Coping with modesty during radiotherapy for breast cancer: a multicentric study.

PURPOSE: Breast cancer is the most frequently diagnosed tumour, representing nearly 30% of all new cases in women. Radiotherapy (RT) plays a crucial role in the management of breast cancer. The objective of this study is to assess modesty in patients undergoing RT for breast cancer and take their suggestions and ideas into consideration to enhance the quality of treatment in this regard. METHODS: The study enrolled 555 breast cancer patients undergoing adjuvant RT in three Italian centres. Patients completed a self-test questionnaire assessing their comfort level concerning modesty during therapy and their relationship with strangers and healthcare professionals. The impact of religious views and potential changes in sexuality were also examined. RESULTS: Results showed that modesty was a common concern across the overall cohort of patients, with discomfort in being undressed during RT correlating with discomfort experienced in other daily life situations. Most patients felt more at ease with same sex healthcare workers. Age was also a major factor with younger patients generally feeling more comfortable with healthcare workers of the same age group. Interestingly, the surgical technique used (mastectomy vs. quadrantectomy) did not significantly influence modesty perceptions. Patients provided valuable suggestions to improve privacy and modesty during RT. CONCLUSION: This study demonstrates that modesty is an important issue for women undergoing RT, which can be influenced by personal characteristics and hospital-related factors. A reflection about the need to address modesty concerns and to incorporate dedicated interventions for protecting patients' physical and emotional well-being is warranted. Initiatives to improve communication, involvement, and body image support should also be integrated into the care path of patients to better their overall therapeutic experience. This study paves the way for broader research and interventions in daily cancer care.

Loss of interleukin 1 signaling causes impairment of microglia- mediated synapse elimination and autistic-like behaviour in mice.

In the last years, the hypothesis that elevated levels of proinflammatory cytokines contribute to the pathogenesis of neurodevelopmental diseases has gained popularity. IL-1 is one of the main cytokines found to be elevated in Autism spectrum disorder (ASD), a complex neurodevelopmental condition characterized by defects in social communication and cognitive impairments. In this study, we demonstrate that mice lacking IL-1 signaling display autistic-like defects associated with an excessive number of synapses. We also show that microglia lacking IL-1 signaling at early neurodevelopmental stages are unable to properly perform the process of synapse engulfment and display excessive activation of mammalian target of rapamycin (mTOR) signaling. Notably, even the acute inhibition of IL-1R1 by IL-1Ra is sufficient to enhance mTOR signaling and reduce synaptosome phagocytosis in WT microglia. Finally, we demonstrate that rapamycin treatment rescues the defects in IL-1R deficient mice. These data unveil an exclusive role of microglial IL-1 in synapse refinement via mTOR signaling and indicate a novel mechanism possibly involved in neurodevelopmental disorders associated with defects in the IL-1 pathway.

Urinary L-FABP is a promising prognostic biomarker of ACLF and mortality in patients with decompensated cirrhosis.

BACKGROUND & AIMS: Decompensated cirrhosis (DC) is associated with high mortality, mainly owing to the development of acute-on-chronic liver failure (ACLF). Identifying the patients with DC who are at high risk of mortality and ACLF development is an unmet clinical need. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemic inflammation. Herein, we aimed to assess the prognostic value of L-FABP in patients with DC. METHODS: A prospective series of 444 patients hospitalized for DC was divided into 2 cohorts: study cohort (305 patients) and validation cohort (139 patients). L-FABP was measured in urine and plasma samples collected at admission. Neutrophil gelatinase-associated lipocalin (NGAL) was also measured in urine samples for comparison. RESULTS: Urine but not plasma L-FABP correlated with 3-month survival on univariate analysis. On multivariate analysis, urine L-FABP and model for end-stage liver disease (MELD)-Na were the only independent predictors of prognosis. Urine L-FABP levels were higher in patients with ACLF than in those without and also predicted the development of ACLF, together with MELD-Na, during follow-up. In patients with ACLF, urine L-FABP correlated with liver, coagulation, and circulatory failure. Urine L-FABP levels were also increased in patients with acute kidney injury, particularly in those with acute tubular necrosis. The ability of urinary L-FABP to predict survival and ACLF development was confirmed in the validation cohort. Urine NGAL predicted outcome on univariate but not multivariate analysis. CONCLUSIONS: Urinary L-FABP levels are independently associated with the 3-month clinical course in patients with DC, in terms of mortality and ACLF development. Urinary L-FABP is a promising prognostic biomarker for patients with DC. LAY SUMMARY: Increased levels of liver fatty acid-binding protein (L-FABP), a protein related to lipid metabolism, have been associated with liver-related diseases. The present study analyzed urinary L-FABP levels in 2 independent groups of patients with decompensated cirrhosis and showed that higher urinary L-FABP levels correlated with increased mortality and risk of acute-on-chronic liver failure development. Therefore, urinary L-FABP levels could be useful as a new tool to predict complications in patients with decompensated cirrhosis.

