Untangling biliary reconstruction in liver transplants for primary sclerosing cholangitis.

BACKGROUND: Biliary reconstruction technique during liver transplant (LT) for primary sclerosing cholangitis (PSC) remains controversial. This study aimed to evaluate the incidence of biliary complications in patients with PSC having a duct-to-duct (DD) anastomosis or Roux-en-Y hepaticojejunostomy (HJ). METHODS: A retrospective medical record review of patients with PSC undergoing LT at a single center between June 1st, 2000 and December 31st, 2022 was performed. Primary and secondary endpoints were the incidence of biliary strictures (anastomotic [BAS] and non-anastomotic strictures [NAS]) and non-stricture complications, respectively. Univariable and multivariable regression analyses were performed to identify associations with BAS formation. Patient survival was assessed using a Kaplan-Meier curve. RESULTS: From 105 transplants performed for 101 patients, 54 (51.4%) and 51 (48.5%) received DD and HJ anastomoses. Mean recipient age and follow-up was 47 ± 13 years and 98 ± 69 months. BAS was more common (48.1% vs. 27.5%, OR 2.45, 95% CI 1.09-5.54, p = 0.03) and occurred earlier (4.8 months, IQR 2.3-13.1 vs. 41.8 months, IQR 7.2-88.7, p = 0.001) in the DD than the HJ group. NAS (seen in 36.2% of transplants) had a comparable incidence (p = 0.53) in HJ (38.9%) and DD (33.3%) groups. No difference was seen between cohorts regarding time to NAS, requirement for extended biliary dilatation programs (clinically significant biliary stricture), bile leak, and graft failure. On multivariable analysis, only the anastomotic technique was associated with BAS (DD adjusted OR 3.00, 95% CI 1.19-7.56, p = 0.02). CONCLUSION: In carefully selected patients with PSC, DD anastomosis yielded similar outcomes to HJ anastomosis after liver transplantation.

Palliative care outpatients in a German comprehensive cancer center-identifying indicators for early and late referral.

PURPOSE: Despite that early integration of palliative care is recommended in advanced cancer patients, referrals to outpatient specialised palliative care (SPC) frequently occur late. Well-defined referral criteria are still missing. We analysed indicators associated with early (ER) and late referral (LR) to SPC of an high volume outpatient unit of a comprehensive cancer center. METHODS: Characteristics, laboratory parameters and symptom burden of 281 patients at first SPC referral were analysed. Timing of referral was categorized as early, intermediate and late (> 12, 3-12 and < 3 months before death). Ordinal logistic regression analysis was used to identify factors related to referral timing. Kruskal-Wallis test was used to determine symptom severity and laboratory parameter in each referral category. RESULTS: LRs (50.7%) had worse scores of weakness, loss of appetite, drowsiness, assistance of daily living (all p < 0.001) and organisation of care (p < 0.01) in contrast to ERs. The mean symptom sum score was significantly higher in LRs than ERs (13.03 vs. 16.08; p < 0.01). Parameters indicative of poor prognosis, such as elevated LDH, CRP and neutrophil-to-lymphocyte ratio (NLR) (p < 0.01) as well as the presence of ascites (p < 0.05), were significantly higher (all p < 0.001) in LRs. In univariable analyses, psychological distress (p < 0.05) and female gender (p < 0.05) were independently associated with an ER. CONCLUSION: A symptom sum score and parameters of poor prognosis like NLR or LDH might be useful to integrate into palliative care screening tools.

Prenatal diagnosis of rhombencephalosynapsis: neuroimaging features and severity of vermian anomaly.

