European Society of Radiotherapy and Oncology (ESTRO) strategy 2024-2026: Growth and diversification in a rapidly changing world.

In 2019, the European Society of Radiotherapy and Oncology (ESTRO) published its 2030 Vision "Radiation Oncology, Optimal Health, For All, Together". However, in 2020, the global pandemic, coinciding with the Society's 40th anniversary, had long-term consequences on global behaviours and on the financial environment for scientific associations worldwide. In 2022, ESTRO conducted a survey among its members, revealing their strong appreciation for networking opportunities and the creation of high-quality interdisciplinary scientific content. In response to the survey findings and to address the evolving landscape following the COVID pandemic, ESTRO initiated a strategic review process to respond to, and refocus on, the opportunities and challenges ahead. This paper, marking a turning point in ESTRO's strategy for achieving its Vision 2030 in a post-pandemic era, describes the 2022-23 strategic review process, discussions, and consequent recommendations. The comprehensive strategic review process involved: (i) pre-meeting preparations with surveys and strategic documents; (ii) a carefully themed three-day retreat in Brussels incorporating a blend of plenary sessions, workshops focusing on ESTRO's role, value creation and capture, strategic objectives; and (iii) a post-retreat phase including qualitative analysis and development of action plans. The strategic review emphasized the need for adaptive tactics for scientific associations to remain current and productive in the face of changing global conditions. The development of key strategic goals for the years 2024-2026 focused on improving research impact, strengthening and diversifying ESTRO's educational offerings and fostering proactive and mutually beneficial partnerships. The Board approved these objectives, alongside prioritising digital innovation, financial sustainability, and community engagement for ESTRO's continued growth and development. In essence, ESTRO aims to advocate, empower, expand, and diversify its community, with the overarching goal of enhancing cancer care for patients in Europe, and beyond.

Leukocytoclastic vasculitis (cutaneous small-vessel vasculitis) after COVID-19 vaccination.

Vaccinations may induce cutaneous adverse events, due to nonspecific inflammation or immuno-mediated reactions. Several types of vasculitis have been observed. We report on a 71-year-old woman who developed cutaneous small-vessel vasculitis after the second dose of Vaxzevria COVID-19 vaccination, showing leukocytoclastic vasculitis on histopathological examination of a skin biopsy. Cutaneous small-vessel vasculitis is a rare condition which can be idiopathic or secondary to underlying infections, connective tissue disorders, malignancy, and medications. The pathogenesis involves immune complex deposition in small blood vessels, leading to activation of the complement system and recruitment of leukocytes. Exacerbation of small-vessel vasculitis has been reported following the administration of various vaccines, particularly influenza vaccine. It is expected that SARS-CoV-2 vaccine results in the activation of B- and T-cells and antibody formation. We hypothesize that leukocytoclastic vasculitis caused by immune complex deposition within cutaneous small vessels could be a rare side effect of Vaxzevria COVID-19 vaccination.

Altered sensorimotor integration in multiple sclerosis: A combined neurophysiological and functional MRI study.

OBJECTIVE: To explore whether abnormal thalamic resting-state functional connectivity (rsFC) contributes to altered sensorimotor integration and hand dexterity impairment in multiple sclerosis (MS). METHODS: To evaluate sensorimotor integration, we recorded kinematic features of index finger abductions during somatosensory temporal discrimination threshold (STDT) testing in 36 patients with relapsing-remitting MS and 39 healthy controls (HC). Participants underwent a multimodal 3T structural and functional MRI protocol. RESULTS: Patients had lower index finger abduction velocity during STDT testing compared to HC. Thalamic rsFC with the precentral and postcentral gyri, supplementary motor area (SMA), insula, and basal ganglia was higher in patients than HC. Intrathalamic rsFC and thalamic rsFC with caudate and insula bilaterally was lower in patients than HC. Finger movement velocity positively correlated with intrathalamic rsFC and negatively correlated with thalamic rsFC with the precentral and postcentral gyri, SMA, and putamen. CONCLUSIONS: Abnormal thalamic rsFC is a possible substrate for altered sensorimotor integration in MS, with high intrathalamic rsFC facilitating finger movements and increased thalamic rsFC with the basal ganglia and sensorimotor cortex contributing to motor performance deterioration. SIGNIFICANCE: The combined study of thalamic functional connectivity and upper limb sensorimotor integration may be useful in identifying patients who can benefit from early rehabilitation to prevent upper limb motor impairment.

