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BACKGROUND: When indicated, ureteroceles and ectopic ureters in duplicated collecting systems can be managed via upper or lower urinary tract surgical approaches, or a combination of both. Open ureteroureterostomy (UU) has been described to address these conditions in the absence of lower pole (LP) vesicoureteral reflux (VUR). We report outcomes from multiple centers worldwide with mid-term follow-up. METHODS: Our study consists of a retrospective review of records and imaging of children who underwent open distal UU via inguinal incision for duplicated collecting system without lower pole VUR in institutions from North America, South America, and the Caribbean. Descriptive statistics and univariate analysis were utilized. RESULTS: The records of 127 patients who underwent open distal UU for double collecting system between 2009 and 2022 were reviewed. Of those, 65% were female (n = 82), with a mean age at operation of 18 months (range 3-180). Main presentation at surgery included prenatal hydronephrosis (64%, n = 81), followed by febrile urinary tract infections (28%, n = 36), and urinary incontinence or other (8%, n = 10). The patients with antenatal or incidental diagnosis of hydronephrosis were classified as preoperative Society for Fetal Urology (SFU) grade 3 (n = 64) and 4 (n = 54) (96%). Those who were classified with SFU grade 0-2 (4%) had symptomatic clinical presentations including febrile urinary tract infections (UTIs) (n = 3), urinary incontinence (n = 3), and a 12-year-old patient with recurrent abdominal pain (n = 1). Mean operative time from skin incision to skin closure was 86 min (range 45-240). Mean hospital stay was estimated at 1.1 days (range 0.5-4). In our cohort of 127 patients, 3 (2%) developed Clavien-Dindo grade I (2 with ureteral stent displacement and 1 with a urine leak/managed conservatively), 6 (5%) with grade II (3 febrile and 3 non-febrile UTIs managed with oral antibiotics), and 2 (2%) with grade IIIb complications (urine leaks requiring surgical management), which were appropriately treated. None presented grade IV or V complications. A double J stent was used in 56 patients (44%), and a Penrose drain was left in 10 (8%). A total of 125 children (98%, n = 125/127) showed sonographic improvement of hydronephrosis, or resolution of symptoms with stable ultrasound findings. Successful outcome was similar for both ureterocele and ectopic ureter subgroups: 49/49 patients with ureterocele showed 100% improvement, 76/78 children with ectopic ureter showed improvement in 97% of the cases. On univariate analysis, outcomes were similar regardless of the use of ureteral stents (p = 0.11). Mean follow-up was 28.2 months (range 12-85). CONCLUSIONS: Open distal UU is a good alternative for the definitive surgical management of ectopic ureters and ureteroceles without LP VUR. This multicentric and mid-term follow-up study demonstrates that open distal UU offers high success rates, low morbidity, short operative times and hospital stays, and satisfactory aesthetic outcomes. Additionally, the surgery is performed extra-peritoneally and may not require the use of stents or drains, depending on surgeon preference. Further investigations are being conducted to determine the role of UU in the settings of double collecting systems associated with ipsilateral LP VUR.

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Cutaneous adverse drug reactions (ADRs) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Maculopapular exanthema and urticaria are the most common types of cutaneous ADR. Serious cutaneous ADRs, which may cause permanent sequelae or have fatal outcome, may represent 2% of all cutaneous ADR and must be quickly identified to guide their management. These serious reactions include bullous manifestations (epidermal necrolysis i.e. Stevens-Johnson syndrome and toxic epidermal necrolysis), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Some risk factors for developing cutaneous ADRs have been identified, including immunosuppression, autoimmunity or genetic variants. All drugs can cause cutaneous ADRs, the most commonly implicated being antibiotics (especially aminopenicillins and sulfonamides), anticonvulsants, allopurinol, antineoplastic drugs, non-steroidal anti-inflammatory drugs and iodinated contrast media. Pathophysiology is related to immediate or delayed "idiosyncratic" immunologic mechanisms, i.e., usually not related to dose, and pharmacologic/toxic mechanisms, commonly dose-dependent and/or time-dependent. If an immuno-allergic mechanism is suspected, allergological explorations (including epicutaneous patch testing and/or intradermal test) are often possible to clarify drug causality, however these have a variable sensitivity according to the drug and to the ADR type. No in vivo or in vitro test can consistently confirm the drug causality. To determine the origin of a rash, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis (especially infectious etiologies) is required, completed with a literature search. Reporting to pharmacovigilance system is therefore essential both to analyze drug causality at individual level, and to contribute to knowledge of the drug at population level, especially for serious cutaneous ADRs or in cases involving newly marketed drugs.

