Assessment of the Zulfiqar Frailty Scale (ZFS) in Primary Healthcare.

INTRODUCTION: The primary aim of the study was to validate the Zulfiqar Frailty Scale (ZFS) and examine its concordance with the modified Short Emergency Geriatric Assessment (mSEGA) scale, Part A. METHODS: A prospective observational study was conducted in Guadeloupe (France) over a two-month duration (from 20 February to 20 April 2024), involving elderly individuals aged 65 and older, deemed self-sufficient with an ADL (Activities of Daily Living) score exceeding four out of six. RESULTS: Within this community cohort of 98 individuals, averaging 75 years in age, frailty according to the modified SEGA criteria was prevalent in 29%. Frailty according to the "ZFS" score was prevalent in 40%. Key predictors of frailty identified in our study included age, comorbidity (Charlson score), polypharmacy (total number of medications and therapeutic classes), and functional ability (ADL scores). Notably, experiences of falls and hospitalizations within the past six months significantly influenced the classification of frailty according to both ZFS and SEGA scales. Significant associations with the presence of home care aides (p < 0.0001), monopodal support test results (p < 0.0001), memory impairments (p < 0.0001), and recent hospitalizations (p = 0.0054) underscored the multidimensional impact of frailty. The Pearson correlation coefficient and its 95% confidence interval between the SEGA and Zulfiqar Frailty Scales stood at 0.73 [0.61: 0.81]. The discernment threshold for frailty was set at three out of six criteria, showcasing a sensitivity of 64% and a negative predictive value of 80%. The area under the curve (AUC) for the Zulfiqar Frailty Scale was reported as 0.8. CONCLUSION: The "ZFS" tool allows for the detection of frailty with a highly satisfactory sensitivity and negative predictive value.

Targeting the EGFR pathway: An alternative strategy for the treatment of tuberous sclerosis complex?

INTRODUCTION: Tuberous sclerosis complex (TSC) is caused by variants in TSC1/TSC2, leading to constitutive activation of the mammalian target of rapamycin (mTOR) complex 1. Therapy with everolimus has been approved for TSC, but variations in success are frequent. Recently, caudal late interneuron progenitor (CLIP) cells were identified as a common origin of the TSC brain pathologies such as subependymal giant cell astrocytomas (SEGA) and cortical tubers (CT). Further, targeting the epidermal growth factor receptor (EGFR) with afatinib, which is expressed in CLIP cells, reduces cell growth in cerebral TSC organoids. However, investigation of clinical patient-derived data is lacking. AIMS: Observation of EGFR expression in SEGA, CT and focal cortical dysplasia (FCD) 2B human brain specimen and investigation of whether its inhibition could be a potential therapeutic intervention for these patients. METHODS: Brain specimens of 23 SEGAs, 6 CTs, 20 FCD2Bs and 17 controls were analysed via immunohistochemistry to characterise EGFR expression, cell proliferation (via Mib1) and mTOR signalling. In a cell-based assay using primary patient-derived cells (CT n = 1, FCD2B n = 1 and SEGA n = 4), the effects of afatinib and everolimus on cell proliferation and cell viability were observed. RESULTS: EGFR overexpression was observed in histological sections of SEGA, CT and FCD2B patients. Both everolimus and afatinib decreased the proliferation and viability in primary SEGA, tuber and FCD2B cells. CONCLUSION: Our study demonstrates that EGFR suppression might be an effective alternative treatment option for SEGAs and tubers, as well as other mTOR-associated malformations of cortical development, including FCD2B.

Challenges of siblings with tuberous sclerosis showing various manifestations and severe complications.

Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that primarily affects the central nervous system and various body organs. This case series describes the case history of 2 siblings from the same parents who were diagnosed with TSC. Case 1 is a 13-year-old girl with bilateral renal AML (angiomyolipoma), multiple fat nodules in the liver, and subependymal nodules with tubers revealed in the brain magnetic resonance imaging (MRI). Case 2 is her brother, a 6-year-old boy, who presented with manifestations of subependymal giant cell astrocytoma (SEGA) and renal AML. TSC must be managed with early diagnosis and intervention due to the risk of hamartoma enlargement. These 2 cases found in siblings underline the varied clinical presentations of TSC and the complexities faced by families with TSC. Early diagnosis is important to avoid TSC-related complications because, as time goes by, the disease will impact the patient's quality of life and increase morbidity and mortality. This case series also highlights the advantages of dermatological screening for the early detection of TSC, family screening, the need for multiple imaging modalities and counseling of family members with TSC, as well as the need for ongoing follow-up of this rare disorder.

