Detecting Mycobacterium tuberculosis complex DNA, based on post-mortem examination of hilar lymph nodes with real-time PCR: initial study

 INTRODUCTION: According to the WHO, almost a third of the world population are thought to be infected with Mycobacterium tuberculosis. Some studies of the prevalence of latent tuberculosis infection (LTBI) have already been performed in Poland, showing that almost a quarter of the Mazovia population could be infected. It also indicated a higher prevalence of LTBI among seniors. Those studies were based on indirect diagnostic methods.MATERIAL AND METHODS: We randomly collected hilar lymph nodes from decedents aged 40 years and older during post-mortem examination. We excluded patients with previous confirmed tuberculosis. In addition, an autopsy was performed in all patients. Finally, we used real-time PCR Xpert MTB/RIF (Cepheid, USA) for the specific capture of mycobacterial DNA.RESULTS: Twenty-two of 23 patients had a negative result of the real-time PCR examination and no signs of caseous necrosis in hilar lymph nodes. We found the only positive sample in a patient with histopathological signs of tuberculosis (the presence of caseous necrosis in the specimens obtained from lymph nodes and lung). Due to the change of cartridges from version G3 to G4, further reactions were inhibited and no more post-mortem samples were tested.CONCLUSIONS: Real-time PCR Xpert MTB/RIF was capable of detecting M. tuberculosis complex DNA in a patient with tuberculosis recognised on autopsy. In the remaining patients, no M. tuberculosis complex DNA was found, in accordance with negative results of histological examination. Since the technology of cartridges has changed, it is no longer possible to use real-time PCR Xpert MTB/RIF (Cepheid USA) on post-mortem material. Wstęp: Zgodnie z danymi Światowej Organizacji Zdrowia, uważa się, że prawie 1/3 światowej populacji jest zakażona prątkiem gruźlicy. Wyniki badań prowadzonych przy użyciu pośrednich metod diagnostycznych nad rozpowszechnieniem utajonego zakażenia prątkiem gruźlicy w Polsce wykazały, że nawet 1/4 populacji Mazowsza może być zakażona, z przewagą u osób starszych.Materiał i metody: Podczas badania post-mortem pobierano w sposób losowy węzły chłonne wnękowe od zmarłych w wieku 40 lat i powyżej. Na podstawie danych z historii chorób wykluczono pacjentów leczonych z powodu gruźlicy w przeszłości. U wszystkich chorych przeprowadzono badanie sekcyjne. Następnie wykonywano badanie real-time PCR, Xpert MTB/RIF, Cepheid, USA w celu wykrycia DNA Mycobacterium tuberculosis complex.Wyniki: U 22 z 23 pacjentów wynik reakcji real-time PCR był negatywny, a w preparatach węzłów chłonnych nie stwierdzono ziarniny serowaciejącej. W jednym przypadku badanie real-time PCR było dodatnie. Dotyczyło to chorego, u którego stwierdzono obecność ziarniny serowaciejącej zarówno w preparatach z węzłów chłonnych, jak i pobranych z nacieku płucnego. Po zmianie kartridży z wersji G3 na G4 w real-time PCR, Xpert MTB/RIF kolejne reakcje były zahamowane i nie testowano większej liczby próbek.Wnioski: Badanie metodą real-time PCR, Xpert MTB/RIF wykazało obecność M. tuberculosis complex DNA u chorego z pośmiertnie stwierdzoną gruźlicą płuc i ww. chłonnych. U pozostałych chorych nie wykryto obecności DNA M. tuberculosis complex w tkankach, co pozostawało w zgodzie z negatywnym wynikiem badania histologicznego. Po zmianie technologii badania real-time PCR, Xpert MTB/RIF zawodzi przy badaniu próbek z materiału uzyskanego pośmiertnie

Leflunomide-induced acute interstitial pneumonia in a patient treated for rheumatoid arthritis

