Gastrointestinal Stromal Tumors (GISTs) Mimicking Primary Ovarian Tumors or Metastasizing to the Ovaries: A Systematic Literature Review.

Background: Gastrointestinal stromal tumors (GISTs) are a rare neoplasm, sometimes mimicking primary ovarian tumors (OTs) and/or metastasizing to the ovaries (M-OT). We performed a systematic literature review (SLR) of OTs and M-OTs, investigating differences in recurrence-free and overall survival. Methods: Our SLR was performed according to PRISMA guidelines, searching in Pubmed, Scopus, and Web of Science databases from inception until 21 April 2024. Results: Overall, 59 OTs (Group 1) and 21 M-OTs (Group 2) were retrieved. The absence of residual disease after surgery was achieved significantly in a higher percentage of patients with Group 1 GISTs (91.5%) compared with Group 2 GISTs (57.1%). Chemotherapy was more frequently administered to Group 2 patients (33% vs. 0%). Recurrence and deaths for disease were significantly more frequent in Group 2 than Group 1 cases (54.5% vs. 6.8%, and 37.5% vs. 9.8%, respectively). Conclusions: GISTs can rarely mimic primary ovarian cancers or even more rarely metastasize to the ovaries. Group 1 GISTs occurred in younger women, were not associated with elevated tumor markers, and had a better prognosis. In contrast, Group 2 GISTs occurred in older women, may exhibit elevated tumor markers, and presented a worse prognosis. However, no significant statistical difference for survival between the two studied groups was detected. Computed tomography scans can define the size of GISTs, which correlate to stage and prognostic risk classes. The gold standard treatment is complete surgical resection, which was achieved in almost all cases of Group 1 GISTs and in half of Group 2. Histopathology and immunohistochemistry are essential for the final diagnosis and guide chemotherapy treatment.

Systemic infection in aged mice causes upregulation of crystallin alpha A in the RPE/choroid.

Aging changes the responsiveness of our immune defense, and this decline in immune reactivity plays an important role in the increased susceptibility to infections that marks progressing age. Aging is also the most pronounced risk factor for development of age-related macular degeneration (AMD), a disease that is characterized by dysfunctional retinal pigment epithelial (RPE) cells and loss of central vision. We have previously shown that acute systemic viral infection has a large impact on the retina in young mice, leading to upregulation of chemokines in the RPE/choroid (RPE/c) and influx of CD8 T cells in the neuroretina. In this study, we sought to investigate the impact of systemic infection on the RPE/c in aged mice to evaluate whether infection in old age could play a role in the pathogenesis of AMD. We found that systemic infection in mice led to upregulation of genes from the crystallin family in the RPE/c from aged mice, but not in the RPE/c from young mice. Crystallin alpha A (CRYAA) was the most upregulated gene, and increased amounts of CRYAA protein were also detected in the aged RPE/c. Increased CRYAA gene and protein expression has previously been found in drusen and choroid from AMD patients, and this protein has also been linked to neovascularization. Since both drusen and neovascularization are important hallmarks of advanced AMD, it is interesting to speculate if upregulation of crystallins in response to infection in old age could be relevant for the pathogenesis of AMD.

Exploring therapeutic interventions for functional neurological disorders: a comprehensive scoping review.

Functional Neurological Disorders (FNDs) are characterized by the symptoms experienced by the individuals but also by how they express personal experiences and concerns related to the clinical condition. Access to care programs for functional neurological symptoms appears challenging and may entail circular, self-perpetuating healthcare pathways. Given the challenging and misleading interpretations around FND, in advocating for care pathways beyond medical therapies, we designed a scoping review to map recently suggested practices and interventions. We identified 31 relevant papers published between January 2018 and December 2022. Most of the literature was gathered from the US and UK healthcare experiences, with documented interventions provided by multi-professional teams or stand-alone psychotherapists. We found different care pathways addressing either motor or non-motor manifestations. Persons with Functional Motor Disorder are more likely to be referred to physical therapy first, while Persons suffering from Non-Epileptic Seizures are to mental health services. A narrow focus was given to minor components of multimodal approaches (e.g. social workers, and occupational therapists). High heterogeneity was found between assessment instruments as well, reflecting different perspectives in selecting treatment outcomes (e.g., reduction of non-epileptic events, psychological functioning, motor symptoms). Among healthcare professionals, neurologists and (neuro)psychiatrists are typically engaged in formulating and delivering diagnoses, while treatment is often administered by physiotherapists and/or psychologists. In the context of FNDs, the complex etiopathological nature of the condition, including comorbidities, suggests the recommendation of multidisciplinary treatments adopting a stepped care model progressing from standard to higher level individualized modules may better suit individual complexities.

