Local antibiotic delivery via intra-articular catheter infusion for the treatment of periprosthetic joint infection: a systematic review.

INTRODUCTION: There is an increasing interest in the use of intra-articular (IA) antibiotic infusion as a stand-alone or adjuvant therapy to standard revision surgery for periprosthetic joint infection (PJI). The objective of this systematic review is to evaluate the evidence with respect to this up-and-coming treatment modality. METHODS: A systematic review of studies published until April 2023 was conducted using PubMed, Embase, MEDLINE and Cochrane databases. Quality assessment was performed with the National Institute of Health quality assessment tool. Inclusion criteria were adult patients (≥ 18 years) with a mean follow-up of ≥ 11 months and a score ≥ 6 on the National Institute of Health quality assessment tool. Primary outcome was eradication of infection. RESULTS: 15 articles, encompassing 631 PJIs in 626 patients, were included in the final analysis, all level IV case series. The majority was treated with single-stage revision with adjuvant IA antibiotic infusion (79.1%). The remaining PJIs were treated with stand-alone IA antibiotic infusion (12.2%), DAIR (debridement, antibiotics and implant retention) with adjuvant IA antibiotic infusion (5.7%) or two-stage revision with adjuvant IA antibiotic infusion (3.0%). Mean duration of IA antibiotic infusion was 19 days (range 3-50). An overall failure rate of approximately 11% was found. In total 117 complications occurred, 71 were non-catheter-related and 46 were catheter-related. The most common catheter-related complications were premature loss of the catheter (18/46) and elevated blood urea nitrogen (BUN) and creatinine levels (12/46). CONCLUSIONS: Due to the lack of comparative studies the (added) benefit of IA antibiotic infusion in the treatment of PJI remains uncertain. Based on the current evidence, we would advise against using it as a stand-alone treatment. A prospective randomized controlled trial using a well-described infusion protocol is needed to see if the potential benefits justify the increased costs and potential complications of this treatment modality.

Pneumocystis jirovecii pneumonia in patients treated for systemic autoimmune disorders: a retrospective analysis of patient characteristics and outcome.

Objectives: Pneumocystis jirovecii is an opportunistic fungus. Pneumocystis jirovecii pneumonia (PJP) is well known in the human immunodeficiency virus (HIV)-infected population, but in non-HIV-related immunosuppressed patients, risk factors are largely unknown. We studied the characteristics and outcome of patients treated for systemic autoimmune disorders infected with P. jirovecii, aiming to clarify risk stratification to guide prophylaxis. Method: Clinical charts collected between 2010 and 2016 at the University Hospital of Leuven (Belgium) were reviewed. Information on type of systemic disorder, organ involvement, immunosuppressant use, and comorbidity was collected, and laboratory results were consulted. Results: In total, 39 cases of non-HIV PJP were retrieved, 24 of whom had pre-existing pulmonary disease. All were on immunosuppressant medication at the time of infection, the majority (36/39) taking glucocorticoids, with a median dose of 16 mg methylprednisolone over the past 3 months. Of the 39 cases, 21 were admitted to the intensive care unit and mortality reached 35%. Age and pulmonary disease correlated positively and methotrexate use negatively with mortality. When applying current prophylactic strategies to our cohort, 50% of infections could theoretically have been prevented. Conclusion: PJP is a rare but relevant clinical problem when caring for immunosuppressed patients with autoimmune systemic disorders. Pulmonary disease and age are risk factors for acquiring the infection and carry a worse prognosis. More studies are needed to further define prophylactic criteria.

Outcome of patients with systemic diseases admitted to the medical intensive care unit of a tertiary referral hospital: a single-centre retrospective study.

OBJECTIVES: Systemic diseases form a rare heterogeneous group of diseases, with important morbidity caused by disease evolution and/or treatment. We describe the clinical features and outcome of patients with these diseases admitted to a referral hospital intensive care unit (ICU). METHOD: We conducted a retrospective case review of all patients with systemic diseases (n = 86) admitted to the medical ICU of Leuven University Hospital between May 2007 and September 2012. RESULTS: The most frequent diagnoses were systemic vasculitis (n = 31), sarcoidosis (n = 15), systemic sclerosis (n = 9), and systemic lupus erythematosus (SLE) (n = 7). The main reason for admission was infection (60%), followed by disease-related organ failure (48%). Respiratory failure was the most common organ dysfunction. The mean APACHE II (Acute Physiology and Chronic Health Evaluation II) score was 28 ± 10. Mortality was 19% during ICU admission, 39% during hospital stay, and 58% at the end of follow-up. Death was caused by infection in the majority of cases (56%), and by evolution of the underlying disease in 32%. Only age and APACHE II score were associated with mortality. CONCLUSIONS: The mortality of patients with systemic diseases admitted to an ICU is high, both during their stay in the ICU and afterwards. Age and APACHE II score, but not infection or immunosuppressive therapy, were associated with mortality.

