Severe Multiorgan Failure Research Articles

Intracranial hemorrhage with electrocardiographic abnormalities and troponin elevation

Electrocardiographic (ECG) abnormalities and cardiac troponin I elevation are seen in addition to the classic clinical symptoms and signs of subarachnoid hemorrhage (SAH). We aimed to show that, in patients with ST elevation, troponin elevation, and altered consciousness, the reason may be SAH. A 36-year-old man presented to emergency service with ECG abnormalities, high level of cardiac troponin I, and neurologic symptoms. In the patient's initial ECG, there were sinus arrhythmia, bradycardia, T-wave inversions inferiorly, and concave ST elevations in V1 to V4. Three hours later, his ECG showed increased ST-segment elevations with normal heart rate. The patient's troponin I value was 10 mg/L. Ejection fraction was 60%, and there were no wall motion abnormalities on echocardiography. Computed tomographic scan of the brain demonstrated SAH with falx sign and midline cerebellar hematoma (3 × 4 cm in size) in the occipital region. The patient died on the 10th day of follow-up because of severe metabolic acidosis, multiorgan failure, and bradycardia. Cardiac evaluation is recommended in patients with intracranial hemorrhage in many studies. In our opinion, if there are neurologic symptoms or signs in patients diagnosed as acute myocardial infarction with ECG changes and troponin elevation, requesting threshold of brain computed tomography should be low before the thrombolytic therapy.

Is Transfemoral Aortic Valve Implantation Possible Without Contrast Medium in Patients With Renal and Multiorgan failure?

Transfemoral aortic valve implantation has recently emerged as a therapeutic option for patients with symptomatic, severe aortic stenosis for whom standard surgical aortic valve surgery is not suitable. Aortic valvuloplasty and valve positioning is normally performed under fluoroscopy and requires several injections of contrast medium. In critically ill patients with advanced renal insufficiency, contrast media administration can further increase renal damage; therefore, an echocardiogram and fluoroscopy-guided procedure, using the calcified contours of the stenotic aortic valve as a landmark may be a useful alternative. We report the first successful transfemoral aortic valve implantation procedure performed under fluoroscopy and transesophageal echocardiogram control, without administration of contrast medium injections in a patient with severe renal insufficiency and multiorgan failure.

Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever

A woman developed Marburg haemorrhagic fever in the Netherlands, most likely as a consequence of being exposed to virus-infected bats in the python cave in Maramagambo Forest during a visit to Uganda. The clinical syndrome was dominated by acute liver failure with secondary coagulopathy, followed by a severe systemic inflammatory response, multiorgan failure, and fatal cerebral oedema. A high blood viral load persisted during the course of the disease. The initial systemic inflammatory response coincided with peaks in interferon-γ and tumour necrosis factor-α concentrations in the blood. A terminal rise in interleukin-6, placental growth factor (PlGF), and soluble vascular endothelial growth factor receptor-1 (sVEGF-R1) seemed to suggest an advanced pathophysiological stage of Marburg haemorrhagic fever associated with vascular endothelial dysfunction and fatal cerebral oedema. The excess of circulating sVEGF-R1 and the high sVEGF-R1:PlGF ratio shortly before death resemble pathophysiological changes thought to play a causative part in pre-eclampsia. Aggressive critical-care treatment with renal replacement therapy and use of the molecular absorbent recirculation system appeared able to stabilise--at least temporarily--the patient's condition.

