A Successful Heart Transplantation Coupled with Temporary Right Ventricular Assist Device Implantation in a Patient with (ir)Reversible Pulmonary Hypertension.

Pulmonary hypertension (PH) constitutes one of the main contraindications to heart transplantation (OHT), and elevated pulmonary vascular resistance (PVR) is associated with high risk of posttransplant right heart failure (RVF). In the present case report, a patient with PH is introduced who qualified for heart lung transplantation (HLT) and underwent successful OHT with temporary right ventricle assist device (tRVAD) due to the lack of a suitable heart-lung donor. Temporary RVAD support coupled with optimal medical management may help reverse pulmonary vascular resistance, which was previously deemed as permanent in patients requiring heart transplantation.

Histopathological Examination of an Explanted Heart in a Long-Term Responder to Cardiac Stereotactic Body Radiotherapy (STereotactic Arrhythmia Radioablation).

Cardiac stereotactic body radiotherapy is an emerging treatment method for recurrent ventricular tachycardia refractory to invasive treatment methods. The single-fraction delivery of 25 Gy was assumed to produce fibrosis, similar to a post-radiofrequency ablation scar. However, the dynamics of clinical response and recent preclinical findings suggest a possible different mechanism. The data on histopathological presentation of post-radiotherapy hearts is scarce, and the authors provide significantly different conclusions. In this article, we present unique data on histopathological examination of a heart explanted from a patient who had a persistent anti-arrhythmic response that lasted almost a year, until a heart failure exacerbation caused a necessity of a heart transplant. Despite a complete treatment response, there was no homogenous transmural fibrosis in the irradiated region, and the overall presentation of the heart was similar to other transplanted hearts of patients with advanced heart failure. In conclusion, our findings support the theorem of functional changes as a source of the anti-arrhythmic mechanism of radiotherapy and show that durable treatment response can be achieved in absence of transmural fibrosis of the irradiated myocardium.

Severe Acute Respiratory Distress Syndrome in Potential Organ Donors-Rescue Prone Positioning: A Case Report.

Organ transplantation is a recognized treatment for many critical organ insufficiencies. One of the main problems in transplantation is the mismatch between organ donation and demand. It is very important to improve donor eligibility after brain stem death and to minimize insult to donatable organs by appropriate donor management. We present prone positioning as an effective supportive method of organ optimization in patients with acute respiratory distress syndrome with severe hypoxemia and hemodynamic instability.

A systematic approach to transoesophageal echocardiography in the intensive care unit - a practical guide for intensivists.

Transoesophageal echocardiography (TOE) has become a useful diagnostic and monitoring tool in critical care settings, especially when transthoracic echocardiography is difficult to perform. It gives valuable information in mechanical ventilation, especially in the prone position, in obese patients, and in patients with surgical dressings and chest tubes. Transthoracic echocardiography allows visualization of deep cardiac structures and their pathologies. It has extensive diagnostic implications. This article describes the systematic approach to critical care TOE examination with a detailed description of the views necessary for rapid haemodynamic assessment in critical care patients. It is concordant with European Diploma in Advanced Echocardiography (EDEC) requirements, and its structural approach is based on the author's experience acquired in the EDEC examination process. Performing TOE in an organized fashion can help to pinpoint most of the pathologies and monitor the treatment process in the intensive care unit.

Utility of tissue Doppler imaging of systolic function to diagnose diastolic dysfunction in critically ill patients.

