Evaluation of the safety and effectiveness after switch from adalimumab originator to biosimilar SB5 in patients with inflammatory bowel disease in a real-life setting.

Background and study aims: Prospective data are lacking on evolution of trough levels, effectiveness, acceptance rate and patient satisfaction after switch from the adalimumab originator to a biosimilar in patients with inflammatory bowel disease. Patients and methods: Patients in clinical remission or stable response and treated with adalimumab originator in 2 Belgian centers were offered to participate in this phase IV, prospective trial in which patients were switched to adalimumab biosimilar SB5. The primary outcome was the description of adalimumab trough levels over time. Secondary outcomes were secondary loss of response, disease activity, patient satisfaction score and drug persistence over 12 months. Results: The study included 110 patients. Mean baseline adalimumab trough level was 9.21 µg/ml. Concentration remained within the therapeutic range over time. No changes were observed in disease activity scores nor in biochemical parameters over time. The acceptance rate of switch was 84.6%. By month 12, 74.5% was still treated with SB5. The most frequent reason for discontinuation was occurrence of adverse events. 50% of these adverse events were injection site pain. The local discomfort was only significant the first 30 minutes after injection. Satisfaction with the decision to switch to SB5 was high and remained stable over time. Conclusions: After being well informed the great majority of patients treated with the adalimumab originator is willing to switch to biosimilar SB5. In our study, there was a persistence rate of 75% over one year. The trough levels remained within the therapeutic range and no change in disease activity was seen over time.

The impact of rifaximin on the hospital burden and infections in patients with hepatic encephalopathy: a retrospective observational study.

Background and study aims: Advanced liver disease frequently culminates in hepatic encephalopathy (HE), which can be classified as covert or overt HE, with subtle or clinically obvious changes respectively. 30-40% of patients with cirrhosis develop overt HE, which negatively affects the patients' quality of life. Next to lactulose, rifaximin-α has been prescribed as a second line therapy to treat and reduce the risk of recurrence of overt HE. In this study, we aimed to evaluate the effect of rifaximin-α therapy, both on the number of occurring infections and on the evolution in hospital admissions of patients with overt HE. Patients and methods: A total of 66 cirrhotic patients, treated for at least 6 months with rifaximin-α at AZ Maria Middelares, between October 1st 2014 and January 1st 2020, were included in the study analysis. Medical records of all patients were evaluated over a period of 6 months prior and after initiation of rifaximin-α therapy. Results: Data analysis revealed that the included cirrhotic patients were severely ill, with a mean model for end-stage liver disease (MELD) score of 21, and a median Child Pugh score of 11. Among these patients, rifaximin-α treatment significantly downgraded the total number of infections, with a main effect on respiratory infections. Furthermore, rifaximin-α therapy led to a significant decrease in HE-related, as well as in other liver-related hospital admissions. Conclusions: This study confirms the potential value of rifaximin-aα in reducing the number of developing infections and hospital admissions in a severely ill cirrhotic patient population.

An atypical cause of right lower abdominal pain: amoebiasis, a family cluster.

In this case report we present a family cluster of amoebiasis in a nonendemic region. A 46-year-old women, diagnosed with Crohn's disease for which she received no maintenance therapy, was evaluated for the suspicion of a flare. At colonoscopy however, atypical findings for Crohn's disease were seen. Histopathologic examination revealed micro-organisms compatible with amoebiasis. Interestingly, 4 years before this event she started a new relationship with a 38-year-old man who was diagnosed with liver-amoebiasis 3 months after the start of their relationship. On top of this, her 18-year-old daughter was diagnosed with amoebiasis 2 years after her diagnosis. The source of the infection remains unknown, but we speculate that the infection was transmitted feco-orally between the different members of this family. These cases illustrate that we should be aware of parasitological causes of colitis, especially in patients with atypical endoscopic images or when a close "relative" is diagnosed with amoebiasis.

[Evaluation of the usefulness of suction drainage in the treatment of nonspecific bone infections monitored with C-reactive protein]. / Procena uspesnosti protocne drenaze u lecenju nespecificne infekcije kosti pracenjem C-reaktivnog proteina.

