Circulating Cell Free DNA and DNA Double-Strand Breakage in Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disease that is characterized by memory loss and multiple cognitive impairments. AD is pathologically characterized by age-dependent accumulation of amyloid-ß protein and the phosphorylation of tau protein in the brains of patients with AD. Clinically, manifestations of AD include cognitive decline, dementia, alterations of high-order brain functions, and movement disorders. Double-stranded DNA breaks are a lethal form of DNA damage and are typically repaired via non-homologous end joining and homologous recombination. However, in AD brain, repair mechanism is disrupted, leading to a cascade of events, cognitive dysfunction, organ failure and reduced lifespan. Increased circulating cell-free DNA in the blood, cerebrospinal fluid, and urine in patients with AD, can be used as early detectable biomarkers for AD. The purpose of our article is to explore the potential uses of cell-free DNA and double-stranded DNA breaks as prognostic markers for AD and examine the recent research on the application of these markers in studies.

Three-dimensional telomere profiling predicts risk of progression in smoldering multiple myeloma.

Smoldering multiple myeloma (SMM) is a precursor stage that precedes multiple myeloma (MM). SMM is heterogenous with nearly 40% of patients progressing to MM in the first 5 years. The high rate of progression of SMM patients highlights the need for early intervention, which underscores the importance of identifying SMM patients with the highest risk of progression. Several risk stratification models showed utility in identifying high-risk SMM patients; however, these systems showed limited sensitivity. To date, identifying high-risk SMM patients remains an important clinical need. In this study, we present the 3-dimensional telomere profiling as a structural biomarker capable of stratifying SMM patients as a function of genomic instability. Quantifying telomere dysfunction using the TeloView technology showed utility in risk stratification of cancer patients, particularly hematological malignancies. In this study, we analyzed 168 SMM patients. We report an AUC in ROC analysis of 0.8 using a subset of the patients as a training dataset. We then conducted a blind validation on a different cohort and demonstrated a positive predictive value of 85% and negative predictive value of 73%, with sensitivity and specificity of 83% and 76%, respectively. We examined the correlation between the TeloView prediction and the 20-2-20 scoring system, and cytogenetic abnormalities. We report a correlation of 53% with the 20-2-20 scores and over 60% correlation with cytogenetic abnormalities. The result of this study presents the telomere profiling as an effective biomarker able to stratify SMM patients to their respective risk groups with high sensitivity and specificity.

Primary Care Physicians' Experiences With and Adaptations to Time Constraints.

Importance: The primary care workforce shortage is significant and persistent, with organizational and policy leaders urgently seeking interventions to enhance retention and recruitment. Time constraints are a valuable focus for action; however, designing effective interventions requires deeper understanding of how time constraints shape employees' experiences and outcomes of work. Objective: To examine how time constraints affect primary care physicians' work experiences and careers. Design, Setting, and Participants: Between May 1, 2021, and September 31, 2022, US-based primary care physicians who trained in family or internal medicine were interviewed. Using qualitative analysis of in-depth interviews, this study examined how participants experience and adapt to time constraints during a typical clinic day, taking account of their professional and personal responsibilities. It also incorporates physicians' reflections on implications for their careers. Main Outcomes and Measures: Thematic analysis of in-depth interviews and a measure of well-being (American Medical Association Mini-Z survey). Results: Interviews with 25 primary care physicians (14 [56%] female and 11 [44%] male; median [range] age, 43 [34-63] years) practicing in 11 US states were analyzed. Two physicians owned their own practice, whereas the rest worked as employees. The participants represented a wide range of years in practice (range, 1 to ≥21), with 11 participants (44%) in their first 5 years. Physicians described that the structure of their work hours did not match the work that was expected of them. This structural mismatch between time allocation and work expectations created a constant experience of time scarcity. Physicians described having to make tradeoffs between maintaining high-quality patient care and having their work overflow into their personal lives. These experiences led to feelings of guilt, disillusionment, and dissatisfaction. To attempt to sustain long-term careers in primary care, many sought ways to see fewer patients. Conclusions and Relevance: These findings suggest that organizational leaders must align schedules with work expectations for primary care physicians to mitigate physicians' withdrawal from work as a coping mechanism. Specific strategies are needed to achieve this realignment, including incorporating more slack into schedules and establishing realistic work expectations for physicians.