Cancer cachexia: A scoping review on non-pharmacological interventions.

Objective: Cancer cachexia occurs in 30%-80% of patients, increasing morbidity and mortality and impacting the health-related quality of life also for caregivers. Pharmacological interventions have been studied but have shown inconsistent effects on patients' lives in terms of relative outcomes and poor adherence to pharmacological treatment. We provide an overview of the evidence on non-pharmacological interventions for cancer cachexia. Methods: We conducted a scoping review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses-extension for scoping review (PRISMA-ScR). On September 21, 2022, plus an update on January 10, 2024, we searched MEDLINE, Embase, CINAHL, Cochrane, PsycINFO, and Scopus for 2012-2024. We excluded pharmacological interventions defined as "any substance, inorganic or organic, natural or synthetic, that can produce functional modifications, through a chemical, physicochemical or physical action." Results: The search retrieved 9308 articles, of which 17 were eligible. Non-pharmacological interventions included nutritional counseling, complementary therapies (acupuncture), rehabilitation, and psychoeducational/psychosocial support. The data showed small and heterogeneous samples and different disease localization and stages. Thirty-nine percent were multimodal interventions and aimed at patients, not families. The common primary outcomes were body weight and composition, biomarkers, quality of life, psychological suffering, and muscular strength. Only three studies focus on the patient-caregiver dyad. Conclusions: Interventions on cancer cachexia should be multimodal and multiprofessional, proposed early, and aimed at quality of life outcomes. The caregiver's involvement is essential. Nurses can play an active role in managing cancer cachexia. More well-designed studies are needed to understand the efficacy and contents of non-pharmacological interventions. Systematic review registration: The review protocol has been registered in the OSF registry (DOI: 10.17605/OSF.IO/H4A29).

Olanzapine, risperidone and ziprasidone differently affect lysosomal function and autophagy, reflecting their different metabolic risk in patients.

The metabolic effects induced by antipsychotics in vitro depend on their action on the trafficking and biosynthesis of sterols and lipids. Previous research showed that antipsychotics with different adverse effects in patients cause similar alterations in vitro, suggesting the low clinical usefulness of cellular studies. Moreover, the inhibition of peripheral AMPK was suggested as potential aetiopathogenic mechanisms of olanzapine, and different effects on autophagy were reported for several antipsychotics. We thus assessed, in clinically-relevant culture conditions, the aetiopathogenic mechanisms of olanzapine, risperidone and ziprasidone, antipsychotics with respectively high, medium, low metabolic risk in patients, finding relevant differences among them. We highlighted that: olanzapine impairs lysosomal function affecting autophagy and autophagosome clearance, and increasing intracellular lipids and sterols; ziprasidone activates AMPK increasing the autophagic flux and reducing intracellular lipids; risperidone increases lipid accumulation, while it does not affect lysosomal function. These in vitro differences align with their different impact on patients. We also provided evidence that metformin add-on improved autophagy in olanzapine-treated cells and reduced lipid accumulation induced by both risperidone and olanzapine in an AMPK-dependent way; metformin also increased the production of bile acids to eliminate cholesterol accumulations caused by olanzapine. These results have different clinical implications. We demonstrated that antipsychotics with different metabolic impacts on patients actually have different mechanisms of action, thus supporting the possibility of a personalised antipsychotic treatment. Moreover, we found that metformin can fully revert the phenotype caused by risperidone but not the one caused by olanzapine, that still activates SREBP2.

A case of a childhood onset developmental encephalopathy with a novel de novo truncating variant in the Membrane Protein Palmitoylated 5 (MPP5) gene.