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INTRODUCTION: Casirivimab and imdevimab (Ronapreve®) are two recombinant human monoclonal antibodies (mAbs) that bind to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, preventing the virus from entering cells. In March 2021, this drug was granted emergency use authorisation (EUA) in France for early treatment of COVID-19 in patients at increased risk of progression to severe COVID-19. In August/September 2021, the indication was expanded to COVID-19 prevention (pre- or post-exposure prophylaxis) and treatment of hospitalised patients requiring non-invasive oxygen therapy. The aim of the study was to better describe the adverse drug reaction (ADR) profile and detect safety signals of this new drug used in COVID-19 treatment. METHODS: We described ADR profile with casirivimab/imdevimab reported as suspect/interacting drug to the French pharmacovigilance network and the pharmaceutical company between 17/03/2021 and 30/06/2022. Data presented correspond to the 2 periods of the pharmacovigilance survey: the first carried out by the pharmaceutical company for curative and prophylactic uses and the second by Toulouse university regional pharmacovigilance center (RPVC). RESULTS: A total of 384 reports were analysed and 256 were "serious". ADR profile was comparable between the 2 periods and between curative and prophylactic use, corresponding to expected ADRs such as infusion-related reactions and hypersensitivity, inefficiencies or worsened infections and deaths. Two potential pharmacovigilance signals were also studied: acute pulmonary oedemas and sudden deaths. DISCUSSION: No pharmacovigilance signal emerged from this 15 months French pharmacovigilance survey. Moreover data from published studies are also reassuring. This pharmacovigilance survey was the first one for the new version of EUA and with a new ADR reporting process i.e. declaration to the RPVC instead of the pharmaceutical company. Casirivimab/imdevimab is no longer used in France today but we continue to monitor this drug for any future evidence of resurgent activity on a new variant of Sars-CoV-2.

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Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), drug reactions with eosinophilia and systemic symptoms (DRESS) have been very rarely reported. The objective of this study is to better define the clinical and histologic features, treatment and prognosis of ICI-related DRESS. This retrospective case series was conducted between 01 January 2015 and 31 December 2021 by the dermatology departments of five international networks involved in drug reactions. Inclusion criteria were age ≥18 years old, DRESS with Regiscar score ≥4 (probable or certain) and ICI as a suspect drug. Clinical, biologic and follow-up data were extracted from the medical charts. Thirteen patients were included. The median time to onset was 22 days (3-11). No patients had a high-risk drug introduced in the past 3 months. A majority of patients presented fever (92%), diffuse exanthema (77%) and facial edema (69%). Biologic features included hypereosinophilia in eight patients (61.5%), hyperlymphocytosis in 3 (23%), elevated liver function tests in 11 (85%, grade 1 or 2 in most cases) and renal involvement in 5 (38%). Two patients (15%) had lung involvement. PCR evidence of viral replication was detected in five patients (38.5%). Treatment involved discontinuation of the suspect ICI and systemic steroids with variable dose and duration regimens. Among the four patients in which ipilimumab + nivolumab combination therapy was initially suspected, one was rechallenged with nivolumab monotherapy with good tolerance. Five patients were switched to another anti-PD-1 plus low-dose systemic steroids, with good tolerance in four cases. No patient died because of DRESS. DRESS induced by ICI are rare and of moderate severity. A consensus for management is still pending.

