The antifracture efficacy of vitamin D in adults - are we assessing it reliably? A systematic review.

INTRODUCTION: The antifracture efficacy of vitamin D is still controversial. The aim of this systematic review was to examine if the vitamin D trials were designed adequately to reliably assess its antifracture activity. MATERIAL AND METHODS: The electronic databases PubMed, Medline, Embase, Web of Science, and Cochrane Library were searched to identify clinical trials evaluating the antifracture efficacy of vitamin D in adults. We compared the protocols of the trials against the opinions of the American Society for Bone and Mineral Research (ASBMR), International Society for Clinical Densitometry (ISCD), National Osteoporosis Foundation (NOF), European Medicines Agency (EMEA) experts, and the consensus statement from the 2nd International Conference on Controversies in Vitamin D, and against the protocols of the trials of the medications with proven antifracture efficacy (bisphosphonates, teriparatide, abaloparatide, raloxifene, denosumab, romosozumab). We assessed the prospective character, study design, group description, number of patients, study duration, and vitamin D (serum examination and dosage) supplementation. A description of the desired characteristics of the study protocol was presented. RESULTS: Thirteen eligible trials were identified. All but 2 were conducted in the elderly population only. Nine trials were included in the final analysis. Serum 25-hydroxy vitamin D (25OHD) was not measured in a representative number of subjects before (except in 2 studies), during, or after treatment in any study. CONCLUSIONS: The analysed studies did not conclusively assess the vitamin D antifracture efficacy in patients with prestudy low serum vitamin levels, due to the lack of assessment of whether sufficient doses of vitamin D were used. They informed about the relevant doses and preparations of vitamin D in particular groups (specific fracture risk, age, place of residence) only.

Should Thorax Thin-Section Computed Tomography Be a Standard Diagnostic Procedure in the Evaluation of Potential Kidney Transplant Recipients? Lessons Learned From the COVID-19 Pandemic.

BACKGROUND: Kidney transplant is the preferred treatment for most patients with end-stage renal disease. Because dialyzed patients often have significant comorbidities or multimorbidities, they should be carefully evaluated before being waitlisted for transplant. The COVID-19 pandemic presents a major challenge for surgery, including transplant surgery. Owing to a fear of COVID-19 symptoms occurring in lungs, thin-section computed tomography (TSCT) became a standard evaluation technique in potential kidney transplant recipients before surgery. METHODS: The aim of the study was to evaluate the rationale and usefulness of TSCT in deceased donor kidney transplant during the COVID-19 pandemic. All adult patients who underwent deceased donor kidney transplant between May 1, 2020, and December 15, 2021, were included in the study. Potential kidney transplant recipients who were admitted to the Department of General, Vascular, and Transplant Surgery at the Medical University of Warsaw in Warsaw, Poland, were tested for COVID-19 (CovGenX rapid test); blood chemistries were performed; dialysis was performed (if needed); and, on a negative reverse transcriptase polymerase chain reaction test, HRCT was performed. RESULTS: From May 2020 until the end of December 2021, 54 patients were transplanted; however, 7 patients were disqualified after TSCT and consulted with a pulmonary specialist. Disqualification from kidney transplant accounted for 13% of the potential kidney allograft recipients. CONCLUSIONS: Despite the possibility of overdiagnosis by TSCT, TSCT should be considered a standard evaluation technique in potential kidney transplant recipients. Potential kidney transplant recipients must be periodically reassessed given the prolonged wait time for a donor kidney and the significant number of comorbid conditions in this patient population. However, more data with longer follow-ups are needed to prove or disprove the rationale to use TSCT in transplant surgery.

THE IMPORTANCE OF MENTAL RESILIENCE AGAINST LONELINESS DURING THE COVID-19 PANDEMIC IN DIALYSIS PATIENTS.

