3-Hydroxykynurenine targets kainate receptors to promote defense against infection.

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an in vivo chemical screen using zebrafish embryos and found that treatment with 3-hydroxykynurenine (3-HK) protects from lethal bacterial infection. 3-HK, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages through a systemic mechanism that targets kainate-sensitive glutamate receptors. These findings reveal a new pathway by which tryptophan metabolism and kainate-sensitive glutamate receptors function and interact to modulate immunity, with important implications for the coordination between the immune and nervous systems in pathological conditions.

Fluorogenic Probes of the Mycobacterial Membrane as Reporters of Antibiotic Action.

The genus Mycobacterium includes species such as Mycobacterium tuberculosis, which can cause deadly human diseases. These bacteria have a protective cell envelope that can be remodeled to facilitate their survival in challenging conditions. Understanding how such conditions affect membrane remodeling can facilitate antibiotic discovery and treatment. To this end, we describe an optimized fluorogenic probe, N-QTF, that reports on mycolyltransferase activity, which is vital for cell division and remodeling. N-QTF is a glycolipid probe that can reveal dynamic changes in the mycobacterial cell envelope in both fast- and slow-growing mycobacterial species. Using this probe to monitor the consequences of antibiotic treatment uncovered distinct cellular phenotypes. Even antibiotics that do not directly inhibit cell envelope biosynthesis cause conspicuous phenotypes. For instance, mycobacteria exposed to the RNA polymerase inhibitor rifampicin release fluorescent extracellular vesicles (EVs). While all mycobacteria release EVs, fluorescent EVs were detected only in the presence of RIF, indicating that exposure to the drug alters EV content. Macrophages exposed to the EVs derived from RIF-treated cells released lower levels of cytokines, suggesting the EVs moderate immune responses. These data suggest that antibiotics can alter EV content to impact immunity. Our ability to see such changes in EV constituents directly results from exploiting these chemical probes.

Chronic Liver Disease and Cirrhosis Mortality Rates Are Disproportionately Increasing in Younger Women in the United States Between 2000-2020.

BACKGROUND & AIMS: Previous studies show that mortality from chronic liver disease (CLD) and cirrhosis is increasing in the United States. However, there are limited data on sex-specific mortality trends by age, race, and geographical location. The aim of this study was to conduct a comprehensive time-trend analysis of liver disease-related mortality rates in the National Center of Health Statistics (NCHS) database. METHODS: CLD and cirrhosis mortality rates between 20002020 (age-adjusted to the 2000 standard U.S. population) were collected from the NCHS database and categorized by sex and age into older adults (≥55 years) and younger adults (<55 years), race (Non-Hispanic-White, Non-Hispanic-Black, Hispanic, Non-Hispanic-American-Indian/Alaska-Native, and Non-Hispanic-Asian/Pacific-Islander), U.S. state, and cirrhosis etiology. Time trends, annual percentage change (APC), and average APC (AAPC) were estimated using Joinpoint Regression using Monte Carlo permutation analysis. We used tests for parallelism and identicalness for sex-specific pairwise comparisons of mortality trends (two-sided P value cutoff = .05). RESULTS: Between 20002020, there were 716,651 deaths attributed to CLD and cirrhosis in the U.S. (35.68% women). In the overall population and in older adults, CLD and cirrhosis-related mortality rates were increasing similarly in men and women. However, in younger adults (246,149 deaths, 32.72% women), the rate of increase was greater in women compared with men (AAPC = 3.04 vs 1.08, AAPC-difference = 1.96; P < .001), with non-identical non-parallel data (P values < .001). The disparity was driven by Non-Hispanic-White (AAPC = 4.51 vs 1.79, AAPC-difference = 2.71; P < .001) and Hispanic (AAPC = 1.89 vs -0.65, AAPC-difference = 2.54; P = .001) individuals. The disparity varied between U.S. states and was seen in 16 states, mostly in West Virginia (AAPC = 4.96 vs 0.88, AAPC-difference = 4.08; P < .001) and Pennsylvania (AAPC = 2.81 vs -1.02, AAPC-difference = 3.84; P < .001). Etiology-specific analysis did not show significant sex disparity in younger adults. CONCLUSIONS: Mortality rates due to CLD and cirrhosis in the U.S. are increasing disproportionately in younger women. This finding was driven by higher rates in Non-Hispanic White and Hispanic individuals, with variation between U.S. states. Future studies are warranted to identify the reasons for these trends with the ultimate goal of improving outcomes.

