Prenatal Neurosurgical Counseling for Myelomeningocele and Treatment-Determining Factors for Fetal Repair.

INTRODUCTION: Spina bifida guidelines recommend neurosurgical involvement in prenatal counseling to inform decision-making between prenatal and postnatal myelomeningocele (MMC) repair. This study examines whether families with MMC presenting to one fetal center had timely neurosurgical prenatal counseling (nPNC) encounters and assesses modifiable and non-modifiable treatment-determining factors. METHODS: History and timing of nPNC were quantified among infants undergoing postnatal and prenatal MMC repair, pregnant patients referred, and MMC studies in a fetal MRI database (2015-2023). Fetal repair exclusions, presentation timing, social determinants, and reported rationale for not selecting offered fetal therapy were assessed. RESULTS: Nearly all patients (34/35; 97%) engaged in nPNC, 82% prior to 24 weeks GA. Fourteen patients were excluded from fetal repair for lack of hindbrain herniation (43%), obstetric exclusions (21%), fetal exclusions (21%), suspected closed defect (7%), and delayed presentation (7%). These patients ultimately underwent postnatal repair (71%), and pregnancy termination (14%). The 20 fetal-repair-eligible patients selected fetal repair (50%), postnatal repair (45%), and pregnancy termination (5%). Reasons for declining fetal repair included risk (55%) and cost (22%). CONCLUSIONS: Among MMC families presenting to a regional fetal therapy center, nPNC was widely extended, in a mostly timely fashion. Very few were deterred from fetal repair by potentially modifiable barriers.

Demographics of first-time donors returning for donation during the pandemic: COVID-19 convalescent plasma versus standard blood product donors.

BACKGROUND: Previous studies have demonstrated low first-time donor return rates (DRR) following catastrophic events. Little is known, however, about the influence of demographic factors on the DRR of first-time donors during the COVID-19 pandemic, including the unique motivation of COVID-19 convalescent plasma (CCP) donors as compared to non-CCP donors. STUDY DESIGN AND METHODS: Thirteen blood collection organizations submitted deidentified data from first-time CCP and non-CCP donors returning for regular (non-CCP) donations during the pandemic. DRR was calculated as frequencies. Demographic factors associated with returning donors: race/ethnicity, gender, and generation (Gen Z: 19-24, Millennial: 25-40, Gen X: 41-56, and Boomer: ≥57 years old), within the CCP and non-CCP first-time cohorts were compared using chi-square test at p < .05 statistical significance. RESULTS: From March 2020 through December 2021, there were a total of 44,274 first-time CCP and 980,201 first-time non-CCP donors. DRR were 14.6% (range 11.9%-43.3%) and 46.6% (range 10.0%-76.9%) for CCP and non-CCP cohorts, respectively. Age over 40 years (Gen X and Boomers), female gender, and White race were each associated with higher return in both donor cohorts (p < .001). For the non-CCP return donor cohort, the Millennial and Boomers were comparable. CONCLUSION: The findings demonstrate differences in returning donor trends between the two donor cohorts. The motivation of a first-time CCP donor may be different than that of a non-CCP donor. Further study to improve first-time donor engagement would be worthwhile to expand the donor base with a focus on blood donor diversity emphasizing engagement of underrepresented minorities and younger donors.

Minimizing Individual Learning Curves in a Mature Endoscopic Fetal Surgery Program.

INTRODUCTION: Twin-to-twin transfusion syndrome affects monochorionic twin pregnancies and can result in fetal death. Endoscopic laser treatment remains a relatively infrequent procedure for this condition. This presents difficulties for maintaining proficiency and for training new personnel. OBJECTIVE: The dual mentoring program at our institution allows for continuous mentoring of new providers. We hypothesize that this approach stabilizes program proficiency despite the addition of new practitioners. METHODS: Query of the fetal treatment program database returned 146 cases of laser ablation between 2000 and 2019. Patient and pregnancy characteristics as well as operative time and outcomes were recorded. The learning curve-cumulative summation method and rolling averages were used to analyze outcomes. RESULTS: Overall survival was 69%, and survival of at least 1 twin was 89%. Mean operative time was 53.6 ± 20.9 min. Overall twin survival stabilized after the first 40 cases. Rolling averages for operative time decreased from 71 to 49 min for the most recent cases. These results were not affected by the introduction of new surgeons. CONCLUSIONS: Creative mentoring can maintain stable overall program outcomes despite changes in team composition. This training approach may be applicable to other rare procedures in fetal surgery.