Combination biologics or targeted synthetic disease-modifying anti-rheumatic drugs in the treatment of spondyloarthritis: a systematic literature review.

INTRODUCTION: The advent of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) have transformed the management of immune-mediated rheumatic diseases, including spondylarthritis (SpA). However, the data about combining b/ts DMARDs in the treatment of SpA are scarce. The study objectives were to assess the efficacy and safety of combination b/tsDMARD in SpA. METHODS: We conducted systematic literature review (PubMed and Medline) with two independent reviewers, one adjudicator, exploring the efficacy and safety of combination b/tsDMARDs in the treatment of SpA. Inclusion criteria were studies published in last 20 years, English language, interventions included use of two b/tsDMARDs, and minimal three-month follow-up. RESULTS: Out of 1936 initial hits, 28 manuscripts fulfilled the inclusion criteria. Two were randomized controlled trials, and the remaining were retrospective cohort studies or case series. Combination of apremilast with bDMARD, or TNF inhibitor plus IL12/23 inhibitor were the commonest and reported good efficacy with no increased safety signal. CONCLUSIONS: There is not enough data to fully evaluate efficacy and safety of combination b/tsDMARDs in SpA treatment. Limited information shows apremilast plus bDMARD, or TNF inhibitor plus IL12/23 inhibitor combination to be efficacious and safe. Randomized controlled trials and larger cohort with a longer follow-up are required.

The Interplay between Mycobacterium tuberculosis and Human Microbiome.

Tuberculosis (TB), a respiratory disease caused by Mycobacterium tuberculosis (Mtb), is a significant cause of mortality worldwide. The lung, a breeding ground for Mtb, was once thought to be a sterile environment, but has now been found to host its own profile of microbes. These microbes are critical in the development of the host immune system and can produce metabolites that aid in host defense against various pathogens. Mtb infection as well as antibiotics can shift the microbial profile, causing dysbiosis and dampening the host immune response. Additionally, increasing cases of drug resistant TB have impacted the success rates of the traditional therapies of isoniazid, rifampin, pyrazinamide, and ethambutol. Recent years have produced tremendous research into the human microbiome and its role in contributing to or attenuating disease processes. Potential treatments aimed at altering the gut-lung bacterial axis may offer promising results against drug resistant TB and help mitigate the effects of TB.

"Good Care Is Slow Enough to Be Able to Pay Attention": Primary Care Time Scarcity and Patient Safety.

BACKGROUND: There is growing, widespread recognition that expectations of US primary care vastly exceed the time and resources allocated to it. Little research has directly examined how time scarcity contributes to harm or patient safety incidents not readily capturable by population-based quality metrics. OBJECTIVE: To examine near-miss events identified by primary care physicians in which taking additional time improved patient care or prevented harm. DESIGN: Qualitative study based on semi-structured interviews. PARTICIPANTS: Twenty-five primary care physicians practicing in the USA. APPROACH: Participants completed a survey that included demographic questions, the Ballard Organizational Temporality Scale and the Mini-Z scale, followed by a one hour qualitative interview over video-conference (Zoom). Iterative thematic qualitative data analysis was conducted. KEY RESULTS: Primary care physicians identified several types of near-miss events in which taking extra time during visits changed their clinical management. These were evident in five types of patient care episodes: high-risk social situations, high-risk medication regimens requiring patient education, high acuity conditions requiring immediate workup or treatment, interactions of physical and mental health, and investigating more subtle clinical suspicions. These near-miss events highlight the ways in which unreasonably large patient panels and packed schedules impede adequate responses to patient care episodes that are time sensitive and intensive or require flexibility. CONCLUSIONS: Primary care physicians identify and address patient safety issues and high-risk situations by spending more time than allotted for a given patient encounter. Current quality metrics do not account for this critical aspect of primary care work. Current healthcare policy and organization create time scarcity. Interventions to address time scarcity and to measure its prevalence and implications for care quality and safety are urgently needed.

