Experience with Tissue Bank Services in 2014 and 2020 in Turku, Finland.

BACKGROUND: The objective of a musculoskeletal tissue bank is to collect, test, store, and provide musculoskeletal tissue allografts required in orthopedic procedures. Strict exclusion criteria are followed when selecting suitable cadaver musculoskeletal tissue donors, and the allografts are procured under sterile conditions to avoid bacterial contamination. Tissue banking in Turku, Finland, began in 1972, and tissue bank services were last reviewed in 2003. This study aimed to review the operation of the musculoskeletal tissue bank in Turku, Finland, between 2014 and 2020 and to analyze the number, types, and contamination rate of the allografts procured from the cadaver donors. Potential donor-related factors causing bacterial contamination of the allografts and whether potential musculoskeletal tissue donors were overlooked among multiorgan donors were also studied. METHODS: A retrospective review of all cadaver musculoskeletal tissue donors used in the Hospital District of Southwest Finland Tyks Orto Musculoskeletal Tissue Bank during the study period was conducted, and data on the procured allograft was collected and presented. The donors were selected among patients treated in the intensive care unit (ICU) of Turku University Hospital (TYKS). RESULTS: A total of 28 cadaver donors were used, and 636 allografts were procured between 2014 and 2020. The bacterial contamination rate was 2.5%, which was lower than that in the previous international literature. The median treatment time in the ICU was significantly longer, and the median value of the highest C-reactive protein level was significantly higher in the group of donors with positive allograft bacterial cultures. CONCLUSIONS: The bacterial contamination rate in the tissue bank was low on an international scale. Some suitable musculoskeletal tissue donors were overlooked among multiorgan donors.

Bacterial contamination of bone allografts in the tissue banks: a systematic review and meta-analysis.

Bone allografts are harvested and transplanted under sterile conditions. However, the risk of bacterial contamination of grafts during these processes is a health concern. Bioburden testing and bacterial contamination detection are conducted to ensure allograft sterility. The present study aimed to determine the incidence of bacterial contamination in bone allografts based on different classifications. A PROSPERO registration number was received for the study. Systematic searches were conducted in PubMed and EMBASE databases with relevant keywords from January 2000 to March 2021. After choosing related studies according to the PRISMA flow diagram, Stata software was used for data analysis. We considered I2˃50% as heterogeneity between studies. The overall incidence of bacterial contamination was 12.6% (95% confidence interval 0.100, 0.152) among 19,805 bone allografts of 17 studies. The bacterial contamination rate among bone allografts was 10.8% before 2010 and 14.7% from January 2010 to March 2021. The contamination frequency in Asia, Europe, and Australia was 11.5%, 14.3% and 5.2%, respectively. Bone contamination rates were higher in cadaver donors (19.9%), retrieval time sampling (13.5%), and swab samples (13.2%) compared with those in living donors (7.5%), implantation time sampling (6.9%), and bone fragments cultures (6.3%). Bacterial contamination was recovered 24.4%, 19.7%, 13.2%, and 21% from tibia, fibula, femoral, and other bones, respectively. Staphylococcus spp. was the predominant isolated bacteria from bones (63.2% of all isolated genera), followed by Propionibacterium spp. (10.6%). In conclusion, the high contamination of bone allografts is a health concern, indicating the need for more health monitoring and improvement of standards.

A Case of In Situ Phage Therapy against Staphylococcus aureus in a Bone Allograft Polymicrobial Biofilm Infection: Outcomes and Phage-Antibiotic Interactions.

