Faster fibrin clot degradation characterizes patients with central pulmonary embolism at a low risk of recurrent peripheral embolism

It is unclear whether thrombus location in pulmonary arteries is associated with particular clot characteristics. We assessed 156 patients following either central or peripheral pulmonary embolism (PE). Plasma clot lysis time, the rate of D-dimer release from plasma clots (D-Drate) with the maximum D-dimer concentration achieved (D-Dmax), as well as fbrin formation on turbidimetry, plasma clot permeation, thrombin generation, and fbrinolytic parameters were measured 3–6 months after PE. Patients following central PE (n=108, 69.3%) were more likely smokers (38.9% vs 18.8%; p=0.01), less likely carriers of factor XIII Val34Leu allele (40.7% vs 62.5%, p=0.01), exhibited 16.7% higher D-Drate and 12.7% higher tissue plasminogen activator antigen (tPA:Ag) compared with peripheral PE (p=0.02 and p<0.0001, respectively). Saddle PE patients (n=31, 19.9%) had 11.1% higher D-Drate and 7.3% higher D-Dmax compared with central PE (both p<0.05). Twenty-three recurrent PE episodes, including 15 central episodes, during a median follow-up of 52.5 months were recorded. Plasma D-dimer and tPA:Ag were independent predictors for central recurrent PE, whereas D-Drate and peak thrombin predicted peripheral recurrent PE. Plasma clots degradation is faster in patients following central PE compared with peripheral PE and fbrinolysis markers might help to predict a type of recurrent PE

Clinical implications of cytogenetic and molecular aberrations in multiple myeloma

Multiple myeloma (MM) is an incurable haematological malignancy affecting approximately 7:100,000 people. Monoclonal gammopathy of undetermined significance (MGUS) and ‘smouldering’ MM precede symptomatic MM. Cytogenetics in MM is the most powerful prognostication tool incorporated into different classifications, including the Revised International Staging System (R-ISS) and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART). Methods commonly used to test for cytogenetic aberrations include conventional karyotyping and fluorescence in situ hybridisation (FISH), although the difficulty of obtaining metaphases in plasma cells results in low yields. Therefore, new genomic tools are essential to explore the complex landscape of genetic alterations in MM. These include next generation sequencing, a highly sensitive method to monitor minimal residual disease. The serial evolution of MGUS to MM is accompanied by a range of heterogenous genetic abnormalities, divided into primary (involving mostly chromosome 14 translocations and trisomies) and secondary genetic aberration events (involving mostly 17p, 1p, 13q deletions, 1q gain, or MYC translocations). Based on the primary genetic aberration results, strong prognostic features of MM have been identified with distinct clinical characteristics. High risk aberrations include 17p deletion, t(4;14), t(14;16), t(14;20) and chromosome 1 abnormalities. The incorporation of novel drugs and maintenance strategies in conjunction with autologous stem cell transplantation partially overcome the adverse effect of some of these genetic aberrations. Nonetheless, survival remains worse in this group compared to standard risk patients. Clinical decisions regarding treatment should be based on the cytogenetic results. The establishment of individualised and mutation-targeted therapies are of the greatest importance in future studies

