The optimal approaches to managing diabetic foot infections remain a challenge for clinicians. Despite an exponential rise in publications investigating different treatment strategies, the various... Show moreThe optimal approaches to managing diabetic foot infections remain a challenge for clinicians. Despite an exponential rise in publications investigating different treatment strategies, the various agents studied generally produce comparable results, and high-quality data are scarce. In this systematic review, we searched the medical literature using the PubMed and Embase databases for published studies on the treatment of diabetic foot infections from 30 June 2018 to 30 June 2022. We combined this search with our previous literature search of a systematic review performed in 2020, in which the infection committee of the International Working Group on the Diabetic Foot searched the literature until June 2018. We defined the context of the literature by formulating clinical questions of interest, then developing structured clinical questions (Patients-Intervention-Control-Outcomes) to address these. We only included data from controlled studies of an intervention to prevent or cure a diabetic foot infection. Two independent reviewers selected articles for inclusion and then assessed their relevant outcomes and methodological quality. Our literature search identified a total of 5,418 articles, of which we selected 32 for full-text review. Overall, the newly available studies we identified since 2018 do not significantly modify the body of the 2020 statements for the interventions in the management of diabetes-related foot infections. The recent data confirm that outcomes in patients treated with the different antibiotic regimens for both skin and soft tissue infection and osteomyelitis of the diabetes-related foot are broadly equivalent across studies, with a few exceptions (tigecycline not non-inferior to ertapenem [+/- vancomycin]). The newly available data suggest that antibiotic therapy following surgical debridement for moderate or severe infections could be reduced to 10 days and to 3 weeks for osteomyelitis following surgical debridement of bone. Similar outcomes were reported in studies comparing primarily surgical and predominantly antibiotic treatment strategies in selected patients with diabetic foot osteomyelitis. There is insufficient high-quality evidence to assess the effect of various recent adjunctive therapies, such as cold plasma for infected foot ulcers and bioactive glass for osteomyelitis. Our updated systematic review confirms a trend to a better quality of the most recent trials and the need for further well-designed trials to produce higher quality evidence to underpin our recommendations. Show less
The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present... Show moreThe International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus.The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations.The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems.We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease. Show less
Pierneef, L.; Malaviya, P.; Hooij, A. van; Sundar, S.; Singh, A.K.; Kumar, R.; ... ; Geluk, A. 2023
Background It has been amply described that levels of IgM antibodies against Mycobacterium leprae (M. leprae) phenolic glycolipid I (PGL-I) correlate strongly with the bacterial load in an infected... Show moreBackground It has been amply described that levels of IgM antibodies against Mycobacterium leprae (M. leprae) phenolic glycolipid I (PGL-I) correlate strongly with the bacterial load in an infected individual. These findings have generated the concept of using seropositivity for antibodies against M. leprae PGL-I as an indicator of the proportion of the population that has been infected. Although anti-PGL-I IgM levels provide information on whether an individual has ever been infected, their presence cannot discriminate between recent and past infections. Since infection in (young) children by definition indicates recent transmission, we piloted the feasibility of assessment of anti-PGL-I IgM seroprevalence among children in a leprosy endemic area in India as a proxy for recent M. leprae transmission.Material and methods A serosurvey for anti-PGL-I IgM antibodies among children in highly leprosy endemic villages in Bihar, India, was performed, applying the quantitative anti-PGL-I UCP-LFA cassette combined with low-invasive, small-volume fingerstick blood (FSB).Results Local staff obtained FSB of 