Randomized controlled trial of sustained release tacrolimus vs twice daily tacrolimus in adult living donor liver transplantation.

BACKGROUND: To compare the safety and efficacy of once-daily tacrolimus (ODT) versus twice-daily tacrolimus (BDT) in adult live donor liver transplantation (LDLT). METHODS: In this open-labelled randomized trial, 174 adult patients undergoing LDLT were randomized into ODT or BDT, combined with basiliximab induction and mycophenolate mofetil (steroid-free regimen). Tacrolimus was started at a total dose of 1 mg and the trough level was aimed at 3-7 ng/ml. The primary endpoint was eGFR at 1,3- and 6 months post-transplant, using CKD- EPI equation. Secondary endpoints included biopsy-proven acute rejection (BPAR), metabolic complications, post-operative bilio-vascular complications and patient survival. RESULTS: There was no statistically significant difference in eGFR between the two groups at 6 months (ODT -96 ± 19, BDT -91 ± 21, p value-0.164). BPAR was comparable (18/84 in ODT, 19/88 in BDT, p value-0.981). For a similar dosage of tacrolimus, the median trough tacrolimus levels attained were significantly lower for ODT than BDT during the first-month post-transplant (p value-0.001). Metabolic complications due to immunosuppression, post-operative bilio-vascular complications and patient survival was similar between the two groups at 6 months. CONCLUSION: Once-daily tacrolimus has similar renal safety and efficacy as twice-daily tacrolimus when used in combination with basiliximab induction and mycophenolate in adult LDLT.

Drug Interactions and Safe Prescription Writing for Liver Transplant Recipients.

Immunosuppression optimization is central to graft function in liver transplant recipients. Post-transplantation patients develop new onset or worsening metabolic syndrome, are prone to atypical infections, and are at higher risk of developing cardiac and brain-related clinical events. In this context, liver transplant recipients are at risk of using multiple comedications alongside immunosuppressants. It is imperative for the transplant physician to understand the various drug-drug interactions that potentially reduce or promote toxicity of immunosuppression, as well as associated synergistic or antagonistic effects on extrahepatic organ systems. This comprehensive review discusses drug-drug interactions in liver transplant recipients and the impact and role of complementary and alternative medicines among individuals on immunosuppression.

Proceedings of the 27th Annual Congress of the International Liver Transplantation Society.

After a virtual congress in 2021 and a previous absence in 2020 because of the coronavirus disease 2019 pandemic, the 27th Annual Congress of the International Liver Transplantation Society was held from May 4 to 7, 2022, in a hybrid format in Istanbul, with 1123 (58% on-site) liver transplant professionals from 61 countries attending the meeting. The hybrid format successfully achieved a balance of much yearned-for "in-person interaction" and global online participation. Almost 500 scientific abstracts were presented. In this report, the Vanguard Committee aims to present a summary of key invited lectures and selected abstracts for the liver transplant community.

Reliability of the scapular dyskinesis test yes-no classification in asymptomatic individuals between students and expert physical therapists

Background@#Scapular dyskinesis is considered a risk factor for the shoulder pain that may warrant screening for prevention. Clinicians of all experience screen scapular dyskinesis using the scapular dyskinesis test yes-no classification (Y-N), yet its reliability in asymptomatic individuals is unknown. We aimed to establish Y-N’s intra- and inter-reliability between students and expert physical therapists. @*Methods@#We utilized a cross-sectional design using consecutive asymptomatic subjects. Six students and two experts rated 100 subjects using the Y-N. Cohen’s kappa (κ) and Krippendorff’s alpha (K-α) were calculated to determine intra- and inter-rater reliability. @*Results@#Intra- and inter-rater values for experts were κ=0.92 (95% confidence interval [CI], 0.91–0.93) and 0.85 (95% CI, 0.84–0.87) respectively; students were κ=0.77 (95% CI, 0.75–0.78) and K-α=0.63 (95% CI, 0.58–0.67). @*Conclusions@#The Y-N is reliable in detecting scapular dyskinesis in asymptomatic individuals regardless of experience.

Liver Transplantation Society of India Guidelines for the Management of Acute Liver Injury Secondary to Yellow Phosphorus-Containing Rodenticide Poisoning Using the Modified Delphi Technique of Consensus Development.

