Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients.

Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed ~140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with ~30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-γ production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.

Nosocomial bloodstream infections in ICU and non-ICU patients.

BACKGROUND: Nosocomial bloodstream infections (BSI) create a serious health problem in hospitals all over the world. The objectives of our study were to explore putative disease markers and potential risk factors with nosocomial BSI in patients in intensive care units (ICU) and non-ICU patients and to determine risk factors associated with increased 28-day mortality rate in patients with nosocomial BSI acquired in combined medical-surgical ICU. However, the major purposes of this report were to identify epidemiologic differences between nosocomial BSI acquired in ICU and non-ICU, as well as analyses outcomes for patients with nosocomial BSI acquired in ICU. METHODS: A 1-year prospective cohort study was performed to determine the incidence of nosocomial BSI in hospitalized patients. Patient characteristics, risk factors related to health care, and source of infection of patients with BSI acquired in non-ICU were compared with those patient with BSI acquired in ICU. Also, nested case-control study of patients to nosocomial BSI acquired in ICU was performed to evaluate outcome. Patients were identified by active surveillance and positive blood culture during the study period. RESULTS: The incidence of nosocomial BSI was 2.2 per 1000 admission in non-ICU patients and 17.4 per 1000 admission in ICU patients. The 28-day crude mortality rate was 69% in ICU patients. A multivariate model showed that nasogastric tube (RR, 25.1; 95% CI: 3.845-163.85; P=.001), mechanical ventilation (RR, 13.04; 95% CI: 1.974-96.136; P=.008), and H2 blockers (RR, 12.16; 95% CI: 1.748-84.623; P=.012) were more prevalent among patients with BSI acquired in ICU, and aggressive procedures (RR, 8.65; 95% CI: 1.70-44.00; P=.009) were more prevalent among patients with BSI acquired in non-ICU patients. Risk factors independently associated with increased 28-day mortality rate in ICU patients were mechanical ventilation (OR, 8.63; 95% CI: 1.5-49.8; P=.016) and SAPS II >40 (OR, 6.0; 95% CI: 1.0-35.7; P=.049). The most common isolated nosocomial BSI pathogens (in both groups of patients) were coagulase-negative staphylococci (21%), Staphylococcus aureus (14%), and Klebsiella species (13%). Klebsiella species was the only organism independently influencing the poor outcome of nosocomial BSI in ICU patients (OR, 4.3; 95% CI: 1.2-15.3; P=.022). CONCLUSIONS: Our results show epidemiologic differences between non-ICU and ICU BSI. Also, this study suggests that severity of underlying host conditions, mechanical ventilation, and microbial agents (Klebsiella species) affect the outcome of NBI in patients in ICU.

Clinical significance of soluble Fas plasma levels in patients with sepsis.

BACKGROUND/AIM: The goal of modern clinical and experimental researches in the field of sepsis is to find one or more sensitive parameters that could predict the severity of sepsis and its outcome. In this study we investigated and compared the relationship of initial soluble Fas (sFas) plasma levels as well as Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) score in 58 septic patients with severity and outcome of sepsis. METHODS: The diagnosis and assessment of disease severity was performed on the same day, based on clinical and laboratory parameters. The blood samples were used for monitoring of laboratory standard parameters necessary for the diagnosis of sepsis, organ dysfunction and assessment of disease severity, as well as for determination of levels of sFas. According to consensus criteria, patients were divided into those with sepsis (n = 16), severe sepsis (n = 30) or septic shock (n = 12), those with (n = 26) and without (n = 32) multiple organ dysfunction syndrome (MODS), and survivors (n = 45) and nonsurvivors (n = 13). RESULTS: Plasma sFas level (9.7 ± 10.1; 0-44.2 U/mL) was elevated in 54.4% of patients. All the patients with septic shock, 76.9% of the patients with MODS and 84.6% patients who died had elevated sFas level. We observed a strong positive correlation between sFas and APACHE II score (p < 0.001). The level of sFas was significantly higher in patients with septic shock compared to normotensive patients (p < 0.001), patients with MODS compared to those without MODS (p < 0.001) and survivors compared to nonsurvivors (p < 0.01). CONCLUSIONS: Our results suggest that initial sFas plasma levels in patients with sepsis correlated with the values of APACHE II score and separated very well the patients with septic shock versus the normotensive patients, the patients with and without MODS, and survivors versus nonsurvivors.