Novel influenza A (H1N1) virus–induced hemophagocytosis: first case reported in Saudi Arabia

H1N1 is a novel subtype of the influenza A virus. Since its reemergence in 2008, it has been reported to cause a variety of illnesses ranging from mild flu-like symptoms to severe multiorgan failure. We report a case of a young immunocompetent man who presented with progressive shortness of breath and rapidly developed multiorgan dysfunction, including pancytopenia from H1N1 infection during the 2010–2011 influenza season. His H1N1 pneumonia caused severe acute respiratory distress syndrome, respiratory failure requiring mechanical ventilation, rhabdomyolysis, myocarditis, hepatitis, encephalitis, and renal failure. During the diagnostic workup, a bone marrow biopsy was performed, showing hemophagocytosis secondary to the H1N1 infection. Unfortunately the patient died despite aggressive measures. Published reports contain only a few records of H1N1-induced hemophagocytosis. This is the first case report from Saudi Arabia with H1N1-induced secondary hemophagocytosis. It also highlights the fact that the virus is still very virulent and will pose a major annual health risk along with the seasonal influenza for at least the next few years.

Defibrotide (DF) in the Treatment of Hepatic Veno-Occlusive Disease (VOD) in Stem Cell Transplant (SCT) and Non-SCT Patients (Pts): Early Intervention Improves Outcome - Updated Results of a Treatment IND Expanded Access Protocol

Abstract 487 Background: Given the life-threatening nature of severe VOD (sVOD) and multi-organ failure (MOF), DF was made available in the US through a prospective treatment IND protocol (T-IND) to gather additional safety and response data from SCT patients (pts) with sVOD who were not eligible for a pivotal Phase 3 trial. Following completion of this Phase 3 trial, the T-IND protocol has continued and been amended to include pts who would have met eligibility criteria for the completed phase 3 trial, as well as pts with non-severe VOD and non-SCT pts who develop VOD after chemotherapy (chemo). This is the largest prospective evaluation of DF for the treatment of sVOD/MOF post SCT and non-SCT pts to date. Methods: Pts were initially required to have a diagnosis of VOD by Baltimore criteria (total bilirubin > 2.0 mg/dL with > 2 of the following: hepatomegaly, ascites or 5% weight gain) with MOF (either renal and/or pulmonary failure) that followed SCT. Following treatment of 104 pts, an amendment expanded eligibility criteria to include pts with VOD after chemo and pts with non-severe VOD (defined as no MOF). Key exclusion criteria included clinically significant bleeding or >1 pressor to maintain BP. CR was defined as bilirubin Results: This interim analysis is based on 269 pts enrolled between December 2007 and March 2011 at 67 centers. Nearly all pts (n=251) had undergone SCT (with allogeneic SCT in 225, 90%); 18 developed VOD after chemo alone. Of the 269 cases of VOD, 200 were severe at study entry, with 25% (66/269) of all pts dialysis dependent and 31% (83/269) ventilator dependent. Median age was 16 years (range 0.1 – 70); 55% were male. In the SCT pts, the most common diagnosis was leukemia (29% AML; 22% ALL; CML 3%; 4% other), with conditioning of CY (71%), BU (46%) and TBI (38%) respectively; 18% had undergone multiple SCTs (>1 SCT). Median onset of VOD was 15 d post-SCT. When presenting after chemo alone (n=18), median onset of VOD was 16 d after the first dose, most frequently after CY (61%), cytarabine (44%) and vincristine (39%), and for treatment of leukemia (AML 33%, ALL 33%, other 6%). Overall mean number of days of DF administration in all pts was 22 (range 1–88).Of 269 pts, 32% (85/269) achieved a CR and 50% [ by Kaplan-Meier estimate] survived to D+100. In the subgroup of SCT pts, 31% (78/251) achieved CR and 50% survived to D+100; 134 pts met entry criteria for the original Phase 3 trial and comparison to the Phase 3 historical control showed a statistically improved outcome in CR (30% vs 9%, p=0.0006) and D+100 survival (46% vs 25%; p=0.006). Of 200 pts with sVOD, CR was 28% and D+100 survival was 44%. In the 18 chemo only pts, CR was 39% and D+100 survival was 50%. CR rate and D+100 survival for the 69 pts with non-severe VOD were 42% and 62%, respectively. Delay of >2 d (vs Conclusions: In 269 pts with mainly sVOD/MOF, DF therapy achieved significantly improved outcome compared to an untreated historical control. Importantly, CR and survival were improved in pts who were treated within 2d of VOD diagnosis (vs. later) and in pts who had not yet progressed to sVOD. As with prior studies, there was a low incidence of DF-associated toxicities. Interestingly, the incidence of GvHD in allo-SCT pts was low, consistent with the reduction of GvHD seen in the large randomized EBMT pediatric prevention study. These results confirm the findings of previous trials and strongly support early intervention with DF once the diagnosis of VOD is made after SCT, as well as its use in pts who have not progressed to advanced MOF. The use of DF for VOD following intensive chemotherapy without SCT also appears promising, but more research in this patient population is needed. Enrollment to the T-IND study continues. Disclosures: Richardson:Gentium: Membership on an entity9s Board of Directors or advisory committees. Arai:Gentium: Research Funding. Symons:Otsuka Pharmaceuticals: Research Funding. Martin:Gentium: Research Funding. Massaro:Gentium: Consultancy. D9Agostino:Gentium: Membership on an entity9s Board of Directors or advisory committees. Hannah:Gentium: Consultancy. Tudone:Gentium: Employment. Hume:Gentium: Employment. Iacobelli:Gentium SpA: Employment. Soiffer:Gentium: Honoraria.

