Association of neurotransmitter pathway polygenic risk with specific symptom profiles in psychosis.

A primary goal of psychiatry is to better understand the pathways that link genetic risk to psychiatric symptoms. Here, we tested association of diagnosis and endophenotypes with overall and neurotransmitter pathway-specific polygenic risk in patients with early-stage psychosis. Subjects included 205 demographically diverse cases with a psychotic disorder who underwent comprehensive psychiatric and neurological phenotyping and 115 matched controls. Following genotyping, we calculated polygenic scores (PGSs) for schizophrenia (SZ) and bipolar disorder (BP) using Psychiatric Genomics Consortium GWAS summary statistics. To test if overall genetic risk can be partitioned into affected neurotransmitter pathways, we calculated pathway PGSs (pPGSs) for SZ risk affecting each of four major neurotransmitter systems: glutamate, GABA, dopamine, and serotonin. Psychosis subjects had elevated SZ PGS versus controls; cases with SZ or BP diagnoses had stronger SZ or BP risk, respectively. There was no significant association within psychosis cases between individual symptom measures and overall PGS. However, neurotransmitter-specific pPGSs were moderately associated with specific endophenotypes; notably, glutamate was associated with SZ diagnosis and with deficits in cognitive control during task-based fMRI, while dopamine was associated with global functioning. Finally, unbiased endophenotype-driven clustering identified three diagnostically mixed case groups that separated on primary deficits of positive symptoms, negative symptoms, global functioning, and cognitive control. All clusters showed strong genome-wide risk. Cluster 2, characterized by deficits in cognitive control and negative symptoms, additionally showed specific risk concentrated in glutamatergic and GABAergic pathways. Due to the intensive characterization of our subjects, the present study was limited to a relatively small cohort. As such, results should be followed up with additional research at the population and mechanism level. Our study suggests pathway-based PGS analysis may be a powerful path forward to study genetic mechanisms driving psychiatric endophenotypes.

Predicting Clinical Improvement in Early Psychosis Using Circuit-Based Resting-State Functional Magnetic Resonance Imaging.

BACKGROUND AND HYPOTHESIS: Identifying biomarkers that predict treatment response in early psychosis (EP) is a priority for psychiatry research. Previous work suggests that resting-state connectivity biomarkers may have promise as predictive measures, although prior results vary considerably in direction and magnitude. Here, we evaluated the relationship between intrinsic functional connectivity of the attention, default mode, and salience resting-state networks and 12-month clinical improvement in EP. STUDY DESIGN: Fifty-eight individuals with EP (less than 2 years from illness onset, 35 males, average age 20 years) had baseline and follow-up clinical data and were included in the final sample. Of these, 30 EPs showed greater than 20% improvement in Brief Psychiatric Rating Scale (BPRS) total score at follow-up and were classified as "Improvers." STUDY RESULTS: The overall logistic regression predicting Improver status was significant (χ2 = 23.66, Nagelkerke's R2 = 0.45, P < .001, with 85% concordance). Significant individual predictors of Improver status included higher default mode within-network connectivity, higher attention-default mode between-network connectivity, and higher attention-salience between-network connectivity. Including baseline BPRS as a predictor increased model significance and concordance to 92%, and the model was not significantly influenced by the dose of antipsychotic medication (chlorpromazine equivalents). Linear regression models predicting percent change in BPRS were also significant. CONCLUSIONS: Overall, these results suggest that resting-state functional magnetic resonance imaging connectivity may serve as a useful biomarker of clinical outcomes in recent-onset psychosis.

Gas tamponade followed by laser treatment for macular retinal detachment secondary to optic pit.