1,857 children (age 3-11 years) living in 12 leprosy endemic villages in Bihar; of these, 215 children (11.58%) were seropositive for anti-PGL-I IgM.Conclusion The anti-PGL-I seroprevalence level of 11.58% among children corresponds with the seroprevalence levels described in studies in other leprosy endemic areas over the past decades where no prophylactic interventions have taken place. The anti-PGL-I UCP-LFA was found to be a low-complexity tool that could be practically combined with serosurveys and was well-accepted by both healthcare staff and the population. On route to leprosy elimination, quantitative anti-PGL-I serology in young children holds promise as a strategy to monitor recent M. leprae transmission in an area. Show less
Arend, B.W.H. van der; Bloemhof, M.M.; Schoor, A.G. van der; Zwet, E.W. van; Terwindt, G.M. 2023
BackgroundThis longitudinal cohort study aimed to investigate changes in migraine-related outcomes following COVID-19 infection and vaccination.MethodsWe identified 547 clinically diagnosed... Show moreBackgroundThis longitudinal cohort study aimed to investigate changes in migraine-related outcomes following COVID-19 infection and vaccination.MethodsWe identified 547 clinically diagnosed migraine patients from the Leiden Headache Center who kept a headache E-diary during the COVID-19 pandemic (February 2020 to August 2022). We sent a questionnaire to register their COVID-19 infection and/or vaccination dates. After applying inclusion criteria, n = 59 participants could be included in the infection analysis and n = 147 could be included in the vaccination analysis. Primary outcome was the change in monthly migraine days (MMD) between 1 month prior and 1 month post COVID-19 infection or vaccination. Secondary outcome variables were change in monthly headache days (MHD) and monthly acute medication days (MAMD).ResultsVaccination against COVID-19 was associated with an increase in MMD (1.06; 95% confidence interval [CI] = 0.57–1.55; p < 0.001), MHD (1.52; 95% CI = 0.91–2.14; p < 0.001) and MAMD (0.72; 95% CI = 0.33–1.12; p < 0.001) in the first month post-vaccination. COVID-19 infection solely increased the number of MAMD (1.11; 95% CI = 0.10–1.62; p < 0.027), but no statistically significant differences in MMD or MHD were observed.ConclusionsOur findings imply that vaccination against COVID-19 is associated with an increase in migraine, indicating a possible role of inflammatory mediators in migraine pathophysiology. Show less
Chen, L.L.; Burgt, A. van de; Smit, F.; Audhoe, R.S.; Boer, S.M. de; Velden, F.H.P. van; Geus-Oei, L.F. de 2023
ObjectiveSince the end of 2019, the coronavirus disease 2019 (COVID-19) virus has infected millions of people, of whom a significant group suffers from sequelae from COVID-19, termed long COVID. As... Show moreObjectiveSince the end of 2019, the coronavirus disease 2019 (COVID-19) virus has infected millions of people, of whom a significant group suffers from sequelae from COVID-19, termed long COVID. As more and more patients emerge with long COVID who have symptoms of fatigue, myalgia and joint pain, we must examine potential biomarkers to find quantifiable parameters to define the underlying mechanisms and enable response monitoring. The aim of this study is to investigate the potential added value of [F-18]FDG-PET/computed tomography (CT) for this group of long COVID patients. MethodsFor this proof of concept study, we evaluated [F-18]FDG-PET/CT scans of long COVID patients and controls. Two analyses were performed: semi-quantitative analysis using target-to-background ratios (TBRs) in 24 targets and total vascular score (TVS) assessed by two independent nuclear medicine physicians. Mann-Whitney U-test was performed to find significant differences between the two groups. ResultsThirteen patients were included in the long COVID group and 25 patients were included in the control group. No significant differences (P < 0.05) were found between the long COVID group and the control group in the TBR or TVS assessment. ConclusionAs we found no quantitative difference in the TBR or TVS between long COVID patients and controls, we are unable to prove that [F-18]FDG is of added value for long COVID patients with symptoms of myalgia or joint pain. Prospective cohort studies are necessary to understand the underlying mechanisms of long COVID. Show less
Chen, L.L.; Burgt, A. van de; Smit, F.; Audhoe, R.S.; Boer, S.M. de; Velden, F.H.P. van; Geus-Oei, L.F. de 2023
