longer be an overt issue in perceived performance of senior staff in transplantation, respondents' use of language and their choice of words display elements of unconscious (covert) engendered views.

Objective: To implement a systematic approach to safely reduce nulliparous cesarean birth rates., Methods: This is a quality improvement project at two rural community hospitals and one urban community hospital in North Carolina. These facilities implemented a systematic approach to reduce nulliparous cesarean birth rates, aligning with recommendations developed by the Council on Patient Safety in Women's Health Care: Patient Safety Bundle on the Safe Reduction of Primary Cesarean Births. Health care providers and nurses received education on contemporary labor management guidelines developed by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine Obstetric Care Consensus regarding safe prevention of primary cesarean deliveries and nurses were instructed on labor support techniques. The preguideline implementation period was January 1, 2015, to June 30, 2015. The postguideline implementation period was July 1, 2016, to December 31, 2016. The primary outcome measured was the nulliparous, term, singleton, vertex cesarean birth rate. Secondary outcomes included maternal and neonatal outcomes. Standard statistical analysis was used and a P value of <.05 was considered significant., Results: There were 434 women identified in the preguideline period and 401 women in the postguideline period. The nulliparous, term, singleton, vertex cesarean birth rate decreased from 27.9% to 19.7% [odds ratio (OR) 0.63, CI 0.46-0.88]. There were improvements in health care provider compliance with following the labor management guidelines from 86.2% to 91.5% (OR 1.73, 95% CI 1.11-2.70), the use of maternal position changes from 78.7% to 87.5% (OR 1.86, 95% CI 1.29-2.68), and use of the peanut birthing ball from 16.8% to 45.2% (OR 3.83, 95% CI 2.84-5.16) as provisions for labor support., Discussion: Implementing a systematic approach for care of nulliparous women is associated with a decrease in term, singleton, vertex cesarean birth rates.

During the last 20 years, waiting lists for renal transplantation (RT) have grown significantly older. However, elderly patients (ie ≥65 years of age) are still more rarely referred or accepted to waiting lists and, if enlisted, have less chances of actually receiving a kidney allograft, than younger counterparts. In this review, we looked at evidence for the benefits and risks of RT in the elderly trying to answer the following questions: Should RT be advocated for elderly patients? What should be the criteria to accept elderly patients on the waiting list for RT? What strategies might be used to increase the rate of RT in waitlisted elderly candidates? For selected elderly patients, RT was shown to be superior to dialysis in terms of patient survival. Virtually all guidelines recommend that patients should not be deemed ineligible for RT based on age alone, although a short life expectancy generally might preclude RT. Concerning the assessment of comorbidities in the elderly, special attention should be paid to cardiac evaluation and screening for malignancy. Comorbidity scores and frailty assessment scales might help the decision making on eligibility. Psychosocial issues should also be evaluated. To overcome the scarcity of organ donors, elderly RT candidates should be encouraged to consider expanded criteria donors and living donors, as alternatives to deceased standard criteria donors. It has been demonstrated that expanded criteria donor RT in patients 60 years or older is associated with higher survival rates than remaining on dialysis, whereas living donor RT is superior to all other options.

Background: B cells play an important role in renal allograft pathology, particularly in acute and chronic antibody-mediated rejection (AMR). B-cell activating factor belonging to the tumor necrosis factor family (BAFF; also known as BLyS) is a cytokine that enhances B-cell survival and proliferation., Methods: We analyzed serum BAFF levels in 32 patients undergoing antibody-incompatible (Ai) renal transplantation and 319 antibody-compatible transplant recipients and sought to determine whether there was a correlation with acute rejection and with transplant function and survival., Results: We demonstrate that, in patients undergoing Ai transplantation, elevated serum BAFF levels at baseline (before both antibody removal/desensitization and transplantation) are associated with an increased risk of subsequent AMR. In antibody-compatible transplant recipients at lower risk of AMR, no statistically significant association was observed between pretransplantation serum BAFF and AMR., Conclusions: These data raise the possibility that, in high immunologic risk patients undergoing Ai transplantation, the presence of elevated pretransplantation serum BAFF might identify those at increased risk of AMR. BAFF neutralization may be an interesting therapeutic strategy to explore in these patients, particularly because such agents are available and have already been used in the treatment of autoimmunity.