PURPOSE: The study aimed to describe anatomic and visual outcomes associated with perfluoropropane intravitreal injection followed by laser treatment for macular retinal detachment secondary to optic disc pit. METHODS: A single-center, retrospective study. Medical records of all patients treated at a tertiary retina referral center were evaluated between 2011 and 2018 for congenital optic disc pit-associated macular detachment with 0.3 ml 100% perfluoropropane intravitreal injection followed by retinal laser photocoagulation along the temporal optic disc margin as the initial treatment. RESULTS: Six patients with optic disc pit-associated macular detachment were identified, with postoperative follow-up ranging from 13 to 52 months (mean: 28 months). Spectral domain optical coherence tomography (SD-OCT) showed complete fluid resolution without recurrence in five of the six cases. Four cases showed complete reabsorption after Intravitreal perfluoropropane plus laser, one patient needed an extra procedure (pars plana vitrectomy with inner limiting membrane peeling and pedicle flap inversion over the temporal optic disc margin) to achieve complete fluid reabsorption, and one patient had persistent intraretinal fluid and denied additional surgeries. The time between the initial procedure and total fluid reabsorption varied from 6.5 to 41 months (mean: 19.5 months). Best-corrected visual acuity improved after surgery on the last follow-up visit in all cases. CONCLUSION: 100% perfluoropropane intravitreal injection followed by photocoagulation along temporal optic disc margin was associated with anatomic and visual improvement in most cases, representing an alternative treatment approach for optic disc pit-associated macular detachment.

A slow-release dexamethasone implant for cancer-associated retinopathy.

This case report aims to show the anatomical and functional results of a patient diagnosed as having cancer-associated retinopathy treated with a controlled-release dexamethasone implant (Ozurdex). Anatomical outcomes were assessed using spectral domain optical coherence tomography; and functional outcomes, by measuring visual acuity, microperimetry, and mutifocal electroretinography. The follow-up period was 1 year.

Association of neurotransmitter pathway polygenic risk with specific symptom profiles in psychosis.

A primary goal of psychiatry is to better understand the pathways that link genetic risk to psychiatric symptoms. Here, we tested association of diagnosis and endophenotypes with overall and neurotransmitter pathway-specific polygenic risk in patients with early-stage psychosis. Subjects included 206 demographically diverse cases with a psychotic disorder who underwent comprehensive psychiatric and neurological phenotyping and 115 matched controls. Following genotyping, we calculated polygenic scores (PGSs) for schizophrenia (SZ) and bipolar disorder (BP) using Psychiatric Genomics Consortium GWAS summary statistics. To test if overall genetic risk can be partitioned into affected neurotransmitter pathways, we calculated pathway PGSs (pPGSs) for SZ risk affecting each of four major neurotransmitter systems: glutamate, GABA, dopamine, and serotonin. Psychosis subjects had elevated SZ PGS versus controls; cases with SZ or BP diagnoses had stronger SZ or BP risk, respectively. There was no significant association within psychosis cases between individual symptom measures and overall PGS. However, neurotransmitter-specific pPGSs were moderately associated with specific endophenotypes; notably, glutamate was associated with SZ diagnosis and with deficits in cognitive control during task-based fMRI, while dopamine was associated with global functioning. Finally, unbiased endophenotype-driven clustering identified three diagnostically mixed case groups that separated on primary deficits of positive symptoms, negative symptoms, global functioning, and cognitive control. All clusters showed strong genome-wide risk. Cluster 2, characterized by deficits in cognitive control and negative symptoms, additionally showed specific risk concentrated in glutamatergic and GABAergic pathways. Due to the intensive characterization of our subjects, the present study was limited to a relatively small cohort. As such, results should be followed up with additional research at the population and mechanism level. Our study suggests pathway-based PGS analysis may be a powerful path forward to study genetic mechanisms driving psychiatric endophenotypes.

Clinical, epidemiological and laboratory characteristics of cases of Covid-19-related maternal near miss and death at referral units in northeastern Brazil: a cohort study.

