Histological Signs Of Infection Research Articles

What's New in Musculoskeletal Infection.

What's New in Musculoskeletal Infection.

Effectiveness of Direct-acting Agents After Liver Transplantation A Real-life Study in Rio de Janeiro

Data concerning hepatitis C virus (HCV) treatment using direct-acting agents (DAAs) post liver transplantation (LT) remains scarce in low- and average-income countries. To evaluate the safety and efficacy of post-LT HCV treatment using DAAs in Rio de Janeiro (Brazil), and to assess the course of hepatic biomarkers after sustained virological response (SVR). Data from LT recipients with recurrent HCV treated using DAAs was retrospectively analyzed. HCV was defined by detectable HCV-RNA with elevated aminotransferases and/or histological signs of infection on liver biopsy post LT. SVR was defined as undetectable HCV-RNA 12 weeks after the end of treatment. Aspartate-to-Platelet Ratio Index (APRI) and Fibrosis-4 score (FIB-4) were calculated before treatment and after SVR. 116 patients (63% male, median age 62 years, 75% genotype 1 and 62% with hepatocellular carcinoma [HCC] prior to LT) were included. Cirrhosis was identified in the allograft of 21 subjects (18%). The overall SVR was 96.6% without differences in SVR proportion according to clinical/demographic characteristics, genotype or presence of cirrhosis. SVR rates were similar in individuals with and without HCC pre-LT (95.8% [95% CI: 87.6-98.7] vs. 97.7% [95% CI: 85.0-99.7%], p=0.588). No serious adverse events were observed and the use of ribavirin was associated with at least one adverse event (OR=8.71 [95% CI: 3.17-23.99]). SVR was associated with regression of APRI (OR=26.00 [95% CI 4.27-1065.94]) and FIB-4 (OR=15.00 [95% CI: 2.30-631.47]). Post-LT HCV treatment with DAAs was safe and effective and associated with a significant decrease in hepatic biomarker levels after SVR.

Клінічна ефективність застосування внутрішньовенного імуноглобуліну у вагітних з внутрішньоутробною інфекцією

Проблема внутрішньоутробної інфекції (ВУІ) і в наш час не втрачає своєї актуальності. Неефективність лікування цієї патології пов’язана з фізіологічним зниженням імунітету у таких пацієнток. Нами запропоновано додаткове використання внутрішньовенного імуноглобуліну для лікування вагітних з ВУІ. Обстежено 75 пацієнток із ВУІ, що була діагностована в них протягом ІІ триместру. І групу становили 40 осіб, які отримували загальноприйняте лікування, ІІ групу сформували 35 жінок, які додатково отримували внутрішньовенний імуноглобулін. На фоні ВУІ перебіг вагітності характеризувався підвищенням частоти загрози її переривання та передчасних пологів, гестозів і плацентарної дисфункції, у пологах були більш поширеними передчасний розрив плодових оболонок і дистрес плода. У таких пацієнток плаценти мали як ультразвукові, так і гістологічні ознаки інфікування. Серед новонароджених було істотне зростання частоти патології, пов’язаної з реалізацією внутрішньоутробного інфікування. Додаткове застосування препарату внутрішньовенного імуноглобуліну при лікуванні ВУІ протягом II триместру вагітності порівняно із загальноприйнятою терапією призводить до вірогідного зниження частоти як акушерських ускладнень, так і перинатальної патології.

Should all patients with a culture-negative periprosthetic joint infection be treated with antibiotics? : a multicentre observational study.

