Dolenc's pretemporal transcavernous approach and Kawase's s anterior transpetrosal approach are the two primary extradural middle cranial fossa approaches (EMFAs) to the central skullbase. The extended extradural phase of the surgery may potentially result in temporal lobe edema, compromising the surgical exposure and sometimes a postoperative temporal lobe venous infarction. The authors describe an alternative technique of cerebrospinal fluid (CSF) drainage called "transdural cisternotomy" in EMFA. In this, CSF is released from the chiasmatic cistern during the extradural stage of surgery. Two illustrative cases are shown, a case of petroclival meningioma and a petroclival intradural chordoma. Both patients underwent gross total tumor resection with good long-term outcome. Transdural cisternotomy was greatly beneficial in both the cases. Based on our experience with several such cases, the transdural cisternotomy described here is an easy, reproducible, and effective method of brain relaxation in EMFAs.

Myasthenia Gravis is an autoimmune disorder of the neuromuscular junction which is divided into three categories in children: neonatal or transient, congenital myasthenic syndromes, and autoimmune or juvenile myasthenia gravis (JMG). JMG differs from adult MG in many aspects. Characteristics of JMG also vary between children of various ethnic groups.

Although common, there is scant data about JMG in India. This study was performed to determine the characteristics of JMG in Indian children.

We did a retrospective chart analysis of all patients who received a diagnosis of myasthenia at a tertiary care pediatric hospital in Mumbai, India from January 2005 to December 2015. We studied the demographic data, clinical features, investigations, history of crises, and records of hospital stay. Treatment modalities and outcomes were reviewed.

Fifteen children received a diagnosis of JMG during the study period. This was a pre-pubertal cohort with a mean age of 3.7 years. Nine patients had generalized symptoms at presentation and six had ocular presentation. The seropositivity rate was 73%. Patients were treated with a combination of pyridostigmine, steroids, and additional immunosuppression. Nearly half the patients needed second-line immunosuppression. Four children underwent thymectomy.

MG in Indian children is a severe disease with high rates of seropositivity and a relatively better outcome if identified and treated appropriately. Thymectomy has an important role in management but requires more scrutiny.

Metabolic reprogramming plays a key role in glioma biology, tumor growth, survival, and resistance to treatment. Given the racial and ethnic differences in glioma epidemiology, metabolomic profiling offers a promising approach to identifying population-specific biomarkers.

This study aimed to evaluate whether serum metabolomic profiling can effectively capture glioma-associated metabolic alterations, investigate grade-specific differences, and compare these profiles with healthy controls-addressing the current scarcity of such research in the Indian population.

Serum samples were collected from 60 treatment-naïve glioma patients (WHO Grades I-IV) and 10 healthy controls between September 2019 and September 2023. Targeted metabolomic profiling of 150 metabolites was performed using liquid chromatography-mass spectrometry. The data were normalized and subjected to quality control, with metabolites having a coefficient of variation >20% excluded. Data analysis was conducted using MetaboAnalyst 5.0. Significant metabolic alterations with a false discovery rate ≤0.25 were identified. Pathway enrichment analysis was performed to identify grade-related metabolic alterations.

Forty-one metabolites were found to be significantly altered in glioma patients compared to controls, especially those related to the metabolism of arginine, tryptophan, and inositol phosphate. Thirty-four metabolites were significantly different in low-grade gliomas, involving pathways such as phenylalanine, tyrosine, and tryptophan biosynthesis. Comparison between low- and high-grade tumors revealed 49 altered metabolites, with high-grade gliomas demonstrating increased activity in the metabolism of glutathione and glycerophospholipids, as well as the biosynthesis of branched-chain amino acids. Grade IV gliomas demonstrated the most extensive metabolic changes, including alterations in pantothenate and coenzyme A biosynthesis and histidine metabolism.

This targeted metabolomic analysis highlights distinct metabolic reprogramming across glioma grades in an Indian cohort. These findings provide insights into glioma biology in the Indian context and highlight the potential of metabolomics in tumor grading, disease monitoring, and personalized therapeutic approaches.

To evaluate telomerase reverse transcriptase (TERT) promoter hyper-methylation as a potential causative epigenetic alteration of elevated mRNA expression in glioblastoma (GBM).

The hyper-methylation and mRNA expression were evaluated by methylation-sensitive high-resolution melting analysis (MS-HRM) and qRT-PCR, respectively. Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database was also performed to obtain similar data. The mechanistic link between the hyper-methylation and mRNA expression was analyzed in vitro in U87MG and LN228 GBM cell lines. A cross-sectional study was conducted. A total of 50 cases of adult hemispheric GBMs (IDH wild type), and five cases of high-grade astrocytoma (IDH mutant, grade 4) (HGA) were included for the study. Eight normal brains (NB) from the autopsy of nonneurological diseases were used as control.