Objective: Covid-19 poses a major risk during pregnancy and postpartum, resulting in an increase in maternal mortality worldwide, including in Brazil; however, little research has been conducted into cases of a near miss. This study aimed to describe the frequency of COVID-19-related near miss and deaths during pregnancy or in the postpartum in referral centers in northeastern Brazil, as well as the clinical, epidemiological, and laboratory characteristics of the women who experienced a severe maternal outcome.Methods: A retrospective and prospective cohort study was performed between April 2020 and June 2021 with hospitalized pregnant and postpartum women with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction (RT-PCR). Data from five tertiary hospitals in northeastern Brazil were evaluated. Descriptive statistical analysis was performed using Epi Info, version 7.2.5.0.Results: A total of 463 patients were included. Of these, 64 (14% of the sample) had a severe maternal outcome, with 42 cases of near miss (9%) and 22 maternal deaths (5%). Patients who had a severe maternal outcome were predominantly young (median age 30 years) and 65.6% were black or brown-skinned. The women had between 6 and 16 years of schooling; 45.3% had a stable partner; 81.3% were pregnant at the time of admission to the study; and 76.6% required a Cesarean section. The great majority (82.8%) had severe acute respiratory syndrome (SARS). Other complications included hypertensive syndromes (40.6%), pneumonia (37.5%), urinary tract infections (29.7%), acute renal failure (25.0%) and postpartum hemorrhage (21.9%). Sepsis developed in 18.8% of cases, neurological dysfunction in 15.6%, and hepatic dysfunction and septic shock in 14.1% of cases each. The relative frequency of admission to an intensive care unit was 87.5%, while 67.2% of the patients required assisted mechanical ventilation, and 54.7% required noninvasive ventilation. Antibiotics were prescribed in 93.8% of cases and corticosteroids in 71.9%, while blood transfusion was required in 25.0% of cases and renal replacement therapy in 15.6%. Therapeutic anticoagulants were administered to 12.5% of the patients. Of the patients who had a severe maternal outcome, the frequency of respiratory dysfunction was 93.8%, with 50.0% developing neurological dysfunction and 37.5% cardiovascular dysfunction. Hematological dysfunction was found in 29.7%, renal dysfunction in 18.8%, and uterine dysfunction in 14.1%. Hepatic dysfunction occurred in 7.8% of the sample. The near-miss ratio for Covid-19 was 1.6/1000 live births and the maternal mortality ratio for Covid-19 was 84.8/100,000 live births, with a mortality index of 34.4% in the sample.Conclusion: This study revealed a low Covid-19-related maternal near miss (MNM) ratio of 1.6/1000 live births and a high Covid-19-related maternal mortality ratio (MMR) of 84.81/100,000 live births. The mortality index was also high. Most of the patients were admitted while pregnant, were young, married and black or brown-skinned, and none had completed university education. The majority had SARS and required admission to an intensive care unit and mechanical ventilation. Most were submitted to a Cesarean section.

ERG and OCT abnormalities in retinoblastoma after melphalan intravitreous injection.

The authors report full-field electroretinogram and optical coherence tomography findings of intravitreal melphalan retinal toxicity. An 18-month-old girl with unilateral group D retinoblastoma was evaluated with light-adapted 3 full-field electroretinogram protocol and optical coherence tomography (I-Stand optical coherence tomography, Optovue) after treatment with intravitreal melphalan for active vitreous seeds. After the third injection, the child developed retinal pigment epithelial changes near the injection site. The photopic response of the full-field electroretinogram standard flash cones showed a decrease in amplitude responses of waves a and b in the affected eye compared to the contralateral eye. Optical coherence tomography showed loss of photoreceptors and outer nuclear layers in the affected eye. Melphalan toxicity is dose-dependent, and despite its treatment benefits, it can affect vision. Our case shows an updated, in-depth retinal toxicity assessment of intravitreal melphalan in the human retina with optical coherence tomography and its correlation with electroretinogram changes.

Decreased Retinal Sensitivity Overlying Choroidal Nevi.

PURPOSE: To report retinal function findings on the choroidal nevus. METHODS: Prospective descriptive case series of 7 patients (n = 7 eyes) presenting a melanocytic choroidal lesion consistent with choroidal nevus and no other ocular disease. Baseline evaluation included measurement of best-corrected visual acuity (BCVA), color and near-infrared fundus pictures, and spectral-domain OCT (Heidelberg Engineering). Retinal function was tested with microperimetry (MAIA; CenterVUE, Padova) using a standard grid (µP1) and a linear grid (µP2) that distribute test points on retinal areas that overlaid the choroidal lesion as well as lesion-free areas equidistantly to the fovea in 3 parallel lines. mfERG was performed following the International Society for Clinical Electrophysiology of Vision (ISCEV) recommendation using a 61-hexyagon protocol. RESULTS: BCVA was 20/25 (0.1 logMAR) or better in all 7 eyes. Microperimetry showed central stable fixation on all eyes, with mean ± SE sensitivity threshold significantly decreased on retinal areas overlaying the lesions (µP1): 21.8 ± 0.6 dB versus 25.2 ± 0.9 dB on nonaffected retinal areas (p < 0.001). Sensitivity was also decreased on µP2: 23.7 ± 0.2 dB for areas overlying the nevi and 25.7 ± 0.3 dB for the nonaffected retina (p < 0.001). mfERG responses showed no focal amplitude or implicit-time changes on the retina in the topographical region corresponding to the nevus for all patients. CONCLUSION: Our results indicate that choroidal nevi may cause significant retinal sensitivity impairment, as shown by microperimetry, but preserved mfERG response indicates that the retinal function may be only partially impaired.