Voice quality after transoral CO2 laser microsurgery (TOLMS): systematic review of literature.

PURPOSE: Transoral laser microsurgery (TOLMS) with carbon dioxide is a safe approach for laryngeal carcinoma. In literature there are three main methods for evaluating speech outcomes: acoustic and aerodynamics analysis, perceptual evaluation and patient-reported outcomes (PROs). The aim of this study was to systematically review the literature about the voice quality outcomes of TOLMS according to type of cordectomy. METHODS: A systematic literature review was performed and all the results until December 2021 were extrapolated. We evaluated the acoustic and aerodynamics parameters (fundamental frequency, harmonics to noise ratio, jitter, shimmer and maximum phonation time), perceptual data (GRBAS scale) and patient-related outcomes (VHI scale). RESULTS: 24 studies met the inclusion criteria for a total number of 1207 patients enrolled. The number for each type of cordectomy are: 287 type I (23.78%), 311 type II (25.78%), 328 type III (27.14%), 129 type 4 (10.69%) and 152 type V (12.60%). Patients are grouped according to the type of cordectomy in: limited cordectomy (type I and II) and extended cordectomy (types III-IV-V). The difference between two groups is statistically significative in terms of acoustic analysis, perceptual data and patient-related outcomes (p < 0.05). CONCLUSIONS: Patients who underwent type I or II cordectomy have significantly better quality of voice in terms of VHI, perceptual voice quality evaluations and acoustic parameters compared to type III, IV and V cordectomies. The effect of TOLMS on the voice should depend from the extent of the resection and in particular from the scar of the vocal muscle.

On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites.

BACKGROUND & AIMS: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. METHODS: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. RESULTS: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5-4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. CONCLUSION: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin - 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. LAY SUMMARY: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.

Extracellular Vesicles from Mesenchymal Stem Cells Exert Pleiotropic Effects on Amyloid-ß, Inflammation, and Regeneration: A Spark of Hope for Alzheimer's Disease from Tiny Structures?

No cure yet exists for devastating Alzheimer's disease (AD), despite many years and humongous efforts to find efficacious pharmacological treatments. So far, neither designing drugs to disaggregate amyloid plaques nor tackling solely inflammation turned out to be decisive. Mesenchymal stem cells (MSCs) and, in particular, extracellular vesicles (EVs) originating from them could be proposed as an alternative, strategic approach to attack the pathology. Indeed, MSC-EVs-owing to their ability to deliver lipids/proteins/enzymes/microRNAs endowed with anti-inflammatory, amyloid-ß degrading, and neurotrophic activities-may be exploited as therapeutic tools to restore synaptic function, prevent neuronal death, and slow down memory impairment in AD. Herein the results presented in the most recently published studies on this topic are critically evaluated, providing a strong rationale for possible employment of MSC-EVs in AD. Also see the video abstract here https://youtu.be/tBtDbnlRUhg.

Neutrophil Gelatinase-Associated Lipocalin for Assessment of Acute Kidney Injury in Cirrhosis: A Prospective Study.

