Recurrent Cryptococcal Meningitis in a Late Presenter of HIV: A Rare Case Report and Review of Literature.

BACKGROUND The highly active antiretroviral treatment (HAART) and the primary prophylaxis in newly diagnosed people living with HIV (PLHIV) have reduced the incidence of opportunistic infections such as cryptococcal meningitis (CM). Relapse of CM is associated with increased morbidity and mortality. The aim of the present case presentation is to report the clinical progress relapse of CM in a man who was a late presenter PLHIV, 1 year after ART initiation with increased CD4 cell count, undetectable viral load, and excellent compliance after disruption of secondary antifungal prophylaxis. CASE REPORT One year after initial diagnosis of HIV and CM, the patient had no neurological or other symptoms, and viral suppression and increased CD4 cell count were achieved. After the completion of 12 months of secondary prophylaxis with fluconazole, an episode of partial seizure with secondary generalization occurred, followed by a short-term memory loss. Magnetic resonance imaging (MRI) indicated a focal lesion in right frontal-parietal brain region. Lumbar puncture was conducted and Cryptococcus neoformans non-resistant to fluconazole was isolated. He received antiepileptic treatment, induction antifungal treatment with liposomal amphotericin and fluconazole, consolidation treatment with fluconazole, and secondary prophylaxis with fluconazole, as in the first episode of CM. One year after the relapse, antiepileptic treatment and secondary prophylaxis with fluconazole continues and no new episode has been reported. The diagnosis of immune reconstitution inflammatory syndrome (IRIS)-related relapse of CM cannot be excluded. CONCLUSIONS Further studies are needed for the evaluation of parameters such as duration of secondary prophylaxis and treatment options for induction and consolidation therapy to reduce the relapse rate of CM.

Association between vitamin D receptor gene polymorphisms and fibrosis susceptibility in Greek patients with HCV infection.

Introduction: Hepatitis C virus (HCV) infection is a prime cause of chronic hepatitis worldwide, that often silently progresses to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Notably, the majority of individuals infected with HCV develop symptoms at late stages, often associated with liver damage that cannot revert after virus clearance. Thus, current antiviral therapy alone is rather insufficient to eliminate the global burden of HCV in the near future.During the past few years, vitamin D deficiency as well as certain single nucleotide polymorphisms in the vitamin D receptor (VDR) gene have been associated with liver fibrosis. Therefore, the aim of the present study was to investigate the possible correlation between VDR polymorphisms ApaI (rs7975232) and TaqI (rs731236) and the fibrosis stage of patients with HCV infection from Thrace, Greece. Methods: Eighty-one patients with HCV infection underwent transient elastography for the assessment of their fibrosis stage, and PCR-restriction fragment length polymorphism (RFLP) genotyping for VDR ApaI and TaqI polymorphisms. VDR genotypes were then statistically associated with the patients' fibrosis stage using ordinal regression models. Results: Non-cirrhotic stages were positively correlated with TaqI TT genotype (p=0.003) and negatively correlated with TaqI TC genotype (p=0.007). In the presence of Hardy-Weinberg equilibrium and linkage disequilibrium between the two VDR polymorphisms, mild fibrosis stages (F0-2) were correlated with ApaI/TaqI GG/TT (p=0.002) and TG/TT (p=0.008) genotypes, while cirrhotic stage F4 was associated with ApaI/TaqI TG/TC genotype (p=0.038). Conclusions: TaqI TT and ApaI/TaqI GG/TT, TG/TT and TG/TC genotypes could be explored as prognostic genetic markers for fibrosis susceptibility in HCV patients.

Local Antibiotic Delivery Systems in the Surgical Treatment of Diabetic Foot Osteomyelitis: Again, No Benefit?

This retrospective study aimed to compare the outcomes and healing parameters of 3 groups of surgical treatment combined with and without local antibiotic administration in diabetic foot osteomyelitis (DFO). Overall, 25 patients with DFO who met the criteria were included in the study. Surgical debridement was used with systemic antibiotic administration alone (group A; n = 8) or combined with local application of antibiotic-loaded polymethylmethacrylate beads (group B; n = 9) or antibiotic-loaded hydroxyapatite and calcium sulfate beads (group C; n = 8). In total, 87.5% patients in group A, 100% in group B, and 87.5% in group C healed (P = .543). Median time to healing was 17 weeks in group A, 18 weeks in group B, and 19 weeks in group C (P = .094). One patient (12.5%) in group A was amputated. DFO recurrence rate was 12.5% in group A and 12.5% in group C (P = .543). Median hospitalization was 9 days in group A, 8 days in group B, and 9 days in group C (P = .081). In conclusion, adjunctive local antibiotic therapy was not shown to improve outcomes in surgically treated DFO.