Phage therapy (PT) shows promising potential in managing biofilm infections, which include refractory orthopedic infections. We report the case of a 13-year-old girl who developed chronic polymicrobial biofilm infection of a pelvic bone allograft after Ewing's sarcoma resection surgery. Chronic infection by Clostridium hathewayi, Proteus mirabilis and Finegoldia magna was worsened by methicillin-susceptible Staphylococcus aureus exhibiting an inducible Macrolides-Lincosamides-Streptogramin B resistance phenotype (iMLSB). After failure of conventional conservative treatment, combination of in situ anti-S. aureus PT with surgical debridement and intravenous antibiotic therapy led to marked clinical and microbiological improvement, yet failed to prevent a recurrence of infection on the midterm. This eventually led to surgical graft replacement. Multiple factors can explain this midterm failure, among which incomplete coverage of the polymicrobial infection by PT. Indeed, no phage therapy against C. hathewayi, P. mirabilis or F. magna could be administered. Phage-antibiotic interactions were investigated using OmniLog® technology. Our results suggest that phage-antibiotic interactions should not be considered "unconditionally synergistic", and should be assessed on a case-by-case basis. Specific pharmacodynamics of phages and antibiotics might explain these differences. More than two years after final graft replacement, the patient remains cured of her sarcoma and no further infections occurred.

Successful use of azithromycin for Escherichia coli-associated renal allograft malakoplakia: a report of two cases.

Malakoplakia is a chronic granulomatous disease associated with incomplete clearance of bacterial pathogens. A multimodal approach to therapy includes antimicrobials with intracellular activity, reduction in immunosuppression, and debulking of lesions. Azithromycin has an intracellular mechanism of action and enhanced Gram-negative activity compared to other macrolides. Despite some in vitro data to support its use, there are no clinical breakpoints or epidemiological cut-off values for most Enterobacterales from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) or the Clinical and Laboratory Standards Institute (CLSI). We present two cases, previously unreported, of Escherichia coli associated renal allograft malakoplakia successfully treated with azithromycin.

A prevalent and culturable microbiota links ecological balance to clinical stability of the human lung after transplantation.

There is accumulating evidence that the lower airway microbiota impacts lung health. However, the link between microbial community composition and lung homeostasis remains elusive. We combine amplicon sequencing and bacterial culturing to characterize the viable bacterial community in 234 longitudinal bronchoalveolar lavage samples from 64 lung transplant recipients and establish links to viral loads, host gene expression, lung function, and transplant health. We find that the lung microbiota post-transplant can be categorized into four distinct compositional states, 'pneumotypes'. The predominant 'balanced' pneumotype is characterized by a diverse bacterial community with moderate viral loads, and host gene expression profiles suggesting immune tolerance. The other three pneumotypes are characterized by being either microbiota-depleted, or dominated by potential pathogens, and are linked to increased immune activity, lower respiratory function, and increased risks of infection and rejection. Collectively, our findings establish a link between the lung microbial ecosystem, human lung function, and clinical stability post-transplant.

Tuberculosis transmission across three states: The story of a solid organ donor born in an endemic country, 2018.

Transmission of tuberculosis (TB) from a deceased solid organ donor to recipients can result in severe morbidity and mortality. In 2018, four solid organ transplant recipients residing in three states but sharing a common organ donor were diagnosed with TB disease. Two recipients were hospitalized and none died. The organ donor was born in a country with a high incidence of TB and experienced 8 weeks of headache and fever prior to death, but was not tested for TB during multiple hospitalizations or prior to organ procurement. TB isolates of two organ recipients and a close contact of the donor had identical TB genotypes and closely related whole-genome sequencing results. Donors with risk factors for TB, in particular birth or residence in countries with a higher TB incidence, should be carefully evaluated for TB.

Differences in airway microbiome and metabolome of single lung transplant recipients.

BACKGROUND: Recent studies suggest that alterations in lung microbiome are associated with occurrence of chronic lung diseases and transplant rejection. To investigate the host-microbiome interactions, we characterized the airway microbiome and metabolome of the allograft (transplanted lung) and native lung of single lung transplant recipients. METHODS: BAL was collected from the allograft and native lungs of SLTs and healthy controls. 16S rRNA microbiome analysis was performed on BAL bacterial pellets and supernatant used for metabolome, cytokines and acetylated proline-glycine-proline (Ac-PGP) measurement by liquid chromatography-high-resolution mass spectrometry. RESULTS: In our cohort, the allograft airway microbiome was distinct with a significantly higher bacterial burden and relative abundance of genera Acinetobacter & Pseudomonas. Likewise, the expression of the pro-inflammatory cytokine VEGF and the neutrophil chemoattractant matrikine Ac-PGP in the allograft was significantly higher. Airway metabolome distinguished the native lung from the allografts and an increased concentration of sphingosine-like metabolites that negatively correlated with abundance of bacteria from phyla Proteobacteria. CONCLUSIONS: Allograft lungs have a distinct microbiome signature, a higher bacterial biomass and an increased Ac-PGP compared to the native lungs in SLTs compared to the native lungs in SLTs. Airway metabolome distinguishes the allografts from native lungs and is associated with distinct microbial communities, suggesting a functional relationship between the local microbiome and metabolome.

