Piotr Małkowski

Human albumin: old, new, and emerging applications.

Human serum albumin has been widely used in an array of clinical settings for nearly 7 decades. Although there is no evidence to support the use of albumin rather than crystalloid in acute volume resuscitation, many clinicians continue to use albumin because it has other important physiologic effects besides the oncotic function. In keeping with the improved understanding of albumin physiology and pathophysiology of many acute and chronic diseases, use of albumin for medical applications has increased in recent years. This, along with increased costs of manufacturing and lower production volume of medical-grade albumin, has lead to an ongoing shortage and rapid increase in albumin prices. This review is based on the analysis of major publications, related to albumin chemistry, physiology, and medical uses including guidelines developed by professional and governmental organizations. Results reflect current knowledge about the role of albumin in health and disease and relevance of albumin therapy in specific clinical settings. Albumin therapy is currently recommended in spontaneous bacterial peritonitis with ascites, refractory ascites not responsive to diuretics, large-volume paracentesis, post-paracentesis syndrome, and the treatment of hepatorenal syndrome as an adjunct to vasoconstrictors. New indications for albumin therapy are linked to the antioxidant activity of albumin and its effects on capillary integrity. In recent years, large-pore hemofiltration and albumin exchange have emerged as promising liver support therapies for liver failure and other toxic syndromes. They are designed to remove a broad range of blood-borne toxins and to restore normal functions of the circulating albumin by replacing defective forms of albumin and albumin molecules saturated with toxins with normal albumin. In view of the ongoing worldwide shortage and high cost of human albumin (native and recombinant), new usage criteria, protocols, and guidelines for appropriate utilization of albumin are needed.

Early everolimus-induced pneumonitis in a renal transplant recipient: A case report.

BACKGROUND Everolimus is a derivative of sirolimus, and is considered to be free of the latters pulmonary toxicity. Recently, a few cases of everolimus-induced lung injury have been reported. Early recognition of drug-induced lung disease is important because it can be reversed if appropriate therapy is instituted soon after the onset of symptoms. CASE REPORT We present the case of an everolimus-induced pneumonitis in a renal transplant recipient, which occurred as early as on the 5th day after everolimus introduction. Shortly after the transplant procedure, the patient presented with typical symptoms of pulmonary infection. Chest radiography and computed tomography showed bilateral patchy lung infiltrates with peribronchial distribution that were suggestive of bacterial pneumonia. However, there was no improvement with empiric antibiotic treatment. Repeated cultures from the blood, sputum, and broncho-alveolar lavage (BAL) also were negative. Tuberculosis, Pneumocystis jiroveci, and Cytomegalovirus infections were excluded. A transbronchial lung biopsy performed 9 days after the onset of symptoms revealed mild nonspecific inflammation with a fibrotic component in the bronchial walls. Withdrawal of everolimus on the third day of hospitalization and after 8 days of its usage resulted in quick clinical recovery and resolution of radiological abnormalities within 1 month. CONCLUSIONS Diagnosis of drug-induced pulmonary toxicity is difficult because it is essentially a diagnosis of exclusion. Lack of response to empiric antibiotic treatment and an imaging pattern of organizing pneumonia should raise suspicion of everolimus-induced pneumonitis in patients undergoing therapy with this drug.

Attitude of Healthcare Professionals: A Major Limiting Factor in Organ Donation from Brain-Dead Donors

Public attitude toward deceased donor organ recovery in Poland is quite positive, with only 15% opposing to donation of their own organs, yet actual donation rate is only 16/pmp. Moreover, donation rate varies greatly (from 5 to 28 pmp) in different regions of the country. To identify the barriers of organ donation, we surveyed 587 physicians involved in brain death diagnosis from regions with low (LDR) and high donation rates (HDR). Physicians from LDR were twice more reluctant to start diagnostic procedure when clinical signs of brain death were present (14% versus 5.5% physicians from HDR who would not diagnose death, resp.). Twenty-five percent of LDR physicians (as opposed to 12% of physicians from HDR) would either continue with intensive therapy or confirm brain death and limit to the so-called minimal therapy. Only 32% of LDR physicians would proceed with brain death diagnosis regardless of organ donation, compared to 67% in HDR. When donation was not an option, mechanical ventilation would be continued more often in LDR regions (43% versus 26.7%; P < 0.01). In conclusion, low donation activity seems to be mostly due to medical staff attitude.