A tropical diabetic foot.

Foot infections are a common problem and an important cause of morbidity in patients with diabetes. We report a patient with type 2 diabetes, presenting with a chronic foot wound resistant to standard care, in whom the diagnosis of eumycetoma was made through histopathological examination of a bone biopsy specimen and confirmed by polymerase chain reaction (PCR). Diagnosis and treatment of eumycetoma are reviewed. Eumycetoma caused by Madurella mycetomatis is an uncommon cause of osteomyelitis in patients with diabetes in Europe, but should be considered in patients from endemic regions when (antibacterial) therapy fails.

Effects of haptoglobin polymorphisms and deficiency on susceptibility to inflammatory bowel disease and on severity of murine colitis.

BACKGROUND: Haptoglobin (Hp) is a haemoglobin-binding protein with immunomodulatory properties. Its gene (16q22) harbours a common polymorphism with two different alleles: Hp1 and Hp2. Genotype Hp22 has been shown to be over-represented in different immune diseases. Results in Crohn's disease (CD) are contradictory. AIMS: To determine whether Hp plays a role in inflammatory bowel disease, both genetically and functionally. METHODS: 1061 patients with CD, 755 with ulcerative colitis (UC) and 152 with primary sclerosing cholangitis, as well as 452 healthy controls, were genotyped using touch-down PCR. To confirm association results, 464 CD trios and 151 UC trios were genotyped. Serum Hp concentrations were determined in 62 individuals of different genotype. Colitis was induced in mice with dextran sulphate sodium (DSS) and oxazolone (Oxa). Cytokine production was evaluated by mRNA quantification in colonic tissue and ELISA on supernatants of mesenteric lymph node cells. RESULTS: Prevalence of Hp2 was higher in CD and UC than in controls. In the confirmatory cohorts, Hp2 was over-transmitted to the affected offspring. Serum Hp concentrations were higher in individuals with genotypes Hp11 and Hp21 than in those with Hp22 (1.38 vs 0.89 g/l). DSS- and Oxa-induced colitis were more severe in Hp-deficient mice than in control mice and accompanied by higher concentrations (although not statistically significantly different) of tissue mRNA for cytokines. Interleukin-17 production was significantly higher in the presence of Hp-deficient serum compared with wild-type serum. CONCLUSIONS: The Hp gene may play a role in susceptibility to inflammatory bowel disease. Its implication in other immune diseases underscores the common pathways between these diseases. Experimental models of colitis showed that Hp has a protective role in inflammatory colitis, most likely by inhibiting the production of Th1 and Th17 cytokines.

Long-term treatment of refractory invasive fungal infection with posaconazole: additive value of therapeutic drug monitoring.

Posaconazole is a recently developed broad-spectrum triazole antifungal with potential for long-term prophylaxis or therapy of invasive fungal infections. This case illustrates the additive value for therapeutic drug monitoring to guide clinical decision-making in high risk patients.

Influence of the type of indigestible carbohydrate on plasma and urine short-chain fatty acid profiles in healthy human volunteers.

BACKGROUND/OBJECTIVES: Health effects of whole grain foods are becoming more evident. In this study, we analysed the short-chain fatty acid profiles in urine and serum derived from the colonic fermentation process of (13)C-barley meals, prepared from barley grown under (13)CO(2) atmosphere. SUBJECTS/METHODS: In a crossover study, five volunteers ingested intact barley kernels (high content of non-starch polysaccharides (NSP) and resistant starch (RS)) and barley porridge (high content of NSP only). Using a newly developed stable isotope technology, we monitored 14 and 24 h postprandially (13)C-acetate, (13)C-propionate and (13)C-butyrate in plasma and urine, respectively. The oro-cecal transit time (OCTT) of the meals was measured with the hydrogen breath test. RESULTS: The OCTT was 6 h and did not differ between the two test meals. An increase of (13)C-acetate was observed already early after ingestion of the meals (<6 h) and was attributed to early fermentation of the test meal. A rise in plasma (13)C-propionate in the fermentation phase could only be detected after the porridge and not after the kernel meal. An increase in (13)C-butyrate was only found in the fermentation phase and was higher after the barley kernels. Urine (13)C-short-chain fatty acids data were consistent with these observations. CONCLUSIONS: The difference in the profiles of (13)C-acetate, (13)C-propionate and (13)C-butyrate indicates that NSP combined with RS results in an altered fermentation profile than dietary fibre alone.

Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study.