AP039 Neuroprotective effect of barbiturates cause successful cerebral recovery after drug induced cardiac arrest and severe multiorganfailure

AP039 Neuroprotective effect of barbiturates cause successful cerebral recovery after drug induced cardiac arrest and severe multiorganfailure

The Incidence of Veno-Occlusive Disease Following Allogeneic Hematopoietic Stem Cell Transplantation Has Diminished and the Outcome Improved over the Last Decade

The evolution of the incidence, morbidity, and mortality of veno-occlusive disease (VOD) was analyzed in 845 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) performed over 24 years. A total of 117 patients and 73 patients developed VOD following the Seattle and the Baltimore diagnostic criteria, respectively (cumulative incidence 13.8% and 8.8%). The cumulative incidence was significantly higher in the period 1985 to 1996 than in 1997 to 2008 (11.5% vs 6.5%; P= .01). This decline was because of the low incidence of VOD among reduced-intensity conditioning-HSCT (RIC-HSCT) (2.1%) and the reduction among those receiving myeloablative-HSCT from unrelated donors (32.7% vs 10.5%, P = .001). A total of 35 patients had severe VOD (26 with multiorgan failure [MOF]), and 20 died by VOD (cumulative mortality rate 17.3%, Seattle, or 22.5%, Baltimore). The mortality declined since 1997 (from 22% to 9%; P = .06, Seattle, and from 36% to 14%; P= .04, Baltimore), with the introduction of defibrotide being the only relevant change in the management of patients. This occurred even though the severity of VOD was similar in both periods. Among those with MOF, only 2 of 8 (25%) receiving defibrotide died versus 14 of 18 (78%) receiving other treatments (P = .007). Myeloablative conditioning, previous liver disease, poor performance status, and alternative donors were the variables with higher impact on VOD development. In summary, although VOD remains a dreaded early complication of HSCT, technical and therapeutic progress in recent decades have notably reduced its incidence and improved the outcome.

Extra-corporeal life support for near-fatal multi-drug intoxication: a case report

IntroductionSevere mixed β-blocker and calcium channel blocker intoxication presents a significant risk for patient mortality. Although treatment is well-established, it sporadically fails to support the patient through massive overdoses, thus requiring non-conventional treatments. We report the use of extra-corporeal life support in a patient with refractory hemodynamic impairment due to multi-drug intoxication. Although sometimes used in clinical practice, extra-corporeal membrane oxygenation for intoxications has rarely been reported.Case presentationA 36-year-old Caucasian man presented to our hospital with refractory hypotension, severe cardiac insufficiency and multi-organ failure due to mixed intoxication with atenolol, nifedipine, Lacidipine and sertraline. Together with standard treatment, we performed extra-corporeal membrane oxygenation to overcome refractory cardiogenic shock and lead the patient to achieve a full recovery.ConclusionStandard of care for β-blocker and calcium channel blocker intoxication is well-defined and condensed into protocols of treatment. Although aimed at clearing the noxious agents from the patient's system, standard measures may fail to provide adequate hemodynamic support to allow recovery. In selected cases, extra-corporeal membrane oxygenation could be considered a bridge to drug clearance while preventing multi-organ failure due to profound shock.