BACKGROUND: Acute liver failure caused by the ingestion of yellow phosphorus-containing rodenticide has been increasing in incidence over the last decade and is a common indication for emergency liver transplantation in Southern and Western India and other countries. Clear guidelines for its management are necessary, given its unpredictable course, potential for rapid deterioration and variation in clinical practice. METHODS: A modified Delphi approach was used for developing consensus guidelines under the aegis of the Liver Transplantation Society of India. A detailed review of the published literature was performed. Recommendations for three areas of clinical practice, assessment and initial management, intensive care unit (ICU) management and liver transplantation, were developed. RESULTS: The expert panel consisted of 16 clinicians, 3 nonclinical specialists and 5 senior advisory members from 11 centres. Thirty-one recommendations with regard to criteria for hospital admission and discharge, role of medical therapies, ICU management, evidence for extracorporeal therapies such as renal replacement therapy and therapeutic plasma exchange, early predictors of need for liver transplantation and perioperative care were developed based on published evidence and combined clinical experience. CONCLUSION: Development of these guidelines should help standardise care for patients with yellow phosphorus poisoning and identify areas for collaborative research.

Randomized trial of steroid free immunosuppression with basiliximab induction in adult live donor liver transplantation (LDLT).

BACKGROUND: Corticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT). METHODS: We randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months. RESULTS: The incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22). CONCLUSION: Following LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine.

Pregnancy After Liver Transplantation: Outcomes From a Single-Center Experience.

BACKGROUND/OBJECTIVES: Although much has been learnt regarding pregnancy after liver transplantation, data from India are scant. Hence, we evaluated the maternal and fetal outcomes of pregnancies after liver transplantation at our center. METHODS: We conducted a retrospective review of all patients who underwent liver transplantation and later conceived at our center between 2006 and 2019. RESULTS: Of the 750 liver transplantations performed at our center, 129 were female and 62 of them were in the childbearing age group (15-44 years). A total of seven conceptions occurred in seven patients during the study period. All the pregnancies occurred spontaneously. The median age of the patients at the time of liver transplantation and conception was 25 years (range, 24-33 years) and 29 years (range, 26-36 years), respectively. The median interval between transplantation and conception was 40 months (range, 7-48 months). All patients were on tacrolimus monotherapy. None of the patients had rejection during pregnancy despite a low median tacrolimus trough level of 2.7 ng/mL. Live birth (five cesarean and one normal) occurred in six of seven pregnancies at a median gestation age of 37.5 weeks. Mean birth weight was 3055.8 g (range, 2470-3635 g). Antenatal rubella infection and grade III intrauterine growth restriction resulting in still birth at 29 weeks occurred in one patient. The median postnatal follow-up was 25 months (range, 2-81 months). All babies and mothers were healthy. CONCLUSIONS: Pregnancy after liver transplantation has a favorable outcome with a multidisciplinary team approach. There is a physiological reduction of tacrolimus trough levels during pregnancy for which dose augmentation is not usually required.

Consequences of chemotherapeutic agents on primordial follicles and future clinical applications

The ovarian reserve is necessary for female fertility and endocrine health. Commonly used cancer therapies diminish the ovarian reserve, thus, resulting in primary ovarian insufficiency, which clinically presents as infertility and endocrine dysfunction. Prepubertal children who have undergone cancer therapies often experience delayed puberty or cannot initiate puberty and require endocrine support to maintain a normal life. Thus, developing an effective intervention to prevent loss of the ovarian reserve is an unmet need for these cancer patients. The selection of adjuvant therapies to protect the ovarian reserve against cancer therapies underlies the mechanism of loss of primordial follicles (PFs). Several theories have been proposed to explain the loss of PFs. The “burn out” theory postulates that chemotherapeutic agents activate dormant PFs through an activation pathway. Another theory posits that chemotherapeutic agents destroy PFs through an “apoptotic pathway” due to high sensitivity to DNA damage. However, the mechanisms causing loss of the ovarian reserve remains largely speculative. Here, we review current literature in this area and consider the mechanisms of how gonadotoxic therapies deplete PFs in the ovarian reserve.

Factors underlying metastatic breast cancer patients' perceptions of symptom importance: a qualitative analysis.

The symptom literature in cancer has primarily examined symptom severity, frequency and distress. Assessing cancer patients' perceptions of symptom importance-how important it is for them to see improvement in a symptom following an intervention-and factors influencing these judgments would also inform patient-centred care, but this analysis has not been undertaken. This qualitative study aimed to identify factors underlying perceptions of symptom importance among 25 symptomatic metastatic breast cancer (MBC) patients. Participants were recruited from a cancer centre in the Midwestern USA. Semi-structured interviews focused on patients' rationale for considering common symptoms (i.e., anxiety, sadness, sleep problems, pain or fatigue) to be important. Thematic analyses revealed five interrelated factors underlying MBC patients' perceptions of symptom importance: activity restriction, concentration difficulties, exacerbation of other physical symptoms, symptom-related long-term health concerns and negative impact on their relationships with others. Patients most frequently stated that a physical or psychological symptom was important because of the resulting activity restriction. Additionally, some patients considered pain to be important because it signalled potential long-term health concerns, such as worsening metastatic disease. Findings suggest that clinicians should take into account MBC patients' perceptions of symptom importance and factors underlying these judgments when making shared treatment decisions.