The pandemic crisis of COVID-19 has caused anxiety and depressive symptoms to increase in many people worldwide. Yet, difficult situations may not only lead to various types of disorders, fears, anxieties and feelings of loss. They can also lead to positive changes, even to development or growth after experienced trauma, to positive adaptation, to changes in self-perception, changes in interpersonal relations or philosophy of life. Patients with chronic kidney disease, especially those on renal replacement therapy, often experience severe psychological problems such as anxiety disorders, depressive disorders, or difficulties related to coping with excessive stress. The aim of our review is to disscus the appropriatness of mental health screening tools in patients with chronic kidney disease, including those on dialyses, during COVID-19 pandemic. Recently published studies indicate the limited available data evaluating the diagnostic accuracy of screening tools for mental status in patients with chronic kidney disease. This, it seems reasonable to stress the mental health associations with situational stress in this group of patients during the SARS-CoV-2 pandemic. It is also worth pointing out the need to research the impact of the mental disorders in this population on morbidity and mortality, taking into account other organ complications and the quality of life of patients not only during the SARS-CoV-2 pandemic. It is worth to to make every effort to reduce the severity of the anxiety and feelings of hopelessness in dialysis patients, to cope with the pandemic.

Potential Effects of Immunosuppression on Oxidative Stress and Atherosclerosis in Kidney Transplant Recipients.

Chronic kidney disease is a public health problem that, depending on the country, affects approximately 8-13% of the population, involving both males and females of all ages. Renal replacement therapy remains one of the most costly procedures. It is assumed that one of the factors influencing the course of chronic kidney disease might be oxidative stress. It is believed that the main mediators of oxidative stress are reactive oxygen species (ROS). Transiently increased concentrations of ROS play a significant role in maintaining an organism's homeostasis, as they are part of the redox-related signaling, and in the immune defense system, as they are produced in high amounts in inflammation. Systemic oxidative stress can significantly contribute to endothelial dysfunction along with exaggeration of atherosclerosis and development of cardiovascular disease, the leading cause of mortality in patients with kidney disease. Moreover, the progression of chronic kidney disease is strictly associated with the atherosclerotic process. Transplantation is the optimal method for renal replacement therapy. It improves better quality of life and prolongs survival compared with hemodialysis and peritoneal dialysis; however, even a successful transplantation does not correct the abnormalities found in chronic kidney disease. As transplantation reduces the concentration of uremic toxins, which are a factor of inflammation per se, both the procedure itself and the subsequent immunosuppressive treatment may be a factor that increases oxidative stress and hence vascular sclerosis and atherosclerotic cardiovascular disease. In the current work, we review the effect of several risk factors in kidney transplant recipients as well as immunosuppressive therapy on oxidative stress.

Uremic Toxins, Oxidative Stress, Atherosclerosis in Chronic Kidney Disease, and Kidney Transplantation.

Patients with chronic kidney disease (CKD) are at a high risk for cardiovascular disease (CVD), and approximately half of all deaths among patients with CKD are a direct result of CVD. The premature cardiovascular disease extends from mild to moderate CKD stages, and the severity of CVD and the risk of death increase with a decline in kidney function. Successful kidney transplantation significantly decreases the risk of death relative to long-term dialysis treatment; nevertheless, the prevalence of CVD remains high and is responsible for approximately 20-35% of mortality in renal transplant recipients. The prevalence of traditional and nontraditional risk factors for CVD is higher in patients with CKD and transplant recipients compared with the general population; however, it can only partly explain the highly increased cardiovascular burden in CKD patients. Nontraditional risk factors, unique to CKD patients, include proteinuria, disturbed calcium, and phosphate metabolism, anemia, fluid overload, and accumulation of uremic toxins. This accumulation of uremic toxins is associated with systemic alterations including inflammation and oxidative stress which are considered crucial in CKD progression and CKD-related CVD. Kidney transplantation can mitigate the impact of some of these nontraditional factors, but they typically persist to some degree following transplantation. Taking into consideration the scarcity of data on uremic waste products, oxidative stress, and their relation to atherosclerosis in renal transplantation, in the review, we discussed the impact of uremic toxins on vascular dysfunction in CKD patients and kidney transplant recipients. Special attention was paid to the role of native and transplanted kidney function.