Severe Leptospirosis Similar to Pandemic (H1N1) 2009, Florida and Missouri, USA

Severe Leptospirosis Similar to Pandemic (H1N1) 2009, Florida and Missouri, USA

First use of the Cardiohelp system in the ECMO-LVAD concept

We describe a 51-year-old man with cardiogenic shock and severe multi-organ failure in whom the new percutanoues extracoporeal life support (ECLS) system Cardiohelp (Maquet CP, Hirrlingen, Germany) was used in 3 different settings. Initially, the system was employed as venoarterial extracorporeal membrane oxygenation (ECMO) to restore cardiopulmonary stability. After successful stabilization, a pulsatile extracorporeal left ventricular assist device (LVAD) was implanted during ECMO support with the heart beating to reduce the negative effects associated with conventional cardiopulmonary bypass (CPB) systems. After LVAD placement, the ECMO was switched to a temporary right ventricular support to avoid right venticular failure, which could be terminated after 5 days. In conclusion, a simple ECLS set-up and integrated systems like the new Cardiohelp system are highly versatile instruments to differenzially stabilize patients in various situations with cardiopulmonary compromise. The miniaturized extracorporeal circulation devices can give significant support from resuscitation until heart transplantation, and thereafter.

Piomiositis del músculo piriforme

Unfortunately, diagnosis of deep pelvic muscle infection is often delayed since they usually present with non-specific physical signs suggesting other more common diseases. The authors communicate a case of a previously healthy 12-year-old male whot practiced dancing regularly and suffered acute pain in the lumbar and right gluteal regions irradiated to the posterior side of the thigh for 1 week. He initially received symptomatic treatment with no success. He continued with diarrhea, fever and malaise. When he was admitted to hospital he suffered severe septic shock and multi-organ failure. Pelvis magnetic resonance imaging showed pyomyositis of the piriformis muscle. Multi-sensitive Staphylococcus aureus was isolated in blood cultures. Antibacterial treatment and multi systemic support were administered, resulting in a good outcome. Pyomyositis of the piriformis muscle is a rare condition that demands a high index of suspicion to make an adequate diagnosis and prompt treatment, including antibacterial treatment and drainage, particularly in case of abscess formation. This treatment should be established promptly since its outcome may be potentially lethal.

Critical Care of Gynecological and Obstetric Patients: A decade of surgical intensive care experience

Despite the emergence of therapeutic advances, the morbidity and mortality still occur in the obstetric patients, although intensive care utilization by obstetric and gynecological patient, are still rare compared to the general population. Majority of obstetric patients needed the intensive care therapy compared to gynecological patients. The aim of our study was to know the indications for the intensive care admission by obstetric and gynecological patients, length of stay and outcome of these patients. Methods: We retrospectively reviewed the medical records of all obstetric and gynecological patients admitted to our Surgical and Trauma Intensive Care Units (SICU and TICU) from February 1995 to March 2005. Indication for admission, nationality, age, and length of stay in ICU, severity of disease and outcome of these patients were recorded. Data analyzed with SPSS program. Results: A total of 182 patients were admitted to the SICU of the Hamad Medical Corporation in Doha, Qatar, from the Women's Hospital. 159 (87%) patients were obstetric patients and 23 (13%) patients gynecological patients, 126 (69.6%) patients were admitted post Lower Segment Caesarean Section (LSCS). The most common indication for admission was 73 (39.3%) patients obstetric hemorrhage and Disseminated Intravascular Coagulation (DIC), and then 44 (25.3%) patients of hypertensive disorder of pregnancy. The major anesthesia related indication was scoline apnea, 21 (11.6%). Total three obstetric patients died, two due to severe sepsis and multi-organ failure and one due to cerebral sinus thrombosis, giving mortality rate of 1.66%. Conclusion: Intensive care therapy required by gynecological and obstetric patient is less than the general population. The commonest indication for admission was obstetric hemorrhage, DIC, and hypertensive disorders of pregnancy. The mortality was due to septic shock with multi-organ failure, and cerebral venous sinus thrombosis.

