Relapsing Anti-GAD65-Associated Encephalitis Responsive to Thymoma Resection, Radiation, and Immunomodulatory Therapy.

Herein we describe a case of relapsing anti-GAD65-associated encephalitis which was responsive to the combination of thymoma resection, external beam radiotherapy, and immunomodulatory therapy. The case illustrates the value of remaining vigilant for the possibility of paraneoplastic syndromes in the context of anti-GAD65 antibodies and thymoma. It also illustrates that tumor-directed therapies may offer additional benefit beyond immunomodulatory therapy alone.

Management of radiation-induced oral mucositis in head and neck cancer patients: a real-life survey among 25 Italian radiation oncology centers.

AIM: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers. METHODS: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy. RESULTS: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity. CONCLUSION: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation.

An Online Mindfulness Program for Teachers: A Feasibility Study of the DeStress Monday at School Program.

Objectives: Stress has deleterious effects on teachers' well-being and interactions with students. While in-person mindfulness programs have demonstrated benefits for teachers' mental health, in-person classes are often not feasible due to teachers' busy schedules. This study assessed four components of feasibility (implementation, demand, acceptability, and limited-efficacy testing) for an online mindfulness intervention for teachers. Method: A volunteer sample of 50 primary school teachers was recruited across three urban public schools and was offered a 9-week online mindfulness program (DeStress Monday at School). The program provided weekly mindfulness practices for (1) self-care and (2) classroom use to promote teacher and student stress management. Surveys and focus group discussions assessed program feasibility. Paired t-tests were used to evaluate pre-post changes in teacher well-being. Results: Most participants had no technical problems, providing general support for implementation. Support for program demand was mixed; while 85% of participants used practices at least once, some never used practices, and over half used practices only 1-3 times. Those who used practices generally rated their acceptability favorably. Qualitative analyses showed significant pre-post improvements in work-related and overall stress, depressive and anxiety symptoms, and sleep; those who used practices reported more benefits than those who did not. Qualitative data corroborated these findings, with teachers describing improved stress- and emotion-management following program use. Conclusions: Our findings suggest mindfulness can be delivered online to teachers and may enhance mental health and wellness. Next steps include conducting more rigorous research with a control condition to better understand potential program impact. Preregistration: This study is not preregistered. Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-023-02142-3.

Daptomycin Pharmacokinetics and Pharmacodynamics in Patients on Methadone Substitution Therapy.

BACKGROUND AND OBJECTIVE: When administered for severe infections in intravenous drug users (IDUs) at a daily dose of 6 mg/kg, daptomycin displayed abnormal pharmacokinetic parameters compared with those seen in healthy volunteers; specifically, decreased trough and maximum concentrations (Ctrough; Cmax) and increased clearance (CL). The objective of this study was to evaluate the pharmacokinetics and pharmacodynamics of daptomycin administered at a daily dosage of 12 mg/kg for Staphylococcus aureus infective endocarditis (IE) in patients concomitantly treated with methadone, and to compare the results with those published in the literature for healthy controls treated with the same daily dose. METHODS: Antibiotic treatment included daptomycin (12 mg/kg daily) in combination with an antistaphylococcal ß-lactam (cefazolin 2 g three times a day). The minimum inhibitory concentration (MIC) of Staphylococcus aureus isolated through blood cultures was used to calculate pharmacokinetic and pharmacodynamic parameters such as the ratio of the area under the concentration-time curve over 24 h to the MIC (AUC0-24/MIC) and Cmax/MIC. RESULTS: Five IDUs hospitalized for IE were enrolled. The mean measured daptomycin Cmax and Ctrough were 54.1 µg/mL (CV: 0.32) and 8.7 µg/mL (CV: 0.59), respectively; the mean calculated AUC0-24 was 742.7 µg × h/mL (CV: 0.31). The estimated average volume of distribution at the steady state (Vd,ss) and the half-life (t1/2) were 316.5 mL/kg (CV: 0.53) and 14.4 h (CV: 0.30), respectively. The mean daptomycin clearance from plasma normalized for body weight (CLwp) was 17.3 mL/(h × kg) (CV: 0.33). The calculated average Cmax and AUC0-24 (183.7 µg/mL and 1277.4 µg × h/mL, respectively) were lower than and statistically significantly different from (p < 0.001 and p = 0.001, respectively) those expected for healthy volunteers. CONCLUSIONS: Treatment of Staphylococcus aureus IE in IDUs on methadone treatment requires the use of high daptomycin daily doses in order to achieve satisfactory pharmacodynamic parameters. Close monitoring of the daptomycin plasma concentration is suggested.