Objective Since the end of 2019, the coronavirus disease 2019 (COVID-19) virus has infected millions of people, of whom a significant group suffers from sequelae from COVID-19, termed long COVID.... Show moreObjective Since the end of 2019, the coronavirus disease 2019 (COVID-19) virus has infected millions of people, of whom a significant group suffers from sequelae from COVID-19, termed long COVID. As more and more patients emerge with long COVID who have symptoms of fatigue, myalgia and joint pain, we must examine potential biomarkers to find quantifiable parameters to define the underlying mechanisms and enable response monitoring. The aim of this study is to investigate the potential added value of [18F]FDG-PET/computed tomography (CT) for this group of long COVID patients.Methods For this proof of concept study, we evaluated [18F]FDG-PET/CT scans of long COVID patients and controls. Two analyses were performed: semi-quantitative analysis using target-to-background ratios (TBRs) in 24 targets and total vascular score (TVS) assessed by two independent nuclear medicine physicians. Mann–Whitney U-test was performed to find significant differences between the two groups.Results Thirteen patients were included in the long COVID group and 25 patients were included in the control group. No significant differences (P < 0.05) were found between the long COVID group and the control group in the TBR or TVS assessment.Conclusion As we found no quantitative difference in the TBR or TVS between long COVID patients and controls, we are unable to prove that [18F]FDG is of added value for long COVID patients with symptoms of myalgia or joint pain. Prospective cohort studies are necessary to understand the underlying mechanisms of long COVID. Show less
Clostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenic C. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human... Show moreClostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenic C. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human recurrent CDI. In this study, we evaluated the efficacy of metronidazole-resistant NTCD-E4 in preventing CDI facilitated by a range of antimicrobials in an in vitro human gut model. NTCD-E4 spores (at a dose of 10(7)) were instilled 7 days before a clinical ribotype (RT) 027 (at the same dose) strain (210). In separate experiments, four different antimicrobials were used to perturb gut microbiotas; bacterial populations and cytotoxin production were determined using viable counting and Vero cell cytotoxicity, respectively. RT027 and NTCD-E4 proliferated in the in vitro model when inoculated singly, with RT027 demonstrating high-level cytotoxin (3-5-log(10)-relative units) production. In experiments where the gut model was pre-inoculated with NTCD-E4, RT027 was remained quiescent and failed to produce cytotoxins. NTCD-E4 showed mutations in hsmA and a gene homologous to CD196-1331, previously linked to medium-dependent metronidazole resistance, but lacked other metronidazole resistance determinants. This study showed that RT027 was unable to elicit simulated infection in the presence of NTCD-E4 following stimulation by four different antimicrobials. These data complement animal and clinical studies in suggesting NTCD offer prophylactic potential in the management of human CDI. Show less
Clostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenicC. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human... Show moreClostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenicC. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human recurrentCDI. In this study, we evaluated the efficacy of metronidazole-resistant NTCD-E4 in preventingCDI facilitated by a range of antimicrobials in an in vitro human gut model. NTCD-E4 spores (ata dose of 107) were instilled 7 days before a clinical ribotype (RT) 027 (at the same dose) strain(210). In separate experiments, four different antimicrobials were used to perturb gut microbiotas;bacterial populations and cytotoxin production were determined using viable counting and Vero cellcytotoxicity, respectively. RT027 and NTCD-E4 proliferated in the in vitro model when inoculatedsingly, with RT027 demonstrating high-level cytotoxin (3-5-log10-relative units) production. Inexperiments where the gut model was pre-inoculated with NTCD-E4, RT027 was remained quiescentand failed to produce cytotoxins. NTCD-E4 showed mutations in hsmA and a gene homologous toCD196-1331, previously linked to medium-dependent metronidazole resistance, but lacked othermetronidazole resistance determinants. This study showed that RT027 was unable to elicit simulatedinfection in the presence of NTCD-E4 following stimulation by four different antimicrobials. Thesedata complement animal and clinical studies in suggesting NTCD offer prophylactic potential in themanagement of human CDI. Show less
Clostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenic C. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human... Show moreClostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenic C. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human recurrent CDI. In this study, we evaluated the efficacy of metronidazole-resistant NTCD-E4 in preventing CDI facilitated by a range of antimicrobials in an in vitro human gut model. NTCD-E4 spores (at a dose of 107) were instilled 7 days before a clinical ribotype (RT) 027 (at the same dose) strain (210). In separate experiments, four different antimicrobials were used to perturb gut microbiotas; bacterial populations and cytotoxin production were determined using viable counting and Vero cell cytotoxicity, respectively. RT027 and NTCD-E4 proliferated in the in vitro model when inoculated singly, with RT027 demonstrating high-level cytotoxin (3-5-log10-relative units) production. In experiments where the gut model was pre-inoculated with NTCD-E4, RT027 was remained quiescent and failed to produce cytotoxins. NTCD-E4 showed mutations in hsmA and a gene homologous to CD196-1331, previously linked to medium-dependent metronidazole resistance, but lacked other metronidazole resistance determinants. This study showed that RT027 was unable to elicit simulated infection in the presence of NTCD-E4 following stimulation by four different antimicrobials. These data complement animal and clinical studies in suggesting NTCD offer prophylactic potential in the management of human CDI. Show less
Background: A spinal epidural abscess (SEA) of the cervical spine is a relatively rare disease and is generally characterized by progressive neurological deterioration due to compression of the... Show moreBackground: A spinal epidural abscess (SEA) of the cervical spine is a relatively rare disease and is generally characterized by progressive neurological deterioration due to compression of the spinal cord. Up to 40% of cervical SEAs are located ventrally of the spinal cord. Urgent surgical intervention is warranted to decompress the spinal cord and collect material for cultures to guide antibiotic treatment. However, the optimal timing of the intervention is unclear, and the associated risk of spinal instability in the presence of an extensive infection is a significant clinical dilemma. Methods: In this paper, we present a novel surgical technique to treat a cervical SEA by anterior decompression through a linear transvertebral midline approach. This technique has the advantage of effectively draining the ventrally located SEA and obtaining material for bacteria culture while maintaining spinal stability without additional instrumentation. Results: This case study presents seven patients with cervical SEAs who were successfully treated with surgical decompression by this transvertebral linear midline technique and antibiotic treatment. Conclusion: Anterior decompression through a linear transvertebral midline approach for a ventrally located cervical SEA is a safe and pragmatic surgical procedure to achieve spinal cord decompression and collect bacteria culture without destabilizing the cervical spine. Show less
Weerd, A.E. de; Fatly, Z. al; Boer-Verschragen, M.; Gestel, J.K.V.A.; Roelen, D.L.; Dieterich, M.; Betjes, M.G.H. 2022
In this randomized-controlled pilot study, the feasibility and safety of tacrolimus monotherapy in immunologically low-risk kidney transplant recipients was evaluated [NTR4824, ]. Low immunological... Show moreIn this randomized-controlled pilot study, the feasibility and safety of tacrolimus monotherapy in immunologically low-risk kidney transplant recipients was evaluated [NTR4824, ]. Low immunological risk was defined as maximal 3 HLA mismatches and the absence of panel reactive antibodies. Six months after transplantation, recipients were randomized if eGFR > 30 ml/min, proteinuria < 50 mg protein/mmol creatinine, no biopsy-proven rejection after 3 months, and no lymphocyte depleting therapy given. Recipients were randomized to tacrolimus/mycophenolate mofetil (TAC/MMF) or to taper and discontinue MMF at month 9 (TACmono). 