Tuning Displacement Fields in a Two-Dimensional Topological Insulator Using Nanopatterned Gates.

Epitaxial heterostructures with topological insulators enable novel quantum phases and practical device applications. Their topological electronic states are sensitive to the microscopic parameters, including structural inversion asymmetry (SIA), which is an inherent feature of many real heterostructures. Controlling SIA is challenging, because it requires the ability to tune the displacement field across the topological film. Here, using nanopatterned gates, we demonstrate a tunable displacement field in a heterostructure of the two-dimensional topological insulator cadmium arsenide. Transport studies in magnetic fields reveal an extreme sensitivity of the band inversion to SIA. We show that a relatively small displacement field (∼50 mV/nm) converts the crossing of the two zeroth Landau levels in magnetic field to an avoided crossing, signaling a change to trivial band order. This work demonstrates a universal methodology for tuning electronic states in topological thin films.

Evaluating thromboprophylaxis in the sickle cell disease population: Navigating the evidence gap.

Sickle cell disease (SCD) arises from beta-globin gene mutations, with global estimates indicating around 500 000 affected neonates in 2021. In the United States, it is considered rare, impacting fewer than 200 000 individuals. The key pathogenic flaw lies in mutant haemoglobin S, prone to polymerization under low oxygen conditions, causing erythrocytes to adopt a sickled shape. This leads to complications like vascular occlusion, haemolytic anaemia, inflammation and organ damage. Beyond erythrocyte abnormalities however, there is a body of literature highlighting the hypercoagulable state that is likely a contributor to many of the complications we see in SCD. The persistent activation of the coagulation cascade results in thromboembolic events, notably venous thromboembolism (VTE) which is independently associated with increased mortality in both adults and children with SCD. While the increased risk of VTE in the SCD population seems well established, there is a lack of guidelines for thromboprophylaxis in this population. This Wider Perspective will describe the hypercoagulable state and increased thrombosis risk in the SCD population, as well as advocate for the development of evidence-based guidelines to aid in the prevention of VTE in SCD.

HLH and Recurrent EBV Lymphoma as the presenting manifestation of MAGT1 Deficiency: A Systematic Review of the Expanding Disease Spectrum.

Magnesium transporter 1 (MAGT1) gene loss-of-function variants lead to X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-glycosylation defect (XMEN), a condition with a variety of clinical and immunological effects. In addition, MAGT1 deficiency has been classified as a congenital disorder of glycosylation (CDG) due to its unique role in glycosylation of multiple substrates including NKG2D, necessary for viral protection. Due to the predisposition for EBV, this etiology has been linked with hemophagocytic lymphohistiocytosis (HLH), however only limited literature exists. Here we present a complex case with HLH and EBV-driven classic Hodgkin lymphoma (cHL) as the presenting manifestation of underlying immune defect. However, the patient's underlying immunodeficiency was not identified until his second recurrence of Hodgkin disease, recurrent episodes of Herpes Zoster, and after he had undergone autologous hematopoietic stem cell transplant (HSCT) for refractory Hodgkin lymphoma. This rare presentation of HLH and recurrent lymphomas without some of the classical immune deficiency manifestations of MAGT1 deficiency led us to review the literature for similar presentations and to report the evolving spectrum of disease in published literature. Our systematic review showcased that MAGT1 predisposes to multiple viruses (including EBV) and adds risk of viral-driven neoplasia. The roles of MAGT1 in the immune system and glycosylation were highlighted through the multiple organ dysfunction showcased by the previously validated Immune Deficiency and Dysregulation Activity (IDDA2.1) score and CDG-specific Nijmegen Pediatric CDG Rating Scale (NPCRS) score for the patient cohort in the systematic review.

Atypical hemolytic uremic syndrome during induction chemotherapy in neuroblastoma, a rare phenomenon or common congenital predisposition?

Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy sometimes associated with germline variants in genes of the complement system. Clinical findings of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury arise due to aberrant complement protein activation in the circulation. A 13-month-old boy with metastatic neuroblastoma (NB) developed aHUS during his first cycle of induction chemotherapy with germline testing revealing a complement factor H (CFH) gene mutation, currently classified as a variant of uncertain significance (VUS). Now he is in disease remission after successful complement blockade therapy, thus highlighting a unique presentation of aHUS in a patient with newly diagnosed NB.