Evaluating the Relationship Between Depression and Cognitive Function Among Children and Adolescents with HIV in Zambia.

Depression is common among people living with HIV. Multiple studies demonstrate a link between depression and cognitive dysfunction in adults with HIV, but the association has been minimally investigated in children and adolescents with HIV in Africa. We conducted a cross-sectional analysis as part of the HIV-associated Neurocognitive Disorders in Zambia study, a prospective cohort study in Lusaka, Zambia. We included 208 perinatally-infected children with HIV ages 8-17 taking antiretroviral therapy and 208 HIV-exposed uninfected (HEU) controls. Cognition was assessed with a comprehensive neuropsychological battery. Depressive symptoms were evaluated using self-report and parent-report versions of the NIH Toolbox Sadness module and the Patient Health Questionnaire-9 (PHQ-9). Risk factors for depression and associations between depressive symptoms and cognition were evaluated in bivariable and multivariable regression models. Participants with HIV demonstrated higher levels of depressive symptoms than controls (mean NIH Toolbox Sadness T-Score 50 vs. 44, p < 0.01; mean PHQ-9 score 2.0 vs. 1.5, p = 0.03), and were more likely to have cognitive impairment (30% vs. 13%, p < 0.001). Risk factors for depressed mood included self-reported poor health (OR 7.8, p < 0.001) and negative life events (OR 1.3, p = 0.004) Depressed mood was associated with cognitive impairment in participants with HIV (OR = 2.9, 95% CI 1.2-7.2, p = 0.02) but not in HEU participants (OR 1.7, 95% CI 0.18-15.7, p = 0.6). In conclusion, depressed mood is common among youth with HIV in Zambia, and is associated with cognitive impairment. Depression may be a result of HIV-related stress and stigma, or may be part of the spectrum of HIV-associated neurocognitive disorders. The causal relationship between depressed mood and cognitive impairment is unclear and should be evaluated in future longitudinal studies.

Utility of the International HIV Dementia Scale for HIV-Associated Neurocognitive Disorder.

BACKGROUND: We assessed the utility of the International HIV Dementia Scale (IHDS) in detecting HIV-associated neurocognitive disorder (HAND) in Uganda in antiretroviral (ART)-naïve and ART-experienced adults. SETTING: A longitudinal observational cohort study in Rakai, Uganda. METHODS: Three hundred ninety-nine HIV+ ART-naïve adults underwent neurological, functional status, and neuropsychological assessments including the IHDS. Three hundred twelve participants who initiated ART were re-evaluated after 2 years. HAND stages [asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia (HAD)] were determined based on Frascati criteria using local normative data. Sensitivity, specificity, and area under the ROC curve were determined for various IHDS thresholds (≤9, ≤ 9.5, and ≤10). RESULTS: At baseline, the participants' mean age was 35 years (SD ± 8), 53% were men, and 84% had less than a high school education. At baseline, sensitivity for detecting any HAND stage, symptomatic HAND [mild neurocognitive disorder, HAD], and HAD alone were maximized at IHDS ≤10 (81%, 83%, 92%, respectively). Among 312 individuals who returned for the 2-year follow-up and had initiated ART, a score of ≤10 provided a lower or equal sensitivity for detecting different stages of HAND (all HAND: 70%; symptomatic HAND: 75%; HAD: 94%). The area under the ROC curve was higher for ART-experienced versus ART-naïve individuals. CONCLUSIONS: The IHDS is a potentially useful screening tool for neurocognitive impairment in rural Uganda for both ART-naïve and ART-experienced adults. A cutoff ≤10 demonstrates higher sensitivity for more severe HAND stages compared with less severe HAND. Future studies should focus on potential modifications to the IHDS to improve its specificity.

Two-year follow-up of the pharmacokinetics of immunosuppressive drugs in a neonate who underwent heart transplantation.

