Epidemiological and clinical insights into the enterovirus D68 upsurge in Europe 2021/22 and the emergence of novel B3-derived lineages, ENPEN multicentre study.

Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 and its clinical impact during the fall-winter season of 2021/22. From 19 European countries, 58 institutes reported 10,481 (6.8%) EV-positive samples of which 1,004 (9.6%) were identified as EV-D68 (852 respiratory samples). Clinical data was reported for 969 cases. 78.9% of infections were reported in children (0-5 years); 37.9% of cases were hospitalised. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases with six reported with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of two novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale EV-D68 European upsurge with severe clinical impact and the emergence of B3-derived lineages.

Menstrual Irregularities and Amenorrhea in Thyroid Eye Disease Patients Treated With Teprotumumab.

PURPOSE: To evaluate the rates of amenorrhea and menstrual irregularities in patients with active thyroid eye disease treated with teprotumumab. METHODS: A retrospective review was conducted of patients with active thyroid eye disease treated between 2020 and 2022 at a single institution. Female thyroid eye disease patients with regular menstruation at baseline who completed 8 infusions of teprotumumab were assessed. Patient-reported irregularities in menstruation or amenorrhea were recorded during routine clinic visits. Two sample t tests were used to assess differences between patients endorsing and denying menstrual irregularities. RESULTS: Twelve patients met the inclusion criteria. The mean age was 38.33 ± 9.6 years (range 25-53 years). The average follow-up after treatment completion was 11.43 months. Nine patients (75%) reported changes from their baseline menstruation. Four patients (33.3%) reported irregularities during treatment only. Three patients (25%) had persistence of irregularities after treatment; these patients regained normal cycles at an average of 3 months following teprotumumab completion. Two patients (16.7%) did not regain their normal cycles at the time of their last follow-up. One 53-year-old patient-reported persistent amenorrhea after treatment completion. One patient-reported menorrhagia at a 4-month follow-up. No significant age difference was found between patients with or without reported menstrual changes ( p = 0.43). CONCLUSION: Abnormalities of menstruation, including amenorrhea, were reported by 75% of patients treated with teprotumumab. These changes reverted to baseline after treatment in most affected patients.

Congenital Orbital Fibrosis With Spontaneous Regression of Orbital Tumor.

Congenital orbital fibrosis (COF) is a rare disorder characterized by an infiltrating orbital mass with secondary involvement of the extraocular muscles that may present with extraocular muscle dysfunction, and globe and eyelid abnormalities in infancy. This condition is thought to be a nonprogressive process and literature on longitudinal assessment of COF is limited. The authors describe a case of COF which was followed for 15 years. The patient had stable symptoms of ocular dysmotility and ptosis but was noted to have spontaneous regression of the orbital mass on serial MRI.

Rare Recombinant GI.5[P4] Norovirus That Caused a Large Foodborne Outbreak of Gastroenteritis in a Hotel in Spain in 2021.

Noroviruses are among the most important causes of acute gastroenteritis (AGE). In summer 2021, a large outbreak of norovirus infections affecting 163 patients, including 15 norovirus-confirmed food handlers, occurred in a hotel in Murcia in southeast Spain. A rare GI.5[P4] norovirus strain was identified as the cause of the outbreak. The epidemiological investigation determined that norovirus transmission might have been initiated through an infected food handler. The food safety inspection found that some symptomatic food handlers continued working during illness. Molecular investigation with whole-genome and ORF1 sequencing provided enhanced genetic discrimination over ORF2 sequencing alone and enabled differentiation of the GI.5[P4] strains into separate subclusters, suggesting different chains of transmission. These recombinant viruses have been identified circulating globally over the last 5 years, warranting further global surveillance. IMPORTANCE Due to the large genetic diversity of noroviruses, it is important to enhance the discriminatory power of typing techniques to differentiate strains when investigating outbreaks and elucidating transmission chains. This study highlights the importance of (i) using whole-genome sequencing to ensure genetic differentiation of GI noroviruses to track chains of transmission during outbreak investigations and (ii) the adherence of symptomatic food handlers to work exclusion rules and strict hand hygiene practices. To our knowledge, this study provides the first full-length genome sequences of GI.5[P4] strains apart from the prototype strain.

Osteopathia striata with cranial sclerosis causing a compressive optic neuropathy.