Kidney biomarkers appear to be useful in differential diagnosis between acute tubular necrosis (ATN) and other types of acute kidney injury (AKI) in cirrhosis, particularly hepatorenal syndrome (HRS-AKI). Distinction is important because treatment is different. However, kidney biomarkers are still not used in clinical practice. The aim of the current study was to investigate the accuracy of several biomarkers in differential diagnosis of AKI and in predicting kidney outcome and patient survival. This was a prospective study of 320 consecutive cases of AKI in patients hospitalized for decompensated cirrhosis. Evaluation of AKI was made with a diagnostic algorithm that included identification and removal/treatment of precipitating factors and albumin administration (1 g/kg for 2 days) to patients with AKI stage 1B or greater. Urinary neutrophil gelatinase-associated lipocalin (NGAL), monomeric NGAL (mNGAL), interleukin-18, and standard biomarkers were measured at diagnosis and on days 3, 7, and 14. Of the 320 cases, 153 were hypovolemia-induced AKI (48%), 93 were HRS-AKI (29%), 39 were ATN (12%), and 35 were due to miscellaneous causes (11%). Among all biomarkers, urinary NGAL measured at day 3 had the greatest accuracy for differential diagnosis between ATN and other types of AKI (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.78-0.95). The cutoff with the best predictive accuracy for ATN diagnosis was 220 µg/g creatinine. Progression of AKI during hospitalization was associated with persistently high NGAL levels, and NGAL was an independent predictive factor of AKI progression. Likewise, NGAL was also an independent predictive factor of 28-day mortality together with Model for End-Stage Liver Disease score. Conclusion: These results support the use of NGAL in clinical practice within the context of a diagnostic algorithm for differential diagnosis of AKI and outcome prediction in cirrhosis.

Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial.

BACKGROUND: Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. METHODS: We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials.gov, number NCT01288794. FINDINGS: From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40-0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events. INTERPRETATION: In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. FUNDING: Italian Medicine Agency.

Validation of a Staging System for Acute Kidney Injury in Patients With Cirrhosis and Association With Acute-on-Chronic Liver Failure.

BACKGROUND & AIMS: In patients with cirrhosis of the liver, acute kidney injury (AKI) is classified into 3 stages. Recent studies indicate that there are 2 subgroups of stage 1 disease, associated with different outcomes and serum levels of creatinine (SCr): stage 1A (SCr <1.5 mg/dL) and stage 1B (SCr ≥1.5 mg/dL). We performed a prospective study to validate, in a large series of patients with cirrhosis, the association between this new description and patient outcomes, and assess the relationship between AKI stage and the presence of acute-on-chronic liver failure. METHODS: We collected data from 547 consecutive patients admitted for cirrhosis with acute decompensation to 2 tertiary hospitals (Italy and Spain), from February 2011 through June 2015. A total of 290 patients had AKI (53%; 197 had stage 1 disease); AKI stages were determined based on levels of SCr at diagnosis. Patients were followed up until death, liver transplantation, or for 90 days. The primary outcome was 90-day survival; secondary outcomes were progression and resolution of AKI and association with acute-on-chronic liver failure. RESULTS: Based on level of sCr at diagnosis, 58 patients had stage 1A disease and 139 had stage 1B disease. Of patients with stage 1A disease, 82% survived for 90 days; of patients with stage 1B disease, 55% survived for 90 days (P = .001). Hepatorenal syndrome and acute tubular necrosis were the most common causes of stage 1B AKI, and hypovolemia was the most common cause of stage 1A AKI. AKI progressed in a higher proportion of patients with 1B than 1A AKI (31% vs 15%; P = .017) and resolved in a higher proportion of patients with 1A disease (90% vs 52% of patients with stage 1B; P < .001). Stage 1B disease, but not 1A, was an independent predictor of AKI progression and mortality. ACLF developed in a significantly greater proportion of patients with stage 1B disease (76%) than stage 1A disease (22%; P < .001), which could account for the poor outcomes of patients with stage 1B disease. CONCLUSIONS: In a large group of patients with decompensated cirrhosis, we validated the association between AKI stages IA and IB (based on level of sCR) with survival times and AKI progression. We also associated these subgroups of AKI with development of acute-on-chronic liver failure. These findings are important for management of patients with decompensated cirrhosis.

Effects of alfapump™ system on kidney and circulatory function in patients with cirrhosis and refractory ascites.