Bleeding solitary SEGA in non-tuberous sclerosis complex adolescent: a case illustration and review of literature.

Subependymal giant cell astrocytoma (SEGA) represents a benign brain tumor occurring in 5-20% of individuals diagnosed with tuberous sclerosis complex (TSC), serving as a major diagnostic criterion. The presence of SEGA in a patient often prompts consideration of TSC as a probable diagnosis, given its unique association with this disorder. Typically, only one additional major criterion or two minor criteria are necessary to fulfill the diagnostic criteria for TSC. However, in rare instances, SEGA may manifest in patients without clinical features of TSC, termed solitary SEGA. The occurrence of solitary SEGA in patients lacking both clinical manifestations of TSC and genetic confirmation is extremely rare. Furthermore, the presentation of SEGA with intratumoral bleeding is exceedingly uncommon. Here, we presented a case of bleeding solitary SEGA in non-TSC adolescent who underwent surgery and has remained free of disease for a minimum of 3 years. Genetic analysis of peripheral blood and tumor tissue yielded negative results for TSC-related mutations. While SEGA occurrence in non-TSC patients is uncommon, it remains one of the possible diagnoses of intraventricular tumors. However, comprehensive genetic and physical evaluations are imperative to confirm the TSC status and guide further investigations and follow-up appropriately.

Isolated subependymal giant cell astrocytoma (SEGA) in the absence of clinical tuberous sclerosis: two case reports and literature review.

PURPOSE: Subependymal giant cell astrocytoma (SEGA) is a WHO grade I pediatric glioma arising in 5-15% of patients with tuberous sclerosis (TSC). Rare cases of isolated SEGA without TSC have been described. The etiology, genetic mechanisms, natural history, and response to treatment of these lesions are currently unknown. We describe two such cases of isolated SEGA with follow-up. METHODS: Retrospective review was performed at a single institution to describe the clinical course of pathology-confirmed SEGA in patients with germline testing negative for TSC mutations. RESULTS: Two cases of isolated SEGA were identified. Genetic analysis of the tumor specimen was available for one, which revealed an 18 base pair deletion in TSC1. Both cases were managed with surgical resection, one with preoperative embolization. In spite of a gross total resection, one patient experienced recurrence after three years. Treatment with an mTOR inhibitor led to a significant interval reduction of the mass on follow-up MRI. The patient tolerated the medication well for 6 years and is now off of treatment for 2 years with a stable lesion. CONCLUSION: Cases of SEGA outside of the context of TSC are exceedingly rare, with only 48 cases previously described. The genetic mechanisms and treatment response of these lesions are poorly understood. To date, these lesions appear to respond well to mTOR inhibitors and may behave similarly to SEGAs associated with TSC. However, given that experience is extremely limited, these cases should be followed long term to better understand their natural history and treatment response.

Laser interstitial thermal therapy compared with open resection for treating subependymal giant cell astrocytoma.