Leflunomid należy do leków przeciwreumatycznych modyfikujących przebieg choroby. Jest on stosowany u chorych z reumatoidalnym zapaleniem stawów, u których leczenie pierwszej linii było nieskuteczne. Leczenie leflunomidem może być jednak związane z istotnymi powikłaniami płucnymi, zwłaszcza u osób predysponowanych. Autorzy przedstawiają opis przypadku chorego na reumatoidalne zapalenie stawów leczonego leflunomidem, u ktorego wystąpiły powikłania ze strony układu oddechowego. Omówiono czynniki ryzyka wystąpienia uszkodzenia płuc w przebiegu leczenia tym preparatem oraz sposób postępowania w przypadku ich wystąpienia.Leflunomide is a disease-modifying anti-rheumatic drug that is used in patients with rheumatoid arthritis (RA), who do not respond well to standard RA treatment. Leflunomide therapy may, however, be related with significant pulmonary complications in predisposed individuals. We present a patient with RA treated with leflunomide, in whom leflunomide lung injury had a fatal outcome. Potential risk factors for pulmonary complications of leflunomide treatment and the management of patients with leflunomide lung injury are discussed

Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts

Background: Takotsubo syndrome (TTS) is a stress-induced disorder affecting mostly postmenopausal women. The aim of the study was to evaluate isoprenaline (ISO) dependent female rat model and histopathological characteristics in TTS. Methods: Forty-nine Sprague Dawley female rats, 12 weeks old, were injected intraperitoneally with a single dose of ISO at doses 50 (n = 8), 75 (n = 6), 100 (n = 3), 150 (n = 27) and 200 (n = 5) mg/kg body weight (bw). The control group (n = 6) was injected with physiological saline. The echocardiographic examination to assess wall motion abnormalities took place 24, 48, 72 h, and 7 days post-ISO. Histopathological analysis was performed on the basis of hematoxylin-eosin staining. Results: The total mortality rate was 3/49 (6.12%). The optimum dose of ISO to induce TTS was 150 mg/kg bw and 21/27 (77.77%) rats showed apical ballooning. Histopathological analysis revealed focal necrosis/apoptosis of cardiomyocytes with inflammatory and fibroblast-like cell infiltration. Foci were the most numerous in the central muscle layer with apical-basal gradient 24,48,72 h post-ISO (p < 0.05). Significant differences were noted 48 h post-ISO in the central layer in apical vs basal segments (p = 0.0032), in the endocardial layer in apical vs basal segments (0.00024) and in mid-cavital vs. basal segments (p = 0.0483). The number of foci in endocardium of apical region differ 48 h post-ISO in rats with a dose of 150 vs. 200 mg/kg bw (p = 0.0084).   Conclusions: The ISO female rat model of TTS is associated with higher optimum dose and lower mortality in comparison with the male TTS model. TTS presents as a singles cardiomyocyte disorder, foci concerned mainly central muscle layer with apical-basal gradient

MARC1 p.A165T variant is associated with decreased markers of liver injury and enhanced antioxidant capacity in autoimmune hepatitis

The clinical picture of autoimmune hepatitis (AIH) varies markedly between patients, potentially due to genetic modifiers. The aim of this study was to evaluate genetic variants previously associated with fatty liver as potential modulators of the AIH phenotype. The study cohort comprised 313 non-transplanted adults with AIH. In all patients, the MARC1 (rs2642438), HSD17B13 (rs72613567), PNPLA3 (rs738409), TM6SF2 (rs58542926), and MBOAT7 (rs641738) variants were genotyped using TaqMan assays. Mitochondrial damage markers in serum were analyzed in relation to the MARC1 variant. Carriers of the protective MARC1 allele had lower ALT and AST (both P < 0.05). In patients treated for AIH for ≥ 6 months, MARC1 correlated with reduced AST, ALP, GGT (all P ≤ 0.01), and lower APRI (P = 0.02). Patients carrying the protective MARC1 genotype had higher total antioxidant activity (P < 0.01) and catalase levels (P = 0.02) in serum. The PNPLA3 risk variant was associated with higher MELD (P = 0.02) in treated patients, whereas MBOAT7 increased the odds for liver cancer (OR = 3.71). None of the variants modulated the risk of death or transplantation. In conclusion, the MARC1 polymorphism has protective effects in AIH. Genotyping of MARC1, PNPLA3, and MBOAT7 polymorphisms might help to stratify patients with AIH

Detecting Mycobacterium tuberculosis Complex DNA, Based on Post-Mortem Examination of Hilar Lymph Nodes with Real-Time PCR: Initial Study