Dissecting quantitative trait nucleotides by saturation genome editing.

Genome editing technologies have the potential to transform our understanding of how genetic variation gives rise to complex traits through the systematic engineering and phenotypic characterization of genetic variants. However, there has yet to be a system with sufficient efficiency, fidelity, and throughput to comprehensively identify causal variants at the genome scale. Here we explored the ability of templated CRISPR editing systems to install natural variants genome-wide in budding yeast. We optimized several approaches to enhance homology-directed repair (HDR) with donor DNA templates, including donor recruitment to target sites, single-stranded donor production by bacterial retrons, and in vivo plasmid assembly. We uncovered unique advantages of each system that we integrated into a single superior system named MAGESTIC 3.0. We used MAGESTIC 3.0 to dissect causal variants residing in 112 quantitative trait loci across 32 environmental conditions, revealing an enrichment for missense variants and loci with multiple causal variants. MAGESTIC 3.0 will facilitate the functional analysis of the genome at single-nucleotide resolution and provides a roadmap for improving template-based genome editing systems in other organisms.

Consumption of 100% Fruit Juice and Body Weight in Children and Adults: A Systematic Review and Meta-Analysis.

Importance: Concerns have been raised that frequent consumption of 100% fruit juice may promote weight gain. Current evidence on fruit juice and weight gain has yielded mixed findings from both observational studies and clinical trials. Objective: To synthesize the available evidence on 100% fruit juice consumption and body weight in children and adults. Data Sources: MEDLINE, Embase, and Cochrane databases were searched through May 18, 2023. Study Selection: Prospective cohort studies of at least 6 months and randomized clinical trials (RCTs) of at least 2 weeks assessing the association of 100% fruit juice with body weight change in children and adults were included. In the trials, fruit juices were compared with noncaloric controls. Data Extraction and Synthesis: Data were pooled using random-effects models and presented as ß coefficients with 95% CIs for cohort studies and mean differences (MDs) with 95% CIs for RCTs. Main Outcomes and Measures: Change in body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was assessed in children and change in body weight in adults. Results: A total of 42 eligible studies were included in this analysis, including 17 among children (17 cohorts; 0 RCTs; 45 851 children; median [IQR] age, 8 [1-15] years) and 25 among adults (6 cohorts; 19 RCTs; 268 095 adults; median [IQR] age among cohort studies, 48 [41-61] years; median [IQR] age among RCTs, 42 [25-59]). Among cohort studies in children, each additional serving per day of 100% fruit juice was associated with a 0.03 (95% CI, 0.01-0.05) higher BMI change. Among cohort studies in adults, studies that did not adjust for energy showed greater body weight gain (0.21 kg; 95% CI, 0.15-0.27 kg) than studies that did adjust for energy intake (-0.08 kg; 95% CI, -0.11 to -0.05 kg; P for meta-regression <.001). RCTs in adults found no significant association of assignment to 100% fruit juice with body weight but the CI was wide (MD, -0.53 kg; 95% CI, -1.55 to 0.48 kg). Conclusion and Relevance: Based on the available evidence from prospective cohort studies, in this systematic review and meta-analysis, 1 serving per day of 100% fruit juice was associated with BMI gain among children. Findings in adults found a significant association among studies unadjusted for total energy, suggesting potential mediation by calories. Further trials of 100% fruit juice and body weight are desirable. Our findings support guidance to limit consumption of fruit juice to prevent intake of excess calories and weight gain.

Atypical eclampsia in a normotensive patient with altered mental status and severely elevated transaminases: Case report and review.