The TMEM16A channel as a potential therapeutic target in vascular disease.

PURPOSE OF REVIEW: The transmembrane protein 16A (TMEM16A) Ca 2+ -activated Cl - channel constitutes a key depolarising mechanism in vascular smooth muscle and contractile pericytes, while in endothelial cells the channel is implicated in angiogenesis and in the response to vasoactive stimuli. Here, we offer a critical analysis of recent physiological investigations and consider the potential for targeting TMEM16A channels in vascular disease. RECENT FINDINGS: Genetic deletion or pharmacological inhibition of TMEM16A channels in vascular smooth muscle decreases artery tone and lowers systemic blood pressure in rodent models. Inhibition of TMEM16A channels in cerebral cortical pericytes protects against ischemia-induced tissue damage and improves microvascular blood flow in rodent stroke models. In endothelial cells, the TMEM16A channel plays varied roles including modulation of cell division and control of vessel tone through spread of hyperpolarisation to the smooth muscle cells. Genetic studies implicate TMEM16A channels in human disease including systemic and pulmonary hypertension, stroke and Moyamoya disease. SUMMARY: The TMEM16A channel regulates vascular function by controlling artery tone and capillary diameter as well as vessel formation and histology. Preclinical and clinical investigations are highlighting the potential for therapeutic exploitation of the channel in a range of maladaptive states of the (micro)circulation.

Palliative care of COVID-19 patients with do-not-resuscitate status in underrepresented minorities.

BACKGROUND: The impact of the COVID-19 pandemic on palliative care intervention (PCIs) in patients with do-not-resuscitate (DNR) status remains uncertain. METHODS: Case-control study of patients with DNR order with RT-PCR confirmed SARS-COV2 infection (cases), and those with DNR order but without SARS-COV2 infection (controls). The primary outcome measures included timing and delivery of PCIs, and secondary measures included pre-admission characteristics and in-hospital death. RESULTS: The ethnicity distribution was comparable between 69 cases and 138 controls, including Black/African Americans (61% vs. 44%), Latino/Hispanics (16% vs. 26%) and White (9% vs. 20%) (trend-p = .54). Cases were employed more (17% vs. 6%, adjusted-p = .012), less frail (fit 47% vs. 21%; mildly frail 22% vs. 36%; frail 31% vs. 43%, trend-p = .018) and had fewer comorbidities than controls. Cases had higher chances of intensive care unit admission (HR 1.76 [95% CI: 1.03-3.02]) and intubation (53% vs. 30%, p = .002), lower chances to be seen by palliative care team (HR .46 [.30-.70]) and a longer time to palliative care visit than controls (ß per ln-day .67 [.00-1.34]). In the setting of no-visiting hospitals policy, we did not find significant increase in utilisation of video conferencing (22% vs. 13%) and religious services (12% vs. 12%) both in case and in controls. CONCLUSION: Do-not-resuscitate patients with COVID-19 had better general health and higher employment status than 'typical' DNR patients, but lower chances to be seen by the palliative care team. This study raises a question of the applicability of the current palliative care model in addressing the needs of DNR patients with COVID-19 during the pandemic.

Selumetinib in the Treatment of Orbital Plexiform Neurofibroma: A Case Report.

