Topical and Subcutaneous Interferon-Alpha for the Treatment of Refractory Inflammatory Macular Edema.

PURPOSE: To evaluate the efficacy of topical interferon alpha-2b (tIFN a2b) and subcutaneous pegylated interferon alpha-2a (peg-IFN a2a) in the treatment of refractory pseudophakic (PME) and uveitic (UME) macular edema. METHODS: Retrospective case series of patients with PME or UME that was non-responsive to conventional therapies. Topical IFN a2b drops (1 MIU/ml) were commenced four times a day. Non-responders were offered treatment with subcutaneous peg-IFN a2a starting at 180 mcg weekly. RESULTS: Seven eyes of seven patients (three UME and four PME) were treated with tIFN a2b. Three eyes had complete ME resolution with tIFN treatment after a mean of 2.66 weeks (range 1-4 weeks) and no recurrence after a mean total course of 11.33 weeks (range 5-20 weeks). Two cases (both PME) had partial responses to tIFN treatment and two cases (both UME) failed to respond. Of the four eyes that incompletely responded to tIFN (treatment range 6 weeks to 4 months), three were treated with peg-IFN a2a, which invariably led to complete and sustained ME resolution. Adverse effects from topical treatment were mild and consisted mainly of superficial irritation. Adverse effects of subcutaneous treatment included nausea, vomiting, anorexia, and leukopenia, though none limited treatment. CONCLUSIONS: Topical IFNa-2b appears safe and effective in isolation or in conjunction with topical steroids for the treatment of inflammatory macular edema (IME) in about half of patients in our small series. All partial and non-responders had complete disease resolution with systemic IFN. Topical IFN a2b should be considered in patients with refractory IME.

A Case of Lepromatous Leprosy (Lucio's Phenomenon) Presenting as Periorbital Edema.

Despite low prevalence of leprosy worldwide, new cases continue to present and require swift evaluation and diagnosis to prevent complications. Here, we describe a case of lepromatous leprosy with Lucio's phenomenon initially presenting with facial and periorbital edema. A 38-year-old Brazilian woman presented to the emergency department with facial swelling and erythema, initially treated as cellulitis. Due to rapid worsening despite broad-spectrum antibiotics, she underwent soft tissue exploration and biopsy due to concern for necrotizing fasciitis. During her course, she also developed retiform purpura of bilateral upper and lower extremities. Periorbital and lower extremity pathological specimens ultimately revealed acid-fast bacilli consistent with Mycobacterium leprae , and the patient improved with multidrug therapy. This case illustrates the diagnostic difficulty of lepromatous leprosy with Lucio's phenomenon, which can initially present with periorbital edema.

Adverse Ocular Effects of Systemic Medications.

While ocular complications of systemic medications are uncommon, it is important to recognize that vision-threatening toxicities can occur. This review details the vision-threatening adverse effects of a select group of commonly prescribed systemic medications and describes the recommended screening guidelines for those that are particularly high risk.

Penicillin Responsive Presumed Seronegative Ocular Syphilis in a Patient with Human Immunodeficiency Virus: A Case Report and Review of the Literature.

Ocular and systemic syphilis are well known to mimic other clinical entities making them challenging to diagnose in many cases. Syphilis testing plays an important role in diagnosis and timely treatment. Here we describe a patient with untreated human immunodeficiency virus (HIV) infection who presented with bilateral panuveitis with repeatedly negative syphilis serologies. In light of worsening retinitis while on aggressive anti-viral treatment and in consideration of the clinical suspicion for syphilitic uveitis, intravenous penicillin was initiated empirically. The patient demonstrated significant improvement subjectively and objectively after treatment. We also review and discuss syphilis testing reliability generally and in HIV co-infected patients in particular. Empiric intravenous penicillin should be considered in patients with clinical features of ocular syphilis despite negative serologic testing, especially in those with HIV co-infection.

Novel Representation of an Integrated Correlator in N=4 Supersymmetric Yang-Mills Theory.

An integrated correlator of four superconformal stress-tensor primaries of N=4 supersymmetric SU(N) Yang-Mills theory (SYM), originally obtained by localization, is reexpressed as a two-dimensional lattice sum that is manifestly invariant under SL(2,Z) S duality. This expression is shown to satisfy a novel Laplace equation in the complex coupling constant τ that relates the SU(N) integrated correlator to those of the SU(N+1) and SU(N-1) theories. The lattice sum is shown to precisely reproduce known perturbative and nonperturbative properties of N=4 SYM for any finite N, as well as extending previously conjectured properties of the large-N expansion.

