Primary lacrimal gland plexiform neurofibroma: a case report and review of the literature.

Neurofibromatosis type 1 (NF1) affects cell growth in neural tissues, resulting in neurofibromas of the internal organs, peripheral nerves and/or autonomic nerves. We describe a highly unusual case of plexiform neurofibroma presenting with lacrimal gland enlargement in an 18 year old male, which led to a diagnosis of NF1.

A rare case of metastatic paraspinal rhabdomyosarcoma presenting with proptosis in an adult patient.

Secondary metastasis of rhabdomyosarcoma (RMS) to the orbit from a distant primary site is extremely rare in adults. In this article, we describe the case of a 24-year-old male presenting with proptosis, diplopia, and headaches concurrently with a histologically confirmed diagnosis of PAX3-FOXO1 positive paraspinal alveolar rhabdomyosarcoma. An orbital MRI revealed a fusiform mass arising from the inferior rectrus, displaying necrotic and irregular morphology consistent with malignancy. The patient is currently undergoing intensive chemotherapy. The objective of this case report is to highlight the rarity of an extraocular metastasis of RMS in an adult patient, alongside the importance of considering metastatic disease in a patient with fulminant unilateral proptosis.

Lacrimal gland extranodal marginal zone B-cell lymphoma in the presence of amyloidosis.

Amyloidosis is a protein metabolism disorder characterised by extracellular deposition of insoluble amorphous hyaline material. Orbital and ocular amyloid lesions account for only 4% of localised disease affecting the head and neck. Ocular adnexal lymphoma accounts for 1-2% of lymphoma, with lacrimal gland lymphomas being relatively uncommon. The most common form affecting the orbit is extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT lymphoma). We report an extremely rare case of co-existent EMZL and amyloidosis of the lacrimal gland. Initial biopsy of the right lacrimal gland confirmed an EMZL with amyloid deposit, and a course of radiotherapy treatment was given. Recurrent lacrimal gland swelling developed within a year. Subsequent biopsy identified amyloidosis with scanty lymphoid tissue. To our knowledge, this is the first reported case of localised lacrimal gland amyloidosis of uncertain type with previous EMZL; the association described in this case report is not yet fully understood.

Metastatic testicular choriocarcinoma presenting as eyelid swelling and ptosis.

A 34-year-old man presented with an 8-day history of swelling and ptosis affecting the right upper eyelid. An MRI scan showed right superior rectus enlargement. Histology of an incisional biopsy of the muscle demonstrated metastatic choriocarcinoma to the orbit, positive for pan-cytokeratins, beta-HCG and GATA3. Possible primary sites included testis. An ultrasound of the testes identified bilateral testicular masses, highly suspicious for primary testicular malignancy. A CT scan of the chest, abdomen and pelvis identified disseminated metastatic disease conferring a poor prognostic germ cell tumour. The overall interpretation was of disseminated testicular choriocarcinoma and the patient is currently undergoing intensive chemotherapy.

Branched-Tail Lipid Nanoparticles Potently Deliver mRNA In Vivo due to Enhanced Ionization at Endosomal pH.

The potential of mRNA therapeutics will be realized only once safe and effective delivery systems are established. Unfortunately, delivery vehicle development is stymied by an inadequate understanding of how the molecular properties of a vehicle confer efficacy. Here, a small library of lipidoid materials is used to elucidate structure-function relationships and identify a previously unappreciated parameter-lipid nanoparticle surface ionization-that correlates with mRNA delivery efficacy. The two most potent materials of the library, 306O10 and 306Oi10 , induce substantial luciferase expression in mice following a single 0.75 mg kg-1 mRNA dose. These lipidoids, which have ten-carbon tails and identical molecular weights, vary only in that the 306O10 tail is straight and the 306Oi10 tail has a one-carbon branch. Remarkably, this small difference in structure conferred a tenfold improvement in 306Oi10 efficacy. The enhanced potency of this branched-tail lipidoid is attributed to its strong surface ionization at the late endosomal pH of 5.0. A secondary lipidoid library confirms that Oi10 materials ionize more strongly and deliver mRNA more potently than lipidoids containing linear tails. Together, these data highlight the exquisite control that lipid chemistry exerts on the mRNA delivery process and show that branched-tail lipids facilitate protein expression in animals.

Bilateral NAION and GPIbα gene.