A Newly Developed Miniaturized Heart‐Lung Machine—Expression of Inflammation in a Small Animal Model

Cardiopulmonary bypass may cause severe inflammatory reactions and multiorgan failure, especially in premature and low-weight infants. This is due in part to the large area of contact with extrinsic surfaces and the essential addition of foreign blood. Thus, we developed a new miniaturized heart-lung machine (MiniHLM) with a total static priming volume of 102mL (including arterial and venous lines) and tested it in a small animal model. Seven Chinchilla Bastard rabbits were perfused with the MiniHLM (dynamic priming volume 127mL). Seven animals serving as a control were perfused using Dideco Kids and a Stöckert roller pump (modified dynamic priming volume 149mL). The rabbits were anesthetized and sternotomized, followed by cannulation of the aorta and the right atrium. The aorta was clamped for 1h. Blood for examination of inflammation (TNF-α, IL-1β, IL-6, IL-8, and IL-10) and blood gas analysis were taken before skin incision, 5min before opening of the aorta, 15min after opening of the aorta, and 4 h after the initiation of cardiopulmonary bypass. The parameters of inflammation were expressed by means of the comparative C(T) method (ΔΔC(T) method). After gradual reduction of perfusion with the HLM, the heart was decannulated, and the sternum was closed. All rabbits were successfully weaned from cardiopulmonary bypass. Blood gas analysis was unremarkable in all cases. Foreign blood was not administered. Although statistical significance was not achieved, there was a reduced expression of inflammatory markers in the MiniHLM group. The newly developed MiniHLM prototype was tested successfully in a small animal model in terms of technical function and expression of inflammation. Upcoming tests with the industrially manufactured MiniHLM may reveal the advantages of the MiniHLM in comparison with the conventional HLM.

Preoperative Optimization of Multi-Organ Failure Following Acute Myocardial Infarction and Ischemic Mitral Regurgitation by Placement of a Transthoracic Intra-Aortic Balloon Pump

The management of acute myocardial infarction with resultant acute ischemic mitral regurgitation and acute multi-organ failure can prove to be a very challenging scenario. The presence of concomitant vascular disease can only serve to further compromise the complexity of the situation. We demonstrate a new indication for the transthoracic intra-aortic balloon pump as a preoperative means of unloading the heart and improving clinical outcome in such high-risk patients with severe vascular disease. We present the case of a 75-year-old man with a history of severe vascular disease who was transferred emergently to Vanderbilt University Medical Center with an acute inferolateral wall myocardial infarction resulting in severe acute ischemic mitral regurgitation and acute multi-organ failure. He presented with shock liver (serum glutamic-oxaloacetic transaminase [SGOT] of 958), renal failure (creatinine of 3.0), and respiratory failure with a pH of 7.18. Emergent cardiac catheterization revealed 100% occlusion of the left circumflex artery as well as severe ileofemoral disease. The advanced nature of his ileofemoral disease was such that the arterial access catheter occluded the right femoral artery. The duration of time that the catheter was in the artery led to transient limb ischemia with an elevation of his creatine phosphokinase (CPK) to 10,809. Balloon angioplasty followed by stent placement was successfully performed, which restored flow to the coronary vessel. Given the grave nature of the patient's condition, we were very concerned that immediate operative intervention for his condition would entail prohibitively high risk. In fact, the Society of Thoracic Surgeons predicted risk adjusted mortality was calculated to be 56%. In order to minimize patient mortality and morbidity, it was critical to help restore perfusion and organ recovery. Therefore, we decided that the chances for this patient's survival would improve if his condition could be optimized by placement of an intra-aortic balloon pump before undergoing surgery. Given the limb ischemia following arterial sheath insertion, femoral placement of an intra-aortic balloon pump was not an option. Placement of the intra-aortic balloon pump was attempted via a left subclavian artery cutdown, but was not successful. Therefore, a sternotomy was performed, and we placed a transthoracic intra-aortic balloon pump in order to stabilize the patient's hemodynamics and allow for organ recovery. The patient showed immediate improvement, and 4 days later, the multi-organ failure resolved and he successfully underwent mitral valve replacement. The patient was ultimately discharged to a local rehabilitation facility in satisfactory condition. This case demonstrates the utility of a transthoracic intra-aortic balloon pump as a preoperative means of stabilization in very high risk patients with severe peripheral vascular disease in whom the conventional approaches are not possible.

