The relationship between the clinical course of SARS-CoV-2 infections and ACE2 and TMPRSS2 expression and polymorphisms.

BACKGROUND: The viral spike (S) protein and host ACE2 and TMPRSS2 genetic variations may act as a barrier to viral infections or determine susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. OBJECTIVES: We investigated the relationship between the expression patterns and polymorphisms of the ACE2 and TMPRSS2 receptor genes associated with coronavirus disease 2019 (COVID-19) and the clinical course of SARS-CoV-2 infections. MATERIAL AND METHODS: We examined 147 COVID-19 patients (41 asymptomatic, 53 symptomatic and 53 cases treated in the intensive care unit (ICU)) and 33 healthy controls. The ACE2 and TMPRSS2 expression was determined using the One-Run RT-qPCR kit. Genotypic distributions of single nucleotide polymorphisms (SNPs) of ACE2 and TMPRSS2 were obtained using reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: The expressions of ACE2 and TMPRSS2 were different between SARS-CoV-2-positive and -negative groups. The ACE2 rs714205GG genotype and G-allele showed significant differences in the asymptomatic SARS-CoV-2-positive group. A significant correlation was found between the expression of TMPRSS2 rs8134378GA, rs2070788GA, rs7364083GA, and rs9974589AC genotypes and SARS-CoV-2 positivity. The rs1978124 C-allele and rs8134378 A-allele expressions were significant in the symptomatic SARS-CoV-2-positive group. The TMPRSS2 rs2070788GA expression was different in all patient groups compared to the control group. There was a difference between SARS-CoV-2-positive and -negative groups regarding the CTTA haplotype formed by ACE2 variants. The AGCAG and AGAAG haplotypes formed by the TMPRSS2 variants were more common in the asymptomatic patient group than in other patient groups. CONCLUSIONS: Identifying the relationship between host genetic variants and COVID-19 susceptibility will contribute to further studies, enabling new vaccines and potential therapeutic approaches to be discovered.

Prognostic value of semi-quantitative CT-based score integrated with cardiovascular risk factors during the first peak of the COVID-19 pandemic: A new score to predict poor outcome.

PURPOSE: Predicting the clinical course of COVID-19 pneumonia is of high clinical importance and may change treatment strategies. This study aimed to compare the semi-quantitative CT score (radiological score), mCHA2DS2-VASc score (clinical score), and R-mCHA2DS2-VASc score (clinical and radiological score) to predict the risk of ICU admission and mortality in COVID 19 pneumonia. METHODS: This study retrospectively evaluated 901 COVID-19 pneumonia cases with positive PCR results. The mCHA2DS2-VASc score was calculated based on clinical risk factors. CT images were evaluated, and the semi-quantitative CT scores were obtained. A new scoring method (R-mCHA2DS2-VASc score) was developed by combining these scores. The performance of the mCHA2DS2-VASc score, semi-quantitative CT score, and a combination of these scores (R-mCHA2DS2-VASc score) was evaluated using ROC analysis. RESULTS: The ROC curves of the semi-quantitative CT, mCHA2DS2-VASc, and R-mCHA2DS2-VASc scores were examined. The semi-quantitative CT, mCHA2DS2-VASc, and R-mCHA2DS2-VASc scores were significant in predicting intensive care unit (ICU) admission and mortality (p < 0.001). The R-mCHA2DS2-VASc score performed best in predicting a severe clinical course, and the cut-off value of 8 for the R-mCHA2DS2-VASc score had 83.9% sensitivity and 91.6% specificity for mortality. CONCLUSIONS: The R-mCHA2DS2-VASc score includes both clinical and radiological parameters. It is a feasible scoring method for predicting a severe clinical course at an early stage with high sensitivity and specificity values. However, prospective studies with larger sample sizes are warranted.

Infections in hematopoietic stem cell transplant patients admitted to Hematology intensive care unit: a single-center study.

