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Euglycemic diabetic ketoacidosis is a metabolic condition characterized by relative euglycemia, ketonemia, and metabolic acidosis that occurs through mechanisms resembling starvation. Pancreaticoduodenectomy is a complex abdominal operation that subjects patients to a prolonged fasting and an inflammatory state. This study examined the incidence of euglycemic diabetic ketoacidosis and potential opportunities for early diagnosis and management in patients undergoing pancreaticoduodenectomy.A single-institution retrospective review of 350 patients who underwent pancreaticoduodenectomy between 2017 and 2020 was performed. Primary endpoints were peak beta-hydroxybutyrate levels, peak lactate levels, lowest pH, peak base deficits, and urinary output within the first 24 hours, postoperatively. Additional endpoints included incidence of postoperative pancreatic fistula, delayed gastric emptying, total complications, postoperative hospital length of stay, readmission rates, and changes in insulin regimen at discharge.Of the 350 cases reviewed, 39 (11.1%) patients developed euglycemic diabetic ketoacidosis. Male sex and pancreatic cancer were associated with a risk for euglycemic diabetic ketoacidosis (P.05). Patients with euglycemic diabetic ketoacidosis had significantly higher peak beta-hydroxybutyrate levels than patients without euglycemic diabetic ketoacidosis (mean difference = 19.8 mg/dL, 95% confidence interval = 14.7-24.9, P.001), and were nearly four times more likely to require insulin at discharge (odds ratio 3.8, 95% confidence interval = 1.1-13.0, P.05).This is the first large descriptive study that investigates euglycemic diabetic ketoacidosis after pancreaticoduodenectomy. Euglycemic diabetic ketoacidosis after pancreaticoduodenectomy is associated with significantly higher beta-hydroxybutyrate levels and new or increased insulin requirement at discharge. Our study demonstrates potential markers for euglycemic diabetic ketoacidosis after pancreaticoduodenectomy, offering an opportunity to identify and successfully treat this disease in a timely manner.

Wallis et al (JAMA 2017) demonstrated use of antithrombotic medications (ATMs) is associated with increased prevalence of hematuria-related complications and subsequent bladder cancer diagnosis within 6 months. Stage of diagnosis was lacking in this highly publicized study. This study examined the association of ATM use on bladder cancer stage at the time of diagnosis.We completed a retrospective chart review of patients with a bladder cancer diagnosis at our institution. Patient demographics and bladder cancer work up information were assessed. Patients were stratified based on use of ATMs at time diagnosis. Descriptive statistics were completed to identify association between ATM use and stage of bladder cancer diagnosis, as stratified by non-muscle invasive bladder cancer (NMIBC) versus muscle invasive bladder cancer (MIBC).A total of 1052 patient charts were reviewed. Eight hundred and forty-four were included and 208 excluded due to unavailability of diagnosis history. At diagnosis, 357 (42.3%) patients were taking ATMs. Patients on ATMs presented with NMIBC at similar rates as patients not taking ATMs (81.2% vs. 77.8%, p = 0.23). Subgroup analysis by ATM class similarly demonstrated no statistically significant differences in staging.While Wallis et al established that patients on blood thinners who present with hematuria are more likely to be diagnosed with genitourinary pathology, this factor does not appear to enable an earlier diagnosis of bladder cancer. Future study may assess hematuria at presentation (gross, microscopic), type of blood thinners, and low versus high risk NMIBC presentation.

Purpose of review Sympathetic ophthalmia is a bilateral granulomatous uveitis that occurs following unilateral trauma or surgery and is sight-threatening in the contralateral eye. Despite significant potential morbidity, disease remains poorly understood. Variable presentations and clinical courses, as well as a lack of definitive diagnostic laboratory tests can complicate the diagnosis and result in delayed treatment, which can beget permanent vision loss. This review focuses on recent advances in areas of pathophysiology, classification, diagnosis and treatment. Recent findings Sympathetic ophthalmia is thought to involve a cell-mediated immune response to retinal and uveal antigens exposed through trauma or surgery. Multiple mechanisms have been implicated, including activation of the interleukin-23/IL-17 pathway. Ongoing emphasis is placed on early disease recognition and prompt treatment with multimodal imaging. Multiple authors advocate for the routine use of optical coherence tomography (OCT) for screening and disease monitoring. Systemic steroids and steroids sparing-immunosuppressive agents remain the mainstay of treatment. Summary Understanding pathophysiology may provide useful targets for drug development, as well as allow for identification of patients at risk. OCT is a useful tool in early diagnosis and management of sympathetic ophthalmia, as OCT changes may precede clinical symptoms and signs, allowing for early disease detection and better visual outcomes.