BACKGROUND: Diastolic dysfunction might be associated with increased mortality in severe sepsis and septic shock. In 2016 new American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) guidelines were published. They simplify our approach to diastolic dysfunction recognition, but they were not validated in critical care settings. The aim of the study was to assess the applicability of systolic tissue Doppler imaging of left ventricle in patients with and without diastolic dysfunction classified on the basis of the new guidelines. METHODS: Two echocardiographers analyzed transthoracic echocardiography (TTE) exa-minations and assigned patients according to ASE/EASCVI guidelines to three groups: patients with systolic dysfunction and diastolic dysfunction, patients with normal systolic function and diastolic dysfunction, and patients with normal systolic and diastolic function. RESULTS: We performed 593 examinations in 320 patients and 390 examinations in 200 patients were included in the study. In 264 examinations with ejection fraction (EF) < 55% systolic and diastolic dysfunction was diagnosed (group 1). In 114 examinations with EF ≥ 55% normal systolic and diastolic function was diagnosed (group 2). In 12 examinations with EF ≥ 55% normal systolic and abnormal diastolic dysfunction was diagnosed (group 3). After analyzing mean systolic tissue Doppler of the mitral annulus we found a statistically significant difference between group 1 and 2 (P < 0.0001) and between group 2 and 3 (P < 0.0001). The difference in values of means in group 1 vs. 3 was not statistically significant (P = 0.853). CONCLUSION: Systolic tissue Doppler analysis of mitral annulus might help to diagnose diastolic dysfunction especially in patients with preserved ejection fraction.

Clinical effectiveness of MARS treatment - multidirectional analysis of positive clinical response to treatment.

AIM OF THE STUDY: Liver failure is a life-threatening condition which often requires intensive care treatment. It is essential to quickly determine whether there are indications for extracorporeal liver support systems for the patient. The aims of the study were: to assess effectiveness of molecular adsorbent recirculating system (MARS) therapy based on selected clinical criteria, to analyze the moment of clinical response and to create a patient's profile, who will benefit clinically from the treatment. MATERIAL AND METHODS: The analysis encompassed medical histories of 65 patients treated with MARS. Effectiveness of treatment was evaluated based on selected clinical parameters. Statistical analysis was performed based on medical data gathered. RESULTS: There were 158 cycles of MARS performed, with effectiveness documented in 57 cycles (36.6%). The first MARS session was effective in 43.1% of patients. They also more often responded to the second cycle (63.6% vs. 15.4%). A significant part of the analysis was devoted to create a profile of the patient in whom positive response can be expected. A low MELD score and low baseline white blood cells (WBC) level are statistically significant factors in multivariate analysis of selected features of positive clinical response to treatment. CONCLUSIONS: MARS therapy is an effective form of treatment in a properly selected group of patients with liver failure. The first MARS session is the most effective one. It is also a good prognostic factor for further clinical response to treatment. Multifactorial analysis of positive clinical response to treatment enables to create a patient's profile based on the lower baseline MELD score and WBC.

Effectiveness and Safety Assessment of Citrate Anticoagulation During Albumin Dialysis in Comparison to Other Methods of Anticoagulation.

Liver failure is a serious and often deadly disease often requiring MARS (Molecular Adsorbent Recirculating System) therapy. Choosing the safe and effective method of anticoagulation during artificial liver support systems seems to be very difficult and extremely important. The aim of this study was to assess effectiveness and safety of regional anticoagulation with citrate in liver failure patients during MARS. We used a single center observational study. We analyzed 158 MARS sessions performed in 65 patients: 105 (66.5%) sessions in 41 patients with heparin anticoagulation, 40 (25.3%) sessions in 19 patients with citrate, and 13 (8%) sessions in only five patients without anticoagulation, that were excluded from part of the analysis. To determine the effectiveness of regional anticoagulation with citrate, probability of filter survival and changes in laboratory parameters were analyzed according to the applied method of anticoagulation. The safety of citrate was determined by Ca/Ca2+ ratio, acid-base balance, bleeding complications, and the need for blood product transfusions. The probability of filter survival in the citrate group was 94% and in the heparin group 82% (P = 0.204). There was no relationship between the method of anticoagulation and effectiveness of MARS therapy in lowering the levels of the analyzed parameters. Only one patient had a Ca/Ca2+ ratio higher than he safety margin. There were no statistically significant changes in pH and lactate level irrespective of anticoagulation; bicarbonate dropped significantly only in the heparin group (P = 0.03). The frequency of bleeding complications and the need for transfusions did not differ significantly between groups. Regional anticoagulation with citrate can be an effective and safe method of anticoagulation during MARS therapy, but requires attentive monitoring and further studies in liver failure patients.

