Discrimination between non-functioning pituitary adenomas and hypophysitis using machine learning methods based on magnetic resonance imaging‑derived texture features

Purpose

Hypophysitis is a heterogeneous condition that includes inflammation of the pituitary gland and infundibulum, and it can cause symptoms related to mass effects and hormonal deficiencies. We aimed to evaluate the potential role of machine learning methods in differentiating hypophysitis from non-functioning pituitary adenomas.

Methods

The radiomic parameters obtained from T1A-C images were used. Among the radiomic parameters, parameters capable of distinguishing between hypophysitis and non-functioning pituitary adenomas were selected. In order to avoid the effects of confounding factors and to improve the performance of the classifiers, parameters with high correlation with each other were eliminated. Machine learning algorithms were performed with the combination of gray-level run-length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray-level co-occurrence entropy.

Results

A total of 34 patients were included, 17 of whom had hypophysitis and 17 had non-functioning pituitary adenomas. Among the 38 radiomics parameters obtained from post-contrast T1-weighted images, 10 tissue features that could differentiate the lesions were selected. Machine learning algorithms were performed using three selected parameters; gray level run length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray level co-occurrence entropy. Error matrices were calculated by using the machine learning algorithm and it was seen that support vector machines showed the best performance in distinguishing the two lesion types.

Conclusions

Our analysis reported that support vector machines showed the best performance in distinguishing hypophysitis from non-functioning pituitary adenomas, emphasizing the importance of machine learning in differentiating the two lesions.

     

Management of infant diarrhea with high-lactose probiotic-containing formula

To study the influence of high-lactose probiotic-containing formula on the course of acute diarrhea, an experiment using a randomized controlled clinical trial with patients having acute diarrhea for 3 days was conducted. One hundred patients were allocated into two groups that were comparable for age, sex, and nutritional status. The test group was administered high-lactose Bifidobacterium bifidum-containing formula, while the control group had no high-lactose probiotic until the end of the experiment. The degree of subsequent diarrhea and recovery were monitored in both groups. The results for the test and control groups were analyzed and compared using the chi-square test and Fisher exact test with a significance level (alpha) of 0.05. The study results revealed that there was no significant difference between the test and control groups (p>0.05) as well as at positive clinical test (13%) and positive floating test (65%). However, the patients receiving probiotic-containing formula had significantly less frequency of stools, when compared with the control group (p<0.05).     

Reversible airway obstruction in rheumatic mitral valve disease

Lung function was studied in 24 patients with advanced mitral stenosis scheduled for mitral valve replacement (MVR), and revealed an obstructive ventilatory pattern [rewording of this sentence OK] . Forty per cent of the patients had a forced expiratory volume in 1 s (FEV₁)<60% of that predicted in the preoperative period. Twenty-five per cent of those operated upon showed a similar pattern up to 110 weeks postoperatively. A blind study of the effect of placebo and β₂ agonist (salbutamol) inhalation was performed preoperatively and 6 months postoperatively, to evaluate the reversibility of airflow obstruction in these patients, flow volume curve and body plethysmographic measurement of airway resistance (Rex) and intrathoracic gas volume (VTG). Patients in the pre and postoperative period showed a significant difference between the placebo and the β₂ agonist responses for FEV₁, FEV₁ as percentage of FVC (FEV₁% FVC), peak expiratory flow rate (PEFR), flow rate of 50% of expiratory vital capacity ([¨max₅₀), Rex and VTG (P<0.001). We conclude that salbutamol inhalation improves obstructive impairment in patients with MVR pre- and postoperatively.     