The TERT promoter methylation was significantly higher in GBM than NB (Median -19.5% vs 6.8%; P value 0.003). Considering 10% methylation as cutoff, hyper-methylation was detected in 65% of GBM, 60% of HGA, and only in a single case of normal brain. There was a significant positive correlation between the methylation level and mRNA expression (correlation coefficient 0.40; P value 0.002) in the study cohort. In the TCGA database, the methylation status of the probes covering the selected promoter region showed a similar association with gene expression. In vitro treatment of the GBM cell lines with demethylase agent Azacitidine led to a significant reduction in the mRNA level and cell proliferation. Hyper-methylation or mRNA expression did not correlate with overall survival.

The present study is the first to assess the TERT promoter methylation status in GBM in an Indian cohort. TERT hyper-methylation is crucially implicated in the pathobiology of GBM by enhancing the gene expression. This epigenetic alteration may be an important therapeutic target, especially with the use of a specific demethylating agent.

Differentiating prolactinomas from non-functioning sellar masses causing hyperprolactinemia due to stalk effect is a common diagnostic challenge. While both can result in elevated serum prolactin, accurate discrimination is essential for appropriate management.

To determine the upper limit of serum prolactin in non-functioning sellar masses attributable to stalk effect.

This retrospective study was conducted at a tertiary care center in South India from January 2015 to December 2024. Patients with both non-pituitary sellar masses and pituitary tumors with negative prolactin immunohistochemistry were included. Patients with functioning pituitary adenomas, hyperprolactinemia-inducing drugs, chronic kidney disease, severe hepatic dysfunction, and PCOS were excluded. The primary objective was to determine the upper limit of serum prolactin levels attributable to stalk effect in patients with non-functioning sellar masses. Preoperative serum prolactin levels were measured using a chemiluminescent immunoassay. The 97th percentile value was taken as the upper limit.

Of 288 cases of non-functioning sellar masses, 57 met inclusion criteria. Most of them (87.7%, 50/57) were >1 cm, with 68% (39/57) classified as pituitary adenomas-49% (19/39) being gonadotroph adenomas and 41% (16/39) null cell adenomas. Hyperprolactinemia was observed in 32% of patients. The median serum prolactin level was 14.8 ng/mL, and the 97th percentile was 70 ng/ml. No significant correlation was found between tumor size and serum prolactin level (r = 0.13, P = 0.35). Gender did not significantly affect serum prolactin levels. A serum prolactin threshold of 70 ng/mL was identified, above which non-functioning sellar masses are highly unlikely.

In patients with non-functioning sellar masses, serum prolactin levels rarely exceed 70 ng/ml. This threshold may serve as a useful diagnostic marker to distinguish stalk effect from prolactinomas. Prospective validation in larger cohorts is warranted.

Real-world data on management and outcomes of patients with simultaneously diagnosed synchronous colorectal liver and lung metastases are limited. This national study evaluated referral patterns, treatment strategies, and survival in a population-based cohort. Patient/material and methods: This retrospective cohort study used Swedish national registries to identify patients with synchronous liver and lung metastatic colorectal cancer (CRC), defined as metastases detected within 6 months of CRC diagnosis between 2008 and 2016. Medical record review provided additional information on diagnosis confirmation, multidisciplinary team (MDT) referral, metastatic burden, and treatment. Logistic regression identified factors associated with MDT referral and curative treatment, and Cox regression with a time-varying covariate assessed survival.

Among 2703 registry-identified patients, medical records were accessible for 855. After exclusion of extrahepatic, non-pulmonary metastases, 556 remained for analysis. A total of 189 patients (34%) were discussed at a liver MDT conference. Referred patients were younger, had lower metastatic burden, and better performance status than non-referred. Median survival was 24 months (95% CI [confidence interval] 21-28) for referred versus 10 months (95% CI 7-12) for non-referred patients. Curative local treatment of liver and/or lung metastases was performed in 101 patients (18%), and complete metastasectomy in 34 (6%), conferring superior survival compared with liver-only intervention (hazard ratio 0.34, 95% CI 0.18-0.61). The main reason for non-referral was presumed non-resectability.

Referral to an MDT and subsequent local treatment were associated with improved survival, although this may partly reflect favorable patient and tumor characteristics influencing referral and treatment decisions. Patients with adequate physiological reserve should routinely be evaluated in an organ-specific MDT for potential curative treatment.

A significant proportion of patients presenting a primary sclerosing cholangitis (PSC) will require liver transplantation (LT). The present study aimed to investigate graft loss and patient death in a large cohort of patients.

We conducted a nationwide multicenter retrospective study including all adult patients transplanted for PSC in France From 1985 to 2019.