Utility of transthoracic echocardiography (TTE) in assessing fluid responsiveness in critically ill patients - a challenge for the bedside sonographer.

Transthoracic echocardiography (TTE) has become one of the most important diagnostic tools in the treatment of critically ill patients. It allows clinicians to recognise potentially reversible life-threatening situations and is also very effective in the monitoring of the fluid status of patients, slowly substituting invasive methods in the intensive care unit. Hemodynamic assessment is based on a few static and dynamic parameters. Dynamic parameters change during the respiratory cycle in mechanical ventilation and the level of this change directly corresponds to fluid responsiveness. Most of the parameters cannot be used in spontaneously breathing patients. For these patients the most important test is passive leg raising, which is a good substitute for fluid bolus. Although TTE is very useful in the critical care setting, we should not forget the important limitations, not only technical ones but also caused by the critical illness itself. Unfortunately, this method does not allow continuous monitoring and every change in the patient's condition requires repeated examination.

Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL.

Minimal residual disease (MRD) enables reliable assessment of risk in acute lymphoblastic leukemia (ALL). However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in VDR (MRD-day15); rs1051266 in RFC (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in IL15 (MRD-day33). The risk alleles for MRD-positivity were: A allele of VDR (OR = 2.37, 95%CI = 1.07-5.21, P = 0.03, MRD-day15); A of RFC (OR = 1.93, 95%CI = 1.05-3.52, P = 0.03, MRD-day33 and MRD-week12, P < 0.01); A of IL15 (OR = 2.30, 95%CI = 1.02-5.18, P = 0.04, MRD-day33). The risk for MRD-day33-positive status was higher in patients with risk alleles in both RFC and IL15 loci than in patients with risk alleles in one locus or no risk alleles: 2 vs. 1 (OR = 3.94, 95% CI = 1.28-12.11, P = 0.024), 2 vs. 0 (OR = 6.75, 95% CI = 1.61-28.39, P = 0.012). Germline variation in genes related to pharmacokinetics/pharmacodynamics of anti-leukemic drugs and to anti-tumor immunity of the host is associated with MRD status and might help improve risk assessment in ALL.

Higher CD34(+) and CD3(+) cell doses in the graft promote long-term survival, and have no impact on the incidence of severe acute or chronic graft-versus-host disease after in vivo T cell-depleted unrelated donor hematopoietic stem cell transplantation in children.

The aim of our study was to compare the results of unrelated donor (UD) peripheral blood stem cell transplantation versus UD bone marrow transplantation and to analyze the impact of infused CD34(+) and CD3(+) cell doses on survival and incidence of severe graft-versus-host disease (GVHD) in 187 children who underwent UD hematopoietic cell transplantation with the use of in vivo T cell depletion (antithymocyte globulin or CAMPATH-1H). HLA typing was performed at the "high-resolution" level. Patients receiving > or =10 x 10(6) CD34(+) cells/kg and > or =4 x 10(8) CD3(+) cells/kg had better overall and disease-free survival. Multivariate analysis has shown that both infused CD34(+) cell dose <10 x 10(6)/kg and CD3(+) cell dose <4 x 10(8)/kg were independent risk factors for mortality (relative risk [RR] 1.8 and 1.71, P = .009 and .016, respectively). Regarding disease-free survival, multivariate analysis has revealed another independent risk factor for poor outcome apart from the 2 earlier-mentioned cell doses, which was the use of donors mismatched at 2 HLA antigens or 3 HLA allele/antigens (RR 2.5, P = .004). In age groups 0-10 years and 10-20 years, CD34(+) cell doses higher than the age-adjusted median dose clearly favored survival. Higher infused doses of CD34(+) and CD3(+) cells did not result in an increased rate of severe GVHD. The use of mismatched donors was the only independent risk factor for the incidence of severe acute GVHD (RR 2.2, P = .046). The report demonstrates for the first time in a pediatric cohort, that higher doses of transplanted CD34(+) and CD3(+) cells lead to an improved survival without an increased risk of severe GVHD. The study findings may be limited to the population of patients receiving in vivo T cell depletion, which is now broadly used in unrelated donor setting in Europe.