79 of the 121 recipients were randomized to either TACmono (n = 38) or TAC/MMF (n = 41). Mean recipient age was 59 years and 59% received a living donor transplant. The median follow-up was 62 months. After randomization, 3 TACmono and 4 TAC/MMF recipients experienced a biopsy-proven rejection. At 5 years follow-up, patient survival was 84% in TACmono versus 76% in TAC/MMF with death-censored graft survival of 97% for both groups and no differences in eGFR and proteinuria. Eleven TACmono recipients had an infectious episode versus 22 TAC/MMF recipients (p < 0.03). Donor-specific anti-HLA antibodies were not detected during follow-up in both groups. Tacrolimus monotherapy in selected immunologically low-risk kidney transplant recipients appears safe and reduces the number of infections. Show less
Weerd, A.E. de; Fatly, Z. al; Boer-Verschragen, M.; Gestel, J.K.V.A.; Roelen, D.L.; Dieterich, M.; Betjes, M.G.H. 2022
In this randomized-controlled pilot study, the feasibility and safety of tacrolimus monotherapy in immunologically low-risk kidney transplant recipients was evaluated [NTR4824, ]. Low immunological... Show moreIn this randomized-controlled pilot study, the feasibility and safety of tacrolimus monotherapy in immunologically low-risk kidney transplant recipients was evaluated [NTR4824, ]. Low immunological risk was defined as maximal 3 HLA mismatches and the absence of panel reactive antibodies. Six months after transplantation, recipients were randomized if eGFR > 30 ml/min, proteinuria < 50 mg protein/mmol creatinine, no biopsy-proven rejection after 3 months, and no lymphocyte depleting therapy given. Recipients were randomized to tacrolimus/mycophenolate mofetil (TAC/MMF) or to taper and discontinue MMF at month 9 (TACmono). 79 of the 121 recipients were randomized to either TACmono (n = 38) or TAC/MMF (n = 41). Mean recipient age was 59 years and 59% received a living donor transplant. The median follow-up was 62 months. After randomization, 3 TACmono and 4 TAC/MMF recipients experienced a biopsy-proven rejection. At 5 years follow-up, patient survival was 84% in TACmono versus 76% in TAC/MMF with death-censored graft survival of 97% for both groups and no differences in eGFR and proteinuria. Eleven TACmono recipients had an infectious episode versus 22 TAC/MMF recipients (p < 0.03). Donor-specific anti-HLA antibodies were not detected during follow-up in both groups. Tacrolimus monotherapy in selected immunologically low-risk kidney transplant recipients appears safe and reduces the number of infections. Show less
Background: The risk of urinary tract infections is increased by the inappropriate placement and unnecessary prolongation of the use of indwelling urinary catheters. Sustained behavior change in... Show moreBackground: The risk of urinary tract infections is increased by the inappropriate placement and unnecessary prolongation of the use of indwelling urinary catheters. Sustained behavior change in infection prevention could be promoted by empowering patients through a smartphone app.Objective: The aim of this study is to assess the feasibility and efficacy of implementation actions on patients' use of the Participatient app on a clinical ward and to compare 3 survey methods for urinary catheter use.Methods: Participatient was introduced for all admitted patients at the surgical nursing ward in a university hospital in the Netherlands. Over a period of 3 months, the number of new app users, days of use, and sessions were recorded. In a comparison of urinary catheter use before and after the implementation of the app, 3 methods for point prevalence surveys of catheter use were tested. Surveys were conducted through manual parsing of the text in patients' electronic medical records, parsing a survey of checkbox items, and parsing nursing notes.Results: In all, 475 patients were admitted to the ward, 42 (8.8%) installed the app, with 1 to 5 new users per week. The actions with the most ensuing app use were the kick-off with the clinical lesson and recruiting of the intake nurse. Between the survey methods, there was considerable variation in catheter use prevalence. Therefore, we used the standard method of manual parsing in further analyses. Catheter use prevalence decreased from 38% (36/96) to 27% (23/86) after app introduction (OR 0.61, 95% CI 0.32-1.14).Conclusions: The clinical application of Participatient, the infection prevention app for patients, could be feasible when implementation actions are also used. For surveying indwelling urinary catheter use prevalence, manual parsing is the best approach. Show less