Kidney Function After Liver Transplantation in a Single Center.

BACKGROUND Renal dysfunction in the peri-transplant period appears to complicate both short- and long-term outcome of liver transplantation (LT). The aim of this study was to analyze the impact of selected clinical features in the peri-liver transplant period, as well calcineurin inhibitor, particularly tacrolimus given after LT, on kidney function in a single liver transplant center's experience. MATERIAL AND METHODS A total 125 consecutive liver-grafted individuals (82 M, 43 F), mean age 50±13 y (with alcohol-related liver disease in 48 (38%) patients) were included into the study. Their clinical data were collected in the database until 46 months of follow-up, and the Python packages Pandas (version 0.22.0) and scikit-learn (version 0.21.3) were used for data analysis. RESULTS More advanced liver disease as judged by Child-Pugh class and MELD score differed significantly patients with preserved (serum creatinine SCr <1.5 mg/dL) and impaired (SCr ≥1.5 mg/dL) kidney function before LT. Older age and higher SCr pre-LT were associated with higher levels of SCr after LT in 2 time-points. SCr before LT was correlated with delta SCr for the highest and last recorded value (P<0.0001). Higher amounts of transfused colloids during surgery were associated with increased delta SCr for the highest value (P=0.019) after grafting in logistic regression analysis. There were no associations between SCr after LT and duration of anhepatic phase, urine output ≤100 mL/h, or post-reperfusion syndrome during transplantation (all P>0.05). There were no associations between SCr after LT and tacrolimus trough levels in analyses of correlations and linear regression analyses (all P>0.05). CONCLUSIONS We found that pretransplant serum creatinine was the only factor affecting kidney function after LT in our liver transplant center. The restricted fluid policy was safe and effective in terms of long-term renal function. The role of kidney-saving immunosuppressive protocols in preserving renal function long-term after LT was also confirmed.

Liver Transplantation for Acute Intermittent Porphyria.

Recurrent attacks of acute intermittent porphyria (AIP) result in poor quality of life and significant risks of morbidity and mortality. Liver transplantation (LT) offers a cure, but published data on outcomes after LT are limited. We assessed the pretransplant characteristics, complications, and outcomes for patients with AIP who received a transplant. Data were collected retrospectively from the European Liver Transplant Registry and from questionnaires sent to identified transplant and porphyria centers. We studied 38 patients who received transplants in 12 countries from 2002 to 2019. Median age at LT was 37 years (range, 18-58), and 34 (89%) of the patients were women. A total of 9 patients died during follow-up, and 2 patients were retransplanted. The 1-year and 5-year overall survival rates were 92% and 82%, which are comparable with other metabolic diseases transplanted during the same period. Advanced pretransplant neurological impairment was associated with increased mortality. The 5-year survival rate was 94% among 19 patients with moderate or no neuropathy at LT and 83% among 10 patients with severe neuropathy (P = 0.04). Pretransplant renal impairment was common. A total of 19 (51%) patients had a GFR < 60 mL/minute. Although few patients improved their renal function after LT, neurological impairments improved, and no worsening of neurological symptoms was recorded. No patient had AIP attacks after LT, except for a patient who received an auxiliary graft. LT is a curative treatment option for patients with recurrent attacks of AIP. Severe neuropathy and impaired renal function are common and increase the risk for poor outcomes. If other treatment options fail, an evaluation for LT should be performed early.

Clinical Relevance of Kidney Biopsy in Patients Qualified for Liver Transplantation and After This Procedure in the Model for End-stage Liver Disease (MELD) Era: Where Are We Today?

