A Deep Intronic PKHD1 Variant Identified by SpliceAI in a Deceased Neonate With Autosomal Recessive Polycystic Kidney Disease.

The etiologies of newborn deaths in neonatal intensive care units usually remain unknown, even after genetic testing. Whole-genome sequencing, combined with artificial intelligence-based methods for predicting the effects of non-coding variants, provide an avenue for resolving these deaths. Using one such method, SpliceAI, we identified a maternally inherited deep intronic PKHD1 splice variant (chr6:52030169T>C), in trans with a pathogenic missense variant (p.Thr36Met), in a newborn who died of autosomal recessive polycystic kidney disease at age 2 days. We validated the deep intronic variant's impact in maternal urine-derived cells expressing PKHD1. Reverse transcription polymerase chain reaction followed by Sanger sequencing showed that the variant causes inclusion of 147bp of the canonical intron between exons 29 and 30 of PKHD1 into the mRNA, including a premature stop codon. Allele-specific expression analysis at a heterozygous site in the mother showed that the mutant allele completely suppresses canonical splicing. In an unrelated healthy control, there was no evidence of transcripts including the novel splice junction. We returned a diagnostic report to the parents, who underwent in vitro embryo selection.

Youth fatal drug overdose and suicide: Trends in Connecticut, 2019-2021.

BACKGROUND AND OBJECTIVES: Increasing rates of fatal drug overdose (FDO) among youth since 2016 have been driven by fentanyl and polysubstance use. Suicide by youth also increased steadily since 2007. The manner of FDO may be accidental (i.e., unintentional) or suicidal (i.e., intentional). This report examines the rate of youth intentional and unintentional FDO as well as specific drug toxicology in Connecticut, between the years 2019 and 2021, compared to a 2016-2018 report. METHODS: We reviewed N = 286 consecutive FDO files of youth, <26 years of age dated for 2019-2021 from the Connecticut Medical Examiner's office. RESULTS: FDO attributed to fentanyl increased significantly from 2016 to 2018 to 2019 to 2021. Xylazine FDO emerged in 2019 and reached 16% in 2021. Intentional FDO rates doubled between these periods from 3.8% to 7.7%. Most FDOs involved individuals aged 20-25 years, whereas 10% were among those aged 15-19. For the first time since 2018, FDO among 10-14 years old was detected. Analysis of gender found no differences. Within each gender, however, FDO attributed to fentanyl increased significantly between these periods. The FDO rate for Hispanics increased significantly, while the rate for Whites decreased significantly. DISCUSSION AND CONCLUSIONS: The availability of high lethality potential drugs leading to youth FDO including an increasing rate of intentional FDO, is a public health concern. It is prudent to identify modifiable acute high-risk circumstances for intentional FDO and prevention-intervention evidence-based approach to reduce FDO. SCIENTIFIC SIGNIFICANCE: This is the first study of FDO among youth examining the manner of death by suicide.

Barriers for recruitment to treatment of youths with co-occurring substance use disorders and depression.

BACKGROUND AND OBJECTIVES: Recruitment challenges for treatment trials of adolescents with substance use disorder (SUD) and co-occurring depression (COD) have not been reported. The objective is to examine whether recruitment and engagement during the pretreatment assessment phase differ between adolescents in a SUD-COD versus SUD-only treatment study. METHODS: A similar recruitment approach compared five-stage progressions in the pretreatment phase between a SUD-only (n = 252) and SUD-COD (n = 212) study. We examined the "gradient" of recruitment and retention along four stages after referral/inquiries; (a) screening for eligibility by phone, (b) meeting eligibility in an interview, (c) completion of baseline assessment, and (d) participation in the first psychotherapy session of each study. RESULTS: Compared to SUD-only, the retention of adolescents with SUD-COD was significantly poorer from referral/inquiry to all subsequent stages. In particular, the odds ratio and 95% confidence interval from referral/inquiry to screening for eligibility by phone, meeting eligibility in an interview, completion of baseline assessment, and participation in the first psychotherapy session were all less than one. Male attrition rates were slightly higher than females but were not statistically significant. DISCUSSION AND CONCLUSIONS: A high proportion of referred adolescents did not meet the study criteria. This indicates a need to examine (1) potential strategies for overcoming recruitment challenges in adolescents and their engagement in the pretreatment phase for studies of COD and (2) baseline variables for predictors and moderators for adequately powered studies. SCIENTIFIC SIGNIFICANCE: This is the first study to assess recruitment challenges for adolescents with COD.

