Thirty Years of Experience With Ocular Adnexal T-Cell Lymphoma.

PURPOSE: To evaluate the disease characteristics and survival of patients with ocular adnexal T-cell lymphoma. METHODS: A retrospective, observational study of patients with a histopathological diagnosis of T-cell lymphoma of the ocular adnexa seen between 1992 and 2022. Demographic data, clinical presentation, imaging, histology, immunohistochemistry, treatment, and outcomes were reviewed. RESULTS: Fifteen patients were included in the study with the mean age at diagnosis of 50 years old (range 7-85). The most common presenting symptoms were ulcerated eyelid skin lesions (40%) followed by eyelid swelling (13.3%), and lacrimal passageways obstruction (13.3%). The anaplastic large cell lymphoma (33%) and primary cutaneous T-cell lymphoma (33%) were the most diagnosed peripheral T-cell lymphoma subtypes, followed by the nasal type natural killer/T-cell lymphoma (27%) and peripheral T-cell lymphoma not otherwise specified (7%). The most prevalent stage of disease progression was stage I and stage IV (Ann Arbor classification) with seven (47%) patients each. Eight (53%) patients succumbed to the disease process of which three (37.5%) deceased in the first six months and six (75%) within the first year of diagnosis. We identified a strong statistical association between stage and disease-related death ( p = 0.003). CONCLUSIONS: Peripheral T-cell lymphoma occurring in the orbit and ocular adnexa is extremely rare. Advanced stage at diagnosis leads to almost certain death from the disease despite aggressive local and systemic treatment. Early diagnosis improves the chances of survival but can be hindered by this condition's ability to simulate benign inflammatory conditions both clinically and histologically.

Long term follow-up of congenital infantile fibrosarcoma of the orbital region.

We present the long-term follow-up of a case of periorbital congenital infantile fibrosarcoma (CIFS) treated with chemotherapy and surgery. The tumor was detected on a routine prenatal ultrasound at 30 weeks of gestation and diagnosed via an orbital biopsy day 9 postnatal age. The patient underwent chemotherapy and surgical debulking within the first 3 months of life and has maintained complete tumor remission for 7 years. The case highlights that early recognition and prompt treatment of periorbital CIFS can lead to complete long-term remission of this uncommon malignancy.

Granulomatosis with polyangiitis-associated sclerokeratitis in a case of ocular adnexal B-cell lymphoma.

We describe the first reported case of granulomatosis polyangiitis (GPA)-associated sclerokeratitis in a patient with treated ocular adnexal lymphoma (OAL). The patient presented with pain and decreased vision in the left eye over several weeks. Past medical history was significant for recent bilateral relapsing OAL that was treated successfully with radiotherapy. Examination of the eyes revealed sectoral scleritis and peripheral ulcerative keratitis. Magnetic resonance imaging (MRI) of the orbits excluded recurrence of OAL and serum antineutrophil cytoplasmic autoantibody (ANCA) titres confirmed the diagnosis of GPA. Disease was poorly responsive to systemic steroids, azathioprine and rituximab. Ultimately, resolution was achieved with successive subconjunctival dexamethasone and subconjunctival triamcinolone injections. This case highlights the need to consider ocular inflammation in patients with a history of malignant hemopathies.

Bridge helix arginines play a critical role in Cas9 sensitivity to mismatches.

The RNA-programmable DNA-endonuclease Cas9 is widely used for genome engineering, where a high degree of specificity is required. To investigate which features of Cas9 determine the sensitivity to mismatches along the target DNA, we performed in vitro biochemical assays and bacterial survival assays in Escherichia coli. We demonstrate that arginines in the Cas9 bridge helix influence guide RNA, and target DNA binding and cleavage. They cluster in two groups that either increase or decrease the Cas9 sensitivity to mismatches. We show that the bridge helix is essential for R-loop formation and that R63 and R66 reduce Cas9 specificity by stabilizing the R-loop in the presence of mismatches. Additionally, we identify Q768 that reduces sensitivity of Cas9 to protospacer adjacent motif-distal mismatches. The Cas9_R63A/Q768A variant showed increased specificity in human cells. Our results provide a firm basis for function- and structure-guided mutagenesis to increase Cas9 specificity for genome engineering.