Influence of quasispecies on virological responses and disease severity in patients with chronic hepatitis C

AIM： To elucidate the influence of quasispecies on virological response and disease severity in patients with chronic hepatitis C.
METHODS： Forty seven patients with hepatitis C [32 with chronic active hepatitis （CAH）, 9 with cirrhosis, and 6 with hepatocellular carcinoma （HCC）] were screened for the presence of quasispecies by single stranded conformational polymorphism （SSCP） analysis in the hypervariable region （HVR） and non-structural 5B （NS5B） viral genes of hepatitis C virus. The 41 patients excluding those with HCC were on therapy and followed up for a year with the determination of virological response and disease severity. Virus isolated from twenty three randomly selected patients （11 non-responders and 12 showing a sustained virological response） was sequenced for the assessment of mutations.
RESULTS： The occurrence of quasispecies was proportionately higher in patients with HCC and cirrhosis than in those with CAH, revealing a significant correlation between the molecular evolution of quasispecies and the severity of disease in patients with hepatitis C. The occurrence of complex quasispecies has a significant association （P 〈 0.05） with the non-responders, and leads to persistence of infection. Significant differences （P 〈 0.05） in viral load （log10 IU/mL） were observed among patients infected with complex quasispecies （CQS）, those infected with simple quasispecies （SQS） and those with no quasispecies （NQS）, after 12 wk （CQS-5.2 ± 2.3, SQS-3.2 ± 1.9, NQS-2.8 ± 2.4） and 24 wk （CQS-3.9 ± 2.2, SQS-3.0 ± 2.2, NQS-2.1 ± 2.3） in the HVR region. However, a statistically significant difference （P 〈 0.05） was observed between the viral loads of patients infected with CQS and those infected with NQS in NS5B viral gene after 24 wk （CQS-3.9 ± 2.2, SQS-3.0 ± 2.2, and NQS-2.1 ± 2.3） and 48 wk （CQS-3.1 ± 2.7, SQS-2.3 ± 2.4, NQS-2.0 ± 2.3） of therapy. Disease severity was significantly associated with viral load during th     

Glycosylated hemoglobin levels in Sudanese sickle cell anemia patients

Glycosylated hemoglobin was measured, by a colorimetric method, in 49 patients with sickle cell anemia attending Khartoum Teaching Hospital. The level obtained (4.9%, SD 1.3) was significantly lower than the control value (5.6%, SD 0.2; p less than 0.0025). Expressed as percentage of the control value, the glycosylated hemoglobin level in these patients was 81%. This falls midway between the 90% reported in a benign form of sickle cell anemia in Saudi Arabia and the 58% reported in a severe form in an American Black group, which gives support to the observed heterogeneity of sickle cell anemia. Alternatively, glycosylated hemoglobin level in 27 subjects with sickle cell trait (5.6%, SD 0.2) was identical to that of the controls. The state of hemolysis in the sickle cell anemia patients, as indicated by bilirubin levels, did not correlate with the glycosylated hemoglobin values. Although glycosylated hemoglobin measurement is affected by red cell survival, it does not reflect the state of ongoing hemolysis.     

Echocardiographic features of carcinoid heart disease

We reviewed the records of the Mayo Clinic patients with known carcinoid syndrome in whom echocardiographic studies had been done. Nineteen patients had M-mode and 2-dimensional echocardiographic examinations, and 1 patient had an M-mode examination only. Of the 20 patients, 8 had no evidence by echocardiogram of carcinoid heart disease; 2 had changes in the tricuspid valve echogram suggestive of early carcinoid heart disease, and the other 10 patients had the following distinctive echocardiographic findings: (1) the pattern of right ventricular volume overload (enlarged right ventricle with abnormal septal motion); (2) abnormal right-sided valves, including (a) a striking appearance of the tricuspid valve, the leaflets appearing thickened, retracted, and fixed in a semiopen position throughout the cardiac cycle, and (b) thickened, retracted pulmonic valve cusps, when visualized; and (3) the left-sided valves and chambers rarely involved. These echocardiographic features are distinctive of advanced carcinoid heart disease and correlate closely with pathologic findings.     

