Search

Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute-on-chronic liver failure (ACLF) in cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation through the kynurenine pathway (KP), giving rise to metabolites that contribute to multiorgan/system damage and immunosuppression. In the current study, we aimed to characterize the KP in patients with cirrhosis, in whom this pathway is poorly known. The serum levels of Trp, key KP metabolites (kynurenine and kynurenic and quinolinic acids), and cytokines (SI markers) were measured at enrollment in 40 healthy subjects, 39 patients with compensated cirrhosis, 342 with AD (no ACLF) and 180 with ACLF, and repeated in 258 patients during the 28-day follow-up. Urine KP metabolites were measured in 50 patients with ACLF. Serum KP activity was normal in compensated cirrhosis, increased in AD and further increased in ACLF, in parallel with SI; it was remarkably higher in ACLF with kidney failure than in ACLF without kidney failure in the absence of differences in urine KP activity and fractional excretion of KP metabolites. The short-term course of AD and ACLF (worsening, improvement, stable) correlated closely with follow-up changes in serum KP activity. Among patients with AD at enrollment, those with the highest baseline KP activity developed ACLF during follow-up. Among patients who had ACLF at enrollment, those with immune suppression and the highest KP activity, both at baseline, developed nosocomial infections during follow-up. Finally, higher baseline KP activity independently predicted mortality in patients with AD and ACLF. Conclusion: Features of KP activation appear in patients with AD, culminate in patients with ACLF, and may be involved in the pathogenesis of ACLF, clinical course, and mortality., info:eu-repo/semantics/published

Background & Aims: Antibiotic resistance has been increasingly reported in patients with decompensated cirrhosis in single-center studies. Prospective investigations reporting broad epidemiological data are scarce. We aimed to analyze epidemiological changes in bacterial infections in patients with decompensated cirrhosis. Methods: This was a prospective evaluation of 2 series of patients hospitalized with decompensated cirrhosis. The Canonic series included 1,146 patients from Northern, Southern and Western Europe in 2011. Data on epidemiology, clinical characteristics of bacterial infections, microbiology and empirical antibiotic schedules were assessed. A second series of 883 patients from Eastern, Southern and Western Europe was investigated between 2017–2018. Results: A total of 455 patients developed 520 infections (39.7%) in the first series, with spontaneous bacterial peritonitis, urinary tract infections and pneumonia the most frequent infections. Nosocomial episodes predominated in this series. Nearly half of the infections were culture-positive, of which 29.2% were caused by multidrug-resistant organisms (MDROs). MDR strains were more frequently isolated in Northern and Western Europe. Extended-spectrum beta-lactamase-producing Enterobacteriaceae were the most frequent MDROs isolated in this series, although prevalence and type differed markedly among countries and centers. Antibiotic resistance was associated with poor prognosis and failure of antibiotic strategies, based on third-generation cephalosporins or quinolones. Nosocomial infection (odds ratio [OR] 2.74; p < 0.001), intensive care unit admission (OR 2.09; p = 0.02), and recent hospitalization (OR 1.93; p = 0.04) were identified as independent predictors of MDR infection. The prevalence of MDROs in the second series (392 infections/284 patients) was 23%; 38% in culture-positive infections. A mild increase in the rate of carbapenem-resistant Enterobacteriaceae was observed in this series. Conclusions: MDR bacterial infections constitute a prevalent, growing and complex healthcare problem in patients with decompensated cirrhosis and acute-on-chronic liver failure across Europe, negatively impacting on prognosis. Strategies aimed at preventing the spread of antibiotic resistance in cirrhosis should be urgently evaluated. Lay summary: Infections caused by bacteria resistant to the main antibiotic families are prevalent in patients with cirrhosis. This study demonstrates that this healthcare problem is increasing and extends through all European regions. Infections caused by these difficult to treat bacteria resolve less frequently and often cause the death of the patient. The type of resistant bacteria varies markedly among different hospitals., SCOPUS: ar.j, info:eu-repo/semantics/published

Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation (AD) of cirrhosis, organ failure(s), and high 28-day mortality. We investigated whether assessments of patients at specific time points predicted their need for liver transplantation (LT) or the potential futility of their care. We assessed clinical courses of 388 patients who had ACLF at enrollment, from February through September 2011, or during early (28-day) follow-up of the prospective multicenter European Chronic Liver Failure (CLIF) ACLF in Cirrhosis study. We assessed ACLF grades at different time points to define disease resolution, improvement, worsening, or steady or fluctuating course. ACLF resolved or improved in 49.2%, had a steady or fluctuating course in 30.4%, and worsened in 20.4%. The 28-day transplant-free mortality was low-to-moderate (6%-18%) in patients with nonsevere early course (final no ACLF or ACLF-1) and high-to-very high (42%-92%) in those with severe early course (final ACLF-2 or -3) independently of initial grades. Independent predictors of course severity were CLIF Consortium ACLF score (CLIF-C ACLFs) and presence of liver failure (total bilirubin ≥12 mg/dL) at ACLF diagnosis. Eighty-one percent had their final ACLF grade at 1 week, resulting in accurate prediction of short- (28-day) and mid-term (90-day) mortality by ACLF grade at 3-7 days. Among patients that underwent early LT, 75% survived for at least 1 year. Among patients with ≥4 organ failures, or CLIF-C ACLFs >64 at days 3-7 days, and did not undergo LT, mortality was 100% by 28 days. Conclusions: Assessment of ACLF patients at 3-7 days of the syndrome provides a tool to define the emergency of LT and a rational basis for intensive care discontinuation owing to futility. (Hepatology 2015;62:243-252)

Background: Prostate-specific membrane antigen (PSMA) is a potential therapeutic target in metastatic castration-resistant prostate cancer (mCRPC). We report our initial clinical experience with a beta-emitting 177Lutetium-labeled PSMA-ligand (177Lu-PSMA I&T) for systemic radioligand therapy in[for full text, please go to the a.m. URL], 42. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie

Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation (AD) of cirrhosis, organ failure(s), and high 28-day mortality. We investigated whether assessments of patients at specific time points predicted their need for liver transplantation (LT) or the potential futility of their care. We assessed clinical courses of 388 patients who had ACLF at enrollment, from February through September 2011, or during early (28-day) follow-up of the prospective multicenter European Chronic Liver Failure (CLIF) ACLF in Cirrhosis study. We assessed ACLF grades at different time points to define disease resolution, improvement, worsening, or steady or fluctuating course. ACLF resolved or improved in 49.2%, had a steady or fluctuating course in 30.4%, and worsened in 20.4%. The 28-day transplant-free mortality was low-to-moderate (6%-18%) in patients with nonsevere early course (final no ACLF or ACLF-1) and high-to-very high (42%-92%) in those with severe early course (final ACLF-2 or -3) independently of initial grades. Independent predictors of course severity were CLIF Consortium ACLF score (CLIF-C ACLFs) and presence of liver failure (total bilirubin 12 mg/dL) at ACLF diagnosis. Eighty-one percent had their final ACLF grade at 1 week, resulting in accurate prediction of short- (28-day) and mid-term (90-day) mortality by ACLF grade at 3-7 days. Among patients that underwent early LT, 75% survived for at least 1 year. Among patients with 4 organ failures, or CLIF-C ACLFs >64 at days 3-7 days, and did not undergo LT, mortality was 100% by 28 days. Conclusions: Assessment of ACLF patients at 3-7 days of the syndrome provides a tool to define the emergency of LT and a rational basis for intensive care discontinuation owing to futility. (Hepatology 2015;62:243-252)

The aims of this study were: 1) to perform brain single photon emission computed tomography (SPECT) in anesthetized rats with high resolution cameras (HRC) equipped with parallel hole collimation resolution of about 1 mm (HRC1) and 2 mm (HRC2); 2) to assess when and with which radio-tracer HRC1 SPECT shows advantages over HRC2. Methods. We used two multicrystal HRCs with parallel square hole collimators, whose pure tungsten septa closely fit the crystals, in turn matched with a 4 inch2 position sensitive photomultiplier. HRC1 showed 1.1 mm and HCR2 2.1 mm resolution at collimator contact. HRCs performed 180° semi-circular orbits around the head of rats: image reconstruction occurred with ordered subsets expectation maximization algorithms. Resolution of SPECT was measured with a Derenzo Phantom, resulting 1.4 mm for HRC1 and 2.3 mm for HRC2. Three rats were studied with [99mTc]HMPAO, 3 rats with [99mTc]bombesin (BN) and 48 h later with [123I]ioflupane (DaTSCAN). SPECT studies were reviewed by two experienced operators. Results. Technetium-99m-HMPAO SPECT showed similar images with HRC1 and HRC2. The uptake of BN by amygdale, hippocampus and olfactory tract was detected by both cameras. DaTSCAN SPECT with HRC1 showed detailed image of the tail of the caudatus: this image was not obtained with HRC2. DaTSCAN and BN SPECT showed amygdale with both HRCs. However, only the central nucleus of amygdale takes up DaTSCAN, whereas central, lateral and basolateral amygdaloid nuclei express BN receptors. Only HRC1 SPECT showed amygdale larger with BN than with DaTSCAN. Conclusion. Spatial resolution of 1.4 mm is appropriate to detect selected subcerebral structures.