A 4-year-old boy with a known diagnosis of neurofibromatosis 1 (NF1) and a diffusely infiltrative plexiform neurofibroma (PN) of the left orbit was started on selumetinib treatment for progressively worsening amblyopia. The patient first presented with new-onset left ptosis at 11 months old. He subsequently developed refractory anisometropic amblyopia of the left eye, in addition to clinically significant left proptosis and hypoglobus that interfered with glasses wear for his amblyopia treatment. The plexiform neurofibroma was not amenable to surgical resection and selumetinib treatment was initiated 3 years after the initial diagnosis. The patient showed remarkable clinical and radiographic improvement in tumor burden after treatment. Best corrected visual acuity improved from 20/50 to 20/20- in his amblyopic eye. Relative proptosis of the affected eye also improved from 4mm to 2mm on Hertel measurements, which allowed for consistent glasses wear. Adverse effects from the treatment were limited to an acneiform rash, which resolved following dose reduction according to the FDA dosing guidelines.

A single-institution review of lacrimal gland biopsies between 1962 and 2017.

PURPOSE: To examine the clinical and histopathologic characteristics of lacrimal gland biopsies at a tertiary academic center. METHODS: A retrospective chart review of patients undergoing lacrimal gland biopsy or excision between 1962 and 2017 was performed via the ocular pathology specimen log. All cases were reviewed for demographics, clinical presentation, and histopathologic diagnoses. RESULTS: Four hundred and two eyes in 356 patients were included in the analysis. Median age was 49 (range 5-91) with a female predominance (255, 72%, p < .001). Most had unilateral involvement (308, 86.5%) and visual acuity of 20/50 or better (332 eyes, 83%). Limitation in extraocular motility was present in 71 eyes (18%), relative afferent pupillary defect in 10 eyes (2.5%), and intraocular pressure 20 mmHg or above in 80 eyes (20%). The pre-operative radiology report commented on the enlargement of the lacrimal gland in 236 eyes (58.7%), and lack thereof in 73 eyes (18.2%). The most common histopathologic diagnoses were nonspecific inflammation or orbital pseudotumor (170, 42%), lymphoma (65, 16%), pleomorphic adenoma (22, 5.5%), adenoid cystic carcinoma (19, 4.7%), granulomatous inflammation (19, 4.7%), and normal lacrimal gland (16, 4%). Three hundred and seven cases were benign (76%) and 95 malignant (24%). The biopsy specimen was diagnostic in 343 (85%), and non-diagnostic in 59 (15%). CONCLUSIONS: This is a comprehensive review of one of the largest ocular pathology databases of lacrimal gland lesions. This study confirms the wide range of inflammatory and neoplastic conditions affecting the lacrimal gland and highlights the nuances of histopathologic diagnoses and diagnostic yield of biopsies in clinical practice.

KCC2 is required for the survival of mature neurons but not for their development.

The K+/Cl- cotransporter KCC2 (SLC12A5) allows mature neurons in the CNS to maintain low intracellular Cl- levels that are critical in mediating fast hyperpolarizing synaptic inhibition via type A γ-aminobutyric acid receptors (GABAARs). In accordance with this, compromised KCC2 activity results in seizures, but whether such deficits directly contribute to the subsequent changes in neuronal structure and viability that lead to epileptogenesis remains to be assessed. Canonical hyperpolarizing GABAAR currents develop postnatally, which reflect a progressive increase in KCC2 expression levels and activity. To investigate the role that KCC2 plays in regulating neuronal viability and architecture, we have conditionally ablated KCC2 expression in developing and mature neurons. Decreasing KCC2 expression in mature neurons resulted in the rapid activation of the extrinsic apoptotic pathway. Intriguingly, direct pharmacological inhibition of KCC2 in mature neurons was sufficient to rapidly induce apoptosis, an effect that was not abrogated via blockade of neuronal depolarization using tetrodotoxin (TTX). In contrast, ablating KCC2 expression in immature neurons had no discernable effects on their subsequent development, arborization, or dendritic structure. However, removing KCC2 in immature neurons was sufficient to ablate the subsequent postnatal development of hyperpolarizing GABAAR currents. Collectively, our results demonstrate that KCC2 plays a critical role in neuronal survival by limiting apoptosis, and mature neurons are highly sensitive to the loss of KCC2 function. In contrast, KCC2 appears to play a minimal role in mediating neuronal development or architecture.