Temporal memory for threatening events encoded in a haunted house.

Despite the salient experience of encoding threatening events, these memories are prone to distortions and often non-veridical from encoding to recall. Further, threat has been shown to preferentially disrupt the binding of event details and enhance goal-relevant information. While extensive work has characterised distinctive features of emotional memory, research has not fully explored the influence threat has on temporal memory, a process putatively supported by the binding of event details into a temporal context. Two primary competing hypotheses have been proposed; that threat can impair or enhance temporal memory. We analysed two datasets to assess temporal memory for an in-person haunted house experience. In study 1, we examined the temporal structure of memory by characterising memory contiguity in free recall as a function of individual levels of heart rate as a proxy of threat. In study 2, we replicated marginal findings of threat-related increases in memory contiguity found in study 1. We extended these findings by showing threat-related increases in recency discriminations, an explicit test of temporal memory. Together, these findings demonstrate that threat enhances temporal memory regarding free recall structure and during explicit memory judgments.

Sn/InAs Josephson Junctions on Selective Area Grown Nanowires with in Situ Shadowed Superconductor Evaporation.

Superconductor-semiconductor nanowire hybrid structures are useful in fabricating devices for quantum information processing. While selective area growth (SAG) offers the flexibility to grow semiconductor nanowires in arbitrary geometries, in situ evaporation of superconductors ensures pristine superconductor-semiconductor interfaces, resulting in strong induced superconductivity in the semiconducting nanowire. In this work, we used high-aspect-ratio SiOx dielectric walls to in situ evaporate islands of superconductor tin on in-plane InAs SAG nanowires. Our technique enables customization in the designs of such hybrid nanostructures, while simultaneously performing the nanowire and superconductor growth without breaking vacuum. Using this technique, we grew super(S)-normal(N)-super(S), NS, and SNSNS junctions. We performed cryogenic electron transport measurements revealing the presence of gate and field tunable supercurrents. We further measured the superconducting gap and critical fields in the hybrid nanostructures and the crossover from 2e to 1e periodicity in the SNSNS junctions as a proof of the usability of these hybrid nanostructures.

Metasurface Light-Emitting Diodes with Directional and Focused Emission.

Phased-array metasurfaces enable the imprinting of complex beam structures onto coherent incident light. Recent demonstrations of photoluminescent phased-array metasurfaces highlight possibilities for achieving similar control in electroluminescent light-emitting diodes (LEDs). However, phased-array metasurface LEDs have not yet been demonstrated owing to the complexities of integrating device stacks and electrodes within nanopatterned metasurfaces. Here, we demonstrate metasurface LEDs that emit directional or focused light. We first design nanoribbon elements that achieve the requisite phase control within typical LED device constraints. Subsequently, we demonstrate unidirectional emission that can be engineered at will via phased-array concepts. This control is further exhibited in metasurface LEDs that directly emit focused beams. Finally, we show that these metasurface LEDs exhibit external quantum efficiencies (EQEs) superior to those of unpatterned LEDs. These results demonstrate metasurface designs that are compatible with high-EQE metal-free LED devices and portend opportunities for new classes of metasurface LEDs that directly produce complex beam structures.

Isolation and characterization of mammalian orthoreovirus from bats in the United States.

Mammalian orthoreovirus (MRV) infects many mammalian species including humans, bats, and domestic animals. To determine the prevalence of MRV in bats in the United States, we screened more than 900 bats of different species collected during 2015-2019 by a real-time reverse-transcription polymerase chain reaction assay; 4.4% bats tested MRV-positive and 13 MRVs were isolated. Sequence and phylogenetic analysis revealed that these isolates belonged to four different strains/genotypes of viruses in Serotypes 1 or 2, which contain genes similar to those of MRVs detected in humans, bats, bovine, and deer. Further characterization showed that these four MRV strains replicated efficiently on human, canine, monkey, ferret, and swine cell lines. The 40/Bat/USA/2018 strain belonging to the Serotype 1 demonstrated the ability to infect and transmit in pigs without prior adaptation. Taken together, this is evidence for different genotypes and serotypes of MRVs circulating in US bats, which can be a mixing vessel of MRVs that may spread to other species, including humans, resulting in cross-species infections.