The aims of this study were: 1) to perform brain single photon emission computed tomography (SPECT) in anesthetized rats with high resolution cameras (HRC) equipped with parallel hole collimation resolution of about 1 mm (HRC1) and 2 mm (HRC2); 2) to assess when and with which radio-tracer HRC1 SPECT shows advantages over HRC2.We used two multicrystal HRCs with parallel square hole collimators, whose pure tungsten septa closely fit the crystals, in turn matched with a 4 inch2 position sensitive photomultiplier. HRC1 showed 1.1 mm and HCR2 2.1 mm resolution at collimator contact. HRCs performed 180 degrees semi-circular orbits around the head of rats: image reconstruction occurred with ordered subsets expectation maximization algorithms. Resolution of SPECT was measured with a Derenzo Phantom, resulting 1.4 mm for HRC1 and 2.3 mm for HRC2. Three rats were studied with [(99m)Tc]HMPAO, 3 rats with [(99m)Tc]bombesin (BN) and 48 h later with [(123)I]ioflupane (DaTSCAN). SPECT studies were reviewed by two experienced operators.Technetium-99m-HMPAO SPECT showed similar images with HRC1 and HRC2. The uptake of BN by amygdale, hippocampus and olfactory tract was detected by both cameras. DaTSCAN SPECT with HRC1 showed detailed image of the tail of the caudatus: this image was not obtained with HRC2. DaTSCAN and BN SPECT showed amygdale with both HRCs. However, only the central nucleus of amygdale takes up DaTSCAN, whereas central, lateral and basolateral amygdaloid nuclei express BN receptors. Only HRC1 SPECT showed amygdale larger with BN than with DaTSCAN.Spatial resolution of 1.4 mm is appropriate to detect selected subcerebral structures.

Aim High resolution scintigraphy ( HRS) can be useful in radio-guided surgery (RGS) and small animal imaging. Devices are generally based on arrays of sensible elements: room temperature semiconductor arrays or scintillating crystals arrays that can be coupled with position sensitive photomultipliers (PSPMT). Here we describe a small Field Of View (FOV) portable cameras based on 1 and 4 inches2 PSPMT. Materials & Methods These cameras show a peculiar crystal- collimator- PSPMT matching that allows the exact positioning of all the scintillating elements inserted in the square holes of a parallel Tungsten collimator. This arrangement ensures no crosstalk of ? rays or light among crystals. The scintillation light emerging from each crystal is revealed by a PSPMT (H8500 or R8520-00-C12). The anodes allow event positioning through the reconstruction of the maximum of the multiplied charge distribution by the centroid algorithm. Data are then selected with an appropriate energy window and transferred to a workstation. We studied the spatial resolution and the homogeneity of two cameras both equipped with 2.4x2.4x5 mm3 CsI (Tl) crystals and a 25 mm long collimator. A thin Plexiglas container filled with 99mTc was used to check homogeneity and pixel identification. A Derenzo phantoms with the diameter of the holes ranging from 2 to 4 mm was positioned at contact, at 1, 2, 3 cm distance from the collimator and filled with 99mTc to assess the camera spatial resolution. Results The energy resolution was 19.1 % FWHM of the 99mTc peak over the whole FOV area. Both cameras showed homogeneity within ± 5% between max and min pixel counts. Pixel identification showed average peak to valley ratio of 20:1. Spatial resolution was 3.3 mm at 1 cm, 4.9 mm at 3 cm, 6.0 mm at 5 cm and 10.9 mm at 10 cm distance. Conclusion Measurement of resolution were performed to foresee the working conditions of HR cameras. Actually when nuclear physicians show to surgeons sentinel nodes or parathyroid glands, they are on contact with the source or at few cm distance. Both detectors were used for RGS and showed hot nodes less than 2 mm large and distant 2.5 mm each other. In several instances a spot detected as single node by Anger camera showed the presence of two near nodes.

