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

What Best Defines Whether an Optic Nerve is Hypoplastic?

The purpose of this study was to propose a new method of quantifying the degree of optic nerve hypoplasia based on optic disc area, retinal nerve fiber layer thickness, and visual field sensitivity

Diagnosis and Treatment of a Case of Acute Onset Childhood Primary Angiitis of the CNS

Childhood primary angiitis of the CNS (cPACNS) is a rare cause of neurologic dysfunction in children. Diagnosis requires angiographic or pathologic evidence of vasculitis in the brain or spinal cord in the absence of systemic vasculitis and after exclusion of other causes of CNS dysfunction. Onset is usually insidious in angiography-negative cases. We present a case of angiography-negative PACNS causing rapid onset of CNS dysfunction mimicking meningoencepahlitis, whcih was successfully treated with immune suppression

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

Variability Within Individual Optic Nerve Optical Coherence Tomography Measures Distinguishes Papilledema from Pseudopapilledema

A longstanding dilemma for the ophthalmologist is determining if an elevated optic nerve represents papilledema or pseudopapilledema. Previous studies looking at OCT have compared quadrant measurements, features of the subretinal fluid space and Bruch's membrane opening. Very little have utilized the clock hour data. We hypothesized that variability and magnitude of the RNFL thickness could differentiate papilledema from pseudopapilledema

Validation of an Optic Nerve Optical Coherence Tomography Model to Distinguish Papilledema from Pseudopapilledema

We previously studied a cohort of 116 eyes with papilledema and pseudopapilledema and analyzed the variability in the optical coherence tomography (OCT) clock-hour data. We created a formula based on the retinal nerve fiber layer (RNFL) thickness and clock hour variability that separated the two diagnoses with an AUC of 98.4%. Here, we sought to validate this formula (titled the Optic Disc Edema Index) on an independent cohort of patients

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)

Occam Rings True (abstract)

A 57-year-old, previously healthy man was referred for vision loss in both eyes. Six weeks before our evaluation, he presented to an outside ophthalmologist with "greying" of the central vision in his right eye that progressed to blindness over a week.Patient Care, Medical Knowledge, PBLI, SBP, Professionalism, IPCS, VBmeningealcarcinomatosis, KBDmetastaticcarcinom

Occam Rings True (video)

A 57-year-old, previously healthy man was referred for vision loss in both eyes. Six weeks before our evaluation, he presented to an outside ophthalmologist with "greying" of the central vision in his right eye that progressed to blindness over a week.Patient Care, Medical Knowledge, PBLI, SBP, Professionalism, IPCS,VBmeningealcarcinomatosis, KBDmetastaticcarcinom