INTRODUCTION: Irrigation suction drainage (ISD) is an additional method in treatment of infected bones. Two liters of saline solution daily with an antibiotic is usually recommended for ISD, although some authors suggest that more fluid should be used without antibiotics, stressing the importance of the mechanical effect. Although the method is nowadays accepted as a routine procedure, the reported results of ISD are based on treatment of a limited number of patients and the only criteria for assessment have been clinical and bacteriologic findings. The aim of this prospective study is to show the importance of the mechanical effect of an increased fluid run and the optimal time necessary for cleaning of the osteomyelitic cavity by follow-up the C-reactive protein (CRP) levels as an indicator of an acute inflammation of the affected bone. METHODS: The prospective study was an open, centralized and randomized clinical investigation including over 105 patients with bone infection treated in the period 1986-1996. Two parameters with possible influence on the CRP levels were determined during investigation: 1. patients were divided in three groups depending on the duration of the irrigation suction drainage (3-6 days, 7-10 days and over 10 days) and 2. quantity of the liquid used for the irrigation suction drainage (two groups: 2000 ml per day and 6000 ml per day). Groups were similar in regard to age, sex, bacteriologic agents, duration of infection, localization and previous operations. C-reactive protein (CRP) is a nonspecific, but extremely sensitive indicator of an acute inflammatory disease. The erythrocyte sedimentation rate is not always a reliable indicator of infection. CRP as a protein of an acute phase appears and disappears quickly. Decreased values are a sign of a healing process used in this study for the estimation of the efficacy of the ISD. The CRP level was controlled semiquantitatively before operation and every third day over three weeks. If the values were below 6 mg/l, the results were classified as negative. RESULTS: There were not significant statistical differences in different groups as far as a preoperative average CRP values were concerned neither in the quantity of employed liquid nor in the duration of the ISD and interaction between these two groups. It was the same on the third postoperative day. The differences appear in the significantly lower average values of the CRP in patients of the second group (6000 ml/day) where the ISD lasted for seven or more days. During further follow up, (6th to 21st day) one can observe a significant statistical difference in average CRP values between the first (2000 ml/day) and second group (6000 ml/day) but there is not difference when the duration and sort of employed liquid is concerned. There is not significant difference in average statistical values of the CRP in blood for interaction of fluid quantity and time of ISD as well. DISCUSSION: The main disadvantage in the function of ISD is nonuniform rinsing of the osteomyelitic cavity. Prolonged ISD has no influence on the clinical result as well as on the average values of the CRP. Starting from the third postoperative day results indicate that the quantity of employed liquid has an important influence on the average level of the CRP, while the duration of ISD is not important. Prolonged ISD can not compensate for an inappropriate surgical intervention because it is only an additional method in the treatment of an osteomyelitic process. CONCLUSION: By observing changes in CRP levels during treatment one can conclude that the efficacy of ISD is based mostly on mechanical rinsing and the removal of debris. This points to the importance of the quantity of fluid employed in irrigation suction drainage. Application of 6000 ml liquid per day without antibiotics during 5-7 days gives opportunity of better rinsing increasing the effect of ISD and reducing the incidence of complications.

Experimental study of the hydrodynamic effects of irrigation suction drainage.

The function of irrigation suction drainage, as an additional method in the treatment of bone infection, is associated with hydrodynamic problems that can only be experimentally examined. The visualization of liquid movement in the experimental model was realized by adding a colored ink to the input drain of the drainage system. When only 2000 ml of liquid was used daily (80 drops/min), the ink penetrated the experimental cavity only through the most proximal holes in the input drain. It spread slowly and irregularly through the liquid in the experimental bottle, forming pocket deposits and leaving sediment. When 6000 ml of liquid was applied daily (240 drops/min), ink quickly penetrated the cavity through all holes in the drain, leading to turbulence and dispersing equally in the bottle. Decoloration of the model bottle was faster because the output drainage was more efficient. With an increased flow, i.e., with more liquid used in the drainage, a better result was achieved. This was manifested in a swift decoloration and rinsing of the cavity.

[The Institute of Surgery in Novi Sad as a trauma center--10 years' experience]. / Institut za hirurgiju u Novom Sadu kao trauma centar--desetogodisnje iskustvo.