The alfapump system has been proposed as a new treatment for the management of refractory ascites. The system removes ascites from the peritoneal cavity to urinary bladder, producing a continuous low-volume paracentesis. The aim of the study is to investigate the effects of treatment with the alfapump™ system on kidney and circulatory function in patients with cirrhosis and refractory ascites. This was a prospective study including 10 patients with cirrhosis and refractory ascites. Primary outcomes were changes in glomerular filtration rate (GFR), as assessed by isotopic techniques, and changes in circulatory function assessed by arterial pressure, cardiac output, and activity of vasoconstrictor systems. Secondary outcomes were the need for large-volume paracentesis and adverse events. Follow-up was 1 year. GFR decreased significantly from 67 mL/minute/1.73 m2 (41-90 mL/minute/1.73 m2 ) at baseline to 45 mL/minute/1.73 m2 (36-74 mL/minute/1.73 m2 ) at month 6 (P = 0.04). Mean arterial pressure and cardiac output did not change significantly; however, there was a marked increase in plasma renin activity and norepinephrine concentration (median percent increase with respect to baseline +191% and 59%, respectively). There were 68 episodes of complications of cirrhosis in 8 patients during follow-up, the most frequent being acute kidney injury. In conclusion, treatment with alfapump™ system was associated with marked activation of endogenous vasoconstrictor systems and impairment of kidney function. The chronological relationship observed between kidney impairment and vasoconstrictor systems activation after device insertion suggests a cause-effect relationship, raising the possibility that treatment with alfapump impairs effective arterial blood volume mimicking a postparacentesis circulatory dysfunction syndrome. In this context, the potential role of albumin in counteracting these effects should be investigated in future studies. Liver Transplantation 23 583-593 2017 AASLD.

Lateral approach for sinus floor elevation: large versus small bone window - a split-mouth randomized clinical trial.

OBJECTIVES: To test whether a reduction of bone window dimension, in a split-mouth randomized study design, focused on lateral sinus floor elevations, can achieve better results than a wider window in terms of augmented bone height and a reduction of patient discomfort and surgical complications. MATERIALS AND METHODS: Of the sixteen subjects enrolled in the study, each underwent a bilateral sinus lift procedure based on two different access flaps to maxillary sinus. Test side: small access window (6 × 6 mm) + bone filling using a special device. Control side: large access window (10 × 8 mm) + manual bone filling. Alveolar bone height and width were measured at pre-op and 6-month post-op CT scans; repeatable measurements were obtained using radiographic stents. Surgical intervention duration was also recorded. Patients' evaluation of surgical discomfort was assessed using a VAS diagram at 7-day, 14-day and 30-day follow-up. RESULTS: A significant bone augmentation in height and width of alveolar crest was obtained in both test (8.71 ± 1.11 mm, 4.70 ± 0.58 mm) and control (8.5 ± 2.02 mm, 4.68 ± 0.70 mm) sides, although no significant differences were found between the two groups. Neither any significant differences emerge in data concerning the duration of the intervention (Test 42.62 ± 6.67 min, Control 41.68 ± 8.34 min). Patients' opinion relating to surgical discomfort showed a preference for test procedure at 7-day, 14-day and 30-day follow-up. CONCLUSIONS: A reduction of window dimensions did not affect the safety of the surgical procedure. The two testing techniques showed no statistically significant differences in surgical intervention duration. Patients' opinion at 7-day and 14-day post-op showed a preference for test procedure.

Severe acute kidney injury associated with non-steroidal anti-inflammatory drugs in cirrhosis: A case-control study.