Selection criteria of solid organ donors in relation to infectious diseases: A Spanish consensus.

The immunosuppressive treatment that recipients receive from a solid organ transplantation hinders the defensive response to infection. Its transmission from the donor can cause dysfunction or loss of the graft and even death of the recipient if proper preventive measures are not established. This potential risk should be thoroughly evaluated to minimise the risk of infection transmission from donor to recipient, especially with organ transplantation from donors with infections, without increasing graft dysfunction and morbidity and mortality in the recipient. This document aims to review current knowledge about infection screening in potential donors and offer clinical and microbiological recommendations about the use of organs from donors with infection based on available scientific evidence.

Encuesta sobre el manejo de injertos del ligamento cruzado anterior contaminados accidentalmente / Survey on management of accidentally contaminated anterior cruciate ligament grafts

OBJETIVO: Encuestar a cirujanos de rodilla en Chile, sobre su conducta en contaminaciones accidentales del injerto, en reconstrucciones de ligamento cruzado anterior (LCA). MÉTODOS: Se realizó una encuesta anónima en relación a la incidencia, tratamiento y resultados clínicos de los injertos de LCA contaminados, a todos los médicos pertenecientes al área de traumatología y ortopedia asistentes al congreso Ateneo de rodilla 2015. RESULTADOS: Se encuestaron 54 médicos, 33 (61%) especialistas en cirugía de rodilla y 21 (39%) médicos en formación. De los cirujanos de rodilla, 15 (45%) reportaron al menos un caso de contaminación, de los cuales 12 (80%) informaron un único evento, 3 (20%) indicaron la eventualidad en 2, 3 y 5 ocasiones respectivamente, para un total de 22 injertos contaminados. De los cirujanos que reportaron injertos contaminados, 11 (73%) realizan 50 o más reconstrucciones al año. La decisión tomada en los casos de contaminación fue en 13 oportunidades (59%), lavar el injerto y utilizarlo de acuerdo al plan inicial; en 6 casos (27%), utilizar aloinjerto; en 2 ocasiones (9%), utilizar autoinjerto alternativo; y en 1 oportunidad (5%); triplicar el semitendinoso. Ninguno de los casos de contaminación reportó infecciones. CONCLUSIONES: En casos de una contaminación accidental, la mayoría de los cirujanos encuestados prefieren optar por la descontaminación del injerto y su utilización en la reconstrucción de acuerdo al plan inicial; para lo cual la clorhexidina y antibióticos sería la solución a usar de preferencia. NIVEL DE EVIDENCIA: Nivel V, opinión de experto.

OBJECTIVE: To survey knee surgeons who perform anterior cruciate ligament (ACL) reconstruction in Chile, about the management when ACL graft contamination occurs. METHODS: An anonymous survey was conducted to all physicians belonging to the area of traumatology and orthopedics who attended the 2015 annual Chilean Knee Society meeting. The survey questioned the incidence, treatment, and outcomes of ACL graft contaminations. RESULTS: Fifty-four physicians were surveyed, of which 33 (61%) where knee surgeons and 21 (39%) physicians in training. Of the 33 knee surgeons, 15 (45%) reported at least one contamination during their career. Of those 15, 12 (80%) had one event, and three surgeons (20%) informed having 2, 3, and 5 episodes respectively, for a total of 22 reported contaminated grafts. Of the surgeons who reported a contaminated graft, 11 (73%) performed 50 or more ACL reconstructions annually. In 13 opportunities (59%) the management for a contaminated graft was cleansing the graft and proceeding as planned. In 6 cases (27%) an allograft was used, in 2 occasions (9%) a different graft was harvested, and in 1 opportunity (5%) a semitendinosus graft triplication was performed. No infections in any of the contaminated grafts were reported. CONCLUSIONS: In case of accidental graft contamination during an ACL reconstruction, knee surgeons most often preferred disinfecting the graft and using it as the initial plan. LEVEL OF EVIDENCE: Level V, expert opinion.