The pharmacokinetic properties of immunosuppressive drugs are quite different in newborns than in adults and few studies describe the pharmacokinetics of these drugs in pediatric heart transplant recipients. We report on the two-year follow up of a neonate who underwent heart transplantation for Hypoplastic Left Heart Syndrome on day of life 9. Two different immunosuppressive regimens were used: cyclosporine, azathioprine and prednisone in the early postoperative period, followed by the routine tacrolimus and mycophenolate mofetil combination plus prednisone from post-transplant day 22. Our findings demonstrate marked variability in immunosuppressive pharmacokinetic profiles early post-transplant. Frequent monitoring of drug levels is required to ensure that they remain within the therapeutic range. After the first 2-3 months post-transplant, changes in immunosuppressive drug levels are less marked and correlate more with the administered dosage.

La vellosidad placentaria en la malformación de Chiari tipo II / Placental villi in Chiari malformation type II

Nuestro propósito es el de evaluar con las técnicas de microscopía de luz una visión general del árbol velloso placentario con sus tipos de estructura vellosa y el grado de maduración en caso de malformación de Chiari II. Muestras de placenta, con grado I de madurez, de las últimas ramificaciones del árbol velloso, en la semana 24 gestación, se comparan con las normales de la misma edad. Laboratorio de Microscopía Electrónica, CIADANA. Vellosidades troncales con un centro estromal fibroso que abarca a todo el estroma fueron observadas. Un predominio de vellosidades intermedias inmaduras con escasas intermedias maduras dominan el campo. Escasas terminales sobresalen de las intermedias maduras. Los resultados indican una madurez vellosa persistente mostrando un retraso de cuatro semanas y media, con respecto al patrón normal, siendo ligeramente asincrónica. Esta malformación blastogenética originada por defecto embrionario de la línea primitiva, frecuentemente letal y multisistémica envuelve defectos de placentación o en la malformación de cordón que tiende a ser severa y compleja provocando bajo peso al nacer y muerte fetal

La placenta y el cordón umbilical del feto papiráceo en la anemia drepanocítica / The placenta and umbilical cord in papyraceous in sickle cell disease

Analizar la placenta y el cordón umbilical de un embarazo gemelar diamniónico-monocoriónico complicado con anemia de células falciformes y muerte intrauterina fetal es el propósito de este estudio. Análisis macro y microscópico de regiones de la placenta y del cordón umbilical del feto muerto fueron realizados, Inserción excéntrica del cordón, edema generalizado y colapso del mismo parecen ser la causa de muerte del feto papiráceo. Cambios degerativos fueron observados en el cordón umbilical y alteraciones placentarias demostraron una incrementada deposición de fobrinoide afectando el 40 por ciento de su disco placentario. Estos hallazgos son de importancia ya que la morbilidad del gemelo sobreviviente está en un alto riesgo. Como el síndrome de transfusión fetofetal ocurre en este tipo de placentación su posible aparición en los estadios tempranos del embarazo se discute en relación con otros factores que también son de elevado riesgo

Cambios degenerativos coriónicos y su relación con desórdenes hipertensivos en casos de desprendimiento prematuro grave de placenta normoinserta / Corionic degenerative changes and its relations with hypertensive disorders in cases of severe premature detachment of normo insert placenta

Se identifican y evalúan los cambios degenerativos en el parénquima placentario en relación con desórdenes hipertensivos en casos de desprendimiento prematuro de placentas normalmente insertadas y graves. Se tomaron diez placentas, siete de pacientes con hipertensión y tres de pacientes sin hipertensión de las cuales se recolectaron las lesiones de placa coriónica, vellosidades, vasos vellositarios y las que afectan al espacio intervelloso cercano a la superficie de desprendimiento, con técnicas de microscopia de luz, para determinar si dichos cambios histopatológicos están bajo la influencia de la presión arterial materna. Los hallazgos indican una mayor presencia de edema, necrosis, polimorfonucleares, fibrinoide, infartos, nódulos sinciciales, fibrosis estromal, cambios e inflamación de la pared de vasos, que son más notables en las placentas de las hipertensas. Las alteraciones probablemente están provocando un mayor porcentaje de la superficie de desprendimiento en las placentas de las hipertensas.