Introduction: According to the WHO, almost a third of the world population are thought to be infected with Mycobacterium tuberculosis. Some studies of the prevalence of latent tuberculosis infection (LTBI) have already been performed in Poland, showing that almost a quarter of the Mazovia population could be infected. It also indicated a higher prevalence of LTBI among seniors. Those studies were based on indirect diagnostic methods. Material and Methods: We randomly collected hilar lymph nodes from decedents aged 40 years and older during post-mortem examination. We excluded patients with previous confirmed tuberculosis. In addition, an autopsy was performed in all patients. Finally, we used real-time PCR Xpert MTB/RIF (Cepheid, USA) for the specific capture of mycobacterial DNA. Results: Twenty-two of 23 patients had a negative result of the real-time PCR examination and no signs of caseous necrosis in hilar lymph nodes. We found the only positive sample in a patient with histopathological signs of tuberculosis (the presence of caseous necrosis in the specimens obtained from lymph nodes and lung). Due to the change of cartridges from version G3 to G4, further reactions were inhibited and no more post-mortem samples were tested. Conclusions: Real-time PCR Xpert MTB/RIF was capable of detecting M. tuberculosis complex DNA in a patient with tuberculosis recognised on autopsy. In the remaining patients, no M. tuberculosis complex DNA was found, in accordance with negative results of histological examination. Since the technology of cartridges has changed, it is no longer possible to use real-time PCR Xpert MTB/RIF (Cepheid USA) on post-mortem material

Surgical treatment of extra-appendiceal colorectal neuroendocrine tumors.

Background: Extra-appendiceal colorectal neuroendocrine tumors are rare neoplasms with variable biological behavior. Materials and Methods: The study group consisted of 15 patients with an extra-appendiceal colorectal neuroendocrine tumor who underwent surgical resection (M/F=3:12, mean age=62.9 years). Lower-grade neuroendocrine tumors (NET G1-G2) and neuroendocrine carcinomas were recognized in 5 and 10 patients, respectively. Data were evaluated retrospectively with regard to clinical and pathologic characteristics and outcomes. Results: The median age of the patients with lower-grade NETs was significantly lower than that in patients with NECs (53 yrs vs. 68 yrs, p=0.03). NETs G1-G2 were significantly smaller than neuroendocrine carcinomas (4.0 cm vs. 6.4 cm, p=0.02). There were no differences between lower-grade NETs and NECs with regard to tumor location, local infiltration, rate of nodal involvement, and distant metastases. All the patients underwent open segmental resection of the colon or rectum. Complete resection was achieved in 3 of 5 patients from the lower-grade NET group, and in 5 of 10 patients in the NEC group (p=1.0). The overall survival was significantly better for lower-grade NETs tumors (p=0.005). The median survival was 4.8 months in the NEC group. The median survival in the lower-grade NET group was not achieved after a median follow-up of 69 months. Three-year overall survival was at a level of 100% for lower-grade NETs, and only 27% for NECs. Conclusion: Lower-grade neuroendocrine tumors seem to exhibit comparable potential for dissemination as neuroendocrine carcinomas, however, prognostic implications of metastases are distinct

Rzadkie przypadki złośliwej przemiany gruczolaka wielopostaciowego ślinianek w raka mioepitelialnego - opis dwóch przypadków

Gruczolak wielopostaciowy jest najczęściej rozpoznawanym łagodnym nowotworem ślinianek. U większości chorych resekcja chirurgiczna guza wraz otaczającym miąższem ślinianki pozwala na całkowite wyleczenie. Pewien odsetek przypadków stanowi nawracający gruczolak wielopostaciowy. Złośliwa przemiana gruczolaka wielopostaciowego w raka jest wyjątkowo rzadka. W pracy przedstawiono dwie chore, u których pierwotnie rozpoznany gruczolak wielopostaciowy uległ złośliwej transformacji do wieloogniskowego raka mioepitelialnego. W obu przypadkach zastosowano leczenie chirurgiczne oraz uzupełniającą radioterapię

Adrenal cyst with both Müllerian and mesothelial differentiation - a clinicopathological and immunohistochemical study with implications for histogenesis