Streptococcal Necrotizing Fasciitis with Toxic Shock Syndrome and Rapid Fatal Outcome.

INTRODUCTION: Streptococcal necrotizing fasciitis (NF) is a serious soft tissue infection with rapid progression of inflammatory process among superficial or deep fascia, systemic host response to infection leading to toxic shock syndrome (TSS), and multiple organ failure. Lethality is high. CASE OUTLINE: A 46-year-old male without co-morbidities was admitted to the Emergency Department with redness, swelling and pain on his right lower leg. He became sick two days earlier with malaise, chills and shivering. On admission he was hypotensive, anuric, with erythematous rash on his face, neck and chest, with acute renal failure and elevated creatine phosphokinase level. During the next several hours, the changes on his right lower leg rapidly spread to the whole leg, followed by skin destruction and subcutaneous bleeding, indicating NF. Aggressive antimicrobial, supportive and symptomatic therapy was initiated immediately and on the same evening surgical intervention was performed. Despite these measures, a rapid development of severe TSS, with lethal outcome, occurred in less than 40 hours after the admission. Streptococcus pyogenes (group A ß-hemolytic Streptococcus) was isolated from the throat, skin and tissue obtained during the surgery. CONCLUSION: Necrotizing fasciitis is a very serious disease with unpredictable course. For that reason doctors must devote a great deal of attention to early, i.e. timely diagnosis of this disease, whose treatment with a multidisciplinary approach is very important.

Surgical site infection surveillance in orthopedic patients in the Military Medical Academy, Belgrade.

BACKGROUND/AIM: Active surveillance is an important component of surgical site infection (SSI) reduction strategy. The aim of this study was to analyze and compare SSI surveillance data in orthopedic patients in the Military Medical Academy (MMA), Belgrade. METHODS: A 4-year prospective cohort study was performed to identify the incidence rate and risk factors for SSI in orthopedic patients in the MMA, Belgrade. We collected data regarding patients characteristics, health care and micro-organisms isolated in SSI. The National Nosocomial Infection Surveillance (NNIS) risk index was subsequently calculated for each patient. The Centers for Disease Control and Prevention criteria were used for the diagnosis of SSI. RESULTS: Assessment of 3,867 patients after different orthopedic operations revealed SSI in 109 patients. The overall incidence rate of SSI was 2.8% with the decrease from 4.6% in 2007 to 1.6% in 2010. Using NNIS risk index for surgical procedures there were: 53.7% (2,077) patients with risk 0--the incidence rate of 1.4%; 38.9% (1,506) patients with risk 1--the incidence rate of 3.1%; 7.3% (281) patients with risk 2--the incidence rate of 11.7%; 0.1% (3) patients with risk 3--without infection within the risk. Multivariate logistic regression analysis identified 6 independent risk factors associated with SSI: contaninated or dirty wounds, smoking, preoperative infection, NNIS risk index, body mass index and the length of hospital stay. CONCLUSION: The results of our study are valuable confirmation of relations between risk factors and SSI in orthopedic patients. A decreasing incidence rate of SSI (from 4.6% to 1.6%) during a 4-year active surveillance approved its implementation as an important component of SSI reduction strategy.

Severe form of streptococcal necrotizing fasciitis of the upper limb--diagnostic and therapeutic challenge: A case report.