BACKGROUND: It has been previously reported that one copy of the variable number tandem repeat (VNTR) B alleles of the GPIbα gene increases the risk of non-arteritic ischaemic optic neuropathy (NAION) and the second eye involvement. This is the first case where the presence of both alleles is associated with bilateral NAION. CASE PRESENTATION: A 52-year-old male presented with loss of vision in one eye and was diagnosed with NAION. The following year, he suffered another attack of NAION in the fellow eye. Genetic testing showed that he had both copies of VNTR B alleles of the GPIbα gene. CONCLUSIONS: We report a case of bilateral NAION in the presence of two copies of VNTR B alleles of the GPIbα gene. This may have further implications for the function of platelet glycoproteins.

Comparing Medicare Fee-for-Service Beneficiaries with ESKD who Switched to Medicare Advantage versus Remained in Traditional Medicare.

ABSTRACT: Patients choosing Medicare Advantage vs. Medicare fee-for-service (FFS) differ with respect to race, socioeconomic status, and burden of disease. However, it is unclear whether these differences also occur among patients with kidney failure, who were newly allowed to switch to Medicare Advantage after the 21st Century Cares Act. We used data from the United States Renal Data System (USRDS) to examine differences in characteristics of dialysis patients and kidney transplant recipients who switched from FFS to Medicare Advantage compared with those who stayed with FFS in 2021, the first year such switching was allowed. We used unadjusted and adjusted logistic regression to compare odds of switching among demographic and geographic subgroups. Among 411,513 patients with FFS coverage in 2020, 10.1% switched to Medicare Advantage in 2021. Switchers constituted 12% of the dialysis population and 5% of the kidney transplant population. In the dialysis population, patients of Black race and Hispanic ethnicity were more likely to switch than patients of White race (adjusted OR 1.69, 95% Confidence Interval [CI] 1.64, 1.73 and OR 1.42, 95% CI 1.40, 1.47, respectively), as were patients with dual eligibility for Medicaid (adjusted OR 1.12, 95% CI 1.09, 1.15). Patients living in the South were also more likely to switch to Medicare Advantage than those living in the West (adjusted OR 1.48, 95% CI 1.43, 1.52). Similar differences were observed among kidney transplant recipients. Patients who switched from FFS to Medicare Advantage were disproportionately from historically marginalized groups, including Black, Hispanic, and low income individuals. They were also more likely to live in the South. These differences may threaten the generalizability of USRDS data that relies on FFS insurance claims and suggest that comparisons of outcomes between FFS and MA beneficiaries with kidney failure should be adjusted for key patient characteristics.

Perturbations in risk/reward decision making and frontal cortical catecholamine regulation induced by mild traumatic brain injury.

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. The present study characterized the effects of rmTBI on risk/reward decision making behavior and catecholamine transmitter regulatory proteins within the PFC. Rats were exposed to sham, single (smTBI), or three closed-head controlled cortical impact (CH-CCI) injuries and assessed for injury-induced effects on risk/reward decision making using a probabilistic discounting task (PDT). In the first week post-final surgery, mTBI increased risky choice preference. By the fourth week, males exhibited increased latencies to make risky choices following rmTBI, demonstrating a delayed effect on processing speed. When levels of tyrosine hydroxylase (TH) and the norepinephrine reuptake transporter (NET) were measured within subregions of the PFC, females exhibited dramatic increases of TH levels within the orbitofrontal cortex (OFC) following smTBI. However, both males and females demonstrated reduced levels of OFC NET following rmTBI. These results indicate the OFC is susceptible to catecholamine instability after rmTBI and suggests that not all areas of the PFC contribute equally to TBI-induced imbalances. Overall, the CH-CCI model of rmTBI has revealed time-dependent and sex-specific changes in risk/reward decision making and catecholamine regulation following repetitive mild head injuries.

Sex-dependent perturbations in risky choice behavior and prefrontal tyrosine hydroxylase levels induced by repetitive mild traumatic brain injury.

