Reacciones sarcoideas relacionadas con inhibidores de puntos de control inmunitario / Sarcoid-like Reactions to Immune Checkpoint Inhibitors

Los inhibidores de puntos de control inmunitario (ICI) pueden producir toxicidades cutáneas inmunomediadas entre las que se encuentran las reacciones sarcoideas. Nuestro objetivo fue analizar retrospectivamente los datos clínicos e histológicos de los pacientes en tratamiento con ICI que desarrollaron reacciones sarcoideas cutáneas entre 2019 y 2022. Se incluyeron siete pacientes (seis mujeres y un varón, con una edad mediana de 65años). La mediana de tiempo de instauración de la clínica fue de 4meses y la forma de presentación más frecuente fue la sarcoidosis papulosa de las rodillas, seguida de la sarcoidosis subcutánea. En todos se confirmó el diagnóstico histológicamente y no se observaron diferencias respecto a la sarcoidosis idiopática. Solo en dos casos fue preciso retirar la inmunoterapia. Las reacciones sarcoideas por ICI suelen ser leves y no suelen requerir la interrupción del tratamiento. Es fundamental obtener una confirmación histológica para distinguirlas de la progresión tumoral (AU)

Immune checkpoint inhibitors (ICIs) can cause immune-mediated cutaneous adverse events, including sarcoid-like reactions. The aim of this study was to retrospectively analyze clinical and histologic data from patients who developed cutaneous sarcoid-like reactions between 2019 and 2022 while under treatment with ICIs. We studied 7 patients (6 women and 1 man) with a median age of 65years. Median time to onset of symptoms was 4months. The most common presentation was papular sarcoidosis of the knees followed by subcutaneous sarcoidosis. Diagnosis was confirmed histologically in all cases, and no differences were observed relative to idiopathic sarcoidosis. Discontinuation of ICI therapy was required in just two patients. ICI-induced sarcoid-like reactions tend to be mild and generally do not require treatment discontinuation. Histologic confirmation is essential for distinguishing these reactions from tumor progression (AU)

[Translated article] Sarcoid-like Reactions to Immune Checkpoint Inhibitors / Reacciones sarcoideas relacionadas con inhibidores de puntos de control inmunitario

Immune checkpoint inhibitors (ICIs) can cause immune-mediated cutaneous adverse events, including sarcoid-like reactions. The aim of this study was to retrospectively analyze clinical and histologic data from patients who developed cutaneous sarcoid-like reactions between 2019 and 2022 while under treatment with ICIs. We studied 7 patients (6 women and 1 man) with a median age of 65years. Median time to onset of symptoms was 4months. The most common presentation was papular sarcoidosis of the knees followed by subcutaneous sarcoidosis. Diagnosis was confirmed histologically in all cases, and no differences were observed relative to idiopathic sarcoidosis. Discontinuation of ICI therapy was required in just two patients. ICI-induced sarcoid-like reactions tend to be mild and generally do not require treatment discontinuation. Histologic confirmation is essential for distinguishing these reactions from tumor progression (AU)

Los inhibidores de puntos de control inmunitario (ICI) pueden producir toxicidades cutáneas inmunomediadas entre las que se encuentran las reacciones sarcoideas. Nuestro objetivo fue analizar retrospectivamente los datos clínicos e histológicos de los pacientes en tratamiento con ICI que desarrollaron reacciones sarcoideas cutáneas entre 2019 y 2022. Se incluyeron siete pacientes (seis mujeres y un varón, con una edad mediana de 65años). La mediana de tiempo de instauración de la clínica fue de 4meses y la forma de presentación más frecuente fue la sarcoidosis papulosa de las rodillas, seguida de la sarcoidosis subcutánea. En todos se confirmó el diagnóstico histológicamente y no se observaron diferencias respecto a la sarcoidosis idiopática. Solo en dos casos fue preciso retirar la inmunoterapia. Las reacciones sarcoideas por ICI suelen ser leves y no suelen requerir la interrupción del tratamiento. Es fundamental obtener una confirmación histológica para distinguirlas de la progresión tumoral (AU)

Sarcoid-like Reactions to Immune Checkpoint Inhibitors. / Reacciones sarcoideas relacionadas con inhibidores de puntos de control inmunitario.