INTRODUCTION: Since delay in recognition and effective treatment of necrotizing fasciitis (NF) caused by invasive group A streptococcus increases the mortality and disability, the early diagnosis and management of this disease are essential for a better outcome. We presented a patient with a severe form of streptococcal NF of the left upper limb in whom amputation was performed as a life saving procedure. CASE REPORT: A 65-year-old man, previously healthy, suffered an injury to his left hand by sting on a fish bone. Two days after that the patient got fever, redness, swelling and pain in his left hand. Clinical examination of the patient after admission indicated NF that spread quickly to the entire left upper limb, left armpit, and the left side of the chest and abdomen. Despite the use of aggressive antibiotic and surgical therapy severe destruction of the skin and subcutaneous tissues developed with the development of gangrene of the left upper limb. In this situation, the team of specialists decided that the patient must be operated on submitted to amputation of the left arm, at the shoulder. After amputation and aggressive debridement of soft tissue on the left side of the trunk, the patient completely recovered. beta-hemolytic streptococcus group A was isolated from the skin and tissue obtained during the surgery. CONCLUSION: In the most severe forms of streptococcal NF of the extremities, adequate multidisciplinary treatment, including limb amputation, can save the life of a patient.

Disseminated Rhodococcus equi infection in a patient with Hodgkin lymphoma.

INTRODUCTION: Rhodococcus (R) equi is an opportunistic, uncommon human pathogen that causes mainly infection in immunocompromised hosts. The disease is usually presented as subacute pneumonia that is mostly cavitary and sometimes bacteremic. CASE REPORT: We reported the extremly rare case of a 43-year-old woman with Hodgkin lymphoma, who developed R equi pulmonary infection after recieving multiple courses of chemotherapy. Secondary, the patient developed bacteremia, leading to sepsis and dissemination of R equi infection in many extrapulmonary sites. At addmission the patient was febrile, tachypnoic, tachycardic, hypotensive, with fa cial edema, splenomegaly, positive meningeal signs, left hemiparesis and paraparesis. Laboratory data included erythrocyte sedimentation rate (ESR) > 140 mm/h, C-reactive protein (CRP) 143.0 mg/L, red blood cells (RBC) 2.14 x 10(12)/L, whyite blood cells (WBC) 2.8 x 10(9)/L, lactate dehydrogenase (LDH) 706 U/L, serum albumin 26 g/L, sodium 127 mmol/L and potassium 2.7 mmol/L. Blood culture and culture of sputum and empyema were positive for R equi. Imaging studies demonstrated a large right cavitary pneumonia and abscess, empyema, pericarditis, mediastinal and intra-abdominal lymphadenopathy, brain and psoas abscesses, osteomyelitis and spondylodiscitis. The patient recovered completely after a 12-month treatment with combinations of parenteral and oral antibiotics (meropenem, vancomycin, teicoplanin, ciprofloxacin, rifampicin, macrolides etc), including drainage of abscesses and empyema. Eight years after completition of the treatment the patient was without recurrence of R equi infection and lymphoma. CONCLUSION: Since the eradication od R equi is very difficult, it is very important to make the diagnosis and initiate appropriate antibiotic therapy as soon as possible.

Atypical form of cat scratch disease in immunocompetent patient.

INTRODUCTION: Cat scratch disease (CSD) is an acute infectious disease with benign course caused by the bacteria Bartonella henselae. Clinically, it is usually manifested as regional lymphadenopathy and mild infective syndrome. Rare forms of the disease which usually occur in immunocompromised presons are: encephalitis, transverse myelitis, neuroretinitis, granulomatosus conjunctivitis, arthritis, hepatitis etc. CASE REPORT: We presented an atypical form of cat scratch disease in a young immunocompetent female person. The disease was manifested with prolonged fever, rash, purulent lymphadenitis and hepatitis. The diagnosis was based on characteristic patohystological finding and exclusion of the other causes of lymphadenopathy. The patient was treated by antibiotics for a few weeks, with surgical incision and drainage of the purulent lymphadenitis. CONCLUSION: Atypical forms of CSD could be an important differential-diagnostic problem, especially if there is no opportunity for serological confirmation of the disease.