OBJECTIVES: To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and criteria for its classification according to the severity of vermian anomaly. METHODS: In this multicenter retrospective study of fetuses with RES between 2002 and 2020, the medical records and brain ultrasound and magnetic resonance images were evaluated comprehensively to determine the severity of the vermian anomaly and the presence of associated brain findings. RES was classified, according to the pattern of vermian agenesis and the extent of the fusion of the hemispheres, as complete RES (complete absence of the vermis) or partial RES (further classified according to the part of the vermis that was missing and, consequently, the region of hemispheric fusion, as anterior, posterior, severe or mixed RES). Findings were compared between cases with complete and those with partial RES. RESULTS: Included in the study were 62 fetuses with a gestational age ranging between 12 and 37 weeks. Most had complete absence of the vermis (complete RES, 77.4% of cases), a 'round-shaped' cerebellum on axial views (72.6%) and a transverse cerebellar diameter (TCD) < 3rd centile (87.1%). Among the 22.6% of cases with partial RES, 6.5% were classified as severe partial, 6.5% as partial anterior, 8.1% as partial mixed and 1.6% as partial posterior. Half of these cases presented with normal or nearly normal cerebellar morphology and 28.5% had a TCD within the normal limits. Infratentorially, the fourth ventricle was abnormal in 88.7% of cases overall, and anomalies of the midbrain and pons were frequent (93.5% and 77.4%, respectively). Ventriculomegaly was observed in 80.6% of all cases, being more severe in cases with complete RES than in those with partial RES, with high rates of parenchymal and septal disruption. CONCLUSIONS: This study provides prenatal neuroimaging criteria for the diagnosis and classification of RES, and identification of related features, using ultrasound and magnetic resonance imaging. According to our findings, a diagnosis of RES should be considered in fetuses with a small TCD (severe cerebellar hypoplasia) and/or a round-shaped cerebellum on axial views, during the second or third trimester, especially when associated with ventriculomegaly. Partial RES is more common than previously thought, but presents an extreme diagnostic challenge, especially in cases with normal or nearly-normal cerebellar morphobiometric features. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

[Evaluation of outpatient medical pain management in Germany : Results of an internet-based cross-sectional survey among pain specialists in outpatient departments]. / Bewertung der ambulanten ärztlichen Schmerztherapie in Deutschland : Ergebnisse einer internetbasierten Querschnittsbefragung unter ambulant tätigen Schmerzmedizinern.

BACKGROUND: On 31 December 2016, a total of 1206 physicians participated in the outpatient care of chronic pain patients according to the criteria of a special pain management program (QSV). Because of the largely existing shortage of treatment resources for chronic pain patients, there is a lack of data regarding the evaluation of outpatient pain management by highly specialized pain therapists. METHODS: In a hybrid Delphi procedure, a questionnaire concerning the content, structural and personal assessment of outpatient pain management in Germany was developed. With the help of this instrument, an internet-based cross-sectional survey of 281 QSV pain therapists from four German states (Berlin, Lower Saxony, Saxony, Baden-Württemberg) and of all the heads of university outpatient pain services (n = 36) in Germany was conducted. RESULTS: The adjusted response rate of the survey was 35.9%. The response rate of the heads of university outpatient pain services was 66.7%. In 91% of the respondents the proportion of chronic pain patients in the medical practices was more than 70%. Whereas 67.3% were satisfied with the situation in their medical practice, 63.4% were dissatisfied with the current organizational structure of the pain management in Germany. They expressed their dissatisfaction especially in terms of budgeting regulations (69.3%), the cooperation with psychotherapists (69.3%) and interdisciplinary networking (50.5%). The 1­year specialist training in pain management (87.1%) and the completion of a psychosomatic basic care course (90.1%) were assessed as a good preparation for the later profession. A multitude of free comments indicated that the pain specialist training is too short and insufficient. Most of the respondents considered the establishment of a specialist board certification for pain management more suitable from the perspective of physicians (61.4%) and the patients (54.5%). Of the heads of university outpatient pain services 70.8% expressed the wish for autonomous structures with separate budgets and 75.0% indicated that under the current conditions their outpatient pain services are not working profitably. Only 39.7% of the QSV pain therapists provided fellowship training for physicians and 57.6% were planning to retire during the next 10 years. CONCLUSION: Highly specialized pain therapists are dissatisfied because of the lack of independence of the organizational structure of pain management care and the insufficient interdisciplinary network in outpatient pain management. A possible solution for a better pain management care and the recruitment problems may be the establishment of a board certification for pain management.

Impact of viral hepatitis aetiology on survival outcomes in hepatocellular carcinoma: A large multicentre cohort study.