Fabry disease in children: correlation between ocular manifestations, genotype and systemic clinical severity

Background/aimsFabry disease is an X linked lysosomal disorder associated with severe multiorgan failure and premature death. This study aims to determine the prevalence of ophthalmic manifestations in children with the...

Primary isolated aortic valve surgery in octogenarians

We reviewed our surgery registry, to identify predictive risk factors for operative results, and to analyse the long-term survival outcome in octogenarians operated for primary isolated aortic valve replacement (AVR). A total of 124 consecutive octogenarians underwent open AVR from January 1990 to December 2005. Combined procedures and redo surgery were excluded. Selected variables were studied as risk factors for hospital mortality and early neurological events. A follow-up (FU; mean FU time: 77 months) was obtained (90% complete), and Kaplan-Meier plots were used to determine survival rates. The mean age was 82+/-2.2 (range: 80-90 years; 63% females). Of the group, four patients (3%) required urgent procedures, 10 (8%) had a previous myocardial infarction, six (5%) had a previous coronary angioplasty and stenting, 13 patients (10%) suffered from angina and 59 (48%) were in the New York Heart Association (NYHA) class III-IV. We identified 114 (92%) degenerative stenosis, six (5%) post-rheumatic stenosis and four (3%) active endocarditis. The predicted mortality calculated by logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) was 12.6+/-5.7%, and the observed hospital mortality was 5.6%. Causes of death included severe cardiac failure (four patients), multi-organ failure (two) and sepsis (one). Complications were transitory neurological events in three patients (2%), short-term haemodialysis in three (2%), atrial fibrillation in 60 (48%) and six patients were re-operated for bleeding. Atrio-ventricular block, myocardial infarction or permanent stroke was not detected. The age at surgery and the postoperative renal failure were predictors for hospital mortality (p value <0.05), whereas we did not find predictors for neurological events. The mean FU time was 77 months (6.5 years) and the mean age of surviving patients was 87+/-4 years (81-95 years). The actuarial survival estimates at 5 and 10 years were 88% and 50%, respectively. Our experience shows good short-term results after primary isolated standard AVR in patients more than 80 years of age. The FU suggests that aortic valve surgery in octogenarians guarantees satisfactory long-term survival rates and a good quality of life, free from cardiac re-operations. In the era of catheter-based aortic valve implantation, open-heart surgery for AVR remains the standard of care for healthy octogenarians.