Efficacy of amifostine in protection against doxorubicin-induced acute cardiotoxic effects in rats.

BACKGROUND/AIM: Amifostine (AMI) is a broad-spectrum cytoprotector which protects against variety of radio- and chemotherapy-related toxicities without decreasing their antitumor action. The aim of the study was to investigate the potential protective effects of AMI against acute cardiotoxic effects of doxorubicin (DOX) in male Wistar rats. METHODS: AMI (300 mg/kg ip) was given 30 min before DOX (6 mg/kg and 10mg/kg b.w., iv). The evaluation of DOX-induced cardiotoxic effects, as well as cardioprotective efficacy of AMI was performed 48 h after their administration by determining serum activities of enzymes known to be markers of cardiac damage (creatine kinase - CK, aspartate aminotransferase - AST, lactate dehydrogenase - LDH, and its isoenzyme alpha-hydroxybutirate dehydrogenase - alpha - HBDH), as well as the histopathological and ultrastructural analysis of the heart tissue. RESULTS: AMI successfully prevented a significant increase in serum activity of CK, AST, LDH and alpha-HBDH in animals treated with DOX in the dose of 6 mg/kg (121.14 +/- 18.37 vs 167.70 +/- 44.24; 771.42 +/- 161.99 vs 1057.00 +/- 300.00; 3230.00 +/- 1031.73 vs 4243.10 +/- 904.06; 202.57 +/- 42.46 vs 294.90 +/- 80.20 UI/l, respectively), and ameliorated DOX-induced structural damage of the rat myocardium. Pretreatment with AMI in rats given 10 mg/kg DOX reduced the cardiac damage score (CDS) from 2.62 +/- 0.51 to 1.62 +/- 0.51, i.e. to the CDS value obtained with the lower dose of DOX (6 mg/kg). The ultrastructural analysis of the rat myocardium showed that AMI successfully protected the sarcolemma of cardiomyocytes and reduced mitochondria damage induced by DOX given in the dose of 6 mg/kg. Besides, capillaries were less morphologically changed and apoptosis of endothelial cells was extremely rare in AMI-protected animals. AMI itself did not cause any prominent changes in the examined parameters in comparison with the control rats. CONCLUSION: AMI provided a significant protection against DOX-induced acute cardiotoxic effects in rats. This finding implies its potential to be a successful cardioprotector in patients treated with DOX due to malignant diseases.

Subdural tuberculous abscess of the lumbar spine in a patient with chronic low back pain.

INTRODUCTION: Despite modern imaging methods, tuberculous abscess in the subdural space of the spine can lead to misdiagnosis and to neurogical complications development, even more up to paraplegia. We presented an extremely rare case of subdural tuberculous abscess of the lumbar (L) spine and paraparesis in imunocompetent a 49-year-old patient. CASE REPORT: A patient with chronic L syndrome and a history of intervertebral (IV) disc L3 and L5 operations got severe back pain late in July 2007. At the same time the patient had a purulent collection in the left knee, and was treated with high doses of corticosteroids and antibiotics. Then, the patient got a high fever, the amplification of pain in the L spine and the development of paraparesis. Erythrocyte sedimentation rate was 108 mm/1 h, C-reactive protein 106.0 mg/L, white blood cell (WBC) 38.4 x 09/L with a left turn. Magnetic resonance imaging (MRI) of the spine was registered expansive formation in the spinal canal, from the level of the IV disc L2 to the mid-L4 vertebral body. This finding is a "spoke" in favor of the extrusion and sequestration of IV disc L3 with the cranial and caudal migration. The patient underwent an emergency neurosurgical operation. The diagnosis of subdural staphylococcal abscess of L spine was made. According to the antibiogram antibiotic therapy was applied but without effect on the course of the disease. Control MRI of the L spine showed spondylodiscitis L3/L4, abscess collection in the spinal canal and paravertebral muscle abscess. Late in September 2007 the patient underwent needle biopsy of the L3 vertebral body guided by computed tomography and the acid-fast bacilli (AFB) were found. Tuberculostatics were introduced in the therapy. Two years later the patient was without significant personal difficulties, and with normal clinical, laboratory and morphological findings. CONCLUSION: Subdural tuberculous abscess of the spine is extremely rare manifestation of spine tuberculosis. The exact and early diagnosis and adequate treatment of atypical form of spine tuberculosis are key factors of good prognosis.