The incorporation of complex medical device technologies into clinical practice is governed by critical oversight of the US Food and Drug Administration. This regulatory process requires a judicious balance between assuring safety and efficacy, while providing efficient review to facilitate access to innovative therapies. Recent contrasting views of the regulatory process have emphasized the difficulties in obtaining an optimal balance. Mechanical circulatory support has evolved to become an important therapy for patients with advanced heart failure with the advent of more durable, implantable ventricular assist devices. The regulatory oversight of these new technologies has been difficult owing to the complexities of these devices, associated adverse event profile, and severity of illness of the intended patient population. Maintaining a regulatory environment to foster efficient introduction of safe and effective technologies is critical to the success of ventricular assist device therapy and the health of patients with advanced heart failure. Physicians representing key surgical and cardiology societies, and representatives from the Food and Drug Administration, National Heart, Lung, and Blood Institute, Centers for Medicare and Medicaid Services, Interagency Registry of Mechanically Assisted Circulatory Support, and industry partners gathered to discuss relevant issues regarding the current regulatory environment assessing ventricular assist devices. The goal of the meeting was to explore innovative ways to foster the introduction of technologically advanced, safe, and effective ventricular assist devices. The following summary reflects opinions and conclusions endorsed by The Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, Heart Failure Society of America, International Society for Heart and Lung Transplantation, and the Interagency Registry of Mechanically Assisted Circulatory Support.

In the United States, endometrial cancer is the most commonly diagnosed cancer of the female reproductive system. Strategies to sensitively and accurately diagnose premalignant endometrial lesions are sorely needed. We reviewed studies pertaining to the diagnostic challenges of endometrial precancers, their predictive value, and evidence to support management strategies. Currently, two diagnostic schemas are in use: the four-class 1994 World Health Organization hyperplasia system, based on morphologic features of architectural complexity and nuclear atypia and, more recently, the two-class endometrial intraepithelial neoplasia system, which is quantitative. Diagnosis should use criteria and terminology that distinguish between clinicopathologic entities that can be managed differently. In some instances, such as for women with hereditary nonpolyposis colon cancer, biomarkers may aid in diagnosis, but the clinical utility of biomarkers has yet to be determined. Total hysterectomy is curative for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, and provides a definitive standard for assessment of a concurrent carcinoma, when clinically appropriate. If hysterectomy is performed for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, then intraoperative assessment of the uterine specimen for occult carcinoma is desirable, but optional. Nonsurgical management may be appropriate for patients who wish to preserve fertility or those for whom surgery is not a viable option. Treatment with progestin therapy may provide a safe alternative to hysterectomy; however, clinical trials of hormonal therapies for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia have not yet established a standard regimen. Future studies will need to determine the optimal nonsurgical management of atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, standardizing agent, dose, schedule, clinical outcomes, and appropriate follow-up.

Objective: This study evaluated how enrollment in special education services in 11-year-old children relates to prenatal cocaine exposure (PCE), psychopathology, and other risk factors., Methods: Participants were 498 children enrolled in The Maternal Lifestyle Study, a prospective, longitudinal, multisite study examining outcomes of children with PCE. Logistic regression was used to examine the effect of PCE and psychopathology on enrollment in an individualized education plan (IEP; a designation specific to children with special education needs), with environmental, maternal, and infant medical variables as covariates., Results: PCE, an interaction of PCE and oppositional defiant disorder, child attention-deficit hyperactivity disorder, parent-reported internalizing behaviors, and teacher-reported externalizing behaviors, predicted enrollment in an IEP. Other statistically significant variables in the model were male gender, low birth weight, being small for gestational age, white race, caregiver change, low socioeconomic status, low child intelligence quotient, caregiver depression, and prenatal marijuana exposure., Conclusions: PCE increased the likelihood of receiving an IEP with adjustment for covariates. Psychopathology also predicted this special education outcome, in combination with and independent of prenatal cocaine exposure.

Background: The role of the complement system in antibody-mediated rejection has been investigated in relation to circulating complement interacting with renal microvascular endothelium, resulting in the formation of peritubular capillary C4d. However, the possible importance of local complement synthesis is less clear. The aim of this study was to determine whether human vascular endothelium could produce C4 in response to stimulation in vitro., Methods: Human microvascular endothelial cells and glomerular endothelial cells were stimulated with endotoxins, cytokines, and human leukocyte antigen-specific antibodies. Synthesis of complement was investigated using western blotting and indirect immunofluorescence. De novo C4 synthesis was confirmed by using C4 small interfering RNA., Results: Glomerular and microvascular endothelium, both produce C3 and C4 complement protein. Complement synthesis was stimulant-specific-C3 was produced mainly after stimulation with lipopolysaccharide whereas C4 synthesis occurred on treatment with gamma interferon. Culture with human leukocyte antigen-specific antibodies resulted in a significant increase of C4 protein synthesis by both cell lines., Conclusions: We have shown for the first time that human microvascular endothelium can be stimulated to synthesize C4 in vitro. The implications of this for clinical transplantation, especially in the context of antibody-mediated rejection, its histological interpretation and as a potential target for therapy would have to be determined by further studies.

