The Risk of Microbial Transmission in Recipients of Donor Livers That Underwent Hypothermic or Normothermic Machine Perfusion.

Background: Ex situ machine perfusion is increasingly used to preserve and assess donor livers before transplantation. Compared with traditional static cold storage (SCS), machine perfusion exposes livers to an additional risk of microbial contamination. However, information on the risk of microbial transmission during machine perfusion is lacking. Methods: All livers that underwent either hypothermic oxygenated machine perfusion (HOPE) or normothermic machine perfusion (NMP) in our center between September 2021 and September 2023, and during which samples were taken from SCS fluid and/or machine perfusion solution for microbiological examination, were included in this retrospective, observational clinical study. Microbial transmission was examined from SCS fluid to machine perfusion solution fluid and, subsequently, to recipients of these livers. Results: A total of 90 cases of liver machine perfusion were included: 59 HOPE and 31 NMP. SCS preservation fluid cultures before HOPE or NMP were positive for at least 1 microorganism in 52% of the cases. After HOPE, there were no cases of positive machine perfusion fluid or evidence of microbial transmission to the recipients. After NMP, in 1 (3%) patient Escherichia coli was grown from abdominal drain fluid, the same bacterial strain that was also grown from the SCS preservation fluid before NMP. This E coli was resistant to the antibiotics that are routinely added to the NMP perfusion fluid. Conclusions: The risk of microbial transmission after machine perfusion is very low but not absent. We recommend routine sampling of machine perfusion fluid at the end of the procedure for microbiological analysis.

A Systematic Review on the Effects of Different Types of Probiotics in Animal Alzheimer's Disease Studies.

Alzheimer's disease (AD) is a global public health priority as with aging populations, its prevalence is expected to rise even further in the future. The brain and gut are in close communication through immunological, nervous and hormonal routes, and therefore, probiotics are examined as an option to influence AD hallmarks, such as plaques, tangles, and low grade inflammation. This study aimed to provide an overview of the available animal evidence on the effect of different probiotics on gut microbiota composition, short chain fatty acids (SCFAs), inflammatory markers, Amyloid-ß (Aß), and cognitive functioning in AD animal models. A systematic literature search was performed in PubMed, SCOPUS, and APA PsychInfo. Articles were included up to May 2021. Inclusion criteria included a controlled animal study on probiotic supplementation and at least one of the abovementioned outcome variables. Of the eighteen studies, most were conducted in AD male mice models (n = 9). Probiotics of the genera Lactobacillus and Bifidobacterium were used most frequently. Probiotic administration increased species richness and/or bacterial richness in the gut microbiota, increased SCFAs levels, reduced inflammatory markers, and improved cognitive functioning in AD models in multiple studies. The effect of probiotic administration on Aß remains ambiguous. B. longum (NK46), C. butyricum, and the mixture SLAB51 are the most promising probiotics, as positive improvements were found on almost all outcomes. The results of this animal review underline the potential of probiotic therapy as a treatment option in AD.

A spatiotemporal simulation study on the transmission of harmful microorganisms through connected healthcare workers in a hospital ward setting.

BACKGROUND: Hand transmission of harmful microorganisms may lead to infections and poses a major threat to patients and healthcare workers in healthcare settings. The most effective countermeasure against these transmissions is the adherence to spatiotemporal hand hygiene policies, but adherence rates are relatively low and vary over space and time. The spatiotemporal effects on hand transmission and spread of these microorganisms for varying hand hygiene compliance levels are unknown. This study aims to (1) identify a healthcare worker occupancy group of potential super-spreaders and (2) quantify spatiotemporal effects on the hand transmission and spread of harmful microorganisms for varying levels of hand hygiene compliance caused by this group. METHODS: Spatiotemporal data were collected in a hospital ward of an academic hospital using radio frequency identification technology for 7 days. A potential super-spreader healthcare worker occupation group was identified using the frequency identification sensors' contact data. The effects of five probability distributions of hand hygiene compliance and three harmful microorganism transmission rates were simulated using a dynamic agent-based simulation model. The effects of initial simulation assumptions on the simulation results were quantified using five risk outcomes. RESULTS: Nurses, doctors and patients are together responsible for 81.13% of all contacts. Nurses made up 70.68% of all contacts, which is more than five times that of doctors (10.44%). This identifies nurses as the potential super-spreader healthcare worker occupation group. For initial simulation conditions of extreme lack of hand hygiene compliance (5%) and high transmission rates (5% per contact moment), a colonised nurse can transfer microbes to three of the 17 healthcare worker or patients encountered during the 98.4 min of visiting 23 rooms while colonised. The harmful microorganism transmission potential for nurses is higher during weeknights (5 pm - 7 am) and weekends as compared to weekdays (7 am - 5 pm). CONCLUSION: Spatiotemporal behaviour and social mixing patterns of healthcare can change the expected number of hand transmissions and spread of harmful microorganisms by super-spreaders in a closed healthcare setting. These insights can be used to evaluate spatiotemporal safety behaviours and develop infection prevention and control strategies.