Major mutations in the NS3 gene region of hepatitis C virus related to the resistance to direct acting antiviral drugs: a systematic review.

Hepatitis C virus (HCV) remains a global public health problem with high prevalence rates and chronicity of infection. Present work aimed to describe the main mutations in the NS3 region of the HCV genome related to the resistance of patients to the currently available direct-acting antivirals (DAAs). To guide the study description, the preferred items in the PRISMA protocol for systematic review were used. The data collected were HCV genotypes and subtypes and mutations in HCV NS3, general and stratified by continent. The 10 papers selected for this systematic review reported studies in seven countries, on three continents, and generated data of 2937 patients. The most frequent HCV subtype was 1a. Prevalence of genotypes suggested that there were few demographic regions reached by the studies, since there were regional variations in the type of genotypes reported in the available bibliographies. Of the total study population, 35.3% (n = 1037) had mutations in the NS3 gene region of HCV, suggesting a high rate of resistance to DAAs and a low sustained virologic response among those who used some therapeutic option. Ten major mutations were identified: Q80K, V170I, S122G, V36L, T54S, D168Q, A156S, Q80G, S122R, and V55A. The Q80K mutation was the highlight of the study, appearing not only with greater representativity (61.6%) but also as the only one described in the three continents analyzed. This systematic review reinforces the need to carry out more studies of detection of these mutations to fill in all information gaps that might help in optimization of treatment.

ERG and OCT abnormalities in retinoblastoma after melphalan intravitreous injection / Anormalidades do ERG e OCT em um caso de retinoblastoma após injeção intravítrea de melfalan

ABSTRACT The authors report full-field electroretinogram and optical coherence tomography findings of intravitreal melphalan retinal toxicity. An 18-month-old girl with unilateral group D retinoblastoma was evaluated with light-adapted 3 full-field electroretinogram protocol and optical coherence tomography (I-Stand optical coherence tomography, Optovue) after treatment with intravitreal melphalan for active vitreous seeds. After the third injection, the child developed retinal pigment epithelial changes near the injection site. The photopic response of the full-field electroretinogram standard flash cones showed a decrease in amplitude responses of waves a and b in the affected eye compared to the contralateral eye. Optical coherence tomography showed loss of photoreceptors and outer nuclear layers in the affected eye. Melphalan toxicity is dose-dependent, and despite its treatment benefits, it can affect vision. Our case shows an updated, in-depth retinal toxicity assessment of intravitreal melphalan in the human retina with optical coherence tomography and its correlation with electroretinogram changes.

RESUMO Os autores relatam os achados de eletrorretinograma de campo total e tomografia de coerência óptica (OCT) da toxicidade retiniana ao melfalan intravítreo. Menina de 18 meses com retinoblastoma foi avaliada com fases fotópicas do eletrorretinograma de campo total e tomografia de coerência óptica após o tratamento com melfalan intravítreo. Após a terceira injeção, a criança desenvolveu alterações do epitélio pigmentar da retina próximo ao local da injeção. A resposta fotópica do eletrorretinograma de campo total mostrou diminuição da amplitude das respostas das ondas a e b no olho afetado comparado com o olho sadio. A tomografia de coerência óptica mostrou alterações significativas nas camadas retinianas externas no olho comprometido. A toxicidade do melfalan é dose dependente e, apesar dos benefícios terapêuticos, podem causar alterações retinianas significativas. Este caso demonstra uma avaliação atual e aprofundada da toxicidade retiniana do melfalan intravítreo na retina humana através da tomografia de coerência óptica e sua correlação com as alterações no eletrorretinograma.