Chronic kidney disease (CKD) has been recognized as an increasingly common complication of liver transplantation (OLTx). Post-transplant renal dysfunction contributes to long-term morbidity and mortality following OLTx and is a very important issue in the management of liver transplant recipients. Its etiology is multifactorial and can be determined by kidney biopsy, which is too rarely done in this patient group. In the clinical context of patients with liver cirrhosis, accurate and reliable evaluation of the renal injury is crucial. We performed a review of kidney biopsies in patients with symptoms of CKD (proteinuria/hematuria/elevated creatinine) before and after liver transplantation in the published literature. Kidney biopsies were performed either before or after liver transplantation using percutaneous technique. There are few reports on transjugular kidney biopsy. Biopsy results prevented unnecessary modification of immunosuppressive therapy or selection of candidates for liver transplantation. In our opinion, kidney biopsy is a clinically relevant diagnostic approach to recognize kidney disease before and after liver transplantation, it also helps with the management of kidney disease in this population, and it is safe. Kidney biopsy should be offered more often in liver transplant patients to ensure appropriate therapy in concomitant CKD in this population. Our decisions today will impact clinical outcomes in the future.

Human Papillomavirus (HPV) DNA Detection Using Self-Sampling Devices in Women Undergoing Long Term Immunosuppressive Therapy.

Immunosuppression is a risk factor of persistent human papillomavirus (HPV) infections, which might lead to development of (pre)malignant lesions of the cervix and lower anogenital tract. Results of HPV DNA testing using cervicovaginal self-samples are comparable to those that are clinician-obtained and therefore might be used in cervical screening. The aim of this study was to assess the prevalence of high-risk HPV (hrHPV) infections, their risk factors and the genotypes distribution among women undergoing immunosuppressive therapy. Women undergoing immunosuppressive therapy for at least three months due to solid organ transplantation or autoimmune disorders were asked to self-collect samples for HPV testing using cervicovaginal brushes and complete questionnaires regarding cervical cancer risk factors. HPV DNA detection and genotyping were performed using Genotyping kit HPV GP version 2. hrHPV was detected in 26/90 (28.9%) specimens. Genotyping revealed a broad range of hrHPV, with type 16 being the most common genotype (11/26). The components of bivalent/quadrivalent or nonavalent vaccines cover all genotypes present in 4.4% and 17.8% women, respectively, and occur as a co-infection with other types in 12.2% and 23.3% of women, respectively. The only feature significantly associated with being hrHPV-positive was having at least two lifetime sexual partners. The high prevalence of hrHPV infections among immunosuppressed women emphasizes the need for regular cervical cancer screening with HPV DNA testing, which might be performed on self-collected specimen.

Treatment of hepatitis C in selected clinical settings.

This article aims to review the treatment strategy of Hepatitis C in compelling indications and provide the literature update, mainly discussing the EASL (European Association for the Study of the Liver) recommendations, which described the current optimal management of patients with acute and chronic HCV infections. The review will focus on HCV infection in selected clinical settings including patients with immune complex-mediated manifestations of chronic hepatitis C, patients with chronic kidney disease (CKD) or renal end-stage renal disease (ESRD), and solid organ transplant recipients.

Approach to a patient with hepatitis c: diagnosis and pretreatment assessment.

Chronic infection with hepatitis virus C affects more than 70 million individuals worldwide. Hepatitis C infection is the leading cause of end-stage liver disease, hepatocellular carcinoma, and multiple extrahepatic manifestations associated with immune system disorders and chronic inflammation. In the era of interferon-free anti-HCV regimens, clinical care for patients with HCV-related liver disease and extrahepatic complications has advanced significantly because of improvements in therapy and prevention. The antiviral capacity of a new generation of direct-acting agents provide high rates of sustained virological response, and it is expected to improve clinical outcomes in these patient populations. The article aims to review published data on the treatment strategy of hepatitis C, including the EASL (European Association for the Study of the Liver) recommendations.

Pretransplant QT Interval: The Relationship with Severity and Etiology of Liver Disease and Prognostic Value After Liver Transplantation.