Adult-onset asthma and periocular xanthogranuloma - A rare infiltrative disease of the orbit and eyelid.

PURPOSE: To present a case of adult onset asthma with periocular xanthogranuloma (AAPOX), and discuss existing literature on adult orbital xanthogranulomatous diseases (AOXGDs) and their treatment. OBSERVATIONS: A 63 year old male presented with progressive bilateral eyelid swelling with overlying yellow plaques associated with asthma. CT scan showed periorbital swelling with enlargement of the superior and lateral rectus muscles bilaterally. Biopsy demonstrated orbital xanthogranulomatous disease with increased IgG4 plasma cells. The patient was treated with intralesional triamcinolone, oral prednisone, and cyclophosphamide without significant improvement. Surgical debulking was eventually performed which improved his external symptoms until he was lost to follow up 15 months later. CONCLUSIONS AND IMPORTANCE: AOXGDs are a group of rare infiltrative diseases of the eyelids and orbit that can be associated with significant systemic morbidities. While they all have similar underlying histopathologic features, appreciating the clinical difference between these diseases is important in understanding patient prognosis and ensuring appropriate clinical monitoring. There is also growing research demonstrating that AAPOX, along with other AOXGDs, may represent part of a continuum of IgG4 related disease, similar to what is seen in this case. There is currently no reliably effective treatment for AOXGDs, and additional research into the management of these diseases is necessary.

Prognosticating Outcomes and Nudging Decisions with Electronic Records in the Intensive Care Unit Trial Protocol.

Expert recommendations to discuss prognosis and offer palliative options for critically ill patients at high risk of death are variably heeded by intensive care unit (ICU) clinicians. How to best promote such communication to avoid potentially unwanted aggressive care is unknown. The PONDER-ICU (Prognosticating Outcomes and Nudging Decisions with Electronic Records in the ICU) study is a 33-month pragmatic, stepped-wedge cluster randomized trial testing the effectiveness of two electronic health record (EHR) interventions designed to increase ICU clinicians' engagement of critically ill patients at high risk of death and their caregivers in discussions about all treatment options, including care focused on comfort. We hypothesize that the quality of care and patient-centered outcomes can be improved by requiring ICU clinicians to document a functional prognostic estimate (intervention A) and/or to provide justification if they have not offered patients the option of comfort-focused care (intervention B). The trial enrolls all adult patients admitted to 17 ICUs in 10 hospitals in North Carolina with a preexisting life-limiting illness and acute respiratory failure requiring continuous mechanical ventilation for at least 48 hours. Eligibility is determined using a validated algorithm in the EHR. The sequence in which hospitals transition from usual care (control), to intervention A or B and then to combined interventions A + B, is randomly assigned. The primary outcome is hospital length of stay. Secondary outcomes include other clinical outcomes, palliative care process measures, and nurse-assessed quality of dying and death.Clinical trial registered with clinicaltrials.gov (NCT03139838).

Telecritical Care Clinical and Operational Strategies in Response to COVID-19.

Background: The cororavirus disease 19 (COVID-19) pandemic has strained intensive care unit (ICU) material and human resources to global crisis levels. The risks of staffing challenges and clinician exposure are of significant concern. One resource, telecritical care (TCC), has the potential to optimize efficiency, maximize safety, and improve quality of care provided amid large-scale disruptions, but its role in pandemic situations is only loosely defined. Planning and Preparation Phase: We propose strategic initiatives by which TCC may act as a force multiplier for pandemic preparedness in response to COVID-19, utilizing a tiered approach for increasing surge capacity needs. The goals involved usage of TCC to augment ICU capacity, optimize safety, minimize personal protective equipment (PPE) use, improve efficiencies, and enhance knowledge of managing pandemic response. Implementation Phase: A phased approach utilizing TCC would involve implementing remote capabilities across the enterprise to accomplish the goals outlined. The hardware and software needed for initial expansion to cover 275 beds included $956,670 for mobile carts and $173,106 for home workstations. Team role deployment and bedside clinical care centering around TCC as critical care capacity expand beyond 275 beds. Surge capacity was not reached during early phases of the pandemic in the region, allowing refinement of TCC during subsequent pandemic phases. Conclusions: Leveraging TCC facilitated pandemic surge planning but required redefinition of typical ICU staffing models. The design was meant to workforce efficiencies, reduce PPE use, and minimize health care worker exposure risk, all while maintaining quality care standards through an intensivist-led model. As health care operations resumed and states reopened, TCC is being used to support shifts in volume and critical care personnel during the pandemic evolution. The lessons applied may help health care systems through variable phases of the pandemic.