Gas tamponade followed by laser treatment for macular retinal detachment secondary to optic pit / Tamponamento com gás seguido de laser para descolamento de retina secundário à fosseta de disco óptico

ABSTRACT Purpose: The study aimed to describe anatomic and visual outcomes associated with perfluoropropane intravitreal injection followed by laser treatment for macular retinal detachment secondary to optic disc pit. Methods: A single-center, retrospective study. Medical records of all patients treated at a tertiary retina referral center were evaluated between 2011 and 2018 for congenital optic disc pit-associated macular detachment with 0.3 ml 100% perfluoropropane intravitreal injection followed by retinal laser photocoagulation along the temporal optic disc margin as the initial treatment. Results: Six patients with optic disc pit-associated macular detachment were identified, with postoperative follow-up ranging from 13 to 52 months (mean: 28 months). Spectral domain optical coherence tomography (SD-OCT) showed complete fluid resolution without recurrence in five of the six cases. Four cases showed complete reabsorption after Intravitreal perfluoropropane plus laser, one patient needed an extra procedure (pars plana vitrectomy with inner limiting membrane peeling and pedicle flap inversion over the temporal optic disc margin) to achieve complete fluid reabsorption, and one patient had persistent intraretinal fluid and denied additional surgeries. The time between the initial procedure and total fluid reabsorption varied from 6.5 to 41 months (mean: 19.5 months). Best-corrected visual acuity improved after surgery on the last follow-up visit in all cases. Conclusion: 100% perfluoropropane intravitreal injection followed by photocoagulation along temporal optic disc margin was associated with anatomic and visual improvement in most cases, representing an alternative treatment approach for optic disc pit-associated macular detachment.

RESUMO Objetivo: Descrever os resultados anatômicos e visuais associados à injeção intravítrea de perfluoropropano seguida de tratamento a laser para descolamento de retina macular secundário à fosseta do disco óptico. Métodos: Estudo retrospectivo em um único centro. Foram revisados os prontuários médicos dos pacientes com descolamento macular associado a fosseta do disco óptico congênito em um centro de referência terciário de retina entre 2011 e 2018. Todos receberam como estratégia de tratamento inicial injeção intravítrea de perfluoropropano 100% seguido por fotocoagulação a laser ao longo da margem temporal do disco óptico. Resultados: Foram identificados seis pacientes com descolamento macular associado a fosseta do disco óptico durante o período do estudo. O seguimento pós-operatório variou de 13 a 52 meses, com média de 28 meses. SD-OCT demonstrou resolução completa do fluido em cindo dos seis casos, sem recorrência. Quatro casos apresentaram reabsorção completa após perfluoropropano intravítreo associado a laser, e um paciente necessitou de procedimento adicional (vitrectomia via pars plana com peeling da membrana limitante interna e inversão do retalho do pedículo sobre a margem temporal do disco óptico) para obter reabsorção completa de fluidos. Um paciente apresentou fluido intrarretiniano persistente e negou tratamentos adicionais. O tempo entre o procedimento inicial e a resolução completa do fluido variou entre 6,5 a 41 meses, com média de 19,5 meses. A acuidade visual corrigida melhorou após a cirurgia, considerando a última consulta de acompanhamento em todos os casos. Conclusão: A injeção intravítrea de perfluoropropano 100% seguida de fotocoagulação ao longo da margem temporal da margem do disco óptico foi associada à melhora anatômica e visual na maioria dos casos e representa uma abordagem terapêutica alternativa para o descolamento macular associado a fosseta do disco óptico.

A slow-release dexamethasone implant for cancer-associated retinopathy / Implante de liberacao lenta de dexametasona para retinopatia associada ao cancer

ABSTRACT This case report aims to show the anatomical and functional results of a patient diagnosed as having cancer-associated retinopathy treated with a controlled-release dexamethasone implant (Ozurdex). Anatomical outcomes were assessed using spectral domain optical coherence tomography; and functional outcomes, by measuring visual acuity, microperimetry, and mutifocal electroretinography. The follow-up period was 1 year.