BACKGROUND: Membrane Protein Palmitoylated 5 (MPP5) is a highly conserved apical complex protein, essential for cell polarity. Defects in neuronal cell polarity are associated with neurologic disorders. Only three patients with heterozygous MPP5 de novo variants have been reported so far, with global developmental delay, behavioral changes and in only one case epileptic seizures. OBJECTIVE: To describe a new patient with a novel truncating de novo mutation in MPP5 and to characterize in detail the epileptic phenotype and electroencephalographic features of the encephalopathy. METHODS: We identified a novel truncating de novo mutation in MPP5 in a 44 year old patient by exome sequencing (p.Ser498Phefs*15). We retrospectively analyzed his clinical and instrumental data along a thirty-year follow up. RESULT: Our patient presents with generalized tonic-clonic seizures, myoclonic and clonic seizures, non-epileptic myoclonus, tremor, severe intellectual disability, mild face dysmorphic traits, and psychosis. DISCUSSION AND CONCLUSION: We present a case of a childhood onset developmental encephalopathy with a likely-pathogenic variant in the MPP5 gene.. This represents the first complete description of the epileptic syndrome associated with the MPP5 gene.

Caregivers' burden and deep brain stimulation for Parkinson disease: A systematic review of qualitative studies.

BACKGROUND AND PURPOSE: The impact of subthalamic nucleus deep brain stimulation (STN-DBS) on caregivers' burden is understudied. We perform a systematic review and meta-synthesis aggregating qualitative studies involving partners of people with Parkinson disease (PwP) to explore their experiences and unmet needs. METHODS: A systematic review for retrieving qualitative studies included six databases: MEDLINE, Embase, CINAHL, Cochrane, PsycInfo, and Scopus. Inclusion criteria were as follows: (i) studies on the experience of caregivers of PwP in the context of STN-DBS, (ii) English peer-reviewed articles, and (iii) qualitative or mixed methods studies reporting caregivers' quotations. After the appraisal of included studies, we performed meta-synthesis of qualitative findings. Descriptive themes and conceptual elements related to PwP partners' experiences and unmet needs were generated. RESULTS: A total of 1108 articles were screened, and nine articles were included. Three categories were identified: (i) dealing with Parkinson disease (PD) every day (the starting situation characterized by the impact of PD on ordinary life; the limitations to partners' socialization; partners' efforts in stepping aside for love and care activities), (ii) facing life changes with STN-DBS (the feeling of being unprepared for changes; the fear and concern due to loved ones' behavioral changes; struggling to find an explanation for those changes), and (iii) rebuilding the role of caregiver and partner after STN-DBS. CONCLUSIONS: This meta-synthesis elucidates concerns, challenges, and unmet needs of partners of PwP who underwent STN-DBS. It is important to provide them with information, education, and adequate support to face these challenges. Professionals need to involve partners in the care and decision process, because STN-DBS-related outcomes do not depend solely on the well-being of PwP but also on the well-being of individuals surrounding them.

The Effect of Diet on Breast Cancer Recurrence: The DIANA-5 Randomized Trial.

PURPOSE: The DIANA-5 randomized controlled trial assessed the effectiveness of a diet based on Mediterranean and macrobiotic traditions (macro-Mediterranean diet) in reducing breast cancer recurrence. PATIENTS AND METHODS: The DIANA-5 study involved 1,542 patients with breast cancer at high risk of recurrence because of estrogen receptor-negative cancer, or metabolic syndrome, or high plasma levels of insulin or testosterone. Women were randomly assigned to an active dietary intervention (IG) or a control group (CG). Both groups received the 2007 American Institute for Cancer Research/World Cancer Research Fund recommendations for cancer prevention. The intervention consisted of meetings with kitchen classes, community meals, and dietary recommendations. Recommended foods included whole grain cereals, legumes, soy products, vegetables, fruit, nuts, olive oil, and fish. Foods to be avoided were refined products, potatoes, sugar and desserts, red and processed meat, dairy products, and alcoholic drinks. A compliance Dietary Index was defined by the difference between recommended and discouraged foods. RESULTS: Over the 5 years of follow-up, 95 patients of the IG and 98 of the CG developed breast cancer recurrence [HR = 0.99; 95% confidence interval (CI): 0.69-1.40]. The analysis by compliance to the dietary recommendations (IG and CG together) showed that the women in the upper tertile of Dietary Index change had an HR of recurrence of 0.59 (95% CI: 0.36-0.92) compared with women in the lower tertile. CONCLUSIONS: The DIANA-5 dietary intervention trial failed to show a reduction in breast cancer recurrence, although self-reported diet at year 1 in IG and CG combined showed a protective association with the higher Dietary Index change. See related commentary by McTiernan, p. 931.

Hospice Patients' End-of-Life Dreams and Visions: A Systematic Review of Qualitative Studies.