Effectiveness of Microinvasive Glaucoma Surgery in the United States: Intelligent Research in Sight Registry Analysis 2013-2019.

PURPOSE: To evaluate the effectiveness of microinvasive glaucoma surgery (MIGS) with and without concurrent phacoemulsification. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Patients in the Intelligent Research in Sight (IRIS®) Registry who underwent Xen gel stent (ab interno) implantation, endoscopic cyclophotocoagulation (ECP), or goniotomy or canaloplasty from 2013 through 2019. METHODS: Kaplan-Meier survival analysis was used to assess reoperation rates. We defined reoperation as any subsequent glaucoma surgery occurring 1 month to 3 years after the initial procedure. Multivariable Cox proportional hazard models were used to determine factors predictive of reoperation. MAIN OUTCOME MEASURES: Reoperation rate, mean intraocular pressure (IOP) and visual acuity (VA), postoperative complications, predictors of reoperation, and reoperation procedure type. RESULTS: A total of 79 363 eyes from 57 561 patients were included, with 15 118 eyes (19%) receiving stand-alone MIGS and 64 245 eyes (81%) receiving MIGS concurrent with phacoemulsification. Overall, patients who underwent MIGS concurrently with phacoemulsification showed lower reoperation rates compared with stand-alone MIGS, most pronounced in ECP and goniotomy or canaloplasty. At postoperative year 2, the cumulative reoperation rate for stand-alone procedures was 15% for ECP, 24% for Xen implantation, and 24% for goniotomy or canaloplasty compared with 3% for ECP, 19% for Xen implantation, and 6% for goniotomy or canaloplasty concurrent with phacoemulsification (P < 0.001 for each stand-alone MIGS vs. MIGS with phacoemulsification). Black race, older age, moderate and severe glaucoma, higher baseline IOP, and glaucoma subtype were associated with higher reoperation risk. Although IOP decreased in all groups, stand-alone MIGS showed a more substantial decrease in mean IOP. Complication rates from MIGS were low overall: 1% for ECP, 1% for Xen implantation, and 2% for goniotomy or canaloplasty. CONCLUSIONS: In current United States clinical practice, MIGS has substantially lower reoperation rates when performed with phacoemulsification, especially for ECP and goniotomy or canaloplasty. Approximately one-sixth of patients undergoing stand-alone ECP and one-quarter of patients undergoing stand-alone Xen implantation or goniotomy or canaloplasty require reoperation by 2 years. Black race, diagnosis coding of moderate to severe glaucoma, and higher baseline IOP were associated with higher risk of reoperation after MIGS procedures. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Hemolysis inhibits humoral B-cell responses and modulates alloimmunization risk in patients with sickle cell disease.

Red blood cell alloimmunization remains a barrier for safe and effective transfusions in sickle cell disease (SCD), but the associated risk factors remain largely unknown. Intravascular hemolysis, a hallmark of SCD, results in the release of heme with potent immunomodulatory activity, although its effect on SCD humoral response, specifically alloimmunization, remains unclear. Here, we found that cell-free heme suppresses human B-cell plasmablast and plasma cell differentiation by inhibiting the DOCK8/STAT3 signaling pathway, which is critical for B-cell activation, as well as by upregulating heme oxygenase 1 (HO-1) through its enzymatic byproducts, carbon monoxide and biliverdin. Whereas nonalloimmunized SCD B cells were inhibited by exogenous heme, B cells from the alloimmunized group were nonresponsive to heme inhibition and readily differentiated into plasma cells. Consistent with a differential B-cell response to hemolysis, we found elevated B-cell basal levels of DOCK8 and higher HO-1-mediated inhibition of activated B cells in nonalloimmunized compared with alloimmunized SCD patients. To overcome the alloimmunized B-cell heme insensitivity, we screened several heme-binding molecules and identified quinine as a potent inhibitor of B-cell activity, reversing the resistance to heme suppression in alloimmunized patients. B-cell inhibition by quinine occurred only in the presence of heme and through HO-1 induction. Altogether, these data suggest that hemolysis can dampen the humoral B-cell response and that B-cell heme responsiveness maybe a determinant of alloimmunization risk in SCD. By restoring B-cell heme sensitivity, quinine may have therapeutic potential to prevent and inhibit alloimmunization in SCD patients.