A rare case of epithelial-myoepithelial carcinoma arising ex pleomorphic adenoma of the lacrimal gland: case report and review of the literature.

A 92-year-old man presented with progressively worsening eye pain, diplopia on lateral gaze and blurred vision for the past 12 months. Radiological imaging confirmed a large left lacrimal gland lesion. The patient subsequently underwent a superio-lateral orbitotomy with left dacryoadenectomy and tumor removal, histopathology subsequently confirmed an epithelial-myoepithelial carcinoma arising ex pleomorphic adenoma of the lacrimal gland. Epithelial-myoepithelial carcinoma is a rare lacrimal gland tumour and the authors believe this case to be the first reported in the Australian population and associated with prolonged eye pain.

Temporal Analysis of Serial Donations Reveals Decrease in Neutralizing Capacity and Justifies Revised Qualifying Criteria for Coronavirus Disease 2019 Convalescent Plasma.

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) received an Emergency Use Authorization by the US Food and Drug Administration (FDA). CCP with a signal-to-cutoff ratio of ≥12 using the Ortho VITROS severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) test (OVSARS2IgG) is permitted to be labeled "high titer." Little is known about the relationship between OVSARS2IgG ratio and neutralizing capacity of plasma/sera against genuine SARS-CoV-2. METHODS: Nine hundred eighty-one samples from 196 repeat CCP donors 0-119 days post-initial donation (DPID) were analyzed. Neutralizing capacity was assessed for 50% (PRNT50) and 90% (PRNT90) reduction of infectious virus using the gold standard plaque reduction neutralization test (PRNT). A subset of 91 donations was evaluated by OVSARS2IgG and compared to PRNT titers for diagnostic accuracy. RESULTS: Of donations, 32.7%/79.5% (PRNT90/PRNT50) met a 1:80 titer initially but only 14.0%/48.8% (PRNT90/PRNT50) met this cutoff ≥85 DPID. Correlation of OVSARS2IgG results to neutralizing capacity allowed extrapolation to CCP therapy results. CCP with OVSARS2IgG ratios equivalent to a therapeutically beneficial group had neutralizing titers of ≥1:640 (PRNT50) and/or ≥1:80 (PRNT90). Specificity and positive predictive value of the OVSARS2IgG for qualifying highly neutralizing CCP was optimal using ratios significantly greater than the FDA cutoff. CONCLUSIONS: This information provides a basis for refining the recommended properties of CCP used to treat COVID-19.

Three Years of Shared Service HIV Nucleic Acid Testing for Public Health Laboratories: Worthwhile for HIV-1 but Not for HIV-2.

BACKGROUND: In 2016, HIV-2 nucleic acid testing (NAT) was added to a shared service program that conducts HIV-1 NAT for public health laboratories performing the recommended algorithm for diagnosing HIV. Here, we evaluate the usefulness of HIV-2 NAT in this program as compared with HIV-1 NAT. METHODS: Specimens eligible for HIV-1 NAT were reactive on an HIV-1/2 antibody or antigen/antibody initial test and nonreactive or indeterminate on a supplemental antibody test or were reactive for HIV-1 antigen-only on an HIV-1/2 antigen/antibody initial test. Specimens eligible for HIV-2 NAT were reactive on an initial test, HIV-2 indeterminate or HIV indeterminate on a supplemental antibody test and had no detectable HIV-1 RNA or were reactive for HIV-2 antibody on an HIV-1/2 antigen/antibody test, and this reactivity was not confirmed with a supplemental antibody assay. All specimens were tested in a reference laboratory using APTIMA HIV-1 qualitative RNA and/or a validated qualitative HIV-2 RNA real-time PCR assay. RESULTS: During 2016 to 2019, HIV-1 RNA was detected in 234 (14%) of 1731 specimens tested. HIV-2 RNA was not detected in 52 specimens tested. Median time from specimen collection to reporting of HIV-1 and HIV-2 NAT results by year ranged from 9 to 10 days and from 22 to 27 days, respectively. Two specimens with HIV-2 indeterminate results on a supplemental antibody test had detectable HIV-1 RNA. CONCLUSIONS: A shared service model for HIV-1 NAT is both feasible and beneficial for public health laboratories. However, because no HIV-2 infections were detected, our data suggest that this program should reconsider the usefulness of HIV-2 NAT testing.