To investigate factors associated with good visual acuity (VA) following repair of rhegmatogenous retinal detachments (RD) with proliferative vitreoretinopathy (PVR) undergoing retinectomy.Interventional, retrospective, case-control study.This single-institution study evaluated patients who underwent retinectomy during repair of RD with PVR from January 1, 2015 to December 31, 2019. A good VA cohort was identified based on a final VA ≥20/70. A 2:1 age-matched and gender-matched poor VA cohort with VA20/70 was subsequently identified. Metrics compared between the two cohorts included time from primary and recurrent RD diagnosis to surgery, lens status, initial RD size, macula involvement, PVR grade, and size of retinectomy.A total of 5355 eyes were diagnosed with primary RD during the study period, of which 345 had PVR and underwent retinectomy. The good VA cohort included 62 eyes with a mean final logMAR VA of 0.32 [Snellen 20/42], while the poor VA cohort included 119 eyes with a mean final logMAR VA of 1.54 [Snellen 20/693; P.0001]. On multivariate analysis, smaller initial RD size (P = .0090), fewer surgeries (P = .0002), shorter time between recurrent RD diagnosis and subsequent surgeries (P = .0006), better preoperative VA (P = .0276), and pseudophakia at final visit (P = .0049) remained significant predictors of good vision.Eyes undergoing retinectomy during repair of RD with PVR can achieve good VA outcomes. The primary modifiable factor associated with better VA was shorter delay between redetachment diagnosis and surgery, particularly in the absence of silicone oil tamponade.

IntroductionMedical providers may not be familiar with the genitourinary and sexual symptoms of transgender and non-binary (TGNB) individuals. This lack of familiarity may hinder a provider's ability to address these issues as patients may hesitate to report symptoms due to fear of stigma, misgendering, and being treated disrespectfully.AimTo describe the array of genitourinary and sexual symptoms in transfeminine individuals.MethodsUpon institutional review board approval, researchers used semi-structured interviews with 25 transfeminine individuals assigned male at birth to explore urinary and sexual symptoms on a sample of convenience. Participants were recruited and interviews were conducted until saturation was achieved. Two research assistants independently coded all de-identified transcripts and resolved discrepancies.OutcomesThematic codes pertaining to genitourinary and sexual symptoms were defined and assessed in this study.ResultsSome genitourinary symptoms unrelated to hormone therapy or genital gender-affirming surgery (GGAS) included frequency, urgency, nocturia, and incontinence, while those attributed to GGAS included slow stream, spraying, and retention. Sexual symptoms unrelated to hormone therapy or GGAS included sexually transmitted infections, erectile dysfunction, and low libido. Sexual symptoms related to GGAS included delayed ejaculation, penile pain, scar tissue pain, and pain with receptive vaginal penetration.Clinical ImplicationsIncreased provider awareness of and accountability for the treatment of genital and sexual symptoms of transfeminine individuals.Strengths and LimitationsOpen-ended questions were used to generate a range of responses and perspectives through conversation instead of quantifiable data. Findings are not applicable to all TGNB people since participants were limited to transfeminine adults assigned male at birth only. Recruitment was limited by the sensitive nature of the topic and hard-to-reach populations and relied on convenience through flyers and a chain-referral sampling approach.ConclusionTransfeminine individuals experience a wide array of genitourinary and sexual symptoms both similar and different to their cis gender counterparts.

In utero base editing has the potential to correct disease-causing mutations before the onset of pathology. Mucopolysaccharidosis type I (MPS-IH, Hurler syndrome) is a lysosomal storage disease (LSD) affecting multiple organs, often leading to early postnatal cardiopulmonary demise. We assessed in utero adeno-associated virus serotype 9 (AAV9) delivery of an adenine base editor (ABE) targeting the Idua G→A (W392X) mutation in the MPS-IH mouse, corresponding to the common IDUA G→A (W402X) mutation in MPS-IH patients. Here we show efficient long-term W392X correction in hepatocytes and cardiomyocytes and low-level editing in the brain. In utero editing was associated with improved survival and amelioration of metabolic, musculoskeletal, and cardiac disease. This proof-of-concept study demonstrates the possibility of efficiently performing therapeutic base editing in multiple organs before birth via a clinically relevant delivery mechanism, highlighting the potential of this approach for MPS-IH and other genetic diseases., Lysosomal storage diseases like mucopolysaccharidosis type I (MPS I) cause pathology before birth and result in early morbidity and mortality. Here, the authors show that in utero base editing mediates multi-organ phenotypic and survival benefits in a mouse model recapitulating a common human MPSI mutation.