Clinical manifestations, therapy and outcome of pandemic influenza A (H1N1) 2009 in hospitalized patients.

BACKGROUND/AIM: Increasing number of epidemiological and clinical studies to date showed that the pandemic influenza A (H1N1) 2009, by its characteristics, significantly differs from infection caused by seasonal influenza. Therefore, the information about clinical spectrum of manifestations, risk factors for severe form of the disease, treatment and outcome in patients with novel flu are still collected. METHODS; A total of 98 patients (mean age 32 +/- 15 years, range 14-88 years) with the signs and symptoms of novel influenza were treated in the Clinic for Infectious and Tropical Diseases, Military Medical Academy. There were 74 (75.5%) patients with suspected influenza A (H1N1) 2009, 10 (10.2%) with the likelihood and 14 (14.3%) with the confirmed influenza. In all the patients we registered the basic demographic data, risk factors for severe disease, symptoms and signs of influenza, laboratory tests and chest radiography. We analyzed antiviral therapy use and disease outcome (survived, died). RESULTS: The average time from the beginning of influenza A (H1N1) to the admission in hospital was 3 days (0-16 days) and from the moment of hospitalization to the Intensive Care Unit (ICU) admission was 2 days (0-5 days). There were 49 (50.0) patients, 20-29 years of age and 5 (5.1) patients older than 65. A total of 21 (21.4%) patients were with underlying disease, 18 (18.4%) were obese, 19 (19.4) were cigarette smokers. All of the patients had fever, 81 (82.6%) cough, while dyspnea and diarrhea were registered in 4 of the patients. In more than 75% of the patients laboratory tests were within normal limits. The real-time polymerase chain reaction (PCR) test for identification of influenza A (H1N1) 2009 was positive in 14 (77.8%), while pneumonia was verified in 30 (30.7%) of the patients. Six (6.1%) patients, mean age of 45 +/- 14 years (31-59 years) were admitted to the ICU, of whom five (5.1%) had Adult Respiratory Distress Syndrome (ARDS). Risk factors were registered more frequently in the patients with acute respiratory failure (14.2% vs 4.9%, p < 0.05). A total of 67 (68.4%) patients received oseltamivir, 89 (90.1%) was applied to antibiotics and 64 (65.3%) were treated with a combined therapy. Antiviral therapy was applied to 43 (43.3%) patients in the first 48 hours from the onset of the disease, of whom only one (3.4) developed ARDS. Fatal outcome was noted in 2.0% of the patients (2 of 98 patients) and in 33.3% of the patients treated in the ICU. CONCLUSION: Novel influenza A (H1N1) is most commonly manifested as a mild acute respiratory disease, which usually affects young healthy adults. A small number of the patients develop severe illness with acute respiratory failure and death. Patients seem to have benefit from antiviral therapy especially in first 48 hours.

[Blood concentrations of lactate, C-reactive protein, and creatinine as early indicators of severity and outcome of sepsis].