Long-term clinical outcomes and healthcare utilization of sickle cell disease patients with COVID-19: A 2.5-year follow-up study.

OBJECTIVES: This study investigated whether patients with sickle cell disease (SCD) had elevated risk of worse long-term clinical outcomes and healthcare utilization 2.5 years post-SARS-CoV-2 infection. METHODS: This study consisted of 178 patients with SCD who tested positive for COVID-19 between February 1, 2020 and January 30, 2022 in a major academic health system in New York City. The control cohort consisted of two-to-one matches of 356 SCD patients without a COVID-19 positive test. The last follow-up was July 18, 2022. The primary outcome was mortality. Secondary outcomes were annualized emergency department visits due to pain, pain hospital admission, length of stay due to pain, acute chest syndrome, episodic transfusion, and episodic exchange transfusion. RESULTS: There was no significant difference in mortality between SCD patients with and without COVID-19 (p > .05). There were no significant differences in secondary outcomes between pre- and postpandemic (p > .05). There were also no significant differences in these outcomes between SCD patients with and without COVID-19 (p > .05). SCD care utilization was not significantly associated with COVID-19 hospitalization status (p > .05). CONCLUSIONS: SCD patients with SARS-CoV-2 infection incurred no additional risk of worse long-term outcomes compared to matched controls of SCD patients not infected by SARS-CoV-2.

Impact of magnetic resonance angiography parameters on stroke prevention therapy in pediatric patients with sickle cell anemia.

BACKGROUND: Degree of cerebrovascular stenosis in pediatric patients with sickle cell anemia (SCA) informs need for chronic transfusion therapy, which has significant risks. Flow artifact, intrinsic to magnetic resonance angiography (MRA), is dependent on technical parameters and can lead to overinterpretation of stenosis. The primary objective of this study was to document any change in stroke prevention therapy that could be attributed to the implementation of a standardized MRA scanning protocol for patients with SCA. METHODS: A standardized MRA scanning protocol with an echo time of less than 5 ms was implemented at Montefiore Medical Center (MMC), NY in May 2016. Retrospective chart review identified 21 pediatric patients with SCA, with an MRA head both pre- and post-May 2016. Arterial stenosis on MRA, machine parameters, and treatment plans were compared pre- and post-implementation. RESULTS: Ten of the 21 patients met inclusion criteria. Previously seen stenosis was re-classified to a lower degree in six of the 10 patients, leading to discontinuation of transfusions in five patients. No patients required escalation of therapy to chronic transfusions. CONCLUSION: Optimizing flow artifact by decreasing echo time to less than 5 ms can improve accurate interpretation of cerebrovascular disease, and ensure appropriate treatment plans are in place for stroke prevention. This is especially important for implementing "TCD With Transfusions Changing to Hydroxyurea (TWiTCH)" clinical trial results in the real-world setting.

Racial and Socioeconomic Differences in Eye Care Utilization among Medicare Beneficiaries with Glaucoma.