While HBV and HCV are risk factors for HCC, uncertainty exists as to whether these viral infections have prognostic significance in HCC. Thus, we compared the overall survival of patients with HBV, HCV and nonviral HCC, and evaluated whether the presence of HBV and HCV predicts patient outcomes. We conducted a multicentre study of HCC cases diagnosed at six Melbourne tertiary hospitals between Jan 2000-Dec 2014. Patient demographics, liver disease and tumour characteristics and patient outcomes were obtained from hospital databases, computer records and the Victorian Death Registry. Survival outcomes were compared between HBV, HCV and nonviral hepatitis cases and predictors of survival determined using Cox proportional hazards regression. There were 1436 new HCC cases identified including 776 due to viral hepatitis (HBV 235, HCV 511, HBV-HCV 30) and 660 from nonviral causes. The median survival of HBV, HCV and nonviral HCC patients was 59.1, 28.4 and 20.9 months, respectively (P<.0001). On multivariate analysis, independent risk factors for survival included HCC aetiology, gender, BCLC stage, serum AFP, total number and size of lesions, and serum creatinine and albumin. After adjusting for these and method of detection, HBV remained an independent predictor of improved overall survival when compared to both nonviral (HR 0.60%, 95% CI 0.35-0.98; P=.03) and HCV-related HCC (HR 0.51%, 95% CI 0.30-0.85; P=.01). In this large multicentre study, HBV is independently associated with improved overall survival compared with HCV and nonviral-related HCC. Further studies are needed to determine the underlying factor(s) responsible.

Does persisting fear sustain catatonia?

OBJECTIVE: To examine the psychological substrate of catatonia. METHOD: Reviewing the historical descriptions and explanations of catatonic behaviours by clinicians from its delineation in the 19th century to the present. RESULTS: Patients with catatonia are often haunted by fears and terrors; this has not been widely appreciated, and certainly was lost from view in the days when catatonia was considered a subtype of schizophrenia. The report contributes to resolving a major question in catatonia: is the mind in stupor inactive, as the blank state that we picture in anesthetized patients, or is the mind active, so preoccupied as to exclude all other influences. THE MAIN FINDING: Persistent fear occupies the mind of catatonic patients. CONCLUSION: The signs of catatonia are adaptations to persistent fear, akin to tonic immobilization. The relief afforded by sedation supports this interpretation.

Detection of human polyomaviruses JC and BK in liver pretransplant patients.

OBJECTIVE: This study aimed to identify and quantify polyomaviruses (BKPyV and JCPyV) in the saliva, mouthwash, blood and urine of liver pretransplant patients. MATERIALS AND METHODS: A case-control study was performed using a convenience sample of 21 end-stage liver disease patients (EG = experimental group) and 20 normoreactive controls (CG = control group). In total, 162 samples were collected. Detection and quantification of polyomaviruses were performed using real-time PCR method. RESULTS: In the EG, 21 samples (25%) were positive for BKPyV and 10 (11.90%) for JCPyV, while in the CG, 27 samples (34.61%) were positive for BKPyV and six (7.69%) for JCPyV. With regard to the number of samples positive for BKPyV and JCPyV, there was no statistically significant difference between EG and CG (p = .52 and p = .25). In the EG, we observed a panorama similar to that of the CG regarding the presence of polyomaviruses in mouthwash, blood and urine. The greatest difference between the samples was that regarding the identification of BKPyV in saliva. CONCLUSION: Cirrhotic patients on the liver transplant waiting list did not show higher prevalence of BKPyV and JCPyV compared to normoreactive controls.

Health resource utilisation associated with skeletal-related events in patients with bone metastases secondary to solid tumours: regional comparisons in an observational study.