Cannabis Use is Associated With Reduced 30-Day All-cause Readmission Among Hospitalized Patients With Irritable Bowel Syndrome: A Nationwide Analysis.

BACKGROUND: Cannabinoid receptors are potential therapeutic targets in a variety of gastrointestinal tract disorders. The authors hypothesize that the use of cannabis use is associated with better control of symptoms associated with irritable bowel syndrome (IBS). This study aimed to examine the utilization of inpatient services by patients with IBS who did and did not report the use of cannabis. METHODS: This is a retrospective cohort study that utilized the 2016 Nationwide Readmissions Database. Inclusion criteria included a principal diagnosis of IBS. The primary outcome was 30-day hospital readmission rates for IBS-specific causes. Secondary outcomes included the 30-day hospital readmission rates for all causes, resource utilization, and the 5 most common principal diagnoses and independent risk factors associated with readmission. RESULTS: Of the 7163 patients with IBS identified in the National Readmission Database, 357 reported the use of cannabis. The 30-day IBS-specific readmission rates were 1.5% in patients who reported cannabis use and 1.1% in those who did not report cannabis use (P=0.53). Among the cannabis users, none of the variables evaluated served as a significant predictor of IBS-specific readmission; median income was a predictor for readmission among those who did not report cannabis use (odds ratio, 2.77; 95% confidence interval, 1.15-6.67; P=0.02). The 30-day readmission rates for all causes were 8.1% and 12.7% for patients who did and did not report cannabis use, respectively. After adjusting for confounders, the odds of 30-day readmission for all causes were lower among patients who reported cannabis use compared with those who did not (adjusted odds ratio, 0.53; 95% confidence interval, 0.28-0.99; P=0.04). The 5 most frequent diagnoses at readmission among patients who did not report cannabis use were enterocolitis because of Clostridioides difficile, IBS without diarrhea, sepsis, noninfective gastroenteritis and colitis, and acute kidney failure. By contrast, the 5 most frequent readmission diagnoses for cannabis users were cyclical vomiting, IBS with diarrhea, endometriosis, right upper quadrant abdominal pain, and nausea with vomiting. A discharge disposition of "against medical advice" was identified as an independent risk factor for 30-day hospital readmission for all causes among patients who reported cannabis use. By contrast, higher comorbidity scores and discharges with home health care were independent predictors of 30-day hospital readmission for all causes among patients who did not report cannabis use. Private insurance was an independent factor associated with lower rates of readmission for all causes among those who did not report cannabis use. CONCLUSION: Our review of the National Readmission Database revealed no statistically significant differences in 30-day readmission rates for IBS-specific causes when comparing patients who reported cannabis use with those who did not. However, the authors found that cannabis use was associated with reduced 30-day hospital readmission rates for all causes.

Complications of Endoscopic Retrograde Cholangiopancreatography in Patients With Previous Bariatric Surgery: A National Inpatient Sample Analysis, 2007-2013.

BACKGROUND: Bariatric surgery (BS) has been proven to be effective in the treatment of obesity and weight-related diseases, but the anatomic changes after BS make endoscopic retrograde cholangiopancreatography (ERCP) technically challenging. This study aims to assess the safety and clinical outcomes of ERCP in patients with previous BS. MATERIALS AND METHODS: The National Inpatient Sample from 2007 to 2013 was queried for hospitalizations of adults over 18 years of age with procedure diagnoses of ERCP. Those with prior BS were selected as cases and those without BS as controls. Case-control matching at a ratio of 1 case to 2 controls was performed based on sex, age, race, comorbidities, and obesity. The primary outcomes were inpatient mortality and ERCP-related complications. Multivariate regression analysis was used to identify independent risk factors associated to the primary outcomes. RESULTS: A total of 1,068,862 weighted hospitalizations with ERCP procedure codes were identified. Of these, 6689 with BS were selected as cases, and 13,246 were matched as controls. The reason for hospital admission was most often biliary stone disease (60.7% vs. 55.5%), followed by malignancy (3.5% vs. 12.1%) and cholangitis (7.7% vs. 4.5%) with and without BS, P<0.05. The BS group had lower rates of post-ERCP pancreatitis (0.1% vs. 1.3%), cholecystitis (0.1% vs. 0.3%), bleeding (1.0% vs. 1.4%), and inpatient mortality (0.2% vs. 0.5%), but had higher rates of cholangitis (5.0% vs. 3.7%) and systemic infections (6.2% vs. 4.8%), all P<0.05. CONCLUSIONS: BS group had lower post-ERCP pancreatitis, cholecystitis and bleeding while had more cholangitis, and systemic infection compared with those without BS. Also, BS was independently associated with reduced inpatient mortality after adjusted for age, race, and comorbidity.