Background: Human leukocyte antigen (HLA) antibody-incompatible renal transplantation has been increasingly performed since 2000 but with few data on the medium-term outcomes., Methods: Between 2003 and 2011, 84 patients received renal transplants with a pretreatment donor-specific antibody (DSA) level of more than 500 in a microbead assay. Seventeen patients had positive complement-dependent cytotoxic (CDC) crossmatch (XM), 44 had negative CDC XM and positive flow cytometric XM, and 23 had DSA detectable by microbead only. We also reviewed 28 patients with HLA antibodies but no DSA at transplant. DSAs were removed with plasmapheresis pretransplant, and patients did not routinely receive antithymocyte globulin posttransplant., Results: Mean follow-up posttransplantation was 39.6 (range 2-91) months. Patient survival after the first year was 93.8%. Death-censored graft survival at 1, 3, and 5 years was 97.5%, 94.2%, and 80.4%, respectively, in all DSA+ve patients, worse at 5 years in the CDC+ve than in the CDC-ve/DSA+ve group at 45.6% and 88.6%, respectively (P<0.03). Five-year graft survival in the DSA-ve group was 82.1%. Rejection occurred in 53.1% of DSA+ve patients in the first year compared with 22% in the DSA-ve patients (P<0.003)., Conclusions: HLA antibody-incompatible renal transplantation had a high success rate if the CDC XM was negative. Further work is required to predict which CDC+ve XM grafts will be successful and to treat slowly progressive graft damage because of DSA in the first few years after transplantation.

Objective: To examine screening results obtained by serial annual behavioral assessment of children with prenatal drug exposure., Method: The Maternal Lifestyle Study enrolled children with prenatal cocaine exposure (PCE) at birth for longitudinal assessments of developmental, behavioral, and health outcomes. At 8, 9, 10, 11, and 12 years of age, caregivers rated participants on the Pediatric Symptom Checklist (PSC). Serial PSC results were compared with an established broad-based behavioral measure at 9, 11, and 13 years. PSC results were analyzed for 1081 children who had at least 2 annual screens during the 5-year time span. Most subjects (87%) had 4 or more annual screens rated by the same caregiver (80%). PSC scores (and Positive screens) over time were compared at different time points for those with and without PCE. Covariates, including demographic factors and exposures to certain other substances, were controlled., Results: Children with PCE had significantly higher scores overall, with more Positive screens for behavior problems than children without PCE. Children with PCE had more externalizing behavior problems. Children exposed to tobacco prenatally and postnatally also showed higher PSC scores. Over time, PSC scores differed slightly from the 8-year scores, without clear directional trend. Earlier PSC results predicted later behavioral outcomes., Conclusion: Findings of increased total PSC scores and Positive PSC screens for behavioral concerns in this group of children with prenatal substance exposure support the growing body of evidence that additional attention to identification of mental health problems may be warranted in this high-risk group.

Introduction: Some Indoasian (IA) patients with established renal failure travel abroad for commercial kidney transplantation. We compared the 1-year outcomes of IA patients from one UK region who received overseas transplants with IA patients receiving local living donor (LD) kidney transplantation, deceased donor (DD) transplantation, and dialysis., Methods: Between 1996 and 2006, 40 adults were transplanted overseas; 38 were IA, and follow-up data were available on 36 patients. Forty IA patients received LD transplants, and 156 patients received DD transplants locally. A cohort of 120 prospective dialysis patients was also used as a comparator group., Results: In the overseas cohort, 20 patients (56%) were not active in the UK transplant waiting list at the time of kidney transplantation overseas. One-year graft survival was 87%, and 1-year patient survival was 83%. Composite graft and patient survival was 69.5% at 1 year. In the local LD transplant recipients, patient survival was 97.5% (39 of 40; P=0.03), and graft survival was 97.5% (39 of 40; P=0.06). Composite graft and patient survival was 95% (P=0.003). In the overseas group, 42% had major infections compared with 15% in the local group (P=0.02). One-year graft survival for DD transplant was 84.6% (132 of 156), and 1-year patient survival was 93% (145 of 156; P=NS and P=0.06, respectively). In the dialysis group, 1-year patient survival was 96.7% (116 of 120; P=0.001)., Conclusion: IA patients who choose to travel overseas for kidney transplantation have poor clinical outcomes and should be counseled accordingly.