Three-dimensional printing and craniosynostosis surgery.

OVERVIEW: The goal of this study was to review the current application and status of three-dimensional printing for craniosynostosis surgery. METHODS: A literature review was performed using the PubMed/MEDLINE databases for studies published between 2010 and 2020. All studies demonstrating the utilization of three-dimensional printing for craniosynostosis surgery were included. RESULTS: A total of 15 studies were ultimately selected. This includes studies demonstrating novel three-dimensional simulation and printing workflows, studies utilizing three-dimensional printing for surgical simulation, as well as case reports describing prior experiences. CONCLUSION: The incorporation of three-dimensional printing into the domain of craniosynostosis surgery has many potential benefits. This includes streamlining surgical planning, developing patient-specific template guides, enhancing residency training, as well as aiding in patient counseling. However, the current state of the literature remains in the validation stage. Further study with larger case series, direct comparisons with control groups, and prolonged follow-up times is necessary before more widespread implementation is justified.

Goal commitment predicts cannabis use for adolescents in treatment.

Background: Commitment to change is an innovative potential mediator and mechanism of behavior change (MOBC) that has not been examined in adolescents with cannabis use. The Adolescent Substance Abuse Goal Commitment (ASAGC) questionnaire is a reliable and valid 2-scale measure developed to assess the adolescent's commitment to either abstinence or harm reduction model for adolescents, which in addition to decrease in negative consequences includes consumption reduction as a stated treatment goal. The objective of this paper is to examine the ASAGC's ability to predict adolescent substance use treatment outcome. Methods: During Sessions 3 and 9 of a 10-week treatment program, therapists completed the ASAGC for 170 adolescents 13-18 years of age with alcohol use disorders, the majority of whom (82%) were diagnosed with co-occurring cannabis use disorder (CUD). Results: Logistic regression analyses assessing goal commitment regarding cannabis use at Session 3 indicated that commitment to both abstinence and harm reduction predicted cannabis use at Session 3. However, only commitment to abstinence predicted later cannabis use (assessed at Session 9 and during aftercare). When goal commitment at Session 9 was examined, only commitment to abstinence predicted cannabis use, concurrently and longitudinally. These results indicated that adolescents who had higher scores for commitment to abstinence were less likely to be positive for cannabis use. In contrast, harm reduction was not a significant predictor of cannabis use. Conclusions: Findings demonstrate that goal commitment consistently predicts cannabis use treatment outcome. Commitment to abstinence specifically is a salient predictor for concurrent and future cannabis use. Further prospective study is necessary to determine whether harm reduction may be an attainable goal for some youth given normative delayed neurodevelopmental processes of inhibitive behaviors.

Mfsd14a (Hiat1) gene disruption causes globozoospermia and infertility in male mice.

The Mfsd14a gene, previously called Hiat1, encodes a transmembrane protein of unknown function with homology to the solute carrier protein family. To study the function of the MFSD14A protein, mutant mice (Mus musculus, strain 129S6Sv/Ev) were generated with the Mfsd14a gene disrupted with a LacZ reporter gene. Homozygous mutant mice are viable and healthy, but males are sterile due to a 100-fold reduction in the number of spermatozoa in the vas deferens. Male mice have adequate levels of testosterone and show normal copulatory behaviour. The few spermatozoa that are formed show rounded head defects similar to those found in humans with globozoospermia. Spermatogenesis proceeds normally up to the round spermatid stage, but the subsequent structural changes associated with spermiogenesis are severely disrupted with failure of acrosome formation, sperm head condensation and mitochondrial localization to the mid-piece of the sperm. Staining for ß-galactosidase activity as a surrogate for Mfsd14a expression indicates expression in Sertoli cells, suggesting that MFSD14A may transport a solute from the bloodstream that is required for spermiogenesis.

BMP9 ameliorates amyloidosis and the cholinergic defect in a mouse model of Alzheimer's disease.