INTRODUCTION: Since the outcome in septic patients can significantly be improved if the appropriate therapy is introduced timely early, the early diagnosis of sepsis and its complications is essential. The aim of this study was to compare mean values of the initial blood concentrations of lactate, C-reactive protein and creatinine and the severity of illness and the outcome of sepsis. MATERIALS AND METHODS: A total of 30 septic patients were included in the study. The diagnosis of sepsis and its complications was made according to consensus criteria. The severity of illness was scored by an acute physiology, age and chronic health evaluation septic score. The patients were subdivided into different groups, those with sepsis, severe sepsis or septic shock, those with or without multiple organ dysfunction syndrome, and survivors and nonsurvivors. RESULTS: The differences in mean values of lactate levels among all studied groups were significantly high, whereas the level of C-reactive protein were significantly higher only in the non-survivors compared to the survivors (p < 0.05). The concentrations of creatinine were significantly higher in the patients with septic shock compared to the patients with sepsis, and in the patients with multiple organ dysfunction syndrome and the non-survivors compared to the corresponding groups (p < 0.05). The septic score clearly discriminated patients with different severity of sepsis, development of multiple organ dysfunction syndrome and survival and positively correlated with the concentrations of lactate, C-reactive protein and creatinine (the best correlation ranks were with lactate levels, p < 0.001). DISCUSSION AND CONCLUSION: Our results suggest that lactate level is a better parameter of illness severity and outcome of sepsis than levels of C-reactive protein and creatinine. When compared to the above parameters, the septic score determined on the day of admission to hospital is a much better criterion to classify patients into groups with different severity of sepsis, with and without multiple organ dysfunction syndrome and into survivors and non-survivors.

[Impossibility of the treatment of inoperable liver multicystic echinococcosis due to adverse reactions to antihelminitics].

INTRODUCTION: In some cases of multicystic forms of liver echinococcal disease, the advanced method for treatment of cystic echinococcosis faces great problems relating to the final outcome of the treatment. CASE REPORT: In May 2005, a computerized tomography of the abdomen obtained in a 27-year-old female patient with abdominal pain revealed more than 20 echinococcal cysts measuring up to 6.7 cm in both lobes of the liver. Laboratory analyses found the value of eosinophils 6.8%, gamma globulins 29.9%, immunoglobulin E 29 600 IU/mL and the indirect hemagglutination for echinococcosis 1:8,196. The treatment started in December that year with the continuous administration of a daily dose of 800 mg (14.5 mg/kg body weight) of albendazole, but it was terminated two months later due to high serum transaminases values. By the end of 2006, the largest cyst detected in the left lobe of the liver had a diameter of 5.7 cm and the one in the right lobe of the liver measured 4.1 cm. There were lesions of germinative membrane found on both cysts. Six months later, praziquantel at daily dose of 2,500 mg (45.3 mg/kg body waight) was introduced into the therapy, but the treatment was terminated after eight days because of the development of exanthema. The computerized tomography of the abdomen obtained in February 2008 revealed the presence of a large number of echinococcal cysts in the liver. The largest among those cysts measured 3.5 cm while calcifications of the cyst walls were observed on some of them. None of the remaining therapeutic options for further treatmetnt of echinococcal disease could be applied. CONCLUSION: The presented case confirms medical therapy as the only option for the treatment of some forms of cystic echinococcosis. Benzimidazole carbamates (albendazole, mebendazole) and praziquantel are only efficacious antihelminitics currently available, and when they have to be withdrawn due to serious adverse affects, futher treatment of a patient with liver multicystic echinococcosis is impossible. Because of that there is a need to search for new and more efficient drugs for the treatment of ehinococcal disease.

[Adverse effects of longterm, continual administration of high doses of albendazole in the treatment of echinococcal disease].