BACKGROUND: Osteopathia striata combined with cranial sclerosis (OS-CS) is an inherited skeletal dysplasia that manifests with macrocephaly, orofacial abnormalities, thickened craniofacial bones, and vertically oriented radiodensities of the long bones. CASE REPORT: Here, we present a severe case of OS-CS in a 4-year-old girl causing optic neuropathy as shown by radiographic evidence, ophthalmic findings, and histopathology. Previous genetic testing in this patient revealed a de novo heterozygous mutation in AMER1 (c.1057C>T, p.Arg353Ter). Although the patient had a pre-existing, appropriately functioning, ventriculoperitoneal (VP) shunt, a subsequent MRI of the brain and orbits showed narrowing of the bilateral optic nerve canals secondary to osseous thickening causing bilateral optic nerve atrophy, worse on the left. The patient underwent staged bilateral orbital osteotomies, optic canal decompression, and bilateral frontal craniotomy, and at 11 months postoperatively, her vision remained stable. Conclusions: While up to 50% of the patients with OS-CS may experience hearing loss due to cranial nerve compression, we present a case of severe visual loss secondary to OS-CS-associated optic nerve compression.

Residual Apical Lamina Papyracea as a Cause for Persistent Dysthyroid Optic Neuropathy After Orbital Decompression.

Two patients had persistent compressive dysthyroid optic neuropathy after decompression of the medial orbital wall and floor. In both cases, there was ~3 mm of unresected lamina papyracea anterior to the Annulus of Zinn, and removal of this residual bone led to resolution of the neuropathy. These illustrative cases suggest that, in some patients, even small amounts of residual crowding at the orbital apex can critically embarrass optic nerve perfusion, with resulting continued ischemic optic neuropathy.

Risk, Prevalence, and Progression of Glaucoma in Eyes With Age-Related Macular Degeneration Treated With Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To examine the risk, prevalence, and progression of glaucoma development in age-related macular degeneration (AMD) eyes receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections compared to controls. DESIGN: Retrospective clinical cohort study. METHODS: Retrospective review of eyes receiving intravitreal anti-VEGF injections from January 1, 2004, to December 31, 2013, for exudative AMD. Age- and sex-matched control groups of eyes included eyes with nonexudative AMD (NEAMD) and no AMD. Eyes with a diagnosis of glaucoma or glaucoma suspect were reviewed for injection details, type and date of glaucoma diagnosis, glaucoma treatments, standard automated perimetry (SAP), and spectral domain optical coherence tomography (SD-OCT). Qualitative progression was determined by indication of glaucoma progression in provider notes. Quantitative progression was assessed based on change in mean deviation (MD) on SAP, retinal nerve fiber layer thickness on SD-OCT, and intraocular pressure (IOP). RESULTS: There were 707 eyes of 504 patients treated with anti-VEGF injections and 1008 eyes in the NEAMD and no-AMD cohorts. There was no difference in glaucoma or suspect prevalence at initial presentation between eyes treated with injections and NEAMD (6.9% vs 9.7%, P = .22) or no-AMD controls (vs 8.5%, P = .55). There was no difference in cumulative 5-year probability of new glaucoma diagnosis after anti-VEGF injections compared to NEAMD (1.9% vs 1.0%, P = .69) or no-AMD controls (vs 1.6%, P = .88). There was no difference in qualitative progression of glaucoma in the injection cohort vs NEAMD (P = .19) or no-AMD controls (P = .61). The rate of MD change in injection eyes was similar to NEAMD eyes (P = .74) but greater than no-AMD eyes (P = .02). Eyes receiving injections required more topical glaucoma medications compared with NEAMD (P = .03) and more glaucoma laser treatments compared with no-AMD controls (P = .009). Eyes receiving injections did not require more frequent incisional glaucoma surgery compared with NEAMD (21.0% vs 15.0%, P = .95) or no-AMD controls (vs 10.0%, P = .10). CONCLUSION: Eyes treated with intravitreal anti-VEGF injections for exudative AMD did not have increased risk of developing glaucoma compared with controls. Of those with a glaucoma diagnosis, exudative AMD eyes receiving injections required a greater number of topical glaucoma medications compared with NEAMD eyes and had a greater rate of MD loss than no-AMD controls.

Dermatological adverse reactions after vaccination with BNT162b2 in a cohort of healthcare workers.