Aim: Osteomyelitis is a heavy complication of diabetic foot and its diagnosis requires an integrate approach, both for the clinicians and for the specialist imaging. Leukocytes scan (WBCS) plays a key role in the diagnosis of osteomyelitis. It is performed to reduce the number of amputation, to improve wound healing and to reduce the mortality of patients. The suboptimal spatial resolution of Anger cameras (AC) represents a limitation to achieve these goals. Some studies suggested the role of High Resolution Scintigraphy (HRS) in the diagnosis, radioguided surgery and biopsy of different diseases. Aim of present study is to verify if WBCS is able to improve the diagnosis of osteomyelitis and to help surgery with the use of an hand held High Resolution Detector (HRD),.Materials and Methods: 10 patients, mean age 64 yrs, with forefoot ulcers, were enrolled. In all patients planar X-ray, MRI and conventional 99mTc-HMPAO-WBCs were performed. 24h after administration of radiolabelled WBC, each patient was studied by HRS with HRD. The hand held HRD showed four inch2 FOV, 2 mm spatial resolution, 18% energy resolution. The patients underwent surgery or bone biopsy using HRS.Results: Three patients showed negative scan with both devices. They showed an ulcer without infection, debridement of lesion was sufficient to obtain healing (Table). Seven patients showed positive scan at AC without bone infection. HRD showed hot spots of radioactivity in the same patients. In four of them, the hot spot was bar-shaped. This bar-shaped radioactivity was considered as sign of osteomyelitis. One patient, with positive WBCs, refused surgery. Two patients, with positive scan and no sign of osteomyelitis at AC as well as at HRD underwent complete curettage of purulent inflammation using HRD during the surgical treatment. Two of the 4 patients showing infection at HRD were treated by amputation of the two distal phalanges of the toe because of osteomyelitis. The other patients underwent to radio-guided bone biopsy. Bone infection was confirmed by culture exam.Conclusions: HRD seems to be able to guide surgical treatment opening a new way in the therapy of infected foot. It is possible to assess if surgical removal of purulent inflammation is complete and to precisely guide biopsy or removal of the bone with osteomyelitis.

Cutaneous melanoma is often characterized by the presence of tumor-infiltrating lymphocytes (TILs). The degree of such infiltration and cell activation are considered significant prognostic factors reflecting the host's immune response to the tumor; thus, patients with peritumoral infiltration may have a better prognosis and may also achieve a better response to interleukin-2 (IL2) immunotherapy. There is evidence that the expression of cluster designation (CD) 25 antigen (IL2 receptor [IL2R]) is a good marker of activity of T lymphocytes against melanoma cells. The aim of this study was to evaluate in vivo the binding of 99mTc-IL2 to lymphocytes infiltrating cutaneous melanoma and to determine whether such uptake correlates with immunologic and histologic data, thus providing useful prognostic information for IL2 therapy in patients with advanced disease.Thirty patients with cutaneous lesions suspected of being melanoma were studied. Planar gamma-camera images over known tumor sites were acquired 1 h after the injection of 111-185 MBq of 99mTc-IL2. Tumor uptake of 99mTc-IL2 was measured as a target-to-background (T/B) radioactivity ratio. All patients underwent surgery, and histologic evaluation of the resected lesion was performed. The percentage of different peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD16, CD25) and the percentage of IL2R-positive tumor cells on histologic sections were also measured.At final histology, 21 lesions were found to be melanoma and 9 were classified as benign. In 15 of 21 (71%) melanomas and 2 of 9 (22%) benign cutaneous lesions, we found uptake of 99mTc-IL2. The calculated T/B ratios correlated significantly with the number of IL2R-positive TILs.99mTc-IL2 scintigraphy provides a means of in vivo measurement of the extent of tumor infiltration of IL2R-positive cells, thereby providing valuable prognostic information for selection of patients who may benefit from IL2 immunotherapy.

Chronic inflammatory diseases usually lead to fibrosis of the target organ and consequent hypo function. They are often relapsing, invalidating and require life-long treatment. In this class of patients it is very important to try and achieve specific immune suppression to extinguish the immune process with the aim of preventing the disease, preventing or delaying complications and avoiding disease relapse, often requiring surgical intervention. It is important that, while attempting to improve the quality of life of these patients by means of anti-inflammatory drugs, side effects are reduced to a minimum via the use of specific immune therapies that block as selectively as possible the pathologic mechanism responsible for the disease. New therapeutic options are being developed for specific targeted therapies. Several trials are being performed to assess the efficacy and safety of this approach. All of them, however, rely on the clinical assessment of the patients to evaluate the effect of treatment. It would be important to use an objective and reliable method to highlight directly the immune process underlying the individual disease. This manuscript reviews the radiopharmaceuticals available or recently developed for imaging chronic inflammatory diseases and their use for therapy decision making and follow-up.