BACKGROUND Prolonged QT interval is an integral part of the definition of cirrhotic cardiomyopathy. The aim of this study was to analyze the relationship between QT corrected (QTc) and the etiology and the severity of liver disease in relation to the complications of cirrhosis in candidates for orthotropic liver transplantation (OLTx). MATERIAL AND METHODS From 360 consecutive patients with end-stage liver disease (ESLD) consulted by a designated cardiologist, 160 patients underwent OLTx. The QTc was calculated according to 3 formulas in 151 ECG tracings with good quality. The severity of liver disease was assessed according to Child-Pugh classification and model for end-stage liver disease (MELD). This was a single-center study with register-based follow-up design. RESULTS Prolonged QTc over 440 ms was found in 51 subjects (33.8%), but none had prolonged QTc >500 ms. QTc corrected by Fridericia (F) formula was more suitable for patients with ESLD. We found no correlation between QTc interval and severity of liver disease. The QTc interval was higher in patients with alcoholic cirrhosis when compared to patients with viral hepatitis and ESLD of other etiologies. We observed a higher QTc interval in patients with gastroesophageal varices and encephalopathy. We did not notice any significant difference in the effect of the QTc interval on survival. CONCLUSIONS QTc interval might be associated with etiology and complication of ESLD. The prolonged QT interval is not associated with higher all-cause mortality after OLTx.

The Pre-Transplant Profile of Cardiovascular Risk Factors and Its Impact on Long-Term Mortality After Liver Transplantation.

BACKGROUND Cardiovascular disease (CVD) is an important aggravating factor for orthotopic liver transplantation (OLT) outcomes. CVD still seems to be one of the most common cause of death in the long-term post-transplant period. Nevertheless, there are some limited data regarding the optimal strategy of risk assessment during OLT candidate evaluation. MATERIAL AND METHODS Routine pre-transplant cardiac workup in 360 patients with end stage liver disease (ESLD) included electrocardiogram, echocardiography, and exercise stress testing. The aim of this retrospective study was an analysis of the impact of cardiovascular risk profile on overall mortality in the 2-year follow-up of 160 patients who underwent liver transplantation. RESULTS Cardiovascular risk factors or a history of CVD were found in 23.1% of patients who received transplants. The cardiovascular risk factors most common in our group of transplant recipients with ESLD were: diabetes (26.3%), hypertension (25.6%), and hepatopulmonary syndrome (23.1%). Only 3.8% of patients had a positive exercise test. Coronary angiography revealed at least 50% stenosis in some epicardial arteries in 1.9% of patients. The risk of death in long-term follow-up of liver transplant recipients was most strongly associated with 3 cardiac variables: history of coronary artery disease (CAD), angiographically confirmed coronary stenosis, and reduced ejection fraction (EF). CONCLUSIONS Our study identified pre-transplant CAD with its consequences as a factor associated with increased risk of negative post-transplant outcomes.

Good outcome following liver transplantation using pericardial-peritoneum window for hepato-atrial anastomosis to overcome advanced hepatic alveolar echinococcosis and secondary Budd-Chiari Syndrome - a case report.

BACKGROUND: This report presents a case of a 57- year old female with advanced Hepatic Alveolar Echinococcosis causing a secondary Budd-Chiari Syndrome due to infiltration of the suprahepatic inferior vena cava treated successfully by liver transplantation. CASE PRESENTATION: A temporary veno-venous bypass was introduced, but a typical end to end cavo-caval anastomosis wasn't possible in this case. In order to access a disease free part of the inferior vena cava, an oval window of the diaphragm was excised, providing communication between the peritoneum and pericardium. A vascular clamp was placed onto the right atrium which allowed for an atrial-caval anastomosis. The remainder of hepatectomy was performed in a conventional manner. In the post-operative period and during the 18 month follow-up there were no complications. The patient remains in good general condition with optimal graft function. CONCLUSIONS: A hepato-atrial anastomosis with a pericardial-peritoneum window during liver transplantation is feasible and extends the curability potential for patients with advanced Hepatic Alveolar Echinococcosis considered for liver transplantation.

Generalized Posttransplant Kaposi Sarcoma without Mucocutaneous Manifestations in the First Liver Transplantation in an HIV-Positive Patient in Poland: A Case Report and Review of Literature.