Skeletal-related events (SREs) including spinal cord compression, pathologic fracture, and radiation or surgery to bone, occur frequently due to bone metastases in advanced cancer. This analysis of a multicentre, observational study was designed to describe cross-regional differences in health resource utilisation (HRU) of SREs in Western Europe and the US. Patients with bone metastases due to breast, lung or prostate cancer, or multiple myeloma who had experienced a SRE within the past 97 days were enrolled. Investigators recorded HRU associated with SREs, including hospitalisation and length of stay (LOS), outpatient visits, procedures and bisphosphonate use. This subanalysis includes 668 patients with solid tumours (US, n = 190 with 354 SREs; EU, n = 478 with 893 SREs). The rate of SREs associated with hospitalisation(s) was higher in the EU vs. the US (30% vs. 15%, P < 0.001) and LOS was longer in the EU [mean (SD) days/SRE: 19.87 (17.31) vs. 10.61 (9.39)]. However, the US was associated with higher rate of SREs with outpatient visits than the EU (88% vs. 74%, P < 0.0001) and more procedures [mean (SD)/SRE: 11.26 (7.94) vs. 6.91 (6.48)]. Bisphosphonates were less often used in the EU (65% vs. 76% of US, P = 0.0033). In patients experiencing SREs due to bone metastases, HRU patterns reflect regional diversity with a substantial burden in both regions.

Assessing particle kinematics via template matching algorithms.

Template matching algorithms represent a viable tool to locate particles in optical images. A crucial factor of the performance of these methods is the choice of the similarity measure. Recently, it was shown in [Gao and Helgeson, Opt. Express 22 (2014)] that the correlation coefficient (CC) leads to good results. Here, we introduce the mutual information (MI) as a nonlinear similarity measure and compare the performance of the MI and the CC for different noise scenarios. It turns out that the mutual information leads to superior results in the case of signal dependent noise. We propose a novel approach to estimate the velocity of particles which is applicable in imaging scenarios where the particles appear elongated due to their movement. By designing a bank of anisotropic templates supposed to fit the elongation of the particles we are able to reliably estimate their velocity and direction of motion out of a single image.

High speed optical holography of retinal blood flow.

We performed noninvasive video imaging of retinal blood flow in a pigmented rat by holographic interferometry of near-infrared laser light backscattered by retinal tissue, beating against an off-axis reference beam sampled at a frame rate of 39 kHz with a high throughput camera. Local Doppler contrasts emerged from the envelopes of short-time Fourier transforms and the phase of autocorrelation functions of holograms rendered by Fresnel transformation. This approach permitted imaging of blood flow in large retinal vessels (∼30 microns diameter) over 400×400 pixels with a spatial resolution of ∼8 microns and a temporal resolution of ∼6.5 ms.

Pre-transplant shedding of BK virus in urine is unrelated to post-transplant viruria and viremia in kidney transplant recipients.

BK virus-(BKV) associated nephropathy (BKVN) is a major cause of allograft injury in kidney transplant recipients. In such patients, subclinical reactivation of latent BKV infection can occur in the pre-transplant period. The purpose of this study was to determine whether urinary BKV shedding in the immediate pre-transplant period is associated with a higher incidence of viruria and viremia during the first year after kidney transplantation. We examined urine samples from 34 kidney transplant recipients, using real-time quantitative polymerase chain reaction to detect BKV. Urine samples were obtained in the immediate pre-transplant period and during the first year after transplant on a monthly basis. If BKV viruria was detected, blood samples were collected and screened for BKV viremia. In the immediate pre-transplant period, we detected BKV viruria in 11 (32.3%) of the 34 recipients. During the first year after transplantation, we detected BKV viruria in all 34 patients and viremia in eight (23.5%). We found no correlation between pre-transplant viruria and post-transplant viruria or viremia (p = 0.2). Although reactivation of latent BKV infection in the pre-transplant period is fairly common among kidney transplant recipients, it is not a risk factor for post-transplant BKV viruria or viremia.

Mathematical modeling and simulation in animal health. Part I: Moving beyond pharmacokinetics.