Acute Hemolytic Transfusion Reaction due to Anti-P1: A Case Report and Review of Institutional Experience.

BACKGROUND: Here we report a case of acute hemolytic transfusion reaction (HTR) due to anti-P1 and review our institutional database for prevalence of anti-P1 antibodies and frequency of anti-P1-mediated HTR. Anti-P1 antibodies, reported to be present in up to two-thirds of P2 individuals, are usually clinically insignificant. However, rare cases of acute HTR due to anti-P1 are reported. Case Report: We report the clinical and laboratory features of a mild acute HTR due to an IgM anti-P1 not detected by a routinely used antibody screening method. We reviewed our institutional database to investigate prevalence of anti-P1 antibodies identified in our patient population and frequency of HTR in patients with anti-P1. RESULTS: Analysis of RBC transfusion recipient data over the 10-year period from 2006 to 2015 showed prevalence of anti-P1 identified in our laboratory of 174 per 100,000 individuals. Frequency of HTR in patients with anti-P1 identified in our laboratory over a 10-year period was 1 in 1,429 RBC transfusions (0.07%). Conclusion: Our reported case of HTR mediated by IgM anti-P1 reactive at 37 °C confirms the potential of antibody screening methods designed to detect IgG antibodies to miss rare clinically significant IgM antibodies.

Clinical and Molecular Epidemiology of Staphylococcal Toxic Shock Syndrome in the United Kingdom.

Staphylococcal toxic shock syndrome (TSS) was originally described in menstruating women and linked to TSS toxin 1 (TSST-1)-producing Staphylococcus aureus. Using UK national surveillance data, we ascertained clinical, molecular and superantigenic characteristics of TSS cases. Average annual TSS incidence was 0.07/100,000 population. Patients with nonmenstrual TSS were younger than those with menstrual TSS but had the same mortality rate. Children <16 years of age accounted for 39% of TSS cases, most caused by burns and skin and soft tissue infections. Nonmenstrual TSS is now more common than menstrual TSS in the UK, although both types are strongly associated with the tst+ clonal complex (CC) 30 methicillin-sensitive S. aureus lineage, which accounted for 49.4% of all TSS and produced more TSST-1 and superantigen bioactivity than did tst+ CC30 methicillin-resistant S. aureus strains. Better understanding of this MSSA lineage and infections in children could focus interventions to prevent TSS in the future.

Correlation of Checkerboard Synergy Testing with Time-Kill Analysis and Clinical Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Respiratory Infections.

We tested 76 extensively drug-resistant (XDR) Acinetobacter baumannii isolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combination in vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%; P = 0.025). The checkerboard platform may have clinical utility for XDR A. baumannii infections.

Characterization of the HBB: c.*233G > C Variant: No Evidence of a ß-Thalassemic Phenotype.

ß-Thalassemia (ß-thal) results from homozygous or compound heterozygous inheritance of ß-globin alleles that yield decreased or absent synthesis of the ß chain. Disease is frequently severe, requiring lifelong transfusion therapy. Heterozygosity for a ß-thal allele results in an asymptomatic carrier state with mild but characteristic hematological findings. More than 200 ß-globin alleles have been demonstrated to produce ß-thal. For populations with a high prevalence of ß-thal, screening for carrier status, genetic counseling and prenatal diagnosis are important components of efforts to both reduce disease incidence and provide early diagnosis and treatment. It is therefore important to define and characterize potential ß-thal alleles. We sought to further characterize the previously reported ß-thal allele, HBB: c.*233G > C. This variant is provisionally included in the HbVar database based on a study of Palestinians in the Gaza Strip with ß-thal disease or carrier status (known or suspected) where 4.2% of subjects were found to have HBB: c.*233G > C. In our patient population, we detected the HBB: c.*233G > C variant in 17.3% of individuals (17 heterozygotes, one homozygote) undergoing ß hemoglobin (Hb) gene sequencing at our laboratory over a 25-month period. Hematological parameters were analyzed to determine if these individuals demonstrated findings consistent with inheritance of a ß-thal allele. Individuals with the HBB: c.*233G > C variant did not demonstrate any abnormalities in hematological parameters characteristic of ß-thal carrier state (17 heterozygotes) or clinical evidence of disease (homozygote). Our data demonstrate no evidence for pathogenicity of the HBB: c.*233G > C variant but rather demonstrate that this variant is a common benign polymorphism.