Were included 571 patients; median follow-up after LT was 89.0 months (IQR, 43.0-151.0). Patient survival at 5, 10 and 20 years after LT was 88.2%, 81.2% and 62.6%. After exclusion of patients who died during the first month after LT, 37 patients (6.6%) died during the first 2 years and the main cause was malignancies (n = 15, 40.5%, including 12 cases of recurrent cholangiocellular carcinoma). After 2 years, 90 patients (17.2%) died; the two main causes were malignancies (n = 36, 40.0%, including 13 cases of colorectal cancer) and sepsis (n = 23, 25.6%, of which 7 were related to recurrent PSC). Graft survival at 5, 10 and 20 years was 89.5%,78.7% and 62.7%. Independent factors associated with late patient death (after 2 years) were an older age at LT, a bilio-digestive anastomosis and the use of preventive UDCA; independent factors associated with late graft loss were recurrent PSC, cellular rejection, a younger age at LT, and the use of tacrolimus (protective).

Our results emphasise that the prognosis after LT for PSC could be improved by better detection of cholangiocellular carcinoma before LT, and colorectal cancer after LT.

Cancer-related transcriptional dysregulation involves complex, incompletely understood epigenetic mechanisms. Chromatin states (CSs), defined by recurrent co-occurrence patterns of epigenetic marks, provide a comprehensive view for epigenomic landscape. However, current CS analyses often produce excessive subtly distinct states, making functional interpretation difficult. Building on single-cell clustering principles, we developed chromIDEAS to overcome this challenge. Recognizing that epigenetic function is context-dependent, chromIDEAS groups CSs into functionally coherent clusters by jointly analyzing their epigenetic composition and genomic distribution. When applying to THP1 leukemia and CD34+ cells, chromIDEAS consistently identified five CS clusters (CSCs) preserved across both cell types, exhibiting distinct functional coherence. These CSCs captured core transcriptional states (active and repressive) and key genomic compartments (promoters, gene bodies, and TES). Notably, differential CSC analysis revealed that Wnt signaling activation in THP1 cells, a hallmark of leukemogenesis, is mediated by KDM4A-dependent removal of repressive states. Mechanistically, KDM4A depletion restored repressive states on Wnt signaling and impaired proliferation, while WNT10B overexpression effectively rescued this phenotype. Our work establishes chromIDEAS as a pioneering tool for functional CS annotation and uncovers KDM4A-mediated epigenetic derepression in leukemia pathogenesis. These findings highlight critical role of CSs in mechanistic studies and introduce a novel paradigm for epigenetic exploration.

The neutropenic diet (ND) has historically been prescribed to reduce infection risk in immunocompromised patients with cancer, despite limited supporting evidence. This study aimed to evaluate current practices surrounding ND use in Australian hospitals.

An online survey was distributed to dietitians working with hospitalised patients with cancer. The survey explored dietary practices, foods restricted, initiation and discontinuation criteria, and dietitians' perspectives on ND use.

Overall, 56% of responding dietitians reported that their hospitals prescribe an ND. Among these, there was broad consistency in the restriction of approximately 85% of foods, though considerable variation existed regarding criteria for ND initiation and discontinuation. Dietitians' personal views on ND use generally aligned with their hospital's practice (87.0%).

More than half of Australian hospitals surveyed continue to prescribe an ND, with general consistency in food restrictions but variation in initiation and discontinuation practices. These findings highlight the need for institutional review of ND practices and support the development of evidence-based food safety education to better guide dietary care for patients with cancer.

The protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway plays a critical role in preventing the accumulation of misfolded or unfolded proteins within the endoplasmic reticulum. In this study, the role of the PERK signaling pathway was evaluated in newly diagnosed, treatment-naïve patients with acute myeloid leukemia (AML).

Plasma levels of eukaryotic translation initiation factor 2-alpha kinase 3 (eIF2AK3), glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), CCAAT/enhancer-binding protein homologous protein (CHOP), hypoxia-inducible factor-1 alpha (HIF-1α), and caspase 3 were measured by enzyme-linked immunosorbent assay in peripheral blood samples obtained from AML patients and healthy controls.

A total of 40 individuals were included, comprising 19 (47%) AML patients and 21 (53%) healthy controls. HIF-1α, eIF2AK3, GRP78, ATF6, CHOP, and caspase 3 levels were significantly higher in the AML group than in the control group (p = 0.019, 0.005, <0.001, 0.006, <0.001, and <0.001, respectively). No significant differences were observed in HIF-1α, GRP78, ATF6, CHOP, and caspase 3 levels between diagnosis and the 30th day of remission-induction therapy in the AML group, whereas a significant decrease was observed in eIF2AK3 levels (p = 0.049). At diagnosis, a strong positive correlation was found between GRP78 and CHOP levels (r = 0.740, p < 0.001), and a moderate positive correlation was detected between CHOP and caspase 3 levels (r = 0.514, p = 0.024) in the AML group. In the Cox regression analysis of the AML cohort, no statistically significant association was identified between overall survival and age, risk category, or biomarker levels (HIF-1α, eIF2AK3, GRP78, ATF6, CHOP, and caspase 3).

PERK and ATF6 signaling pathways were activated in patients with AML. Targeting the unfolded protein response pathway may represent a promising therapeutic strategy for patients with AML.