Genetic predisposition to ocular surface disorders and opportunities for gene-based therapies.

The ocular surface, comprised of the corneal and conjunctival epithelium, innervation system, immune components, and tear-film apparatus, plays a key role in ocular integrity as well as comfort and vision. Gene defects may result in congenital ocular or systemic disorders with prominent ocular surface involvement. Examples include epithelial corneal dystrophies, aniridia, ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome, xeroderma pigmentosum (XP), and hereditary sensory and autonomic neuropathy. In addition, genetic factors may interact with environmental risk factors in the development of several multifactorial ocular surface disorders (OSDs) such as autoimmune disorders, allergies, neoplasms, and dry eye disease. Advanced gene-based technologies have already been introduced in disease modelling and proof-of-concept gene therapies for monogenic OSDs. For instance, patient-derived induced pluripotent stem cells have been used for modelling aniridia-associated keratopathy (AAK), XP, and EEC syndrome. Moreover, CRISPR/Cas9 genome editing has been used for disease modelling and/or gene therapy for AAK and Meesmann's epithelial corneal dystrophy. A better understanding of the role of genetic factors in OSDs may be helpful in designing personalized disease models and treatment approaches. Gene-based approaches in monogenic OSDs and genetic predisposition to multifactorial OSDs such as immune-mediated disorders and neoplasms with known or possible genetic risk factors has been seldom reviewed. In this narrative review, we discuss the role of genetic factors in monogenic and multifactorial OSDs and potential opportunities for gene therapy.

A Review of Monkeypox Ocular Manifestations and Complications: Insights for the 2022 Outbreak.

Monkeypox (MPVX) infection has been associated with multiorgan presentations. Thus, monkeypox infection's early and late complications are of particular concern, prompting health systems to decipher threatening sequels and their possible countermeasures. The current article will review the clinical signs and symptoms of the present and former outbreaks, differential diagnoses, workup and treatment of the ocular manifestations of MPXV infection in detail. One of the uncommon yet considerable MPXV complications is ocular involvement. These injuries are classified as (1) more frequent and benign lesions and (2) less common and vision-threatening sequels. Conjunctivitis, blepharitis and photophobia are the most uncomplicated reported presentations. Moreover, MPXV can manifest as eye redness, frontal headache, orbital and peri-ocular rashes, lacrimation and ocular discharge, subconjunctival nodules and, less frequently, as keratitis, corneal ulceration, opacification, perforation and blindness. The ocular manifestations have been less frequent and arguably less severe within the current outbreak. Despite the possibility of underestimation, the emerging evidence from observational investigations documented rates of around 1% for ocular involvement in the current outbreak compared to a 9-23% incidence in previous outbreaks in the endemic countries. The history of smallpox immunization is a protective factor against these complications. Despite a lack of definite and established treatment, simple therapies like regular lubrication and prophylactic use of topical antibiotics may be considered for MPXV ocular complications. Timely administration of specific antivirals may also be effective in severe cases. Monkeypox usually has mild to moderate severity and a self-limited course. However, timely recognition and proper management of the disease could reduce the risk of permanent ocular sequelae and disease morbidity.

Improved Right Ventricular Systolic Function After Cardiac Resynchronization Therapy in Patients With Heart Failure.