UNLABELLED: Trauma is a surgical disease and a leading cause of death in the population in the age of forties. The Institute for Surgery in Novi Sad (trauma center of the first rank) takes care of all injured people brought to the Institute either directly from the place of accident or from other centers. AIM OF THE STUDY: Retrospective analysis of the injured people treated at the Institute for Surgery in the period 1987-1996. MATERIAL AND METHODS: Multivariate analysis of the traumas from the register of the Institute for Surgery according to the trauma system elements: number of injured individuals, sex and age structure, categorization of injuries, etiology of injuries, distribution of serious injuries by regions, results obtained from the treatment of serious injuries. RESULTS: They show a global representation of all elements involved with injured people: due to moderately serious, serious and critically serious injuries 21.6% of patients were hospitalized; in the age of 29-30 years men with traumas caused on work or in traffic were predominant, while women with injuries caused by falling were predominant in the age of 60-69 years; drastically increased injuries caused by fire-arms in the period 1991-1993 were directly caused by the state of war and these injuries are still numerous; in case of hospitalized patients isolated trauma (80%) was predominant, multiple trauma was under 20% and polytrauma was registered in 5% of patients; after surgical treatment of injuries approximately 17% of patients were indicated for postoperative prolonged treatment and in intensive care unit at the Institute for Surgery; the average mortality of hospitalized patients was 5-7% but with extremely high mortality rate (< 70%) in the group of patients with polytraumas.

[Registar of injuries--a specific data base]. / Registar povreda--specificna racunarska baza podataka.registar provreda

The existing data bases - on the number and distribution of the injured are unfortunately unreliable and very poor. There is also a shortage of information needed in assessing human and financial aspect of the trauma as well as physical, social, economic and psychological circumstances under wich injuries have heppened. That is why the bases of all activities linked with solving the existing problems in traumatism in the traumawork of Trauma System presents epidemiological methods in the form of Trauma Register. Trauma Register is intended for creation of data base wich would identify, describe, quantity and quality injuries and traumatic deaths including even risk factors and it is expected to help in planning of the future health policy, volume and quality of preventive measures and activities wich would be useful for more accurate monitoring of preventive measures and acitivities wich would be useful for more accurate monitoring of preventive role in decreasing values of frequency of injuries and accidental deaths.

Vasculitides associated with infections, immunization, and antimicrobial drugs.

Many pathogenic microbes can induce a complex series of immunologic, endothelial-cell, and hemorheological activation cascades and dysfunctions and can cause interactions of various components of the vessel wall with formed and noncellular elements of the blood. These interactions can result in manifold vasculitides. This article reviews the pathogenetic, clinicopathologic, and therapeutic aspects of infection-related vasculitides; it includes a brief discussion of parasitic, drug-related, and immunization-associated vasculitides as well as of the infection-related features of vasculitides of the central nervous system, retinal vasculitides, ecthyma gangrenosum, and erythema nodosum. Viruses are mainly associated with small-vessel vasculitides, whereas bacterial infections affect vessels of all sizes, including the aorta. The vasculitides associated with fungal infection usually are characterized by erythema nodosum and involve large vessels. The search for microbes as causes of or contributors to vasculitides should continue. Infectious vasculitides may become increasingly important as the number of immunocompromised patients grows.

Isolated dislocation of the carpal scaphoid: two case reports.

Two unusual cases of isolated dislocation of the carpal scaphoid are presented. They were treated in a conservative way, and both of them achieved good functional results.

[Fracture of a transfixed intramedullary nail in a patient with pseudoarthrosis of the femoral diaphysis]. / Prelom transfiksiranog intramedularnog klina u bolesnika s pseudoartrozom dijafize femura.

This is a case report on a patient with a multiple femur's fracture where a transfixed intramedullar nailing of Grosse-Kempf type has been done. "The nail dynamization" was not carried out before the beginning of vertical loading. Seven months after the full vertical loading had begun, at a sudden torsian movement of the extremity, the nail had broken. Analyzing the cause of the fixative material fracture, a conclusion has been made that, apart from the presence of adequate trauma, the nail fracture happened also due to the development of pseudoarthrosis of femur and the unfulfilled "nail dynamization".