Iatrogenic Preterm Premature Rupture of Membranes after Fetoscopic Laser Ablative Surgery.

INTRODUCTION: To describe the incidence and risk factors for iatrogenic premature preterm rupture of membranes (iPPROM) after fetoscopic laser surgery for the twin-to-twin-transfusion syndrome. MATERIALS AND METHODS: This is a retrospective review of all patients who have undergone fetoscopic laser surgery at a single fetal treatment center since 2000. We defined iPPROM as spontaneous rupture of membranes before the onset of labor prior to 34 weeks of gestation. The iPPROM cohort was compared to the cohort without iPPROM for several preoperative, operative, and delivery characteristics. RESULTS: Ninety-two consecutive patients were reviewed. The overall rate of iPPROM was 18.5% (n = 17). The rates of iPPROM within 1 and 4 weeks were 5.4 and 10.9%, respectively. The median interval from surgery to delivery was significantly shorter in the iPPROM group (21 vs. 62 days, p = 0.01). The mean gestational age at delivery (27.0 vs. 31.1 weeks, p = 0.02) was lower in the iPPROM group. No other characteristics studied differed significantly between the groups. DISCUSSION: The incidence of iPPROM was substantially lower than in recent multicenter reports; however, no risk factors of iPPROM could be identified. Whether this is related to variations in surgical or anesthetic management will require further investigation.

A qualitative investigation into nurses' perceptions of factors influencing staff injuries sustained during physical interventions employed in response to service user violence within one secure learning disability service.

AIMS AND OBJECTIVES: The aim of the study was to examine learning disability nurses' perceptions of incidents involving physical intervention, particularly factors contributing to injuries sustained by this group. BACKGROUND: This article reports on a qualitative study undertaken within one secure NHS Trust to respond to concerns about staff injuries sustained during physical interventions to prevent incidents of service user violence from escalating out of control. The context of the study relates to increasing debate about the most effective approaches to incidents of violence and agression. DESIGN: A qualitative research design was utilized for the study. METHODS: Semi-structured interviews were undertaken with 20 participants, two from each of the 10 incidents involving staff injury sustained during physical intervention. RESULTS: Four themes were produced by the analysis, the first, knowledge and understanding, contextualized the other three, which related to the physical intervention techniques employed, the interpretation of the incident and the impact on staff. CONCLUSION: Service user violence consistently poses nurses with the challenge of balancing the need to respond in order to maintain the safety of everyone whilst simultaneous supporting and caring for people with complex needs. This study highlights the need for further exploration of the contributory factors to the escalation of potentially violent situations. RELEVANCE TO CLINICAL PRACTICE: Services may have good systems in place for responding to and managing service user violence but appear less effective in understanding the reasons for and developing strategies to prevent violence occurring.

Successes and Challenges in Patient Care Transition Programming: One Hospital's Journey.

The 2013 addition of the Care Transition Measures to the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey; enactment of the Patient Protection and Affordable Care Act (2010); and a greater focus on population health have brought a heightened awareness and need for action with patient transitions. Data are emerging from the additional Care Transition Measures and benchmarks have been developed. This article briefly describes the context of care transition. We describe the journey of Indiana University Health North Hospital to overcome patient care transition obstacles, ultimately achieving designation as a top performer. We will discuss our efforts to personalize patient outcomes and transition through activation and improve transitions for vulnerable populations, specifically in the bariatric and orthopedic patient populations. The article concludes with discussion of overcoming obstacles and future directions with continued focus on collaboration and improvement.