Utility of Radiographs, Computed Tomography, and Three Dimensional Computed Tomography Pelvis Reconstruction for Identification of Acetabular Defects in Residency Training / 대한고관절학회지

PURPOSE: The Paprosky classification system of acetabular defects is complex and its reliability has been questioned. The purpose of this study was to evaluate the effectiveness of different radiologic imaging modalities in classifying acetabular defects in revision total hip arthroplasty (THA) and their value of at different levels of training. MATERIALS AND METHODS: Bone defects in 8 revision THAs were classified by 2 fellowship-trained adult reconstruction surgeons. A timed presentation with representative images for each case (X-ray, two-dimensional computed tomography [CT] and three-dimensional [3D] reconstructions) was shown to 35 residents from the first postgraduate year of training year of training (PGY-1 to PGY-5), 2 adult reconstruction fellows and 2 attending orthopaedic surgeons. The Paprosky classification of bone defects was recorded. The influence of image modality and level of training on classification were analyzed using chi-square analysis (alpha=0.05). RESULTS: Overall correct classification was 30%. The level of training had no influence on correct classification (P=0.531). Using X-ray led to 37% correctly identified defects, CT scans to 33% and 3D reconstructions to 20% of correct answers (P < 0.001). There was no difference in correct classification based defect type (P < 0.001). Regardless of level of training or imaging, 64% of observers recognized type 1 defects, compared to only 16% correct recognition of type 3B defects. CONCLUSION: Using plain X-rays led to an increased number of correct classification, while regular CT scan and 3D CT reconstructions did not improve accuracy. The classification system of acetabular defects can be used for treatment decisions; however, advanced imaging may not improve its utilization.

Immediate Postoperative Intraocular Pressure Adjustment Reduces Risk of Cystoid Macular Edema after Uncomplicated Micro Incision Coaxial Phacoemulsification Cataract Surgery

PURPOSE: To determine the accuracy of visual estimation of immediate postoperative intraocular pressure (IOP) following microincision cataract surgery (MICS) and the effect of immediate postoperative IOP adjustment on prevention of cystoid macular edema (CME). SETTING: Ambulatory surgical center. METHODS: Prospective, randomized analysis of 170 eyes in 135 patients with MICS, performed in a Medicare approved outpatient ambulatory surgery center. Surgical parameters included a keratome incision of 1.5 mm to 2.8 mm, topical anesthetic, case completion IOP estimation by palpation and patient visualization of light, and IOP adjustment before exiting the operating theater. IOPs were classified into three groups: low (21 to 30 mmHg). IOP measurements were repeated 1 day after surgery. Optical coherence tomography (Stratus OCT, Zeiss) was measured at 2 weeks. An increase in foveal thickness greater than 15 µm was used to indicate CME. Statistical analysis was performed using one- and two-tailed Student's t-tests. RESULTS: Mean minimal foveal thickness averaged 207.15 µm in the low pressure group, 205.14 µm in the normal IOP group, and 210.48 µm in the elevated IOP group 2 weeks following surgery. CME occurred in 14 of 170 eyes (8.2%) at 2 weeks (low IOP, 35.7%; normal IOP, 14.2%; elevated IOP, 50.0%). Change in IOP from the operating theater to 1 day after surgery was within +/−5 mmHg in 54 eyes (31.7%), elevated by 6 to 15 mmHg in 22 eyes (12.9%), and elevated more than 15 mmHg in four eyes (2.3%). IOP was reduced by 6 mmHg to 15 mmHg in 39 eyes (22.9%) and reduced by more than 15 mmHg in nine eyes (5.3%). CONCLUSIONS: Immediate postoperative adjustment of IOP may prevent CME in MICS. Physicians can improve their ability to estimate postoperative IOP with experience in tonometry to verify immediate postoperative IOP. There are patient safety and economic benefits to immediate IOP adjustment in the operating theater. SYNOPSIS: Immediate postoperative IOP adjustment following cataract surgery before the patient leaves the operating theater may reduce the incidence of CME and provide patient safety and economic benefits.