Background: After human leukocyte antigen (HLA) antibody-incompatible transplantation, donor specific and third party HLA antibodies may be found, and their levels fall in a donor-specific manner during the first month. However, these changes have not been previously described in detail., Methods: Donor-specific HLA antibody (DSA) and third-party HLA antibody (TPA) levels were measured using the microbead method in 44 presensitized patients who had renal transplantation., Results: DSA+TPA fell in the first 4 days after transplantation, and greater falls in DSA indicated absorption by the graft. This occurred for class I (57.8% fall compared with 20.2% for TPA, P<0.0005), HLA DR (63.0% vs. 24.3%, P<0.0004), and for HLA DP/DQ/DRB3-4 (34% vs. 17.5%, P=0.014). Peak DSA levels occurred at a mean of 13 days posttransplant, and they were higher than pretreatment in 25 (57%) patients and lower in 19 (43%) patients (P=ns). The risk of rejection was associated with peak DSA levels; 15 of 25 (60%) patients with DSA at median fluorescence intensity (MFI) more than 7000U experienced rejection, compared with 4 of 7 (57%) patients with peak DSA MFI 2000 to 7000U, and 2 of 12 (17%) patients with peak DSA MFI less than 2000U (P<0.02). DSA levels subsequently fell in a donor specific manner compared to TPA., Conclusion: DSA levels may change markedly in the first month after antibody incompatible transplantation, and the risk of rejection was associated with higher pretreatment and peak levels.

Objective: We evaluated whether living arrangements of children with or without prenatal drug exposure would be associated with their behavior outcomes and adaptive functioning., Methods: A total of 1388 children with or without prenatal cocaine or opiate exposure were enrolled in a longitudinal cohort study at 1 month of age, were seen at intervals, tracked over time for their living situation, and evaluated for behavior problems and adaptive functioning at 3 years of age. The Child Behavior Checklist and Vineland Adaptive Behavior Scales were administered. Using multiple regression models, we determined the factors that would predict behavior problems and adaptive functioning., Results: Of the children enrolled, 1092 children were evaluated. Total and externalizing behavior problems T scores of children in relative care were lower (better) than those in parental care; externalizing behavior scores were lower than those in nonrelative care (p < .05). Total behavior problem scores increased 2.3 and 1.3 points, respectively, with each move per year and each year of Child Protective Services involvement. Compared to children in nonrelative care, those in parental or relative care had higher (better) scores in the Vineland Adaptive Behavior Scales total composite (p < .023), communication (p < .045), and daily living (p < .001). Each caretaker change was associated with a decrease of 2.65 and 2.19 points, respectively, in communication and daily living scores., Conclusion: Children's living arrangements were significantly associated with childhood behavior problems and adaptive functioning. The instability of living situation was also a significant predictor of these outcomes. While family preservation continues to be the goal of the child welfare system, expediting decision toward permanency remains paramount once children are placed in foster care.

Background: Accommodation to antibody is an important mechanism in successful ABO-incompatible transplantation, but its importance in human leukocyte antigen (HLA) antibody-incompatible transplantation is less clear, as sensitive techniques facilitating daily measurement of donor-specific HLA antibodies (DSAs) have only recently been developed., Methods: We report 24 patients who had HLA antibody-incompatible kidney transplantation (21 living donors, 3 deceased), 21 of whom had pretransplant plasmapheresis. Eight had positive complement-dependent cytotoxic (CDC) crossmatch (XM) pretransplant plasmapheresis, nine had positive flow cytometric (FC) XM, and seven had DSA detectable by microbead analysis only. After transplant, DSA levels were monitored closely with microbead assays., Results: Rejection occurred in five of eight (62.5%) CDC-positive cases, in three of nine (33%) FC-positive cases, and in two of seven (29%) of microbead-only cases at a median of 6.5 days after transplantation. Resolution occurred at a median of 15 days after transplantation, in 8 of 10 cases when the microbead level of DSA had median fluorescence intensity (MFI) >2000 U, in 6 of 10 when the microbead MFI >4000 U. In 8 of 10 cases, the microbead MFI at the time of resolution was greater than at the onset. DSA did not always cause clinical rejection. In five cases with a posttransplant DSA peaking at MFI >2000 U on microbead assay, rejection did not occur., Conclusion: These data suggest that the dominant method of successful transplantation was function of the transplant in the presence of circulating DSA, and they also define the period during which this occurred.