Immune checkpoint inhibitors (ICIs) can cause immune-mediated cutaneous adverse events, including sarcoid-like reactions. The aim of this study was to retrospectively analyze clinical and histologic data from patients who developed cutaneous sarcoid-like reactions between 2019 and 2022 while under treatment with ICIs. We studied 7 patients (6 women and 1 man) with a median age of 65years. Median time to onset of symptoms was 4months. The most common presentation was papular sarcoidosis of the knees followed by subcutaneous sarcoidosis. Diagnosis was confirmed histologically in all cases, and no differences were observed relative to idiopathic sarcoidosis. Discontinuation of ICI therapy was required in just two patients. ICI-induced sarcoid-like reactions tend to be mild and generally do not require treatment discontinuation. Histologic confirmation is essential for distinguishing these reactions from tumor progression.

[Translated article] Sarcoid-like Reactions to Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) can cause immune-mediated cutaneous adverse events, including sarcoid-like reactions. The aim of this study was to retrospectively analyze clinical and histologic data from patients who developed cutaneous sarcoid-like reactions between 2019 and 2022 while under treatment with ICIs. We studied 7 patients (6 women and 1 man) with a median age of 65years. Median time to onset of symptoms was 4months. The most common presentation was papular sarcoidosis of the knees followed by subcutaneous sarcoidosis. Diagnosis was confirmed histologically in all cases, and no differences were observed relative to idiopathic sarcoidosis. Discontinuation of ICI therapy was required in just two patients. ICI-induced sarcoid-like reactions tend to be mild and generally do not require treatment discontinuation. Histologic confirmation is essential for distinguishing these reactions from tumor progression.

¿Qué sucede con la docencia en Oftalmología? / What happens with teaching in Ophthalmology?

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Comparison of pneumococcal vaccination response in children with sickle cell disease: HbSS and HbSC.

INTRODUCTION: Sickle cell disease (SCD) children are at increased risk of invasive pneumococcal disease and rely on penicillin prophylaxis and vaccination for infection prevention. Post-vaccination antibody levels in SCD may wane overtime. HbSC are believed to have better immunological response than HbSS. OBJECTIVE: To compare antibody response to 23-valent pneumococcal polysaccharide vaccine (PPSV-23) between HbSS and HbSC. METHODS: Patients with HbSS (n=33) and HbSC (n=11), aged 7-18 years, were prospectively recruited. Luminex pneumococcal antibody levels were measured for 23-serotypes, after two PPSV-23 doses. RESULTS: Absolute median titer for 20 of the 23 serotypes was higher in HbSC than HbSS and significantly higher for serotypes 22 (3.9 vs. 1.6mcg/ml; p=0.039) and 43 (2.9 vs. 0.8mcg/ml; p=0.007). HbSC mounted a better immune anti-pneumococcal response compared to HbSS (≥1.3mcg/ml) for 18 of 23 serotypes, albeit not significant for any of the serotypes. More HbSC (64%) than HbSS (42%) were good vaccine responders (p=0.303). Two of 21 (10%) good vaccine responders and nine of 23 (39%) poor vaccine responders SCD participants subsequently developed acute chest syndrome or pneumonia (p=0.036). None of the HbSC patients developed ACS after receiving PPSV-23. HbSS poor vaccine responders were at increased future recurrence risk for ACS (p=0.003), pneumonia (p=0.036) or both (p=0.011), compared to good vaccine responders. CONCLUSION: HbSC possess better pneumococcal vaccine response than HbSS. Poor vaccine response is concerning for future acute pulmonary events. Current vaccination strategy for SCD sub-types are lacking, therefore further study to evaluate utility of vaccine boosters is necessary.