Pandemic 2009 Influenza A in Argentina

The rapid spread of the 2009 Influenza A (H1N1) around the world underscores the need for a better knowledge of epidemiology, clinical features, outcomes, and mortality predictors, especially in the most severe presentations. To describe these characteristics in patients with confirmed, probable, and suspected viral pneumonia caused by 2009 influenza A (H1N1) admitted to 35 intensive care units with acute respiratory failure requiring mechanical ventilation in Argentina, between June 3 and September 7. Inception-cohort study including 337 consecutive adult patients. Data were collected in a form posted on the Argentinian Society of Intensive Care website. Proportions of confirmed, probable, or suspected cases were 39%, 8%, and 53% and had similar outcomes. APACHE II was 18 +/- 7; age 47 +/- 17 years; 56% were male; and 64% had underlying conditions, with obesity (24%), chronic obstructive respiratory disease (18%), and immunosupression (15%) being the most common. Seven percent were pregnant. On admission, patients had severe hypoxemia (Pa(O(2))/Fi(O(2)) 140 [87-200]), extensive lung radiologic infiltrates (2.87 +/- 1.03 quadrants) and bacterial coinfection, (25%; mostly with Streptococcus pneumoniae). Use of adjuvants such as recruitment maneuvers (40%) and prone positioning (13%), and shock (72%) and acute kidney injury requiring hemodialysis (17%), were frequent. Mortality was 46%, and was similar across all ages. APACHE II, lowest Pa(O(2))/Fi(O(2)), shock, hemodialysis, prone positioning, and S. pneumoniae coinfection independently predicted death. Patients with 2009 influenza A (H1N1) requiring mechanical ventilation were mostly middle-aged adults, often with comorbidities, and frequently developed severe acute respiratory distress syndrome and multiorgan failure requiring advanced organ support. Case fatality rate was accordingly high.

Necrotising Fasciitis in the Elderly: A Double Delay

Necrotising fasciitis is an uncommon and rapidly progressive infection of the subcutaneous tissues and fascia which results in necrosis. Without prompt and aggressive surgical intervention, it inevitably leads to severe sepsis and multiorgan failure with a high mortality rate. In general, the diagnosis of infection in the elderly is often difficult, regardless of the type of infection. We report a case of necrotising fasciitis in a 95-year-old lady. The patient presented with bowel and urinary symptoms as well as left leg pain suggestive of sciatica. There was no sign of cellulitis and intravenous antibiotic was started for a presumed urinary tract infection. The diagnosis of necrotising fasciitis was made only much later when crepitus was noted in her leg and radiological studies confirmed gas in the soft tissues. The patient and her family declined surgery and she subsequently died from septicaemia. This condition posed a diagnostic dilemma in the absence of fever, sudden onset of severe pain, and cutaneous findings. In order to reduce morbidity and mortality a high degree of suspicion is required to reach an early diagnosis for prompt surgical intervention.

Surgical treatment of isolated right-sided infective endocarditis

To analyze the surgical treatment and outcomes of isolated right-sided infective endocarditis. From January 1994 to February 2009, 28 patients with isolated right-sided infective endocarditis underwent operation whose clinical data was retrospectively reviewed. There were 18 male and 10 female, age ranged from 10 to 72 years with a mean of 38 years. All of the patients presented intermittent fever, 14 patients presented heart failure (NYHA class III or IV), 25 patients had a history of pulmonary embolism or pneumonia, 18 patients had positive culture; 27 patients had intra-cardiac vegetations confirmed by echocardiogram. All the operations were performed under cardiopulmonary bypass. Antibiotic therapy continued for another 2 to 3 weeks after surgery. One patient had underwent re-operation due to mediastinal bleeding, 2 patients needed mechanical ventilation for more than 1 week after surgery, renal dysfunction occurred in 3 patients. After surgery, 11 patients presented with mild or moderate tricuspid regurgitation before discharge. One patient (3.6%) died in hospital after surgery due to severe infection and multi-organ failure, the other 27 patients were cured and discharged. Patients were followed up for 6 months to 15 years.NYHA class decreased in all patients, and the symptoms of heart failure improved significantly after surgery. No recurrent case was found. Surgery is an effective treatment for isolated right-sided infective endocarditis with congenital heart disease or right heart implants. Good outcomes are observed in these settings.

Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease and Multiorgan Failure after Stem Cell Transplantation: A Multicenter, Randomized, Dose-Finding Trial

Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for > or =14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day +100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day +100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD.