The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series

IntroductionStroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (>= 500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome. Materials and MethodsWe retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study. ResultsThe underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4-34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (+/- 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (+/- 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients. ConclusionsSLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management

Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17–74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Changes in ductus venosus velocity ratios after fetoscopic laser surgery for twin–twin transfusion syndrome

Wohlmuth et al.1described changes in ductus venosus waveforms (DV-FVW) in 149 pairs of monochorionic diamniotic (MCDA) twin pregnancies referred for twin-twin transfusion syndrome (TTTS) requiring fetoscopic laser surgery. We hypotesize that DV-FVW might also change after placental laser ablation

Management of discordant body stalk anomaly in monochorionic twin pregnancies

A 31-year-old woman, gravida 4 para 1 was referred to our center at 11(+1) weeks of gestation: the ultrasound examination revealed a monochorionic monoamniotic twin pregnancy, and one fetus was affected by body stalk anomaly. Chorionic villus sampling revealed a 46,XX karyotype. Extensive counselling about the prognosis of the affected fetus and possible complications of the pregnancy was provided

The use of ultrasound-indicated cerclage or cervical pessary in asymptomatic twin pregnancies with a short cervix at midgestation

Introduction: Spontaneous preterm birth in women with a twin pregnancy is one of the main causes of perinatal mortality and morbidity. Our aim was to review the perinatal outcome of asymptomatic twin pregnancies with a sonographic short cervical length during the second trimester treated with an ultrasound-indicated cerclage or cervical pessary. Material and methods: Retrospective study on asymptomatic twin pregnancies with a short cervix (≤ 25 mm) at transvaginal ultrasound examination during the second trimester treated with a cervical cerclage or pessary (2001-2017). The rate of preterm birth < 28, 32 and 34 weeks of gestation, neonatal mortality, neonatal morbidity and composite adverse neonatal outcome were compared in the groups of women treated with cerclage or pessary. Results: Seventy-four twin pregnancies underwent a cerclage while a cervical pessary was inserted in 34 women with twins at our Department: 36 women with an ultrasound-indicated cerclage and 20 with a pessary were included in the analysis. Median gestational age at delivery was higher in women treated with cerclage compared with those with pessary placement (P =.02) and the rate of preterm birth before 34 weeks of gestation was lower in the cerclage group (P =.03). Admissions to the Neonatal Intensive Care Unit were more frequent in pregnancies with pessary (P =.01), the length of admission was longer (P =.005) and composite adverse neonatal outcome occurred more often (P =.03) compared with the cerclage group. Conclusions: Ultrasound-indicated cerclage appears to reduce the rate of preterm birth before 34 weeks of gestation in asymptomatic twin pregnancies with a short cervix during the second trimester, and also the composite adverse neonatal outcome compared with pessary. © 2018 Nordic Federation of Societies of Obstetrics and Gynecolog

Liver and spleen stiffness for the diagnosis of oesophageal varices in adults with chronic liver disease

Objectives: This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows:. To assess the diagnostic accuracy of liver stiffness and spleen stiffness, separately or in combination, as measured by vibration-controlled transient elastography (VCTE) in detection of any oesophageal varices in adults with chronic liver disease. We will regard a combination of tests as positive when at least one is positive. To compare the diagnostic accuracy of individual tests (liver stiffness and spleen stiffness measured by VCTE) directly and versus the combination of both tests (considering positive when at least one is positive) in detecting any oesophageal varices. To assess the diagnostic accuracy of liver stiffness and spleen stiffness, separately or in combination, as measured by other elastography techniques (2D-shear wave elastography (2D-SWE), point shear wave elastography (pSWE), magnetic resonance elastography (MRE)) in detection of any oesophageal varices in adults with chronic liver disease. We will regard a combination of tests as positive when at least one is positive. To compare the diagnostic accuracy of liver stiffness and spleen stiffness measured by VCTE with other techniques (pSWE, 2D-SWE, MRE) in detection of any oesophageal varices in adults with chronic liver disease. Secondary objectives To assess the diagnostic accuracy of liver stiffness and spleen stiffness, separately or in combination, as measured by vibration-controlled transient elastography (VCTE) in detection of high-risk oesophageal varices (HROVs) in adults with chronic liver disease. We will consider a combination of tests as positive when at least one is positive. To compare the diagnostic accuracy of individual tests (liver stiffness and spleen stiffness measured by VCTE) directly and versus the combination of both tests (considering positive when at least one is positive) in detecting HROVs. To assess the diagnostic accuracy of liver stiffness and spleen stiffness, separately or in combination, as measured by other different elastography techniques (2D-shear wave elastography (2D-SWE), point shear wave elastography (pSWE), magnetic resonance elastography (MRE)) in detection of HROVs in adults with chronic liver disease. We will regard a combination of tests as positive when at least one is positive. To compare the diagnostic accuracy of liver stiffness and spleen stiffness measured by VCTE with other techniques (pSWE, 2D-SWE, MRE) in detection of HROVs in adults with chronic liver disease. To investigate potential sources of heterogeneity in the results of liver stiffness and spleen stiffness, separately or in combination, as measured by VCTE, in detection of any oesophageal varices and HROVs

Un monastero sul mare

The remains of the monastery of San Quirico stand on the slopes of Poggio Tondo, a hill not far from the ancient city of Populonia. They overlook the Tyrrhenian Sea, dotted with the islands of the Tuscan archipelago. Field research at this site, carried out in the first decade of the new millennium by two different teams, from Siena University and Venice’s Ca’ Foscari University, respectively, was part of ongoing efforts to expand the Baratti-Populonia Archeological Park, and to further explore the features present within it. This volume contains the results of this research work: a scientific publication of the excavation, and a critical analysis of the material found. Processing of the data collected during these investigations, together with a re-reading of written documentation, has made it possible to piece together the complex history of this important monastery, in a totally new narration. In this narration, the history of the monastery, and of the features which existed prior to it, are closely interwoven with the history of the promontory of Populonia and the surrounding area, ultimately producing a new overview which sets out the historical boundaries of this area, between Late Antiquity and the modern era.I resti del monastero di San Quirico si trovano sulle pendici del poggio Tondo, a poca distanza dall’antica città di Populonia, rivolti verso lo specchio del mare Tirreno costellato dalle isole dell’arcipelago toscano. Le ricerche archeologiche in questo sito, realizzate nel primo decennio del nuovo millennio da due differenti équipe, rispettivamente dell’Università di Siena e Ca’ Foscari di Venezia, si sono svolte nell’ambito degli interventi di ampliamento e di valorizzazione del parco archeologico di Baratti-Populonia. Questo volume contiene i risultati di quelle ricerche: l’edizione scientifica dello scavo e l’analisi critica dei materiali rinvenuti. La rielaborazione dei dati raccolti durante tali indagini, unita ad una rilettura della documentazione scritta, ha poi permesso di ricomporre le complesse vicende di questo importante monastero, in una nuova ed inedita narrazione. In tale narrazione le vicende del cenobio e delle sue preesistenze si intrecciano con quelle del promontorio di Populonia e dei territori limitrofi fino a delineare un quadro di sintesi che ridisegna i confini storici di questo territorio tra la Tarda Antichità e l’Età Moderna