Mentors' perceptions and experiences of supporting student nurses in practice.

This paper reports on a funded project that explored the perceptions and experiences of mentors regarding student nurse support in practice. The study employed a mixed-method approach, using questionnaires and focus groups with mentors from one acute Trust and one community Trust. The findings highlighted the multifaceted nature of student learning in practice, with mentors reporting that clinical skills, adjustment to the placement and integrating into the team were the aspects students needed most support with. Mentors were aware of their roles and responsibilities in supporting students and recognized the importance of their own personal attributes. The participants reported a number of challenges, particularly time, competing demands and paperwork, and suggested that a team approach and support groups could help to overcome these. The support for students provided by peers and health-care assistants was recognized, as was the need to ensure that students are prepared to take responsibility for their learning.

The contribution of Langerhans cells to cutaneous malignancy.

The skin is at the forefront of environmental exposures, such as ultraviolet radiation and a myriad of chemicals, and is at risk for malignant transformation. The skin is a highly responsive immunological organ that contains a unique population of immature intraepidermal dendritic cells (DCs) called Langerhans cells (LCs). Although LCs show morphological and migratory changes in response to epidermal perturbation, and can function as antigen-presenting cells to activate T cells, their role in carcinogenesis is unknown. Here we review recent studies that have provided clues to the potential roles that LCs might play in the pathogenesis of skin cancer, beyond their stimulation or regulation of adaptive immunity. Understanding this role of LCs might provide new perspectives on the relevance of DC populations that are resident within other epithelial tissues for cancer.

Primary care experiences in the 'Let's test for HPV' study: a qualitative analysis.

Introduction The National Cervical Screening Programme (NCSP) will switch from cervical cytology to Human Papillomavirus (HPV) testing as the primary cervical screening modality in 2023. To prepare for rollout an implementation study of HPV testing in primary care commenced in August 2022 in three different geographic regions in NZ. Aims This study explores Primary Care Staff's experience of using the HPV testing pathway in the 'Let's test for HPV' study so that recommendations can be made to improve the testing process before nationwide roll-out. Method Thirty-nine primary care staff were interviewed across all 17 practices in the Capital and Coast, Canterbury and Whanganui region participating in the 'Let's Test For HPV' study. In total 19 interviews took place which followed a semi-structured approach. These interviews were recorded and transcribed. Template analysis was carried out on transcripts to aid in identifying themes. Results Three key themes, with additional subthemes, were identified. Staff were strongly supportive of the new testing regime. Interviewees identified some issues with the new pathway. Educational needs for both patients and clinicians were identified. Conclusion Primary care staff described the experience of using the HPV testing pathway positively; however, there were requests for ongoing additional support and nationwide rollout to be supported by practitioner and patient education programmes. With the right support this new pathway for cervical cancer screening has the potential to improve access for previously underserved and unserved groups.

Postnatal Myelomeningocele Repair in the United States: Rates and Disparities Before and After the Management of Myelomeningocele Study Trial.

BACKGROUND AND OBJECTIVES: Evolving technologies have influenced the practice of myelomeningocele repair (MMCr), including mandatory folic acid fortification, advances in prenatal diagnosis, and the 2011 Management of Myelomeningocele Study (MOMS) trial demonstrating benefits of fetal over postnatal MMCr in select individuals. Postnatal MMCr continues to be performed, especially for those with limitations in prenatal diagnosis, health care access, anatomy, or personal preference. A comprehensive, updated national perspective on the trajectory of postnatal MMCr volumes and patient disparities is absent. We characterize national trends in postnatal MMCr rates before and after the MOMS trial publication (2000-2010 vs 2011-2019) and examine whether historical disparities persist. METHODS: This retrospective, cross-sectional analysis queried Nationwide Inpatient Sample data for postnatal MMCr admissions. Annual and race/ethnicity-specific rates were calculated using national birth registry data. Time series analysis assessed for trends relative to the year 2011. Patient, admission, and outcome characteristics were compared between pre-MOMS and post-MOMS cohorts. RESULTS: Between 2000 and 2019, 12 426 postnatal MMCr operations were estimated nationwide. After 2011, there was a gradual, incremental decline in the annual rate of postnatal MMCr. Post-MOMS admissions were increasingly associated with Medicaid insurance and the lowest income quartiles, as well as increased risk indices, length of stay, and hospital charges. By 2019, race/ethnicity-adjusted rates seemed to converge. The mortality rate remained low in both eras, and there was a lower rate of same-admission shunting post-MOMS. CONCLUSION: National rates of postnatal MMCr gradually declined in the post-MOMS era. Medicaid and low-income patients comprise an increasing majority of MMCr patients post-MOMS, whereas historical race/ethnicity-specific disparities are improving. Now more than ever, we must address disparities in the care of MMC patients before and after birth.