Smell and Taste Loss Recovery Time in COVID-19 Patients and Disease Severity.

A significant proportion of people infected with SARS-CoV-2 report a new onset of smell or taste loss. The duration of the chemosensory impairment and predictive factors of recovery are still unclear. We aimed to investigate the prevalence, temporal course and recovery predictors in patients who suffered from varying disease severity. Consecutive adult patients diagnosed to be infected with SARS-CoV-2 via reverse-transcription-polymerase chain reaction (RT-PCR) at two coronavirus disease-2019 (COVID-19) Reference Hospitals were contacted to complete a survey reporting chemosensory loss, severity, timing and duration, nasal symptoms, smoking, allergic rhinitis, chronic rhinosinusitis, comorbidities and COVID-19 severity. In a cross-sectional study, we contacted 182 patients and 150 responded. Excluding the critically ill patients, 38% reported gustatory and 41% olfactory impairment (74% severe/anosmia). Most of the patients (88%) recovered their sense of smell by two months (median: 11.5 days; IQR: 13.3). For 23%, the olfactory loss lasted longer than a month. There were no significant differences in the prevalence and duration of chemosensory loss between groups of varying COVID-19 severity, and sexes (all p > 0.05). Moderate hyposmia resolved quicker than more severe loss (p = 0.04). Smell and taste loss are highly prevalent in COVID-19. Most patients recover fast, but nearly one out of ten have not recovered in two months.

Immune and Metabolic Interactions of Human Erythrocytes: A Molecular Perspective.

Apart from their main function as oxygen carriers in vertebrates, erythrocytes are also involved in immune regulation. By circulating throughout the body, the erythrocytes are exposed and interact with tissues that are damaged as a result of a disease. In this study, we summarize the literature regarding the contribution of erythrocytes to immune regulation and metabolism. Under the circumstances of a disease state, the erythrocytes may lose their antioxidant capacity and release Damage Associated Molecular Patterns, resulting in the regulation of innate and adaptive immunity. In addition, the erythrocytes scavenge and affect the levels of chemokines, circulating cell-free mtDNA, and C3b attached immune complexes. Furthermore, through surface molecules, erythrocytes control the function of T lymphocytes, macrophages, and dendritic cells. Through an array of enzymes, red blood cells contribute to the pool of blood's bioactive lipids. Finally, the erythrocytes contribute to reverse cholesterol transport through various mechanisms. Our study is highlighting overlooked molecular interactions between erythrocytes and immunity and metabolism, which could lead to the discovery of potent therapeutic targets for immunometabolic diseases.

Inverse association between Helicobacter pylori infection and childhood asthma in Greece: a case-control study.

INTRODUCTION: Helicobacter pylori infection is a well-established etiological factor for a variety of diseases such as peptic ulcer and gastric cancer. On the other hand, there is ongoing research suggesting that H. pylori might have a beneficial effect through a pivotal influence in the immunological response especially in asthma. The aim of the current case-control study was to evaluate the prevalence of H. pylori infection in asthmatic children. METHODS: Twenty-seven children with exacerbation of persistent asthma, aged 8.6±4.5 years (18 males, 9 females) and 54 age-sex-matched non-asthmatic controls were enrolled. Clinical examination and laboratory investigations were performed. Detection of H. pylori antigen (HpSA) in stool samples was performed by a commercial kit (bioNexia® kit, BioMérieux). Serum specific IgG antibodies were detected by a rapid chromatographic immunoassay (DIAsourceImmunoAssays). Serum IgE concentration was determined by electrochemiluminescence (ECL) (Roche Elecsys) and IgE levels ≥ 90 IU/mL were considered significantly elevated. RESULTS: In 3 (11.1%) of the 27 asthmatic children H. pylori infection (based on both detection of HpSA and specific IgG-Abs) was established, whereas as many as 16 of the 54 (29.6%) non-asthmatic ones were found infected (odds ratio 0.1; 95%CI, 0.039-0.305, p=0.026). CONCLUSIONS: Our findings reveal an inverse relationship between H. pylori infection and children's persistent asthma in Greece.