BACKGROUND & AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) may cause impairment of kidney function in patients with cirrhosis. Investigational studies demonstrated reversibility of kidney dysfunction after drug withdrawal, but information based on clinical practice is lacking. The aim of the study was to investigate the characteristics and outcome of Acute Kidney Injury (AKI) developing in patients with cirrhosis treated with NSAIDs. METHODS: Prospective cohort study in a tertiary referral center of all patients with NSAIDs-associated AKI seen from 2002 to 2014. For comparison, three control groups of patients with hypovolemic-induced AKI, type-1 HRS and ATN, respectively, were also evaluated. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) was measured in a subset of patients. RESULTS: Thirty patients with cirrhosis and NSAIDs-associated AKI were identified. In 19 patients (63%) AKI was transient and kidney function rapidly recovered (4±3 days) after NSAIDs withdrawal. In the remaining 11 patients (37%) AKI was more severe and persisted during hospitalization despite drug withdrawal. Patients with persistent AKI had remarkably higher uNGAL levels compared with those of patients with transient AKI (953±1,198 vs. 83±79 µg/g of creatinine, respectively, p=0.008). Moreover, seven of the 11 patients with persistent AKI (64%) died within three months compared with only one of the 19 (5%) patients with transient AKI (p=0.001). Mortality of persistent AKI was similar in NSAIDs patients compared to control groups. The only independent predictive factor of three-month mortality was persistent AKI. CONCLUSIONS: Patients with cirrhosis treated with NSAIDs may develop severe AKI which may be irreversible and associated with poor short-term outcome.

Treatment of type 2 hepatorenal syndrome in patients awaiting transplantation: Effects on kidney function and transplantation outcomes.

There is little information on the effects of treatment with vasoconstrictors plus albumin in patients with type 2 hepatorenal syndrome (HRS), particularly those awaiting liver transplantation (LT). This study reports the effects of treatment of type 2 HRS in patients on the waiting list for LT. We included 56 patients with type 2 HRS who were awaiting LT. Out of these 56 patients, 31 were treated with terlipressin and albumin. Nineteen (61%) of these 31 patients had response to therapy, and 11 of them relapsed after treatment withdrawal. There were no differences in mortality on the waiting list between responders and nonresponders. Among the 46 (82%) patients who underwent transplantation, 15 underwent transplantation with reversal of type 2 HRS, whereas the remaining 31 underwent transplantation with type 2 HRS. There were no significant differences in serum creatinine or estimated glomerular filtration rate between the 2 cohorts of patients at 3, 6, and 12 months after transplantation. There were no significant differences regarding development of acute kidney injury, need for renal replacement therapy, frequency of chronic kidney disease 1 year after transplant, length of hospitalization, and survival. In conclusion, treatment of patients with type 2 HRS with terlipressin and albumin does not appear to have beneficial effects either in pretransplantation or in posttransplantation outcomes.

Urinary neutrophil gelatinase-associated lipocalin predicts kidney outcome and death in patients with cirrhosis and bacterial infections.

BACKGROUND & AIMS: Infections in cirrhosis are frequently complicated by kidney dysfunction that entails a poor prognosis. Urinary biomarkers may be of potential clinical usefulness in this setting. We aimed at assessing the value of urinary neutrophil gelatinase-associated lipocalin (uNGAL), a biomarker overexpressed in kidney tubules during kidney injury, in predicting clinical outcomes in cirrhosis with infections. METHODS: One-hundred and thirty-two consecutive patients hospitalized with infections were evaluated prospectively. Acute kidney injury (AKI) was defined according to AKIN criteria. uNGAL was measured at infection diagnosis and at days 3 and 7 (ELISA, Bioporto, DK). RESULTS: Patients with AKI (n=65) had significantly higher levels of uNGAL compared to patients without AKI (203 ± 390 vs. 79 ± 126 µg/g creatinine, p<0.001). Moreover, uNGAL levels were significantly higher in patients who developed persistent AKI (n=40), compared to those with transient AKI (n=25) (281 ± 477 vs. 85 ± 79 µg/g creatinine, p<0.001). Among patients with persistent AKI, uNGAL was able to discriminate type-1 HRS from other causes of AKI (59 ± 46 vs. 429 ± 572 µg/g creatinine, respectively; p<0.001). Moreover, the time course of uNGAL was markedly different between the two groups. Interestingly, baseline uNGAL levels also predicted the development of a second infection during hospitalization. Overall, 3-month mortality was 34%. Independent predictive factors of 3-month mortality were MELD score, serum sodium, and uNGAL levels at diagnosis, but not presence or stage of AKI. CONCLUSIONS: In patients with cirrhosis and infections, measurement of urinary NGAL at infection diagnosis is useful in predicting important clinical outcomes, specifically persistency and type of AKI, development of a second infection, and 3-month mortality.