PURPOSE: Evaluate differences in eye care utilization among patients with glaucoma by race and socioeconomic status (SES). DESIGN: Retrospective cohort study. PARTICIPANTS: Representative 5% sample of Medicare beneficiaries aged > 65 years with continuous part A/B enrollment between January 1, 2014, and July 1, 2014, at least 1 diagnosis code for glaucoma within that period, and a glaucoma diagnosis in the Chronic Conditions Warehouse before January 1, 2014. METHODS: The following race/ethnicity categories were defined in our cohort: non-Hispanic White, Black/African American, Hispanic, and Asian/Pacific Islander. Low SES was defined as having 2 or more enrollment-based low-income indicators (dual eligibility for Medicare/Medicaid, Part D limited income subsidies, and eligibility for Part A and B State buy-in). Negative binomial regression analyses were carried out to compare relative rate ratios (RRs) of eye care utilization among racial groups stratified by low and non-low SES. MAIN OUTCOME MEASURES: Measured from July 1, 2014, to December 31, 2016: eye examinations and eye care-related office visits; eye care-related inpatient and emergency department (ED) encounters; eye care-related nursing home and home-visit encounters; visual field and retinal nerve fiber OCT tests; glaucoma lasers and surgeries. RESULTS: Among 78 526 participants with glaucoma, mean age was 79.1 years (standard deviation, 7.9 years), 60.9% were female, 78.4% were non-Hispanic White, and 13.8% met enrollment-based criteria for low-SES. Compared with White beneficiaries, Blacks had lower counts of outpatient visits (RR, 0.92; 95% confidence interval [CI], 0.90-0.93), visual field (VF) tests (RR, 0.92; 95% CI, 0.90-0.94), but more inpatient/ED encounters (RR, 2.42; 95% CI, 1.55-3.78) and surgeries (RR, 1.14; 95% CI, 1.03-1.27). Hispanics had fewer outpatient visits (RR, 0.97; 95% CI, 0.95-0.98) and retinal nerve fiber layer (RNFL) OCT tests (RR, 0.89; 95% CI, 0.86-0.93), but more inpatient/ED encounters (RR, 2.32; 95% CI, 1.18-4.57) and selective laser trabeculoplasty (SLT) (RR, 1.25; 95% CI, 1.11-1.42) versus non-Hispanic Whites. In the non-low SES group, Black versus White disparities persisted in outpatient visits (RR, 0.93; 95% CI, 0.92-0.95), VF (RR, 0.96; 95% CI, 0.94-0.98), RNFL OCT (RR, 0.81; 95% CI, 0.78-0.83), and inpatient/ED encounters (RR, 2.57; 95% CI, 1.55-4.26). CONCLUSIONS: Disparities were found in eye care utilization among Black and Hispanic patients with glaucoma. These differences persisted among Blacks after stratification by SES, suggesting that systemic racism may be an independent driver in this population.

Successful expanded clinic network collaboration and patient tracing for retention in HIV care.

BACKGROUND: There are more than 7,800 people living with human immunodeficiency virus (HIV) in Victoria, Australia. Crucial in maximising the individual and population level benefits from antiretroviral therapy (ART) is understanding how to achieve patient retention in care and the factors that drive it. This study was an expansion of a 2015 assessment of HIV-care retention in Victoria, which sought out to determine whether the inclusion of a broader range of HIV-healthcare sites would yield more accurate estimates of retention in HIV-care. We aimed to improve our understanding of HIV-care retention in Victoria, Australia, identify people living with HIV (PLHIV) with unknown outcomes, and attempt to re-engage PLHIV in care. METHODS: A network of 15 HIV-care sites was established in Victoria, Australia across diverse care settings which ranged from low-caseload rural sites to high-caseload metropolitan GP clinics and hospitals. Individuals who had an HIV viral load (VL) performed in both calendar years of 2016 and 2017 were classified as retained in care. Individuals with a VL test in 2016 but not in 2017 were considered to potentially have unknown outcomes as they may have been receiving care elsewhere, have disengaged from care or died. For this group, an intervention of cross-referencing partially de-identified data between healthcare sites, and contact tracing individuals who still had unknown outcomes was performed. RESULTS: For 5223 individuals considered to be retained in care across 15 healthcare sites in the study period, 49 had unconfirmed transfers of care to an alternative provider and 79 had unknown outcomes. After the intervention, the number of unconfirmed care transfers was reduced to 17 and unknown outcomes reduced to 51. These changes were largely attributed to people being reclassified as confirmed transfers of care. Retention in care estimates that did not include the patient outcome of confirmed transfer of care ranged from 76.2 to 95.8% and did not alter with the intervention. However, retention in care estimates which considered confirmed transfers and those that re-entered care at a new site as retained in care significantly increased across five of the sites with estimates ranging from 80.9 to 98.3% pre-intervention to 83.3-100% post-intervention. Individuals whose outcomes remained unknown post-intervention were more often men who have sex with men (MSM) when compared to other categories (person who injects drugs (PWID), combined PWID/MSM, men who identify as heterosexual or unknown) (74.5% vs. 53.5%, [p = 0.06]) and receiving ART at their last HIV-care visit (84.3% vs. 67.8% [p = 0.09]). CONCLUSION: This study confirmed high retention in HIV-care and low numbers of people disengaged from HIV-care in Victoria. This was demonstrated across a larger number of sites with varying models of care than a prior assessment in 2015. These data align with national and state targets aiming for 95% of PLHIV retained in HIV-care.