The added value of hepatitis E diagnostics in determining causes of hepatitis in routine diagnostic settings in the Netherlands.

OBJECTIVES: Hepatitis E virus (HEV) genotype 3 is endemic in Europe and an underdiagnosed and emerging (public) health issue. In recent years commercial enzyme immunoassays (EIAs) that detect antibodies to HEV more adequately, became available. We investigated the added value of this HEV serology in the diagnostic work flow to detect viral causes of recent hepatitis. METHODS: During a 2-year period (May 2013 to May 2015), HEV serology was added to the hepatitis work flow, consisting of serological detection of hepatitis viruses A, B and C (HAV, HBV, HCV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Samples positive for HEV IgM were also analysed using PCR to detect HEV RNA. If positive, HEV sequencing was performed for genotyping purposes. RESULTS: In 235 out of 2521 patients (9.3%), a viral cause for hepatitis was found. Recent HAV, HBV, HCV, EBV or CMV infections were serologically diagnosed in 3, 34, 10, 69 and 42 patients, respectively. Seventy-eight patients (3.1%) had a recent HEV infection. In 49 of them, sufficient HEV RNA was present for genotyping. All patients were infected with HEV genotype 3. CONCLUSIONS: In our region, an HEV infection is the most frequently diagnosed viral cause for recent hepatitis. These results indicate that, in a country where HEV is endemic, serological HEV diagnostics should be added to the standard work-up for viral hepatitis.

Immediate dynamic lymphoscintigraphy delivers no additional value to lymphoscintigraphy 3 hr after tracer injection in sentinel lymph node biopsy in breast cancer patients.

OBJECTIVE: Immediate dynamic imaging enables accurate definition of sentinel lymph nodes, whereas imaging 3 hr after tracer injection may lead to overestimation of the number of sentinel lymph nodes. A study was performed to define the value of lymphoscintigraphy immediately versus 3 hr after tracer injection in sentinel lymph node biopsy for breast cancer management. METHODS: In 165 sentinel lymph node biopsy procedures preoperative immediate and 3 hr post-injection lymphoscintigraphy was performed after intraparenchymal tracer administration. RESULTS: Lymph node visualization occurred in 63 immediate procedures (38%) versus in 163 procedures 3 hr post-injection (99%). In 17 procedures (10%) in which immediate lymphoscintigraphy had visualized sentinel lymph nodes, additional nodes had been seen on 3 hr post-injection lymphoscintigraphy. In eight of these procedures (5%) all nodes were detected in the same draining lymph node basin. Non-axillary sentinel lymph nodes were identified by preoperative lymphoscintigraphy in 28 procedures (17%) and improved staging in three patients (5%). CONCLUSION: The only impact of immediate lymphoscintigraphy was the possible omission of removal of 1-2 sec-echelon nodes per patient in 5% of patients. We consider this yield too low to continue immediate lymphoscintigraphy in breast cancer patients.

Axillary recurrence after sentinel lymph node biopsy.