OBJECTIVE: Subependymal giant cell astrocytomas (SEGAs) are WHO grade 1 tumors associated with tuberous sclerosis that classically arise from the ventricular wall near the caudate groove and foramen of Monro. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical technique, which works by heating a stereotactically placed laser fiber to ablative temperatures under MRI thermometry monitoring. In this paper, the authors present LITT as a surgical alternative to open resection of SEGAs. METHODS: Twelve patients with SEGAs who underwent 16 procedures between 2007 and 2022 at a single institution were retrospectively reviewed. These patients underwent either open resection or LITT. Clinical data, imaging, recurrence rate, further treatments, and related complications were analyzed. RESULTS: Among the 16 procedures, 9 were open resection and 7 were LITT. An external ventricular drain was placed in 66% (6/9) of open procedures and 57.1% (4/7) of LITT cases. A septostomy was performed in 56% (5/9) of open procedures and 29% (2/7) of LITT cases. Complication rates were higher in open cases than in LITT procedures (44% vs 0%, p < 0.05). Complications included hydrocephalus, transient venous ischemia, wound infection, and bone flap migration. The median length of hospital stay was 4 days (IQR 3.3-5.5 days) for open cases and 4 days (IQR 3.0-7.0 days) for LITT procedures. Recurrence or progression occurred after 3 open cases and 2 LITT cases (33% vs 33%, p = 0.803). For the recurrences, 2 open cases underwent stereotactic radiosurgery, 1 open case underwent LITT, and 1 LITT case underwent repeat LITT. Among the LITT cases, only the patients with no decrease in tumor size by 6 months experienced tumor progression afterward. The 2 LITT cases with progression were the only ones with calcification present on preoperative imaging. The median follow-up times for cases assessed for progression were 8.4 years (IQR 3.8-14.4 years) for open resection and 3.9 years (IQR 3.4-5.1 years) for LITT. CONCLUSIONS: The small size of this case series limits generalizability or adequate comparison of safety. However, this series adds to the literature supporting LITT as a less invasive surgical alternative to open resection of SEGAs and demonstrates that LITT has similar recurrence and/or progression rates to open resection. Additional studies with more data are necessary for comprehensive comparisons between open resection and LITT for treating SEGA.

SEGA-like circumscribed astrocytoma in a non-NF1 patient, harboring molecular profile of GBM. A case report.

Subependymal giant cell astrocytoma (SEGA) is a low-grade periventricular tumor that is closely associated with tuberous sclerosis complex (TSC). SEGA typically arises during the first two decades of life and rarely arises after the age of 20-25 years. Nevertheless, it has also been reported that glioma histologically resembling SEGA, so-called SEGA-like astrocytoma, can arise in neurofibromatosis type 1 (NF1) patients, even in the elderly. Herein, we report a case of SEGA-like circumscribed astrocytoma arising in the lateral ventricle of a 75-year-old woman. Whole-exome sequencing revealed a somatic variant of NF1. Methylation array analysis led to a diagnosis of "methylation class glioblastoma, IDH-wildtype, mesenchymal-type (GBM, MES)" with a high calibrated score (0.99). EGFR amplification, CDKN2A/B homozygous deletion, chromosomal +7/-10 alterations, and TERT promoter mutation, typical molecular abnormalities usually found in GBM, were also observed. While most reported cases of SEGA-like astrocytoma have arisen in NF1 patients, the patient was neither TSC nor NF1. Near total removal was accomplished with endoscopic cylinder surgery. At the 36-month follow-up, there was no tumor recurrence without adjuvant therapies. This clinical behavior did not match GBM. SEGA-like astrocytoma of the elderly is rare, and this is the oldest case reported so far. In addition, high-grade molecular features found in circumscribed tumor remain unclear. Further investigations among larger series are needed for clarifying the underlying molecular mechanisms.

Neoadjuvant Therapy with Everolimus for Subependymal Giant Cell Astrocytoma: A Case Report.

Direct surgical resection remains to be the standard treatment for tuberous sclerosis complex (TSC) with subependymal giant cell astrocytoma (SEGA). Medical therapy with everolimus (mammalian target of rapamycin inhibitor or mTOR) serves as a second-line treatment for patients with SEGA who are determined to be ineligible for surgical resection. Some recent studies have reported that neoadjuvant therapy for SEGA may be a useful, novel treatment. In this study, we herein present a case of SEGA and demonstrate the efficacy of preoperative everolimus therapy. We have also examined the utility and safety of neoadjuvant therapy for SEGA and investigated four previously reported cases of preoperative administration of mTOR inhibitors. In these cases, everolimus was administered preoperatively to shrink the tumor although the duration of treatment varied. Afterward, gross total tumor removal was conducted in all the cases. No postoperative complications were reported during the follow-up period. These findings indicate that neoadjuvant therapy with an mTOR inhibitor can be a potential treatment for SEGA. The findings of this present study also suggested that a short administration period of about 2 months may be sufficient to achieve preoperative tumor reduction.