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PURPOSE: PCSK9 might affect central nervous system development, neuronal apoptosis, and differentiation. We investigate the neurocognitive adverse events associated with the use of PCSK9 inhibitors (alirocumab and evolocumab) using pharmacovigilance reports. METHODS: We used the World Health Organization pharmacovigilance database (VigiBase) to perform a disproportionality analysis comparing the proportion of neurocognitive adverse events reported with PCSK9 inhibitors versus the proportion of these effects reported since August 14, 2015 (date of first post-marketing report suspecting a PCSK9 inhibitor), for all drugs in the database. Associations between PCSK9 inhibitor use and neurocognitive adverse events were assessed using both proportional reporting ratio (PRR) and information component (IC). Complementary analyses were performed on other neurologic events, and different sensitivity analyses were conducted to evaluate the robustness of results. RESULTS: Among the 81,108 reports involving at least one PCSK9 inhibitor, 1,941 concerned the occurrence of neurocognitive disorders. Most of patients (52.3%) were aged 45-74 years, and 58.0% were women. Signals of disproportionate reporting were found for PCSK9 inhibitors (PRR 1.22, 95% CI 1.17; 1.28; IC 0.28, IC025 0.21) and for each drug individually. No signal of disproportionality was found for any of the other neurologic events investigated. Signals of disproportionate reporting were found for the positive control (benzodiazepines), but not for the negative control (aspirin). The results of the main analysis were confirmed by sensitivity analyses. CONCLUSIONS: This study identified a signal of neurocognitive disorders associated with PCSK9 inhibitors and encourages paying attention to at-risk populations.

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This data paper summarizes the data of a first survey of terrestrial ferns at Mashpi Biodiversity Reserve, an Ecuadorian Chocó forest relict, one of the most biodiverse areas in the world. We established 10 permanent plots of 400 m2 distributed in two elevational levels (800 and 1000 m a.s.l.) to register all species per plot and the abundance per species. In addition, we measured two morphological leaf functional traits of the species. We include a file with three tables, the first one includes a species list with scientific names and vouchers. The second one includes the abundance of each species per plot. The third one contains measurements of the leaf length and leaf thickness of several leaf samples of 28 species, representing the leaf functional traits of the species. This article also includes a table with coordinates and elevations of the plots and five figures with information about the number of genus and species per family, geographic location of plots and, the methodology for data collection. These data can be useful for plant ecologists to assess future changes of fern species composition and leaf functional traits of ferns caused by climate change and other threats at the study area.

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Reports suggested the potential occurrence of peripheral neuropathies (PN) in patients treated with BRAF (BRAFi) and/or MEK inhibitors (MEKi) for BRAF-activated tumours. We aimed to better characterize these PN. We queried the French pharmacovigilance database for all cases of PN attributed to BRAFi and/or MEKi. Fifteen patients were identified. Two main clinical PN phenotypes were seen. Six patients presented a length-dependent, axonal polyneuropathy: symptoms were mostly sensory and affecting the lower limbs; management and outcome were variable. Nine patients developed a demyelinating polyradiculoneuropathy: symptoms affected the four limbs and included hypoesthesia, weakness and ataxia; cranial nerves were involved in four cases; most patients received intravenous immunoglobulins or glucocorticoids, with variable outcome; one patient was rechallenged with a different BRAFi/MEKi combination with a rapid relapse in symptoms. In conclusion, patients under BRAFi/MEKi therapy may develop treatment-induced PN. Two main phenotypes can occur: a symmetric, axonal, length-dependent polyneuropathy and a demyelinating polyradiculoneuropathy.