Bilateral Leukemic Infiltration of the Lacrimal Sac in a Child.

An 8-year-old boy with a history of refractory acute lymphoblastic leukemia presented with left-sided periorbital erythema and painless enlargement of the lacrimal sac. MRI revealed a soft tissue mass on the floor of the left orbit, extending into the nasolacrimal sac and duct. Lacrimal sac biopsy was consistent with B-lymphoblastic leukemia. The patient was treated with chemotherapy and radiation with satisfactory remission of local disease. However, similar symptoms emerged shortly after on the contralateral side, and repeat MRI was concerning for new leukemic infiltration of the right lacrimal sac. Bone marrow biopsy revealed concurrent medullary relapse. Systemic chemotherapy was adjusted and radiation therapy of the right orbit was initiated. This is the first reported pediatric case of bilateral leukemic involvement of the lacrimal sac.

Ocular Adnexal MALT Lymphoma in Association With Rosai-Dorfman Disease in a Child.

A 12-year-old boy presented with persistent proptosis and periorbital swelling after a school altercation. MRI revealed a mass in the right superonasal orbit extending along the orbital roof to the frontal bone and right frontal sinus, and intracranially to the dura of the right frontal lobe. Immunohistochemistry revealed CD20- and CD43-positive B cells consistent with a low-grade B-cell lymphoma. The patient was diagnosed with stage I ocular adnexal MALT lymphoma and treated with radiation therapy, followed by systemic chemotherapy. However, an enhancing orbital and intracranial mass remained on follow-up imaging, leading to a repeat biopsy, which was consistent with a diagnosis of Rosai-Dorfman disease. This is the first reported pediatric case of ocular adnexal MALT lymphoma with subsequent development of Rosai-Dorfman disease.

Basal Cell Carcinoma and Eccrine Porocarcinoma of the Eyelid.

An 81-year-old woman presented with a progressively enlarging indurated, firm lesion encompassing one-third of the left upper eyelid. Four years prior, a similar lesion at that same site had been excised and diagnosed as a basal cell carcinoma. The patient underwent a full-thickness excision of the lesion with frozen section, cryotherapy, and reconstruction. A free tarsal graft and hard palate composite graft was used to reconstruct the posterior lamella. A Mustarde myocutaneous rotational flap was used to reconstruct the anterior lamella. Histopathology illustrated nests of pleomorphic basophilic cells with varying mitotic activity and immunohistochemical staining consistent with eccrine porocarcinoma. This case highlights similarities in the presentation and appearance of basal cell carcinoma and periorbital eccrine porocarcinoma. It is possible that there was de novo development of the 2 tumors on the eyelid or recurrence of a misdiagnosed eccrine porocarcinoma. Eccrine porocarcinomas are rare malignant sweat gland tumors associated with a risk of recurrence after excision and metastasis.

Orbital Hemorrhagic Necrosis, Globe Rupture, and Death From Intraorbital Injection of 1% Sodium Deoxycholate in a Murine Model.