Amyloidoza pęcherza moczowego — opis przypadku i przegląd piśmiennictwa

Amyloidosis is a heterogeneous group of protein misfolding diseases caused by extracellular deposition of abnormal beta-fibrils resistant to proteolysis. The most common type is light-chain amyloidosis (AL amyloidosis) which can be systemic or localized. Localized amyloidosis mostly affects the respiratory airways, genitourinary tract, gastrointestinal system or skin. We present diagnostic and therapeutic approach in a 25-year-old female patient diagnosed with urinary bladder amyloidosis. The main complaint was macroscopic hematuria occurring periodically for 2 years. Abdominal and pelvic computed tomography revealed single 25-mm-thick soft-tissue lesion of the left bladder wall. Histopathological examination of the lesion biopsied during transurethral resection of bladder tumor showed amyloid deposits with strong positive immunostaining for transthyretin, weaker for light chain (AL) and weak for serum amyloid A (AA). Serum protein electrophoresis and immunofixation did not reveal monoclonal protein. X-rays of flat bones presented without lytic lesions. There were no amyloid deposits both in trephine biopsy and subcutaneous fat biopsy. Primary systemic AL amyloidosis was excluded. According to the results of (99m)Tc-DPD scintigraphy and genetic analysis of transthyretin gene (TTR), the ATTRm amyloidosis was also excluded. Consultative histopathological analysis of the bladder biopsy made in the National Amyloidosis Center in London revealed amyloid deposits stained to lambda light chains, confirming the diagnosis of localized AL lambda bladder amyloidosis. The patient was qualified for surgical treatment. Partial resection of the bladder wall with no need for left ureter transplantation was performed. Primary localized bladder amyloidosis is a very rare entity. In the diagnostic approach the most important is the exclusion of primary systemic amyloidosis due to a completely different treatment method.Amyloidoza to heterogenna grupa chorób wywołanych pozakomórkową depozycją białek o nieprawidłowej strukturze beta-kartki, nieulegających proteolizie. Najczęstszym typem jest amyloidoza łańcuchów lekkich (amyloidoza AL), która może występować w postaci systemowej lub zlokalizowanej — ograniczonej do jednego układu. Amyloidoza zlokalizowana dotyczy głównie dróg oddechowych, układu moczowo-płciowego, przewodu pokarmowego lub skóry. W artykule przedstawiono ścieżkę diagnostyczno-terapeutyczną 25-letniej pacjentki ze zlokalizowaną amyloidozą pęcherza moczowego z wywiadem krwiomoczu pojawiającego się okresowo od 2 lat. W tomografii komputerowej jamy brzusznej i miednicy w ścianie lewobocznej pęcherza moczowego uwidoczniono miękkotkankową zmianę grubości około 25 mm, bez istotnego wzmocnienia pokontrastowego. W badaniu histopatologicznym bioptatu pobranego w czasie przezcewkowej resekcji guza pęcherza moczowego stwierdzono złogi amyloidu, z najsilniejszym odczynem w kierunku transtyretyny, nieco słabszym w kierunku AL i słabym AA. W elektroforezie białek surowicy i immunofiksacji nie ujawniono obecności białka monoklonalnego. Radiogram kości płaskich był pozbawiony zmian litycznych. Złogi amyloidu były nieobecne zarówno w trepanobiopsji, jak i w bioptacie tkanki tłuszczowej. Wykluczono pierwotną układową amyloidozę AL. Na podstawie scyntygrafii serca 99mTc-DPD oraz analizy genetycznej genu transtyretyny (TTR) wykluczono także amyloidozę serca ATTRm. W badaniu konsultacyjnym bioptatu z pęcherza moczowego, wykonanym w National Amyloidosis Centre w Londynie, wykazano obecność amyloidu z łańcuchów lambda, ostatecznie potwierdzając rozpoznanie amyloidozy pęcherza moczowego AL lambda. Pacjentkę zakwalifikowano do leczenia operacyjnego. Ze względu na nasilone objawy ze strony układu moczowego wykonano częściową resekcję ściany pęcherza moczowego metodą klasyczną z zaoszczędzeniem moczowodów. Amyloidoza zlokalizowana pęcherza moczowego jest rzadkością. W postępowaniu diagnostycznym najistotniejsze pozostaje wykluczenie pierwotnej amyloidozy układowej ze względu na całkowicie odmienny sposób leczenia

Mortality Following Clostridioides difficile Infection in Europe : A Retrospective Multicenter Case-Control Study

We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from seven European countries. A total of 624 patients were included, of which 415 were deceased (cases) and 209 were still alive 90 days after a CDI diagnosis (controls). The most common antibiotics used previously in both groups were β-lactams; previous exposure to fluoroquinolones was significantly (p = 0.0004) greater in deceased patients. Multivariate logistic regression showed that the factors independently related with death during CDI were older age, inadequate CDI therapy, cachexia, malignancy, Charlson Index, long-term care, elevated white blood cell count (WBC), C-reactive protein (CRP), bacteraemia, complications, and cognitive impairment. In addition, older age, higher levels of WBC, neutrophil, CRP or creatinine, the presence of malignancy, cognitive impairment, and complications were strongly correlated with shortening the time from CDI diagnosis to death. CDI prevention should be primarily focused on hospitalised elderly people receiving antibiotics. WBC, neutrophil count, CRP, creatinine, albumin and lactate levels should be tested in every hospitalised patient treated for CDI to assess the risk of a fatal outcome

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) with probable mesentery involvement with associated hemophagocytic syndrome (HPS) - how to treat it?

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare, cutaneous lymphoma involving subcutaneous adipose tissue. SPTL is associated in less than 20% with hemophagocytic syndrome (HPS). A 5-year overall survival rate is inferior in patients with SPTL and HPS (46%) as compared with 91% in patients without HPS. No standardized therapy for SPTCL has yet been established. This is a case of 35-year-old Caucasian man with a one-month history of B symptoms with the suspicion of Still’s disease, at admission with leucopenia, high LDH, ferritin, sIl-R2, and triglycerides levels, hepatosplenomegaly, small right supraclavicular nodule, and irregular thickening of trunk subcutaneous tissue. The abdomen MRI showed generalized thickening of mesentery and colonic mucosa. In the patient, diagnosis of SPTCL was established with secondary HPS. CHOEP chemotherapy and modified HLH 2014 protocol were applied with subsequent high dose chemotherapy (BEAM) supported by autologous stem cells transplantation. Treatment was complicated by pancytopenia and pneumonia. The outcome of the disease treated by intensive protocol seems to be good