Treatment of a patient with chronic immune thrombocytopenic purpura with rituximab and monitoring by flow cytometric analysis

Treatment modalities of patients with chronic immune thrombocytopenic purpura (ITP) include the administration of intravenous immunoglobulins (IVIG), corticosteroids, anti-D(Rh) immunoglobulin (anti-D), and splenectomy. Approximately 25-30% of patients with chronic ITP do not respond to established therapeutic regimens. We describe a 19-year-old patient with chronic ITP refractory to standard therapies treated with rituximab (anti-CD20 antibody). Initially, the therapy with rituximab appeared to be successful; however, the patient relapsed after a surveillance of 57 weeks documenting that the rituximab therapy has failed. Flow cytometric analyses during and after the administration of rituximab revealed new aspects of monitoring rituximab therapy.     

The lack of influence of CagA positive Helicobacter pylori strains on gastro-oesophageal reflux disease

OBJECTIVE: Helicobacter pylori infection of the gastric mucosa may influence gastro-oesophageal reflux disease (GORD). The protein of cytotoxin associated gene A (CagA) is assumed to be a virulence factor of H. pylori. CagA positive strains may induce severe gastroduodenal peptic ulcer disease. The aim of this study was to evaluate the association between H. pylori strains expressing CagA and GORD. SUBJECTS AND METHODS: Nine hundred and thirty patients were examined by endoscopy. Antral and corpus biopsies for the urease test and serum samples for the detection of IgG antibodies to CagA were taken. Serum samples were assayed by using the western blot technique. RESULTS: The results from 811 patients were analysed statistically. This study population consisted of 264 H. pylori infected patients (264/811, 32%). The H. pylori prevalence was 33% (89/266) in patients with reflux oesophagitis and did not differ from those patients without oesophagitis (175/545, 32%). In contrast, patients with Barrett's oesophagus showed a significantly lower prevalence of H. pylori infection than the other three groups (8/35, 23%). There was no significant influence of CagA, as one of the H. pylori virulence factors, on GORD. Antibodies against CagA were slightly, but insignificantly, more frequent in patients with oesophagitis (55/89, 62%) than in patients without oesophagitis (94/175, 54%). CONCLUSIONS: In a large cohort of GORD patients no significant difference in the prevalence of H. pylori in patients with and without GORD was found. In addition, there is no correlation between patients carrying CagA positive strains and development of reflux oesophagitis. However, in the case of histopathologically proven Barrett's oesophagus the prevalence of H. pylori was significantly lower. The influence of CagA positive strains on oesophageal mucosa is discussed.     

Complications in the clinical course of tako-tsubo cardiomyopathy

Objective

This study evaluated the frequency, severity and outcome of complications in the clinical course of tako-tsubo cardiomyopathy (TTC).

Background

TTC is regarded as a benign disease since left ventricular (LV) function returns to normal within a short time. However, severe complications have been reported in selected patients.

Methods

From 37 hospitals, 209 patients (189 female, age 69 ± 12 years) were prospectively included in a TTC registry.

Results

Complications developed in 108/209 patients (52%); 23 (11%) had > 2 complications. Complications occurred median 1 day after symptom onset, and 77% were seen within 3 days. Arrhythmias were documented in 45/209 patients (22%) including atrial fibrillation in 32 (15%) and ventricular tachycardia in 17 (8%). Of 8 patients resuscitated (4%), 6 survived. Additional complications were right ventricular involvement (24%), pulmonary edema (13%), cardiogenic shock (7%), transient intraventricular pressure gradients (5%), LV thrombi (3%) and stroke (1%). During hospitalization, 5/209 patients (2.5%) died. Patients with complications were older (70 ± 13 vs 67 ± 10 years, p = 0.012), had a higher heart rate (91 ± 26 vs 83 ± 19/min, p = 0.025), more frequently Q\ waves on the admission ECG (36% vs 21%, p = 0.019) and a lower LV ejection fraction (47 ± 15 vs 54 ± 14%, p = 0.002). Multivariate regression analysis identified Q-waves on admission (OR 2.49, 95% CI 1.23–5.05, p = 0.021) and ejection fraction ≤ 30% (OR 4.03, 95% CI 1.04–15.67, p = 0.022) as independent predictors for complications.

Conclusions

TTC may be associated with severe complications in half of the patients. Since the majority of complications occur up to day 3, monitoring is advisable for this time period.     

Heat Stress is Associated with Reduced Health Status in Pulmonary Arterial Hypertension: A Prospective Study Cohort

Background

Summer heat waves with temperature extremes are becoming more frequent with growing numbers in morbidity and mortality in patients with respiratory diseases. The aim of this study was to evaluate the ramifications of heat stress (temperature >25 °C) on the health status of patients with pulmonary arterial hypertension (PAH).

Methods

Fifteen patients with PAH (mean age = 66.7 ± 5.2 years) continuously wore an accelerometer from April 1 to September 30, 2011, and their daily step count was recorded. In addition, patients kept a diary to record data on seven standardized questions regarding their daily symptoms. Echocardiography, 6-minute walk test, NTproBNP, and Modified Medical Research Council Scale (MMRC) were assessed at baseline and at the end of the study after 6 months.

Results

On heat-stress days, patients showed significantly more symptoms and lower total steps/day compared to thermal comfort days (3,995 ± 2,013 steps/day vs. 5,567 ± 2,434 steps/day, respectively; P < 0.001). There was a significant negative correlation between total steps/day and Temp_max (R = ?0.47; P < 0.001) and humidity (R = ?0.34; P < 0.001). A significant positive correlation was found between daily symptoms and Temp_max (R = +0.79; P < 0.001) and humidity (R = +0.23; P < 0.001).

