Hemodynamic Evaluation of Nonselective \u3b2-Blockers in Patients with Cirrhosis and Refractory Ascites

BACKGROUND:Nonselective \u3b2-blockers (NSBB) have been associated with increased incidence of paracentesis-induced circulatory dysfunction (PICD) and reduced survival in patients with cirrhosis and refractory ascites. AIM:To prospectively evaluate a hemodynamic response to NSBB in cirrhotics listed for liver transplantation with refractory ascites undergoing large volume paracentesis (LVP). METHODS:Patients with cirrhosis and refractory ascites, with an indication to start NSBB in primary prophylaxis for variceal bleeding, were enrolled. During two consecutive LVP, while being, respectively, off and on NSBB, cardiac output (CO), systemic vascular resistances (SVR), peripheral vascular resistances (PVR), and plasma renin activity (PRA) were noninvasively assessed. RESULTS:Seventeen patients were enrolled, and 10 completed the study. Before NSBB introduction, SVR (1896 to 1348\u2009dyn\ub7s\ub7cm-5; p = 0.028) and PVR (47 to 30\u2009mmHg\ub7min\ub7dl\ub7ml-1; p = 0.04) significantly decreased after LVP, while CO showed an increasing trend (3.9 to 4.5\u2009l/m; p = 0.06). After NSBB introduction, LVP was not associated with a significant increase in CO (3.4 to 3.8\u2009l/m; p = 0.13) nor with a significant decrease in SVR (2002 versus 1798\u2009dyn\ub7s\ub7cm-5; p = 0.1). Incidence of PICD was not increased after NSBB introduction. CONCLUSION:The negative inotropic effect of NSBB was counterbalanced by a smaller decrease of vascular resistances after LVP, probably due to splanchnic \u3b22-blockade. This pilot study showed that NSBB introduction may be void of detrimental hemodynamic effects after LVP in cirrhotics with refractory ascites

Improved quality of life in patients with refractory or recidivant ascites after insertion of transjugular intrahepatic portosystemic shunts

Background. We have recently shown that the transjugular intrahepatic portosystemic shunt (TIPS) is more effective than paracentesis in the treatment of cirrhotic patients with severe ascites and can prolong survival in selected patients. Although an improved quality of life (QOL) has been suggested in these patients after the TIPS procedure, so far there are no data available to substantiate this assumption. Therefore, the aim of this study was to determine the effect of TIPS on the QOL in cirrhotic patients with refractory or recidivant ascites. Methods: 21 cirrhotic patients who underwent TIPS for refractory or recidivant ascites were investigated. All patients were pretreated with repeated paracentesis for at least 1 year. Before the procedure and at 3 and 6 months during follow-up, the patients themselves rated QOL, fatigue and physical performance on a visual analogue scale (range 0-100). Furthermore, QOL was determined by the QOL index (range 0-10) according to Spitzer. Results: Patients' rating of the QOL on the visual analogue scale significantly increased from 35 +/- 25 (baseline) to 64 +/- 28 (3 months), and 66 +/- 24 (6 months; p = 0.02). Similarly, the QOL index significantly increased from 6.9 +/- 2.0 (baseline) to 8.3 +/- 2.1 (3 months), and 8.6 +/- 1.7 (6 months; p < 0.001). The increase of QOL was more pronounced in patients with complete response to TIPS. Conclusions: We demonstrate that TIPS for refractory or recidivant ascites improves the QOL in patients with cirrhosis. Our data indicates that this improvement is dependent on the response to therapy. Copyright (C) 2002 S. Karger AG, Basel

A double masked randomised 4-week, placebo-controlled study in the USA, Thailand and Taiwan to compare the efficacy of oral valganciclovir and topical 2% ganciclovir in the treatment of cytomegalovirus anterior uveitis: study protocol.

IntroductionCytomegalovirus (CMV) anterior uveitis is a recognised cause of anterior uveitis in immunocompetent patients and is preventable cause of vision loss. Ocular sequelae include corneal endothelial damage which can cause corneal oedema and failure, as well as glaucoma. Recurrences of inflammation are common and therefore patients are often exposed to long-term therapy. Oral therapy is available in the form of valganciclovir, although with the caveat of systemic side effects such as bone marrow suppression and renal failure necessitating regular interval laboratory monitoring. Recent reports have demonstrated that topical 2% ganciclovir solution may offer promising treatment outcomes in patients with CMV anterior uveitis with superior safety, cost-effectiveness and convenience profiles. An investigation into the relative equipoise of these therapies is warranted for these reasons.Methods and analysisThe Systemic and Topical Control of Cytomegalovirus Anterior uveitis: Treatment Outcomes (STACCATO) trial is designed as a multicentre, block randomised by site, double-masked, placebo-controlled trial comparing the efficacy of oral valganciclovir, 2% topical ganciclovir and placebo in treating PCR-proven CMV anterior uveitis. Participant clinical evaluation will occur at three study time points by a masked study ophthalmologist over a 28-day period to assess resolution of ocular inflammation (secondary outcome). A control group will provide additional information about the possible impact that the infected host's immune response may play in controlling local viral replication. The primary analysis is an analysis of covariance (three arms) correcting for baseline to compare quantitative CMV viral load in the anterior chamber (AC) aqueous fluid before and 7 days after treatment.Ethics and disseminationThe University of California San Francisco Committee on Human Research and the Khon Kaen University Institutional Review Board have given ethical approval. The results of this trial will be presented at local and international meetings and submitted for peer-reviewed journals for publication.Trial registration numberNCT03576898

Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for Peritoneal Metastasis.

Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM. IP delivery of CAR-T cells has shown demonstrable suppression of tumors expressing carcinoembryonic antigen. This response was enhanced when IP injected CAR-T cells were combined with anti-PD-L1 or anti-Gr1. Similarly, CAR-T cells against folate receptor α expressing tumors improved T-cell tumor localization and survival when combined with CD137 co-stimulatory signaling. Moreover, IP immunotherapy with catumaxomab, a trifunctional antibody approved in Europe, targets epithelial cell adhesion molecule (EpCAM) and has shown considerable promise with control of malignant ascites. Herein, we discuss immunologic approaches under investigation for treatment of PM

The use of non-selective beta-blockers in patients with cirrhosis: more doubts than certainties

In conclusion, prospective RCT would be needed on the use of NSBBs in decompensated cirrhotic patients with ascites however these trials are difficult to organize and will need a large sample size. A case control study could be useful if the two groups were patients matched for MELD, MELD Na, creatinine, mean arterial pressure, with the same type of ascites (refractory, recurrent, severe) taking or not taking NSBBs. The better and more relevant end pointshould probably be survival. In the meanwhile, the Baveno recommendations can be utilized in clinical practice to remind that severe hypotension is a well-known contraindication for NSBBs which may suggest dose reduction or even therapy discontinuation. Last but not least, NSBBs may have several beneficial effects in patients with cirrhosis beyond the reduction in portal hypertension. They reduce markers of intestinal permeability, bacterial translocation and systemic inflammation, and also the risk of SBP (15,16). The risk to enlarge the indication to stop NSBBs in cirrhotic patients without a real evidence could be as to “throw the baby out with the bath water

A case of abdominal sarcoidosis in a patient with acute myeloid leukemia.

The allogeneic bone marrow transplantation usually preceded by induction chemotherapy, in fit patients, represents the gold standard in the acute myeloid leukaemia. In the last years, many trials have been set up with the view of improving the number of remissions during the induction by adding new drugs. Several early or late side effects have been described in the literature. We herein present a patient with acute myeloid leukaemia patient who, after chemotherapy, developed ascites that turned out to be abdominal sarcoidosis

Metagenomic deep sequencing of aqueous fluid detects intraocular lymphomas.

IntroductionCurrently, the detection of pathogens or mutations associated with intraocular lymphomas heavily relies on prespecified, directed PCRs. With metagenomic deep sequencing (MDS), an unbiased high-throughput sequencing approach, all pathogens as well as all mutations present in the host's genome can be detected in the same small amount of ocular fluid.MethodsIn this cross-sectional case series, aqueous fluid samples from two patients were submitted to MDS to identify pathogens as well as common and rare cancer mutations.ResultsMDS of aqueous fluid from the first patient with vitreal lymphoma revealed the presence of both Epstein-Barr virus (HHV-4/EBV) and human herpes virus 8 (HHV-8) RNA. Aqueous fluid from the second patient with intraocular B-cell lymphoma demonstrated a less common mutation in the MYD88 gene associated with B-cell lymphoma.ConclusionMDS detects pathogens that, in some instances, may drive the development of intraocular lymphomas. Moreover, MDS is able to identify both common and rare mutations associated with lymphomas

Awareness and knowledge of intra-abdominal hypertension and abdominal compartment syndrome: results of an international survey