Background: The risk of urinary tract infections is increased by the inappropriate placement and unnecessary prolongation of the use of indwelling urinary catheters. Sustained behavior change in... Show moreBackground: The risk of urinary tract infections is increased by the inappropriate placement and unnecessary prolongation of the use of indwelling urinary catheters. Sustained behavior change in infection prevention could be promoted by empowering patients through a smartphone app.Objective: The aim of this study is to assess the feasibility and efficacy of implementation actions on patients’ use of the Participatient app on a clinical ward and to compare 3 survey methods for urinary catheter use.Methods: Participatient was introduced for all admitted patients at the surgical nursing ward in a university hospital in the Netherlands. Over a period of 3 months, the number of new app users, days of use, and sessions were recorded. In a comparison of urinary catheter use before and after the implementation of the app, 3 methods for point prevalence surveys of catheter use were tested. Surveys were conducted through manual parsing of the text in patients’ electronic medical records, parsing a survey of checkbox items, and parsing nursing notes.Results: In all, 475 patients were admitted to the ward, 42 (8.8%) installed the app, with 1 to 5 new users per week. The actions with the most ensuing app use were the kick-off with the clinical lesson and recruiting of the intake nurse. Between the survey methods, there was considerable variation in catheter use prevalence. Therefore, we used the standard method of manual parsing in further analyses. Catheter use prevalence decreased from 38% (36/96) to 27% (23/86) after app introduction (OR 0.61, 95% CI 0.32-1.14).Conclusions: The clinical application of Participatient, the infection prevention app for patients, could be feasible when implementation actions are also used. For surveying indwelling urinary catheter use prevalence, manual parsing is the best approach. Show less
Oevelen, M. van; Heggen, B.D.C.; Abrahams, A.C.; Rotmans, J.I.; Snoeijs, M.G.J.; Vernooij, R.W.M.; ... ; DUCATHO Study Grp 2022
Background: Central venous catheters (CVC) remain a commonly used vascular access option in haemodialysis, despite guidelines advising to preferably use arteriovenous fistulae. Compared to younger... Show moreBackground: Central venous catheters (CVC) remain a commonly used vascular access option in haemodialysis, despite guidelines advising to preferably use arteriovenous fistulae. Compared to younger patients, the risk-benefit ratio of CVC in older patients might be more beneficial, but previous studies mainly focussed on catheter-related bacteraemia and/or assessed tunnelled CVC (TCVC) only. This study's aim was to compare all catheter-related infections and malfunctions in older patients with younger patients using all CVC subtypes. Materials and methods: We used data from DUCATHO, a multicentre observational cohort study in The Netherlands. All adult patients in whom a CVC was placed for haemodialysis between 2012 and 2016 were included. The primary endpoint was the occurrence of catheter-related infections, comparing patients aged > 70 years with patients aged <70 years (reference). As secondary endpoints, catheter malfunctions and catheter removal due to either infection or malfunction were assessed. Using Cox proportional hazards and recurrent events modelling, hazard ratios (HR) with 95% confidence intervals (CI) were calculated with adjustment of prespecified confounders. Additionally, endpoints were assessed for non-tunnelled CVC (NTCVC) and TCVC separately. Results: A total of 1595 patients with 2731 CVC (66.5% NTCVC, 33.1% TCVC) were included. Of these patients, 1001 (62.8%) were aged <70 years and 594 (37.2%) > 70 years. No statistically significant difference was found for the occurrence of catheter-related infections (adjusted HR 0.80-95% CI 0.62-1.02), catheter malfunction (adjusted HR 0.94-95% CI 0.75-1.17) and catheter removal due to infection or malfunction (adjusted HR 0.94-95% CI 0.80-1.11). Results were comparable when assessing NTCVC and TCVC separately. Conclusion: Patients aged > 70 to <70 years have a comparable risk for the occurrence of catheter-related infections and catheter malfunction. These findings may help when discussing treatment options with older patients starting haemodialysis and may inform the current debate on the best vascular access for these patients. Show less