UNLABELLED: Sentinel lymph node biopsy (SLNB) without further axillary dissection in patients with sentinel node-negative breast carcinoma appears to be a safe procedure to ensure locoregional control. During a median follow-up of 35 months the false-negative rate was 1% in our study population of 185 patients. BACKGROUND: The objective of this prospective study is to provide data on follow-up of patients with primary operable breast carcinoma staged with SLNB without axillary lymph node dissection (ALND) if the sentinel lymph nodes (SLNs) were tumour-negative. METHODS: One hundred and eighty-five patients were enrolled. Preoperative dynamic and static lymphoscintigraphy were performed; both a vital blue dye and a gamma detection probe were used intraoperatively. Patients with tumour-positive SLNs received completion ALND or if no SLNs could be identified. All patients were monitored according to regional follow-up protocols. RESULTS: The SLNs were identified in 179 out of the 185 patients. In 73 patients the SLNs were tumour-positive and in 106 patients tumour-negative. The median follow-up was 35 months (range 17-59). In one SLN-negative patient an axillary recurrence occurred 26 months after the SLNB (false-negative rate: 1%). CONCLUSIONS: SLNB without ALND appears to be a safe procedure to ensure locoregional control in SLN-negative breast carcinoma, if carried out by an experienced team.

Is sentinel node biopsy beneficial in melanoma patients? A report on 200 patients with cutaneous melanoma.

AIM: The aim of this study was to evaluate the reliability and clinical impact of sentinel node biopsy, including preoperative lymphoscintigraphy and intraoperative lymphatic mapping in patients with cutaneous melanoma of the head, neck, trunk or extremities. METHODS: Two hundred patients (103 women, 97 men), median age 57 (range 21-86) years with cutaneous melanoma > or =1.0mm Breslow thickness and clinically negative lymph nodes participated in a single institutional prospective study from May 1995 to January 2000. Primary melanoma sites included: 22 head and neck (11%), 67 trunk (34%), 29 upper extremity (14%) and 82 lower extremity (41%). The median Breslow thickness was 2.5 (range 1.0-20.0)mm. Preoperative dynamic and static lymphoscintigraphy, intraoperative blue dye and a gamma detection probe were used. If histological examination with HE or IHC showed metastases, therapeutic lymph node dissection (TLND) was performed. RESULTS: Sentinel node(s) could be identified in 197 patients (99%); 393 sentinel nodes (mean: 2.0 per patient, range 1-7) were removed from 241 basins. Three procedures failed in the head and neck region. In 167 patients, the sentinel nodes were both blue and radioactive (85%); in 26 patients, they were only radioactive (13%) and in four patients only blue (2%). In total, 150 patients had tumour-negative sentinel nodes (76%). During a median follow-up of 47 (range 24-79) months, nodal recurrence in a negative mapped basin was documented in six patients of which isolated recurrence was in two patients and recurrence together with locoregional recurrence in four patients (false negative rate 6/54=11%). Estimated three-year recurrence-free survival in the node-negative patients and node-positive patients was 83 and 66% respectively (P<0.05). The overall survival at three years was 92 and 73% respectively (P<0.05). CONCLUSION: Sentinel node biopsy provides accurate staging and important prognostic information. The final place of sentinel node biopsy is still undefined, and therefore sentinel node biopsy is still considered as an experimental surgical staging procedure.

Clinical relevance of sentinel lymph nodes outside the axilla in patients with breast cancer.

BACKGROUND: Lymphatic mapping in patients with breast cancer can reveal sentinel lymph nodes that are not located at level I-II of the axilla. Little is known about the clinical relevance of these nodes. METHODS: Some 113 consecutive patients with clinical stage T1-3 N0 M0 breast cancer were studied. Based on preoperative lymphoscintigraphy, sentinel node biopsy was performed guided by a gamma probe and patent blue dye. All sentinel nodes that were visible on lymphoscintigraphy were sought. Pathological examination of the sentinel nodes included step-sections and staining with CAM 5. 2. Axillary node dissection was performed regardless of sentinel lymph node status. RESULTS: Twenty-one (19 per cent) of 113 patients had sentinel lymph nodes outside level I-II of the axilla, mostly in the internal mammary chain. Twenty-two of the 30 sentinel nodes at these sites were harvested. Three patients had sentinel nodes only outside the axilla. Four other patients had metastases outside the axilla. This changed postoperative treatment in three patients. No postoperative complication occurred. CONCLUSION: Sentinel lymph nodes outside level I-II of the axilla were present in 19 per cent of patients with breast cancer in this series. Biopsy of these nodes was technically demanding but was performed without additional morbidity. The clinical impact was limited; treatment changed in only 3 per cent. Presented to the 52nd annual meeting of the Society of Surgical Oncology in Orlando, Florida, USA, March 1999 and the First International Congress on the Sentinel Node in Diagnosis and Treatment of Cancer in Amsterdam, The Netherlands, April 1999, and published in abstract form as Eur J Nucl Med 1999; 26(Suppl): S71

Lymphatic mapping with intralesional tracer administration in breast carcinoma patients.