The application of mathematical modeling to problems in animal health has a rich history in the form of pharmacokinetic modeling applied to problems in veterinary medicine. Advances in modeling and simulation beyond pharmacokinetics have the potential to streamline and speed-up drug research and development programs. To foster these goals, a series of manuscripts will be published with the following goals: (i) expand the application of modeling and simulation to issues in veterinary pharmacology; (ii) bridge the gap between the level of modeling and simulation practiced in human and veterinary pharmacology; (iii) explore how modeling and simulation concepts can be used to improve our understanding of common issues not readily addressed in human pharmacology (e.g. breed differences, tissue residue depletion, vast weight ranges among adults within a single species, interspecies differences, small animal species research where data collection is limited to sparse sampling, availability of different sampling matrices); and (iv) describe how quantitative pharmacology approaches could help understanding key pharmacokinetic and pharmacodynamic characteristics of a drug candidate, with the goal of providing explicit, reproducible, and predictive evidence for optimizing drug development plans, enabling critical decision making, and eventually bringing safe and effective medicines to patients. This study introduces these concepts and introduces new approaches to modeling and simulation as well as clearly articulate basic assumptions and good practices. The driving force behind these activities is to create predictive models that are based on solid physiological and pharmacological principles as well as adhering to the limitations that are fundamental to applying mathematical and statistical models to biological systems.

What was learned: studies by the consortium for research in ECT (CORE) 1997-2011.

OBJECTIVE: To review the findings of the four-hospital collaborative studies of electroconvulsive therapy (ECT) in unipolar depressed patients known as CORE between 1997 and 2011. Unipolar depressed patients were treated with bilateral ECT, and on remission were randomly assigned to a fixed schedule continuation ECT or to combined lithium and nortriptyline for 6 months. A second study compared three electrode placements in unipolar and bipolar depressed patients. METHOD: Nineteen published reports were reviewed. The findings are compared with those of a parallel multi-hospital study of ECT led by a Columbia University Collaboration (CUC) team that studied right unilateral ECT in a similar population with similar inclusion/exclusion and remission criteria. Successful ECT was followed by placebo, nortriptyline alone, or combined lithium, and nortriptyline. RESULTS: Relapse rates after remission were similar with fixed schedule ECT as with medications. Predictors of outcome (psychosis, suicide risk, polarity, melancholia, atypical depression, age) and technical aspects (electrode placement, seizure threshold, speed of response) are discussed, CONCLUSION: The findings offer criteria to optimize the selection of patients, the technique, and outcome of ECT for unipolar and bipolar depressed patients. Continuation ECT is an effective alternative to continuation treatment with lithium and nortriptyline. Bilateral electrode placement is more efficient than alternative placements. ECT relieves both bipolar and unipolar depression.

Identifying the superior measure of rapid fibrosis for predicting premature cirrhosis after liver transplantation for hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) recurrence post liver transplant is universal, with a subgroup of patients developing rapid hepatic fibrosis. Various clinical definitions of rapid fibrosis (RF) have been used to identify risks for rapid progression, but their comparability and efficacy at predicting adverse outcomes has not been determined. METHODS: Retrospective data analysis was conducted on 100 adult patients with HCV who underwent liver transplantation at a single center. We measured year 1 fibrosis progression (RF defined as METAVIR F score ≥ 1 at 1-year liver biopsy), time to METAVIR F2-stage fibrosis, and fibrosis rate (calculated using liver biopsies graded by METAVIR scoring F0-4; fibrosis rate = fibrosis stage/year post transplant). RF was defined as ≥ 0.5 units/year. RESULTS: Multivariate analysis revealed that donor age and peak HCV viral load were significant risks for RF, when fibrosis rate was used to define RF. Advanced donor age was a risk for rapid progression to F2-stage fibrosis, whereas genotype 2 or 3 HCV infection was protective. Fibrosis rate had the strongest correlation with time to cirrhosis development (P < 0.0001, r = -0.76) and was the most accurate predictor of rapid graft cirrhosis (P < 0.0001, area under the curve 0.979, sensitivity 100%, specificity 94%). CONCLUSION: Different measures of RF progression identify different risks for RF and are not directly comparable. Fibrosis rate was the most accurate predictor of rapid graft cirrhosis.

Field-expedient screening and injury risk algorithm categories as predictors of noncontact lower extremity injury.