Anaerobic bioburden in transport solution of human cardiovascular tissues.

Although reports of infections caused by anaerobes after tissue transplantation are uncommon, contamination of allografts may result in substantial complications. Anaerobic incubation and testing of organ transport solution (TS) are not routine. The aim of this study was to determine the bioburden of strict anaerobic bacteria and oxygen tension of heart-TS. Forty TS from different donors were evaluated cultured using membrane filtration (MF), direct inoculation on broth and automated blood culture bottle (ABCB). Bacterial identification was performed by MALDI-TOF. The transport conditions were simulated to verify the bacterial recovery. A sterile bag fulfilled with 250 ml-1 of sterile saline was spiked with 100 CFU ml-1 of Clostridium perfringens and the fluid recovered 0 h, 1 h, 2 h, 6 h, 12 h, 24 h and 48 h for culture and oxygen measurement. Strict anaerobic bacteria were not isolated in heart-TS. The recovery of C.perfringens spiked in heart-TS was 100% using automated blood culture bottles. MF method detected >100 CFU only after 6 h of spiking. The manual culture was not able to recover C.perfringens after the process. The percentage of O2 measures varied from 77.6 to 87.9%. MF or ABCB are better than direct inoculation for recovery of anaerobes from heart-TS. Although all samples from heart donors were negative for anaerobes (probably due to low incidence of contamination), C.perfringens were all recovered in the simulated transport condition.

National Variation in Increased Infectious Risk Kidney Offer Acceptance.

BACKGROUND: Despite providing survival benefit, increased risk for infectious disease (IRD) kidney offers are declined at 1.5 times the rate of non-IRD kidneys. Elucidating sources of variation in IRD kidney offer acceptance may highlight opportunities to expand use of these life-saving organs. METHODS: To explore center-level variation in offer acceptance, we studied 6765 transplanted IRD kidneys offered to 187 transplant centers between 2009 and 2017 using Scientific Registry of Transplant Recipients data. We used multilevel logistic regression to determine characteristics associated with offer acceptance and to calculate the median odds ratio (MOR) of acceptance (higher MOR indicates greater heterogeneity). RESULTS: Higher quality kidneys (per 10 units kidney donor profile index; adjusted odds ratio [aOR], 0.94; 95% confidence interval [CI], 0.92-0.95), higher yearly volume (per 10 deceased donor kidney transplants; aOR, 1.08, 95% CI, 1.06-1.10), smaller waitlist size (per 100 candidates; aOR, 0.97; 95% CI, 0.95-0.98), and fewer transplant centers in the donor service area (per center; aOR, 0.88; 95% CI, 0.85-0.91) were associated with greater odds of IRD acceptance. Adjusting for donor and center characteristics, we found wide heterogeneity in IRD offer acceptance (MOR, 1.96). In other words, if listed at a center with more aggressive acceptance practices, a candidate could be 2 times more likely to have an IRD kidney offer accepted. CONCLUSIONS: Wide national variation in IRD kidney offer acceptance limits access to life-saving kidneys for many transplant candidates.

Irradiation sterilization used for allogenetic tendon: a literature review of current concept.

Tendon injury is a very common type of sports trauma, and its incidence has increased over the past decades. Surgical reconstruction with tendon allograft has been increasingly used to restore the motor function and stability of the injured site. However, the risk of disease transmission caused by allogeneic tendon transplantation has been a major problem for tissue bank researchers and clinicians. In order to eliminate the risk of disease transmission, a process of terminal sterilization is necessary. Ionizing irradiation, including gamma irradiation and electron beam irradiation is the most commonly used method for the terminal sterilization, which has been widely proved to be able to effectively inactivate the contained pathogens. Nevertheless, some accompanying damage to the mechanical and histological properties of collagen fibers in tendons will be caused. Therefore, more and more studies have begun to pay attention to the protective effect of radiation protection agents, including the radical scavengers and cross-linking agents, in the irradiation sterilization of allogeneic tendons.