Bone morphogenetic protein 9 (BMP9) promotes the acquisition of the cholinergic phenotype in basal forebrain cholinergic neurons (BFCN) during development and protects these neurons from cholinergic dedifferentiation following axotomy when administered in vivo. A decline in BFCN function occurs in patients with Alzheimer's disease (AD) and contributes to the AD-associated memory deficits. We infused BMP9 intracerebroventricularly for 7 d in transgenic AD model mice expressing green fluorescent protein specifically in cholinergic neurons (APP.PS1/CHGFP) and in wild-type littermate controls (WT/CHGFP). We used 5-mo-old mice, an age when the AD transgenics display early amyloid deposition and few cholinergic defects, and 10-mo-old mice, by which time these mice exhibit established disease. BMP9 infusion reduced the number of Aß42-positive amyloid plaques in the hippocampus and cerebral cortex of 5- and 10-mo-old APP.PS1/CHGFP mice and reversed the reductions in choline acetyltransferase protein levels in the hippocampus of 10-mo-old APP.PS1/CHGFP mice. The treatment increased cholinergic fiber density in the hippocampus of both WT/CHGFP and APP.PS1/CHGFP mice at both ages. BMP9 infusion also increased hippocampal levels of neurotrophin 3, insulin-like growth factor 1, and nerve growth factor and of the nerve growth factor receptors, tyrosine kinase receptor A and p75/NGFR, irrespective of the genotype of the mice. These data show that BMP9 administration is effective in reducing the Aß42 amyloid plaque burden, reversing cholinergic neuron abnormalities, and generating a neurotrophic milieu for BFCN in a mouse model of AD and provide evidence that the BMP9-signaling pathway may constitute a therapeutic target for AD.

The efficacy of contingency management for adolescent cannabis use disorder: a controlled study.

BACKGROUND: This study was performed to investigate the efficacy of a voucher-based reinforcement therapy (VBRT) rewarding drug-free urine for adolescents with cannabis use disorder. METHODS: A controlled 10-week study where 59 adolescents aged 14-18 years were assigned by cohorts into groups of either an integrated cognitive-behavioral therapy (CBT) and VBRT or CBT with attendance-based reward program. Substance use was monitored by twice-weekly urinalysis. Other measures were collected at pre- and posttreatment and at 3-month follow-up. RESULTS: There was no significant difference in the linear change between conditions for cannabis use either from Sessions 1 to 10 or between end-of-treatment to 3-month follow-up. Also, self-efficacy and coping response did not show improvement during treatment. CONCLUSIONS: In this study, the addition of contingency management (CM) to CBT in youth was not found to be more efficacious than similar compensation rewarding attendance only. Continued examination of the efficacy of CM and its interaction with the associated mechanisms of behavior change of CBT in youth is necessary. Examination of the effect of the magnitude of the reward as well as considering the emotional and cognitive developmental differences from adults is warranted.

Characterization of Pediatric Infratentorial Arteriovenous Malformations: A Retrospective, Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: Infratentorial arteriovenous malformations (AVMs) harbor different characteristics compared with supratentorial AVMs. This study aims to explore the unique characteristics of pediatric infratentorial AVMs and their response to single session stereotactic radiosurgery (SRS). METHODS: The International Radiosurgery Research Foundation database of pediatric patients with AVM (age <18 years) who underwent SRS was retrospectively reviewed. Baseline demographics, AVM characteristics, outcomes, and complications post-SRS were compared between infratentorial and supratentorial pediatric AVMs. Unfavorable outcome was defined as the absence of AVM obliteration, post-SRS hemorrhage, or permanent radiation-induced changes at last follow-up. RESULTS: A total of 535 pediatric AVMs managed with SRS with a median follow-up of 67 months (IQR 29.0-130.6) were included, with 69 being infratentorial and 466 supratentorial. The infratentorial group had a higher proportion of deep location (58.4% vs 30.3%, P = <.001), deep venous drainage (79.8% vs 61.8%, P = .004), and prior embolization (26.1% vs 15.7%, P = .032). There was a higher proportion of hemorrhagic presentation in the infratentorial group (79.7% vs 71.3%, P = .146). There was no statistically significant difference in the odds of an unfavorable outcome (odds ratio [OR] = 1.36 [0.82-2.28]), AVM obliteration (OR = 0.85 [0.5-1.43]), post-SRS hemorrhage (OR = 0.83 [0.31-2.18]), or radiologic radiation-induced changes (OR = 1.08 [0.63-1.84]) between both cohorts. No statistically significant difference on the rates of outcomes of interest and complications were found in the adjusted model. CONCLUSION: Despite baseline differences between infratentorial and supratentorial pediatric AVMs, SRS outcomes, including AVM obliteration and post-SRS hemorrhage rates, were comparable amongst both groups. SRS appears to have a similar risk profile and therapeutic benefit to infratentorial pediatric AVMs as it does for those with a supratentorial location.

Proposed Screening for Congenital Hyperinsulinism in Newborns: Perspective from a Neonatal-Perinatal Medicine Group.