Oevelen, M. van; Heggen, B.D.C.; Abrahams, A.C.; Rotmans, J.; Snoeijs, M.G.J.; Vernooij, R.W.M.; ... ; DUCATHO Study Grp 2022
Background: Central venous catheters (CVC) remain a commonly used vascular access option in haemodialysis, despite guidelines advising to preferably use arteriovenous fistulae. Compared to younger... Show moreBackground: Central venous catheters (CVC) remain a commonly used vascular access option in haemodialysis, despite guidelines advising to preferably use arteriovenous fistulae. Compared to younger patients, the risk-benefit ratio of CVC in older patients might be more beneficial, but previous studies mainly focussed on catheter-related bacteraemia and/or assessed tunnelled CVC (TCVC) only. This study's aim was to compare all catheter-related infections and malfunctions in older patients with younger patients using all CVC subtypes. Materials and methods: We used data from DUCATHO, a multicentre observational cohort study in The Netherlands. All adult patients in whom a CVC was placed for haemodialysis between 2012 and 2016 were included. The primary endpoint was the occurrence of catheter-related infections, comparing patients aged > 70 years with patients aged <70 years (reference). As secondary endpoints, catheter malfunctions and catheter removal due to either infection or malfunction were assessed. Using Cox proportional hazards and recurrent events modelling, hazard ratios (HR) with 95% confidence intervals (CI) were calculated with adjustment of prespecified confounders. Additionally, endpoints were assessed for non-tunnelled CVC (NTCVC) and TCVC separately. Results: A total of 1595 patients with 2731 CVC (66.5% NTCVC, 33.1% TCVC) were included. Of these patients, 1001 (62.8%) were aged <70 years and 594 (37.2%) > 70 years. No statistically significant difference was found for the occurrence of catheter-related infections (adjusted HR 0.80-95% CI 0.62-1.02), catheter malfunction (adjusted HR 0.94-95% CI 0.75-1.17) and catheter removal due to infection or malfunction (adjusted HR 0.94-95% CI 0.80-1.11). Results were comparable when assessing NTCVC and TCVC separately. Conclusion: Patients aged > 70 to <70 years have a comparable risk for the occurrence of catheter-related infections and catheter malfunction. These findings may help when discussing treatment options with older patients starting haemodialysis and may inform the current debate on the best vascular access for these patients. Show less
Treatment of bacterial infections with broad-spectrum antibiotics is a strategy severely limited by the decreased ability of the perturbed resident microbiota to control expansion of antibiotic... Show moreTreatment of bacterial infections with broad-spectrum antibiotics is a strategy severely limited by the decreased ability of the perturbed resident microbiota to control expansion of antibiotic-resistant pathogens. Live biotherapeutic products (LBPs) could provide an alternative to antibiotics in infection control by restoring gut colonization resistance and controlling expansion of resistant strains, an important therapeutic need not being addressed with existing anti-infective drug modalities. We review opportunities and challenges in developing LBPs for multidrug-resistant organisms colonization and infection control, with a focus on commercial fecal microbiota transplantation-like products and defined bacterial consortia, and spanning considerations related to availability of models for rational drug candidate selection and dose regimen selection, good manufacturing practice, intellectual property, and commercial viability. Show less
Casna, M.; Burrell, C. L.; Schats, R.; Hoogland, M. L. P.; Schrader, S. A. 2021
The aim of this study was to investigate the relationship between urbanization and upper respiratory health in two early modern populations from the Netherlands. For this purpose, we analyzed the... Show moreThe aim of this study was to investigate the relationship between urbanization and upper respiratory health in two early modern populations from the Netherlands. For this purpose, we analyzed the prevalence of chronic maxillary sinusitis in the adult urban population of Arnhem (n = 83) and in the rural village of Middenbeemster (n = 74). A slightly higher prevalence of chronic maxillary sinusitis was observed in the Arnhem sample (55.4%) compared with the Middenbeemster sample (51.3%), and these variations were not statistically significantly different. Although historical sources attest to the fact that life in the postmedieval