Impact of donor with evidence of bacterial infections on deceased donor liver transplantation: a retrospective observational cohort study in Taiwan.

OBJECTIVE: The shortage of available donor organs is an unsolvable concern leading to an expansion in the donor criteria for organ transplantation. Here, we describe our experience and assess the outcomes in recipients who obtained a graft from a donor with bacterial infections in deceased donor liver transplantation (DDLT). METHODS: All DDLTs between January 1991 and February 2017 were retrospectively reviewed. Patients were categorised into two groups based on the recipients who obtained a graft from a donor with (group I) or without (group II) evidence of bacterial infections. Outcomes and bacterial infections were compared between the two groups of recipients. RESULTS: Overall, a total of 285 DDLTs were performed from 248 donors consisting of 48 split liver grafts and 208 whole liver grafts. Of those, 98 recipients (group I, 34.3%) were transplanted with a graft from 78 donors with positive bacterial cultures. Donor sputum cultures had the highest rate of positive bacterial growth, accounting for 26.6% of donors. Overall survival (OS) was not significantly different between the two groups (p=0.9746). The OS rates at 1 and 3 years were 73.5% and 69.2%, respectively, in the group I recipients versus 68.8% and 62.4% in the group II recipients. Importantly, no hospital mortality was related to donor-derived bacterial infections. CONCLUSION: Transmission of bacteria from the donor to the recipient is infrequent in DDLT. Therefore, potential donors with positive bacterial infections should not be excluded for organ transplantation to increase organ availability and ameliorate the organ shortage.

Risk factors associated with contamination of allograft valves in a tissue bank.

The contamination of the transport solution used in cardiovascular allografts can occur from different sources. Risk factors associated with positive microbiological test of transport solution have not been reported previously. This study aimed to determine the risk factor for contamination of transport solution used in the heart valve allografts stored in a Brazilian tissue bank. This retrospective study was conducted on all donors of cardiovascular allografts stored in a tissue bank from December 2008 to December 2017. Microbiological cultures for aerobic and anaerobic bacteria, fungi/yeasts were carried out in TS. Clinical variables were included. From 1001 transport solution, 52% were contaminated. A total of 770 microorganisms were identified, and Staphylococcus spp. was identified in 248 isolates (32.2%). Skin bacteria from skin microbiota were the most commonly identified microorganisms (Staphylococcus spp., Cutibacterium spp., Corynebacterium spp., and Bacillus spp.), occurring in 49.6%. The presence of a diagnosis of healthcare-associated infection was not associated with skin contamination (odds ratio [OR] 0.62 [0.41-0.94]; p = 0.014). Conditions like fever, use of antibiotics, and leukocytosis were less likely associated with contamination of transport solution. A longer warm ischemic time was associated with higher frequency of contamination. In the multivariable analysis, warm ischemic time was independently associated with contamination, and antibiotic therapy was a factor that decreased the rate of contamination (p < 0.05). Contamination of transport solution is associated with modifiable risk factors, such as warm ischemic time. Measures to minimize contamination should be employed to avoid unnecessary tissue discharges.

Bacterial contamination rate and associated factors during bone and tendon allograft procurement from Spanish donors: exploring the contamination patterns.