BACKGROUND Kaposi sarcoma (KS) is the most frequent skin cancer in solid organ recipients, and also a typical malignancy in HIV-infected persons. CASE REPORT We describe here a rare case of primary nodal KS without mucocutaneous manifestations, diagnosed in a 20-year-old HIV/HBV co-infected patient 12 months after liver transplantation (LT), the first one performed in a HIV-positive patient in Poland. The course of the disease was very aggressive; the patient died four weeks after general lymphadenopathy appearance. In the autopsy, KS infiltration was found in numerous lymph nodes and in the lung' apexes without skin or other organs' involvement. CONCLUSIONS In conclusion, posttransplant KS may present as general lymphadenopathy without mucocutaneous manifestations, thus mimicking posttransplant lymphoproliferative disorder, which is often the first clinical suspicion. Lymph node histopathological examination is necessary to make the right diagnosis.

Acetaminophen (Paracetamol) induced acute liver failure - A social problem in an era of increasing tendency to self-treatment.

INTRODUCTION: The widespread availability of medication without prescription, so-called over the counter (OTC), and the rapid development of health consciousness of Poles is associated with broad access to medical information in the mass media. This causes patients to recognize their own disease, cancel doctor's appointments, and begin self-treatment. This time and money-saving behavior, often signaled by pain, usually leads to the treatment of symptoms alone, without seeking the cause of the disease.The aim of the study was to present life-threatening paracetamol poisoning, and the treatment of acute liver failure. MATERIAL AND METHODS: In 2002-2014, 35 patients were hospitalized due to acute paracetamol poisoning: 17 female and 18 male patients aged between 17-59 (mean 32.3 years). Patients were treated in the surgical intensive care unit, where their parameters of liver and renal function were continuously monitored. If there was no improvement in the liver function, patients underwent albumin dialysis with the Prometheus system and were qualified for liver transplantation (LTx). RESULTS: 26 patients were treated pharmacologically and 7 out of 9 patients who underwent LTx were dialyzed. Overall, 11 patients had 26 albumin dialysis in total; 4 patients died - 1 post-transplant and 3 pre-transplant. CONCLUSIONS: Paracetamol is the cause of many poisonings resulting from the lack of public awareness about toxic interactions with alcohol, and suicide attempts. Acetaminophen-induced acute liver failure concerns a small percentage of patients but can be successfully treated with albumin dialysis, and in extreme cases by liver transplantation.

Evolution Of The Results Of 1500 Liver Transplantations Performed In The Department Of General, Transplant And Liver Surgery Medical University Of Warsaw.

UNLABELLED: Liver transplantation is a well-established treatment of patients with end-stage liver disease and selected liver tumors. Remarkable progress has been made over the last years concerning nearly all of its aspects. The aim of this study was to evaluate the evolution of long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw). MATERIAL AND METHODS: Data of 1500 liver transplantations performed between 1989 and 2014 were retrospectively analyzed. Transplantations were divided into 3 groups: group 1 including first 500 operations, group 2 including subsequent 500, and group 3 comprising the most recent 500. Five year overall and graft survival were set as outcome measures. RESULTS: Increased number of transplantations performed at the site was associated with increased age of the recipients (p<0.001) and donors (p<0.001), increased rate of male recipients (p<0.001), and increased rate of piggyback operations (p<0.001), and decreased MELD (p<0.001), as well as decreased blood (p=0.006) and plasma (p<0.001) transfusions. Overall survival was 71.6% at 5 years in group 1, 74.5% at 5 years in group 2, and 85% at 2.9 years in group 3 (p=0.008). Improvement of overall survival was particularly observed for primary transplantations (p=0.004). Increased graft survival rates did not reach the level of significance (p=0.136). CONCLUSIONS: Long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery are comparable to those achieved in the largest transplant centers worldwide and are continuously improving despite increasing recipient age and wider utilization of organs procured from older donors.