Incidental Diagnosis of Four Lid Orbital Lymphoma during a Blepharoplasty.

Chronic lymphocytic leukemia is characterized by the accumulation of mature CD5-positive B-cells in the lymphoid organs.1 Extranodal involvement occurs in up to 10% of cases and can arise in various tissues, including the orbit. Less than 400 cases of orbital lymphoma are diagnosed per year in the United States, typically manifesting as a form of B-cell non-Hodgkin lymphoma, with extranodal marginal zone B-cell lymphoma being the most common subtype. Orbital lymphoma typically presents with proptosis and a palpable mass; however, patients may also have a relatively benign examination. Here, we present a 76-year-old man with symmetric dermatochalasis and marked fat prolapse of all four lids, who was incidentally diagnosed with secondary orbital lymphoma in all four eyelids during a cosmetic four lid blepharoplasty. His history was significant for RAI Stage 0 chronic lymphocytic leukemia diagnosed 15 years before consultation. Orbital lymphoma presenting as orbital fat prolapse has only been reported a few times in the literature. To our knowledge, this is the first case of secondary orbital lymphoma in all four eyelids found incidentally during an aesthetic four lid blepharoplasty.

Impact of maternal depression on malnutrition treatment outcomes in older children with sickle cell anemia.

BACKGROUND: Malnutrition and sickle cell anemia (SCA) result in high childhood mortality rates. Although maternal depression is an established risk factor for malnutrition in younger children, little is known about its impact on treatment response in children with malnutrition. We aimed to determine the relationship, if any, between maternal depression scores and malnutrition treatment outcomes in older children with SCA. METHODS: We conducted a planned ancillary study to our randomized controlled feasibility trial for managing severe acute malnutrition in children aged 5-12 with SCA in northern Nigeria (NCT03634488). Mothers of participants completed a depression screen using the Patient Health Questionnaire (PHQ-9).We used a multivariable linear regression model to describe the relationship between the baseline maternal PHQ-9 score and the trial participant's final body mass index (BMI) z-score. RESULTS: Out of 108 mother-child dyads, 101 with maternal baseline PHQ-9 scores were eligible for inclusion in this analysis. At baseline, 25.7% of mothers (26 of 101) screened positive for at least mild depression (PHQ-9 score of 5 or above). The baseline maternal PHQ-9 score was negatively associated with the child's BMI z-score after 12 weeks of malnutrition treatment (ß=-0.045, p = 0.041). CONCLUSIONS: Maternal depressive symptoms has an impact on malnutrition treatment outcomes. Treatment of malnutrition in older children with sickle cell anemia should include screening for maternal depression and, if indicated, appropriate maternal referral for depression evaluation and treatment. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (#NCT03634488) on January 30, 2018, https://clinicaltrials.gov/study/NCT03634488 .

Feasibility trial for the management of severe acute malnutrition in older children with sickle cell anemia in Nigeria.

Children with sickle cell anemia (SCA) living in Nigeria are at an increased risk of malnutrition, which contributes to increased morbidity and mortality. However, evidence-based guidelines for managing malnutrition in children with SCA are lacking. To address this gap, we conducted a multicenter, randomized controlled feasibility trial to assess the feasibility and safety of treating children with SCA aged from 5 to 12 years and having uncomplicated severe acute malnutrition (body mass index z score of <-3.0). Children with SCA and uncomplicated severe acute malnutrition were randomly allocated to receive supplemental ready-to-use therapeutic food (RUTF) with or without moderate-dose hydroxyurea therapy (20 mg/kg per day). Over a 6-month enrollment period, 3190 children aged from 5 to 12 years with SCA were evaluated for eligibility, and 110 of 111 children who were eligible were enrolled. During the 12-week trial, no participants withdrew or missed visits. One participant died of unrelated causes. Adherence was high for hydroxyurea (94%, based on pill counts) and RUTF (100%, based on the number of empty sachets returned). No refeeding syndrome event or hydroxyurea-related myelosuppression occurred. At the end of the trial, the mean change in body mass index z score was 0.49 (standard deviation = 0.53), and 39% of participants improved their body mass index z score to ≥-3.0. Our findings demonstrate the feasibility, safety, and potential of outpatient treatment for uncomplicated severe acute malnutrition in children with SCA aged from 5 to 12 years in a low-resource setting. However, RUTF sharing with household and community members potentially confounded the response to malnutrition treatment. This trial was registered at clinicaltrials.gov as #NCT03634488.