Background: Surveys have demonstrated a lack of physician awareness of intra-abdominal hypertension and abdominal compartment syndrome (IAH/ACS) and wide variations in the management of these conditions, with many intensive care units (ICUs) reporting that they do not measure intra-abdominal pressure (IAP). We sought to determine the association between publication of the 2006/2007 World Society of the Abdominal Compartment Syndrome (WSACS) Consensus Definitions and Guidelines and IAH/ACS clinical awareness and management. Methods: The WSACS Executive Committee created an interactive online survey with 53 questions, accessible from November 2006 until December 2008. The survey was endorsed by the WSACS, the European Society of Intensive Care Medicine (ESICM) and the Society of Critical Care Medicine (SCCM). A link to the survey was emailed to all members of the supporting societies. Participants of the 3rd World Congress on Abdominal Compartment Syndrome meeting (March 2007, Antwerp, Belgium) were also asked to complete the questionnaire. No reminders were sent. Based on 13 knowledge questions, an overall score was calculated (expressed as percentage). Results: A total of 2,244 of the approximately 10,000 clinicians who were sent the survey responded (response rate: 22.4%). Most of the 2,244 respondents (79.2%) completing the survey were physicians or physicians in training and the majority were residing in North America (53.0%). The majority of responders (85%) were familiar with IAP/IAH/ACS, but only 28% were aware of the WSACS consensus definitions for IAH/ACS. Three quarters of respondents considered the cut-off for IAH to be at least 15 mm Hg, and nearly two thirds believed the cut-off for ACS was higher than the currently suggested consensus definition (20 mm Hg). In 67.8% of respondents, organ dysfunction was only considered a problem with IAP of 20 mm Hg or higher. IAP was measured most frequently via the bladder (91.9%), but the majority reported that they instilled volumes well above the current guidelines. Surgical decompression was frequently used to treat IAH/ACS, whereas medical management was only attempted by about half of the respondents. Decisions to decompress the abdomen were predominantly based on the severity of IAP elevation and presence of organ dysfunction (74.4%). Overall knowledge scores were low (43 +/- 15%); respondents who were aware of the WSACS had a better score compared to those who were not (49.6% vs 38.6%, P < 0.001). Conclusions: This survey showed that although most responding clinicians claim to be familiar with IAH and ACS, knowledge of published consensus definitions, measurement techniques, and clinical management is inadequate

Myelomatous Pleural Effusion

ABSTRACT Multiple myeloma (MM) is a common hematologic malignancy. Pleural effusion is a rare presenting feature of multiple myeloma which carries a poor prognosis. Few cases of multiple myeloma with pleural involvement have been reported in the medical literature. We report a patient with MM diagnosed by cytologic examination of pleural fluid. Our patient was a 64- year old man with multiple myeloma who was receiving chemotherapy. He had developed dry coughs and exertional dyspnea about a month prior to the admission. Radiographic examination showed left pleural effusion with mediastinal shift to the opposite side. Diagnostic thoracentesis of pleural fluid was performed for the patient. Pathologic examination of pleural fluid showed plasmocytes and plasmablast type mononuclear cells with atypical nuclei, consistent with the diagnosis of pleural effusion due to multiple myeloma. In view of multiple etiologies of pleural effusion in malignant diseases, rare etiologies should also be considered in order to treat the effusion appropriately. (Tanaffos 2007; 6(2): 68-72) Key words: Multiple myeloma, Pleural effusion, Plasmablas

Usefulness of bioelectrical impedance analysis for monitoring patients with refractory ascites

Background: bioelectrical impedance analysis is a technique for the determination of the hydropic component. The hydropic component, determined by blood volume, could be a reflection of the hemodynamic situation. This study aimed to evaluate the usefulness of peripheral bioelectrical impedance analysis (BIA) for the prediction of hemodynamic changes in large-volume paracentesis and prognosis. Methods: this was a proof-of-concept prospective study of 14 patients with liver cirrhosis and refractory ascites. Peripheral bioimpedance was measured three times using a portable device, IVOL®, before and after large-volume paracentesis, at different frequencies (5, 10, 20, 50, 100 and 200 kHz). Consequently, resistance, reactance and phase angle were obtained, both pre- and post-paracentesis (the difference between them was defined as Δ). Results: the mean age of patients was 62.2 ± 9.6 years, the Child-Pugh was 8.4 ± 1.3 and the MELD score was 15.2 ± 3.9. A direct correlation between the extraction of ascitic fluid and Δresistance (10 kHz [r = 0.722; n = 12; p = 0.008], 20 kHz [r = 0.658; n = 12; p = 0.020] and 50 kHz [r = 0.519; n = 14; p = 0.057]) was observed. The presence of edema was related to lower values of both pre-paracentesis resistance (10 Hz [23.9 ± 8 vs 32.2 ± 4; p = 0.043]) and phase angle (5 kHz [-1.9 ± 2.8 vs 5.9 ± 7.3; p = 0.032]). Pre-paracentesis phase angle was directly correlated with the decline in blood pressure after paracentesis at lower frequencies (5 kHz [r = 0.694; n = 13; p = 0.008] and 10 kHz [r = 0.661; n = 13; p = 0.014]). Lower frequencies of Δphase-angle impacted on patient prognosis (5 kHz [-8.6 ± 5 vs -2.5 ± 2.7; p = 0.021]), patients with Δphase-angle 5 kHz > -4 had a higher rate of mortality (83.3% [5/6] vs 0% [0/6]; logRank 7.306, p = 0.007). Δresistance values were associated with overt HE at six months (10 kHz [4.9 ± 2.5 vs -0.4 ± 4.7; p = 0.046]). Conclusions: in conclusion, a significant correlation between peripheral impedance and hemodynamic changes was found. Impedance was also significantly related to prognosis and overt hepatic encephalopathy