The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld. A multicentre observational study was undertaken: 1,553 acute and 1,556 chronic PJIs, diagnosed between 2013 and 2018, were retrospectively analyzed. Culture-negative PJIs were diagnosed according to the Muskuloskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and European Bone and Joint Society (EBJIS) definitions. The primary outcome was recurrent infection, and the secondary outcome was removal of the prosthetic components for any indication, both during a follow-up period of two years. None of the acute PJIs and 70 of the chronic PJIs (4.7%) were culture-negative; a total of 36 culture-negative PJIs (51%) were treated with antibiotics, particularly those with histological signs of infection. After two years of follow-up, no recurrent infections occurred in patients in whom antibiotics were withheld. The requirement for removal of the components for any indication during follow-up was not significantly different in those who received antibiotics compared with those in whom antibiotics were withheld (7.1% vs 2.9%; p = 0.431). When adequate methods of culture are used, the incidence of culture-negative PJIs is low. In patients with culture-negative PJI, antibiotic treatment can probably be withheld if there are no histological signs of infection. In all other patients, diagnostic efforts should be made to identify the causative microorganism by means of serology or molecular techniques. Cite this article: Bone Joint J2022;104-B(1):183-188.

The Potential Role of Increasing the Release of Mouse β- Defensin-14 in the Treatment of Osteomyelitis in Mice: A Primary Study

Mammalian β-defensins are small cationic peptides that have been implicated in mediating innate immune defenses against microbial infection. Mouse β-defensin-14 (MBD-14), based on structural and functional similarities, appears to be an ortholog of human β-defensin-3 (HBD-3). Previous studies identified signaling pathway p38 mitogen-activated protein kinase (MAPK) that contributed to the expression of MBD-14 in mouse osteoblasts upon contacted with methicillin-resistance Staphylococcus aureus (MRSA) supernatant, which provided a theoretical basis as a promising therapeutic target in the treatment of intramedullary infection with MRSA in vivo. In this study, the medullary cavities of tibiae were contaminated with MRSA 103 colony forming units and different doses of p38 MAPK agonists anisomycin were followed as group III or IV in 30 mice. Fifteen animals that received phosphate- buffered saline served as group II and 15 mice were not contaminated with MRSA and received phosphate-buffered saline served as controls (group I). Follow-up was 7 days. In day 1, day 4 and day 7 postoperatively, infection was evaluated by blood routine, microbiological and histological analyses after sacrifice. All animals of group II developed microbiological and histological signs of infection. Histological signs of infection, white blood counts and cultures of group III and IV showed significantly reduced bacterial growth compared to cultures of group II. Simultaneously, different doses of anisomycin significantly induced the expression of osteoblast-associated genes, including alkaline phosphatase, osteocalcin and collagen type I. In addition, the expression of HBD-3 in human interfacial membranes around infected periprosthetic joint by staphylococcus contaminated was evaluated, and the expression pattern changed with significant induction of HBD-3 in infected periprosthetic joint compared with aseptic loosening under inflammatory conditions. Our primary study indicated that the potential antibacterial role of increased MBD-14 in the osteomyelitis mouse model.

Candida albicans impairs macrophage function and facilitates Pseudomonas aeruginosa pneumonia in rat*

To determine whether Candida albicans airway colonization influences Pseudomonas aeruginosa pneumonia prevalence in rats and by which mechanism. Prospective, randomized, controlled animal study. Research laboratory of a university. Male adult Wistar rats weighing 275-300 g. In vivo: P. aeruginosa pneumonia was induced by bronchial instillation of P. aeruginosa in rats previously instilled or not with live or ethanol-killed C. albicans. In vitro: Alveolar macrophages were incubated with or without live or ethanol-killed C. albicans. Quantitative cultures of lung were done. Lung tumor necrosis factor alpha, interferon gamma, and interleukin-6 levels were measured along with reactive oxygen species (ROS) production by alveolar macrophages. P. aeruginosa pneumonia prevalence was higher in rats given live but not ethanol-killed C. albicans. Instilling live C. albicans alone increased lung tumor necrosis factor-alpha and interferon-gamma but not interleukin-6, and was not associated with clinical or histologic signs of infection. These three cytokines were more abundant in lungs instilled with live C. albicans and P. aeruginosa than in those instilled with P. aeruginosa alone or with ethanol-killed C. albicans and P. aeruginosa. Alveolar macrophages incubated with live C. albicans had decreased ROS production. C. albicans impedes alveolar macrophage ROS production and is correlated with an increase of P. aeruginosa pneumonia prevalence in rats. These results highlight the previously overlooked impact of airway fungal colonization on lung bacterial infection, and indicate the need for studies on the potential for antifungal therapy to prevent the onset of ventilator-associated pneumonia caused by P. aeruginosa.