Salmonella Typhimurium expressing chromosomally integrated Schistosoma mansoni Cathepsin B protects against schistosomiasis in mice.

Schistosomiasis threatens hundreds of millions of people worldwide. The larval stage of Schistosoma mansoni migrates through the lung and adult worms reside adjacent to the colonic mucosa. Several candidate vaccines are in preclinical development, but none is designed to elicit both systemic and mucosal responses. We have repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to express Cathepsin B (CatB), a digestive enzyme important for the juvenile and adult stages of the S. mansoni life cycle. Previous studies have demonstrated the prophylactic and therapeutic efficacy of our plasmid-based vaccine. Here, we have generated chromosomally integrated (CI) YS1646 strains that express CatB to produce a viable candidate vaccine for eventual human use (stability, no antibiotic resistance). 6-8-week-old C57BL/6 mice were vaccinated in a multimodal oral (PO) and intramuscular (IM) regimen, and then sacrificed 3 weeks later. The PO + IM group had significantly higher anti-CatB IgG titers with greater avidity and mounted significant intestinal anti-CatB IgA responses compared to PBS control mice (all P < 0.0001). Multimodal vaccination generated balanced TH1/TH2 humoral and cellular immune responses. Production of IFNγ by both CD4+ and CD8+ T cells was confirmed by flow cytometry (P < 0.0001 & P < 0.01). Multimodal vaccination reduced worm burden by 80.4%, hepatic egg counts by 75.2%, and intestinal egg burden by 78.4% (all P < 0.0001). A stable and safe vaccine that has both prophylactic and therapeutic activity would be ideal for use in conjunction with praziquantel mass treatment campaigns.

Intracranial Hypertension in a Transgender Man.

Objective: Case description of recurrent idiopathic intracranial hypertension (IIH) in a transgender man on gender-affirming hormone therapy. Methods: Case report. Results: A 24-year-old transmasculine patient (assigned female at birth), with a body mass index (BMI) of 37.3, presented with headaches, transient visual obscurations (TVOs), pulsatile tinnitus, Frisén 5 papilledema, and scotomas. He was diagnosed with IIH after normal magnetic resonance imaging (MRI) and magnetic resonance venogram (MRV), an elevated opening pressure of 27 cm water, and normal cerebrospinal fluid studies. IIH resolved with acetazolamide and optic nerve sheath fenestration (ONSF). He then started gender-affirming testosterone therapy and was on this for 20 months when his headaches, pulsatile tinnitus, TVOs, and Frisén 3 papilledema recurred at a BMI of 31. Brain MRI and MRV were normal. Opening pressure was elevated at 31 cm. water. Acetazolamide 4 g/day did not improve the papilledema, thus a left ONSF was repeated resulting in eventual resolution of the IIH. Discussion: Several reports have been published of IIH development in patients receiving testosterone therapy. Hormone prescribers for gender affirmation may wish to screen for visual loss and optic nerve edema in patients undergoing testosterone therapy, which may also stimulate appetite weight gain.

A low dose adenovirus vectored vaccine expressing Schistosoma mansoni Cathepsin B protects from intestinal schistosomiasis in mice.

BACKGROUND: Schistosomiasis is an underestimated neglected tropical disease which affects over 236.6 million people worldwide. According to the CDC, the impact of this disease is second to only malaria as the most devastating parasitic infection. Affected individuals manifest chronic pathology due to egg granuloma formation, destroying the liver over time. The only FDA approved drug, praziquantel, does not protect individuals from reinfection, highlighting the need for a prophylactic vaccine. Schistosoma mansoni Cathepsin B (SmCB) is a parasitic gut peptidase necessary for helminth growth and maturation and confers protection as a vaccine target for intestinal schistosomiasis. METHODS: An SmCB expressing human adenovirus serotype 5 (AdSmCB) was constructed and delivered intramuscularly to female C57BL/6 mice in a heterologous prime and boost vaccine with recombinant protein. Vaccine induced immunity was described and subsequent protection from parasite infection was assessed by analysing parasite burden and liver pathology. FINDINGS: Substantially higher humoral and cell-mediated immune responses, consisting of IgG2c, Th1 effectors, and polyfunctional CD4+ T cells, were induced by the heterologous administration of AdSmCB when compared to the other regimens. Though immune responses favoured Th1 immunity, Th2 responses provided by SmCB protein boosts were maintained. This mixed Th1/Th2 immune response resulted in significant protection from S. mansoni infection comparable to other vaccine formulations which are in clinical trials. Schistosomiasis associated liver pathology was also prevented in a murine model. INTERPRETATION: Our study provides missing preclinical data supporting the use of adenoviral vectoring in vaccines for S. mansoni infection. Our vaccination method significantly reduces parasite burden and its associated liver pathology - both of which are critical considerations for this helminth vaccine. FUNDING: This work was supported by the Canadian Institutes of Health Research, R. Howard Webster Foundation, and the Foundation of the McGill University Health Centre.

Case Report: A Neuro-Ophthalmological Assessment of Vision Loss in a Pediatric Case of McCune-Albright Syndrome.

Patients diagnosed with McCune-Albright Syndrome (MAS) frequently manifest craniofacial fibrous dysplasia (FD). Craniofacial FD can impinge nerve fibers causing visual loss as well as craniofacial pain. Surgical decompression of affected nerves is performed, with variable efficacy, in an attempt to restore function or alleviate symptoms. Here, we present a case of a 12-year-old MAS patient with visual deficits, particularly in the left eye (confirmed by enlarged blind spots on Goldmann visual field testing), and craniofacial pain. Decompression surgery of the left optic nerve mildly improved vision, while persistent visual deficits were noted at a 3-month follow-up assessment. An in-depth, imaging-based evaluation of the visual system, including the retinal nerve fiber layer, optic nerves, and central nervous system (CNS) visual pathways, revealed multiple abnormalities throughout the visual processing stream. In the current FD/MAS patient, a loss of white matter fiber density within the left optic radiation and functional changes involving the left primary visual cortex were observed. Aberrant structural and functional abnormalities embedded within central visual pathways may play a role in facilitating deficits in vision in FD/MAS and contribute to the variable outcome following peripheral nerve decompression surgery.

Traumatic Orbital Floor Fracture Causing Therapeutic Orbital Decompression in Thyroid Eye Disease.

This is a case of a 67-year-old female with a history of Graves' disease and associated thyroid eye disease who presented to the emergency room after falling and hitting her head. Subsequently, she noted periorbital air on the left side when blowing her nose. A CT scan in the emergency room revealed a left orbital floor fracture and decompression of the left orbit. While nonsurgical orbital decompression in the setting of Graves' eye disease has been reported in several instances, spontaneous ethmoid bone remodeling or fracture has been the most cited mechanism, with rarer instances of true spontaneous orbital floor fracture. Furthermore, there exist only two known case reports of traumatic orbital floor fractures with subsequent orbital decompression in the setting of thyroid eye disease. In only one of the two known cases, therapeutic effect was established. However, no significant follow-up period was noted. This case represents a rare traumatic orbital floor fracture resulting in orbital decompression with demonstrably improved exophthalmos. It is the first to include definitive follow-up both before and after operative management of the contralateral orbit.

Correction: Vaccination against the digestive enzyme Cathepsin B using a YS1646 Salmonella enterica Typhimurium vector provides almost complete protection against Schistosoma mansoni challenge in a mouse model.

[This corrects the article DOI: 10.1371/journal.pntd.0007490.].

Therapeutic activity of a Salmonella-vectored Schistosoma mansoni vaccine in a mouse model of chronic infection.