Classically, pre-eclampsia and eclampsia are considered hypertensive disorders of pregnancy, and current diagnostic criteria include hypertension with proteinuria or other laboratory abnormalities or symptoms suggestive of end-organ damage. However, atypical presentations can occur in the absence of elevated blood pressures. We present the case of a pregnant patient who developed status epilepticus at 24 weeks and 4 days of gestation, followed by altered mental status and severely elevated transaminases. She had no elevated blood pressures during her prenatal care or hospital course. Following delivery, she experienced normalization of transaminase levels and a return to her baseline mental status. Pre-eclampsia and eclampsia can occur in the absence of elevated blood pressures, which highlights the limitations of using standard diagnostic criteria in normotensive patients with end-organ damage. In such cases, it is important to include pre-eclampsia and eclampsia in the differential diagnosis, as the diagnosis usually warrants preterm delivery to minimize maternal morbidity and mortality.

Pharmacist furnishing of hormonal contraception in California's Central Valley.

BACKGROUND: In the United States, more than 19 million people of reproductive age need access to publicly funded hormonal contraception or live in areas where it is not readily available. These include rural areas of the country, commonly known as contraception deserts. Pharmacist prescribing has been proposed to increase access, but little is known about its implementation in such areas. OBJECTIVE: This study quantified the extent of pharmacists' furnishing (prescribing) of hormonal contraception in California's Central Valley community pharmacies and identified barriers and facilitators to implementation. METHODS: The researchers conducted a cross-sectional, mixed methods, observational study by (1) contacting all community pharmacies in the 11 counties of the Central Valley to determine furnishing rates and (2) surveying and interviewing pharmacies that indicated they furnished hormonal contraception. RESULTS: Overall, 13% of pharmacies within the Central Valley reported that they furnished hormonal contraception. Pharmacists reported that barriers to furnishing included costs to patients and the pharmacy, lack of time and staff, lack of training and certifications, limited patient awareness of pharmacists' ability to furnish, pharmacists' limited confidence in furnishing, and patient use of emergency contraception as an alternative to hormonal contraception. Pharmacists reported that patients often sought hormonal contraception from pharmacists owing to ease of accessibility to a pharmacist; some other facilitators included advertising, confidentiality, low cost to patients, and referrals from other providers. CONCLUSIONS: Common barriers were identified across pharmacies that furnished hormonal contraception, indicating the need for strategies that reduce these barriers to help expand patient's access to these services and to increase pharmacists' ability and confidence to prescribe.

Varicella zoster virus reactivation reported with isatuximab use.

Isatuximab is a CD38-directed antibody indicated for the treatment of relapsed or refractory multiple myeloma. The Division of Pharmacovigilance at the U.S. Food and Drug Administration (FDA) reviewed case reports from postmarketing sources, including the FDA Adverse Event Reporting System (FAERS), PubMed, and Embase, to investigate a potential association between isatuximab and the risk of varicella zoster virus (VZV) reactivation. We identified 20 reports of which 15 met our case definition and causality criteria. All 15 patients (80% male, median age = 60 years) received isatuximab for a hematologic neoplasm; eight (53%) for previously untreated multiple myeloma. All cases described additional risk factors for VZV reactivation, including concomitant proteasome inhibitor and/or immunomodulatory drug (n = 10, 67%) use. Based on this postmarket analysis, the U.S. Prescribing Information for isatuximab was updated to include this new safety information, including recommendations for antiviral prophylaxis.

Circulating miRNA profiles in COVID-19 patients and meta-analysis: implications for disease progression and prognosis.