SOD2 genetic polymorphism (rs4880) has no impact on 6‐month response to antidepressant treatment and inflammatory biomarkers in depressed patients

Two thirds of patients suffering from a major depressive episode (MDE) do not reach a complete response with antidepressant drugs. This lack of response is due to several factors, including genetic determinants. Since major depressive disorder is associated with inflammatory and oxidative stress abnormalities, the metabolism of superoxide anions might be involved in non‐response to antidepressant drugs. Superoxide anions are metabolized by manganese‐dependent superoxide dismutase (SOD2) in the mitochondria. A functional genetic polymorphism (SOD2, rs4880), responsible of a 40% reduction in enzyme activity, is associated with anti‐inflammatory response of rosuvastatin. We investigated the association of ala‐allele of SOD2 rs4880 and both antidepressant efficacy and inflammatory parameters in patients treated for a MDE with antidepressant drugs. The Hamilton Depression Rating Scale (HDRS) score and levels of plasma CRP and inflammatory cytokines were assessed at baseline, one month (M1), 3 months (M3) and 6 months (M6) after antidepressant treatment. They were compared according to SOD2 genetic polymorphism. Of the 484 patients studied, 361 (74.6%) carried the ala‐allele (Ala group), 123 (25.4%) of them had Val/Val genotype (Val/Val group). No significant difference was observed between the Ala and Val/Val groups neither for baseline clinical characteristics, nor for HDRS scores, response/remission rates, plasma CRP and cytokine levels throughout the study. The rs4880 SOD2 genetic polymorphism was not associated with the clinical response and cytokines levels after antidepressant treatment. These data suggest that SOD2 is not a major genetic determinant of antidepressant response. Other genes of the oxidative stress pathways should be explored in further studies.     

Non homologous end joining-mediated DNA break repair is impaired in B lymphocytes of aging mice

Aging is an irreversible physiological process characterized by increased risk of diseases, reduced effectiveness of vaccines, and decreased immune responses. One of the most prominent paradigms of aging and age related conditions is the progressive accumulation of un-repaired DNA breaks leading to apoptosis and exhaustion of stem cells. Here we hypothesized that B lymphocytes from old mice have reduced DNA repair mechanisms as a contributing factor for DNA break accumulation. We analyzed class switch recombination (CSR) of naïve B lymphocytes from old and adult mice to delineate the DNA double strand repair mechanisms during aging. In vitro CSR assays and DNA break analysis by labeling phosphorylated histone H2AX showed that old mice had significantly reduced DNA repair efficiency following DNA breaks. Functional efficiency analysis of DNA break repairs using plasmid ligation method showed that B lymphocytes from old mice had poor repair efficiency and increased misrepair of linear plasmid. Diminished DNA repair in old age can contribute to reduced immune cell repertoire and impaired immunity; increased occurrence of cancer; and reduced stem cell reserve.     

HLA-DO increases bacterial superantigen binding to human MHC molecules by inhibiting dissociation of class II-associated invariant chain peptides

HLA-DO (H2-O in mice) is an intracellular non-classical MHC class II molecule (MHCII). It forms a stable complex with HLA-DM (H2-M in mice) and shapes the MHC class II-associated peptide repertoire. Here, we tested the impact of HLA-DO and H2-O on the binding of superantigens (SAgs), which has been shown previously to be sensitive to the structural nature of the class II-bound peptides. We found that the binding of staphylococcal enterotoxin (SE) A and B, as well as toxic shock syndrome toxin 1 (TSST-1), was similar on the HLA-DO⁺ human B cell lines 721.45 and its HLA-DO⁻ counterpart. However, overexpressing HLA-DO in MHC class II⁺ HeLa cells (HeLa-CIITA-DO) improved binding of SEA and TSST-1. Accordingly, knocking down HLA-DO expression using specific siRNAs decreased SEA and TSST-1 binding. We tested directly the impact of the class II-associated invariant chain peptide (CLIP), which dissociation from MHC class II molecules is inhibited by overexpressed HLA-DO. Loading of synthetic CLIP on HLA-DR⁺ cells increased SEA and TSST-1 binding. Accordingly, knocking down HLA-DM had a similar effect. In mice, H2-O deficiency had no impact on SAgs binding to isolated splenocytes. Altogether, our results demonstrate that the sensitivity of SAgs to the MHCII–associated peptide has physiological basis and that the effect of HLA-DO on SEA and TSST-1 is mediated through the inhibition of CLIP release.