BACKGROUND: Since the introduction of cardiac resynchronization therapy (CRT) to improve left ventricular function, the effect of CRT on the right ventricle in patients with heart failure has not been well described. METHODS: We evaluated the effect of CRT on right ventricular systolic function in 20 patients (80% men; mean [SD] age, 58.5 [9.8] y) with cardiomyopathy and right ventricular systolic dysfunction (New York Heart Association class III or IV, left ventricular ejection fraction ≤35%, and QRS interval ≥120 ms). The median follow-up time was 15 months. Right ventricular systolic function, defined as a tricuspid annular plane systolic excursion (TAPSE) index of 16 mm or less, was evaluated in patients before and after CRT. RESULTS: Twelve (60%) patients had ischemic cardiomyopathy, and 12 (60%) patients had left bundle branch block detected using surface electrocardiogram. The mean (SD) QRS duration was 160.5 (24.4) ms. From before CRT to the time of follow-up after CRT, the mean (SD) ejection fraction increased significantly from 22.5% (5.6%) to 29.4% (7.4%) (P < .001). The mean (SD) TAPSE index also increased significantly from 13.70 (1.78) mm to 16.50 (4.77) mm (P = .018). Eleven (55%) patients showed improved right ventricular systolic function (TAPSE ≥16 mm) after CRT. Patients with a favorable right ventricular response to CRT were significantly older (64.6 [8.2] y vs 53.6 [8.4] y, respectively) and more likely to have nonischemic origin of cardiomyopathy than were patients with unimproved right ventricular function (66.7% vs 18.2%, respectively). CONCLUSION: Our findings indicate that CRT is associated with improved right ventricular systolic function in patients with heart failure and right ventricular systolic dysfunction. Patients with nonischemic heart disease more often show improved right ventricular function after CRT.

Idiopathic methicillin-susceptible Staphylococcus aureus associated tricuspid valve endocarditis and pneumothorax in a patient without apparent predisposing factor: a case report.

Pneumothorax following right-sided bacterial endocarditis is an infrequent medical complication usually reported in cases with a history of intravenous drug abuse. The following report describes the condition of a girl without congenital heart disease or a history of intravenous drug abuse who developed pneumothorax secondary to endocarditis.

Neurological Manifestations and their Correlated Factors in COVID-19 Patients; a Cross-Sectional Study.

INTRODUCTION: COVID-19 might present with other seemingly unrelated manifestations; for instance, neurological symptoms. This study aimed to evaluate the neurologic manifestations and their correlated factors in COVID-19 patients. METHODS: This retrospective observational study was conducted from March 17, 2020 to June 20, 2020 in a tertiary hospital in Iran. The study population consisted of adult patients with a positive result for COVID-19 real-time reverse transcriptase polymerase chain reaction (RT-PCR) using nasopharyngeal swabs. Both written and electronic data regarding baseline characteristic, laboratory findings, and neurological manifestations were evaluated and reported. RESULTS: 727 COVID-19 patients with the mean age of 49.94 ± 17.49 years were studied (56.9% male). At least one neurological symptom was observed in 403 (55.4%) cases. Headache (29.0%), and smell (22.3%) and taste (22.0%) impairment were the most prevalent neurological symptoms, while seizure (1.1%) and stroke (2.3%) were the least common ones. Patients with neurological manifestations were significantly older (p = 0.04), had greater body mass index (BMI) (p = 0.02), longer first symptom to admission duration (p < 0.001) and were more frequently opium users (p = 0.03) compared to COVID-19 patients without neurological symptoms. O2 saturation was significantly lower in patients with neurological manifestations (p = 0.04). In addition, medians of neutrophil count (p = 0.006), neutrophil-lymphocyte ratio (NLR) (p = 0.02) and c-reactive protein (CRP) (p = 0.001) were significantly higher and the median of lymphocyte count (p = 0.03) was significantly lower in patients with neurological manifestations. CONCLUSION: The prevalence of neurological manifestations in the studied cases was high (55.4%). This prevalence was significantly higher in older age, grated BMI, longer lasting disease, and opium usage.

Autoimmune Haemolytic Anaemia and Multiple Autoimmune Syndrome.

The presence of different autoimmune disorders in the same individual is called multiple autoimmune syndrome (MAS). One of these co-occurring conditions is autoimmune haemolytic anaemia (AIHA), which is characterized by the production of autoantibodies against red blood cells due to immune system malfunction and which results in severe tissue oxygenation disturbance. AIHA is not uncommon but occurs rarely in MAS; if it does, MAS is then classified as MAS type III. Herein, we describe a case of MAS type III including AIHA which was successfully treated with hydrocortisone with gradual resolution of symptoms. LEARNING POINTS: The co-occurrence of multiple autoimmune disorders in the same individual is called multiple autoimmune syndrome (MAS).Autoimmune haemolytic anaemia is not uncommon but rarely occurs in MAS.The presence of one autoimmune disease should alert the physician to the possible presence of others.