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.

[Collagenofibrotic glomerulopathy--rare glomerulonephritis]. / Kolagenofibrotická glomerulopatia--raritná glomerulonefritída.

Glomerulopathies with fibrillary deposits form a heterogeneous group of renal diseases that can be identified only by means of electron microscopy. A case of a rare type of such a nephropathy, the collagenofibrotic glomerulopathy with focus on differential diagnostics is presented and current knowledge relating to this renal disease is reviewed.

Tubular basement membrane thickening in diabetes mellitus.

Authors measured the thickness of the basement membranes of the proximal and distal tubuli in the renal cortex in 20 patients with verified diabetes mellitus. The test group consisted of 20 patients with small abnormalities of glomeruli (or in the range of variable norm), of the same sex and comparable age. Measurements were performed in locations without tubulo-interstitial changes. The average thickness of TBM in patients with diabetes mellitus was 1540 +/- 616 nm, and in the test group 360 +/- 86 nm, which is a statistically significant difference (p < 0.000000). In spite of the small number of cases and possible error in the manual measurement of electron microscopic pictures, a significant thickening of TBM in diabetes mellitus has been found. We consider this to be of diagnostic value.

[Variations in histologic and ultrastructural findings in renal glomerular biopsies]. / Rozdielne histologické a ultrastruktúrne nálezy v glomeruloch renálnej biopsie.

On the basis of 506 renal biopsies performed within a six-year period (237 of which were evaluated electron-microscopically) the authors discovered that in 11 cases the diagnosis based on electron microscopic examination had to be corrected or supplemented by the diagnostic statement of membranous glomerulonephritis. These cases included 1 boy (HBsAg positive), 2 men and 8 women were middle aged. 5 women were treated due to polyarthritis. All cases when examined light-microscopically yielded a pattern evaluated as normal, or as minute abnormalities of glomeruli. Half-thick sections were not sufficient for the diagnosis. 3 cases of biopsies yielded a variously developed chronic tubulointerstitial nephritis, two cases were accompanied with polyarthritis. On the basis of the latter the authors consider the electron microscopic examination as indicated: 1. in cases when the diagnosis statement is not achieved by other examinations, 2. findings are in the range of the so-called variable norm, 3. in all cases of minute abnormalities in glomeruli detected without electron microscopy, 4. the impact of any of effective drugs cannot be excluded, 5. the diagnostic conclusion based on renal biopsy and the clinical-laboratory pattern of the disease are inconsistent. The authors assume that especially the fourth and fifth groups are going to be gradually supplemented and made more precise. (Fig. 1, Ref. 5.).

[Minor glomerular abnormalities in chronic tubulointerstitial nephritis]. / Malé abnormality glomerulov pri chronických tubulointersticiálnych nefritídach.

The authors examined consecutive renal biopsies from 43 patients with minor glomerular abnormalities and from 35 patients with chronic tubulointerstitial nephritis (in the least affected glomeruli). The findings were evaluated according to WHO criteria of minor abnormalities. They found that significantly more frequently lipid drops were found in minor abnormalities (6:0), as well as changes in the capillaries of glomeruli (breakdown 1:7), wrinkling (15:29-highly significant even after correction of p)) in tubulointerstitial nephritis. The incidence in another 15 compared indicators there was not significantly different. With regard to the assembled results the authors consider the morphological finding of minor glomerular abnormalities as non-specific changes, and adaptational glomerular changes in response to various noxious substances. Therefore it is necessary to evaluate purely morphological findings of minor abnormalities carefully and in a differentiated manner, in particular in conjunction with treatment.

"Clusters" of CJD in Slovakia: the first laboratory evidence of scrapie.

Epidemic-like occurrence of Creutzfeldt-Jakob disease was observed in 1987 in Slovakia (Orava). Search for the cause of CJD focus indicated a coincidence of genetic and environmental risks in clustering patients. Since Spongiform Encephalopathies might be transmitted orally, (Bovine Spongiform Encephalopathy), the possibility of zoonotic source of CJD cases in Orava was also considered. A deficient knowledge about the occurrence of scrapie in Slovakia stimulated an examination of sheep with signs of CNS disorders in two flocks of Valasky breed in Orava. In one flock, neurohistopathological examination revealed in sheep brains lesions characteristic for scrapie. Frozen brain tissue of these animals were used for the detection of scrapie associated fibrils. They were found in 2 animals from the same flock. This is the first laboratory confirmation of scrapie in Czecho-Slovakia. The possible epidemiological and economical implications are emphasized.