[Megachemotherapy and autologous stem cell transplantation in children with Ewing sarcoma - Polish experience]. / Megachemioterapia i autologiczne przeszczepienie hematopoetycznych komorek macierzystych u dzieci z miesakiem ewinga-doswiadczenia Polskie.

AIM: To present results of megachemotherapy and autologus hematopoietic stem cell transplantation in children with Ewing sarcoma in 4 Polish pediatric transplantation centres. MATERIAL AND METHODS: Between the years 1995-2007 autologous stem cell transplantation was performed in 54 patients (25 girls and 29 boys) with Ewing sarcoma. 26 patients were in complete remission before megachemotherapy, 23 were in partial remission, 3 patients had progression of the disease and the status of 2 patients was unknown. 41 children received busulfan 16 mg/kg and melphalan 140 mg/m(2), 8 children carboplatin 1500 mg/m(2), VP-16 40 mg/kg, melfalan 160 mg/m(2) and 5 children other megachemotherapy protocols. RESULTS: Probability of survival of patients after transplantation, in complete remission is 0,79 with median 35 months of observation time. For patients after transplantation in partial remission probability of survival was 0,25 with median observation time of 14 months. Patients in progressive disease died 1,3 and 7 months after transplantation. 32 children are alive and 22 patients died, 21 of them due to disease progression. CONCLUSIONS: 1. Megachemotherapy and autologous hematopoietic stem cell transplantation is a safe therapy in patients with high risk Ewing sarcoma in complete remission. 2. Proportion of patients with sustained remission after transplantation in greater as compared to the published data related to high risk group without megachemotherapy. 3. According to our data megachemotherapy did not improve outcome in patients with partial remission of the disease.

[Megachemotherapy and autologous hematopoietic stem cell transplantation in children with solid tumours excluding neuroblastoma--experience of Polish paediatric centres]. / Megachemotherapia i przeszczepianie autologicznych hematopoetycznych komórek macierzystych u dzieci z guzami litymi innymi niz neuroblastoma--doswiadczenia polskich osrodków pediatrycznych.

UNLABELLED: AIM OF THE STUDY was to present the experience of four Polish transplantation centres (Wroclaw, Bydgoszcz, Kraków and Lublin) with use of megachemotherapy (MCT) and autologous hematopoietic stem cell transplantation (autoHSCT) in children with high risk solid tumours. PATIENTS AND METHODS: Between 1994 and 2005 in 67 patients, whose age ranged form 1.5 to 20 years, 74 procedures of megachemotherapy and auto HSCT were performed. 25 children were treated for Ewing Sarcoma, 13 for rhabdomyosarcoma embryonale (RMS), 7 for germinal tumours, 6 for medulloblastoma, 4 for PNET, 4 for Wilm's tumours, 2 for glioblastoma and single patients with mesenchymoma, astrocytoma, ependymoma, angioblastoma, carcinoma ovarian and carcinoma embryonale glutei. Most common megachemotherapy protocols consisted of: Melphalan, Etopozyd i Carboplatin (MEC)--applied in 24 children and Busulfan plus Melphalan (Bu Mel) administered in 19 patients. In 29 children MCH was introduced in first complete remission, in 14 the procedure was performed in second or subsequent remission and 24 patients did not achieve remission before megachemotherapy was started. RESULTS: 30 children are alive (44%), 28 of them in complete remission of disease. 23 out of 29 (79%) patients were transplanted in first complete remission and median observation time in that group is 29 months (range 2-74 months). Only 5 out of 38 children transplanted in second complete remission or without complete remission survived. 39 patients relapsed at a median time 11 months after MCT and 37 of them subsequently died of disease at a median time of 16 months. One toxic death was noted--it was a boy, transplanted with progressive disease. CONCLUSIONS: 1. Megachemotherapy with autologous stem cell can rescue children with high risk solid tumours. It is a safe procedure especially when performed in remission. 2. Children with resistant or relapsed solid tumours are unlikely to benefit from megachemotherapy.