Recommendations for the treatment of hepatitis C in 2017

The goals of treatment is to eliminate HCV infection, stop or reverse histological changes, reduce the risk of hepatocellular carcinoma development and transmission of the infection to other individuals. According to the recommendation of the Polish Group of Experts for HCV in 2017 all patients with chronic HCV infection should receive treatment, but it is not recommended in patients at high risk of short overall survival. If access to therapy is restricted, priority should be given to patients whose HCV infection can lead to an unfavourable outcome of the disease within a short time frame, particular to individuals with liver cirrhosis, rapidly progressing liver fibrosis, extrahepatic manifestations of HCV infection, chronic kidney diseases, patients before and after organ transplantation. Current recommendations of Polish Group of Experts for HCV provide guidelines to select optimal medication, assessment of liver fibrosis, treatment efficacy, dealing with resistance to direct acting antivirals, monitoring for hepatocellular carcinoma, management of HBV/HCV coinfection and drug interactions. It constains also advice on treatment of special patients populations such as renal failure, liver transplant and hepatic decompensation, as well as retreatment of patients which failed interferon free therapy. Moreover specific recommendations of management patients infected with different genotypes with currently reimbursed regimens or those expected to become available shortly in Poland are also included.

Recommendations for the treatment of hepatitis C issued by the Polish Group of HCV Experts – 2016

BACKGROUND Diseases of HCV aetiology are rarely diagnosed on the basis of the clinical picture, as their course is usually asymptomatic or only mildly symptomatic for many years. Consequently, diagnosis is frequently preceded by an incidental detection of laboratory markers indicative of HCV infection. Studies conducted in Poland in recent years have shown that anti-HCV antibodies are found in 0.9-1.9% of the Polish population, depending on the study population and the methodology applied. The studies have consistently confirmed the presence of HCV-RNA in the blood, indicating active infection, at 0.6%. The figure corresponds to approx. 200,000 adult Poles who require immediate diagnosis and treatment. The number of patients diagnosed during the period of HCV therapy availability is estimated to be approx. 35,000, which is equivalent to the detection rate of 17.5% [1-3]. HCV genotype (GT) 1 is the most prevalent one among the Polish population: it is found in 80% of all infected individuals, the most common (98%) sub-genotype being GT1b. GT3 (14%) and GT4 (5%) are less common, and infections with genotypes 2, 5 and 6 may be diagnosed sporadically [4]. Around 20-40% of acute infections are thought to resolve spontaneously. Chronic HCV infection only manifests itself after many years, and one in five patients develop advanced pathological changes in the liver including cirrhosis or hepatocellular carcinoma. HCV infection also induces a number of extrahepatic syndromes, most typically cryoglobulinemia which gives rise to clinical manifestations in 5-25% of cases, and B-cell non-Hodgkin lymphoma (B-NHL) [5]. All patients with chronic HCV infection should receive treatment. The sooner the therapy is initiated, the better the outcome and the lower the cost. However, if access to therapy is restricted, priority should be given to those patients whose HCV infection, in the assessment of an infectious diseases specialist, can lead to a deterioration of the quality of life or death within a short time. The aims of treatment are to eliminate HCV infection and, consequently, to stop or reverse histological lesions, and to reduce the risk of development of hepatocellular carcinoma and prevent the spread of the infection to other people [6, 7].

Progress in abdominal organ transplantation

Summary The excellent results of vascularized organ transplantation have resulted in an increasing number of end-stage organ failure patients seeking such treatment. The results of organ transplantation depend on a number of factors – the quality of the donor (and an organ), living vs. deceased donation, magnitude of ischemic injury (and its prevention), and recipient-dependent factors. Ischemia/reperfusion injury in organ transplantation is a multifactorial process, which may lead to delayed graft function. In addition, surgical and preservation techniques, type of immunosuppressive regimens, complications after transplantation and post-transplant management may also have a significant impact on short- and long-term results of transplantation. In this paper we describe advances in transplantation in recent years, with particular emphasis on kidney, liver, intestines, whole pancreas and pancreatic islets.

A comparison between two tacrolimus-based immunosuppression regimens in renal transplant recipients: 7-year follow-up.