Head trauma often impairs cognitive processes mediated within the prefrontal cortex (PFC), leading to impaired decision making and risk-taking behavior. Mild traumatic brain injury (mTBI) accounts for approximately 80 % of reported head injury cases. Most neurological symptoms of a single mTBI are transient; however, growing evidence suggests that repeated mTBI (rmTBI) results in more severe impairments that worsen with each subsequent injury. Although mTBI-induced disruption of risk/reward decision making has been characterized, the potential for rmTBI to exacerbate these effects and the neural mechanisms involved are unknown. Catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), modulate PFC-mediated functions. Imbalances in catecholamine function have been associated with TBI and may underlie aberrant decision making. We used a closed head-controlled cortical impact (CH-CCI) model in rats to evaluate the effects of rmTBI on performance of a probabilistic discounting task of risk/reward decision making behavior and expression levels of catecholamine regulatory proteins within the PFC. RmTBI produced transient increases in risky choice preference in both male and female rats, with these effects persisting longer in females. Additionally, rmTBI increased expression of the catecholamine synthetic enzyme, tyrosine hydroxylase (TH), within the orbitofrontal (OFC) region of the PFC in females only. These results suggest females are more susceptible to rmTBI-induced disruption of risk/reward decision making behavior and dysregulation of catecholamine synthesis within the OFC. Together, using the CH-CCI model of rodent rmTBI to evaluate the effects of multiple insults on risk-taking behavior and PFC catecholamine regulation begins to differentiate how mTBI occurrences affect neuropathological outcomes across different sexes.

Cogan's syndrome associated with orbital inflammation.

Cogan's syndrome is a relatively rare inflammatory disorder presenting with a combination of ocular and vestibuloauditory symptoms. The first cases were described by David Cogan in 1945. Typically the ocular signs involve the anterior segment; however there are no descriptions of orbital inflammation associated with Cogan's syndrome. We describe such a case. A 66-year-old immunosuppressed male patient with known Cogan's syndrome presented to the eye department with right-sided proptosis, chemosis and ocular injection. Ocular motility was reduced. Other than Cogan's syndrome there were no other systemic disorders. Medical treatment included: Azathioprine 125 mg/day and low dose Tab Prednisolone 30 mg/day. A provisional diagnosis of orbital cellulitis was made and intravenous antibiotics started. Blood investigations showed raised CRP levels 475 mg/L and raised WCC (24 × 10(9)/l). An urgent CT scan of the head and orbits ruled out orbital cellulititis. The diagnosis was revised and the patient was treated for orbital inflammatory disease. Pulsed intravenous methlyprednisolone was commenced and oral steroids were increased to 60 mg/day, the Azathioprine was continued. Over the following week, the proptosis had resolved, and oral steroids were reduced back to the maintenance dose. To our knowledge this is the first description of orbital inflammatory disease associated with Cogan's syndrome.

Increased Access, Persistent Disparities: Trends in Disparities in Peritoneal Dialysis (PD) Use, 2009-2019.

Peritoneal dialysis (PD) use has increased in the United States since 2009, but how this has affected disparities in PD use is unclear. We used data from the United States Renal Data System to identify a cohort of incident dialysis patients from 2009 to 2019. We used logistic regression models to examine how odds of PD use changed by demographic characteristics. The incident PD population increased by 203% from 2009 to 2019, and the odds of PD use increased in every subgroup. PD use increased more among older people because the odds for those aged 75 years or older increased 15% more per 5-year period compared with individuals aged 18-44 years (odds ratio [OR] 1.68, 95% confidence interval [CI], 1.64 to 1.73 versus OR 1.46, 95% CI, 1.42 to 1.50). The odds of PD use increased 5% more per 5-year period among Hispanic people compared with White people (OR 1.58, 95% CI, 1.53 to 1.63 versus OR 1.51, 95% CI, 1.48 to 1.53). There was no difference in odds of PD initiation among people who were Black, Asian, or of another race. The odds of PD use increased 5% more for people living in urban areas compared with people living in nonurban areas (5-year OR 1.54, 95% CI, 1.52 to 1.56 versus 5-year OR 1.46, 95% CI, 1.42 to 1.50). The odds of PD use increased 7% more for people living in socioeconomically advantaged areas compared with people living in more deprived areas (5-year OR 1.60, 95% CI, 1.56 to 1.63 for neighborhoods with lowest Social Deprivation Index versus 5-year OR 1.50, 95% CI, 1.48 to 1.53 in the most deprived areas). Expansion of PD use led to a reduction in disparities for older people and for Hispanic people. Although PD use increased across all strata of socioeconomic deprivation, the gap in PD use between people living in the least deprived areas and those living in the most deprived areas widened.

The impact of low-dose aspirin in the Brain Injury Guidelines on outcomes in traumatic brain injury: A retrospective cohort study.