Anterior uveitis secondary to intraocular fiber from a hair enhancement product.

PURPOSE: To report a case of anterior uveitis caused by migration of cosmetic "hair-building fibers" into the anterior chamber and discuss previous literature describing ocular disease caused by small foreign fibers. OBSERVATIONS: A 73 year old male presented with his first episode of acute anterior uveitis. He was found to have a white fiber penetrating through the cornea into the anterior chamber. This foreign body was removed. The patient identified the material as a being from the cosmetic hair-building fiber product he had been using called Toppik. He was treated with topical steroids and antibiotic drops. The uveitis resolved without recurrence by six weeks after his initial presentation. CONCLUSIONS: Small synthetic and non-synthetic fibers represent sources of both superficial and intraocular injury. Careful examination of the anterior chamber is critical in patients with new acute uveitis to identify possible foreign fibers that can migrate through the cornea. While medical therapy with topical steroids may suffice for treatment in many cases, intraocular persistence of these materials can result in recurrent inflammation, ocular hypertension, or further migration into the posterior chamber which may require surgical intervention.

High fat diet induces pre-type 2 diabetes with regional changes in corneal sensory nerves and altered P2X7 expression and localization.

Type 2 diabetes is one of the leading pathologies that increases the risk of improper wound healing. Obesity has become a major risk factor for this disease that is now considered to be the 4th highest cause of preventable blindness according to the World Health Organization. The cornea is the most densely innervated structure in the human body and senses even the slightest injury. In diabetes, decreased corneal sensitivity secondary to diabetic peripheral neuropathy can lead to increased corneal abrasion, ulceration, and even blindness. In this study, a diet induced obesity (DIO) mouse model of pre-Type 2 diabetes was used to characterize changes in sensory nerves and P2X7, a purinoreceptor, a pain receptor, and an ion channel that is expressed in a number of tissues. Since our previous studies demonstrated that P2X7 mRNA was significantly elevated in diabetic human corneas, we examined P2X7 expression and localization in the DIO murine model at various times after being fed a high fat diet. Fifteen weeks after onset of diet, we found that there was a significant decrease in the density of sub-basal nerves in the DIO mice that was associated with an increase in tortuosity and a decrease in diameter. In addition, P2X7 mRNA expression was significantly greater in the corneal epithelium of DIO mice, and the increase in transcript was enhanced in the central migrating and peripheral regions after injury. Interestingly, confocal microscopy and thresholding analysis revealed that there was a significant increase in P2X7 distal to the injury, which contrasted with a decrease in P2X7-expressing stromal sensory nerves. Therefore, we hypothesize that the P2X7 receptor acts to sense changes at the leading edge following an epithelial abrasion, and this fine-tuned regulation is lost during the onset of diabetes. Further understanding of the corneal changes that occur in diabetes can help us better monitor progression of diabetic complications, as well as develop new therapeutics for the treatment of diabetic corneal dysfunction.

Nondecoupling of maximal supergravity from the superstring.

We consider the conditions necessary for obtaining perturbative maximal supergravity in d dimensions as a decoupling limit of type II superstring theory compactified on a (10-d) torus. For dimensions d=2 and d=3, it is possible to define a limit in which the only finite-mass states are the 256 massless states of maximal supergravity. However, in dimensions d>or=4, there are infinite towers of additional massless and finite-mass states. These correspond to Kaluza-Klein charges, wound strings, Kaluza-Klein monopoles, or branes wrapping around cycles of the toroidal extra dimensions. We conclude that perturbative supergravity cannot be decoupled from string theory in dimensions>or=4. In particular, we conjecture that pure N=8 supergravity in four dimensions is in the Swampland.

Ultraviolet properties of maximal supergravity.

We argue that recent results in string perturbation theory indicate that the four-graviton amplitude of four-dimensional N=8 supergravity might be ultraviolet finite up to eight loops. We similarly argue that the h-loop M-graviton amplitude might be finite for h<7+M/2.

A curious truncation of N=4 supersymmetric Yang-Mills theory.

The coupling constant dependence of correlation functions of Bogomol'nyi-Prasad-Sommerfield operators in the N=4 supersymmetric Yang-Mills theory can be expressed in terms of integrated correlation functions. We approximate these integrated correlators by using a truncated operator product expansion. This leads to differential equations for the coupling dependence. When applied to a particular 16 point correlator, the coupling dependence we find agrees with the corresponding amplitude computed via the gauge theory/string theory correspondence. We conjecture that this truncation becomes exact in the large N and large 't Hooft coupling limit.