Fluordeoxyglucose positron emission tomography contributes to management of pediatric liver transplantation candidates with fever of unknown origin

Fever of unknown origin (FUO) frequently complicates the management of pediatric patients with terminal chronic liver failure during the pretransplantation period and may lead to increased morbidity and mortality. Nonhepatic origins of systemic infections may render the patient unsuitable for transplantation whereas infections within the liver may require organ resection for a cure. Therefore, accurate localization of the infection focus is critical for optimal management of children on the waiting list for liver transplantation. Here we report our experience using [18 F]fluordeoxyglucose (FDG)-positron emission tomography (PET) to detect the origin of infection in 11 children with biliary cirrhosis presenting with FUO during the waiting period for liver transplantation. In 5 children, positive intrahepatic FDG-PET signals correlated with bacterial cultures of the excised liver and/or anatomic or histologic signs of infection. Based on the FDG-PET findings, these patients underwent transplantation after continuous antibiotic treatment with ongoing, recurrent episodes of fever. In 6 children, no abnormal hepatic FDG-PET signals were found and no infections could be detected in the liver. Transplantation in these patients was performed only after becoming afebrile. Standard imaging techniques did not reveal abnormalities compatible with infection in any of the children. In conclusion, in children with biliary cirrhosis and FUO on the waiting list for liver transplantation, information obtained by FDG-PET imaging may be useful for decisions on therapy and suitability for liver transplantation.

Morphologic Features of Hepatitis C Recurrence in Patients After Orthotopic Liver Transplantation-Preliminary Analysis of our Case Observations

Introduction Hepatitis C virus (HCV) recurrence is almost universal in patients after liver transplantation. The diagnosis of reinfection is more difficult than that of a primary process, as shown by our pathomorphologic analysis of cases of HCV recurrence. Material During 5.5 years, 240 liver biopsies included 54 obtained from liver transplant recipients with primary HCV infections, among whom 26 (56.5%) had clinical signs and symptoms of hepatitis. Nineteen patients from this population underwent 30 liver biopsies. In addition, seven biopsies were performed in five patients without clinical signs of reinfection. Results In 44.2% of patients with HCV recurrence and 15% without reinfection, the intensity of the primary process in the native livers was assessed as high. Reinfection was found in all patients with liver carcinoma and 67% with hepatocyte dysplasia. Histologic signs of infection were estimated as minimal ( n = 4), mild ( n = 19), or moderate ( n = 4). In five patients with reinfections and one without recurrence, histologic manifestations of acute rejection were also observed. In conclusion, HCV was the indication for liver transplantation in 22.4% cases. Clinical manifestation of recurrence was found in 56.5% of the patients, who tended to be older than those without disease recurrence. Upon microscopy, lobular lesions predominated over the portal changes. Factors predisposing to HCV recurrence were coexistence of other liver disorders, a high intensity of the inflammatory process, hepatocyte dysplasia, and/or hepatocellular carcinoma in the native liver and acute rejection episodes.