Chronic inflammatory demyelinating polyradiculoneuropathy: can a diagnosis be made in patients not fulfilling electrodiagnostic criteria?

BACKGROUND AND PURPOSE: The aim was to identify the clinical and diagnostic investigations that may help to support a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in patients not fulfilling the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria. METHODS: The data from patients with a clinical diagnosis of CIDP included in a national database were retrospectively reviewed. RESULTS: In all, 535 patients with a diagnosis of CIDP were included. This diagnosis fulfilled the EFNS/PNS criteria in 468 patients (87.2%) (definite in 430, probable in 33, possible in three, while two had chronic immune sensory polyradiculopathy). Sixty-seven patients had a medical history and clinical signs compatible with CIDP but electrodiagnostic studies did not fulfill the EFNS/PNS criteria for CIDP. These patients had similar clinical features and frequency of abnormal supportive criteria for the diagnosis of CIDP compared to patients fulfilling EFNS/PNS criteria. Two or more abnormal supportive criteria were present in 40 (61.2%) patients rising to 54 (80.6%) if a history of a relapsing course as a possible supportive criterion was also included. Increased cerebrospinal fluid proteins and response to immune therapy most frequently helped in supporting the diagnosis of CIDP. Response to therapy was similarly frequent in patients fulfilling or not EFNS/PNS criteria (87.3% vs. 85.9%). CONCLUSIONS: Patients with a clinical diagnosis of CIDP had similar clinical findings, frequency of abnormal supportive criteria and response to therapy compared to patients fulfilling EFNS/PNS criteria. The presence of abnormal supportive criteria may help in supporting the diagnosis of CIDP in patients with a medical history and clinical signs compatible with this diagnosis but non-diagnostic nerve conduction studies.

Double isolated asynchronous duodenal perforation due to abdominal blunt trauma in a child: A case report.

BACKGROUND: Isolated duodenal perforation following blunt abdominal trauma is a rare injury in children. Bicycle accidents (falling on to the handlebar) are a frequent cause of blunt abdominal trauma in children and may occasionally be associated with isolated duodenal perforation (IDP). Prompt diagnosis and surgical treatment are vital to prevent increased morbidity and mortality. CASE PRESENTATION: We report the rare case of an 11-year-old boy admitted for blunt abdominal trauma and treated for an asynchronous double IDP. The first perforation, located on the 2nd/3rd portion of the duodenum, was promptly diagnosed by contrast-enhanced abdominal CT scan after a negative US scan, five hours after injury, and the lesion repaired with a single stitch suture. The second duodenal perforation appeared in the duodenal bulb as a worsening biliary leakage, 48 h after the primary suture of the initial lesion. The perforation was initially seen by digestive endoscopy and sutured in the same way as the first lesion. A third laparotomy was needed 4 days later due to an intestinal obstruction, after which the patient was recovered completely and was discharged home. DISCUSSION AND CONCLUSION: IDP is a rare consequence of blunt abdominal trauma, and is normally associated with a lesion of other organs, such as the pancreas or bile duct. A delayed diagnosis strongly increases the incidence of morbidity and mortality, and different kinds of surgical management have been proposed, depending on the type of lesion. To our knowledge, this is the first case described in literature of a double isolated asynchronous duodenal perforation following blunt abdominal trauma in children.

Risk factors for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): antecedent events, lifestyle and dietary habits. Data from the Italian CIDP Database.

BACKGROUND AND PURPOSE: The role of lifestyle and dietary habits and antecedent events has not been clearly identified in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Information was collected about modifiable environmental factors and antecedent infections and vaccinations in patients with CIDP included in an Italian CIDP Database. Only patients who reported not having changed their diet or the lifestyle habits investigated in the study after the appearance of CIDP were included. The partners of patients with CIDP were chosen as controls. Gender-matched analysis was performed with randomly selected controls with a 1:1 ratio of patients and controls. RESULTS: Dietary and lifestyle data of 323 patients and 266 controls were available. A total of 195 cases and 195 sex-matched controls were used in the analysis. Patients eating rice at least three times per week or eating fish at least once per week appeared to be at decreased risk of acquiring CIDP. Data on antecedent events were collected in 411 patients. Antecedent events within 1-42 days before CIDP onset were reported by 15.5% of the patients, including infections in 12% and vaccinations in 1.5%. Patients with CIDP and antecedent infections more often had an acute onset of CIDP and cranial nerve involvement than those without these antecedent events. CONCLUSIONS: The results of this preliminary study seem to indicate that some dietary habits may influence the risk of CIDP and that antecedent infections may have an impact on the onset and clinical presentation of the disease.