In athletics, efficient screening tools are sought to curb the rising number of noncontact injuries and associated health care costs. The authors hypothesized that an injury prediction algorithm that incorporates movement screening performance, demographic information, and injury history can accurately categorize risk of noncontact lower extremity (LE) injury. One hundred eighty-three collegiate athletes were screened during the preseason. The test scores and demographic information were entered into an injury prediction algorithm that weighted the evidence-based risk factors. Athletes were then prospectively followed for noncontact LE injury. Subsequent analysis collapsed the groupings into two risk categories: Low (normal and slight) and High (moderate and substantial). Using these groups and noncontact LE injuries, relative risk (RR), sensitivity, specificity, and likelihood ratios were calculated. Forty-two subjects sustained a noncontact LE injury over the course of the study. Athletes identified as High Risk (n = 63) were at a greater risk of noncontact LE injury (27/63) during the season [RR: 3.4 95% confidence interval 2.0 to 6.0]. These results suggest that an injury prediction algorithm composed of performance on efficient, low-cost, field-ready tests can help identify individuals at elevated risk of noncontact LE injury.

A severe case of haemodynamic instability during anidulafungin administration.

WHAT IS KNOWN AND OBJECTIVE: Anidulafugin is an echinocandin used for the treatment of candida infections in non-neutropenic adults. Echinocandins show few drug-drug interactions and are usually well tolerated. We report a case of acute hypotension, bradycardia and haemodynamic instability with consecutive cardiopulmonary resuscitation during anidulafungin administration. CASE SUMMARY: A 41-year-old man ICU patient received anidulafungin for a suspected Candida glabrata infection. During the first administration of the drug, he developed acute haemodynamic instability with hypotension and bradycardia. The infusion was discontinued immediately and cardiopulmonary resuscitation was performed successfully. The patient regained haemodynamic stability. WHAT IS NEW AND CONCLUSION: To the authors' knowledge, this is the first report of a life-threatening adverse event due to haemodynamic instability during anidulafungin administration. Cardiac toxicity associated with echinocandins has been described. Further studies seem to be mandatory to investigate this potential risk.

EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 1: Basic principles and technology.

The technical part of these Guidelines and Recommendations, produced under the auspices of EFSUMB, provides an introduction to the physical principles and technology on which all forms of current commercially available ultrasound elastography are based. A difference in shear modulus is the common underlying physical mechanism that provides tissue contrast in all elastograms. The relationship between the alternative technologies is considered in terms of the method used to take advantage of this. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided on optimisation of scanning technique, image display, image interpretation and some of the known image artefacts.

EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 2: Clinical applications.

The clinical part of these Guidelines and Recommendations produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology EFSUMB assesses the clinically used applications of all forms of elastography, stressing the evidence from meta-analyses and giving practical advice for their uses and interpretation. Diffuse liver disease forms the largest section, reflecting the wide experience with transient and shear wave elastography . Then follow the breast, thyroid, gastro-intestinal tract, endoscopic elastography, the prostate and the musculo-skeletal system using strain and shear wave elastography as appropriate. The document is intended to form a reference and to guide clinical users in a practical way.

Capturing the dynamics of systemic Renin-Angiotensin-Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs.

In dogs, activation of the Renin-Angiotensin-Aldosterone System (RAAS) is an important feature of congestive heart failure (CHF). Long-term increases in angiotensin II (AII) and aldosterone (ALD) lead to the progression of heart failure to its end stage. Angiotensin-converting enzyme inhibitors (ACEIs) are the foremost therapeutic option in the management of CHF. Recent literature has challenged the efficacy of ACEIs, based on modest reduction in urinary aldosterone (UALD) excretion despite marked inhibition of ACE activity. This study was designed to heighten the understanding of the effect of benazepril, a potent ACEI, on the RAAS, using a low-sodium diet as an experimental model of RAAS activation. Time course profiles of RAAS peptides and related areas under the curve (AUC) were used for comparison between benazepril and placebo groups. Results indicated substantial changes in the dynamics of these biomarkers. At presumed benazeprilat steady state, significant differences in AUC of plasma renin activity (+90%), angiotensin I (+43%), and AII (-53%) were found between benazepril and placebo-treated dogs. ALD decreased by 73% in plasma but only by 5% in urine. In conclusion, despite modest reduction in UALD excretion, benazepril markedly influences RAAS dynamics in dogs.