Terlipressin and albumin for type-1 hepatorenal syndrome associated with sepsis.

BACKGROUND & AIMS: Terlipressin and albumin is the standard of care for classical type-1 hepatorenal syndrome (HRS) not associated with active infections. However, there is no information on efficacy and safety of this treatment in patients with type-1 HRS associated with sepsis. Study aim was to investigate the effects of early treatment with terlipressin and albumin on circulatory and kidney function in patients with type-1 HRS and sepsis and assess factors predictive of response to therapy. METHODS: Prospective study in 18 consecutive patients with type-1 HRS associated with sepsis. RESULTS: Treatment was associated with marked improvement in arterial pressure and suppression of the high levels of plasma renin activity and norepinephrine. Response to therapy (serum creatinine <1.5mg/dl) was achieved in 12/18 patients (67%) and was associated with improved 3-month survival compared to patients without response. Non-responders had significantly lower baseline heart rate, poor liver function tests, slightly higher serum creatinine, and higher Child-Pugh and MELD scores compared to responders. Interestingly, non-responders had higher values of CLIF-SOFA score compared to responders (14±3 vs. 8±1, respectively p<0.001), indicating greater severity of acute-on-chronic liver failure (ACLF). A CLIF-SOFA score ⩾11 had 92% sensitivity and 100% specificity in predicting no response to therapy. No significant differences were observed between responders and non-responders in baseline urinary kidney biomarkers. Treatment was safe and no patient required withdrawal of terlipressin. CONCLUSIONS: Early treatment with terlipressin and albumin in patients with type-1 HRS associated with sepsis is effective and safe. Patients with associated severe ACLF are unlikely to respond to treatment.

Unexplained common bile duct dilatation with normal serum liver enzymes: diagnostic yield of endoscopic ultrasound and follow-up of this condition.

BACKGROUND: There is scant literature about common bile duct (CBD) dilatation with normal liver function tests (LFTs). AIMS: The aims of this study were to assess the diagnostic yield of endoscopic ultrasound (EUS) in patients with CBD dilatation, normal LFTs, and prior inconclusive imaging tests, and to assess the natural history of these subjects. METHODS: We retrospectively reviewed our EUS database for patients referred for evaluation of CBD dilatation, normal LFTs, and prior inconclusive imaging. We excluded patients with a prior endoscopic retrograde cholangiopancreatography or a history of biliary obstruction, pancreatitis, or jaundice. Follow-up data were retrieved from medical records or by calling the general practitioners, referring specialists, patients, or their closest relatives. RESULTS: A total of 57 patients were enrolled. The mean CBD diameter was 12.5±3.6 mm. The majority of patients (50.8%) were asymptomatic. Abnormal EUS findings were recorded in 12 (21%) subjects: 6 patients had a periampullary diverticulum, 2 had ampullary adenoma, 2 had signs of chronic pancreatitis, 1 had a cancer of the pancreatic head, and 1 had a 7 mm CBD stone. Neither age, sex, prior cholecystectomy, clinical presentation, CBD diameter, nor a dilated main pancreatic duct were predictors of abnormal EUS findings. None of the patients complained of biliary symptoms or showed abnormal LFTs on long-term follow-up. CONCLUSIONS: CBD dilatation with normal liver chemistry is not always a benign condition. Even when prior imaging tests are negative, EUS may allow to diagnose conditions overlooked by standard diagnostic imaging.

Psychometric validation of the Italian version of the I-QoL questionnaire: clinical and urodynamic findings.