We compared circulating miRNA profiles of hospitalized COVID-positive patients (n = 104), 27 with acute respiratory distress syndrome (ARDS) and age- and sex-matched healthy controls (n = 18) to identify miRNA signatures associated with COVID and COVID-induced ARDS. Meta-analysis incorporating data from published studies and our data was performed to identify a set of differentially expressed miRNAs in (1) COVID-positive patients versus healthy controls as well as (2) severe (ARDS+) COVID vs moderate COVID. Gene ontology enrichment analysis of the genes these miRNAs interact with identified terms associated with immune response, such as interferon and interleukin signaling, as well as viral genome activities associated with COVID disease and severity. Additionally, we observed downregulation of a cluster of miRNAs located on chromosome 14 (14q32) among all COVID patients. To predict COVID disease and severity, we developed machine learning models that achieved AUC scores between 0.81-0.93 for predicting disease, and between 0.71-0.81 for predicting severity, even across diverse studies with different sample types (plasma versus serum), collection methods, and library preparations. Our findings provide network and top miRNA feature insights into COVID disease progression and contribute to the development of tools for disease prognosis and management.

The Effect of Pharmacist-Initiated Deprescribing Interventions in Older People: A Narrative Review of Randomized Controlled Trials.

Background Polypharmacy is common among older people and may be associated with adverse drug events (ADEs) and poor health outcomes. Pharmacists are well-positioned to reduce polypharmacy and potentially inappropriate medications. Objective The objective of this narrative review was to summarize the results from randomized-controlled trials that evaluated pharmacist-led interventions with the goal or effect to deprescribe medications in older individuals. Data Sources We searched Medline, Embase, CINAHL Complete, APA PsycInfo, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials. Data Synthesis Of the 25 studies included, the interventions were conducted in nursing facilities (n = 8), outpatient/community dwellings (n = 8), or community pharmacies (n = 9). Interventions were categorized as comprehensive medication reviews (n = 10), comprehensive medication reviews with pharmacist follow-up (n = 11), and educational interventions provided to patients and/or providers (n = 4). Pharmacist-led interventions had a beneficial effect on 22 out of 32 total medication-related outcomes (eg, number of medications, potentially inappropriate medications, or discontinuation). Most (n = 18) studies reported no evidence of an effect for other outcomes such as health care use, mortality, patient-centered outcomes (falls, cognition, function, quality of life), and ADEs. Discussion Interventions led to improvement in 69% of the medication-related outcomes examined across study settings. Five studies measured ADEs with none accounting for adverse drug-withdrawal events. Large well-designed studies that are powered to find an effect on patient-centered outcomes are needed. Conclusion Pharmacist-led interventions had a significant beneficial effect on medication-related outcomes. There was little evidence of benefit on other outcomes.

Reproductive psychiatric advance directives: promoting autonomy for perinatal people with serious mental illness diagnoses.

People with serious mental illness (SMI) diagnoses who become pregnant are particularly vulnerable to symptom recurrence and resulting potential lack of decision-making capacity (Taylor et al. J Psychiatr Res 104:100-107, 2018; Bagadia et al. Int J Soc Psychiatry 66:792-798, 2020). In these situations, prenatal and behavioral health providers have little legally viable guidance on what medical and/or psychiatric care the patient desires (Aneja and Arora Indian J Med Ethics V:133-139, 2020). We created a "Reproductive Psychiatric Advance Directive (PAD)," grounded in Reproductive Justice principles, that promotes patient autonomy by proactively articulating perinatal medical and psychiatric care preferences. We conducted a medical and legal literature review using two sets of terms related to (1) PADs and (2) reproductive health. We convened an expert working group of legal, medical, psychiatric, peer, and advocacy leaders and community-based organizations to develop a Reproductive PAD. Our literature review yielded no results about Reproductive PADs. We created de novo a Reproductive PAD template with sections on medical and psychiatric history, informed consent for critical medical and psychiatric care, family planning and custody preferences, and optional sections on abortion and on electroconvulsive therapy. The Reproductive PAD provides a possible legal mechanism for people of childbearing age with SMI diagnoses to articulate their medical and psychiatric care choices around reproduction and pregnancy. Future research should evaluate the Reproductive PAD as an effective tool for protecting patient autonomy during pregnancy and postpartum and guiding medical and psychiatric providers.