Timing Matters - Influenza Vaccination to HIV-Infected Patients.

OBJECTIVES: Patients with HIV infection vaccinated early in the flu season are more likely to contract influenza or influenza-like illness (ILI) compared with those receiving late vaccination. It is known that antibody titres wane over time, particularly among individuals with HIV infection. It is unclear if the timing of influenza vaccination within the flu season affects the probability of an influenza infection later during the flu season. The aim of this study is to evaluate if there is a relationship between the timing of influenza vaccination and incidence of influenza or ILI in patients with HIV infection. METHODS: A retrospective cohort study of HIV-infected patients in care at the Department of Veterans Affairs San Diego Healthcare System was conducted from 1 September 2005 to 31 May 2013. Among these patients, we evaluated whether there was a relationship between the timing of influenza vaccination and the incidence of laboratory-confirmed influenza, influenza diagnosed by a physician, or ILI. RESULTS: Patients who received influenza vaccine early in the season were more likely to contract influenza or ILI than patients who were vaccinated late (P < 0.01). Vaccinated patients who developed influenza or ILI were more likely to do so later in the season (P < 0.01). CONCLUSIONS: HIV-infected patients vaccinated early in the flu season were more likely to contract influenza or ILI than those vaccinated later in the season.

Potential for development of haemophilia link nurse role within UK hospitals.

Link nurses are practising nurses with an expressed interest in a given specialty, with formal links to clinical nurse specialists and other specialist staff. The role involves attending meetings to discuss ideas and new developments, and relaying findings to other ward nurses to improve their practice. Such nurses are common in many specialties such as diabetes and tissue viability. In haemophilia, the role has the potential to enhance the care of haemophilia patients on general hospital wards. In April 2012, a focus group of five haemophilia nurses was convened to discuss their experiences of 'link nurse' programmes within district general hospitals and the potential value of developing the haemophilia link nurse role, and to consider the materials needed to support such role development. It was agreed to test whether other haemophilia nurses perceived such a need by means of a short five-item questionnaire devised by the group and made available to all members of the UK's Haemophilia Nurse's Association via Survey-Monkey. Final responses from 59 haemophilia nurses across the UK have been analysed. Most nurses agreed that there was value in the development of a haemophilia link nurse role within UK hospitals and thought their trusts would support it. While barriers and potential downsides were acknowledged, this was seen as a useful way of sharing information and knowledge with colleagues from different specialties and of raising awareness of bleeding disorders among the general nursing community. Haemophilia nurses should coordinate the development of a Haemophilia Link Nurse training and education pack.

Genetic and epigenetic regulation of the organic cation transporter 3, SLC22A3.

Human organic cation transporter 3 (OCT3 and SLC22A3) mediates the uptake of many important endogenous amines and basic drugs in a variety of tissues. OCT3 is identified as one of the important risk loci for prostate cancer, and is markedly underexpressed in aggressive prostate cancers. The goal of this study was to identify genetic and epigenetic factors in the promoter region that influence the expression level of OCT3. Haplotypes that contained the common variants, g.-81G>delGA (rs60515630) (minor allele frequency 11.5% in African American) and g.-2G>A (rs555754) (minor allele frequency>30% in all ethnic groups) showed significant increases in luciferase reporter activities and exhibited stronger transcription factor-binding affinity than the haplotypes that contained the major alleles. Consistent with the reporter assays, OCT3 messenger RNA expression levels were significantly higher in Asian (P<0.001) and Caucasian (P<0.05) liver samples from individuals who were homozygous for g.-2A/A in comparison with those homozygous for the g.-2G/G allele. Studies revealed that the methylation level in the basal promoter region of OCT3 was associated with OCT3 expression level and tumorigenesis capability in various prostate cancer cell lines. The methylation level of the OCT3 promoter was higher in 62% of prostate tumor samples compared with matched normal samples. Our studies demonstrate that genetic polymorphisms in the proximal promoter region of OCT3 alter the transcription rate of the gene and may be associated with altered expression levels of OCT3 in human liver. Aberrant methylation contributes to the reduced expression of OCT3 in prostate cancer.

The UCSF-FDA TransPortal: a public drug transporter database.

Drug transporters play a key role in the absorption, distribution, and elimination of many drugs, and they appear to be important determinants of therapeutic and adverse drug activities. Although a large body of data pertaining to drug transporters is available, there are few databases that inform drug developers, regulatory agencies, and academic scientists about transporters that are important in drug action and disposition. In this article, we inform the scientific community about the UCSF-FDA TransPortal, a new and valuable online resource for research and drug development.