Esclerosis tuberosa / Tuberous sclerosis

La esclerosis tuberosa es un síndrome genético infrecuente caracterizado por la mutación patogénica de los genes TSC1 o TSC2, que condiciona la activación descontrolada de la vía mTOR y la aparición subsecuente de hamartomas. Presenta una expresión clínica muy variable, siendo el diagnóstico genético y clínico. Puede producir afectación neurológica, dermatológica, dental, cardiaca, renal, ocular, pulmonar o a otros niveles. Se trata de una patología probablemente infradiagnosticada, en la que el diagnóstico precoz es fundamental para el tratamiento precoz de las complicaciones, mejorando así el pronóstico de la enfermedad. En este documento se revisan las principales manifestaciones que puede producir esta patología, así como los criterios diagnósticos actualizados y las recomendaciones de estudio al diagnóstico y durante el seguimiento de esta patología. (AU)

Tuberous sclerosis is a rare genetic syndrome characterized by the pathogenic mutation of the TSC1 or TSC genes, thus inducing an uncontrolled overactivation of the mTOR pathway and subsequent hamartoma formation. Clinical manifestations include neurological, dermatological, dental, cardiac, renal, ophthalmologic and pulmonary, although it can affect other systems. A timely diagnosis is essential to promptly institute proper management measures and treat complications, thus improving the patient’s prognosis. In this manuscript, authors review the main clinical manifestations, current diagnostic criteria and present-day recommendations on diagnosis and follow-up in these patients. (AU)

Subependymal giant-cell astrocytomas in the absence of tuberous sclerosis.

OBJECTIVE: Tuberous sclerosis is a rare genetic condition caused by TSC1 or TSC2 mutations that can be inherited, sporadic, or the result of somatic mosaicism. Subependymal giant-cell astrocytoma (SEGA) is a major diagnostic feature of tuberous sclerosis complex (TSC). This study aimed to present a series of cases in which a pathological diagnosis of SEGA was not diagnostic of tuberous sclerosis. METHODS: The authors retrospectively reviewed a clinical case series of 5 children who presented with a SEGA tumor to Johns Hopkins All Children's Hospital and St. Louis Children's Hospital between 2010 and 2022 and whose initial genetic workup was negative for tuberous sclerosis. All patients were treated with craniotomy for SEGA resection. TSC genetic testing was performed on all SEGA specimens. RESULTS: The children underwent open frontal craniotomy for SEGA resection from the ages of 10 months to 14 years. All cases demonstrated the classic imaging features of SEGA. Four were centered at the foramen of Monro and 1 in the occipital horn. One patient presented with hydrocephalus, 1 with headaches, 1 with hand weakness, 1 with seizures, and 1 with tumor hemorrhage. Somatic TSC1 mutation was present in the SEGA tumors of 2 patients and TSC2 mutation in 1 patient. Germline TSC mutation testing was negative for all 5 cases. No patient had other systemic findings of tuberous sclerosis on ophthalmological, dermatological, neurological, renal, or cardiopulmonary assessments and thus did not meet the clinical criteria for tuberous sclerosis. The average follow-up was 6.7 years. Recurrence was noted in 2 cases, in which 1 patient underwent radiosurgery and 1 was started on a mammalian target of rapamycin (mTOR) inhibitor (rapamycin). CONCLUSIONS: There may be intracranial implications of somatic mosaicism associated with tuberous sclerosis. Children who are diagnosed with SEGA do not necessarily have a diagnosis of tuberous sclerosis. Tumors may carry a TSC1 or TSC2 mutation, but germline testing can be negative. These children should continue to be followed with serial cranial imaging for tumor progression, but they may not require the same long-term monitoring as patients who are diagnosed with germline TSC1 or TSC2 mutations.

Evaluation of Nutritional Status in an Acute Geriatric Unit: Retrospective Study and Analysis of Frailty Syndrome.