BACKGROUND/AIM: Modern treatment of cystic echinococcosis, except for surgical treatment and percutaneous drainage of cyst considers also administration of albendazole as a type of individual therapy. However, clinicians fear of the serious adverse effects of high doses of albendazole, first of all the elevation of serum transaminases activity, very frequently results in subdosing of albendazole and wrong conclusions its efficacy and safety. The aim of this study was to investigate adverse effects of a longterm, continual administration of high doses of albendazole in the treatment of patients with echinococcal disease. METHODS: A total of 42 patients (mean age 40.4 +/- 18.3 years) with echinococcal disease were included in the study. They were treated with continual administration of high doses of albendazole within the period of 4 to 6 months. The subgroups of 27 and 15 patients were treated with 15-20 mg/kg/day and with 21-25 mg/kg/day albendazole, respectively. The patients in the control group (18 with surgical treatment, 6 with percutaneous drainage of cyst) were treated with 800 mg albendazole per day (< 15 mg/kg body weight) in the cycles of 28 days (1-3 cycles) and a two-week pause between them. RESULTS: In the study group adverse effects of albendazole were registered in 20 (47.6%), whereas in the control group in 6 (30.0%) of the patients. In both subgroups elevated activity of serum transaminases were found more frequently in the study group compared to the control one (35.7% vs 25%, p < 0.05), especially in the patients who were treated with higher doses of albendazole. The patients in the study group, compared to the patients in the control group had significantly higher mean activity of serum alanin aminotransferase in the course of the second and third month of the therapy (p < 0.05). Administration of albendazole due to adverse effects was stopped in 3 (7.1%) of the patients in the study group. Two (4.8%) of them had a very high activity of serum transaminases and one had a muscle pains and high activity of serum creatine kinase. After the interruption of the therapy we documented a nonnalization of serum enzyme levels in all the patients. CONCLUSION: Longterm, continual administration of high doses of albendazole in the patients with echinococcal disease results in significant elevation of serum transaminases activity, compared to the patients treated with albendazole in the cycles, but in the majority of the patients serum transaminases activity was normalizated by the end of a 6-month period.

[Primary localized cutaneous amyloidosis--lichen amyloidosis]. / Primarna lokalizovana kutana amiloidoza--lichen amyloidosus.

This case report presented a female patient with primary-localized-cutaneous-amyloidosis in the form of lichen amyloidosus. Primary-localized-cutaneous-amyloidosis is a rare idiopathic dermatosis caused by abnormal deposition of amyloid composed primarily of degenerated keratin filaments. In order to establish the final diagnosis, detailed clinical and laboratory investigations were performed, with a particular emphasis on pathohistological analysis of skin specimens, special stains, and electron microscopy.

[Multiorgan tuberculosis]. / Multiorganska tuberkuloza.

Tuberculosis is an unusual infectious disease because of the latent period between the infection and the appearance of the disease may be prolonged for many weeks, months, or years as it is in case of the secondary tuberculosis. Tuberculosis in organs other than the lung has been observed for many years but has not always been recognized as tuberculosis, and it has been given many names. Extrapulmonary tuberculosis gained new importance, because it represented a progressively greater proportion of new cases. Multiple extrapulmonary sites were reported rarely except for one anatomical site, which was reported frequently. Extrapulmonary rates increase with age, so there are marked differences in age in specific rate patterns among the sites. Extrapulmonary tuberculosis occurred in respiratory organs other than lung, such as lymphatic, urogenital, and central nervous system, abdominal, osteoarticular, as well as tuberculosis of other organs such as skin, pericardium and endocrine glands. This case was reported to analyse clinical, morphologic and laboratory characteristics, method of diagnosis and the outcome in patients with multiorgan tuberculosis in order to explore the factors which might contribute to the decision making, concerning these forms of tuberculosis. Recent knowledge of pathogenesis was summarized as well as clinical presentation and the effects of cytokines produced by T lymphocytes and cellular population on antimycobacterial immune defences, and also susceptibility to tuberculosis. Mortality remains high and the treatment should start as soon as tuberculosis is suspected.

[Necrotizing fasciitis caused by group A streptococcus]. / Nekrotizujuci fasciitis uzrokovan streptokokom grupe A.

The first case of the confirmed necrotizing fasciitis caused by Group A Streptococcus in Yugoslavia was presented. Male patient, aged 28, in good health, suddenly developed symptoms and signs of severe infective syndrome and intensive pain in the axillary region. Parenteral antibiotic, substitutional and supportive therapy was conducted along with the radical surgical excision of the necrotizing tissue. The patient did not develop streptococcal toxic shock syndrome thanks to the early established diagnosis and timely applied aggressive treatment. He was released from the hospital as completely cured two months after the admission.