La vellosidad placentaria en caso de anemia drepanocítica / The placentary villi to case of drepanocytic anemia

Describir los efectos de la hemoglobinopatía SS en la organización histoarquitectónica de las últimas ramificaciones periféricas del árbol velloso maduro. Se tomaron imágenes de micrografías de luz y electrónica de barrido con las alteraciones sufridas. Centro de Investigación y Análisis Docente Asistencial del Núcleo Aragua. facultad de Ciencias de la Salud. Laboratorio de Microscopia Electrónica. Maracay. Estado Aragua. Deposición de fibrinoide intravelloso incrementado se observó en las diferentes vellosidades infiltrado por células X trofoblástica. Es notorio el incremento de nódulos sincitiales. Hay necrosis del trofoblasto. El estroma contiene vasos dilatados y congestionados con uno o tres eritrocitos nucleados. Se identificó hemorragia estronal, necrosis endotelial, fibrosis y desorganización estromal por edema hidrópico, calcificación, infartos vellosidades intermedias maduras con deficiencia de vellosidad terminal. Los resultados indican cambios degenerativos a nivel de la barrera placentaria que pronostican retardo del crecimiento intrauterino similar al encontrado con mala perfusión de la vellosidad placentaria de origen fetal o materno.

Vellosidades placentarias terminales filiformes en la anemia drepanocítica / Terminal filiform placental villi in sickle cell disease

Describir las vellosidades placentarias filiformes, descritas anteriormente como vellosidades intermedias maduras con deficiencia de vellosidades terminales, en la hemoglobinopatía ss, con técnicas de microscopia de luz y electrónica de barrido, es el propósito de nuestro trabajo. Cincuenta láminas de hemotoxilina-eosina fueron observadas de regiones marginales, centrales e intermedias próximas a la placa basal de la placenta y especímenes fueron tomados para su observación con el microscopio electrónico de barrido. Los resultados indican la presencia de vellosidades terminales filiformes, que sobresalen del conglomerado con un eje longitudinal muy alargado diferente a las vellosidades terminales normales. Se destacan por la ausencia de citotrofoblastos, trofoblasto sincisial de grosor variable y reducción de membrana vasculosincisiales. La distancia del centro de la luz del capilar a la superficie del trofoblasto es relativamente grande. Este último carácter y el estancamiento de eritrocitos en los capilares alargados dañan la superficie de intercambio de gases y nutrientes que pronostican retardo del crecimiento intrauterino

Necrosis celular en placa placentaria y su relación con desórdenes hipertensivos en casos de desprendimiento prematuro de placenta / Cellular necrosis in basal plate on the placenta and its relationship with hypertensive disorders in cases of premature placental detachment

Evaluar la muerte celular en células desiduales o trofoblásticas en la decidua placentaria en relación con desórdenes hipertensivos en casos de desprendimiento prematuro de placenta graves. Se tomaron diez placentas, siete de pacientes con desórdenes hipertensivos y tres sin hipertensión. Se recolectaron las características microscópicas referidas a lesiones maternas placentarias ocurridas durante en desprendimiento de la placenta y las microscópicas correspondientes a muerte celular en placa basal. Laboratorio de microscopia electronica de barrido del CIDANA y Departamento de Obstetricia y Ginecología del Hospital Central de Maracay área de postgrado. No se encontraron diferencias morfológicas en los razgos analisados tanto macro como microscópicamente que permitieran distinguir las hipertensas de las no hipertensas excepto una mayor depresión en las últimas

La vellosidad placentaria en caso de primigesta infectada por plasmodium vivax y tratada con cloroquina / The hairiness placental in the event of infected primigesta for plasmodium vivax and tried with cloroquine

Se describen los cambios histológicos en una placenta obtenida de paciente primigesta infectada por P. Vivax y tratada con cloroquina antes del parto de un recien nacido de bajo peso. Técnicas de análisis macroscópica y microscópica se aplicaron a vellosidades cerca de la región materna de la placenta. Los hallazgos revelaron la presencia de extensas áreas del parénquima infartadas con bloqueo del flujo sanguíneo intervelloso, ausencia de eritrocitos infectados y de infiltración inflamatoria mononuclear. Presencia de nódulos sinciciales, pérdida de la estructura estromal vellositaria, congestión y vasodilatación de capilares estromales, presencia de eritrocitos nucleados en la luz de estos últimos. Además se notaron cambios degenerativos del trofoblasto, deposición de fibrina o fibrinoide perivelloso y calificación distrófica. Ellos indican una disfunción placentaria que pronostica retardo del crecimiento intrauterino