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Distinct genes are mutated in different regions of a single patient’s tumor. Point mutations seem to have less adverse effect on relapse-free survival than copy-number heterogeneity. Chromosome instability appears to be an important adverse prognostic factor. Lung cancer is the leading cause of cancer-related death worldwide, 1 , 2 with non–small-cell lung cancer (NSCLC) being the most common type. Large-scale sequencing studies have revealed the complex genomic landscape of NSCLC 3 – 6 and genomic differences between lung adenocarcinomas and lung squamous-cell carcinomas. 7 However, in-depth exploration of NSCLC intratumor heterogeneity (which provides the fuel for tumor evolution and drug resistance) and cancer genome evolution has been limited to small retrospective cohorts. 8 , 9 Therefore, the clinical significance of intratumor heterogeneity and the potential for clonality of driver events to guide therapeutic strategies have not yet been defined. Tracking Non–Small-Cell Lung Cancer . . .

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies. Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process. Tracking tumour evolution Circulating tumour DNA (ctDNA) has proven useful for detecting and monitoring cancer progression from plasma samples. The authors have applied a bespoke multiplex-PCR next-generation sequencing approach to profile ctDNA in the prospective TRACERx lung cancer clinical trial study. The assay tracks clonal and subclonal variants, in pre- and post-surgery samples. In pre-surgery samples ctDNA detection is associated with histological subtype and other pathological variables and correlates with tumour volume. Blinded longitudinal profiling suggests that ctDNA detection also associates with relapse, and provides insight into the evolutionary patterns of tumour cell subclones during progression. These results advance our understanding of how liquid biopsies can be applied clinically to improve monitoring of cancer.

Malignant peripheral nerve sheath tumors (MPNST) are rare heterogeneous group of soft tissue neoplasms. In most cases, they originate within the pre-existing neurofibromatosis. The emergence of glandular structures in MPNST is curious and enigmatic. We report a case of recurrent MPNST with glandular differentiation arising in the background of neurofibroma in a 20-year-old lady. By immunohistochemistry, MPNST showed focal positive staining for S100 and negative staining for SOX10 while adjacent neurofibroma showed diffuse positivity for S100 and SOX10. The glandular tumor cells showed positive staining for CDX2, Cam5.2, CK19, and CK7 (focal), while negative for SOX10 and S100. MPNST with glandular differentiation is quite rare which may pose a diagnostic challenge. The glandular differentiation in MPNST should be excluded from the metastasis from second primary with the aid of clinical and radiological correlation.

This corrects the article DOI: 10.1038/nature22364.

Nature 545, 446–451 (2017); doi:10.1038/nature22364 For 6 of the 96 patients included in this Article (patients CRUK0014, CRUK0030, CRUK0048, CRUK0059, CRUK0096 and CRUK0097) incorrect tumour volumetric data and positron emission tomography (PET) tumour background ratio (TBR) data were analysed. This error occurred because of the incorrect assignment of patient identifiers during the anonymization mandated by the independent review board of pre-operative computed tomography (CT) scans belonging to these patients.

This study aims to assess the vulnerability of groundwater in the Nile Delta to contamination and evaluate its suitability for drinking and irrigation. A total of 28 groundwater wells (ranging from 23 to 120 m in depth) and two Nile surface water samples were analyzed for total dissolved solids (TDS), heavy metals, groundwater quality index (GWQI), and hazard quotient (HQ). The findings reveal that deep groundwater (60–120 m) displays paleo-water characteristics, with low TDS, total hardness, and minimal heavy metal contamination. In contrast, shallow groundwater (<60 m) is categorized into three groups: paleo-water-like, recent Nile water with elevated TDS and heavy metals, and mixed water. Most groundwater samples (64%) are of the Ca-HCO3 type, while 28% are Na-HCO3, and 8% are Na-Cl, the latter associated with sewage infiltration. Most groundwater samples were deemed suitable for irrigation, but drinking water quality varied significantly—4% were classified as “excellent”, 64% as “good”, and 32% as “poor”. HQ analysis identified manganese as a significant health risk, with 56% of shallow groundwater samples exceeding safe levels. These findings highlight the varying groundwater quality in the Nile Delta, emphasizing concerns regarding health risks from heavy metals, particularly manganese, and the need for improved monitoring and management.

This study aims to investigate the prevalence of hypothyroidism in T2DM patients and its relationship with lipid profiles and clinical parameters. The results indicate that 82% of the T2DM patients did not have hypothyroidism, whereas 18% had hypothyroidism. People with both conditions had a higher average body mass index (BMI) of 32.1 ± 6.1 kg/m² than those with only T2DM did (mean: 34.4 ± 6.8 kg/m², p  < 0.001). Compared with the control group, the hypothyroid group presented higher glycosylated hemoglobin (HbA1c) levels (mean: 10.1% vs. 5.48%, p  < 0.001). Compared with T2DM patients without hypothyroidism, T2DM patients with hypothyroidism presented significantly poorer lipid profiles, with lower high-density lipoprotein and higher low-density lipoprotein and triglyceride. T2DM patients with hypothyroidism had a greater prevalence of vitamin D deficiency (average: 28.2 ± 20.0 ng/mL) than control patients did (average: 59.5 ± 11.7 ng/mL, p  < 0.001). In conclusion, T2DM with hypothyroidism is associated with poorer metabolic indicators than those of T2DM patients without hypothyroidism. Individuals who have both conditions have an increased BMI, higher FBS levels, poorer lipid profiles, and decreased vitamin D levels. These results highlight the importance of implementing specific management plans for T2DM patients who also have hypothyroidism.

Background Chronic Kidney Disease (CKD) complications, like cardiovascular complications, are one of the leading causes of mortality. Managing the biochemical profile is essential in slowing the progression of CKD and its associated consequences. This study aimed to assess the effect of cinacalcet add-on therapy on clinical outcomes in patients with End-Stage Renal Disease (ESRD) on Hemodialysis (HD) who developed Secondary Hyperparathyroidism and are receiving hemodialysis. Method A mixed retrospective-prospective cohort multicenter study was conducted in three hospitals in Saudi Arabia between December 1st, 2019, and January 31st, 2021. Results One hundred and seventy-four subjects were analyzed; the incidence of the cardiovascular events and the first cardiovascular events in patients on cinacalcet was significantly decreased compared to the patients on the conventional therapy ( p  = 0.02 & 0.005, respectively ). The incidence of coronary artery diseases was significantly decreased by 61% in the patients on cinacalcet ( HR = 0.39 , p  = 0.04). Patients on Cinacalcet were 69% less in all-cause first hospitalization hazard ratio; HR  =  0.31 , 95% CI: 0.16–0.63 , p  = 0.001. There was no significant reduction in the risk of all-cause and cardiovascular mortality in the patients on Cinacalcet ( p  = 0.06 & 0.12, respectively ), but patients with Hypertension and “Diabetes Mellitus & Hypertension” etiology had a lower mortality HR (Hypertension: HR = 0.46 , 95% CI = 0.21-1.00 , p  = 0.05; “Diabetes Mellitus & Hypertension”: HR  =  0.42 , 95% CI = 0.2-1.00 , p  = 0.04). There was no significant difference in the frequency of incidence of bone fractures between the two groups ( p  = 0.26). Conclusion Cinacalcet is superior in decreasing the frequency of cardiovascular events. However, it is not effective in reducing the risk of all-cause and cardiovascular mortality, except in patients with “Hypertension” and “Diabetes Mellitus & Hypertension” etiology, and it might offer a somewhat protective trend in males and older patients. Clinical trial number Not applicable.