Orbital Schwannoma-Management and Clinical Outcomes.

PURPOSE: To evaluate the clinical features, management, and outcomes of orbital schwannomas. METHODS: Retrospective study analyzing 20 orbital schwannomas in 18 patients managed in an orbital service over 26 years. Clinical, radiological, histological, and surgical procedural data were analyzed. RESULTS: Mean age of the study population was 40.89 ± 20.84 years. The most common nerve of origin was frontal nerve (50%), and majority of patients (70%) had a superior and/or posteriorly located tumor. Five patients (27.8%) had optic neuropathy at presentation, and 3 of them showed improved vision after intervention. Surgical resection was performed for all except for 1 patient who underwent fractionated stereotactic radiotherapy. Six subjects had extension of tumor into the cavernous sinus, and 3 of them underwent combined neurosurgical intervention with stereotactic neuronavigation. Outcomes were largely favorable with majority achieving complete excision. Two out of 6 incomplete resections experienced regrowth requiring second surgical intervention. Surgical complications include decreased vision, diplopia, ptosis, and mydriasis. CONCLUSION: Orbital schwannomas are uncommon slow-growing tumors which can result in visual loss. Prognosis can be favorable even in presence of pre-operative optic neuropathy if there is early intervention. Schwannomas confined to the orbit can usually be completely excised with good outcomes. Schwannomas extending intra-cranially may undergo incomplete excision to preserve vital structures, leaving residual disease, but generally have satisfactory results. Stereotactic neuronavigation and frozen section are useful intra-operative tool to aid management and minimize complications. Fractionated radiotherapy can be considered as an alternative or adjunctive treatment for patients not amenable for surgical resections.

Primitive Myxoid Mesenchymal Tumor of Infancy in the Orbit: A New Location for a Rare Tumor.

Primitive myxoid mesenchymal tumor of infancy is a rare subtype of sarcoma. With the advent of relevant immunohistochemical and genetic analysis, it was defined by Alaggio et al. in a 2006 case series. Since then, 25 further cases are described in the literature-arising variably from the neck, chest, scalp, abdomen, back, or limbs. Here it is described for the first time arising in the orbit, confirmed by identification of BCOR immunopositivity with internal tandem duplication. All specialties involved in the management of orbital masses should be aware of the subtypes of sarcomas found in the orbit as approaches to their management may change depending on the diagnosis. As more cases are identified, a better understanding of this tumor's clinical behavior and appropriate management can be established.

Bony orbital changes in allergic fungal sinusitis are reversible after treatment.

Allergic fungal sinusitis (AFS) arises from a host hypersensitivity reaction to fungi residing within the sino-nasal tract. Computed tomography imaging may show heterogenous sinus opacification with bony erosion and expansion into the orbits. With advanced orbital involvement there is a risk of optic neuropathy and irreversible vision loss. We present a patient with AFS who presented with bilateral proptosis and early optic neuropathy. Radiologically, there was evidence of bony erosion and orbital wall compression. Following oral corticosteroids and full-house endoscopic sinus surgery, these changes reversed considerably. This case shows that bony and anatomical orbital changes from AFS are reversible with adequate surgical treatment.

Project ESTEEM protocol: a randomized controlled trial of an LGBTQ-affirmative treatment for young adult sexual minority men's mental and sexual health.