Fetal thymic involution: A sonographic marker of the fetal inflammatory response syndrome

The purpose of this study was to evaluate whether there is a relationship between the sonographic fetal thymus size and the presence of an intrauterine infection in patients with preterm labor. Thirty-one women who had been admitted with preterm labor and intact membranes between 24 and 32 weeks of gestation were included. Fetal thymus perimeter was measured sonographically, and amniocentesis for the microbiologic assessment of the amniotic cavity was performed. Placentas and umbilical cords were examined for the presence of chorioamnionitis/funisitis. The prevalence of preterm delivery and intra-amniotic infection was 51.6% (16/31 women) and 32.3% (10/31 women), respectively. In all cases with intrauterine infection and in 23.8% of cases without intrauterine infection, the fetal thymus perimeter was below the 5th percentile for gestational age (10/10 women vs 5/21 women; P < .01). Isolated histologic chorioamnionitis and funisitis were found in 22.6% and 25.8% of fetuses, respectively. The fetal thymus was below the 5th percentile for gestational age in 100%, 71.4%, and 12.5% of patients with histologic signs of funisitis and isolated chorioamnionitis and without histologic signs of infection, respectively. Fetal thymus involution in preterm labor patients is strongly associated with funisitis, which is the histologic manifestation of the fetal inflammatory response syndrome.

Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats

Antibiotic prophylaxis is a routine procedure in orthopedic surgery. Various local antibiotic delivery techniques are used to reduce bone- and soft tissue-related infection. The objective of this study was to evaluate the efficacy of a new biodegradable, gentamicin-loaded poly( d, l-lactide) (PDLLA) coating of orthopedic devices in preventing implant-related osteomyelitis. The medullary cavities of tibiae in 30 Sprague Dawley rats were contaminated with Staphylococcus aureus (10 3 colony forming units). Simultaneously titanium Kirschner wires, uncoated (group II), coated with PDLLA (group III), or coated with PDLLA + 10% gentamicin (group IV), were implanted. Ten animals that received phosphate-buffered saline and uncoated Kirschner wires served as controls (group I). Follow-up was 6 weeks. In weekly intervals X-rays of the tibiae were performed, blood counts were taken, and body temperature and weight were determined. After sacrifice infection was evaluated by histological and microbiological analysis. All animals of groups II and III developed microbiological, histological, and radiological signs of infection, including osseous destruction and soft tissue swelling. All animals of the control group remained sterile. Cultures of implants of group IV showed significantly reduced bacterial growth compared to cultures of groups II and III, and three implants of group IV remained sterile. Further radiological and histological signs of infection were significantly reduced in the gentamicin-coated group compared to groups II and III. No significant differences in body weight, body temperature, and blood parameters between all groups were observed. Local application of antibiotic-coated orthopedic devices containing PDLLA and 10% gentamicin significantly reduced implant-related infection in this animal model.

Osseointegration of hydroxyapatite-coated, polyethylene-intruded and uncoated, sandblastered pure titanium implants in an infected implantation site. An experimental investigation in miniature pigs

The authors studied the ingrowth dynamics of bone tissue into the pores of Hydroxyapatite-coated and uncoated wire-meshs of pure titanium in an infected implantation site. Samples of the tested materials were implanted into femora of 15 adult Göttingen minipigs. Just before implantation they were contaminated with Staphylococcus aureus. The animals were killed after 4, 8, 12 and 24 weeks. Undecalcified groundsections of bone tissue were prepared (app. 100 µm) for comparative histological evaluation. The HA-coated implants demonstrated advanced new bone formation after 4 weeks and nearly complete osseointegration after 12 weeks although all samples showed gross and histological signs of infection. Comparable reactions to the uncoated implants could only be observed after 24 weeks. Signs of degradation of the Hydroxyapatite-coating could be seen in contact to soft tissue and were more extensive compared to the behaviour in an uninfected site.