INTRODUCTION: The aim of our study is to evaluate the nutritional status of patients in an acute geriatric unit. METHODS: Patients included in the study were hospitalized in an acute geriatric unit over a period of 6 months. The nutritional status of each patient was evaluated with anthropometric measurements (the BMI and MNA scales), and biological measurements (albumin). Frailty was evaluated using three scales: the Fried scale, the CFS and the modified SEGA scale. RESULTS: A total of 359 patients were included, comprising 251 women (70%) with an average age of 85.28 years. The study showed that 102 elderly subjects were considered undernourished according to the BMI scale, 52 subjects were undernourished according to the MNA scale, and 50 subjects were undernourished according to their albumin levels. The relationships between undernutrition and frailty syndrome studied in our work show that elderly subjects who are undernourished according to the BMI and MNA scales are significantly frail according to Fried and Rockwood, whereas those who are undernourished according to their albumin levels are significantly frail according to Fried and the modified SEGA scale. CONCLUSION: The relationship between undernutrition and the frailty syndrome is close, and their joint screening is necessary, whether on an outpatient or in-hospital basis, in order to prevent negative events related to comorbidities and geriatric syndromes.

Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex-Current Views on Their Pathogenesis and Management.

Introduction, Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder caused by mutations inactivating TSC1 or TSC2 genes and characterized by the presence of tumors involving many organs, including the brain, heart, kidneys, and skin. Subependymal giant cell astrocytoma (SEGA) is a slow-growing brain tumor almost exclusively associated with TSC. STATE OF THE ART: Despite the fact that SEGAs are benign, they require well-considered decisions regarding the timing and modality of pharmacological or surgical treatment. In TSC children and adolescents, SEGA is the major cause of mortality and morbidity. CLINICAL IMPLICATIONS: Until recently, surgical resection has been the standard therapy for SEGAs but the discovery of the role of the mTOR pathway and the introduction of mTOR inhibitors to clinical practice changed the therapeutic landscape of these tumors. In the current paper, we discuss the pros and cons of mTOR inhibitors and surgical approaches in SEGA treatment. FUTURE DIRECTIONS: In 2021, the International Tuberous Sclerosis Complex Consensus Group proposed a new integrative strategy for SEGA management. In the following review, we discuss the proposed recommendations and report the results of the literature search for the latest treatment directions.

Recent management trends of subependymal giant cell astrocytoma associated with tuberous sclerosis complex.

Subependymal giant cell astrocytomas (SEGA) are benign cranial tumours typically found in patients with tuberous sclerosis complex (TSC). Surgical resection has been the standard treatment for SEGA, however, medical management through mTOR inhibitors has now predominantly replaced surgery as the primary treatment modality. Additionally, newer treatment modalities have emerged with the hopes of providing safer methods for treating the tumour such as laser interstitial thermal therapy (LITT). However, very few reports have addressed these newer methods and analysed the results.

Hyperactivation of mTORC1 in a double hit mutant zebrafish model of tuberous sclerosis complex causes increased seizure susceptibility and neurodevelopmental abnormalities.

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by pathogenic variants in TSC1 and TSC2 genes. TSC patients present with seizures and brain abnormalities such as tubers and subependymal giant cells astrocytoma (SEGA). Despite common molecular and clinical features, the severity of the disease varies greatly, even intrafamilially. The second hit hypothesis suggests that an additional, inactivating mutation in the remaining functional allele causes a more severe phenotype and therefore explains the phenotypic variability. Recently, second hit mutations have been detected frequently in mTORopathies. To investigate the pathophysiological effects of second hit mutations, several mouse models have been developed. Here, we opted for a double mutant zebrafish model that carries a LOF mutation both in the tsc2 and the depdc5 gene. To the best of our knowledge, this is the first time a second-hit model has been studied in zebrafish. Significantly, the DEP domain-containing protein 5 (DEPDC5) gene has an important role in the regulation of mTORC1, and the combination of a germline TSC2 and somatic DEPDC5 mutation has been described in a TSC patient with intractable epilepsy. Our depdc5 -/- x tsc2 -/- double mutant zebrafish line displayed greatly increased levels of mammalian target of rapamycin (mTORC1) activity, augmented seizure susceptibility, and early lethality which could be rescued by rapamycin. Histological analysis of the brain revealed ventricular dilatation in the tsc2 and double homozygotes. RNA-sequencing showed a linear relation between the number of differentially expressed genes (DEGs) and the degree of mTORC1 hyperactivity. Enrichment analysis of their transcriptomes revealed that many genes associated with neurological developmental processes were downregulated and mitochondrial genes were upregulated. In particular, the transcriptome of human SEGA lesions overlapped strongly with the double homozygous zebrafish larvae. The data highlight the clinical relevance of the depdc5 -/- x tsc2 -/- double mutant zebrafish larvae that showed a more severe phenotype compared to the single mutants. Finally, analysis of gene-drug interactions identified interesting pharmacological targets for SEGA, underscoring the value of our small zebrafish vertebrate model for future drug discovery efforts.