BACKGROUND: The description of the skin reactions produced by the different vaccines against SARS-CoV-2 has focused on the symptoms reported by the general population. There are few studies with very different measurement methods focused on healthcare workers. METHODS: A longitudinal observational study was conducted on all the healthcare workers from the Hospital Universitario San Cecilio that received vaccination against COVID-19 with BNT162b2. The recruitment period was from December 2020 to September 2021. The recommended regimen was double, with a minimum interval of 21 days between doses. All dermatological reactions reported as adverse effects of the vaccine were evaluated by the Staff of the Dermatology Unit of our center. RESULTS: A total of 3969 healthcare workers of our center were followed. Only 0.7% of them reported dermatological adverse reactions. The most frequently reported reactions were morbilliform rash and COVID arm. In the multivariate analysis, the vaccination regimen (one dose) and the history of COVID-19 infection remained the main factors associated with the report of dermatological adverse reactions. CONCLUSION: The rate of dermatological adverse reactions after vaccination with BNT162b2 (Pfizer-BioNTech) is extraordinarily low. No patient required hospitalization, which supports the safety of this vaccination in a population of healthcare workers.

Orbital Cyst with Ependymal Differentiation Associated with Microphthalmia.

BackgroundOrbital cysts associated with microphthalmia are colobomatous lesions that typically present unilaterally and posterior to the globe. Case Report: A male infant had an orbital cyst associated with microphthalmia located anterior to the globe composed of a neuroglial wall, ependymal-like epithelial lining, with synaptophysin-positive cells resembling the retinal neuronal layer. Conclusion: This orbital cyst may represent a malformation of the eye rather than an encephalocele.

Respiratory adverse events during upper digestive endoscopies in children under ketamine sedation.

BACKGROUND: There is no evidence of the need for oxygen supplementation during upper digestive endoscopies under ketamine sedation in children, and the latest recommendations specifically state that it is not mandatory for the procedure. The aim of our study is to assess the incidence of respiratory adverse events during upper digestive endoscopies in children under Ketamine sedation when performed without oxygen supplementation, in accordance with the latest recommendations. METHODS: Eighty-eight children undergoing ketamine sedation for programmed upper digestive endoscopy at our Pediatric Intensive Care Unit were included. Patients needing other sedative agents different from ketamine were excluded. No patients received previous oxygen therapy. Suction equipment, oxygen, a bag-valve-mask, and age-appropriate equipment for advanced airway management were immediately available. The primary outcome measure was the incidence of desaturation episodes (i.e. FiO2 below 90% requiring an intervention). RESULTS: Fifty-five patients (62.5%) presented a desaturation episode during the procedure. Most desaturation episodes occurred during the endoscope introduction (78.2%), and 5 episodes were previous to the endoscope introduction (minute 0). Around sixty percent of patients (58.9%) required oxygen therapy and four patients required bag-mask ventilation. Once oxygen therapy was initiated, 34 patients (70.5%) required it during the complete procedure or part of it. CONCLUSIONS: Desaturation episodes occur frequently early on in the procedure. Our data suggest that the role of oxygen supplementation prior to, and during upper digestive endoscopies under ketamine sedation in children should be thoroughly assessed for future recommendations.

Idiopathic Intracranial Hypertension Triggering Hemifacial Spasm.

ABSTRACT: Idiopathic intracranial hypertension (IIH) is a syndrome associated with increased intracranial pressure without a clear underlying cause that is classically seen in young women. Patients typically present with headache and ocular findings, including disc edema and, less frequently, an abduction deficit. To make a diagnosis of IIH, other than cranial nerve 6 or 7 dysfunction, patients must have a normal neurologic examination. When cranial nerve 7 is affected patients can present with hemifacial spasm. We present the case of a young woman with IIH who had hemifacial spasm as one of the presenting symptoms. Her symptoms resolved once she was treated for IIH with acetazolamide.

Cobalt toxic optic neuropathy and retinopathy: Case report and review of the literature.