Detection of yeasts in blood cultures by the Luminex xTAG fungal assay.

A multiplex-PCR Luminex xMAP bead probe fluid array using xTAG analyte-specific reagents (multiplex xTAG fungal ASR assay) was employed for detection of clinically significant Candida species, Cryptococcus neoformans, Histoplasma capsulatum, and Blastomyces dermatitidis from blood cultures. We tested 132 blood cultures negative (n = 10) or positive (n = 97) for yeasts and/or bacteria (n = 25). The assay showed sensitivity and specificity of 100% and 99%, respectively. The xTAG fungal ASR assay is a rapid assay that allows simultaneous identification of multiple yeast species.

Minimally invasive groin dissection.

INTRODUCTION: Melanoma of the lower extremity with a positive sentinel lymph node biopsy (SLNB) mandates a groin dissection. This procedure has been associated with numerous complications; therefore we devised a modified approach. METHODS: All patients presenting with lower extremity melanomas that met criteria for SLNB had this procedure performed through an incision in the inguino-femoral region. In the event of a positive SLND, this same incision was used for the minimally invasive groin dissection (MIGD). A lighted retractor was used to improve visualization and a Ligasure (Valley-lab) was used to prevent seroma formation. RESULTS: Twenty patients met criteria for this investigation and five underwent MIGD. All patients tolerated the procedure well. There was no incidence of flap necrosis nor wound dehiscence. There was one case of seroma and cellulitis, one seroma, and one patient with lymphedema. All patients preferred the MIGD incision over traditional incisions. CONCLUSIONS: This new algorithm utilizing MIGD is well tolerated in patients. Complications appear to be minimal and patient satisfaction superior to traditional groin dissection.

Protocol for a cluster randomised controlled feasibility study of Prehospital Optimal Shock Energy for Defibrillation (POSED).

Aims: The Prehospital Optimal Shock Energy for Defibrillation (POSED) study will assess the feasibility of conducting a cluster randomised controlled study of clinical effectiveness in UK ambulance services to identify the optimal shock energy for defibrillation. Methods: POSED is a pragmatic, allocation concealed, open label, cluster randomised, controlled feasibility study. Defibrillators within a single UK ambulance service will be randomised in an equal ratio to deliver one of three shock strategies 120-150-200 J, 150-200-200 J, 200-200-200 J. Consecutive adults (≥18 years) presenting with out of hospital cardiac arrest requiring defibrillation will be eligible. The study plans to enrol 90 patients (30 in each group). Patients (or their relatives for non-survivors) will be informed about trial participation after the initial emergency has resolved. Survivors will be invited to consent to participate in follow-up (i.e., at 30 days or discharge).The primary feasibility outcome is the proportion of eligible patients who receive the randomised study intervention. Secondary feasibility outcomes will include recruitment rate, adherence to allocated treatment and data completeness. Clinical outcomes will include Return of an Organised Rhythm (ROOR) at 2 minutes post-shock, refibrillation rate, Return of Spontaneous Circulation (ROSC) at hospital handover, survival and neurological outcome at 30 days. Conclusion: The POSED study will assess the feasibility of a large-scale trial and explore opportunities to optimise the trial protocol.Trial registration: ISRCTN16327029.

Homozygous deletion of glycogen synthase kinase 3beta bypasses senescence allowing Ras transformation of primary murine fibroblasts.