BACKGROUND: The objectives of the study were to determine how often a sentinel lymph node is visualized by lymphoscintigraphy in breast carcinoma patients, how often the sentinel lymph node is identified during surgery, and the sensitivity of these procedures to identify the presence of axillary lymph node metastasis. METHODS: A total of 136 patients were enrolled in 2 hospitals. Preoperative dynamic and static lymphoscintigraphy were performed; in addition, both a vital dye and a gamma detection probe were used intraoperatively. The tracers were injected into the primary lesion. Sentinel lymph node biopsy was followed by completion axillary lymph node dissection. The sentinel lymph nodes and other axillary lymph nodes were examined routinely and by immunohistochemical staining. RESULTS: A sentinel lymph node was visualized by lymphoscintigraphy in 118 patients (87%). During the operation a sentinel lymph node was localized in 126 patients (93%). A total of 224 sentinel lymph nodes were harvested (average of 1.7 and range of 1-4 sentinel lymph nodes per patient). Of all the sentinel lymph nodes, 37 were blue (17%), 68 were radioactive (30%), and 119 were both blue and radioactive (53%). The sentinel lymph nodes contained metastatic disease in 56 patients (44%). Three sentinel lymph node biopsies were false-negative (sensitivity 95%). CONCLUSIONS: Sentinel lymph node biopsy with preoperative lymphoscintigraphy after intralesional tracer administration and intraoperative use of both a gamma detection probe and a vital dye is a reliable technique for staging the axilla of breast carcinoma patients.

Sentinel node biopsy for melanoma in the head and neck region.

BACKGROUND: Lymphatic drainage in the head and neck region is known to be particularly complex. This study explores the value of sentinel node biopsy for melanoma in the head and neck region. METHODS: Thirty consecutive patients with clinically localized cutaneous melanoma in the head and neck region were included. Sentinel node biopsy was performed with blue dye and a gamma probe after preoperative lymphoscintigraphy. Average follow-up was 23 months (range, 1-48). RESULTS: In 27 of 30 patients, a sentinel node was identified (90%). Only 53% of sentinel nodes were both blue and radioactive. A sentinel node was tumor-positive in 8 patients. The sentinel node was false-negative in two cases. Sensitivity of the procedure was 80% (8 of 10). CONCLUSIONS: Sentinel node biopsy in the head and neck region is a technically demanding procedure. Although it may help determine whether a neck dissection is necessary in certain patients, further investigation is required before this technique can be recommended for the standard management of cutaneous head and neck melanoma.

Sentinel node biopsy as a surgical staging method for solid cancers.

The sentinel node is the first lymph node that drains a primary tumour. If this lymphatic drainage occurs in a step-wise fashion, this lymph node reflects the pathological status of the remaining lymph node basin. The day before the operation, a total dose of 60 MBq 99mTc nanocolloid is injected around the primary tumour for lymphoscintigraphy. On the day of surgery, 1 ml of blue dye is injected around the primary tumour to facilitate sentinel lymph node detection. After making a small incision over the regional lymph node region, the sentinel node can be detected using a hand-held gamma ray detection probe; the sentinel lymph node and the afferent lymphatic vessels will be stained blue. Sentinel node biopsy has proved useful for malignant melanoma, breast cancer, penile cancer, vulvar cancer, Merkel cell carcinoma and thyroid cancer. New studies are described on breast cancer and malignant melanoma. Gamma-probe-guided localization of radiolabelled lymph nodes can direct the surgeon non-invasively to the exact location of the sentinel node. Once localized with a gamma probe, it is quick and easy to remove the sentinel node through a small incision. Discriminating the node from other tissue can be aided by blue dye which stains the lymph node. It appears that both radioactivity and blue dye are complementary for locating the sentinel node.

Improved staging of breast cancer through lymphatic mapping and sentinel node biopsy.

Sentinel node biopsy is a less invasive technique for staging breast cancer than complete axillary lymph-node dissection and may be as accurate. In the case of a 71-year-old woman with a T1 breast cancer, sentinel node biopsy improved staging. Metastases were discovered in sentinel nodes outside the axilla while the axillary nodes were tumour-free.