Next steps in addressing the prevention, screening, and treatment of substance use disorder in active duty and veteran Operation Enduring Freedom and Operation Iraqi Freedom populations.

The two articles presented previously in this volume provide state-of-the-art reviews of the etiology, epidemiology, screening and treatment of substance use disorder (SUD). This article identifies next steps in research and development for understanding and treating SUD in Operation Enduring Freedom/Operation Iraqi Freedom service members and veterans. Four promising areas are reviewed: advances in psychopharmacological treatment of SUD, innovations in behavioral treatments, the use of technological advances for the screening and treatment of SUD, and integration of treatment services. Future directions are explored and suggestions for research, development and implementation of each of these trends are discussed.

Left atrial function in cats with left-sided cardiac disease and pleural effusion or pulmonary edema.

BACKGROUND: Congestive heart failure (CHF) in cats with left-sided heart disease is sometimes manifest as pleural effusion, in other cases as pulmonary edema. HYPOTHESIS: Those cats with pleural effusion have more severe left atrial (LA) dysfunction than cats with pulmonary edema. ANIMALS: 30 healthy cats, 22 cats with pleural effusion, and 12 cats with pulmonary edema. All cats were client owned. METHODS: Retrospective study. Measurements of LA size and function were made using commercial software on archived echocardiograms. Cases were identified through searches of medical records and of archived echocardiograms for cats with these conditions. RESULTS: There was no difference (P = .3) in LA size between cats with pleural effusion and cats with pulmonary edema. Cats with pleural effusion had poorer (P = .04) LA active emptying and increased (P = .006) right ventricular (RV) diameter when compared with cats with pulmonary edema and healthy cats. Cats that exhibited LA active emptying of <7.9%, total emptying of <13.6% (diameter) or <19.4% (area), or RV diameter of >3.6 mm were significantly (P < .001) more likely to manifest pleural effusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Poorer LA function and increased RV dimensions are associated with pleural effusion in cats with left-sided heart disease.

Outcome in dogs with surgically resected oral fibrosarcoma (1997-2008).

Oral fibrosarcoma (FSA) is a common oral tumour in dogs, and historically reported survival times after surgical excision range from 7.0 to 12.2 months with local recurrence rates of 32-57%. The purpose of this retrospective study was to report outcome in a cohort of dogs with oral FSA treated with surgical excision with or without adjuvant radiation therapy. Twenty-nine dogs with a histological diagnosis of FSA arising from the oral cavity that underwent surgical resection of their oral FSA were included in this study. Twenty-one dogs were treated with surgical excision alone and eight dogs with both surgery and radiation therapy. The median progression-free interval was >653 days. The median survival time was 743 days. The 1- and 2-year survival rates were 87.7 and 57.8%, respectively. Seven (24.1%) dogs developed local recurrence. Seven dogs (24.1%) developed metastasis.

Exploring the sensitivity of the zone of inhibition test for leachable biocides from paper and board food contact materials, and improvements thereof.

The zone of inhibition method to test the release of biocides from paper and board food contact materials was evaluated. The method tests the paper by placing a small specimen directly onto culture plates of Bacillus subtilis and Aspergillus niger. The principle is that any extractable biocide will diffuse from the paper into the surrounding nutrient medium and so inhibit growth of the microorganism in the vicinity. The test was found to have insufficient sensitivity for assuring food safety, where detection limits for migration at or below the mg l(-1) (parts per million) level are needed. Also, the test does not mimic the actual or foreseeable conditions of use since most paper/board materials are not intended for direct contact with an aqueous medium for up to 3 days at 30°C (B. subtilis) or 25°C (A. niger), which are the incubation conditions used. The sensitivity of the test was increased approximately 100-fold by preparing a concentrated extract of the paper to be tested and applying this extract to the assay via a blank paper carrier. This was done using methanol as a good solvent for most biocides, as a proof of principle. Other solvents or food simulants could be used to mimic the conditions of use intended for the particular paper/board samples under examination, e.g. contact with dry, fatty, aqueous or acidic foods, hot or cold. Twenty-four plain (unconverted) paper and board samples and 100 food packaging samples were evaluated using the modified procedure. The results revealed that the method has been developed to the stage where background cytotoxic action of normal paper constituents gives a weak response. Unlike the original method, therefore, the modified method with its improved sensitivity and the facility to link with the intended food contact conditions may be considered a suitable bioassay screening test to complement chemical analysis of paper/board for composition and migration.