PURPOSE: We detail a case of cobalt toxicity with visual and systemic complications, review the pathogenic process for the optic neuropathy and retinopathy, and discuss the controversy of metallic hip prosthesis. OBSERVATIONS: A 59-year-old female with a history of multiple left hip arthroplasties presented to our clinic with bilateral visual loss. The year prior, she had failure of the hip implant necessitating revision surgery with placement of a chrome-cobalt head. A few months after surgery, she began experiencing blurred and "white, spotty" vision in both eyes in addition to hypothyroidism, cardiomyopathy and neuropathy. The possibility of the patient's symptoms being due to cobalt toxicity from her hip prosthesis was proposed and she was found to have a serum cobalt level >1000 µg/L (normal 0-0.9 ng/mL). Visual acuity was 20/600 in the right and 20/800 in the left eye. There was bilateral temporal optic disc pallor. Goldmann visual field testing demonstrated bilateral central scotomas, optical coherence tomography (OCT) showed severe ganglion cell layer-inner plexiform layer (GCLIPL) thinning and multifocal electroretinography (mfERG) demonstrated decreased amplitudes in both eyes. She underwent a total hip revision arthroplasty with extensive debridement of "black sludge" found within a pseudocapsule. Four days after surgery, cobalt serum levels had significantly decreased to 378 ng/mL. One month after surgery, she had significant improvement in visual acuity (20/150 right eye, 20/250 left eye), Goldmann visual field testing, and mfERG. OCT showed retinal nerve fiber thinning and persistent GCLIPL thinning in both eyes. CONCLUSIONS AND IMPORTANCE: Excessive cobalt levels can result in systemic toxicity leading to visual changes, peripheral neuropathy, hearing loss, cognitive deficits, cardiomyopathy and hypothyroidism. In recent years it has become apparent that cobalt toxicity can be associated with metal-on-metal total hip arthroplasty, or the grinding effects of retained ceramic particles from a fractured ceramic head on a cobalt-chromium femoral head prosthesis.

The impact of vascular burden on behavioural and psychological symptoms in older adults with dementia: the BEVASDE study.

OBJECTIVES: Behavioural and psychological symptoms (BPS) worsen quality of life and increase institutionalization in dementia, but the relationship between BPS and vascular burden on neuroimaging is unclear. Our aim is to explore whether the profile of BPS differs between patients with large-vessel or cortical vascular dementia (cVaD), small-vessel or subcortical vascular dementia (sVaD) and Alzheimer's disease (AD). METHODS: The BEVASDE study comprised 806 demented patients (cVaD-136, sVaD-184, AD-486) recruited from outpatient consultations in Salamanca and Avila, Spain. The Clinical Dementia Rating Scale (CDR) and the 12-item Neuropsychiatric Inventory (NPI) were used to evaluate dementia severity and BPS. RESULTS: BPS were reported in 98.5%, 97.3% and 96.9% of the cVaD, sVaD and AD cases, respectively. The median NPI score was 36 in both cVaD and sVaD and 34 in AD, with a median number of four symptoms per patient. The most frequent disorders were depression (64.4%), apathy (61.8%) and sleep disturbance (60.5%). Multivariate regression analyses after controlling for possible confounders showed a higher risk of euphoria (p = 0.011), apathy (p = 0.007), irritability (p = 0.002) and sleep disturbance (p = 0.020) in cVaD than in AD and more apathy (p = 0.0001) and irritability (p = 0.0001) in sVaD than in AD. In contrast, AD subjects had a higher risk of delusions (p = 0.007) and hallucinations (p = 0.023) than patients with cVaD as well as more aberrant motor behaviour than both cVaD (p = 0.0001) and sVaD (p = 0.003). CONCLUSION: BPS are common in dementia and may help in differential diagnosis of the various subtypes. We should inquire about them and treat as necessary.

Intussusceptive Lymphangiogenesis in Lymphatic Malformations/Lymphangiomas.

Intussusception in lymphatic vessels has received less attention than in blood vessels. In tumors and pseudotumors of blood vessels with intravascular papillary structures, including sinusoidal hemangioma and intravascular papillary endothelial hyperplasia, we observed exuberant intussusceptive angiogenesis, as well as the similarity between papillae (term used by pathologists) and pillars/folds (hallmarks of intussusceptive angiogenesis). A similar response could be expected in lymphangiomas (lymphatic malformations and reactive processes rather than tumors) with papillae. The aim of this work is to assess whether papillae/pillars/folds and associated structures (vessel loops and septa) are present in lymphangiomas, and to establish the characteristics and formation of these structures. For this purpose, we selected lymphangiomas with intraluminal papillae (n = 18), including cystic, cavernous, circumscriptum, and progressive types, of which two cases of each type with a greater number of papillae were used for serial histologic sections and immunohistochemistry. The studies showed a) dilated lymphatic spaces giving rise to lymphatic-lymphatic vascular loops, which dissected and encircled perilymphatic structures (interstitial tissue structures/ITSs and pillars/posts), b) ITSs and pillars, surrounded by anti-podoplanin-positive endothelial cells, protruding into the lymphatic spaces (papillary aspect), and c) splitting, remodeling, linear arrangement, and fusion of papillae/pillars/folds, forming papillary networks and septa. In conclusion, as occurs in blood vessel diseases, the development of lymphatic vessel loops, papillae/pillars/folds, and septa (segmentation) supports intussusceptive lymphangiogenesis and suggests a piecemeal form of intussusception. This intussusceptive lymphangiogenesis in lymphatic diseases can provide a basis for further studies of lymphatic intussusception in other conditions, with clinical and therapeutic implications. Anat Rec, 302:2003-2013, 2019. © 2019 American Association for Anatomy.