BACKGROUND AND AIMS: This study evaluates the long-term safety of infliximab in patients with inflammatory bowel disease (IBD) treated with the drug over a 14-year period. METHODS: The medical records of 734 patients with IBD treated with infliximab and 666 control patients not treated with infliximab were reviewed for adverse events. The time of onset and outcome, severity and concomitant medication were recorded. RESULTS: Patients and controls were followed up for serious adverse events for a median time of 58 months (IQR 33-88) and 144 months (IQR 83-163), respectively. 112 severe adverse events occurred in 93 patients (13%) treated with infliximab and 157 occurred in 126 (19%) control patients (OR 1.33 (95% CI 0.56 to 3.00, p = 0.45). There was no difference between the two groups in mortality, malignancies and infection rate. Tuberculosis was diagnosed in two patients receiving infliximab who had negative skin tests at baseline whereas none of 16 patients with positive skin tests who received prophylaxis developed tuberculosis. Concomitant treatment with steroids was the only independent risk factor for infections in patients treated with infliximab (OR 2.69 (95% CI 1.18 to 6.12), p = 0.018). The most commonly observed systemic side effects were skin eruptions including psoriasiform eruptions in 150 patients (20%). CONCLUSIONS: Long-term infliximab treatment had a good overall safety profile in the patient cohort studied.

Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts.

BACKGROUND: DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. METHODS: DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. RESULTS: The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men. CONCLUSION: DLG5 30Q is associated with a small reduction in risk of CD in women.

CT and MR imaging of gastrointestinal tuberculosis.

The purpose of this study was to describe the CT and MR imaging findings of tuberculosis of the gastrointestinal tract. Abdominal and pelvic CT scans and MRI studies of 6 patients with histopathological and microbiological proven intestinal tuberculosis were reviewed by two radiologists in consensus. Location and pattern of bowel wall involvement, signal intensities in relation to the normal bowel wall, pattern of enhancement and associated abdominal abnormalities were evaluated. Gastrointestinal tract tuberculosis may be limited to one bowel segment, with the cecum and ileocecal valve as the predominant site of disease, or may involve multiple bowel segments. Asymmetric thickening of the bowel wall is a common finding. Associated findings include pericecal and mesenteric fat stranding, regional lymphadenopathy showing peripheral, heterogeneous and/or homogeneous enhancement patterns and less commonly, tuberculous 'dry plastic' peritonitis. On magnetic resonance (MR) imaging, tuberculous bowel involvement results in intermediate decreased signal intensities on T1-weighted images, and intermediate increased, slight heterogeneous signal intensities on T2-weighted images. On contrast-enhanced images, slight heterogeneous enhancement is seen.

Polymorphisms in apoptosis genes predict response to infliximab therapy in luminal and fistulizing Crohn's disease.

BACKGROUND: Infliximab treatment is effective in 70-80% of patients with refractory luminal and fistulizing Crohn's disease. The effect of infliximab is ascribed to induction of apoptosis. AIM: To study whether polymorphisms in apoptosis genes predict the response to infliximab and whether they interact with clinical predictors. METHODS: Cohort of 287 consecutive patients treated with infliximab for refractory luminal (n = 204) or fistulizing (n = 83) Crohn's disease was genotyped for 21 polymorphisms in apoptosis genes. Short-term clinical response was assessed at week 4 (luminal Crohn's disease) or 10 (fistulizing Crohn's disease) after the first infliximab infusion. RESULTS: The response rate was 69% in luminal and 80% in fistulizing Crohn's disease. In luminal Crohn's disease, two genetic predictors were identified: (i) patients with the Fas ligand -843 CC/CT genotype (n = 135) responded in 75%, with the TT genotype (n = 21) in 38% only (P = 0.002; OR = 0.11; 95% CI: 0.08-0.56). (ii) Patients with the caspase-9 93 TT (n = 9) genotype all responded, in contrast with 67% (n = 147) with the CC and CT genotype (P = 0.04; OR = 1.50; 95% CI: 1.34-1.68). Concomitant azathioprine/mercaptopurine therapy overcame the effect of unfavourable genotypes. In the fistulizing Crohn's disease cohort, the same Fas ligand -843 CC/CT genotype was the only predictor of response (P = 0.002; OR = 1.66; 95% CI: 1.21-2.29), interacting with caspase-9 93 polymorphism but not with azathioprine/mercaptopurine. CONCLUSION: We observed that polymorphisms in FasL/Fas system and caspase-9 influence the response to infliximab in luminal and fistulizing Crohn's disease. The strongest association was seen between the Fas ligand -843 TT genotype and non-response. Concomitant mercaptopurine/azathioprine therapy, however, was able to overcome the effect of unfavourable genotypes in luminal disease.