PURPOSE: Deoxycholic acid (DCA) 1% is an injectable detergent indicated for submental fat reduction, although clinically it is being injected off-label for orbital fat prolapse. It is known to cause severe inflammation, local nerve dysfunction, and tissue necrosis, all of which could be catastrophic in the orbit and periocular region. This study evaluated the effects of periocular DCA on orbital and ocular adnexal tissues in a murine model. METHODS: Mice were treated via split-face intraorbital injections, subcutaneous injections, and topical cornea application with DCA versus phosphate-buffered saline. Whole heads were fixed, decalcified, and sectioned for orbital histology after 1-7 days. Matched pairs of human globes and mouse globes were immersed in either phosphate-buffered saline or 1% DCA for 72 hours. RESULTS: Six of 11 mice receiving intraorbital DCA injections died within minutes. Surviving mice developed severe orbital inflammatory necrosis. All orbits injected with phosphate-buffered saline were clinically and histologically normal. Six mice were treated with lower concentrations of DCA and all developed variable amounts of orbital inflammation, hemorrhage, and globe necrosis. Mice receiving subcutaneous DCA injection to the lower eyelid showed inflammatory necrosis, edema, and lid malposition. Topical application of DCA to mouse corneas caused no external or histologic changes. Human and mouse globes immersed ex vivo in DCA developed corneal edema and cataract formation without observable scleral changes. CONCLUSION: Intraorbital and periocular injection of DCA can cause devastating complications in a murine model, and significant caution is advised for off-label use in the periocular region.

Cutaneous eyelid melanoma in an African American child.

Cutaneous melanoma of the eyelid constitutes less than 2% of all eyelid malignancies. Such cases in the pediatric population are even rarer, and exceedingly so in darkly pigmented individuals. A 9-year-old African American boy presented with a left upper eyelid lesion. Biopsy was consistent with deep penetrating melanoma, and the patient underwent a wide local excision and sentinel node biopsy. One upper parotid sentinel node was positive, leading to further parotidectomy and selective neck dissection. The eyelid defect was reconstructed by primary closure after margin clearance. This is the first reported case of cutaneous eyelid melanoma in an African American child with nodal metastasis. Clinical features of melanoma in the pediatric population can be more atypical and higher index of suspicion is indicated. While rare, the diagnosis of melanoma in darkly pigmented patients is still possible and cannot be excluded without a definitive biopsy.

The chaperone Chs7 forms a stable complex with Chs3 and promotes its activity at the cell surface.

The polytopic yeast protein Chs3 (chitin synthase III) relies on a dedicated membrane-localized chaperone, Chs7, for its folding and expression at the cell surface. In the absence of Chs7, Chs3 forms high molecular weight aggregates and is retained in the endoplasmic reticulum (ER). Chs7 was reported to be an ER resident protein, but its role in Chs3 folding and transport was not well characterized. Here, we show that Chs7 itself exits the ER and localizes with Chs3 at the bud neck and intracellular compartments. We identified mutations in the Chs7 C-terminal cytosolic domain that do not affect its chaperone function, but cause it to dissociate from Chs3 at a post-ER transport step. Mutations that prevent the continued association of Chs7 with Chs3 do not block delivery of Chs3 to the cell surface, but dramatically reduce its catalytic activity. This suggests that Chs7 engages in functionally distinct interactions with Chs3 to first promote its folding and ER exit, and subsequently to regulate its activity at the plasma membrane.

Ankyrin-B p.S646F undergoes increased proteasome degradation and reduces cell viability in the H9c2 rat ventricular cardiomyoblast cell line.

Ankyrin-B (AnkB) is scaffolding protein that anchors integral membrane proteins to the cardiomyocyte cytoskeleton. We recently identified an AnkB variant, AnkB p.S646F (ANK2 c.1937 C>T) associated with a phenotype ranging from predisposition for cardiac arrhythmia to cardiomyopathy. AnkB p.S646F exhibited reduced expression levels in the H9c2 rat ventricular-derived cardiomyoblast cell line relative to wildtype AnkB. Here, we demonstrate that AnkB is regulated by proteasomal degradation and proteasome inhibition rescues AnkB p.S646F expression levels in H9c2 cells, although this effect is not conserved with differentiation. We also compared the impact of wildtype AnkB and AnkB p.S646F on cell viability and proliferation. AnkB p.S646F expression resulted in decreased cell viability at 30 h after transfection, whereas we observed a greater proportion of cycling, Ki67-positive cells at 48 h after transfection. Notably, the number of GFP-positive cells was low and was consistent between wildtype AnkB and AnkB p.S646F expressing cells, suggesting that AnkB and AnkB p.S646F affected paracrine communication between H9c2 cells differentially. This work reveals that AnkB levels are regulated by the proteasome and that AnkB p.S646F compromises cell viability. Together, these findings provide key new insights into the putative cellular and molecular mechanisms of AnkB-related cardiac disease.