This perspective work by academic neonatal providers is written specifically for the audience of newborn care providers and neonatologists involved in neonatal hypoglycemia screening. Herein, we propose adding a screen for congenital hyperinsulinism (CHI) by measuring glucose and ketone (i.e., ß-hydroxybutyrate (BOHB)) concentrations just prior to newborn hospital discharge and as close to 48 h after birth as possible, at the same time that the mandated state Newborn Dried Blood Spot Screen is obtained. In the proposed protocol, we do not recommend specific metabolite cutoffs, as our primary objective is to simply highlight the concept of screening for CHI in newborns to newborn caregivers. The premise for our proposed screen is based on the known effect of hyperinsulinism in suppressing ketogenesis, thereby limiting ketone production. We will briefly discuss genetic CHI, other forms of neonatal hypoglycemia, and their shared mechanisms; the mechanism of insulin regulation by functional pancreatic islet cell membrane KATP channels; adverse neurodevelopmental sequelae and brain injury due to missing or delaying the CHI diagnosis; the principles of a good screening test; how current neonatal hypoglycemia screening programs do not fulfill the criteria for being effective screening tests; and our proposed algorithm for screening for CHI in newborns.

Characteristics Associated With Mexican-American Hospice Use: Retrospective Cohort Study Using the Hispanic Established Population for the Epidemiologic Study of the Elderly (H-EPESE).

BACKGROUND: Hospice use is lower among ethnic/racial minorities in the United States, though little is known about trends, associated factors and duration of hospice use by Mexican-Americans. AIM: The purpose of this study is to examine Mexican-American characteristics associated with hospice stay, both ≤ and > 7 days. DESIGN: This retrospective cohort study used data from the Hispanic Established Population for the Epidemiological Study of the Elderly (H-EPESE) and the Centers for Medicare and Medicaid Services. Multivariate logistic regression models were used to estimate the ORs and 95% CIs for hospice stay among Mexican-Americans, both ≤ and > 7 days. SETTING AND PARTICIPANTS: The first cohort (N = 970) includes H-EPESE participants who died between 2004 and 2016 who had Medicare parts A and B. The second cohort (N = 403) includes participants who completed the H-EPESE survey within the last 2 years of life. RESULTS: Although hospice use increased among Mexican-Americans between 2004 and 2016 (OR 1.88, 95% CI 1.19-2.97), 38% of participants died within the first week of hospice care. Mexican-Americans in New Mexico and Arizona were 2-4 times more likely to use hospice than those in Texas and Colorado. Dementia was associated with hospice use (OR 1.47, 95% CI 1.11-1.94). Characteristics, like church attendance and living alone, were not associated with hospice use. CONCLUSIONS: The substantial proportion of Mexican-Americans with 7 days or less of hospice use underscores the need for early palliative/hospice intervention to mitigate variation in use.

A Case Report of Treatment-Resistant Agitation in Dementia With Lewy Bodies: Medical Marijuana as an Alternative to Antipsychotics.

Palliative care teams are often consulted to assist in treating persistent dementia-related behavioral issues. Delta-9-tetrahydrocannabinol (THC) offers an alternative to traditional antipsychotic drugs in the long-term management of dementia with behavioral change. We present the case of an 85-year-old man with dementia with Lewy bodies with worsening aggression refractory to antipsychotic management. Multiple regimens of antipsychotics failed both in the outpatient and inpatient settings. After exhausting other options and in the setting of worsening agitation, a tincture of THC was prescribed. After starting THC tincture, the patient's behavior rapidly improved, and he was discharged home to the care of his spouse. The challenges of prescribing and obtaining THC are discussed.

The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study*.