BACKGROUND: Current Brain Injury Guidelines (BIG) characterize patients with intracranial hemorrhage taking antiplatelet or anticoagulant agents as BIG 3 (the most severe category) regardless of trauma severity. This study assessed the risk of in-hospital mortality or need for neurosurgery in patients taking low-dose aspirin who otherwise would be classified as BIG 1. METHODS: This was a retrospective study at an academic level 1 trauma center. Patients were included if they were admitted with traumatic intracerebral hemorrhage and were evaluated by the BIG criteria. Exclusion criteria included indeterminate BIG status or patients with missing primary outcomes documentation. Patients were categorized as BIG 1, BIG 2, BIG 3, or BIG 1 on aspirin (patients with BIG 1 features taking low-dose aspirin). The primary endpoint was a composite of neurosurgical intervention and all-cause in-hospital mortality. Key secondary endpoints include rate of intracranial hemorrhage progression, and intensive care unit- and hospital-free days. RESULTS: A total of 1,520 patients met the inclusion criteria. Median initial Glasgow Coma Scale was 14 (interquartile range [IQR], 12-15), Injury Severity Scale score was 17 (IQR, 10-25), and Abbreviated Injury Scale subscore head and neck (AIS Head ) was 3 (IQR, 3-4). The rate of the primary outcome for BIG 1, BIG 1 on aspirin, BIG 2, and BIG 3 was 1%, 2.2%, 1%, and 27%, respectively; the difference between BIG 1 on aspirin and BIG 3 was significant ( p < 0.001). CONCLUSION: Patients taking low-dose aspirin with otherwise BIG 1-grade injuries experienced mortality and required neurosurgery significantly less often than other patients categorized as BIG 3. Inclusion of low-dose aspirin in the BIG criteria should be reevaluated. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Association of the End-Stage Renal Disease Treatment Choices Payment Model With Home Dialysis Use at Kidney Failure Onset From 2016 to 2022.

Importance: The Centers for Medicare & Medicaid Services designed a mandatory payment model to incentivize home dialysis use: the End-Stage Renal Disease Treatment Choices (ETC). Outpatient dialysis facilities and health care professionals providing nephrology services were randomly assigned to ETC participation at the hospital referral region level. Objective: To assess the association between ETC and home dialysis use in the incident dialysis population in its first 18 months of implementation. Design, Setting, and Participants: A cohort study with controlled, interrupted time series analysis of the US End-Stage Renal Disease Quality Reporting System database was conducted, using generalized estimating equations. All adults initiating home-based dialysis in the US between January 1, 2016, and June 30, 2022, without a prior kidney transplant were included in the analysis. Exposures: Prior to vs after ETC onset in January 1, 2021, and random assignment to ETC participation of facilities and health care professionals involved in patient care. Main Outcomes and Measures: Percentage of patients started on incident home dialysis and yearly change in percentage initiating home dialysis. Results: A total of 817 177 adults initiated home dialysis during the study period, of whom 750 314 were included in the study cohort. The cohort included 41.4% women; 26.2% of the patients were Black, 17.4% were Hispanic, and 49.1% were White. Approximately half (49.6%) of the patients were aged at least 65 years. A total of 31.2% received care from health care professionals assigned to ETC participation, and 33.6% had Medicare fee-for-service coverage. Overall, home dialysis use increased from 10.0% in January 2016 to 17.4% in June 2022. Home dialysis use increased more in ETC markets than in non-ETC markets after January 2021 (by 1.07%; 95% CI, 0.16%-1.97%). The rate of increase in home dialysis use in the entire cohort nearly doubled after January 2021 to 1.66% per year (95% CI, 1.14%-2.19%) compared with before 2021, when the rate was 0.86% per year (95% CI, 0.75%-0.97%), but the difference in rate of increase in home dialysis use was not significant between ETC and non-ETC markets. Conclusions and Relevance: This study noted that, although the overall rate of dialysis use at home was greater after ETC implementation, the increase occurred more among patients in ETC markets than among those in non-ETC markets. These findings suggest that federal policy and financial incentives affected care for the entire incident dialysis population in the US.

Vertical optokinetic nystagmus in Parkinson's disease.

Parkinson's disease (PD) is associated with a number of oculomotor deficits; however, little is known about changes in vertical optokinetic nystagmus (OKN) associated with PD. We recorded eye movements in 14 PD patients and 14 age-matched controls in response to large field OKN stimulation using stimulus velocities of 20 degrees /second and 40 degrees /second. We compared asymmetry of horizontal and vertical responses in the two groups. We found vertical OKN to be strongly asymmetric in PD with reduced gains for downward-moving stimuli. This asymmetry was significantly greater than that recorded in control volunteers. We postulate that this could result from an abnormal pursuit/early OKN system in PD leading to greater influence of the delayed OKN system.