settlements of Arnhem and Middenbeemster greatly differed, our results suggest that both environments exposed people to certain respiratory hazards. Furthermore, sinusitis prevalence was also investigated in correlation to sex, as urbanization in the Netherlands often involved women in factory work in direct contrast to the traditional domestic role they kept covering in rural environments. No significant differences were observed between males and females, both in an intersite (Arnhem males vs. Middenbeemster males; Arnhem females vs. Middenbeemster females) and in an intrasite (males vs. females at Arnhem; males vs. females at Middenbemster) comparison. As men and women in Arnhem worked on similar tasks, our results confirm that they were both exposed to similar risk factors. In Middenbeemster, where women mainly stayed inside taking care of the house while men worked the fields, the adverse weather conditions and continuous exposure to pollens and allergens may have enhanced men's chances of contracting chronic maxillary sinusitis. This study suggests that urbanization in the early modern Netherlands was in fact not inherently more detrimental than rural living. Future research incorporating a larger sample from other Dutch sites is being considered to better frame the complex etiology of sinusitis within the present understanding of historic regional variation in urbanization patterns. Show less
Busselaar, J.; Tian, S.; Eenennaam, H. van; Borst, J. 2020
Persistent antigen exposure in chronic infection and cancer has been proposed to lead to cytotoxic T lymphocyte (CTL) "exhaustion", i.e., loss of effector function and disease control. Recent work... Show morePersistent antigen exposure in chronic infection and cancer has been proposed to lead to cytotoxic T lymphocyte (CTL) "exhaustion", i.e., loss of effector function and disease control. Recent work identifies a population of poorly differentiated TCF-1(+)PD-1(+)CD8(+)T cells as precursors of the terminally exhausted CTL pool. These "predysfunctional" CTLs are suggested to respond to PD-1 targeted therapy by giving rise to a pool of functional CTLs. Supported by gene expression analyses, we present a model in which lack of CD4(+)T cell help during CD8(+)T cell priming results in the formation of predysfunctional CTLs. Our model implies that predysfunctional CTLs are formed during priming and that the remedy for CTL dysfunction is to provide "help" signals for generation of optimal CTL effectors. We substantiate that this may be achieved by engaging CD4(+)T cells in new CD8(+)T cell priming, or by combined PD-1 blocking and CD27 agonism with available immunotherapeutic antibodies. Show less
[F-18]-FDG-PET/CT ([F-18]-fluoro-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)) is increasingly used as a diagnostic tool in suspected infectious or inflammatory... Show more[F-18]-FDG-PET/CT ([F-18]-fluoro-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)) is increasingly used as a diagnostic tool in suspected infectious or inflammatory conditions. Studies on the value of FDG-PET/CT in children are scarce. This study assesses the role of FDG-PET/CT in suspected infection or inflammation in children. In this multicenter cohort study, 64 scans in 59 children with suspected infection or inflammation were selected from 452 pediatric FDG-PET/CT scans, performed in five hospitals between January 2016 and August 2017. Main outcomes were diagnostic information provided by FDG-PET/CT for diagnostic scans and impact on clinical management for follow-up scans. Of these 64 scans, 50 were performed for primary diagnosis and 14 to monitor disease activity. Of the positive diagnostic scans, 23/27 (85%) contributed to establishing a diagnosis. Of the negative diagnostic scans, 8/21 (38%) contributed to the final diagnosis by narrowing the differential or by providing information on the disease manifestation. In all follow-up scans, FDG-PET/CT results guided management decisions. CRP was significantly higher in positive scans than in negative scans (p= 0.004). In 6% of diagnostic scans, relevant incidental findings were identified. In conclusion, FDG-PET/CT performed in children with suspected infection or inflammation resulted in information that contributed to the final diagnosis or helped to guide management decisions in the majority of cases. Prospective studies assessing the impact of FDG-PET/CT results on diagnosis and patient management using a structured diagnostic protocol are feasible and necessary. Show less