OBJECTIVE: The aim of this study was to investigate the data of HSCT patients who were admitted to our Hematology ICU due to infections or infectious complications. MATERIALS AND METHODS: HSCT patients who were admitted to our Hematology ICU between 01 January 2014 and 01 September 2017 were analyzed retrospectively. RESULTS: 62 HSCT patients were included in this study. The median age was 55.5 years and 58% of the patients were allogeneic HSCT patients. Major underlying hematologic disorders were multiple myeloma (29%) and lymphoma (27.4%). The most common reasons for ICU admission were sepsis/septic shock (61.3%) and acute respiratory failure (54.8%). Overall ICU mortality rate was 45.2%. However, a lot of factors were related with ICU mortality of HSCT patients in univariate analysis, only APACHE II score was found to be an independent risk factor for ICU mortality. While there was infection in 58 patients at ICU admission, new infections developed in 38 patients during ICU stay. The most common new infection was pneumonia/VAP, while the most frequently isolated bacteria were Acinetobacter baumannii. Length of ICU stay, sepsis/septic shock as a reason for ICU admission and the presence of urinary catheter at ICU admission were determined factors for ICU-acquired infections. There was no difference between autologous and allogeneic stem cell transplant patients in terms of ICU morbidities and mortality. However, pneumonia/VAP developed in the ICU was higher in autologous HSCT patients, while bloodstream/catheter-related bloodstream infection was higher in allogeneic HSCT patients. CONCLUSION: It was concluded that early or late post-HSCT infections and related complications (sepsis, organ failure, etc.) constituted a major part of the reasons for ICU admission, ICU mortality and ICU morbidities.

The prognostic role of neopterin in COVID-19 patients.

In Coronavirus disease-2019 (COVID-19) cases, hyper inflammation is associated with the severity of the disease. High levels of circulating cytokines were reported in severe COVID-19 patients. Neopterin produced by macrophages on stimulation with interferon-gamma, which is an important cytokine in the antiviral immune response, hence it can be used to predict the severity of disease in COVID-19 cases. In this study, it was aimed to determine the prognostic value of the neopterin for the prediction of severe disease in patients with COVID-19. This single-center, prospective study was conducted in hospitalized COVID-19 patients and healthy volunteers. Severe and mild COVID-19 cases were compared in terms of clinical and laboratory findings as well as serum neopterin levels on hospital admission. To assess the prognostic utility of neopterin between the severe and mild COVID-19 groups, a receiver-operating characteristic (ROC) curve was generated, and the area under the curve (AUC) was calculated. The median serum neopterin level was four times higher in COVID-19 patients than the healthy controls (46 vs. 12 nmol/L; p < .001). The AUC value of serum neopterin was 0.914 (95% confidence interval, 0.85-0.97). The sensitivity and specificity of serum neopterin for the cut-off value of 90 nmol/L to identify severe COVID-19 cases were 100% and 76%, respectively. Serum neopterin levels on hospitalization were significantly higher in severe COVID-19 disease than mild COVID-19 patients. Neopterin levels can be used as an early prognostic biomarker for COVID-19 on admission.

Daptomycin vs. glycopeptides in the treatment of febrile neutropenia: results of the Izmir matched cohort study.