MoS2 pixel arrays for real-time photoluminescence imaging of redox molecules.

Measuring the behavior of redox-active molecules in space and time is crucial for understanding chemical and biological systems and for developing new technologies. Optical schemes are noninvasive and scalable, but usually have a slow response compared to electrical detection methods. Furthermore, many fluorescent molecules for redox detection degrade in brightness over long exposure times. Here, we show that the photoluminescence of "pixel" arrays of monolayer MoS2 can image spatial and temporal changes in redox molecule concentration. Because of the strong dependence of MoS2 photoluminescence on doping, changes in the local chemical potential substantially modulate the photoluminescence of MoS2, with a sensitivity of 0.9 mV / Hz on a 5 µm × 5 µm pixel, corresponding to better than parts-per-hundred changes in redox molecule concentration down to nanomolar concentrations at 100-ms frame rates. This provides a new strategy for visualizing chemical reactions and biomolecules with a two-dimensional material screen.

Mandibular bi-directional distraction osteogenesis: A technique to manage both transverse and sagittal mandibular diameters via a lingual tooth-borne acrylic plate and double-hinge bone anchorage.

PURPOSE: Mandibular hypoplasia can develop transversely, sagittally, or in both diameters simultaneously. Current techniques achieve either sagittal or transverse expansion with different surgeries. Here, we present a novel method to obtain transverse and sagittal mandibular distraction in one stage. MATERIALS AND METHODS: The technique consists of a double osteotomy: a dento-alveolar osteotomy comprising four or six anterior teeth and a vertical symphysiotomy underneath. The mandibular basal bone is immediately expanded transversely and fixed to the lower symphysis via a miniplate carrying only one screw on each side that functions as a hinge during active distraction. The plate is connected to the anterior dento-alveolar block with a metal wire ligature. A teeth-anchored lingual distraction system can expand transversely at the alveolar bone level and then sagittally with the anterior dento-alveolar segment wired to the lower plate. RESULTS: Satisfying and stable results were achieved, confirmed by measurements on serial plaster casts. CONCLUSION: To the best of our knowledge, this is the first proposal for ortho-surgical correction of both transversal and sagittal mandibular hypoplasia via a bi-directional distraction procedure. A combination of bone-hardware anchorage and dental-anchored distraction systems is suggested. Transmucosal hardware emergence and need for a second surgery to remove bone-borne appliances are avoided.

Long term effectiveness of electrochemotherapy for the treatment of lower lip squamous cell carcinoma.

PURPOSE: Electrochemotherapy (ECT) is a therapeutic approach based on the local application of electrical pulses that permeabilize cell membranes to enhance the uptake of low-permeant chemotherapeutic agents, thus increasing their cytotoxic effects. MATERIALS AND METHODS: Twenty-one patients with SCC of the lower lip were treated according to the European Standard Operating Procedures of Electrochemotherapy. Bleomycin (15,000 IU/m2 body surface area) was administered intravenously over a 1-min period. Eight electrical pulses (amplitude, 1000 V/cm; duration, 100 µs) were generated and delivered at a repetition frequency of 5 kHz. Changes in tumor volume were used to assess treatment response. RESULTS: Objective response (OR), complete response (CR), and partial response (PR) rates of 100%, 71.4%, and 28.6% respectively were demonstrated following a single session of ECT. ECT was well tolerated, and no adverse events occurred. CONCLUSIONS: Intravenous bleomycin-based ECT is a safe and effective therapy for SCC of the lower lip. ECT improves the quality-of-life of patients by preserving the function and the aesthetic appearance of the affected area. ECT provides a therapeutic option for elderly and frail patients who, due to their state of health, are not suitable for, or refuse surgical interventions.

Altered TDP-43-dependent splicing in HSPB8-related distal hereditary motor neuropathy and myofibrillar myopathy.