Schistosomiasis is an important fresh-water-borne parasitic disease caused by trematode worms of the genus Schistosoma. With > 250 million people infected worldwide and approximately 800 million people at risk, the World Health Organization considers schistosomiasis to be the most important human helminth infection. Several prophylactic non-living vaccines are in pre-clinical and clinical development, but only one has been assessed for therapeutic effect in an animal model with modest results. Live attenuated Salmonella have multiple potential advantages as vaccine vectors. We have engineered an attenuated Salmonella enterica Typhimurium strain (YS1646) to produce a vaccine that targets the parasite digestive enzyme Cathepsin B (CatB). A multi-modality immunization schedule was used in chronically infected mice that included three oral (PO) doses of this CatB-bearing YS1646 strain on days one, three, and five as well as an intramuscular (IM) dose of recombinant CatB on day one. Parasite burden (worm count, intestinal and liver egg numbers) were 46.5 - 50.3% lower than in control animals 1 month post-vaccination and relative reductions further increased to 63.9 - 73.3% at 2 months. Serum anti-CatB IgG increased significantly after vaccination with the development of a more balanced TH1/TH2 pattern of response (ie: a shift in the IgG1:IgG2c ratio). Compared to control animals, a broad and robust CatB-specific cytokine/chemokine response was seen in splenocytes isolated 1 month post-vaccination. A vaccine that has both prophylactic and therapeutic activity would be ideal for use in conjunction with mass treatment campaigns with praziquantel in schistosome-endemic countries.

Complex Fistula Formations After Orbital Fracture Repair With Teflon: A Review of 3 Case Reports.

ABSTRACT: The authors present 3 unique cases of complex fistula formations because of orbital fracture repair with a Teflon (polytetrafluroethylene) implant. A 26-year-old man presented with dacryocystitis and a cutaneous fistula 8 years after left orbital floor and medial wall fracture repair with a Teflon implant. A 46-year-old woman suffered orbital trauma after a motor vehicle accident as a teenager and the fracture was repaired with Teflon implant. Thirty-two years later, she presented with lower eyelid fistula, ectropion, and retraction. A 65-year-old woman also previously had Teflon implants for the repair of her left inferior and lateral orbital rim after a motor vehicle accident. Twenty-five years later, she presented with chronic infections involving the repaired areas, as well as left lower lid ectropion and fistula formation. The woven material nature of Teflon acted as a nidus for infection, inflammation, and led to complex cutaneous fistula formations in these patients.

Adjuvanted Schistosoma mansoni-Cathepsin B With Sulfated Lactosyl Archaeol Archaeosomes or AddaVax™ Provides Protection in a Pre-Clinical Schistosomiasis Model.

Schistosomiasis threatens 800 million people worldwide. Chronic pathology manifests as hepatosplenomegaly, and intestinal schistosomiasis caused by Schistosoma mansoni can lead to liver fibrosis, cirrhosis, and blood in the stool. To assist the only FDA-approved drug, praziquantel, in parasite elimination, the development of a vaccine would be of high value. S. mansoni Cathepsin B (SmCB) is a well-documented vaccine target for intestinal schistosomiasis. Herein, we test the increased efficacy and immunogenicity of SmCB when combined with sulfated lactosyl archaeol (SLA) archaeosomes or AddaVax™ (a squalene based oil-in-water emulsion). Both vaccine formulations resulted in robust humoral and cell mediated immune responses. Impressively, both formulations were able to reduce parasite burden greater than 40% (WHO standard), with AddaVax™ reaching 86.8%. Additionally, SmCB with both adjuvants were able to reduce granuloma size and the amount of larval parasite hatched from feces, which would reduce transmission. Our data support SmCB as a target for S. mansoni vaccination; especially when used in an adjuvanted formulation.

The Analgesic Effect of Transcranial Direct Current Stimulation (tDCS) combined with Physical Therapy on Common Musculoskeletal Conditions: A Systematic Review and Meta-Analysis.