EBV-related Cold Agglutinin Disease Presenting With Conjugated Hyperbilirubinemia: A Pediatric Case Report and Mini Review.

Hemolytic anemia occurs in only 1% to 3% of hospitalized patients with infectious mononucleosis. The authors describe an 8-year-old girl without cervical lymphadenopathy or splenomegaly, who presented with conjugated hyperbilirubinemia and was diagnosed with cold agglutinin disease caused by an immunoglobulin M autoantibody with anti-i specificity. Acute Epstein-Barr virus infection was confirmed by serologic and molecular methods. She recovered uneventfully after a 3-week course of methylprednisolone. Epstein-Barr virus infection should be considered in any case of hemolytic anemia associated with hepatic dysfunction, especially when direct antiglobulin test is positive for C3d. In these cases, a course of corticosteroids seems safe and may be beneficial.

Study of Antiphospholipid Antibodies in Patients with Arterial Hypertension.

Antiphospholipid syndrome (APS) is a multifactorial, autoantibody-mediated disease. Antiphospholipid antibodies (aPL) directed against negatively charged phospholipids or various combinations of phospholipid-binding proteins seem to be an independent pathogenic factor that plays a critical role in APS. Unfortunately, their role in hypertension is not fully elucidated. The aim of our study was to determine aPL titers in hypertension patients and investigate the association of aPL with renal impairment parameters. Forty-seven patients with arterial hypertension (22 males, 46.8% and 25 females, 53.2%), aged 41⁻85 years old (mean 65.9 ± 10.1 years), and 21 age-sex-matched subjects without severe hypertension as control group (8 males, 13 females, 38.1% vs. 61.9%), mean age 61 ± 11.3 years, were enrolled in this study. Patients with other risk factors like Rheumatoid Arthritis and Systematic Lupus Erythematosus (SLE), both viral and bacterial acute infections, and cancer were excluded from the study. The aPL (anticardiolipin (ACA) and anti-b2GPI antibodies, IgG and IgM) were measured by ELISA (Aesculisa, Aesku Diagnostics, Wendelsheim, Germany) with a cutoff of 15 GPL/MPL for ACA and 15 U/mL for b2GPI. Serum Neutrophil gelatinase-associated lipocalin (sNGAL) was measured by ELISA kits (BioVendor, Brno, Czech Republic). Biochemical analysis such as serum creatinine (Cr), were measured by automated analyzer and finally estimated glomerular filtration rate (e-GFR) was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Fifteen patients were positive for ACA IgG (31.9%), two for anti-b2GPI IgM (4.2%), and three for anti-b2GPI IgG (6.3%). Furthermore, three persons from control group were positive in anti-b2GPI IgG (14.27%). The serum level of anti-b2GPI IgG was significantly higher in patients compared to healthy controls (p = 0.013). The level of sNGAL (59.63 ± 41.5 ng/mL vs. 45.5 ± 21.5 ng/mL, p = 0.14) was not higher in hypertensive patients than in the age-sex-matched control group. Additionally, the sNGAL level was found to be directly and positively correlated in patients with positive ACA IgG (r² = 0,945, p < 0.0001). These results demonstrate that autoimmunity may be one of the pathogenetic factors of hypertension and aPL antibodies might be a potential marker of renal involvement.

Point-prevalence survey of healthcare facility-onset healthcare-associated Clostridium difficile infection in Greek hospitals outside the intensive care unit: The C. DEFINE study.

