Fatal myocarditis after the first dose of nivolumab.

BACKGROUND: Thymic carcinoma (TC) is a rare subtype of thymic epithelial malignancy. Surgical resection is a mainstay in the treatment of TC, while radiotherapy and chemotherapy are modalities used in adjuvant or palliative setting. Immune checkpoint inhibitors (ICI) including anti-PD-1 (programmed cell death 1) antibodies represent an emerging treatment modality in TC; however, their administration could be associated with life-threatening toxicity. CASE: We present a case of a 59-year-old female with grade III TC, who had received neoadjuvant chemotherapy followed by surgery and subsequent adjuvant radio-immunotherapy with an ICI, nivolumab. We provide our experience with the toxicity of an administered treatment. RESULTS: Fourteen days after the first dose of nivolumab and on 21st day after starting of radiotherapy (total dose of 40 Gy), the patient developed fulminant myocarditis with subsequent heart failure. Despite immunosuppressive therapy with high-dose glucocorticoids and mycophenolate mofetil and intensive support, the patient died within 6 days after the onset of first symptoms. CONCLUSION: Physicians should be aware of these extremely rare, but potentially fatal complications of immunotherapy.

HSP60, oxidative stress parameters and cardiometabolic risk markers in hypertensive and normotensive Slovak females.

BACKGROUND: The aim of our study was to analyse the relationships between hypertension, HSP60, oxidative stress, lipid profile and cardiometabolic risk in 126 females with arterial hypertension (AHW) and 39 normotensive females (AH-). RESULTS: Females with AH+ were significantly older and more frequently suffered from ischemic heart disease, angina pectoris, prior MI, abdominal obesity, obesity, metabolic syndrome and diabetes mellitus. On the other hand, normotensive females smoked significantly more often. Plasma levels of HSP60 were similar in both AH+ and AH- groups. However, hypertensive females exhibited almost two times lower values of oxidative glutation and lower levels of carbonyl protein, but significantly higher levels of homocysteine. In normotensive females, the total glutathione was the only parameter predicting females with the plasma level of HSP60 = 60 ng/ml. The independent predictors in hypertensive females were angina pectoris, triglycerides and the mean arterial pressure (MAP). MAP had also a borderline significance in normotensive females suggesting an association between HSP60 and blood pressure. MAP formed a J shaped curve with HSP60. CONCLUSION: Results suggest the association of blood pressure and heart shock protein 60 Kda in form of the J curve (Tab. 11, Fig. 3, Ref. 29).

MCP-1 -2518 A/G gene polymorphism is associated with blood pressure in ischemic heart disease asymptomatic subjects.

Monocyte chemoattractant protein-1 (MCP-1), one of the key inflammatory chemokines, plays an important role in the initiation of atherosclerosis, and represents a risk for coronary artery disease and myocardial infarction. A recent animal study showed that MCP-1 gene might be a candidate gene for salt-sensitive hypertension in Dahl salt sensitive rats. This effect has not been yet studied in asymptomatic humans. We tested the MCP-1 -2518 A/G single nucleotide polymorphism (SNP) in 66 hypertensive ischemic heart disease asymptomatic subjects. Inflammatory markers, classic risk factors and absolute cardiovascular risk (SCORE system) were also investigated in these subjects. Our results showed that both, systolic and diastolic values of blood pressure were associated with MCP-1 -2518 A/G SNP at the level of both, genotype and allele frequencies. Subjects with mutant G allele had higher levels of both values of blood pressure, systolic (p = 0.035) and diastolic (p = 0.040) than subjects with allele A. Statistically significantly higher levels of both values of blood pressure, systolic (p = 0.037) and diastolic (p = 0.021) were found also in IHD asymptomatic subjects with AG and GG genotypes. Subjects with AG and GG genotypes had also an increased absolute cardiovascular risk (1.62% vs 3.17%; p = 0.004) and an increasing trend for elevated plasma level of high-sensitive CRP (2.858 vs 2.062 mg/l; p = 0.076). We did not find any significant correlation between the serum level of MCP-1 and blood pressure. To our best knowledge, this is the first study concerning the association between MCP-1 polymorphism and arterial blood pressure in IHD asymptomatic subjects. These results indicate that the expression of MCP-1 may be increased before the onset of hypertension but further observations from larger cohorts are needed to confirm this finding (Tab. 6, Ref. 41).

The MCP-1 -2518 (A/G) single nucleotide polymorphism is associated with ischemic heart disease and myocardial infarction in men in the Slovak population.

We investigated the MCP-1 -2518 (A/G) single nucleotide polymorphism (SNP) in Slovak cohort of patients with ischemic heart disease (IHD). Our study comprised 270 patients with IHD, out of them 92 with myocardial infarction (MI). We found that the frequencies of the mutant GG genotype in Slovak patients with IHD (10.7%; p=0.019) and MI (12.0%; p=0.046) were significantly higher than those in the control subjects (5.8%). After subdividing the groups according to the sex, statistically significant difference was found only in men (IHD: p=0.013, MI: p=0.009). We also found a higher rate of GG homozygous genotype in patients with early (< or =50 years of age) MI (18.4%; p=0.004)--statistically significant again only in men (23.1%; p=0.002). The frequencies of G alleles in IHD male patients (30.3%, p=0.046) and in early MI male patients (38.5%, p=0.019) were also statistically significantly higher than in control group. Our results confirm that IHD and MI are linked to MCP-1 -2518 (A/G) single nucleotide polymorphism (Tab. 4, Ref. 34). Full Text (Free, PDF) www.bmj.sk.

Deformable mirror device spatial light modulators and their applicability to optical neural networks.

All neural networks are characterized by a large number of interconnections between processor nodes. In general, the value of these interconnections (weights) must be modifiable. However, current semiconductor technology does not lend itself well to modifiable interconnection technology. A novel type of spatial light modulator, the deformable mirror device, is proposed as the breakthrough needed to solve the neural network interconnect problem.