Traditional tissue engineering methods often fail to promote robust cell growth and differentiation, limiting the development of functioning tissues. However, the microgravity conditions created by rotating wall vessel bioreactors minimize shear stress and unload the gravitational force usually placed on cells. In a microgravity environment, cell proliferation, cell differentiation, and the 3D organization of cells are altered, potentially encouraging the formation of more biosimilar artificial tissues for certain cell types. Additionally, cells in these engineered tissues display lowered immunogenicity, pointing to the transplantation potential of tissues engineered in microgravity conditions. However, these benefits are not consistent across all cell types, and the long-term impact of microgravity on tissue development and stability remains an unanswered question. Even so, there is potential that with further research, microgravity tissue engineering will have productive clinical applications for medical and pharmaceutical purposes.

Stroke is a leading cause of long-term disability worldwide, intensifying the need for effective recovery therapies. Stem cells are a promising stroke therapeutic, but creating ideal conditions for treatment is essential. Here we developed a conductive polymer system for stem cell delivery and electrical modulation in animals. Using this system, electrical modulation of human stem cell transplants improve functional stroke recovery in rodents. Increased endogenous stem cell production corresponds with improved function. Transcriptome analysis identified stanniocalcin 2 (STC2) as one of the genes most significantly upregulated by electrical stimulation. Lentiviral upregulation and downregulation of STC2 in the transplanted stem cells demonstrate that this glycoprotein is an essential mediator in the functional improvements seen with electrical modulation. Moreover, intraventricular administration of recombinant STC2 post-stroke confers functional benefits. In summation, our conductive polymer system enables electrical modulation of stem cells as a potential method to improve recovery and identify important therapeutic targets.

The application of induced pluripotent stem cells (iPSCs) in disease modeling and regenerative medicine can be limited by the prolonged times required for functional human neuronal differentiation and traditional 2D culture techniques. Here, a conductive graphene scaffold (CGS) to modulate mechanical and electrical signals to promote human iPSC‐derived neurons is presented. The soft CGS with cortex‐like stiffness (≈3 kPa) and electrical stimulation (±800 mV/100 Hz for 1 h) incurs a fivefold improvement in the rate (14d) of generating iPSC‐derived neurons over some traditional protocols, with an increase in mature cellular markers and electrophysiological characteristics. Consistent with other culture conditions, it is found that the pro‐neurogenic effects of mechanical and electrical stimuli rely on RhoA/ROCK signaling and de novo ciliary neurotrophic factor (CNTF) production respectively. Thus, the CGS system creates a combined physical and continuously modifiable, electrical niche to efficiently and quickly generate iPSC‐derived neurons., Induced pluripotent stem cells are exciting cells for understanding development and in regenerative medicine. Stem cells respond to their environment to perform their functions and mature. A newly designed conductive scaffold is capable of shaping the mechanical and electrical environment. Utilizing this conductive polymer platform, enhanced stem cell neuronal maturation of the stem cells and important pathways can be identified.

Nerve injury often causes neuronal loss and glial scar formation. We have recently demonstrated NeuroD1-mediated direct conversion of reactive glial cells into functional neurons in adult mouse brains. Here, we further investigate whether such direct glia-to-neuron conversion technology can reverse glial scar back to neural tissue in a severe stab injury model of the mouse cortex. Using adeno-associated virus (AAV)-based gene therapy approach, we ectopically expressed single neural transcription factor NeuroD1 in reactive astrocytes in the injured areas.We discovered that the reactive astrocytes were efficiently converted into neurons both before and after glial scar formation, and the remaining astrocytes proliferated to repopulate themselves.The astrocyte-converted neurons were highly functional, capable of firing action potentials and establishing synaptic connections with other neurons. Unexpectedly, expression of NeuroD1 in reactive astrocytes resulted in a significant reduction of toxic A1 astrocytes, together with a significant decrease of reactive microglia and neuroinflammation. Furthermore, accompanying the regeneration of new neurons and repopulation of new astrocytes, new blood vessels emerged and blood-brain-barrier was restored. These results demonstrate an innovative neuroregenerative gene therapy that can directly reverse glial scar back to neural tissue, opening a new avenue for brain repair after injury.• Glial scar can be reversed back to neural tissue through neuroregenerative gene therapy• Astrocytes are not depleted after neuronal conversion• Neuron to glia ratio after injury can be rebalanced through in vivo cell conversion• Conversion of reactive astrocytes into neurons reduces neuroinflammation• Astrocyte-to-neuron conversion restores blood vessels and blood-brain-barrierBrain repair, brain injury, NeuroD1, astrocyte-to-neuron conversion, in vivo reprogramming, neuron to astrocyte ratio, neuroinflammation, blood-brain-barrier

