Human Kidney Spheroids and Monolayers Provide Insights into SARS-CoV-2 Renal Interactions

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Evaluation of EGFR,KRAS, and TP53 mutations as predictive of disease recurrence in resected early non-small cell lung carcinomas (NSCLCs)

Purpose

Identification of non-small cell lung carcinoma (NSCLC) patients at high-risk for recurrence after complete resection would potentially direct surveillance frequency and administration of adjuvant treatments. Genetic profiling of tumors could provide clinicians with information regarding recurrence risk. Conflicting evidence exists regarding EGFR, KRAS, and TP53 mutations as prognostic for recurrence. We aimed to test such mutations for prognostic significance in a cohort of early-resected NSCLC specimens.

Materials and methods

Formalin-fixed paraffin-embedded stage I NSCLC specimens resected in our institute during 1988–2008 were sampled. DNA was extracted and a panel of common EGFR, KRAS, and TP53 mutations was tested using a mass-spectrometry-based technique. Clinical data were extracted from patients’ files.

Results

A total of 96 NSCLC stage I patients were included in this study. EGFR mutation frequency of 15.6?%, KRAS mutation frequency of 15.6?%, and a TP53 mutation frequency of 6.2?% were found. A nonsignificant trend for longer relapse-free survival (RFS) was seen for patients with an EGFR mutation, and a nonsignificant trend for worse RFS was found for patients with a KRAS mutation.

Conclusion

EGFR mutation and KRAS mutation were not found to be prognostic for RFS in our cohort of early NSCLC. Larger cohorts and a broader genetic screen for mutations are required.     

Epigenetic control of recombination in the immune system

Immune receptor gene expression is regulated by a series of developmental events that modify their accessibility in a locus, cell type, stage and allele-specific manner. This is carried out by a programmed combination of many different molecular mechanisms, including region-wide replication timing, changes in nuclear localization, chromatin contraction, histone modification, nucleosome positioning and DNA methylation. These modalities ultimately work by controlling steric interactions between receptor loci and the recombination machinery.     

Red cell membrane omega-3 fatty acids are decreased in nondepressed patients with social anxiety disorder.

The "phospholipid hypothesis" attributes a pathophysiologic role to the polyunsaturated fatty acid (PUFA) composition of phospholipids in depression. The aim of the present study was to determine whether the hypothesis is relevant to social anxiety disorder (SAD). The study sample consisted of 27 untreated, nondepressed patients with SAD (DSM-IV) and 22 controls. Severity of SAD was assessed with the Liebowitz Social Anxiety Scale (LSAS). Erythrocyte PUFA concentrations were measured by gas-liquid chromatography. Concentrations of most n-3 PUFAs were lower in the patients: 18:3n-3 by 32% (p < 0.002), 20:3n-3 by 34%, 20:5n-3 by 36% (all p < 0.001) and 22:6n-3 by 18% (p = 0.002). No significant differences were observed in other fatty acids. Significant inverse correlations were obtained between levels of n-3 PUFAs and LSAS scores. In conclusion, the phospholipid hypothesis may apply to SAD, thereby opening new therapeutic options. The robust relationship between low erythrocyte n-3 PUFA concentrations and SAD justifies exploration of relevant neuropathophysiological mechanisms.     

The I1307K adenomatous polyposis coli gene variant does not contribute in the assessment of the risk for colorectal cancer in Ashkenazi Jews.

Ashkenazi Jews with the I1307K adenomatous polyposis coli gene variant were suggested to confer a higher risk for colorectal cancer (CRC). We assessed the clinical importance of this polymorphism in Israeli Jews at average and elevated risk for CRC. Among 1,370 consecutive subjects that were examined, 975 Ashkenazi Jews were stratified into those at average risk (no personal or family history of colorectal neoplasia) and those at high risk. DNA was obtained from peripheral leukocytes and amplified by PCR, with primers designed to detect the I1307K variant. Overall, I1307K polymorphism was found in 7.1% (9.1% among Ashkenazi and 1.7% among non-Ashkenazi Jews). The carrier rate was 8.3 and 9.3% in average and high-risk Ashkenazim, respectively (P = 0.65). The overall odds ratio for neoplasia in carriers was 1.43 (95% confidence interval, 0.89-2.30). Age, gender, and the histopathological features of adenomas and cancers did not differ between carriers and noncarriers. No interaction on the CRC risk was found between I1307K variant and lifestyle modifiers (such as cigarette smoking, alcohol consumption, high body mass index, low physical activity, and vitamins/antioxidant intake). The I1307K adenomatous polyposis coli gene variant is not an important marker for increased risk for CRC. It confirms previous reports of a slight nonsignificant increase (OR, 1.4) in the risk of CRC in these carriers. There is no interaction effect on the risk of colorectal neoplasia between the I1307K variant and various lifestyle risk factors. The usual recommended screening and surveillance strategies should be used for carriers of this polymorphism.     