BACKGROUND: Young gay and bisexual men disproportionately experience depression, anxiety, and substance use problems and are among the highest risk group for HIV infection in the U.S. Diverse methods locate the source of these health disparities in young gay and bisexual men's exposure to minority stress. In fact, minority stress, psychiatric morbidity, substance use, and HIV risk fuel each other, forming a synergistic threat to young gay and bisexual men's health. Yet no known intervention addresses minority stress to improve mental health, substance use problems, or their joint impact on HIV risk in this population. This paper describes the design of a study to test the efficacy of such an intervention, called ESTEEM (Effective Skills to Empower Effective Men), a 10-session skills-building intervention designed to reduce young gay and bisexual men's co-occurring health risks by addressing the underlying cognitive, affective, and behavioral pathways through which minority stress impairs health. METHODS: This study, funded by the National Institute of Mental Health, is a three-arm randomized controlled trial to examine (1) the efficacy of ESTEEM compared to community mental health treatment and HIV counseling and testing and (2) whether ESTEEM works through its hypothesized cognitive, affective, and behavioral minority stress processes. Our primary outcome, measured 8 months after baseline, is condomless anal sex in the absence of PrEP or known undetectable viral load of HIV+ primary partners. Secondary outcomes include depression, anxiety, substance use, sexual compulsivity, and PrEP uptake, also measured 8 months after baseline. DISCUSSION: Delivering specific stand-alone treatments for specific mental, behavioral, and sexual health problems represents the current state of evidence-based practice. However, dissemination and implementation of this one treatment-one problem approach has not been ideal. A single intervention that reduces young gay and bisexual men's depression, anxiety, substance use, and HIV risk by reducing the common minority stress pathways across these problems would represent an efficient, cost-effective alternative to currently isolated approaches, and holds great promise for reducing sexual orientation health disparities among young men. TRIAL REGISTRATION: Registered October 10, 2016 to ClinicalTrials.gov Identifier: NCT02929069 .

Endovascular treatment of carotid-cavernous sinus fistulas: ophthalmic and visual outcomes.

Purpose: The main objective was to report the epidemiology, clinical manifestations, angiography features, treatment modality and post-treatment outcomes in patients diagnosed with carotid cavernous fistulas (CCF). Methods: A retrospective review of the medical imaging database in conjunction with medical records from 2004 to 2017 at the Royal Brisbane and Women's Hospital (RBWH) was conducted.We identified 39 patients with CCF (16 direct, 23 indirect). A total of 37 diagnoses were confirmed by direct catheter angiography. The remaining two cases were diagnosed using magnetic resonance imaging/magnetic resonance angiography. Results: Coils were deployed in 100% of direct and 83% of treated indirect fistulas that were treated. Other embolic agents were deployed alone or in combination with coils. Successful angiographic closure was achieved in 93% of direct and 92% of indirect fistulas. Multiple treatments were required in 33% of direct and 16% of indirect fistulas. Visual acuity improved in patients with direct fistulae(p = 0.02) and was preserved in those with indirect fistulae. Post-treatment diplopia persisted in six patients with direct fistulas and three patients with indirect fistulas. Four patients with indirect fistulas experienced persistent ocular hypertension post-treatment compared to two patients with direct fistulas. Conclusions: Endovascular coils are the most commonly deployed treatment for CCF. Both indirect and direct fistulas achieved high rates of closure; however, indirect fistulas were less likely to require multiple treatments. Good post-procedural vision was achieved for both groups.

Observed Emotional Expressivity, Posttraumatic Stress Disorder Symptoms, and Intimate Partner Violence Perpetration Among Community Couples.

Impaired emotional processes are related to posttraumatic stress disorder (PTSD) and are implicated in intimate partner violence (IPV) perpetration. To address the interpersonal context of PTSD, emotion, and IPV, we examined interactions among one's own and one's partner's emotional expressivity and PTSD symptom severity in association with IPV perpetration. Heterosexual couples (N = 56) in which at least one partner met screening criteria for PTSD engaged in two video-recorded discussions about negative and positive aspects of their relationships. Videos were coded for observed emotional expressiveness during moments participants reported experiencing significant emotions. Actor-partner interdependence models revealed few main effects of emotional expressivity, except that women's expressivity of positive emotions was positively associated with men's IPV perpetration, r2adj = .14. Emotional expressivity played a larger role among couples managing PTSD symptoms; that is, the association between one's own PTSD symptom severity and more IPV perpetration was stronger among men who expressed more negative emotions, r2adj = .19, and women who expressed fewer negative emotions, r2adj = .21. Several partner effects suggested the importance of understanding the dyadic nature of these constructs. For example, men's PTSD symptom severity was differentially associated with each partners' IPV perpetration based on women's expressivity of positive emotion, r2adj = .22-.27. Understanding of emotional expressivity in the link between PTSD and IPV must include consideration of gender differences in how these constructs operate interpersonally. Strategies to promote moderate and safe communication of positive and negative emotions may prevent IPV escalation, particularly among couples managing PTSD symptoms.