BACKGROUND Immunosuppression (IS) following transplantation should focus on improving long-term graft and patient survival. The objective of this study was to assess patient and graft survival rates and adverse event (AE) incidence in patients treated with combinations of tacrolimus (TAC) and steroids (ST) with either azathioprine (AZA) or mycophenolate mofetil (MMF). MATERIAL AND METHODS Seventy-seven renal transplant recipients (RTRs) treated with TAC/AZA/ST (n=37) or TAC/MMF/ST (n=40) in a single center were studied retrospectively. For 6 months after transplantation, patients were managed according to the COSTAMP study protocol. Afterwards, the follow-up visits were performed yearly for 7 years. Intent-to-treat (ITT) and on randomized therapy (ORT) groups were compared. Primary endpoints were graft function, graft loss, and death. Secondary endpoints included incidence of post-transplant diabetes mellitus (PTDM) and other AEs as estimated by the length of the hospitalization per patient per year. RESULTS Demographic characteristics were similar in both groups of patients. Patient and graft survival at 7 years were 89.2% and 70.3% in TAC/AZA ITT; 97.5% and 77.5% in TAC/MMF ITT; and 100% in both ORT groups, respectively (ns). Differences in renal function, PTDM, and other AE incidence were also non-significant. CONCLUSIONS Our results indicate that TAC-based IS with either MMF or AZA is equally effective with respect to patient and graft survival and AE incidence. Taking into account the costs of both regimens and those of related AE therapies, our results raise the question of whether increasing MMF use in RTRs is justified from the perspective of the long-term results.

Recommendations for the treatment of hepatitis B in 2017

The therapeutic goal which is currently unfrequent but realistic in HBV infected patients is sustained HBsAg clearance. It is preceded by the loss or significant suppression of HBV replication and leads to inhibition of the progression of liver fibrosis, normalization of biochemical indicators of liver damage, reduction in the risk of hepatocellular carcinoma, prolongation of survival, prevention of HBV infection in the transplanted organ in post-transplant patients, enhancement of the quality of life, inhibition or reversal of extrahepatic changes associated with HBV infection, and halting of the spread of HBV infections. Recommendations of Polish Group of Experts for HBV for 2017 provide guidelines to assess treatment eligibility, choice of the first-line drug, monitoring and duration of treatment, management of treatment failure as well as therapy of HBV associated cirrhosis or hepatocellular carcinoma. Moreover it contains advice for treatment of HBV infection in children, females planning pregnancy or pregnant. We also included recommendations for pre- and post-exposure prophylaxis, prevention of HBV transmission from mother to infant, after liver transplantation, on immunosuppressive therapy and during HCV treatment.

Do all well-differentiated thyroid cancers constitute a definite contraindication to obtaining organs for transplantation? A case report.

In this case a thyroid gland tumor was diagnosed with fine needle aspiration (FNA) in a 34-year-old female donor of a liver fragment for living related liver transplantation. This diagnosis disqualified her as a donor. The increased incidence of thyroid cancer in Poland presents the possibility of their occurrence in potential donors. Well-differentiated thyroid papillary carcinomas larger than 1 cm in diameter, as well as follicular and medullary carcinomas (regardless their size and or clinical staging), present absolute contraindication to donation. Papillary microcarcinoma restricted to the thyroid gland (with no metastases in local lymph nodes) because of its specific behavior and almost always benign course, requires an individualized approach. It seemed that when a recipient is in a life-threatening condition, we should consider taking organs from a donor suffering of papillary microcarcinoma restricted to the thyroid gland.

Albumin Apheresis for Artificial Liver Support: In Vitro Testing of a Novel Filter: Albumin Apheresis for Liver Support

Currently there is no direct therapy for liver failure. We have previously described selective plasma exchange therapy using a hemofilter permeable to substances that have a molecular mass of up to 100 kDa. The proof‐of‐concept studies and a Phase I study in patients with decompensated cirrhosis demonstrated that hemofiltration using an albumin‐leaking membrane is safe and effective in removing target molecules, alleviating severe encephalopathy and improving blood chemistry. In this study a novel large‐pore filter for similar clinical application is described. The performance of the filter was studied in vitro; it was found to effectively remove a wide spectrum of pathogenic factors implicated in the pathophysiology of hepatic failure, including protein bound toxins and defective forms of circulating albumin. Data on mass transport characteristics and functionality using various modes of filtration and dialysis provide rationale for clinical evaluation of the filter for artificial liver support using albumin apheresis.