PURPOSE: In this multicentre, retrospective, matched cohort study we aimed to evaluate the outcomes of neutropenic fever cases that were treated with daptomycin or a glycopeptide (vancomycin or teicoplanin). METHODS: Data and outcomes of adult (aged > 18-years old) patients with neutropenic fever [(1) without clinical and radiological evidence of pneumonia, (2) who were treated with daptomycin or a glycopeptide (teicoplanin or vancomycin) for any reason and for at least 72 h] were extracted from the hospital databases. Matching was performed with all of the three following criteria: (1) underlying disease, (2) reason for starting daptomycin or glycopeptide (microbiologic evidence vs. microbiologic evidence, clinical infection vs. clinical infection and empirical therapy vs. empirical therapy) and (3) neutropenic status. RESULTS: Overall 128 patients [(69/123) (56.1%) in the daptomycin cohort (D) and 59/123 (48%) in the glycopeptide cohort (G)] had a resolution of fever at the end of 72 h antibiotic treatment (p = 0.25). There was no significant difference in cured, improved and (cured + improved) rates between (D) and (G) cohorts as well as fever of unknown origin cases or microbiologically confirmed infections or clinically defined infections subgroups (p > 0.05). There was also no significant difference (p > 0.05), in terms of persistent response in the (D) versus (G) cohorts, CONCLUSIONS: These findings suggest that although not better, daptomycin efficacy is comparable to vancomycin if used as empiric therapy in the treatment of adult febrile neutropenia. We conclude that daptomycin may be used at least as a salvage therapy alternative to glycopeptides in the treatment of adult febrile neutropenia cases. A large, randomized-controlled trial may further consolidate the evidence related to this question.

The incidence of tuberculosis infection in hematopoietic stem cell transplantation recipients: A retrospective cohort study from a center in Turkey.

BACKGROUND: Immune-compromised patients with latent TB infection (LTBI) are at risk for TB reactivation and should receive prophylaxis. Whereas the tuberculin skin test (TST) has limitations particularly in immune-compromised patients. AIMS: This retrospective study was conducted to determine the incidence of TB infection in adult HSCT recipients whose preventive therapy for LTBI was determined according to the guidance of targeted TST. PATIENTS AND METHODS: Five hundred and fifty-eight consecutive HSCT recipients (287 autologous and 271 allogeneic) who survived ≥100 days post-transplantation were included in this analysis. RESULTS: Tuberculin skin test results were available in 493 of 558 transplants (88.3%). The incidence of negative TST was 54.5% (269 of 493 patients). One multiple myeloma patient with a history of TB and negative TST result and was not on INH prophylaxis developed reactivation of TB infection. None of the recipients under INH prophylaxis (151 of 558 transplants; 27.1%) and none of the 224 patients with TST ≥5 mm developed TB infection. DISCUSSION: Despite the limitations of being a retrospective analysis and variable prophylaxis thresholds of TST, there are some remarkable results of this analysis. We had no TB infection in the allogeneic HSCT recipients. The high incidence of negative TST results may be attributed to the underlying immune-deficiency. TST may not be a reliable guide for predicting TB reactivation risk in hematology patients. CONCLUSION: Tuberculin skin test may have a high rate of false-negative and false-positive results in HSCT recipients. The general guidelines for targeted TST to guide treatment of LTBI may not apply to all regions and situations. More reliable methods are required to predict and treat LTBI in these specific conditions.

Miliary tuberculosis: Epidemiologicaland clinical analysis of large-case series from moderate to low tuberculosis endemic Country.

The aim of this study was to determine the clinical features, and outcome of the patients with miliary tuberculosis (TB).We retrospectively evaluated 263 patients (142 male, 121 female, mean age: 44 years, range: 16-89 years) with miliary TB. Criteria for the diagnosis of miliary TB were at least one of the followings in the presence of clinical presentation suggestive of miliary TB such as prolonged fever, night sweats, anorexia, weight loss: radiologic criterion and pathological criterion and/or microbiological criterion; pathological criterion and/or microbiological criterion.The miliary pattern was seen in 88% of the patients. Predisposing factors were found in 41% of the patients. Most frequent clinical features and laboratory findings were fever (100%), fatigue (91%), anorexia (85%), weight loss (66%), hepatomegaly (20%), splenomegaly (19%), choroid tubercules (8%), anemia (86%), pancytopenia (12%), and accelerated erythrocyte sedimentation rate (89%). Tuberculin skin test was positive in 29% of cases. Fifty percent of the patients met the criteria for fever of unknown origin. Acid-fast bacilli were demonstrated in 41% of patients (81/195), and cultures for Mycobacterium tuberculosis were positive in 51% (148/292) of tested specimens (predominantly sputum, CSF, and bronchial lavage). Blood cultures were positive in 20% (19/97). Granulomas in tissue samples of liver, lung, and bone marrow were present in 100% (21/21), 95% (18/19), and 82% (23/28), respectively. A total of 223 patients (85%) were given a quadruple anti-TB treatment. Forty-four (17%) patients died within 1 year after diagnosis established. Age, serum albumin, presence of military pattern, presence of mental changes, and hemoglobin concentration were found as independent predictors of mortality. Fever resolved within first 21 days in the majority (90%) of the cases.Miliary infiltrates on chest X-ray should raise the possibility of miliary TB especially in countries where TB is endemic. Although biopsy of the lungs and liver may have higher yield rate of organ involvement histopathologicaly, less invasive procedures including a bone marrow biopsy and blood cultures should be preferred owing to low complication rates.