Bilateral Poorly Differentiated Adenocarcinoma of the Lacrimal Gland With Tumor Regression After Treatment With Pembrolizumab.

An 85-year-old man presented with a 6-month history of worsening left proptosis and painless ophthalmoplegia. Imaging revealed an extensive intraconal and extraconal tumor extending to the level of the optic foramen, as well as the scalp, cheek, and the nasal bridge. Incisional biopsy was consistent with lacrimal gland adenocarcinoma. The patient underwent a left orbital exenteration followed by immunotherapy with pembrolizumab. The treatment was stopped prematurely after 5 cycles due to development of autoimmune colitis. Four months later, the patient developed new contralateral disease in the right orbit and an incisional biopsy again showed lacrimal gland adenocarcinoma. Following the incisional biopsy, no further treatment was administered, but over the ensuing 6 months, there was dramatic spontaneous regression of the tumor both clinically and radiographically. At 28 months, the patient is still alive with relatively stable disease.

Hard palate-dermis fat composite graft for reconstruction of contracted anophthalmic socket.

Purpose: To describe a novel technique of using a hard palate-dermis fat composite graft (HPDFG) for reconstruction of a contracted anophthalmic socket. Methods: Retrospective, noncomparative, interventional case series of four patients who underwent HPDFG placement by one surgeon between 2010 and 2017. Results: Six harvested HPDFGs were placed in four patients with contracted anophthalmic sockets. A harvested hard palate graft (HPG) and a dermis fat graft (DFG) were adjoined with sutures to form a composite graft. All adhesions and symblephara between the eyelid and the anterior surface of the anophthalmic socket were lysed. The HPG component was attached to the tarsal margin to vertically lengthen the eyelid. The free edge of the DFG was sutured to the cut edge of the bulbar conjunctiva to simultaneously expand the anterior conjunctival surface area and fornix volume. The line of union between the two grafts formed the apex of the new fornix. Four HPDFG were used to reconstruct both the upper and lower lid fornices in two severely contracted sockets. Three patients received post-operative 5-fluorouracil (5-FU) injections. Three patients underwent additional revisions with buccal mucous membrane graft, amniotic membrane graft, full-thickness skin graft, pedicle flap, and dermal fillers. All four patients achieved excellent cosmesis and comfortable prosthesis fit. Conclusions: Composite HPDFG is an effective method of reconstructing a contracted anophthalmic socket by restoring volume, lengthening the posterior lamella, and expanding the fornix to allow for successful prosthesis retention. Adjunctive use of 5-FU injections can delay post-operative cicatrization.

Ocular and cerebral infarction from periocular filler injection.

A 20-year-old woman presented with loss of vision in her right eye and a "black nose" after receiving hyaluronic acid filler injections in her right glabella 1 month prior. Her vision was no light perception, and external examination revealed resolving skin necrosis at the nasal tip. A dilated fundus exam showed a fibrotic membrane emanating from a pale optic nerve and a diffusely atrophic retina with sclerotic vessels. An MRI demonstrated scattered right-sided parietal lobe infarcts. These findings were consistent with inadvertent cannulation of the supraorbital artery, followed by injection of filler into the internal carotid circulation. The product traveled in a retrograde fashion, occluding the right ophthalmic artery, right dorsal nasal artery, and arterial segments to the Circle of Willis. This case highlights the importance of understanding the complex vascular architecture of the periorbita and the mechanism by which such occlusions occur.