Once pulmonary disease progresses to end-stage pulmonary disease, treatment options are very limited. An important advance in the field is the development of a bioartificial lung derived from a generic matrix scaffold populated with patients' own cells. Significant progress has already been made in the engineering of bioartificial lungs.This review explains how previous and current research contributes to the goal of creating a successful bioartificial lung, and the barriers faced in doing so. We will also highlight some of the design considerations being explored to optimize bioartificial lungs and considerations for clinical translation.While current bioartificial lungs are able to provide short-term gas exchange in large-animal studies, much work is still required to combine the disciplines of cell biology, materials science, and tissue engineering to create such clinically useful and functioning artificial lungs.

Objective To describe perspectives and experiences related to urology care-seeking of transgender and non-binary (TGNB) individuals assigned male at birth. Materials and Methods This HIPAA-compliant study was IRB approved and followed Consolidated Criteria for Reporting Qualitative Studies (COREQ) guidelines. Through semistructured interviews, perspectives, and experiences of individuals related to urology care-seeking were explored. Open-ended questions were designed to elicit a range of responses rather than quantifiable data. Thematic codes were developed and explicitly defined. Codes pertaining to patient experiences were assessed and described. Results Twenty-five TGNB individuals assigned male at birth were interviewed. Participants reported an array of factors that informed and inhibited care-seeking, factors that framed individual urologic care experiences, and their overall impression of the healthcare system's ability to effectively and respectfully serve the TGNB population. Specifically, participants reported that prior negative healthcare experiences dissuaded them from seeking care such as feeling discriminated against and having a lack of trust in providers. Additionally, participants reported feeling a need and responsibility to “educate” providers on both their medical needs and psychosocial experiences. Participants were also unclear how best to identify “trans-friendly” urologists who are culturally competent and have appropriate medical knowledge. Conclusion TGNB individuals face significant barriers to care for unique healthcare needs. TGNB participants described care avoidance and reported experiences of healthcare discrimination. These data highlight the importance for urologists to understand the perspectives and historical experiences of these individuals who may seek urological care.

Purpose To report the long-term core outcome set of patients with simple gastroschisis. Methods This was a retrospective chart review of all patients with simple gastroschisis managed at our hospital between August 2008 and July 2016. We collected all data included in the core outcome set developed for the standardization of gastroschisis outcomes reporting. We conducted a phone survey of the patients' parents using the PedsQL™ Pediatric Quality of Life Inventory, Cognitive Functioning Scale, and Gastrointestinal Symptoms Scale (GSS). Additionally, parents reported their subjective evaluation of the patients' cosmetic result and overall quality of life. Results There were 124 patients included in the study. The majority (76.5%) was born prematurely at a median gestational age of 36 (range 27.6–38) weeks. At neonatal discharge (median 36 days [18–150] days) most patients were below the 10th percentile for height (81.4%) and weight (87%). Their growth, however, normalized during early childhood. Seven patients (5.6%) required at some point an operation for acute abdominal complications. One-third of patients required long-term treatment for constipation and one-third of patients required long-term treatment for gastroesophageal reflux disease (GERD). Thirty-five parents participated in the phone survey. Mean parent-reported quality of life score was better than healthy controls (87.5% vs. 82.3%, p = 0.049). Cognitive functions and gastrointestinal symptoms scores were similar to healthy controls. All patients are alive. Conclusion Growth restriction in patients with simple gastroschisis is common at birth and during the neonatal period, but it improves during the first three years of life. Abdominal operations are rarely needed in patients with simple gastroschisis. GERD and constipation, on the other hand, are common and often require long-term medical management. The overall parent-reported quality of life of patients with simple gastroschisis is excellent. Level of evidence Level II.