Brain abscess caused by Nocardia cyriacigeorgica in two patients with multiple myeloma: novel agents, new spectrum of infections.

OBJECTIVE AND IMPORTANCE: Introduction of high-dose chemotherapy and the novel agents including bortezomib, Lenalidomide, and Thalidomide has provided a significant progress in the treatment of multiple myeloma (MM) with an increase in median overall survival up to 6-8 years. However, the advances in myeloma treatment comes at a price with new spectrum of treatment-related infectious complications which should be taken into consideration while treating these patients. CLINICAL PRESENTATION: We report here two patients with Ig G λ MM presenting with intracerebral mass lesions in the abscence of constitutional symptoms that would suggest an infectious etiology. Both patients had severe hypogammaglobulinemia and lymphopenia, which was attributed to treatment regimens including bortezomib. Intervention The surgical intervention-revealed abscess in both cases caused by Nocardia cyriacigeorgica, a relatively new pathogen which rarely causes infections in humans and also an unexpected pathogen in myeloma patients. CONCLUSION: Although every aspect of immune system is known to be affected in MM, humoral immune deficiency is the hallmark of the inherent immune defect in this disease. Introduction of the novel agents, bortezomib in particular seems to have changed the characteristics of the immune dysfunction and the spectrum of the opportunistic infections by causing qualitative and quantitative changes in cellular immunity. The new spectrum of infectious agents might not be limited to hepatitis B and herpes zoster. Monitoring lymphopenia and administration of prophylactic antimicrobial agents accordingly could be considered in patients treated with bortezomib.

Visceral leishmaniasis mimicking autoimmune hepatitis, primary biliary cirrhosis, and systemic lupus erythematosus overlap.

Visceral leishmaniasis (VL) is a life-threatening infection caused by Leishmania species. In addition to typical clinical findings as fever, hepatosplenomegaly, and cachexia, VL is associated with autoimmune phenomena. To date, VL mimicking or exacerbating various autoimmune diseases have been described, including systemic lupus erythematosus (SLE), rheumatoid arthritis, and autoimmune hepatitis (AIH). Herein, we presented a patient with VL who had overlapping clinical features with SLE, AIH, as well as antimitochondrial antibody (AMA-M2) positive primary biliary cirrhosis.

Acinetobacter baumannii infection in patients with hematologic malignancies in intensive care unit: risk factors and impact on mortality.

PURPOSE: We investigated the characteristics of Acinetobacter baumannii infection in critically ill patients with hematologic malignancies. MATERIALS AND METHODS: The prospectively collected data of patients with hematologic malignancies admitted to a medical intensive care unit of a university hospital from 2007 through 2010 were reviewed retrospectively. RESULTS: One hundred twenty-eight patients were included in the study, among whom 35 (27%) developed 39 A baumannii infections. Pneumonia was the most common infection site of A baumannii. Presence of neutropenia, underlying hematologic malignancy, and the disease status did not affect the acquisition of the infection. Advancing age, prior exposure to aminoglycosides, central venous catheterization, and presence of nasogastric tube were the independent risk factors for the development of A baumannii infections. The mortality rate was higher in patients with A baumannii infections compared with the ones without (P = .009). However, in multivariate analysis, low Glasgow coma scale, prior immunosuppressive treatment, neutropenia, invasive mechanical ventilation, and severe sepsis were independently associated with mortality, whereas presence of A baumannii infection was not. CONCLUSIONS: Despite the high mortality rate in critically ill patients with hematologic malignancies, presence of A baumannii infection was not an independent risk factor for mortality.