When conscious, about 50% to 60% of hospice patients report a "visitation" by someone who is not there while they dream or are awake: a phenomenon known as End-of-Life Dreams and Visions (ELDVs). Since the dying process is frequently complicated by delirium, ELDVs risk being misidentified as such by professionals and caregivers. To observe these phenomena from patients' perspectives, we conducted a systematic review to aggregate and synthesize the findings from the qualitative studies about ELDVs of patients assisted in hospices to indicate future directions for research and care. MEDLINE/PubMed, Embase, CINAHL, PsycINFO, Scopus, and Web of Science databases were searched, yielding 293 documents after duplicates were removed. Six qualitative articles reporting on five unique studies conducted in hospice settings were included in the meta-synthesis. We generated three main categories: i) typologies of ELDVs reported, ii) emotional consequences, and iii) intersubjective meaning-making. The ELDVs reported were experiences that remained intimate and unsocialized and thus preventing participants from defining a shared sense in their relationships. Training healthcare professionals to recognize ELDVs and take advantage of them in the care relationship is desirable. We also encourage the patient's family members to listen and understand ELDVs when they occur actively. For caregivers to know how to interpret these phenomena may provide them with additional strategies for supporting, reassuring, and strengthening their relationships with their loved ones. The review allowed us to inform healthcare professionals and caregivers about how to help patients share their emotional and identity-related experiences and meaning-making in end-of-life.

The meaning of dignity in care during the COVID-19 pandemic: a qualitative study in acute and intensive care.

BACKGROUND: The pandemic Era has forced palliative care professionals to use a dignity-in-care approach in different settings from the classic ones of palliative care: acute and intensive care. We explored the meanings of dignity for patients, their family members, and clinicians who have experienced COVID-19 in the acute and intensive care setting. METHODS: A qualitative, prospective study by means of semi-structured interviews with patients hospitalized for COVID-19, family members, and clinicians who care for them. FINDINGS: Between March 2021 and October 2021, we interviewed 16 participants: five physicians, three nurses, and eight patients. None of the patients interviewed consented for family members to participate: they considered it important to protect them from bringing the painful memory back to the period of their hospitalization. Several concepts and themes arose from the interviews: humanity, reciprocity, connectedness, and relationship, as confirmed by the literature. Interestingly, both healthcare professionals and patients expressed the value of informing and being informed about clinical conditions and uncertainties to protect dignity. CONCLUSIONS: Dignity should be enhanced by all healthcare professionals, not only those in palliative care or end-of-life but also in emergency departments.

Recruitment strategies and interventions to increase participation in lung cancer screening programmes: a systematic review protocol.

INTRODUCTION: Despite strong evidence for the efficacy of low-radiation dose CT (LDCT) in reducing lung cancer (LC) mortality, implementing LC screening (LCS) programmes remains a challenge. We aim to systematically review the evidence on the strategies used to recruit the adult population at risk of LC to LDCT within LCS programmes and to estimate the effectiveness of interventions identified, used to reach the potentially eligible population, increase participation and informed choice, and ensure equitable access. METHODS AND ANALYSIS: This sequential systematic literature review will consist of three steps: (1) a scoping review of existing strategies and organisational models for LCS; (2) selecting papers reporting relevant outcomes (test coverage, screening participation and informed choice) and comparing results among different models; (3) a systematic review of interventions implemented to increase participation in LCS programmes. Each step will follow the methodological guidelines provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data sources include electronic databases such as Medline (PubMed version), Embase, CINAHL (Ebsco version), Scopus and Cochrane CENTRAL. The search will be limited to studies published from January 2000 to March 2023 in English, Italian, French, Spanish, Serbian and Croatian language. Findings will be synthesised quantitatively and qualitatively as appropriate. Risk of bias assessment will be only applied to studies selected in the second and third steps. The quality of evidence will be summarised for each outcome using the Grading Recommendation Assessment, Development and Evaluation methodology. ETHICS AND DISSEMINATION: Given that this is a review of existing literature, ethics approval is not required. The results will be published in peer-reviewed scientific journals and presented at relevant conferences. The findings of this review will help guide health authorities in organising LCS programmes and developing recommendations, policies, and actions at national and regional levels. PROSPERO REGISTRATION NUMBER: CRD42023408357.