Late Manifestation of Subependymal Giant Cell Astrocytoma With Hydrocephalus in an Adult Patient With Tuberous Sclerosis Complex.

Subependymal giant cell astrocytoma (SEGA) is a unique brain tumor that constitutes one of the major diagnostic criteria of tuberous sclerosis complex (TSC). It rarely occurs de novo after adolescence. SEGA tends to originate from the ventricular walls, provoking obstructive hydrocephalus, raised intracranial pressure, and papilledema with plausible visual problems. We present a case of large SEGA in a 33-year-old-TSC patient with a higher-than-expected age for the first presentation. His chief complaint was visual acuity deterioration combined with headaches. Microsurgical removal of the tumor was carried out. Obstructive hydrocephalus and papilledema resolved after treatment. Although SEGA-TSC is considered a tumor of children and adolescents, it can present for the first time in adulthood. In TSC patients, periodic imaging follow-up is recommended and any visual symptoms should prompt exclusion of intracranial tumors.

TTF-1: A Well-Favored Addition to the Immunohistochemistry Armamentarium as a Diagnostic Marker of SEGA.

BACKGROUND: Subependymal giant cell astrocytoma (SEGA) is a World Health Organization grade 1 neoplasm, which, due to its dubious morphologic features, may be misdiagnosed as a high-grade tumor at times. This tumor shows binary immunoexpression including both glial and neural markers, leading to a state of diagnostic quandary. Recent evidences have surmised the diagnostic utility of thyroid transcription factor 1 (TTF-1), spurring us to study the practicality of this marker in distinguishing SEGAs from its mimics. METHODS: In this study, TTF-1 immunohistochemistry using clone 8G7G3/1 (1:50) was performed in 38 cases of SEGA, 30 cases of central neurocytoma, 10 cases each of intraventricular glioblastoma and ependymoma, and 5 cases of cortical tubers. Additionally, serine/threonine-protein kinase B-Raf (BRAFV600E) mutation, a common genetic alteration in pediatric low-grade-glial tumors with neuronal-differentiation, was analyzed using Ventana immunohistochemistry platform. RESULTS: TTF-1 immunopositivity was seen in all 38 cases (100%) of SEGAs, with 20 cases (52.6%) showing diffuse (>50% of tumor area) expression while focal (<50%) immunopositivity was seen in 18 cases (47.3%). None of the cases demonstrated serine/threonine-protein kinase B-Raf immunolabeling. Barring 2 cases of neurocytoma (6.6%), all other cases including ependymoma, glioblastoma, and cortical tubers were immunonegative for TTF-1. CONCLUSIONS: The congruous finding of TTF-1 expression in SEGA and cells of the developing neuroepithelium in the medial ganglionic eminence hint toward a primogenitor cell with neoplastic potential in the presence of impelling factors.

Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathway and extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs n = 42, periventricular control n = 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response.

Validation of the Zulfiqar Frailty Scale (ZFS): A New Tool for General Practitioners.

INTRODUCTION: The early detection of frailty, a frequent transient state that can be reversible in the elderly and is responsible for significant morbidity and mortality, helps prevent complications from it. OBJECTIVE: To evaluate the performance of the "ZFS" tool to screen for frailty as defined SEGA scale criteria in an ambulatory population of patients at least 65 years of age. METHODS: A prospective non-interventional study conducted in Alsace for a duration of six months that included patients aged 65 and over, judged to be autonomous with an ADL > 4/6. RESULTS: In this ambulatory population of 102 patients with an average age of 76 years, frailty, according to modified SEGA criteria grid A, had a prevalence of 19.6%. Frailty, according to the "ZFS" tool, had a prevalence of 35.0%, and all of its elements except weight loss were significantly associated with frailty. Its threshold for identifying frailty is three criteria out of six. It was rapid (average completion time: 87 s), had a sensitivity of 100%, and a negative predictive value of 100%. CONCLUSIONS: The "ZFS" tool makes it possible to screen for frailty with a high level of sensitivity and a negative predictive value.