Conclusions

Heat stress is associated with a compromised clinical status in patients with PAH. Adaptation strategies must be implemented to prevent heart-related morbidity, including therapeutic adjustments and adequate room cooling in the patient’s home and at the hospital.     

Developments in pediatric liver transplantation since implementation of the new allocation rules in Eurotransplant

Liver allocation in the Eurotransplant (ET) region has changed from a waiting time to an urgency‐based system using the model of end‐stage liver disease (MELD) score in 2006. To allow timely transplantation, pediatric recipients are allocated by an assigned pediatric MELD independent of severity of illness. Consequences for children listed at our center were evaluated by retrospective analysis of all primary pediatric liver transplantation (LTX) from deceased donors between 2002 and 2010 (110 LTX before/50 LTX after new allocation). Of 50 children transplanted in the MELD era, 17 (34%) underwent LTX with a high‐urgent status that was real in five patients (median lab MELD 22, waiting time five d) and assigned in 12 patients (lab MELD 7, waiting time 35 d). Thirty‐three children received a liver by their assigned pediatric MELD (lab MELD 15, waiting time 255 d). Waiting time in the two periods was similar, whereas the wait‐list mortality decreased (from about four children/yr to about one child/yr). One‐ and three‐yr patient survival showed no significant difference (94.5/97.7%; p = 0.385) as did one‐ and three‐yr graft survival (80.7/75.2%; and 86.5/82%; p = 0.436 before/after). Introduction of a MELD‐based allocation system in ET with assignment of a granted score for pediatric recipients has led to a clear priorization of children resulting in a low wait‐list mortality and good clinical outcome.     

Clinicopathologic and molecular features of intracranial desmoplastic small round cell tumors

Desmoplastic small round cell tumors (DSRCTs) are highly aggressive sarcomas that most commonly occur intra‐abdominally, and are defined by EWSR1‐WT1 gene fusion. Intracranial DSRCTs are exceptionally rare with only seven previously reported fusion‐positive cases. Herein, we evaluate the clinical, morphologic, immunohistochemical and molecular features of five additional examples. All patients were male (age range 6–25 years; median 11 years), with four tumors located supratentorially and one within the posterior fossa. The histologic features were highly variable including small cell, embryonal, clear cell, rhabdoid, anaplastic and glioma‐like appearances. A prominent desmoplastic stroma was seen in only two cases. The mitotic index ranged from <1 to 12/10 HPF (median 5). While all tumors showed strong desmin positivity, epithelial markers such as EMA, CAM 5.2 and other keratins were strongly positive in only one, focally positive in two and negative in two cases. EWSR1‐WT1 gene fusion was present in all cases, with accompanying mutations in the TERT promoter or STAG2 gene in individual cases. Given the significant histologic diversity, in the absence of genetic evaluation these cases could easily be misinterpreted as other entities. Desmin immunostaining is a useful initial screening method for consideration of a DSRCT diagnosis, prompting confirmatory molecular testing. Demonstrating the presence of an EWSR1‐WT1 fusion provides a definitive diagnosis of DSRCT. Genome‐wide methylation profiles of intracranial DSRCTs matched those of extracranial DSRCTs. Thus, despite the occasionally unusual histologic features and immunoprofile, intracranial DSRCTs likely represent a similar, if not the same, entity as their soft tissue counterpart based on the shared fusion and methylation profiles.     

Extensive subpial cortical demyelination is specific to multiple sclerosis

Cortical demyelinated lesions are frequent and widespread in chronic multiple sclerosis (MS) patients, and may contribute to disease progression. Inflammation and related oxidative stress have been proposed as central mediators of cortical damage, yet meningeal and cortical inflammation is not specific to MS, but also occurs in other diseases. The first aim of this study was to test whether cortical demyelination was specific for demyelinating CNS diseases compared to other CNS disorders with prominent meningeal and cortical inflammation. The second aim was to assess whether oxidative tissue damage was associated with the extent of neuroaxonal damage. We studied a large cohort of patients diagnosed with demyelinating CNS diseases and non‐demyelinating diseases of autoimmune, infectious, neoplastic or metabolic origin affecting the meninges and the cortex. Included were patients with MS, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), viral and bacterial meningoencephalitis, progressive multifocal leukoencephalopathy (PML), subacute sclerosing panencephalitis (SSPE), carcinomatous and lymphomatous meningitis and metabolic disorders such as extrapontine myelinolysis, thus encompassing a wide range of adaptive and innate cytokine signatures. Using myelin protein immunohistochemistry, we found cortical demyelination in MS, ADEM, PML and extrapontine myelinolysis, whereby each condition showed a disease‐specific histopathological pattern. Remarkably, extensive ribbon‐like subpial demyelination was only observed in MS, thus providing an important pathogenetic and diagnostic cue. Cortical oxidative injury was detected in both demyelinating and non‐demyelinating CNS disorders. Our data demonstrate that meningeal and cortical inflammation alone accompanied by oxidative stress are not sufficient to generate the extensive subpial cortical demyelination found in MS, but require other MS‐specific factors.     

Sub-angiographic peripheral emboli in high resolution DWI after endovascular recanalization

Journal of Neurology - To analyze the incidence of peripheral emboli after successful mechanical thrombectomy (MT) of intracranial large vessel occlusions (LVO). We performed a prospective analysis...     

CRISPR-Cas9-Edited Tacrolimus-Resistant Antiviral T Cells for Advanced Adoptive Immunotherapy in Transplant Recipients

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