In primary mammalian cells, expression of oncogenes such as activated Ras induces premature senescence rather than transformation. We show that homozygous deletion of glycogen synthase kinase (GSK) 3beta (GSK3beta-/-) bypasses senescence induced by mutant Ras(V12) allowing primary mouse embryo fibroblasts (MEFs) as well as immortalized MEFs to exhibit a transformed phenotype in vitro and in vivo. Both catalytic activity and Axin-binding of GSK3beta are required to optimally suppress Ras transformation. The expression of Ras(V12) in GSK3beta-/-, but not in GSK3beta+/+ MEFs results in translocation of beta-catenin to the nucleus with concomitant up-regulation of cyclin D1. siRNA-mediated knockdown of beta-catenin decreases both cyclin D1 expression and anchorage-independent growth of transformed cells indicating a causal role for beta-catenin. Thus Ras(V12) and the lack of GSK3beta act in concert to activate the beta-catenin pathway, which may underlie the bypass of senescence and tumorigenic transformation by Ras.

Factors affecting opioid management for injured children after hospital discharge.

INTRODUCTION: Prescription opioid misuse is a national crisis. Injured children often receive opioid medication at hospital discharge, but the role these prescriptions play in the opioid crisis has not been fully elucidated. Whether these opioids are administered, the duration of severe pain requiring opioids, and what the final disposition of unused opioids is in this population remain unknown. METHODS: A survey of parent/guardian perceptions of their child's pain after injury, duration of opioid administration, opioid storage and disposal, and perceptions of opioid education was designed. During a 12-month period, parents of injured children admitted to an ACS Level 1 Pediatric Trauma Center were prospectively enrolled by convenience sample. Surveys were in two steps with an enrollment survey prior to discharge and a follow-up survey 7-10 days after discharge. RESULTS: Seventy of 114 (61.4%) enrolled parents/guardians completed follow-up survey. Of the 79.1% that reported an opioid prescription for their child, 92.5% filled it. Of those reporting on opioid usage, 10.4% never used the opioid, 75% used opioids <3 days, 12.5% 4-7 days, 2% >7 days. Of those who filled the opioid prescription, 83.7% reported having leftover doses. Reasons for discontinuing opioids included the child no longer had pain (87.2%), the child ran out of medication (5.1%), other (7.7%). Regarding storage, 53.3% reported utilizing an unlocked bathroom cabinet, and 81.3% unlocked kitchen space. Of those reporting unused opioids, 83.3% reported not disposing them, and 38.2% reported no plan for disposal. CONCLUSION: The majority of parents/guardians of injured children report resolution of severe pain requiring opioids within 72 h of hospital discharge, and virtually all by 7 days. The majority of injured children were prescribed a greater number of doses than they needed to treat their pain. Many parents/guardians store opioids in unsecure locations and a significant proportion report no plan to dispose of unused opioid doses. Further investigation is warranted to quantify and address the gap between pain control needs and opioid prescribing practices. The rate of unsecure storage and plan to retain unused opioids are potential targets for discharge opioid education. TYPE OF STUDY: Cross-sectional survey. LEVEL OF EVIDENCE: Level IV.

Paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT): An e-survey of the experiences of parents and clinicians.

BACKGROUND: Little evidence exists about parental satisfaction and their influence on referral to paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT). AIM: This study aimed to examine the experiences of parents, children and clinicians of OPAT at a large tertiary children's hospital. METHOD: A prospective e-survey, using closed and open questions, of parents (n = 33) of 33 children who had received OPAT (3 children completed a survey), and clinicians (n = 31) involved in OPAT at a tertiary hospital. Data were collected September 2016 to July 2018. RESULTS: Data were analysed using simple descriptive statistics. The results show that OPAT offered benefits (less stress, re-establishment of family life) compared to hospital-based treatment for parents and children, although some were anxious. Clinicians' referral judgements were based on child, home, and clinical factors. Some clinicians found the process of referral complex. CONCLUSION: Most parents and children were satisfied with the OPAT service and preferred the option of home-based treatment as it promoted the child's comfort and recovery and supported family routines.