Respuesta a antiangiogénicos en el edema macular secundario a necrosis retiniana aguda / Hypertensive choroidopathy and adrenal carcinoma: A new association

Mujer de 55 años con necrosis retiniana aguda (NRA) unilateral que desarrolló edema macular (EM) después de la resolución del cuadro agudo. El EM fue tratado con inyecciones intravítreas de antiangiogénicos (anti-VEGF), siendo controlado durante 4 años. La terapia antiangiogénica puede ser útil en el tratamiento del EM secundario a la NRA, al igual que en el EM secundario a panuveítis donde su eficacia ha sido demostrada

A 55 year-old female patient with unilateral Acute Retinal Necrosis (ARN) developed macular oedema (MO) after the resolution of her necrosis. The macular oedema (MO) was managed and controlled for four years with intravitreal anti-VEGF injections. Anti-VEGF therapy could be useful for the treatment of MO secondary to ARN, the same as for treating MO resulting from panuveitis, where its efficacy has been already demonstrated

Response to anti-VEGF therapy in macular oedema secondary to acute retinal necrosis. / Respuesta a antiangiogénicos en el edema macular secundario a necrosis retiniana aguda.

A 55 year-old female patient with unilateral Acute Retinal Necrosis (ARN) developed macular oedema (MO) after the resolution of her necrosis. The macular oedema (MO) was managed and controlled for four years with intravitreal anti-VEGF injections. Anti-VEGF therapy could be useful for the treatment of MO secondary to ARN, the same as for treating MO resulting from panuveitis, where its efficacy has been already demonstrated.

Severe Hepatopulmonary Syndrome in a Child with Caroli Syndrome.

Hepatopulmonary Syndrome (HPS) is a potential complication of chronic liver disease and is more commonly seen in the adult population. Caroli Syndrome is a rare inherited disorder characterized by intrahepatic ductal dilation and liver fibrosis that leads to portal hypertension. In children with liver disease, HPS should be considered in the differential diagnosis of prolonged, otherwise unexplained, hypoxemia. The presence of HPS can improve patient priority on the liver transplantation wait list, despite their Pediatric End-Stage Liver Disease (PELD) score. We present a 6-year-old girl with Caroli Syndrome and End-Stage Renal Disease who presented with persistent hypoxemia. The goal of this report is to increase awareness of HPS in children.

[Syphilitic bilateral panuveitis: a case report]. / Panuveítis bilateral sifilítica: a propósito de un caso.

CASE REPORT: A 57-year-old immunocompetent woman was diagnosed with syphilitic bilateral panuveitis after the onset of dramatic bilateral visual loss with inflammation of the anterior segment of the eye, severe vitritis and chorioretinitis which improved after treatment. DISCUSSION: Syphilis is a complex disease of increasing prevalence. If diagnosis is delayed ocular syphilis can produce severe visual loss due to neuritis, chorioretinitis with panuveitis, affecting both eyes in 50% of cases. Nevertheless, syphilis is considered one of the few causes of uveitis in which a cure can be obtained with proper treatment.

Panuveítis bilateral sifilítica: a propósito de un caso / Syphilitic bilateral panuveitis: a case report

Caso clínico: Mujer de 57 años inmunocompetentees diagnosticada de panuveítis bilateral sifilíticatras presentar un cuadro dramático de déficit visualsevero y bilateral con inflamación del segmentoanterior, importante vitritis y coriorretinitis que seresuelven favorablemente tras el tratamiento.Discusión: La sífilis es una enfermedad cuya frecuenciaestá en aumento. A nivel ocular puede provocarpérdida severa de visión si no se diagnosticaa tiempo ya que puede originar neuritis y coriorretinitiscon panuveítis, siendo el 50% de ellas bilaterales.Sin embargo, se considera una de las pocascausas de uveítis que con tratamiento específico sepueden curar(AU)

Case report: A 57-year-old immunocompetentwoman was diagnosed with syphilitic bilateralpanuveitis after the onset of dramatic bilateralvisual loss with inflammation of the anterior segmentof the eye, severe vitritis and chorioretinitiswhich improved after treatment.Discussion: Syphilis is a complex disease of increasingprevalence. If diagnosis is delayed ocularsyphilis can produce severe visual loss due to neuritis,chorioretinitis with panuveitis, affecting botheyes in 50% of cases. Nevertheless, syphilis is consideredone of the few causes of uveitis in which acure can be obtained with proper treatment(AU)

First report of a family with Lynch syndrome type II in Puerto Rico

Colorectal cancer (CRC) incidence in Puerto Rico has increased prodigiously since incidence figures were first recorded in 1950. Implications for hereditary nonpolyposis colorectal cancer (HNPCC) in concert with this increased CRC incidence are discussed. A family with the Amsterdam-positive criteria of the Lynch syndrome II variant, identified in the eastern area of Puerto Rico, is described. As far as we can determine, this is the first such report of this disorder in Puerto Rico

Synthesis and structural study of pyrimidyl carbocyclic analogues of nucleosides based on cyclopentene rings.