Outcome measures for assessing the effectiveness of physiotherapy interventions on equinus foot deformity in post-stroke patients with triceps surae spasticity: A scoping review.

OBJECTIVE: Equinus foot deformity (EFD) is the most common deviation after stroke. Several physiotherapy interventions have been suggested to treat it. However, studies evaluating the efficacy of these treatments vary widely in terms of assessment modalities, type of data analysis, and nomenclature. This scoping review aimed to map current available evidence on outcome measures and the modalities employed to assess the effectiveness of physiotherapy programs for the reduction of triceps surae (TS) spasticity and EFD in patients with stroke. METHODS: Scoping review methodological frameworks have been used. Three databases were investigated. Primary literature addressing TS spasticity in adult patients with stroke using physiotherapy interventions was included. Findings were systematically summarized in tables according to the intervention used, intervention dosage, control group, clinical, and instrumental outcome measures. RESULTS: Of the 642 retrieved studies, 53 papers were included. TS spasticity was assessed by manual maneuvers performed by clinicians (mainly using the Ashworth Scale), functional tests, mechanical evaluation through robotic devices, or instrumental analysis and imaging (such as the torque-angle ratio, the H-reflex, and ultrasound images). A thorough critical appraisal of the construct validity of the scales and of the statistics employed was provided, particularly focusing on the choice of parametric and non-parametric approaches when using ordinal scales. Finally, the complexity surrounding the concept of "spasticity" and the possibility of assessing the several underlying active and passive causes of EFD, with a consequent bespoke treatment for each of them, was discussed. CONCLUSION: This scoping review provides a comprehensive description of all outcome measures and assessment modalities used in literature to assess the effectiveness of physiotherapy treatments, when used for the reduction of TS spasticity and EFD in patients with stroke. Clinicians and researchers can find an easy-to-consult summary that can support both their clinical and research activities.

Patient-reported outcome measure to implement routine assessment of cancer survivors' unmet needs: An overview of reviews and COSMIN analysis.

As the number of cancer survivors (CSs) is increasing worldwide, providing services relevant to the specific, unmet needs of these individuals is crucial. There are currently various patient-reported outcome measures (PROMs) whose aim is to identify the unmet needs of CSs. Still, limited guidance supports healthcare providers in choosing the most valid and reliable PROMs for this purpose. We conducted this overview of systematic reviews (SRs) on the psychometric properties of PROMs addressing the unmet needs of adult CSs suffering from non-cutaneous cancers. We searched databases for SRs published between 2012 and January 2023. Two SRs were included, covering 14 PROMs tested on 19,151 CSs. These were assessed according to the COSMIN methodology for SRs of PROMs for the quality of their measurement properties and risk of bias, thus providing guidance in selecting PROMs that appropriately reflect the unmet needs of CSs.

Insights into Healthcare Professionals' Perceptions and Attitudes toward Nanotechnological Device Application: What Is the Current Situation in Glioblastoma Research?

Nanotechnology application in cancer treatment is promising and is likely to quickly spread worldwide in the near future. To date, most scientific studies on nanomaterial development have focused on deepening the attitudes of end users and experts, leaving clinical practice implications unexplored. Neuro-oncology might be a promising field for the application of nanotechnologies, especially for malignant brain tumors with a low-survival rate such as glioblastoma (GBM). As to improving patients' quality of life and life expectancy, innovative treatments are worth being explored. Indeed, it is important to explore clinicians' intention to use experimental technologies in clinical practice. In the present study, we conducted an exploratory review of the literature about healthcare workers' knowledge and personal opinions toward nanomedicine. Our search (i) gives evidence for disagreement between self-reported and factual knowledge about nanomedicine and (ii) suggests the internet and television as main sources of information about current trends in nanomedicine applications, over scientific journals and formal education. Current models of risk assessment suggest time-saving cognitive and affective shortcuts, i.e., heuristics support both laypeople and experts in the decision-making process under uncertainty, whereas they might be a source of error. Whether the knowledge is poor, heuristics are more likely to occur and thus clinicians' opinions and perspectives toward new technologies might be biased.

A Novel De novo Heterozygous Mutation in the SON Gene Associated with Septo-optic Dysplasia: A New Phenotype.