Zur Wertigkeit von Leukozyten, C-reaktivem Protein und Granulozytenelastase bei Patientinnen mit vorzeitigem Blasensprung und Amnioninfektion

Serum concentrations of leucocytes, C-reactive protein (CRP) and elastase-alpha 1-proteinase inhibitor (E alpha 1 PI) have been determined in 85 women during pregnancy and after birth to assess their diagnostic value in case of amniotic infections (AI). In ten patients clinically diagnosed AI could be confirmed by histopathological examination, three patients who fulfilled the clinical criteria showed no histological signs of infection. E alpha 1 PI-levels were found to be elevated to over 200 meg/l in six patients with clinical and histological infection and remained below this value in all other cases whereas leucocyte- and CRP concentrations raised in five out of these eight women but also showed false positive values in patients without AI. The application of betamethasone led to a marked elevation of leucocyte concentration. CRP levels were raised substantially after birth, whereas E alpha 1 PI remained unchanged. It is suggested that all three parameters should be taken into consideration to increase diagnostic reliability in case of suspected amniotic infections.

Effects of Anti-Thymocyte Serum on Lymphocytic Choriomeningitis (LCM) Virus Infection in Mice

SummaryRabbit anti-mouse thymocyte serum significantly modified the course of mouse LCM virus infection. Clinical and histologic signs of infection were absent so long as therapy was regularly maintained, and the severity of the host response to the virus was reduced following discontinuation of prolonged therapy. Treatment in the early period of incubation was more protective than at later times.

Studies on entry and egress of poliomyelitic infection. IV. Atraumatic oral entry distribution of lesions and virus during the incubation period with notes on asymptomatic poliomyelitis.

Within 48 hours after simple oropharyngeal exposures of cynomolgus monkeys to poliomyelitis virus, histological signs of infection were found in ganglia supplying the exposed mucous membranes. At 3 days, virus was found in the Gasserian, petrosal-nodose, and superior cervical sympathetic ganglia. Lesions were most extensive and severe in the Gasserian. Virus continued to be detected daily from the 3rd to the 8th day, inclusive, in the Gasserian but not on the 9th; from the 3rd to the 6th day, inclusive, in the petrosal-nodose but not on the 7th, 8th, or 9th; on the 3rd and 6th days only, in the superior cervical sympathetic; and on the 5th day only, in the celiac. In all the ganglia examined, the histological signs of infection increased to a maximum on the 5th day, and thereafter declined. In the sympathetic ganglia, a secondary late increase was observed on the 7th day. During the first 7 days, no signs of infection were found in the CNS in 84 per cent of the animals examined, and in the remainder such lesions as were found were probably not significant. In control animals permitted to survive, the median period before the onset of symptoms of poliomyelitis, when these occurred, was 9 days (range 7 to 16 days), and in the animals with symptoms typical extensive lesions were found in the CNS. In two control animals failing to show symptoms and sacrificed at 26 and 30 days respectively, histological signs of infection were present in the Gasserian and other ganglia but none in the CNS.

Factors Affecting the Propagation of Theiler's Gdvii Mouse Encephalomyelitis Virus in Tissue Cultures

Summary The GDVII strain of Theiler's mouse encephalomyelitis has been carried through 50 serial passages in flasks of Simms' solution with minced brains of embryonic or one day mice; brains from mice as old as 9 days may be used. Temperature range for growth is 31–37 C; optimal pH is 7–9, the higher pH favors more rapid virus production. Culture flasks of medium and tissue stored for as long as 2 days at 5 C or 35 C before virus was added still yielded as much virus after incubation as if fresh tissue was used. Glucose increased yield of virus at pH 7 but not at pH 9. The following substances did not affect yield of virus in culture: CO, NH4Cl, NaF, Al, Cr, Sr, d-ribose, lactate, succinate, pyruvate, thiamine, riboflavin, nucleic acid, choline, alanine, phenylalanine, glutamic acid, thyroxin, sulfadiazine, para-aminobenzoic acid. The following substances decreased yield of virus, Mn, Zn, Fe, Cu, Co, Ni, NaCN, NaN3, iodoacetate and 2,4-dinitrophenol. Virus was also carried through 26 passages in tissue cultures of chick embryo brain but not other chick embryo tissues. Virus was passed 20 times in embryonated eggs of 8–16 days by intracerebral injection. Embryos usually survived without gross or histologic signs of infection.