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The two clinico-pathological patterns are 'Sweet-like syndrome' and 'Multiple COVID-Arm'. 'Sweet-like syndrome' presents clinically as erythematous and oedematous papules or plaques, sometimes developing vesiculation or bullae. Histology shows classical Sweet syndrome with a diffuse dermal neutrophilic infiltrate, or an infiltrate of histiocyte-like immature myeloid cells consistent with a histiocytoid Sweet syndrome. 'Multiple COVID-arm' is characterized by multiple large inflammatory plaques with histological analyses showing a perivascular and interstitial inflammatory infiltrate with eosinophils.

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AIMS: At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there were no clinically-tested medications for the effective treatment of coronavirus disease. In this context, on 5 March 2020, the French Public Health Council issued several recommendations for the therapeutic management of this new disease, including the use of hydroxychloroquine (HCQ). An unexpected cardiovascular safety signal was quickly identified as being more frequent than expected thanks to the reports of adverse drug reactions (ADRs) submitted to French regional pharmacovigilance centres (RPVC). The objective of this study was to compare all ADRs reported with HCQ used in its usual indication, collected before the pandemic period (1985 to 31 December, 2019) with those reported with the coronavirus disease 2019 (COVID-19) indication (1 January to 21 July, 2020). METHODS: For this purpose, reports were extracted from the French pharmacovigilance database and analysed for these two periods. RESULTS: Our study showed a different safety profile in COVID-19 patients with more cardiac disorders (57% of ADRs versus 5% before the pandemic period), especially QT interval prolongation, resulting from an interaction with azithromycin in more than 20% of cases. Hepatobiliary disorders were also significantly more frequent. CONCLUSIONS: These observations could be associated with the effect of the virus itself on the various organs, the profile of the patients treated, and concomitant drug treatments.

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INTRODUCCIÓN: El embarazo ectópico en el cuerno rudimentario de un útero unicorne tiene una incidencia de 1 en 76.000 embarazos. La aproximación diagnóstica se realiza con la ecografía y como estudio complementario con la resonancia magnética. El diagnóstico temprano con tratamiento oportuno es fundamental para la prevención de la morbimortalidad materna asociada. El objetivo es describir el diagnóstico y el tratamiento temprano de un caso de embarazo ectópico de 15 semanas en cuerno rudimentario no comunicante de útero unicorne. CASO CLÍNICO: Mujer de 38 años con embarazo de 15 semanas, asintomática, que ingresa al servicio de urgencias referida desde el servicio de ecografía por sospecha de embarazo ectópico. Se realizan ecografía y resonancia magnética que muestran embarazo con feto único de 15 semanas en cuerno uterino izquierdo rodeado de miometrio, sin comunicación con la cavidad endometrial. Con impresión diagnóstica de embarazo ectópico cornual en paciente con malformación mülleriana, se realizó manejo quirúrgico que confirmó útero unicorne con embarazo ectópico en cuerno rudimentario no comunicante. CONCLUSIONES: El embarazo ectópico en un cuerno rudimentario de útero unicorne es infrecuente y presenta un alto riesgo de rotura, con aumento de la morbimortalidad obstétrica. El tratamiento estándar, al igual que la confirmación diagnóstica, es la escisión quirúrgica completa.

INTRODUCTION: Ectopic pregnancy in the rudimentary horn of a unicornuate uterus has an incidence of 1 in 76,000 pregnancies; the diagnostic approach is carried out with ultrasound and magnetic resonance imaging as a complementary study; Early diagnosis with timely treatment is essential for the prevention of associated maternal morbidity and mortality. The objective is to describe the early diagnosis and treatment of a case of 15-week ectopic pregnancy in a rudimentary non-communicating horn of the unicornuate uterus. CASE REPORT: A 38-year-old patient with an asymptomatic 15-week pregnancy was admitted to the emergency department, referred to the ultrasound service for suspected ectopic pregnancy. Ultrasound and magnetic resonance imaging were performed with pregnancy with a single fetus of 15 weeks in the left uterine horn surrounded by myometrium, without communication with the endometrial cavity. With a diagnostic impression of cornual ectopic pregnancy in a patient with a Müllerian malformation, a surgical management was performed where a unicornuate uterus with a rudimentary non-communicating ectopic horn was confirmed. CONCLUSIONS: Ectopic pregnancy in rudimentary horn of the unicornuate uterus is rare, it presents a high risk of rupture with increased obstetric morbidity and mortality. The standard treatment as well as the diagnostic confirmation is complete surgical excision.