Patching an aortic tear using the side-arm and surrounding skirt of a physician-modified ascending aortic graft.

BACKGROUND AND AIM OF STUDY: Aortic complications during cannulation must be managed urgently and often require hypothermic circulatory arrest. We report a unique management strategy to repair an aortic tear without dissection by modifying a Dacron ascending aortic graft with side-arm. CASE PRESENTATION: A 32-year-old female patient undergoing reoperative cardiac surgery suffered an unexpected aortic tear during cannulation for cardiopulmonary bypass. The tear was repaired by utilizing a physician-modified ascending aortic graft with side-arm, in which the surrounding skirt of the side-arm was cut from the circumferential graft to patch the defect. The patient was rewarmed with the side-arm serving as arterial inflow for the bypass circuit, and the remainder of the operation proceeded without complication. CONCLUSION: This type of aortic repair for aortic tears without dissection can offer the patient the benefit of avoiding multiple aortotomies in a weakened aorta, reducing circulatory arrest time, and re-establishing a central cannulation strategy for cardiopulmonary bypass.

Routine Laboratory Tests are not Necessary After Primary Total Joint Arthroplasty: A Prospective Study Utilizing a Selective Algorithmic Approach.

BACKGROUND: Laboratory tests are obtained following total joint arthroplasty (TJA) despite a lack of supporting evidence. No prior study has prospectively analyzed the effect of discontinuing routine laboratory tests. This study aimed to determine whether discontinuing routine laboratory tests in TJA patients resulted in a difference in 90-day complications. METHODS: This was a prospective protocol change study at a high-volume center. Prior to protocol change, patients underwent routine laboratory tests following primary unilateral TJA (control group). After the change, an algorithmic approach was used to selectively order laboratory tests (protocol group). Patients with bleeding disorders, chronic obstructive pulmonary disease, arrhythmia, coronary artery disease, congestive heart failure, chronic renal failure, dementia, abnormal preoperative sodium, potassium, or hemoglobin <10 g/dL were excluded. In-hospital and 90-day data were collected. Student's t-test was used to analyze continuous variables and chi-squared test was used for categorical variables. A pre-hoc analysis examining the primary outcome required 607 patients per group to achieve 80% power. RESULTS: The protocol group included 937 patients, whereas the control group included 891 patients. The protocol group had fewer females and total hip arthroplasties. There were no differences in age, body mass index, American Society of Anesthesiologists classification, tranexamic acid administration, or estimated blood loss between the protocol and control groups. There were also no differences in transfusions, electrolyte corrections, unplanned consults, length of stay, or transfers. The protocol cohort had more fluid boluses and home discharges. There was no difference in 90-day complications between the 2 groups. CONCLUSIONS: This study utilizing an algorithmic approach to laboratory collection demonstrates that discontinuing routine laboratory tests following TJA is safe and effective. We believe this protocol can be implemented for most patients undergoing primary unilateral TJA.

Optimizing the surgical instrument tray to immediately increase efficiency and lower costs in the operating room.