Effect of distance upon horizontal and vertical look and stare OKN.

Previous reports suggest that distance influences horizontal stare OKN gains; however, the effect of distance on vertical OKN and look OKN is unknown. Horizontal and vertical look and stare OKN gains were recorded in 16 healthy volunteers (velocity 38.4 degrees /s) at three distances (0.3 m, 1 m, and 2.5 m) and two different stimulus sizes. Asymmetry of responses and correlation of gains in different directions were compared. Measurements at near were compared with and without glasses. Distance did not significantly affect horizontal look and stare OKN or vertical look OKN, however, downward stare OKN gains were reduced at greater distances (p = 0.002). Mean downward stare OKN gains recorded in each individual were strongly correlated to leftward and rightward gains but not upward gains. In contrast, upward OKN gains were not correlated to gains in leftward, rightward, or downward directions. Downward stare OKN responses are significantly sensitive to the effects of distance, whereas stare OKN in other directions and look OKN responses in all directions are not. Individual mean downward stare OKN gains are more closely related to horizontal responses rather than upward responses. This suggests that the downward OKN system is more functionally related to the horizontal system rather than the upward OKN system.

Horizontal and vertical look and stare optokinetic nystagmus symmetry in healthy adult volunteers.

PURPOSE: Look optokinetic nystagmus (OKN) consists of voluntary tracking of details in a moving visual field, whereas stare OKN is reflexive and consists of shorter slow phases of lower gain. Horizontal OKN is symmetrical in healthy adults, whereas symmetry of vertical OKN is controversial. Horizontal and vertical look and stare OKN symmetry was measured, and the consistency of individual asymmetries and the effect of varying stimulus conditions were investigated. METHODS: Horizontal and vertical look and stare OKN gains were recorded in 15 healthy volunteers (40 degrees /s) using new methods to delineate look and stare OKN. Responses with right and left eye viewing were compared to investigate consistency of individual OKN asymmetry. In a second experiment, the symmetry of stare OKN was measured in nine volunteers varying velocity (20 degrees /s and 40 degrees /s), contrast (50% and 100%), grating contrast profile (square or sine wave), and stimulus shape (full screen or circular vignetted). RESULTS: There was no horizontal or vertical asymmetry in look or stare OKN gain for all volunteers grouped together. However, individual vertical asymmetries were strongly correlated for left and right eye viewing (look: r = 0.77, P = 0.0008; stare: r = 0.75, P = 0.001) and for look and stare OKN (r = 0.66, P = 7.3 x 10(-5)) because of a strong correlation for downward moving stimuli (r = 0.73, P = 0.002). Horizontal and vertical asymmetries were not significantly affected by variations in stimulus parameter. CONCLUSIONS: Although no horizontal or vertical OKN asymmetries existed for volunteers grouped together, vertical OKN was characterized by idiosyncratic asymmetries that remained consistent for an individual. Look and stare OKN gain is strongly associated for downward moving stimuli.

Lipid nanoparticle siRNA cocktails for the treatment of mantle cell lymphoma.

Mantle cell lymphoma is an aggressive and incurable subtype of non-Hodgkin B cell lymphoma. Patients typically present with advanced disease, and most patients succumb within a decade of diagnosis. There is a clear and urgent need for novel therapeutic approaches that will affect mantle cell lymphoma through a unique mechanism compared to current therapies. This study examined the use of RNA interference (RNAi) therapy to attack mantle cell lymphoma at the mRNA level, silencing genes associated with cancer cell proliferation. We identified a lipid nanoparticle formulated with the lipidoid 306O13 that delivered siRNA to JeKo-1 and MAVER-1 mantle cell lymphoma cell lines. Three therapeutic gene targets were examined for their effect on lymphoma growth. These included Cyclin D1, which is a cell cycle regulator, as well as Bcl-2 and Mcl-1, which prevent apoptosis. Gene knockdown with siRNA doses as low at 10 nM increased lymphoma cell apoptosis without carrier-mediated toxicity. Silencing of Cyclin D1 induced apoptosis despite a twofold "compensation" upregulation of Cyclin D2. Upon simultaneous silencing of all three genes, nearly 75% of JeKo-1 cells were apoptosing 3 days post-transfection. Furthermore, cells proliferated at only 15% of their pretreatment rate. These data suggest that lipid nanoparticles-formulated, multiplexed siRNA "cocktails" may serve as a beneficial addition to the treatment regimens for mantle cell lymphoma and other aggressive cancers.