BACKGROUND: The analgesic effects of transcranial Direct Current Stimulation (tDCS) combined with physical therapy remain unclear. OBJECTIVE: To systematically review available evidence comparing tDCS with any physical therapy modality (PTM) to PTM alone or PTM with sham tDCS on pain relief on common musculoskeletal (MSK) conditions, namely knee osteoarthritis (KOA), chronic low back pain (CLBP), myofascial pain syndrome (MPS) and fibromyalgia. METHODS: EMBASE and MEDLINE were searched from inception to April 2019 for randomized controlled trials. Reviewers independently assessed the studies quality and extracted data according to the PRISMA protocol. The GRADE approach was used to asses quality of evidence and a "Summary of Findings" table was created. The analyses used random-effects model. The primary outcome was pain reduction after treatment. RESULTS: Eight articles were included. Only one study had low risk of bias. Quality of evidence was considered low or very low. Significant reduction in pain scores were found for fibromyalgia and KOA (Standardized mean difference (SMD) = -1.94 [95% CI: -3.37 to -0.49; I 2=76.4%] and SMD = -2.35 [95% CI: -3.63 to -1.06; I 2=69.7%] respectively). Subgroup analysis considering the type of PTM despite MSK condition revealed significant reduction in pain scores for exercise, SMD = -1.20 [95% CI: -1.683 to -0.717; I 2=10.8%]. CONCLUSIONS: Large heterogeneity and low quality of evidence and limited number of studies were found. Results suggest a potential analgesic effect of tDCS in combination with a PTM for fibromyalgia and KOA. Subgroup analysis suggests a stronger effect of tDCS when combined with an exercise based PTM.

Supernumerary Lacrimal Caruncle: A Case Series.

A 12-year-old boy and 63-year-old woman were incidentally found to have a solitary, well-defined, raised, ovoid lesion involving the inferomedial palpebral conjunctiva. Both lesions were separate from the lacrimal caruncle with normal conjunctiva surrounding the lesions. Excisional biopsies were consistent with caruncular tissue. In the English literature, supernumerary lacrimal caruncle has only been previously described in adults despite the congenital nature of the lesion.

Vaccination against the digestive enzyme Cathepsin B using a YS1646 Salmonella enterica Typhimurium vector provides almost complete protection against Schistosoma mansoni challenge in a mouse model.

Schistosoma mansoni threatens hundreds of millions of people in >50 countries. Schistosomulae migrate through the lung and adult worms reside in blood vessels adjacent to the intestinal mucosa. Current candidate vaccines aren't designed to elicit a mucosal response. We have repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to produce such a vaccine targeting Cathepsin B (CatB), a digestive enzyme important for parasite survival. Promoter-Type 3 secretory signal pairs were screened for protein expression in vitro and transfected into YS1646 to generate candidate vaccine strains. Two strains were selected for in vivo evaluation (nirB_SspH1 and SspH1_SspH1). Female C57BL/6 mice were immunized twice, 3 weeks apart, using six strategies: i) saline gavage (control), ii) the 'empty' YS1646 vector orally (PO) followed by intramuscular (IM) recombinant CatB (20µg IM rCatB), iii) two doses of IM rCatB, iv) two PO doses of YS1646-CatB, v) IM rCatB then PO YS1646-CatB and vi) PO YS1646-CatB then IM rCatB. Serum IgG responses to CatB were monitored by ELISA. Three weeks after the second dose, mice were challenged with 150 cercariae and sacrificed 7 weeks later to assess adult worm and egg burden (liver and intestine), granuloma size and egg morphology. CatB-specific IgG antibodies were low/absent in the control and PO only groups but rose substantially in other groups (5898-6766ng/mL). The highest response was in animals that received nirB_SspH1 YS1646 PO then IM rCatB. In this group, reductions in worm and intestine/liver egg burden (vs. control) were 93.1% and 79.5%/90.3% respectively (all P < .0001). Granuloma size was reduced in all vaccinated groups (range 32.9-52.8 x103µm2) and most significantly in the nirB_SspH1 + CatB IM group (34.7±3.4 x103µm2vs. 62.2±6.1 x103µm2: vs. control P < .01). Many eggs in the vaccinated animals had abnormal morphology. Targeting CatB using a multi-modality approach can provide almost complete protection against S. mansoni challenge.