Effects of temperature and salinity on prevalence and intensity of infection of blue crabs, Callinectes sapidus, by Vibrio cholerae, V. parahaemolyticus, and V. vulnificus in Louisiana.

Coastal marine and estuarine environments are experiencing higher average temperatures, greater frequency of extreme temperature events, and altered salinities. These changes are expected to stress organisms and increase their susceptibility to infectious diseases. However, beyond these generalities, little is known about how environmental factors influence host-pathogen relationships in the marine realm. We investigated the prevalence and intensity of infections by Vibrio cholerae, V. parahaemolyticus, and V. vulnificus in blue crabs, Callinectes sapidus, from Louisiana saltmarshes in relation to temperature and salinity. We evaluated relationships for single measurements taken at the time of collection and for more complex measurements representing accumulated exposure to physiologically-stressful environmental conditions for up to 31 days prior to collection. We found that: (1) prevalence of infection varied across the Louisiana coast, (2) prevalence of all three Vibrio species was influenced by temperature and salinity, and (3) measurements that represent accumulated exposure to extreme conditions are useful predictors of infection prevalence and can provide insights into underlying biological mechanisms.

Soft Tissue Metrics in Thyroid Eye Disease: An International Thyroid Eye Disease Society Reliability Study.

PURPOSE: To determine the reliability of 3 scales for assessing soft tissue inflammatory and congestive signs associated with thyroid eye disease. METHODS: This was a multicentered prospective observational study, recruiting 55 adults with thyroid eye disease from 9 international centers. Six thyroid eye disease soft tissue features were measured; each sign graded using 3 scales (presence/absence [0-1], 3-point scale [0-2], and percentage [0-100]). Each eye was graded twice by 2 independent raters. Accuracy (fraction of agreement) was calculated between the 2 trials for each rater (intrarater reliability) and between raters for all trials (interrater reliability) to determine the most sensitive scale for each feature that maintained a threshold of agreement greater than 0.70. Trial, intrarater reliability, and interrater reliability were determined by accuracy measurement of agreement for each inflammatory/congestive feature. RESULTS: Fifty-five patients had 218 assessments for 6 thyroid eye disease metrics. The intrarater reliability for each feature was consistently better than the interrater reliabilities. Using an agreement of 0.70 or better, for the interrater tests, conjunctival and eyelid edema could be reliably measured using the 0-1 or 0-2 scale while conjunctival and eyelid redness could only be reliably measured with the binary 0-1 scale. Caruncular edema and superior conjunctival redness could not be measured reliably between 2 raters with any scale. The percentage scale had poor agreement unless slippage intervals of >20% were allowed on either side of the measurements. CONCLUSIONS: Of the specific periocular soft tissue inflammatory features measured between raters in the Clinical Activity Score and Vision, Inflammation, Strabismus, Appearance scales, edema of the eyelids and conjunctiva could reliably be measured by both 0-1 and 0-2 scales, erythema of the eyelid and bulbar conjunctiva could reliably be measured only by the 0-1 scale, and the other parameters of superior bulbar erythema and caruncular edema were not reliably measured by any scale.

Loss of ecosystem services due to chronic pollution of forests and surface waters in the Adirondack region (USA).