RESUMO Este relato de caso tem como objetivo mostrar os resultados anatômicos e funcionais de um paciente com diagnóstico de retinopatia associada ao câncer tratado com implante de liberação controlada de dexametasona (Ozurdex®). Os resultados anatômicos foram avaliados por SD-OCT e os resultados funcionais por medida de acuidade visual, microperimetria e eletrorretinograma multifocal. O período de acompanhamento foi de um ano.

A case of atypical nocardia asteroides sclerouveitis resistant to fourth-generation fluoroquinolones / Um caso atípico de esclero-uveíte por Nocardia Asteroides resistente a fluorquinolona de quarta-geração

ABSTRACT We describe an unusual case of Nocardia spp scleritis in a health girl resistant to topical fourth-generation fluoroquinolones. Clinically, there was only partial response of the scleritis to initial therapy. Treatment was changed to meropenem intravenously and topical amikacin. Following several weeks of antibiotic treatment, the patient's infection resolved but her vision was reduced to no light perception. Nocardia asteroides must be considered as a possible agent in cases of necrotizing scleritis in patients without a clear source. Antibiotic sensitivity testing has a definitive role in view of the resistance to these new medications.

RESUMO Nós descrevemos um raro caso de esclerite por Nocardia spp em uma criança sadia resistente a utilização tópica de fluorquinolona de quarta-geração. Clinicamente, a paciente apresentou apenas uma resposta parcial do quadro de esclerite a terapêutica inicial. O tratamento foi então modificado para meropenem intravenoso e amicacina tópica. Após várias semanas de tratamento com antibiótico, o quadro infeccioso regrediu porém a visao da pacientes evoluiu para perda da percepção luminosa. Em casos de esclerite necrotizante em pacientes sem fatores de risco aparente é necessário considerer a Nocardia Asteroides como possível agente causador. Os testes de sensibilidade medicamentosa apresentam importância significativa em virtude do aparecimento de resistência aos novos medicamentos.

Índice de massa corporal em pacientes co-infectados pela tuberculose-HIV em hospital de referência da cidade de Recife, Estado de Pernambuco, Brasil / Body Mass Index of Patients Co-Infected with Tuberculosis and HIV in a Reference Hospital for HIV Patients in the City of Recife, State of Pernambuco, Brazil

O objetivo deste trabalho foi avaliar o índice de massa corporal (IMC) e principais características biológicas, sociais, clínicas e imunológicas de pacientes com tuberculose infectados pelo HIV/aids, comparando-os com aqueles encontrados nos pacientes com HIV/aids sem tuberculose em um hospital de referência para HIV/aids da Cidade de Recife, Estado de Pernambuco, Brasil. Foram selecionados 80 pacientes com HIV/aids, dos quais 40 estavam co-infectados pela tuberculose. Os pacientes foram medidos e pesados, além de responderem a um questionário padronizado elaborado especialmente para a pesquisa. A associação da infecção pelo HIV/aids e tuberculose-doença com IMC inferior a 18,5 kg/m2, indicativo de desnutrição, foi estatisticamente significante. Essa associação poderá ser um sinal sentinela nos serviços de saúde que atendem pacientes infectados pelo HIV, visando proporcionar a eles aporte calórico adequado. Estudos prospectivos dever-se-ão empreender para melhor compreensão da desnutrição como expressão da interação tuberculose-HIV e fator de agravo do quadro clínico de seus pacientes.

The objective of this study was to evaluate the body mass index (BMI) and the main biological, social, clinical and immunological characteristics of patients infected with HIV/AIDS and tuberculosis disease, compared to those HIV infected but with no tuberculosis, in a reference hospital for HIV/AIDS patients in the City of Recife, State of Pernambuco, Brazil. The study population consisted of 80 HIV/AIDS patients, of whom 40 were co-infected with tuberculosis. The patients had their weight and height measured, and answered a structured questionnaire designed specifically for the purpose of the study. The association between a BMI below 18.5 kg/m2 (underweight) and tuberculosis disease-HIV co-infection was statistically significant. That association may be a sentinel sign in health services attended by HIV infected patients, aiming to provide them adequate caloric intake. Prospective studies should be carried out to obtain a better understanding of malnutrition as expression of tuberculosis-HIV co-infection, and as an aggravating factor to clinical conditions of their patients.