Objective The aim of this study is to assess the diagnostic yield and economic cost of radiologic imaging for urgent and emergent ophthalmic conditions in an emergency room (ER) setting Design Retrospective, consecutive case series. Methods Charts of all patients who underwent radiologic imaging in a dedicated eye ER over a single year were reviewed. Data collected included age, patient reported chief complaint, visual acuity, principal examination finding, indication for imaging, imaging modalities performed, and the current procedural terminology (CPT) codes billed for the imaging performed. Imaging results were classified into three groups with binary outcomes: normal or abnormal; significant if it led to a change in patient management, and relevant if the imaging findings were related to the chief complaint or principal examination finding. Imaging costs were calculated using the billed CPT codes. Results A total of 14,961 patients were evaluated during the 1-year study and 1,371 (9.2%) patients underwent imaging. Of these, 521 patients (38.0%) had significant findings. A majority of this group had significant and relevant findings (469, 34.2% of total). Subgroup analysis was performed based upon patient chief complaint, principal examination finding, and indication for imaging. Overall, the total cost of imaging was $656,078.34 with an average cost of $478.54 per patient. Conclusion Imaging for urgent and emergent ophthalmic conditions in an eye ER resulted in significant management changes in 38.0% of patients. Radiographic imaging contributes to healthcare expenditures; however, these costs must be weighed against the substantial costs of delayed and misdiagnoses, especially when patients present with acute ophthalmological symptoms.

Referring professionals correctly diagnose urgent or emergent ocular conditions in 65.1% of referrals. Telephone triaging ophthalmology residents make the correct diagnosis in 69.9% of referrals. Both are more accurate when sight or life-threatening diagnoses are referred.

Extracellular matrix (ECM) properties affect multiple cellular processes such as cell survival, proliferation, and protein synthesis. Thus, a polymeric‐cell delivery system with the ability to manipulate the extracellular environment can act as a fundamental regulator of cell function. Given the promise of stem cell therapeutics, a method to uniformly enhance stem cell function, in particular trophic factor release, can prove transformative in improving efficacy and increasing feasibility by reducing the total number of cells required. Herein, a click‐chemistry powered 3D, single‐cell encapsulation method aimed at synthesizing a polymeric coating with the optimal thickness around neural progenitor cells is introduced. Polymer encapsulation of neural stem cells significantly increases the release of neurotrophic factors such as VEGF and CNTF. Cell encapsulation with a soft extracellular polymer upregulates the ADCY8‐cAMP pathway, suggesting a mechanism for the increase in paracrine factors. Hence, the described single‐cell encapsulation technique can emerge as a translatable, nonviral cell modulation method and has the potential to improve stem cells' therapeutic effect., Through the use of cell glycoengineering techniques and click chemistry, single‐cell polymer encapsulation is possible. This polymeric extracellular matrix can modify the trophic factor production of neural progenitor cells. The cyclic adenosine monophosphate pathway and actin interactions are important in trophic factor regulation, specifically for VEGFB. The ability to encapsulate cells has implications for optimizing stem cell therapeutics.

Introduction: Stem cells have emerged as an exciting stroke therapy but can also serve to determine important pathways for recovery. Utilizing an implantable, electrically conductive polymer scaffold for human progenitor cell (NPC) delivery, we propose the use of transcriptome analysis to determine essential recovery mechanisms. Materials and Methods: NPC cDNA (Aruna) was isolated to evaluate transcriptome changes. Furthermore, NPCs were lentiviral modification to reduce (NPC KD ) or increase (NPC STC2KI ) STC2 production (with NPC ScrambleKD groups as a negative control). Immunocompromised rats underwent a distal middle cerebral artery occlusion stroke. At 1 week post-stroke, implantation surgeries were performed. NPC Stim , NPC KD+Stim and NPC ScrambleKD+Stim received electrical stimulation daily for 3 consecutive days (AC: ±800 mV/100Hz for 1 hr, starting 1 day after implantation, n=10). Blinded, behavior testing was performed for 6 weeks. Results and Discussion: Transcriptome analysis confirmed that NPC Stim had a distinct upregulation of neurotrophic factors, specifically STC2 (Fig. a, b). If STC2 was knocked-down (NPC STC2KD and NPC STC2KD+Stim ), STC2 was not upregulated with electrical stimulation; and the enhanced stroke recovery observed in animals that received NPCs and stimulation (NPC Stim , with NPC ScrambleKD+Stim as a positive control) was not seen (Fig. b-c). If NPCs had lentiviral increased STC2 production (NPC STC2KI ), improved recovery was also observed. Conclusions: Our platform enables the manipulation of NPCs in vivo to optimize recovery and evaluate the important mechanisms for functional improvement such as STC2 - a protein important in stem cell production. Figure. a. Transcriptome analysis of NPCs. Electrical stimulation augmented neurotrophic factors such as STC2. b. ELISA analysis of STC2 (**, p < .01 from unstimulated, n=4). c. Improved functional recovery in whisker paw (WP) test with NPC Stim , NPC ScrambleKD+Stim , and NPC STCKI (**, p < .01 from unstimulated NPC and other groups, n=10, two-tailed Mann-Whitney U test)