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AIMS: Analgesics are the most widely used medicines worldwide. In parallel, opioid abuse has increased and is of major concern. The accessibility of pharmacologically powerful medicines and the addictovigilance signals in France about the risk of opiates addiction call for an overview of analgesic use. The objective of this study was to investigate the use of analgesics reimbursed in France over a 10-year period through its prevalence. METHODS: A cross-sectional study repeated yearly was conducted by using data from the French reimbursement database from 2006 to 2015. Analgesics were classified according to their pharmacological potency: prevalence of use for each category and sociodemographic characteristics of patients treated were analysed. RESULTS: The annual prevalence of analgesic use was high and increased during the study period (59.8%, 253 976 users in 2015). In 2015, prevalence was always higher in women and increased with age, except for those older than 84 years. Peripheral analgesics were the most used (55.3%, 234 739 users). The prevalence of weak analgesic use decreased (21.3%, 90 257 users), mainly due to the definitive withdrawal of dextropropoxyphene in France in 2011, which was not offset by an increase in the consumption of other weak analgesics. For strong analgesics (1.2%, 5129 users), morphine was the most widely used, with a dramatic increase in oxycodone use, especially in the elderly. CONCLUSION: The prevalence of analgesic use is high: approximately 31 million adults had at least 1 analgesic reimbursed in 2015. The most widely used analgesics were peripheral analgesics, far ahead of opioid analgesics.

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INTRODUCTION: Evidence regarding a possible association between psoriatic manifestations and use of calcium channel blockers (CCBs) is sparse. Currently, psoriatic manifestations are not listed in the summary of product characteristics (SmPC) of CCBs. In this context, we aimed to investigate the association between psoriasis and CCB exposure. METHODS: We reviewed spontaneous reports recorded in the French national pharmacovigilance database (FPVD) between 1985 and 2019. The association between CCB exposure and risk of psoriasis was assessed using the case/non-case method. We also analyzed literature data. RESULTS: Ninety-four reports of psoriatic manifestations after CCB exposure were recorded in the FPVD. Both induction and exacerbation cases were observed. Time to onset was less than 2 years in 64% of reports and outcome was favorable in 71% of reports after CCB discontinuation. These features were concordant with those of literature reports. The reporting odds ratio (ROR) was 2.45 (95% CI 1.99-3.02). Concomitant use of betablockers or angiotensin II receptor blockers did not interact with the association between CCB exposure and psoriasis risk. The ROR for the stratum "use of angiotensin converting enzyme inhibitors" (ACEI) was 2.14 (95% CI 1.29-3.55), while the ROR for the stratum ACEI non-use was 0.12 (95% CI 0.10-0.15). Large-scale epidemiologic studies were focused only on first diagnoses and did not include exacerbations; psoriasis risk was therefore probably underestimated. CONCLUSION: We found a statistically significant association between CCB exposure and psoriasis risk, which constitutes a safety signal. This risk is a class effect, time to onset is mostly less than 2 years and outcome is favorable after CCB discontinuation. Psoriasis should be mentioned in the SmPCs of all CCBs, and healthcare workers should be aware of this risk. Attention should be paid to patients taking CCB and ACEI concomitantly.