UNLABELLED: In sub-Saharan Africa, sepsis is an important cause of mortality. Optimal sepsis management including fluid resuscitation, early antibiotic administration, and patient monitoring is limited by lack of supplies and skilled health workers. OBJECTIVE: To evaluate whether early, monitored sepsis management provided by a study medical officer can improve survival among patients with severe sepsis admitted to two public hospitals in Uganda. DESIGN, SETTING, AND PATIENTS: A prospective before and after study of an intervention cohort (n = 426) with severe sepsis receiving early, monitored sepsis management compared to an observation cohort (n = 245) of similarly ill patients with severe sepsis receiving standard management after admission to the medical wards of two Ugandan hospitals. INTERVENTION: Early sepsis management provided by a dedicated study medical officer comprising fluid resuscitation, early antibiotics, and regular monitoring in the first 6 hrs of hospitalization. MEASUREMENTS: Kaplan-Meier survival and unadjusted and adjusted Cox proportional hazards analysis were used to compare the effect of early, monitored sepsis management on 30-day mortality between the intervention cohort (enrolled May 2008 to May 2009) and observation cohort (enrolled July 2006 to November 2006). RESULTS: The majority (86%) of patients in both cohorts were human immuno-deficiency virus-infected. Median fluid volume provided in the first 6 hrs of hospitalization was higher in intervention than observation cohort patients (3000 mL vs. 500 mL, p < .001) and a greater proportion of intervention cohort patients received antibacterial therapy in <1 hr (67% vs. 30.4%, p < .001). Mortality at 30 days was significantly lower in the intervention cohort compared to the observation cohort (33.0% vs. 45.7%, log-rank p = .005). After adjustment for potential confounders, the hazard of 30-day mortality was 26% less in the intervention cohort compared to the observation cohort (adjusted hazards ratio 0.74, 95% confidence interval 0.55-0.98). Mortality among the 13% of intervention patients who developed signs of respiratory distress was associated with baseline illness severity rather than fluid volume administered. CONCLUSION: Early, monitored management of severely septic patients in Uganda improves survival and is feasible and safe even in a busy public referral hospital.

Risk factors for delirium among SARS-CoV-2 positive veterans.

There have been increasing reports of atypical neuropsychological symptoms among patients hospitalized with Coronavirus Disease 2019 (COVID-19). Although numerous pathophysiological mechanisms have been proposed to account for the association between COVID-19 and delirium, few studies have examined factors associated with its development and none have done so in the context of a veteran sample. The current study exploratorily examined demographic and medical variables that might be associated with delirium among a cohort of SARS-CoV-2 positive veterans. Demographic and medical data were extracted from the computerized patient records of 162 veterans who were admitted to a large southeastern Veterans Affairs hospital for COVID-19 complications between March 1, 2020 and April 20, 2020. At the zero-order level, age, a history of cardiovascular illness, length of stay, intensive care unit admission, initiation of new dialysis, and the development of new thromboembolic or cardiac findings were associated with delirium. However, when simultaneously examining the impact of these predictor variables in a logistic regression, only length of stay and new cardiac findings increased the odds of delirium. Findings highlight the importance of continued investigation into factors that may account for neuropsychiatric dysfunction among COVID-19 patients.

Grief and Bereavement in the Latino/a Community: A Literature Synthesis and Directions for Future Research.

Introduction: Bereavement and grief are social phenomena influenced by a multitude of cultural factors. Prior studies of bereavement adjustment have primarily focused on bereaved survivors who identify racially as white; knowledge of the experience of grief and bereavement among racial/ethnic and other minority groups, particularly among Latino/a groups, in the United States is limited. Objective: The purpose of this review is to synthesize the literature documenting the bereavement experiences of the Latino/a community, evaluate the strength of the current evidence, and provide recommendations to guide future research. Method: A narrative review of research on grief and bereavement in the Latino/a community published between 1990 and 2021. Two authors used a thematic, deductive approach to categorize emergent prevalent themes from the literature and used The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and The Oxford Center for Evidence-Based Medicine-Evidence Quality Rating Scale (OCEBM) approaches to evaluate the strength of the qualitative and quantitative reports reviewed. Results: Searches revealed 26 reports that were categorized into six themes: cultural values, mourning rituals, immigration, spirituality, disparities related to the COVID-19 pandemic, and the effects of COVID-19 on Latino/a communities. Our evaluation concludes that the evidence in this area is weak, with limited methodologically rigorous research examining the influence of culture on bereavement among Latino/a groups. Conclusion: Research is needed to identify Latino/a groups' mental health, cultural, social, and family needs and how fulfillment of mourning rituals and other cultural factors may promote or impede bereavement adjustment. Investigation into factors that may protect bereaved survivors against adverse mental health outcomes is also needed. A better understanding of Latino/a grief and bereavement is a step toward the development of culturally competent interventions designed to promote the mental health and psychosocial adjustment of Latino/a mourners.

Adaptive Treatment for Youth With Substance Use and Depression: Early Depression Response and Short-term Outcomes.