A series of 1,2-disubstituted carbonucleoside analogues of pyrimidine and 5-halopyrimidines with the unsaturated carbocycle cyclopentene was synthesized. AIM theory was applied to analyse the conformational and electronic effects of 5-halogenation.

First report of a family with Lynch syndrome type II in Puerto Rico.

Colorectal cancer (CRC) incidence in Puerto Rico has increased prodigiously since incidence figures were first recorded in 1950. Implications for hereditary nonpolyposis colorectal cancer (HNPCC) in concert with this increased CRC incidence are discussed. A family with the Amsterdam-positive criteria of the Lynch syndrome II variant, identified in the eastern area of Puerto Rico, is described. As far as we can determine, this is the first such report of this disorder in Puerto Rico.

Synthesis and 5-HT3 receptor affinity of new quinolinecarboxylic acid derivatives.

A series of quinolinecarboxylic acid amides and an ester with a quinuclidine moiety were synthesized and their in vitro affinities at 5-HT3, 5-HT4, and D2 receptors evaluated by radioligand binding assays. Highest affinity at 5-HT3 receptor corresponded to derivative 5 with Ki = 9.9 nM and with selectivity over 5-HT4 and D2 receptors. Compounds displayed moderate 5-HT3 antagonist activity (ED50 = 10.5-21.5 microg/kg i.v.). The obtained data suggest that the 5-HT3 receptor sites can accommodate the acyl group of the 2-quinoline derivatives. The results indicate the existence of an optimal distance between the lone electron pair of the quinoline nitrogen atom and the azabicyclic nitrogen atom, and a no-pharmacophoric pocket in the 5-HT3 receptor which would hold the fragment at the position 4 of the quinoline ring.

2,3-Dihydro-2-oxo-1H-benzimidazole-1-carboxamides with selective affinity for the 5-HT(4) receptor: synthesis and structure-affinity and structure-activity relationships of a new series of partial agonist and antagonist derivatives.

A series of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxamide derivatives bearing a piperazine moiety was synthesized. Their in vitro 5-HT(4), 5-HT(3), and D(2) receptors affinities were evaluated by radioligand binding assay. For selected compounds functional studies at the 5-HT(4) receptor were made by using precontracted (by carbachol) preparations of rat esophageal tunica muscularis mucosae (TMM). The influence of the 3-substituent of the benzimidazole ring, the 4-substituent of the piperazine moiety, and the alkylene spacer was studied. Compounds with an ethyl or a cyclopropyl substituent in the 3-position of the benzimidazole ring showed moderate to high affinity (K(i) = 6.7-75.4 nM) for the 5-HT(4) receptor with selectivity over 5-HT(3) and D(2) receptors and moderate antagonist activity (pK(b) = 6.19-7.73). Compounds with an isopropyl substituent in the 3-benzimidazole position exhibited moderate and selective 5-HT(4) affinity (K(i) >/= 38.9 nM) and a partial agonist activity (5a, i.a. = 0.94) higher than that of the reference compound BIMU 8 (i.a. = 0.70). This reversal of the pharmacological activity due only to a small structural difference might confirm the existence of two binding sites on the 5-HT(4) receptor. In the alkylene spacer, a two-methylene chain is favorable to optimize the affinity and the antagonist or the partial agonist activity. In the ethyl and cyclopropyl series, 5-HT(4) antagonist activity seems to be unrelated to the size of the 4-substituent of the piperazine moiety, whereas a methyl group is optimal for high partial agonist activity in the isopropyl series; however, the presence of a butyl substituent is a favorable pattern for 5-HT(4) antagonism and even causes a reversal of the pharmacological profile in the isopropyl series (5h, pK(b) = 7.94). N-Butyl quaternization of 5a led to an improvement in affinity for the 5-HT(4) receptor and mantained the high partial agonist activity (5r, K(i) = 66.3 nM, i.a. = 0.93).