Septo-optic dysplasia (SOD) syndrome is a rare congenital disorder characterized by a classic triad of optic nerve/chiasm hypoplasia, agenesis of septum pellucidum and corpus callosum, and hypoplasia of the hypothalamic-pituitary axis.Herein, we report the clinical case of 2-year-old boy presenting with psychomotor delay, nystagmus, congenital hypothyroidism, and a clinically relevant growth delay. The neuroradiological examination showed partial segmental agenesis of the corpus callosum, agenesis of the septum pellucidum, optic nerve hypoplasia, and a small pituitary gland with a small median pituitary stalk. A whole-exome sequencing analysis detected a novel heterozygous de novo variant c.1069_1070delAG in SON, predicted as likely pathogenic.To date, SON pathogenic variants have been described as responsible for Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, a multisystemic neurodevelopmental disorder mainly characterized by intellectual disability, facial dysmorphisms, visual abnormalities, brain malformations, feeding difficulties, and growth delay. The herein described case is the first recognized clinic-radiological occurrence of SOD syndrome with hypothalamic-pituitary dysfunction in a patient carrying a SON gene variant, considered responsible of ZTTK syndrome, suggesting a possible relationship between SOD and SON gene alterations, never described so far, making the search for SON gene mutations advisable in patients with SOD.

Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias.

Although the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it difficult to discern genotype-phenotype correlations. We therefore screened individuals who had been found to bear variants in a non-expansion SCA-associated gene through genetic testing, and after we eliminated genetic groups that had fewer than 30 subjects, there were 756 subjects bearing single-nucleotide variants or deletions in one of seven genes: CACNA1A (239 subjects), PRKCG (175), AFG3L2 (101), ITPR1 (91), STUB1 (77), SPTBN2 (39), or KCNC3 (34). We compared age at onset, disease features, and progression by gene and variant. There were no features that reliably distinguished one of these SCAs from another, and several genes-CACNA1A, ITPR1, SPTBN2, and KCNC3-were associated with both adult-onset and infantile-onset forms of disease, which also differed in presentation. Nevertheless, progression was overall very slow, and STUB1-associated disease was the fastest. Several variants in CACNA1A showed particularly wide ranges in age at onset: one variant produced anything from infantile developmental delay to ataxia onset at 64 years of age within the same family. For CACNA1A, ITPR1, and SPTBN2, the type of variant and charge change on the protein greatly affected the phenotype, defying pathogenicity prediction algorithms. Even with next-generation sequencing, accurate diagnosis requires dialogue between the clinician and the geneticist.

Reduction of EpCAM-Positive Cells from a Cell Salvage Product Is Achieved by Leucocyte Depletion Filters Alone.

Intraoperative cell salvage reduces the need for allogeneic blood transfusion in complex cancer surgery, but concerns about the possibility of it re-infusing cancer cells have hindered its application in oncology. We monitored the presence of cancer cells on patient-salvaged blood by means of flow cytometry; next, we simulated cell salvage, followed by leucodepletion and irradiation on blood contaminated with a known amount of EpCAM-expressing cancer cells, assessing also residual cancer cell proliferation as well as the quality of salvaged red blood cell concentrates (RBCs). We observed a significant reduction of EpCAM-positive cells in both cancer patients and contaminated blood, which was comparable to the negative control after leucodepletion. The washing, leucodepletion and leucodepletion plus irradiation steps of cell salvage were shown to preserve the quality of RBCs in terms of haemolysis, membrane integrity and osmotic resistance. Finally, cancer cells isolated from salvaged blood lose their ability to proliferate. Our results confirm that cell salvage does not concentrate proliferating cancer cells, and that leucodepletion allows for the reduction of residual nucleated cells, making irradiation unnecessary. Our study gathers pieces of evidence on the feasibility of this procedure in complex cancer surgery. Nevertheless, it highlights the necessity of finding a definitive consensus through prospective trials.

Case report: A novel FARS2 deletion and a missense variant in a child with complicated, rapidly progressive spastic paraplegia.

Defects in FARS2 are associated with either epileptic phenotypes or a spastic paraplegia subtype known as SPG77. Here, we describe an 8-year-old patient with severe and complicated spastic paraplegia, carrying a missense variant (p.Pro361Leu) and a novel intragenic deletion in FARS2. Of note, the disease is unexpectedly progressing rapidly and in a biphasic way differently from the previously reported cases. Our study provides the first detailed molecular characterization of a FARS2 deletion and its underlying molecular mechanism, and demonstrates the need for combining different tools to improve the diagnostic rate.