BACKGROUND: Surgical trays are often poorly configured and can be ongoing sources of frustration and excess costs. We conducted an observational study to determine if the use of a customized mathematical inventory optimization model would result in a greater reduction in the number of instruments on a surgical tray than a clinician review of the tray. METHODS: Utilization of instruments on the major orthopedic tray at a large academic hospital was documented over 80 procedures. Processes in the medical device reprocessing department and operating room were observed to comprehensively quantify all associated costs. Results of the observations were applied to a customized mathematical model to determine the ideal tray configuration. For comparison, a clinician review was also performed. RESULTS: The mathematical model alone produced an ideal tray size of 47 instruments, a reduction of 41 instruments from the original size of 88 instruments (47% reduction). This represented $34 440 in annual savings. In contrast, the clinician review alone suggested an ideal tray size of 67 instruments (23% reduction), representing $17 640 in annual savings. When clinicians were provided with the additional information from the model, they reduced the tray size to 51 instruments (42% reduction), producing $31 870 in savings. The mathematical model yielded an additional 22% instrument reduction and $14 230 in savings compared with clinician review alone. CONCLUSION: Our mathematical model is generalizable and can be applied to all specialties and hospitals to determine optimal tray configuration. As such, the financial implications are broad; at our institution, application to all surgical trays would result in $205 000 of savings annually. Surgeons and managers looking to streamline surgical trays should consider this evidence-based approach.

Respiratory Distress: Three Patient Cases.

As mentioned in the January 2022 Pediatrics in Review Commentary, we now present three patients who have a common chief complaint followed by 5 questions for CME credit. All three cases have discussions on presentation, the differential diagnosis, and management that collectively serve as a Review article. The common theme here is that all three patients have difficulty breathing. We hope you will enjoy this review format.

Modification of the Pulmonary MyD88 Inflammatory Response Underlies the Role of the Yersinia pestis Pigmentation Locus in Primary Pneumonic Plague.

Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing bronchopneumonia involving focal bacterial growth, neutrophilic congestion, and alveolar necrosis. Within a short time after inhalation of Y. pestis, inflammatory cytokines are expressed via the Toll/interleukin-1 (IL-1) adaptor myeloid differentiation primary response 88 (MyD88), which facilitates the primary lung infection. We previously showed that Y. pestis lacking the 102-kb chromosomal pigmentation locus (pgm) is unable to cause inflammatory damage in the lungs, whereas the wild-type (WT) strain induces the toxic MyD88 pulmonary inflammatory response. In this work, we investigated the involvement of the pgm in skewing the inflammatory response during pneumonic plague. We show that the early MyD88-dependent and -independent cytokine responses to pgm- Y. pestis infection of the lungs are similar yet distinct from those that occur during pgm+ infection. Furthermore, we found that MyD88 was necessary to prevent growth of the iron-starved pgm- Y. pestis despite the presence of iron chelators lactoferrin and transferrin. However, while this induced neutrophil recruitment, there was no hyperinflammatory response, and pulmonary disease was mild without MyD88. In contrast, growth in blood and tissues progressed rapidly in the absence of MyD88, due to an almost total loss of serum interferon gamma (IFN-γ). We further show that the expression of MyD88 by myeloid cells is important to control bacteremia but not the primary lung infection. The combined data indicate distinct roles for myeloid and nonmyeloid MyD88 and suggest that expression of the pgm is necessary to skew the inflammatory response in the lungs to cause pneumonic plague.

Association Between Diabetes, Diabetic Retinopathy, and Glaucoma.

PURPOSE OF REVIEW: The strength of the relationship between diabetes, diabetic retinopathy (DR), and glaucoma remains controversial. We review evidence supporting and refuting this association and explore mechanistic pathological and treatment relationships linking these diseases. RECENT FINDINGS: While studies have shown diabetes/DR may increase the risk for glaucoma, this remains inconsistently demonstrated. Diabetes/DR may contribute toward glaucomatous optic neuropathy indirectly (either by increasing intraocular pressure or vasculopathy) or through direct damage to the optic nerve. However, certain elements of diabetes may slow glaucoma progression, and diabetic treatment may concurrently be beneficial in glaucoma management. Diabetes plays a significant role in poor outcomes after glaucoma surgery. While the relationship between diabetes/DR and glaucoma remains controversial, multiple mechanistic links connecting pathophysiology and management of diabetes, DR, and glaucoma have been made. However, a deeper understanding of the causes of disease association is needed.