OBJECTIVE: To investigate prevalence and predictors of early depression response (EDR) in adolescents with substance use and depression receiving cognitive-behavioral therapy (CBT) for substance use and to test the efficacy of supplemental CBT targeting depression (CBT-D) for non-EDR adolescents in an adaptive treatment approach. METHOD: At 2 sites, 95 youths (ages 14-21, mean [SD] = 17.4 [1.8]) with alcohol or cannabis use and depressive symptoms received up to 12 sessions of CBT for substance use over 14 weeks. Assessments were at baseline and weeks 4, 9, and 14. The Children's Depression Rating Scale-Revised was the primary depression measure, with a reduction of 50% or more on this scale at week 4 defining EDR. The primary substance use outcomes of alcohol use, heavy alcohol use, and cannabis use frequency were assessed via interview report on the Alcohol Consumption Questionnaire and the Drug Checklist. Urinalysis provided a secondary measure of cannabis use. Non-EDR adolescents were randomly assigned to supplemental CBT-D or enhanced treatment as usual (ETAU). RESULTS: Thirty-five adolescents (37%; 95% CI, 27%-47%) demonstrated EDR. Fewer days of cannabis use (odds ratio 0.977; 95% CI, 0.961-0.992) and absence of conduct disorder (odds ratio 0.149; 95% CI, 0.031-0.716) predicted EDR. Frequency of drinking (F1,82 = 11.09, η2 = 0.119, p = .001), heavy drinking (F1,82 = 19.91, η2 = 0.195, p < .0001), and cannabis use (F1,220 = 35.01, η2 = 0.137, p < .001) decreased over time for EDR, CBT-D, and ETAU adolescents, with EDR adolescents evidencing earlier lower cannabis use (F2,220 = 4.16, η2 = 0.036, p = .0169). Negative (clean) urine screens increased over time (F1,219 = 5.10, η2 = 0.023, p = .0249). Comparison of CBT-D and ETAU indicated that depression significantly decreased over time in both groups (F1,48 = 64.20, η2 = 0.572, p < .001), with no advantage for CBT-D. CONCLUSION: Approximately one-third of adolescents with substance use and depression attain EDR during substance use treatment. Less frequent cannabis use facilitates depression response. The relatively small sample may have precluded identification of additional EDR predictors. CLINICAL TRIAL REGISTRATION INFORMATION: Treatment for Teens With Alcohol Abuse and Depression; https://clinicaltrials.gov/; NCT02227589.

Predictors of Functional Dependence After COVID-19: A Retrospective Examination Among Veterans.

OBJECTIVE: The aim of this study was to examine the impact of demographics, preexisting medical conditions, and in-hospital complications of COVID-19 infection on functional status at discharge. DESIGN AND PARTICIPANTS: A retrospective chart review was conducted on 119 patients hospitalized for COVID-19 infection between March 1, 2020, and April 20, 2020. Demographics, preexisting medical conditions, and newly diagnosed COVID-19 complications were collected from electronic medical records and entered in a deidentified database. MAIN OUTCOME: The primary outcome was functional status at discharge, as measured by independence in activities of daily living. RESULTS: Older age, respiratory failure, cardiac conditions, and thromboembolic complications all made a statistically significant contribution to functional dependence at discharge, with thromboembolic complications evincing the strongest association (odds ratio, 25.58). CONCLUSION AND RELEVANCE: New diagnosis of thrombosis during COVID-19 hospitalization, a measure of COVID-19 disease severity, was the factor most associated with dependence in activities of daily living at discharge. Interestingly, preexisting conditions including hypertension, severe obesity, lung disease, and diabetes did not correlate with dependent functional status at discharge.

Giant pituitary macroadenoma of stem cell origin: illustrative case.

BACKGROUND: Giant pituitary macroadenomas with a diameter >4 cm are rare tumors, accounting for only about 5% of pituitary adenomas. They are more difficult to maximally resect safely owing to limited access as well as encasement of adjacent structures. Acidophil stem cell adenomas are rare immature neoplasms proposed to derive from common progenitor cells of somatotroph and lactotroph cells. These adenomas comprise about 4.3% of surgically removed pituitary adenomas. No previous reports have described acidophil stem cell adenomas that grow to the size of giant macroadenomas. This rare entity poses special challenges given the need for maximal safe resection in an immature neoplasm. OBSERVATIONS: The authors report a 21-year-old female who presented with 3 years of progressive visual decline and a giant macroadenoma. She underwent endoscopic transsphenoidal surgery for decompression. Given the tumor size and involvement of adjacent critical structures, gross-total resection was not achieved. The authors review the literature on giant pituitary adenomas and provide a discussion on clinical management for this rare entity. LESSONS: The authors present a very rare case of a giant pituitary adenoma of acidophil stem cell origin and discuss the technical and management challenges in this rare entity.