True epithelial-lined cysts are rare forms of adrenal cystic lesions, the pathogenesis of which is still not fully understood. In this report we present a case of an adrenal cyst diagnosed incidentally on imaging in a 31-year-old, previously healthy, obese woman. Due to non-specific hormonal disorders and enlargement of the lesion, a right-sided laparoscopic adrenalectomy was performed. The cyst was lined predominantly by ciliated cuboidal-to-columnar, Müllerian-type epithelium, and focally by flat-to-cuboidal, mesothelium-like lining. Immunohistochemistry demonstrated a strong positive reaction in the cells of both types of lining for CKAE1/AE3, CK19, CK7 and WT1, and both had a negative reaction for CK20, CD34, Melan-A, SF1, TTF1, SMA and CDX2. The cells of the ciliated cuboidal-to-columnar epithelium were strongly positive for PAX8, ER, Ep-CAM and EMA, focally positive for PR, and were negative for calretinin, whereas the cells of the flat-to-cuboidal lining were positive for calretinin and podoplanin and showed only a weak positive response in individual cells for PAX8, EMA and EpCAM, but were negative for ER and PR. This is the first reported case of an adrenal ciliated epithelial cyst with Müllerian differentiation (confirmed immunohistochemically) in the English literature. The differences in morphology and immunophenotype of the two types of lining (epithelial Müllerian phenotype versus mesothelial phenotype), suggest that some adrenal epithelial cysts probably form due to metaplasia of mesothelium-derived lining. A similar mechanism may also be involved in the pathogenesis of at least some of the so-called Müllerian cysts (or inclusions) in other location

Malignant transformation of the salivary gland pleomorphic adenoma in myoepithelial carcinoma – the report of two cases

A multiform adenoma is the most commonly diagnosed benign tumor of the salivary glands. In the majority of patients, surgical resection of the tumor with the adequate surrounding tissue of salivary gland allows for complete recovery. A small percentage of the cases is a recurring pleomorphic adenoma. Even more rarely the diagnosis of carcinoma ex pleomorphic adenoma is made. The study presents two clinical cases of the malignant transformation of pleomorphic adenoma into the myoepithelial carcinoma. The surgical treatment and additional radiotherapy were performed in both cases

Leczenie chirurgiczne guzów neuroendokrynnych jelita grubego w lokalizacji pozawyrostkowej

Wstęp: Guzy neuroendokrynne jelita grubego w lokalizacji pozawyrostkowej stanowią rzadkie nowotwory przewodu pokarmowego o zróżnicowanym charakterze biologicznym. Materiał i metody: Grupę badaną stanowiło 15 chorych leczonych chirurgicznie z powodu guza neuroendokrynnego okrężnicy lub odbytnicy (M/K = 3:12, średnia wieku: 62,9 lat). Zróżnicowany guz neuroendokrynny (NET G1-G2) rozpoznano u 5 chorych, a raka neuroendokrynnego stwierdzono u 10 chorych. Przeprowadzono retrospektywną analizę cech kliniczno-patologicznych i wyników leczenia chirurgicznego. Wyniki: Mediana wieku chorych ze zróżnicowanym NET była znamiennie niższa niż mediana wieku chorych z rakiem neuroendokrynnym (53 lata vs 68 lat; p = 0,03). Guzy NET G1-G2 były znamiennie mniejsze niż raki neuroendokrynne (4 cm vs 6,4 cm; p = 0,02). Nie było różnic między grupami pod względem umiejscowienia guza, miejscowego naciekania, częstości przerzutów do węzłów chłonnych i przerzutów odległych. U wszystkich chorych wykonano częściową resekcję jelita grubego. Resekcja była doszczętna onkologicznie u trzech z pięciu chorych w grupie z NET G1-G2 i u pięciu z 10 chorych w grupie z NEC (p = 1,0). Ogólne przeżycie było znamiennie wyższe w grupie NET G1-G2 w porównaniu z chorymi z rakiem neuroendokrynnym (p = 0,005). Mediana przeżycia chorych z rakiem neuroendokrynnym wyniosła tylko 4,8 miesięcy, podczas gdy mediana przeżycia u chorych z guzami NET G1-G2 nie została osiągnięta w okresie obserwacji o medianie 69 miesięcy. Trzyletnie przeżycie w grupie chorych z NET G1-G2 wynosiło 100% , w grupie z NEC tylko 27%. Wnioski: Zróżnicowane guzy neuroendokrynne i rak neuroendokrynny jelita grubego cechują się porównywalną skłonnością do rozsiewu, ale różnym znaczeniem prognostycznym przerzutów