Frequency doubling technology threshold testing in the pediatric age group

PURPOSE: To evaluate the feasibility of performing visual field with the Frequency Doubling Technology (FDT) in children aged 5 to 10 years. PATIENTS AND METHODS: Forty healthy children and fifteen healthy adults, all with no previous experience with visual field testing, underwent visual field testing with the C20 threshold test of the Carl Zeiss Meditec FDT analyzer in both eyes. The subjects were divided into three groups. Group A (age 5-7), group B (age 8-10), and group C (adults). RESULTS: The mean explanation time for the test was 83 +/- 43 seconds for group A, 68 +/- 31 seconds for group B, and 37 +/- 15 seconds for group C (P < 0.001 for the difference between group C and groups A and B). Test performance time for the right eye was 347 +/- 57 seconds, 301 +/- 21 seconds, and 298 +/- 35 seconds for groups A to C, respectively (P < 0.001 for the difference between group A and groups B and C). Forty percent of the children, but none of the adults required two demonstrations prior to initiation of the test. In children fixation losses for the right and left eye were 10% and 37% respectively. No fixation losses occurred in adults. In both eyes a mean deviation <0.5% occurred significantly more often in group A than in group C (P = 0.013). CONCLUSION: Visual field testing with FDT in the young age group is feasible. Test reliability was similar between children aged 5 to 7 and 8 to 10. Pre-selection of children is suggested to achieve reliable results.     

Syncytial giant-cell hepatitis due to autoimmune hepatitis type II (LKM1+) presenting as subfulminant hepatitis

Giant cell hepatitis (GCH) in adults is a rare event. The diagnosis of GCH is based on findings of syncytial giant hepatocytes. It is commonly associated with either viral infection or autoimmune hepatitis type I. A patient with GCH due to autoimmune hepatitis type II (LKM1+) is described, a combination that has not been previously reported. Corticosteroid therapy was effective in decreasing serum liver enzymes; however, the patient deteriorated rapidly and developed subfulminant hepatic failure. Although an emergency orthotopic liver transplantation was performed, the patient died because of reperfusion injury. Interestingly, only a few giant hepatocytes were noted in the explanted liver. This case stresses the association of GCH with autoimmune disorders, the possible immune mechanism involved in the formation of giant cell hepatocytes, and illustrates the rapidly progressive course and unfavorable prognosis that these patients can develop.     

Admission albumin levels and functional outcome of elderly hip fracture patients: is it that important?

BACKGROUND AND AIMS: Low serum albumin level is considered a marker of poor health outcome in various medical conditions. A relationship between low albumin levels and poor functional outcome has been found in the elderly, lower albumin predicting a greater functional decline. The objective of this study was to evaluate to what extent admission albumin levels may affect the functional outcome of elderly hip fracture patients. METHODS: This retrospective chart review study was conducted in an orthogeriatric unit of a university-affiliated referral hospital. The participants were 449 elderly patients with hip fractures, admitted for a standard rehabilitation course. Functional outcome of patients with normo-albuminemia and hypo-albuminemia was assessed by Functional Independence Measurement (FIM) at admission and discharge. Data were analyzed by t-test, Pearson's correlation, Chi-square test and Linear Regression. RESULTS: 38.8% of patients were hypoalbuminemic upon admission. These patients were older (p<0.001) and had lower Mini-Mental State Examination (MMSE) scores (p=0.003), compared with normo- albuminemic patients. Discharge FIM scores were higher in normo-albuminemic compared with hypo-albuminemic patients (total FIM 86.1+/-23.9 and 77.0+/-26.4, respectively; p<0.001; motor-FIM 60.0+/-16.3 and 53.4+/-18.0, respectively; p<0.001). Linear regression analysis showed that total FIM at discharge was inversely associated with pre-fracture function (beta -0.13; p<0.001). A high MMSE score (beta 0.16; p<0.001), female gender (beta 0.05; p=0.02) and higher admission total FIM scores (beta 0.69; p<0.001) emerged as predictors of higher total FIM scores upon discharge. Albumin levels did not independently predict better total FIM scores upon discharge (beta -0.02; p=0.36). CONCLUSIONS: Normo-albuminemic patients present with better admission FIM scores and have higher discharge FIM scores. After controlling for possible confounders, albumin remains a non-significant predictor of higher discharge FIM scores. We suggest that low albumin levels should not be considered as adversely affecting the rehabilitation of elderly hip fracture patients.     

Non-Hodgkin's lymphoma presenting as an endobronchial tumor: report of eight cases and literature review

Non-Hodgkin's lymphoma (NHL) involving the endobronchial tree is uncommon, and the initial presentation of NHL as an endobronchial tumor is extremely rare. In a series of 441 patients with newly diagnosed non-Hodgkin's lymphoma over a 7-year period, we reviewed the clinical features of eight patients who presented with an endobronchial tumor. All patients had local pulmonary disease without extrathoracic involvement. The major presenting symptoms were dyspnea, chest pain, cough, and hoarseness. None of the patients had systemic symptoms. Radiographs revealed lobar collapse in all cases. Five patients had mediastinal masses and three had isolated endobronchial lesions. Although MALT lymphoma is the most common primary pulmonary lymphoma, it was present in only one of our patients, while seven patients had aggressive lymphoma. All patients received chemotherapy. Six of the eight patients responded favorably to treatment with complete remission. The prognosis of patients with isolated endobronchial lymphoma is not worse than other local presentations of lymphoma. Bronchoscopic examination with biopsy is essential to differentiate these lesions from primary bronchongenic carcinoma.