Isolated cutaneous aspergillosis in an acute lymphoblastic leukemia patient after allogeneic stem cell transplantation.

Cutaneous aspergillosis is very rare and occurs predominantly in immunocompromised patients including transplant recipients. We report a 26-year-old male with acute lymphoblastic leukemia who developed cutaneous aspergillosis after undergoing combined immunosuppressive treatment including corticosteroid, cyclosporine A, mychophenolate mofetil and mesenchymal stem cells for steroid refractory skin acute graft versus host disease after myeloablative haematopoietic stem cell transplantation.  The patient was treated with oral voriconazole therapy and recovered partially. 

Nosocomial imipenem-resistant Acinetobacter baumannii infections: epidemiology and risk factors.

The incidence, clinical characteristics, risk factors, antimicrobial susceptibility, and outcomes of nosocomial imipenem-resistant A. baumannii (IRAB) infections during a 5-y period (2003-2007) were retrospectively analyzed. A total of 720 patients with 925 episodes of A. baumannii infection were included in the study. A. baumannii infections were seen mostly in intensive care units. The incidence was 6.2 per 1000 admissions. The most common infections were pneumonias and bloodstream infections. Imipenem resistance among Acinetobacter strains increased significantly each y of the study (from 43.3% to 72.9%). Mortality was related to the presence of imipenem resistance, stay in intensive care unit, female gender, old age, and pneumonia. Haemodialysis, malignancy, and mechanical ventilation were significant risk factors for IRAB infections. Imipenem resistance was higher in strains isolated from patients with pneumonia. IRAB strains showed higher resistance rates to other antibiotics than imipenem-susceptible strains. The most active antimicrobial agents against A. baumannii were cefoperazone-sulbactam and netilmicin. The incidence of A. baumannii infections and imipenem resistance increased during the study period. IRAB infections should be considered in patients on mechanical ventilation and haemodialysis and in patients with malignancies.

High ferritin levels are associated with hepatosplenic candidiasis in hematopoietic stem cell transplant candidates.

OBJECTIVES: Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Hepatosplenic candidiasis (HSC) is defined as a distinct form of invasive candidiasis, with liver, spleen, and kidney involvement, in patients with hematological disorders. METHODS: The charts of 255 patients (male/female 168/87; median age 35 (range 16-71) years) who were evaluated pre-HSCT at the Gazi University Hospital Stem Cell Transplantation Unit between 2003 and 2008, were retrospectively reviewed. RESULTS: HSC, which was demonstrated in six (2.3%) patients, was found to be more common in allogeneic HSCT recipients than in autologous HSCT recipients and in patients who had received two or more previous chemotherapy courses than in patients who had received fewer than two (p>0.05). Patients with HSC tended to have a worse performance status than patients without HSC according to the World Health Organization (p=0.001) and Karnofsky scale (p=0.007). Pre-transplantation ferritin (p=0.008) and acute phase reactant levels, including erythrocyte sedimentation rate (p=0.025) and C-reactive protein (p=0.007), were significantly higher in patients with HSC than in patients without HSC. CONCLUSIONS: This study shows the predictive role of pre-transplantation ferritin levels in selecting a subset of patients at increased risk for HSC. Pre-transplantation risk assessment and targeted strategies might lower the morbidity and mortality of IFI in HSCT recipients.