Sustaining recent progress in mitigating acid pollution could require lower emissions caps that will give rise to real or perceived tradeoffs between healthy ecosystems and inexpensive energy. Because most impacts of acid rain affect ecosystem functions that are poorly understood by policy-makers and the public, an ecosystem services (ES) framework can help to measure how pollution affects human well-being. Focused on the Adirondack region (USA), a global 'hot-spot' of acid pollution, we measured how the chronic acidification of the region's forests, lakes, and streams has affected the potential economic and cultural benefits they provide to society. We estimated that acid-impaired hardwood forests provide roughly half of the potential benefits of forests on moderate to well-buffered soils - an estimated loss of ∼ $10,000 ha-1 in net present value of wood products, maple syrup, carbon sequestration, and visual quality. Acidic deposition has had only nominal impact - relative to the effects of surficial geology and till depth - on the capacity of Adirondack lakes and streams to provide water suitable for drinking. However, as pH declines in lakes, the estimated value of recreational fishing decreases significantly due to loss of desirable fish such as trout. Hatchery stocking programs have partially offset the pollution-mediated losses of fishery value, most effectively in the pH range 4.8-5.5, but are costly and limited in scope. Although any estimates of the monetary 'damages' of acid rain have significant uncertainties, our findings highlight some of the more tangible economic and cultural benefits of pollution mitigation efforts, which continue to face litigation and political opposition.

Molecular detection of the parasitic dinoflagellate Hematodinium perezi from blue crabs Callinectes sapidus in Louisiana, USA.

The dinoflagellate Hematodinium perezi is a prolific pathogen of the blue crab Callinectes sapidus along the Atlantic and Gulf of Mexico coasts of North America. High prevalence, sometimes approaching 100%, and outbreaks with high mortality are associated with higher salinities. H. perezi has not been reported previously in blue crabs from Louisiana, USA, where salinities in coastal habitats are generally below the parasite's favorable range. However, the possibility that H. perezi infects blue crabs in higher salinity habitats offshore has not been investigated. A PCR-based test for H. perezi was used to screen blue crabs collected from both high and low salinity areas. These included juvenile and adult crabs from inshore marshes where salinities are relatively low and from higher salinity offshore shoals that are spawning sites for females. H. perezi was detected in blue crabs from offshore shoals (prevalence=5.6%) but not in juvenile or adult crabs from inshore habitats. Megalopae (post-larvae) were also collected from inshore locations. Although megalopae settle inshore where salinities are relatively low, the megalopal stage is preceded by a planktonic phase in higher salinity offshore waters. We detected H. perezi in 11.2% of settling megalopae tested. Although the prevalence of H. perezi was relatively low within our samples, if spawning females and megalopae are especially vulnerable, the impact on the population could be compounded. This is the first report of H. perezi from blue crabs in Louisiana and demonstrates the importance of examining all life stages in determining the prevalence of a harmful parasite.

Surgical Management of Cicatricial Ectropion in Pityriasis Rubra Pilaris.

Pityriasis rubra pilaris is an idiopathic, papulosquamous dermatological disease. It is clinically and histologically distinct from, but may resemble, psoriasis. Pityriasis rubra pilaris can be self-limiting but may also run a protracted, relapsing course. Medical treatment may involve topical emollients, systemic retinoids, methotrexate, and/or tumor necrosis factor antagonists. Ocular complications include cicatricial ectropion. The authors describe the surgical management of 3 patients with cicatricial ectropion secondary to pityriasis rubra pilaris. All patients had procedures involving skin grafts; 1 patient required multiple operations. The management principles are discussed, including the role and timing of surgery, within the context of emerging treatments for pityriasis rubra pilaris. Patients with pityriasis rubra pilaris and cicatricial ectropion should be closely managed by both ophthalmologist and dermatologist. The eyelid position may improve with conservative or surgical measures. If surgery is required, the limitations of skin grafting under these circumstances should be anticipated and patients counseled appropriately.

Ocular Findings in Alemtuzumab (Campath-1H)-induced Thyroid Eye Disease.

Alemtuzumab (Campath-1H) is a humanized anti-CD52 monoclonal antibody used in the treatment of multiple sclerosis (MS). Studies demonstrate significant reduction in relapse risk and the risk of accumulating sustained disability. Adverse events include infusion-associated reactions, infections, and secondary autoimmunity. Systemic thyroid disease is the most common secondary autoimmune event and affects up to approximately 30% of treated patients. This is the first description of the ocular findings and management in a case of thyroid eye disease (Graves' Ophthalmopathy [GO]) following alemtuzumab therapy. The ocular disease was managed conservatively while the systemic Graves' was managed with thyroidectomy.