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BACKGROUND: Several clusters of encephalopathy occurred after the market change from Holoxan® (ifosfamide lyophilized powder) to Ifosfamide EG® (liquid formulation) and justified a formal survey in 2015. In June 2016, the regulatory authority decided to apply a precautionary measure in reducing the shelf life of Ifosfamide EG® at 7 months. One-year study from spontaneous reports lead to suspect a potential residual risk. Due to the many limitations associated with spontaneous notifications, we performed a multicentric observational study, aiming to better explore this pharmacovigilance signal. METHODS: We performed a case-control study in pediatric oncology Departments of 25 university hospitals between July 1st, 2016 and July 1st, 2018. All children (<18 y.o.) receiving liquid formulation or lyophilized powder formulation during the study period were included. Patients with at least one occurrence of encephalopathy were considered as cases. Logistic regression model was used to estimate the odds ratio of encephalopathy between exposure groups. RESULTS: During the study period, 52 cases and 495 controls were included. A residual over-risk of encephalopathy was associated with ifosfamide 7-month shelf-life liquid formulation compared to lyophilized powder (adjusted OR 1.91, 95% CI: 1.03-3.53). CONCLUSIONS: Observed difference does not seem to be related to the pathology treated, the doses used, the co-medications, a meningeal localization and/or an irradiation of the central nervous system. This study confirms data from spontaneous reports that led to the precautionary measure for the liquid formulation. Even if the risk of encephalopathy seems reduced, our study suggests the persistence of a residual risk of encephalopathy associated with liquid formulation compared to the lyophilized powder.

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Introducción: las coinfecciones con hepatitis virales y el VIH representan un riesgo por su alta transmisibilidad y complicaciones. Es de vital importancia que se puedan identificar las barreras de acceso y manejo de las coinfecciones del VIH y la Hepatitis B y C. El propósito del estudio es describir la cascada de atención para la coinfección de las hepatitis virales en personas viviendo con VIH/SIDA. Métodos: se delimitaron los indicadores de manejo y seguimiento de los pacientes monitoreados actualmente en clínicas de primer nivel de atención en Santo Domingo y Santiago. Los datos recopilados fueron analizados a partir de los registros escritos de los pacientes en seguimiento, para evaluar los datos epidemiológicos y serológicos que se obtuvieron de los archivos clínicos. Resultados: se demostró que un 100 % de los pacientes fueron enrolados, 85.7 % se consideraron como retenidos en el manejo de la coinfección VIH/VHB y solamente 71.4 % recibieron TARV basado en Tenofovir. La cascada de atención para la coinfección VIH/VHC muestra un vínculo de 87.5 % de los pacientes, 75 % fueron retenidos y ninguno recibió tratamiento. Conclusión: la identificación de los factores de riesgo que influyen en las brechas de la cascada es fundamental para optimizar el manejo y monitoreo de los pacientes coinfectados, teniendo en cuenta que es preciso poder reconocer aquellos infectados para iniciar tratamiento de inmediato y así prever secuelas citopatológicas hepáticas

Introduction: Co-infections of viral hepatitis and HIV represent a risk due to their high transmissibility and complications. It is vitally important that barriers to access and management of HIV and Hepatitis B and C co-infections can be identified. The purpose of the study is to describe the cascade of attention for the preparation of viral hepatitis in people living with HIV/AIDS. Methods: The management and follow-up indicators of the patients currently monitored in first-level care clinics in Santo Domingo and Santiago were delimited. The data collected was analyzed from the written records of the patients in follow-up to evaluate the epidemiological and serological data that was obtained from the clinical files. Results: It was demonstrated that 100% of the patients were enrolled, 85.7% were considered as retained in care of HIV / HBV coinfection and only 71.4% received ARTbased on Tenofovir. The cascade of care for HIV / HCV coinfection shows a linkage to care of 87.5% of patients, 75% were retained and none received treatment. Conclusions: Identifying the risk factors that influence the gaps in the cascade of care is essential to optimize the management and monitoring of coinfected patients, with special interest in those that might receive immediate treatment to prevent liver cytopathological sequelae

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