Health, social and legal supports for migrant agricultural workers in France, Italy, Spain, Germany, Canada, Australia and New Zealand: a scoping review.

Introduction: We carried out a scoping review to examine what previous literature can teach us about practices and possibilities for support services for migrant agricultural workers. Methods: Following guidelines for scoping reviews as outlined by Arksey and O'Malley (2005) and further refined by Levac et. al (2010) we conducted searches of several databases and two additional searches to capture regions of focus and more current literature. We used a thematic analysis to generate our themes. Results: Our analysis yielded four key themes: (1) political, economic and legal factors; (2) living and working conditions; (3) facilitators/barriers to navigating services and supports and; (4) potential and existing strategies for social support for migrant agricultural workers. The first two themes pointed more to structural and material conditions that both posed barriers for this population to access supports, but also illustrated vulnerabilities that pointed to the need for a variety of services and protections. Under the third, we highlighted the ways that the design of services and supports, or their degree of accessibility, could shape the level of help available to this population. Lastly, potential and existing strategies for social support discussed in the literature included an emphasis on mental health and wellbeing, occupational health and safety training and documentation, and policy reforms to secure the status and address the precarity of this workforce. Discussion: While research on social support and service provision for migrant agricultural workers is still in its infancy, a strength of this body of work is its attention to macro-level issues that advocate for strategies that address root factors that shape this group's health. Further research is required to expand our understanding of social support roles and possibilities across other domains and sectors for this population.

Impact of Clinical Decision Support Within the Electronic Medical Record on Opioid Prescribing and Dispensing.

INTRODUCTION: Clinical decision support tools support prescribers and pharmacists as they select and verify appropriate opioid regimens in efforts to combat the high variability in opioid prescribing. This study seeks to examine the impact of alerts within the electronic medical record and pharmacy system on day supply of initial opioid prescribing and dispensing. METHODS: This retrospective study compared a 6-month pre- and postimplementation of clinical decision support tool alerts at an integrated health care system. Data were analyzed to assess changes in the day supply of an opioid at the point of initial prescribing and dispensing based on alerts. RESULTS: The best practice alert in the electronic medical record was associated with a 27% change (p = 0.007) in prescribing by the physician, which resulted in a reduction of average day supply from 12.09 to 6.58 days. The alert in the pharmacy system was associated with a 41.3% change (p < 0.001) in dispensing, which resulted in a reduction of average day supply from 13.46 to 6.96 days. DISCUSSION: To promote judicious opioid prescribing, the best practice alert in the electronic medical record led to a statistically significant change in prescribing. To support appropriate dispensing, the alert in the pharmacy system led to a statistically significant change in dispensing. CONCLUSION: Implementation of two clinical decision support tools that mirrored Centers for Disease Control and Prevention recommendations of prescribing less than a 7-day supply when initiating opioids resulted in a decrease in day supply of the opioid prescription for patients identified as opioid-naïve at the point of prescribing and dispensing.

Using a Linear Probe Ultrasound for the Detection of First-Trimester Pregnancies in the Emergency Department.

Linear probe point-of-care ultrasound (LPUS) presents a less invasive alternative for identifying intrauterine pregnancies (IUPs) compared to usual practice (transabdominal (TAUS) or transvaginal (TVUS) ultrasound). TAUS and TVUS can be invasive or produce lower-resolution images than LPUS. The purpose of this study is to determine whether a linear probe alone can identify first-trimester IUPs. A convenience sample of 21 patients were enrolled at the University of California Irvine ED during a 7-month period. The inclusion criteria were English- or Spanish-speaking women (≥18 years) in their first trimester of pregnancy (≤12 weeks pregnant) with a body mass index (BMI) of <35. The exclusion criteria were psychiatric, incarcerated, or cognitively impaired patients. An ED physician performed LPUS and ordered a confirmatory ultrasound. The 21 patients enrolled had a mean age of 28.6 ± 6.60 years, BMI of 26.6 ± 5.03, and gestational age of 7.4 ± 2.69 weeks. Considering the 95% confidence interval, we are 97.5% confident that the sensitivity and specificity of LPUS to identify IUPs does not exceed 67.1% and 93.2%, respectively. Our pilot data did not demonstrate that LPUS can independently visualize IUPs in first-trimester patients.