BACKGROUND: Allograft contamination during extraction represents a major limiting factor for tissue bank availability. Contamination rates remain persistently high independent of the hospital, country or year considered. AIM: To analyse the factors associated with contamination of bone and tendon samples extracted from Spanish donors. METHODS: Data for 1162 bone and tendon samples extracted from 102 donors between 2014 and 2017 were collected retrospectively from the hospital database. Descriptive statistics, potentially associated factors and correlation of contamination between samples extracted from different anatomical locations of the same donor were analysed. FINDINGS: In total, 227 (19.54%) of the extracted samples [131 (18.49%) bone samples and 96 (20.92%) tendon samples] rendered positive cultures and were discarded. Male sex [odds ratio (OR) 2.023; P=0.019], extraction of >10 samples per donor (OR 1.997; P<0.001) and extraction time >240 min (OR 1.755; P=0.001) were factors independently associated with a higher contamination rate. Meanwhile, the tissue sample type 'bone-patellar tendon-bone' was associated with a significantly lower contamination rate (OR 0.446; P=0.001). Significant correlation between certain localization of contaminated samples and the concordance of bacterial species was also observed. CONCLUSION: Factors related to the extraction procedure, such as total extraction time, extraction sequence, number of samples extracted and anatomical location of extracted samples, play a major role in allograft contamination. Further optimization of procedures, guided by the contamination patterns analysed in this study, should help to increase tissue bank availability.

Microbial contamination and tissue procurement location: A conventional operating room is not mandatory. An observational study.

BACKGROUND: Standard operating rooms (SOR) are assumed to be the best place to prevent microbial contamination when performing tissue procurement. However, mobilizing an operating room is time and cost consuming if no organ retrieval is performed. In such case, non-operating dedicated rooms (NODR) are usually recommended by European guidelines for tissue harvesting. Performing the tissue retrieval in the Intensive care unit (ICU) when possible might be considered as it allows a faster and simpler procedure. OBJECTIVE: Our primary objective was to study the relationship between the risk of microbial contamination and the location (ICU, SOR or NODR) of the tissue retrieval in heart-beating and non-heart-beating deceased donors. MATERIALS AND METHOD: We retrospectively reviewed all deceased donors' files of the local tissue banks of Montpellier and Marseille from January 2007 to December 2014. The primary endpoint was the microbial contamination of the grafts. We built a multivariate regression model and used a GEE (generalized estimating equations) allowing us to take into account the clustered structure of our data. RESULTS: 2535 cases were analyzed involving 1027 donors. The retrieval took place for 1189 in a SOR, for 996 in a hospital mortuary (NODR) and for 350 in an ICU. 285 (11%) microbial contaminations were revealed. The multivariate analysis found that the location in a hospital mortuary was associated with a lower risk of contamination (OR 0.43, 95% CI [0.2-0.91], p = 0.03). A procurement performed in the ICU was not associated with a significant increased risk (OR 0.62, 95% CI [0.26-1.48], p = 0.4). CONCLUSION: According to our results, performing tissue procurement in dedicated non-sterile rooms could decrease the rate of allograft tissue contamination. This study also suggests that in daily clinical practice, transferring patients from ICU to SOR for tissue procurement could be avoided as it does not lead to less microbial contamination.

Contamination profile in allografts retrieved from multitissue donors: longitudinal analysis.

Microbiological contamination of retrieved tissues has become an issue of key importance and is a critical aspect of allograft safety, especially in the case of multi-tissue donations, which frequently become contaminated during retrieval and handling. We analysed contamination in 11,129 tissues with a longitudinal contamination profile for each individual tissue. Specifically, 10,035 musculoskeletal tissues and 1094 cardiovascular tissues were retrieved from a total of 763 multi-tissue donors, of whom 105 heart-beating organ donors and 658 deceased tissue donors. Of the 1955 tissues found to be contaminated after the first decontamination step, 1401 tissues (72%) were contaminated by the same species as the one(s) isolated at retrieval (Time1) and 554 (28%) by different species. Among the 113 tissues testing positive after the 2nd decontamination (Time3), 36 tissues (32%) were contaminated by the same species detected at Timel while the contaminating species differed from Time1 in 77 tissues (68%). The higher the number of contaminating species per tissue the higher the percentage of tissues in which contamination changed over time compared to Time1. The analysis revealed a 28% incidence of new species in tissues already testing positive after retrieval and of 3.5% of tissues becoming positive after admission to the tissue bank. Of these, coagulase-negative Staphylococcus accounted for over 70% of new contaminations.