[High-dose therapy followed by auto HSCT in children--with advanced neuroblastoma in four transplant centres in Poland]. / Megachemotherapia z autologicznym przeszczepieniem komórek krwiotwórczych u dzieci z neuroblastoma wysokiego ryzyka w 4 dzieciecych osrodkach przeszczepiania szpiku hostnego w Polsce.

AIM OF THE STUDY: Posttransplant morbidity and clinical outcome in children with advanced neuroblastoma (NBL) who underwent megachemotherapy followed by HSCT were investigated. PATIENTS AND METHODS: In the study 73 children with advanced NBL treated in four Departments of Paediatric Haematology and Oncology in Lublin, Kraków, Wroclaw and Bydgoszcz from 1995 to 2004 were analysed. Median age of children was 4.9 years (range 1.8 to 15). Reinfusion of CD34 cells followed myeloablative chemotherapy with Busulfan / Melfalan in 58 patients; Treosulfan / Melfalan in 2 patients; Melfalan / VP16/ Carbo in 9 patient, Melfalan alone in 3 patients and Thiotepa /CTX/ Carbo in 1 patient. Stem cells from peripheral blood were used in 57 cases, bone marrow in 10 patients, bone marrow and peripheral blood in 6 patients. RESULTS: 41/73 (56%) children are alive with median follow up 12 months (range 3 to 68 months), 29 children are in complete remission (CR), 12 patients are in partial remission (PR). 32/73 (44%) children died, 26 of them due to progressive disease; six children died due to posttransplantation complications. Overall survival (OS) at median observation time 12 months is 0.65; disease free survival (DFS) is 0.58. Probability of 5-year OS and DFS in the group of children transplanted in first partial/complete remission are 0.42 and 0.4 respectively. CONCLUSIONS: Treatment with megachemotherapy followed by autoHSCT in patients with advanced neuroblastoma has not many adverse effects. Probabilities of 5-year OS and DFS are higher in the group of transplanted children in 1 partial/complete remission than in children transplanted after relapse.

Incidence, clinical outcome, and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation.

We analyzed the incidence, etiology, risk factors, and clinical management of hemorrhagic cystitis (HC) in 102 children who underwent allogeneic stem cell transplantation: 28 from matched siblings, 57 from unrelated donors, and 17 from mismatched relatives. Conditioning regimens consisted of high-dose chemotherapy (n=83) or total body irradiation (n=19). In all children, urine and plasma were prospectively screened for human polyomavirus (HPV; BK virus [BKV] and JC virus [JCV]) or adenovirus (AdV) DNA with a polymerase chain reaction-based assay. Viral DNA was detected in the urine of 56 children (54.9%): BKV in 48 (47%), JCV in 4 (3.9%), and AdV in 4 (3.9%). HC occurred in 26 children (25.5%), and viruria was detected in all of them: BKV in 21 (80.8%), AdV in 4 (14.4%), and JCV in 1 (3.8%). All patients with AdV viruria developed HC. The cumulative incidence of HC in patients with HPV viruria was 0.43. The only significant risk factor for HC in patients with HPV-positive urine was conditioning with high-dose chemotherapy. Twenty-two children were treated with cidofovir, with no significant toxicity. In all treated patients but 1, the clinical symptoms were moderate, and no HC-related death was observed. We conclude that virus-induced HC is a frequent complication after allogeneic hematopoietic cell transplantation. Treatment with cidofovir is feasible, and further studies are warranted to evaluate its activity in HC mediated by BKV or JCV.