BACKGROUND Non- albicans Candida prosthetic joint infections (PJIs) are rare. Optimal treatment involves a two-stage revision surgery in combination with an antifungal agent. However, no clear guidelines have been developed regarding the agent or treatment duration. Hence, a broad range of antifungal and surgical treatments have been reported so far. AIM To clarify treatment of non- albicans Candida PJIs. METHODS A literature review of all existing non- albicans Candida PJIs cases through April 2018 was conducted. Information was extracted about demographics, comorbidities, responsible species, duration and type of antifungal treatment, type of surgical treatment, time between initial arthroplasty and symptom onset, time between symptom onset and definite diagnosis, outcome of the infection and follow-up. RESULTS A total of 83 cases, with a mean age of 66.3 years, were located. The causative yeast isolated in most cases was C. parapsilosis (45 cases; 54.2%), followed by C. glabrata (18 cases; 21.7%). The mean Charlson comorbidity index was 4.4 ± 1.5. The mean time from arthropalsty to symptom onset was 27.2 ± 43 mo, while the mean time from symptom onset to culture-confirmed diagnosis was 7.5 ± 12.5 mo. A two stage revision arthroplasty (TSRA), when compared to one stage revision arthroplasty, had a higher success rate (96% vs 73%, P = 0.023). Fluconazole was the preferred antifungal agent (59; 71%), followed by amphotericin B (41; 49.4%). CONCLUSION The combination of TSRA and administration of prolonged antifungal therapy after initial resection arthroplasty is suggested on the basis of limited data.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years, including a considerable amount of genetic factors. Multiple mechanisms are involved in the pathogenesis of GERD including: (1) motor abnormalities, such as impaired lower esophageal sphincter (LES) resting tone, transient LES relaxations, impaired esophageal acid clearance and delayed gastric emptying; and (2) anatomical factors, such as hiatal hernia and obesity. Genetic contribution seems to play a major role in GERD and GERD- related disorders development such Barrett’s esophagus and esophageal adenocarcinoma. Twin and family studies have revealed an about 31% heritability of the disease. Numerous single-nucleotide polymorphisms in various genes like FOXF1, MHC, CCND1, anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk. GERD, Barrett’s esophagus and esophageal adenocarcinoma share several genetic loci. Despite GERD polygenic basis, specific genetic loci such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.

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Non-albicans Candida prosthetic joint infection (PJI) is extremely rare. A case of a Candida glabrata knee PJI is a 68-year-old splenectomised female smoker, suffering from chronic obstructive pulmonary disease (COPD) and alcoholism is reported. The patient presented with a peri-prosthetic fracture, 15 years after total knee replacement surgery. Cultures of the intraoperative peri-prosthetic tissue and materials yielded C. glabrata, as well as a methicillin-resistant S. epidermitis. The patient was treated with anidulafungin and vancomycin. The knee prosthetic joint was removed and cement-spacer with vancomycin and gentamycin was placed. Additionally, an external fixation was performed. A second stage revision surgery was planned, after completion of the antimicrobial and antifungal treatment. The patient is followed up for 4 months without signs, symptoms or findings of infection. PJI Candida infections require a high clinical suspicion index. It is of utmost importance to report these cases, since there is no consensus yet of the proper antifungal treatment. Furthermore, a literature review regarding treatment of those cases is provided. First-line treatment with an echinocandin seems most proper, due to their fungicidal properties, their effectiveness against biofilm, as well as their minimal toxicity, making them ideal for long-term use. Further experience is needed, for better understanding the disease's pathogenesis and optimal treatment.

Background: Fungal prosthetic joint infections (PJIs) are rare, especially those caused by non-Candida species. Treatment has not been fully elucidated, since a plethora of antifungal and surgical interventions have been proposed. Τhis study represents an effort to clarify the optimal management of non-Candida fungal PJIs, by reviewing all relevant published cases. Methods: A thorough review of all existing non-Candida fungal PJIs in the literature was conducted. Data regarding demographics, responsible organisms, antifungal treatment (AFT), surgical intervention, time between initial arthroplasty and onset of symptoms, and time between onset of symptoms and firm diagnosis, as well as the infection’s outcome, were evaluated. Results: Forty-two PJIs, in patients with mean age of 66.2 years, were found and reviewed. Aspergillus spp. were isolated in most cases (10; 23.8%), followed by Coccidioides spp. (7; 16.7%) and Pichiaanomala (5; 11.9%). Fluconazole was the preferred antifungal regimen (20 cases; 47.6%), followed by amphotericin B (18 cases; 42.9%), while the mean AFT duration was 9.4 months (SD = 7.06). Two-stage revision arthroplasty (TSRA) was performed in 22 cases (52.4%), with the mean time between stages being 5.2 months (SD = 2.9). The mean time between initial joint implantation and onset of symptoms was 42.1 months (SD = 50.7), while the mean time between onset of symptoms and diagnosis was 5.8 months (SD = 14.3). Conclusions: Non-Candida fungal PJIs pose a clinical challenge, demanding a multidisciplinary approach. The present review has shown that combination of TSRA separated by a 3–6-month interval and prolonged AFT has been the standard of care in the studied cases.