Objective Brow Height Measurements Following Pretrichial Brow Lift and Upper Lid Blepharoplasty.

BACKGROUND: As the ptotic brow drops below the supraorbital rim, it can exacerbate dermatochalasis by pushing the adjacent skin of the upper lid further down. AIM: The purpose of this study was to evaluate the outcomes associated with a combined pretrichial brow lift and upper lid blepharoplasty in patients with dermatochalasis and mild to moderate brow ptosis. MATERIALS AND METHODS: A retrospective case series of 46 patients with dermatochalasis and mild to moderate brow ptosis treated with a combined, bilateral pretrichial brow lift and upper lid blepharoplasty from January 2008 to December 2011. Main outcome measures included measurements of brow lift at 3 months post-operatively, complications encountered, patient satisfaction and surgeon satisfaction. RESULTS: Outcomes from 46 patients were evaluated. The mean brow lift was 1.85 mm at the lateral canthus, 1.54 mm at the lateral limbus, 1.31 mm at the mid-pupil, and 1.07 mm at the medial limbus. Brow lift at the lateral canthus was significantly more elevated than at the medial limbus (P < 0.001). Minor complications were encountered in seven of 46 patients (15.2%). Mean patient satisfaction score was 3.20 and surgeon satisfaction 3.24 (max = 4, very satisfied). CONCLUSIONS: The modified pretrichial brow lift offered effective lateral lift that complements an upper lid blepharoplasty. This technique was met with a high degree of patient and surgeon satisfaction, and had a minimal complication profile.

Wolff-Parkinson-White (WPW) syndrome: the detection of delta wave in an electrocardiogram (ECG).

The delta wave remains an important indicator to diagnose the WPW syndrome. In this paper, a new method of detection of delta wave in an ECG signal is proposed. Firstly, using the continuous wavelet transform, the P wave, the QRS complex and the T wave are detected, then their durations are computed after determination of the boundary location (onsets and offsets of the P, QRS and T waves). Secondly, the PR duration, the QRS duration and the upstroke of the QRS complex are used to determine the presence or absence of the delta wave. This algorithm has been tested on the Physionel database (ptbdb) in order to evaluate its robustness. It has been applied to clinical signals from patients affected by WPW syndrome. This method can provide assistance to practitioners in order to detect the WPW syndrome.

Assessment of Office-Based Practice Patterns on Protective Eyewear Counseling for Patients With Monocular Vision.

PURPOSE: To investigate the practice patterns of office-based counseling on the importance of protective eyeglasses in monocular patients and to offer our counseling recommendations. METHODS: In this cross-sectional study, data were collected in the form of surveys. Surveys were administered at an oculoplastic ophthalmology clinic in Michigan. Inclusion criteria included adults with vision of 20/400 or worse in only 1 eye. Survey questions were focused on whether patients with monocular vision recall being previously counseled by their primary ophthalmologist about wearing eye protection. RESULTS: A total of 60 surveys were completed. The average age was 62.2 years old (range: 23-90 years old). Of the completed surveys, 56.7% (34/60) did not recall receiving education about wearing protective glasses over their better seeing eye, while 35.0% (21/60) recalled having received education from their referring ophthalmologist about eye protection, and 8.3% (5/60) were uncertain about receiving eye protection counseling. Twenty (33.3%) patients reported the reason for decreased vision. Of those, 35% (7/20) of patients reported monocular vision resulting from trauma, while 65% (13/20) reported vision loss due to other reasons. There was no significant difference in recall of receiving counseling about the importance of eye protection between the 2 groups (p = 0.74). CONCLUSIONS: The results of this study highlight the current counseling short-comings, as more than half (56.7%) of patients surveyed did not recall being counseled on the importance of protecting their better seeing-eye, or ways of doing so. More counseling on protective eyewear needs to be incorporated into the preferred practice pattern for care of patients with monocular visual impairment because these patients are vulnerable to the devastating consequences of complete blindness as a result of an injury to their functioning eye.