BACKGROUND: The correlation of Clostridium difficile infection (CDI) with in-hospital morbidity is important in hospital settings where broad-spectrum antimicrobial agents are routinely used, such as in Greece. The C. DEFINE study aimed to assess point-prevalence of CDI in Greece during two study periods in 2013. METHODS: There were two study periods consisting of a single day in March and another in October 2013. Stool samples from all patients hospitalized outside the ICU aged ≥18 years old with diarrhea on each day in 21 and 25 hospitals, respectively, were tested for CDI. Samples were tested for the presence of glutamate dehydrogenase antigen (GDH) and toxins A/B of C. difficile; samples positive for GDH and negative for toxins were further tested by culture and PCR for the presence of toxin genes. An analysis was performed to identify potential risk factors for CDI among patients with diarrhea. RESULTS: 5,536 and 6,523 patients were screened during the first and second study periods, respectively. The respective point-prevalence of CDI in all patients was 5.6 and 3.9 per 10,000 patient bed-days whereas the proportion of CDI among patients with diarrhea was 17% and 14.3%. Logistic regression analysis revealed that solid tumor malignancy [odds ratio (OR) 2.69, 95% confidence interval (CI): 1.18-6.15, p = 0.019] and antimicrobial administration (OR 3.61, 95% CI: 1.03-12.76, p = 0.045) were independent risk factors for CDI development. Charlson's Comorbidity Index (CCI) >6 was also found as a risk factor of marginal statistical significance (OR 2.24, 95% CI: 0.98-5.10). Median time to CDI from hospital admission was shorter with the presence of solid tumor malignancy (3 vs 5 days; p = 0.002) and of CCI >6 (4 vs 6 days, p = 0.009). CONCLUSIONS: The point-prevalence of CDI in Greek hospitals was consistent among cases of diarrhea over a 6-month period. Major risk factors were antimicrobial use, solid tumor malignancy and a CCI score >6.

Tissue and swab culture in diabetic foot infections: neuropathic versus neuroischemic ulcers.

We evaluated the diagnostic performance of swabs versus tissue cultures in 28 diabetic patients with neuropathic (group A) and 22 diabetic patients with neuroischemic foot ulcer (group B) and the differences in bacterial isolates between the 2 groups. In group A, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of swab cultures for the diagnosis of infection were 100%, 40%, 88.5%, and 100%, respectively. In group B, the corresponding values were 100%, 22.2%, 65%, and 100%. In group A, sensitivity, specificity, PPV, and NPV of swab cultures for the identification of pathogens were 100%, 14.3%, 53.8%, and 100%, respectively. In group B, the corresponding values were 100%, 18.2%, 55%, and 100%. In each group, Staphylococcus aureus and Pseudomonas aeruginosa were the most common isolates. The number of isolates was significantly higher on swab versus tissue cultures only in group A (P = .033). No differences were observed between groups in number of isolates and colony forming units. In conclusion, swab cultures are highly sensitive but less specific and have an excellent NPV both in diabetic patients with neuropathic and in those with neuroischemic foot ulcer. There are no differences between the groups in microbial load.

Bacterial translocation in a rat model of large volume hepatic radiofrequency ablation.

BACKGROUND: In this experimental study, we investigated the possibility of bacterial translocation, constituting a potential cause of infectious complications, after performing large volume hepatic radiofrequency ablation (RFA). MATERIALS AND METHODS: Wistar rats were subjected to RFA of the left median liver lobe (approximately 28.5% of the liver volume) after midline laparotomy. At 30 min, 24 h, 48 h, 72 h or 1 wk postoperatively, (1) blood samples were collected from the portal and systemic circulation for assessment of endotoxin concentration, (2) tissue specimens were excised from mesenteric lymph nodes, non-ablated liver, pancreas, spleen, kidneys, and lungs for bacterial culture, and (3) segments of terminal ileum were excised for histopathologic examination, morphometric analysis, and apoptotic and mitotic rate estimation. At 1 and 48 h, ileal mucosa was collected for oxidative state assessment on the basis of glutathione to glutathione disulfate (GSH/GSSG) ratio. RESULTS: Endotoxin levels were increased in both the portal and systemic circulation. Intestinal bacteria were isolated from all the organs at all time points. Ileal mucosa became gradually atrophic, with a decrease in villous height and density. There was an increase of crypt apoptotic rate, a decrease of GSH/GSSG ratio, while there were only mild signs of inflammation. CONCLUSIONS: Large volume liver RFA in the rat resulted to endotoxemia and translocation of intestinal bacteria to proximal and distal to the intestine organs at both the early and late post-RFA periods. The intestinal mucosa barrier was disrupted as suggested by ileal mucosal atrophy, increased crypt apoptosis, and induction of oxidative stress.