Thrombo-embolic and vascular complications in vasculitis syndromes.

The vasculitides are relatively rare diseases characterized by inflammation and necrosis of vessel walls and, hence, often complicated by vascular and thromboembolic manifestations. The causes and pathogenesis of most vasculitides are only partially known. However, in many there are strong implications of both immune-complex and cell-mediated pathogenetic mechanisms. Tissue ischaemia, thrombosis as well as mediators and end-products of vascular endothelial inflammation are thought to cause most of the vasculitic manifestations. Thrombo-embolic and cardiovascular manifestations and complications are most commonly found in the vasculitides with necrotizing vascular inflammation, i.e. Behçet's disease, Buerger's disease, Kawasaki's syndrome, polyarteritis nodosa and vasculitis of rheumatoid arteritis. The granulomatous vasculitides are less frequently complicated by thrombo-embolic manifestations. Vasculitis may also be an iatrogenic complication of a therapeutic intervention, such as an IC-mediated hypersensitivity vasculitis after streptokinase treatment or an anti-endothelial cell antibody-associated coronary vasculitis after heart transplantation.

Fibrillar protein deposits with tubular substructure in a systemic disease beginning as cutis laxa.

BACKGROUND: The homogeneous material found in the skin is commonly identified as amyloid. We describe a previously unknown disease that is caused by proteinaceous deposits and that does not fulfill the criteria of the earlier recognized amyloid diseases. OBSERVATIONS: The unusual deposits, which were initially found in the dermis, were ultrastructurally composed of fibrillar material with a tubular substructure. Immunohistologically, the material was tested using a large panel of antibodies, and the results revealed that it was unlike any commonly known proteinaceous material. The deposits later spread to other organs and disturbed the vital functions of the body. CONCLUSIONS: We describe a unique syndrome characterized by fibrillar extracellular deposits that was recognized and differentiated from other similar clinical syndromes by ultrastructural examination. Further biochemical analysis is necessary to identify the origin of the material.

Disorders of blood viscosity.

In clinical situations associated with disturbed blood flow, the primary focus is usually on improving cardiovascular performance. However, during recent decades, both basic science and clinical literature reports have presented evidence that the flow properties of blood must also be considered in these situations. Thus, the relatively new fields of haemorheology and clinical haemorheology have evolved; the former deals with the flow and deformation behaviour of blood, plasma and the formed elements of blood, whereas the latter relates to alterations of their behaviour in various pathophysiologic states. This review therefore summarizes some of the salient aspects of clinical haemorheology and of the determinants of blood flow properties (flow rate, haematocrit, plasma viscosity, red cell aggregation, red cell deformability). In addition, it briefly describes several clinical disorders associated with abnormal blood, plasma or cell rheology ('hyperviscosity syndromes' occurring in polycythaemia, leukaemia, sickle cell disease, paraproteinaemias).

[Morphologic characteristics and static resistance of transplanted patellar ligaments after replacement of the cruciate ligaments in the knee--an experimental study in a dog]. / Morfoloske osobine i staticka otpornost autotransplantata ligamenta patele nakon zamene prednjeg ukrstenog ligamenta kolena--eksperimentalna studija u psa.

An experimental study on transplantation validity of patella's ligament, when transplanting front crossed ligament, was performed on 106 knees in 53 grown-up dogs. The investigation had three stages. Three months after the transplantation of the front crossed ligament with the medial third part of the patella's ligament animals were sacrificed and in one group the static resistance and the resistance to elongation, by using special tweezers (Alfred Amsler Co., Schafhausen, Switzerland), was investigated. The results showed that the patella's ligament is very suitable for transplantation because its resistance and strength were almost identical with the same parameters of intact front crossed ligament. Revascularization of the new ligament using Spaltenholz's technique was done in the second group, and three months after the operation, complete revascularization of transplants took place. The synovial membrane which covers the new ligament represents the main source of fresh blood vessels on one side, while similar process takes place along the bone tunnels where the new ligament was fixed. The new ligament histologic analysis carried out in the third group of experimental animals showed that after three months the transplant acquires the structure which is very similar to the front crossed ligament. The obtained results of the investigation show that the patella's ligament is a very good biologic material for transplantation of the crossed ligament.