Classification of Strokes in Patients Receiving Intravitreal Anti-Vascular Endothelial Growth Factor.

BACKGROUND AND OBJECTIVE: The purpose of this study was to identify the differences in the types of strokes seen in patients receiving intravitreal anti-vascular endothelial growth factor (VEGF) compared with normal control populations. PATIENTS AND METHODS: We performed a retrospective consecutive review of all patients receiving intravitreal anti-VEGF injections in Olmsted County, Minnesota, from January 1, 2004, to December 31, 2013, for exudative age-related macular degeneration (AMD), diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), or retinal vein occlusion (RVO). A 2-year follow-up period was required for study inclusion. Three age- and sex-matched cohorts were identified. RESULTS: A total of 2,541 patients were examined. There were 690 patients identified during the study period as receiving an intravitreal injection for AMD, DME, PDR, or RVO. Of these patients, 38 (5.8%) suffered a stroke after starting intravitreal injection therapy. Of these strokes, 27 (71.1%) were ischemic, six (15.8%) were embolic, and five (13.2%) were hemorrhagic. There were no differences in the types of strokes identified among the patients receiving intravitreal injections between the case cohort and the control cohorts (P > .05 for all). CONCLUSION: The authors' data suggest there is no predilection to the development of ischemic infarcts or hemorrhagic strokes in those patients receiving intravitreal anti-VEGF compared with control populations. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e140-e157.].

Dysregulated uterine natural killer cells and vascular remodeling in women with recurrent pregnancy losses.

PROBLEM: Angiogenesis and vascular remodeling in secretory endometrium represent one of the crucial steps in pregnancy establishment, for which uterine NK (uNK) cells have an important role. Impairment of these steps may proceed to implantation and instigate initial pathology of recurrent pregnancy losses (RPL). In this study, we aim to investigate vascular development and density of uNK cells in secretory endometrium of women with RPL. METHODS OF STUDY: Mid-secretory phase endometrial tissues from women with RPL (n = 15) and fertile controls (n = 7) were investigated. CD56+ and CD16+ uNK cells, CD31+ vascular endothelial cells and smooth muscle myosin (SMM)+ . Vascular smooth muscle cells (VSMC) expressing SMM were investigated using immunohistochemistry and western blot. High-throughput quantitative real-time polymerase chain reaction (qRT-PCR) was used as well. RESULTS: CD56+ uNK number was significantly higher in women with RPL compared to controls (P < 0.0001). uNK cell density by immunohistochemistry was positively correlated with CD56 mRNA expression by qRT-PCR (r2  = 0.43, P = 0.0137). The number of blood vessels represented by the expression of either CD31 or SMM was higher in women with RPL as compared to controls (P < 0.05 and P < 0.0001, respectively), and correlated with the number of uNK cell (r2  = 0.18, P < 0.04, and r2  = 0.65, P < 0.0001, respectively). The wall thickness of spiral arteries was significantly higher in women with RPL as compared with that of controls (P = 0.0027). CONCLUSION: Increased uNK cells in mid-secretory endometrium are associated with increased vascularization and defective vascular transformation of spiral arteries in women with RPL.

Inflammation induced preterm labor and birth.

Preterm birth which occurs before 37 weeks gestation is one of the most common obstetrical complication in humans. After many studies, it appears that "not one answer fits all" regarding the risk factors, causes and the treatments for this syndrome. However, it is becoming more evident that one of the major risk factors is inflammation and/or infection in the fetoplacental unit. In animal models (usually consisting of mice injected with lipopolysaccharide at 14 days of gestation), IL-22 and IL-6 have been identified as factors related to preterm birth. There are some clinical tests available to determine the risk for preterm labor and delivery, which can be identified before, during early, or at mid-gestation. However, treatment of preterm birth with antibiotics so far has not been "curable" and studies using anti-inflammatory treatments are not readily available. More studies regarding causes and treatments for preterm labor and delivery in humans are necessary to prevent neonatal deaths and/or developmental abnormalities associated with this common syndrome.