Part I. SARS-CoV-2 triggered \u27PANIC\u27 attack in severe COVID-19

The coronavirus disease 2019 (COVID-19) pandemic has produced a world-wide collapse of social and economic infrastructure, as well as constrained our freedom of movement. This respiratory tract infection is nefarious in how it targets the most distal and highly vulnerable aspect of the human bronchopulmonary tree, specifically, the delicate yet irreplaceable alveoli that are responsible for the loading of oxygen upon red cell hemoglobin for use by all of the body\u27s tissues. In most symptomatic individuals, the disease is a mild immune-mediated syndrome, with limited damage to the lung tissues. About 20% of those affected experience a disease course characterized by a cataclysmic set of immune activation responses that can culminate in the diffuse and irreversible obliteration of the distal alveoli, leading to a virtual collapse of the gas-exchange apparatus. Here, in Part I of a duology on the characterization and potential treatment for COVID-19, we define severe COVID-19 as a consequence of the ability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to trigger what we now designate for the first time as a ‘Prolific Activation of a Network-Immune-Inflammatory Crisis’, or ‘PANIC’ Attack, in the alveolar tree. In Part II we describe an immunotherapeutic hypothesis worthy of the organization of a randomized clinical trial in order to ascertain whether a repurposed, generic, inexpensive, and widely available agent is capable of abolishing ‘PANIC’; thereby preventing or mitigating severe COVID-19, with monumental ramifications for world health, and the global pandemic that continues to threaten it

Part II. high-dose methotrexate with leucovorin rescue for severe COVID-19: An immune stabilization strategy for SARS-CoV-2 induced \u27PANIC\u27 attack

Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish \u27PANIC\u27, thereby \u27left-shifting\u27 severe COVID-19 patients to the group majority of those infected with SARS-CoV-2, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this disease. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon SARS-CoV-2 triggered \u27PANIC Attack\u27. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons which could be leveraged to more effectively prepare for the next challenge to global health

Retinal arterial but not venous tortuosity correlates with facioscapulohumeral muscular dystrophy severity

Background Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disease beginning with facial and shoulder girdle weakness with variable progression. Exudative retinal detachment, retinal vessel irregularities on fluorescein angiography, and retinal vessel tortuosity have been found in association with FSHD. Methods In this retrospective study, muscle affectedness severity was rated as mild, moderate, or severe by a neurologist masked to the retinal images. Three ophthalmologists masked to disease severity graded the degree of arterial and venous tortuosity on a scale of 1 to 4. An automated method estimated an index of tortuosity for arteries and veins from color fundus photographs. Spearman rank correlation coefficients were used to describe the relationship between retinal vessel tortuosity and disease severity. Results Seven patients with an average age of 13 years (range, 7-36 years) were selected. Correlation between the subjective tortuosity for arteries, and the severity of FSHD was 0.78 (p = 0.039). The correlation coefficient for venous tortuosity was −0.06 and was not significant (p = 0.882). The correlation coefficient between the average algorithmic computer-generated tortuosity indices for arteries and FSHD severity was high (0.85, p = 0.016), but for veins it was low and not significant (0.19, p = 0.662). Conclusions The authors of previous reports have shown retinal vascular abnormalities did not correlate to FSHD disease severity. Our results suggest a correlation between the tortuosity of arteries and the severity of disease in FSHD patients. These results suggest the tortuosity of arteries can serve as a biomarker of severity of disease in these FSHD patients, either as determined by human experts or by an automated method

Cilioretinal Artery Occlusion: A Rare Complication of Severe Papilledema (.pdf)

Central vision loss in the setting of papilledema can result from optic neuropathy, macular pathology (e.g., subretinal fluid, choroidal folds), or a combination of optic neuropathy and macular pathology. The central vision loss is largely reversible when due to macular pathology, whereas it is not reversible when due to optic neuropathy. We report 3 patients who developed irreversible central vision loss due to cilioretinal artery occlusion associated with severe papilledema in the setting of idiopathic intracranial hypertension (IIH)

Variability Within Optic Nerve Optical Coherence Tomography Measurements Distinguishes Papilledema From Pseudopapilledema

To report a linear risk score obtained using clock-hour optical coherence tomography (OCT) data from papilledema and pseudopapilledema nerves that differentiates between the 2 diagnoses with high sensitivity and specificity

Subretinal Fluid in Idiopathic Intracranial Hypertension

"A retrospective review of 660 patients with IIH (2009-2013) identified 10 eyes from 8 patients (1.2%) with SRF on OCT and 8 eyes from 5 patients (0.75%) with photoreceptor disruption (disruption of the IS/OS junction) without SRF on OCT, producing best-corrected visual acuity (BCVA) of 20/25 or worse on presentation. Fundus photography, spectral-domain OCT of the disc and macula, and perimetry were used to evaluate SRF, photoreceptor disruption, and visual prognosis. The volume of SRF was determined by segmentation of the macula OCT with the Iowa Reference Algorithm.

Risk factors for poor visual outcome in patients with idiopathic intracranial hypertension

OBJECTIVES: Determine potential risk factors for progressive visual field loss in the Idiopathic Intracranial Hypertension Treatment Trial, a randomized placebo-controlled trial of acetazolamide in patients with idiopathic intracranial hypertension and mild visual loss concurrently receiving a low sodium, weight reduction diet. METHODS: Logistic regression and classification tree analyses were used to evaluate potential risk factors for protocol-defined treatment failure (>2 dB perimetric mean deviation [PMD] change in patients with baseline PMD −2 to −3.5 dB or >3 dB PMD change with baseline PMD −3.5 to −7 dB). RESULTS: Seven participants (6 on diet plus placebo) met criteria for treatment failure. The odds ratio for patients with grades III to V papilledema vs those with grades I and II was 8.66 (95% confidence interval [CI] 1.65–∞, p = 0.025). A 1-unit decrease in the number of letters correct on the ETDRS (Early Treatment Diabetic Retinopathy Study) chart at baseline was associated with an increase in the odds of treatment failure by a factor of 1.16 (95% CI 1.04–1.30, p = 0.005). Compared with female participants, the odds ratio for male participants was 26.21 (95% CI 1.61–433.00, p = 0.02). The odds of treatment failure were 10.59 times higher (95% CI 1.63–116.83, p = 0.010) for patients with >30 transient visual obscurations per month vs those with ≤30 per month. CONCLUSIONS: Male patients, those with high-grade papilledema, and those with decreased visual acuity at baseline were more likely to experience treatment failure. All but one of these patients were treated with diet alone. These patients should be monitored closely and be considered for aggressive treatment of their idiopathic intracranial hypertension