BACKGROUND AND PURPOSE: Mutations in the small heat-shock protein 22 gene (HSPB8) have been associated with Charcot-Marie-Tooth disease type 2L, distal hereditary motor neuropathy (dHMN) type IIa and, more recently, distal myopathy/myofibrillar myopathy (MFM) with protein aggregates and TDP-43 inclusions. The aim was to report a novel family with HSPB8K141E -related dHMN/MFM and to investigate, in a patient muscle biopsy, whether the presence of protein aggregates was paralleled by altered TDP-43 function. METHODS: We reviewed clinical and genetic data. We assessed TDP-43 expression by qPCR and alternative splicing of four previously validated direct TDP-43 target exons in four genes by reverse transcriptase-polymerase chain reaction. RESULTS: The triplets and their mother presented in the second to third decade of life with progressive weakness affecting distal and proximal lower limb and truncal muscles. Nerve conduction study showed a motor axonal neuropathy. The clinical features, moderately raised creatin kinase levels, selective pattern of muscle involvement on magnetic resonance imaging and pathological changes on muscle biopsy, including the presence of protein aggregates, supported the diagnosis of a contemporary primary muscle involvement. In affected muscle tissue we observed a consistent alteration of TDP-43-dependent splicing in three out of four TDP-43-target transcripts (POLDIP3, FNIP1 and BRD8), as well as a significant decrease of TDP-43 mRNA levels. CONCLUSIONS: Our study confirmed the role of mutated HSPB8 as a cause of a combined neuromuscular disorder encompassing dHMN and MFM with protein aggregates. We identified impaired RNA metabolism, secondary to TDP-43 loss of function, as a possible pathological mechanism of HSPB8K141E toxicity, leading to muscle and nerve degeneration.

Effects of daily tadalafil on lower urinary tract symptoms in young men with multiple sclerosis and erectile dysfunction: a pilot study.

PURPOSE: Men affected by multiple sclerosis often experience neurogenic overactive bladder (OAB), lower urinary tract symptoms and erectile dysfunction (ED). The aim of the study was to investigate modifications of urinary and sexual functions after administration of daily tadalafil (TAD) 5 mg. METHODS: Twenty men were enrolled in a single-blind, 4-week prospective study while 10 men without treatment served as controls. Primary outcomes were changes from baseline of International Prostate Symptom (IPSS), OAB questionnaire (OAB-q-short form) and International Index of Erectile Function (IIEF-5) scores. To evaluate the influence of bladder filling on somatic reflexes, we studied variations of the H-reflex evoked by electrical stimuli applied to the tibial nerve at the popliteal fossa and recorded from the soleus muscle. Also testosterone/estradiol (T/E) ratio was measured before and after treatment. RESULTS: In TAD group, an improvement in IPSS (p < 0.001), OAB-q (p < 0.001) and IIEF-5 (p < 0.001) scores was found. Also, an increase in Q max (p < 0.01) and T/E ratio (p < 0.01) was found with a concomitant reduction in post-void residual volume (p < 0.001) without any changes in the H-reflex. CONCLUSIONS: The study demonstrates for the first time that daily TAD in patients with multiple sclerosis improves storage symptoms, post-void residual volume, steroid hormone pattern and ED without urodynamic changes.

Validation of plasma microRNAs as biomarkers for myotonic dystrophy type 1.

Non-invasive and simple to measure biomarkers are still an unmet need for myotonic dystrophy type 1 (DM1). Indeed, muscle biopsies can be extremely informative, but their invasive nature limits their application. Extracellular microRNAs are emerging humoral biomarkers and preliminary studies identified a group of miRNAs that are deregulated in the plasma or serum of small groups of DM1 patients. Here we adopted very stringent selection and normalization criteria to validate or disprove these miRNAs in 103 DM1 patients and 111 matched controls. We confirmed that 8 miRNAs out of 12 were significantly deregulated in DM1 patients: miR-1, miR-27b, miR-133a, miR-133b, miR-206, miR-140-3p, miR-454 and miR-574. The levels of these miRNAs, alone or in combination, discriminated DM1 from controls significantly, and correlated with both skeletal muscle strength and creatine kinase values. Interestingly, miR-133b levels were significantly higher in DM1 female patients. Finally, the identified miRNAs were also deregulated in the plasma of a small group (n = 30) of DM2 patients. In conclusion, this study proposes that miRNAs might be useful as DM1 humoral biomarkers.

Laryngeal and phrenic nerve involvement in a patient with hereditary neuropathy with liability to pressure palsies (HNPP).