Subclassification of fetal growth restriction type IIa vs type IIb applied to twin-twin transfusion syndrome.

BACKGROUND: Subclassification of monochorionic twins with selective fetal growth restriction type II into IIa vs IIb has been proposed because of differing neonatal survival outcomes of the fetus with growth restriction after laser surgery based on preoperative Doppler findings in the middle cerebral artery and ductus venosus. There is substantial clinical overlap between selective fetal growth restriction and twin-twin transfusion syndrome. OBJECTIVE: This study aimed to compare donor twin neonatal survival after laser surgery in cases of twin-twin transfusion syndrome with concomitant donor fetal growth restriction type IIa vs IIb. STUDY DESIGN: This was a retrospective study of monochorionic multifetal pregnancies treated with laser surgery for stage III twin-twin transfusion syndrome and concomitant donor twin fetal growth restriction type II at a referral center from 2006 to 2021. Donor fetal growth restriction type II was defined as having an estimated fetal weight <10th percentile with persistent absent and/or reversed end-diastolic velocity in the umbilical artery. Moreover, patients were subclassified as type IIa (having normal middle cerebral artery peak systolic velocities and ductus venosus Doppler waveforms) vs type IIb (having middle cerebral artery peak systolic velocities ≥1.5 multiples of the median and/or ductus venosus with persistent absent or reversed atrial systolic flow). This study compared 30-day neonatal survival of the donor twin by fetal growth restriction type IIa vs IIb using logistic regression to adjust for relevant preoperative covariates (P<.10 in bivariate analysis). RESULTS: Of 919 patients who underwent laser surgery for twin-twin transfusion syndrome, 262 had sstage III donor or donor and recipient twin-twin transfusion syndrome; of these patients, 189 (20.6%) had concomitant donor fetal growth restriction type II. Moreover, 12 patients met the exclusion criteria, yielding 177 patients (19.3%) who composed the study cohort. Patients were subclassified as donor fetal growth restriction type IIa (146 [82%]) vs type IIb (31 [18%]). Donor neonatal survival for fetal growth restriction type IIa vs IIb was 71.2% vs 41.9% (P=.003). Recipient neonatal survival did not differ between the 2 types (P=1.000). Patients classified with twin-twin transfusion syndrome and concomitant donor fetal growth restriction type IIb were 66% less likely to have neonatal survival of the donor after laser surgery (adjusted odds ratio, 0.34; 95% confidence interval, 0.15-0.80; P=.0127). The logistic regression model was adjusted for gestational age at the procedure, estimated fetal weight percent discordance, and nulliparity. The c-statistic was 0.702. CONCLUSION: For patients with stage III twin-twin transfusion syndrome and concurrent donor fetal growth restriction with persistent absent or reversed end-diastolic velocity in the umbilical artery (ie, fetal growth restriction type II), subclassification into fetal growth restriction type IIb based on elevated middle cerebral artery peak systolic velocity and/or abnormal ductus venosus flow in the donor conveyed poorer prognosis. Although donor neonatal survival after laser surgery was lower for patients with stage III twin-twin transfusion syndrome with donor fetal growth restriction type IIb than patients with stage III twin-twin transfusion syndrome with donor fetal growth restriction with type IIa, laser surgery for fetal growth restriction type IIb in the setting of twin-twin transfusion syndrome (as opposed to pure selective fetal growth restriction type IIb) still allows for the possibility of dual survivorship and should be offered with shared decision-making when counseling patients on management options.