Purpose: Beliefs about the etiology of coronary heart disease (CHD) can influence patient outcomes following an acute cardiac event. However, past research has focused predominantly on male patients. The present study investigated causal attributions and their associations with actual risk profiles in female cardiac patients., Methods: Female cardiac patients consecutively admitted to hospital after an acute myocardial infarction (AMI) or for coronary artery bypass graft surgery (CAGS) were interviewed in hospital at 2, 4, and 12 months postdischarge., Results: Among 260 women (mean age = 68.6, SD = 10.4), there was little correspondence between actual and perceived risk factors. Hypertension was least recognized: only 5% of the 180 women who had hypertension acknowledged it as a cause of their CHD. High cholesterol, obesity, and high-fat diet were also underacknowledged, with only 14%, 15%, and 17% of women with these risk factors implicating them in their CHD. A higher percentage, 44%, of smokers and 40% of women with a positive family history acknowledged these risk factors as a cause of their CHD. Women who had no idea about the cause of their CHD constituted 20%. There was little change in causal attributions over the 12-month study period and little apparent impact of cardiac rehabilitation (CR) program attendance on causal beliefs., Conclusions: Women were more likely to attribute their CHD to smoking or positive family history than to other major modifiable risk factors. The lack of correspondence between actual and perceived risk factors and the lack of impact of CR attendance on causal attributions highlight the need for personalized advice and support regarding risk factor modification.

The aim of this pilot study was to evaluate the effect of albuterol in children with spinal muscular atrophy (SMA). Thirteen patients (five with SMA II and eight with SMA III) were given oral albuterol for 6 months. There was a significant increase in myometry, forced vital capacity, and lean body mass between the baseline and the 6-month assessments (p < 0.05). Albuterol may have a beneficial effect in patients with SMA without causing any significant adverse effects. Larger randomized, placebo-controlled trials are needed to confirm this observation.

The Towne strain of attenuated CMV vaccine was compared with placebo in seronegative renal transplants who later received kidneys from seropositive donors. This was a double-blind, randomized, placebo-controlled trial conducted at 3 different institutions. The results were consistent with 2 prior studies, in that whereas mild CMV disease was only slightly and insignificantly reduced in vaccine recipients, severe disease was markedly reduced. In the current study, all 4 severe cases of CMV disease occurred in placebo recipients, for an incidence of 17%, versus 0% in vaccine recipients (P < 0.03). Thus, prior immunization rendered seronegative patients more resistant to the effects of CMV infection.

Although conventional histology (CH) of needle core biopsies has been accepted as the gold standard for diagnosis of renal allograft rejection, this assumption has never been tested. Fine-needle aspiration cytology (FNAC) and monoclonal antibody (panleukocyte) staining of needle core biopsies (MABS) have been suggested to be superior to CH. A total of 50 patients received a cadaveric renal transplant followed by immunosuppression with triple therapy. Biopsies were taken routinely at days 7,14,21,28, and 90, with additional biopsies taken between these times if rejection was suspected (total biopsy sessions = 219). Specimens were taken for CH, FNAC, and MABS at each biopsy session, but only the result of one technique (previously randomly allocated) was communicated back to the clinical team, using a standardized grading system. Subsequently the presence or absence of rejection was determined by retrospective analysis of the clinical and biochemical course by 4 clinicians, without reference to the biopsy result. Graft survival was not significantly different in the three groups. The sensitivities for CH, FNAC, and MABS were 75%, 59%, and 77%, respectively, while the specificities were 87%, 96%, and 80%, respectively. Inadequate samples for analysis occurred frequently with the MABS technique--and, to a lesser extent, with CH--and both techniques tended to overdiagnose rejection. FNAC most often gave an answer but did miss clinically important rejection episodes. Needle-core biopsy processed for CH remains the most reliable biopsy technique for the diagnosis of rejection of renal allografts. FNAC is a useful technique for monitoring grafts with stable function or nonfunction. MABS does provide information equivalent to CH, but, in this study, had a high incidence of inadequate samples.

The effects of supplemental albumin infusion on serum protein homeostasis were studied in 94 seriously injured patients who received an average of 14.4 transfusion, 9.2 L electrolyte solution, and 829 ml fresh frozen plasma before and during operation. Based on randomization, 46 patients received an average of 31 gm albumin during operation followed by 150 gm/day for 5 days; 48 patients received no albumin. Supplemental albumin caused a significant (p = less than 0.05) increase in total serum protein and albumin concentrations. In contrast, supplemental albumin caused a significant decrease in alpha 1 globulin, alpha 2 globulin, beta globulin, gamma globulin, and fibrinogen levels. The prothrombin time used as index of prothrombin concentration was significantly prolonged in albumin patients. These changes, not previously documented, need further evaluation to determine clinical significance.