INTRODUCTION AND HYPOTHESIS: The aim was to validate the Italian version of the Incontinence-Quality of Life questionnaire (I-QoL) in women with clinical and urodynamic urinary incontinence (UI). A secondary end point was to compare the results of women with reported UI, but negative urodynamic findings. METHODS: The Italian translation of the I-QoL was administered to 267 Italian women with pelvic organ prolapse < stage III, and who had undergone previous surgical or medical therapy for UI. Cronbach's alpha was calculated to assess internal consistency of the I-QoL items. Reproducibility was assessed using the intraclass correlation coefficient (ICC). Convergent validity involved comparison of I-QoL scores and the Short Form-36 Health questionnaire. RESULTS: One hundred and sixty-seven patients were considered for the primary end point: 47 had a negative history of UI and a normal urodynamic test, 120 complained of UI confirmed by a urodynamic test, 59 had a positive history for UI and a urodynamic test negative for UI, and 35 patients not reporting UI had a positive urodynamic test. The I-QoL score revealed that the QoL was lower in patients with reported UI, irrespective of urodynamic findings. The overall I-QoL summary score and subscales showed high internal consistency (alpha ranges from 0.88 to 0.96). ICC ranged from 0.98 to 0.99, demonstrating the stability of the scores. The physical domain of the I-QoL showed a 0.27 correlation with the physical functioning subscale of the SF-36. No significant difference in I-QoL scores was found among various types of UI. CONCLUSION: The Italian translated version of the I-QoL is reliable, consistent and a valid instrument for assessing impact on quality of life in Italian speaking women with UI.

Ligand-engaged urokinase-type plasminogen activator receptor and activation of the CD11b/CD18 integrin inhibit late events of HIV expression in monocytic cells.

Urokinase-type plasminogen activator (uPA) signaling via its receptor uPAR inhibits late events in HIV-1 replication in acutely infected primary monocyte-derived macrophages (MDMs) and promonocytic U937 cells. Here we show that U937-derived, chronically infected U1 cells stimulated with phorbol 12-myristate 13-acetate (PMA) express integrins, uPA, and soluble uPAR at levels similar to those of MDMs. uPA inhibited HIV expression in U1 cells incubated with either PMA or tumor necrosis factor-alpha (TNF-alpha), but not with other HIV-inductive cytokines or lipopolysaccharide. Of interest, only PMA and TNF-alpha, but not other HIV-inductive stimuli, induced surface expression of the alpha(M) chain CD11b in U1 cells constitutively expressing CD18, the beta(2) chain of the Mac-1 integrin. Like uPA, fibrinogen, a Mac-1 (CD11b/CD18) ligand, and M25, a peptide homologous to a portion of the beta-propeller region of CD11b preventing its association with uPAR, inhibited HIV virion release in PMA-stimulated U1 cells. Both uPAR small-interference RNA (siRNA) and soluble anti-beta(1)/-beta(2) monoclonal antibodies abolished the anti-HIV effects of uPA, whereas CD11b siRNA reversed the anti-HIV effect of M25, but not that induced by uPA. Thus, either uPA/uPAR interaction, Mac-1 activation, or prevention of its association with uPAR triggers a signaling pathway leading to the inefficient release of HIV from monocytic cells.

Nissen fundoplication and dyspeptic symptoms: is the water load test useful?

BACKGROUND: The water load test is a simple, cheap and standardized method to evaluate gastric distension and gastric motility responses. We have previously shown that in patients with mild erosive or non-erosive esophagitis this test is frequently abnormal, suggesting an altered gastric function. The aim was to evaluate the water load test score before and after Nissen fundoplication in reflux patients. METHODS: Thirty-one patients (16 men, 15 women, mean age 46.5 y) were studied before and 3 months after Nissen fundoplication by stationary esophageal manometry, wireless Bravo pH system monitoring (48 hours), and water load test. A dyspepsia symptom questionnaire was also completed before and after surgery. Data were compared with those of 35 controls. RESULTS: All patients had pH-monitoring positive for pathological acid exposure and/or related-reflux symptoms in the absence of motility disorders. Basal symptoms scores were higher in patients compared to controls and improved after surgery, except than postprandial fullness, early satiation, and bloating, that were significantly increased. At baseline, all patients ingested significantly lower water volumes than controls, with a tendency to early onset of fullness and nausea, respectively. After surgery, the water volumes were significantly lower than presurgery. CONCLUSIONS: In patients with reflux-related symptoms, with or without esophagitis, the water load test is frequently abnormal, suggesting an altered gastric function. Nissen fundoplication is associated with a relatively higher incidence of bloating, epigastric pain and fullness. These preliminary data could explain the incomplete resolution of symptoms after surgery in some patients, and suggest the use of additional studies to explore the gastric function in presurgical evaluation.