Lower cranial and phrenic nerve involvement is exceptional in hereditary neuropathy with liability to pressure palsies (HNPP). Here we report the occurrence of reversible laryngeal and phrenic nerve involvement in a patient with HNPP. The patient recalled several episodes of reversible weakness and numbness of his feet and hands since the age of 30 years. His medical history was uneventful, apart from chronic obstructive pulmonary disease (COPD). At age 44, following severe weight loss, he presented with progressive dysphonia and hoarseness. EMG of cricoarytenoid and thyroarytenoid muscles and laryngeal fibroscopy confirmed vocal cord paralysis. These speech disturbances gradually regressed. Two years later, he reported rapidly worsening dyspnea. Electroneurography showed increased distal latency of the right phrenic nerve and diaphragm ultrasonography documented reduced right hemi-diaphragm excursion. Six months later and after optimization of CODP treatment, his respiratory function had improved and both phrenic nerve conduction and diaphragm excursion were completely restored. We hypothesize that chronic cough and nerve stretching in the context of CODP, together with severe weight loss, may have triggered the nerve paralysis in this patient. Our report highlights the need for optimal management of comorbidities such as CODP as well as careful control of weight in HNPP patients to avoid potentially harmful complications.

Combined central and peripheral demyelination: Clinical features, diagnostic findings, and treatment.

Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center study. In 20 patients (65%) CCPD presented, after an infection, as myeloradiculoneuropathy, encephalopathy, cranial neuropathy, length-dependent peripheral neuropathy, or pseudo-Guillain-Barré syndrome. Demyelinating features of peripheral nerve damage fulfilling European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria for CIDP were found in 23 patients (74%), and spatial dissemination of demyelinating lesions on brain MRI fulfilling the 2010 McDonald criteria for multiple sclerosis (MS) in 11 (46%). Two thirds of the patients had a relapsing or progressive disease course, usually related to the appearance of new spinal cord lesions or worsening of the peripheral neuropathy, and showed unsatisfactory responses to high-dose corticosteroids and intravenous immunoglobulins. The clinical presentation of CCPD was severe in 22 patients (71%), who were left significantly disabled. Our data suggest that CCPD has heterogeneous features and shows frequent post-infectious onset, primary peripheral nervous system or central nervous system involvement, a monophasic or chronic disease course, inadequate response to treatments, and a generally poor outcome. We therefore conclude that the current diagnostic criteria for MS and CIDP may not fully encompass the spectrum of possible manifestations of CCPD, whose pathogenesis remains largely unknown.

Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area.

Tafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed a multi-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Sixty-one (42 males) patients were recruited. Only 28 % of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59 years) and 18 % was in advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One-third of patients did not show significant progression along 36 months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6 months but progression slowed significantly thereafter. Autonomic function remained stable in 33 %, worsened in 56 % and improved in 10 %. Fifteen percent of patients showed cardiac disease progression and 30 % new onset of cardiomyopathy. Overall, Tafamidis was not able to prevent functional progression of the disease in 23 (43 %) subjects, including 16 patients who worsened in their walking ability and 12 patients who reached a higher NYHA score during the follow-up period. A higher mBMI at baseline was associated with better preservation of neurological function. In conclusion, neuropathy and cardiomyopathy progressed in a significant proportion of patients despite treatment. However, worsening of neurological function slowed after the first 6 months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from treatment. Body weight preservation is an important favorable prognostic factor.

Health Technology Assessment: introducing a vacuum-based preservation system for biological materials in the anatomic pathology workflow.

INTRODUCTION: The objective of this work is to assess the implementation of a newly introduced medical equipment technology for the vacuum-based preservation of biological materials within an Anatomic Pathology service. METHODS: The approach selected for the analysis is the Health Technology Assessment (HTA ), a comprehensive evaluation method based on relevant scientific evidence and designed to support healthcare decision makers in purchasing, replacing or disposing of technologies. The analysis focused on specific domains such as Technology, Organization, Safety and Economy. RESULTS: The study proves that the use of such technology ensures the biological specimen to be suitably preserved (up to 72 hours), both reducing the amount of fixative being employed in the diagnostic process (30% to 55%) and resulting, in the particular context under examination, in savings of 93%. DISCUSSION: The HTA reported no significant drawbacks related to the use of the technology being examined. Nonetheless, the workflow for managing the transfer of biological materials from the Operating Room to the Anatomic Pathology department needs to be redefined - in terms of handling, processing, storage and disposal. Other elements concerned the monitoring of storage temperature, fresh tissue handling and especially fixative amount reduction, which positively impacts on the operators' safety with regard to chemical hazards.