Nosocomial Burkholderia cepacia infections in a Turkish university hospital: a five-year surveillance.

BACKGROUND: Burkholderia cepacia has the potential to cause fatal infections in ICUs, and multidrug resistance makes them a serious threat in hospital settings. The aim of this study was to evaluate the epidemiology of B. cepacia infections in our hospital. METHODOLOGY: The incidence, clinical characteristics, antimicrobial susceptibility, and outcomes of nosocomial B. cepacia infections during a five-year period were retrospectively analysed according to the infection control committee records. RESULTS: A total of 39 cases with nosocomial B. cepacia infection were included in the study. B. cepacia was identified from 0.7% of the nosocomial isolates. Its incidence was 0.26 per 1,000 admissions with 53.8% crude mortality rate. The most frequent nosocomial B. cepacia infection was pneumonia (58.9%), followed by bloodstream infections (25.6%), surgical site infections (7.6%), urinary tract infections, (5.1%), and skin-soft tissue infections (2.5%). Nosocomial B. cepacia infections were most commonly observed in intensive care units (61.5%). The most active antimicrobial agents were piperacillin-tazobactam, cefoperazone-sulbactam, and carbapenems. CONCLUSIONS: The incidence of nosocomial B. cepacia infections was rare in our hospital, and no outbreak was detected during the study period. However, infections caused by B. cepacia should be taken into consideration because of their high mortality due to multidrug resistance in ICU settings.

Cases of Opsi syndrome still candidate for medical ICU

Splenectomized patients are likely to suffer from severe infections, such as sepsis and meningitis, which is called overwhelming postsplenectomy infection (OPSI) syndrome. It seems to be more common in children, but occurs at all ages. The risk is greatest in the early months and years after operation, but never disappears entirely. The course is rapid, the clinical symptoms are serious, and the prognosis is very poor. In this paper, three cases of OPSI syndrome are described, in which infection developed 8, 8 and 15 years after splenectomy; two of the patients died. With the help of these case reports, we want to again emphasize the importance of vaccination, antibiotic prophylaxis and seeking earlier medical attention in splenectomized patients.

Cases of OPSI syndrome still candidate for medical ICU.

Splenectomized patients are likely to suffer from severe infections, such as sepsis and meningitis, which is called overwhelming postsplenectomy infection (OPSI) syndrome. It seems to be more common in children, but occurs at all ages. The risk is greatest in the early months and years after operation, but never disappears entirely. The course is rapid, the clinical symptoms are serious, and the prognosis is very poor. In this paper, three cases of OPSI syndrome are described, in which infection developed 8, 8 and 15 years after splenectomy; two of the patients died. With the help of these case reports, we want to again emphasize the importance of vaccination, antibiotic prophylaxis and seeking earlier medical attention in splenectomized patients.

[The frequency of Clostridium difficile toxin in neutropenic and non-neutropenic patients with antibiotic-associated diarrhea and analysis of the risk factors]. / Antibiyotige bagli ishal gelisen nötropenik ve nötropenik olmayan hastalarda clostridium difficile toksin sikligi ve risk faktörlerinin analizi.

This study was carried out in order to investigate the frequency of Clostridium difficile toxin in the stool samples of hospitalized 74 neutropenic (mean age: 41.78 +/- 14.3 years; 40 male) and 75 non-neutropenic patients (mean age: 44.09 +/- 15.6 years; 30 male) who developed antibiotic-associated diarrhea between January 2003-September 2004 in a university hospital and also to analyze the related risk factors. C. difficile toxin A and toxin A/B were searched by immunochromatographic method (Toxin Detection Kit, Oxoid, UK), and commercial ELISA (Clostridium difficile Antigen, Generic Assays GmbH, Germany) kit, respectively. Stool samples were also analysed in terms of the presence of other bacterial and parasitic agents which may cause diarrhea. Statistical evaluation were performed by Kaplan-Meier survival analysis and by Cox regression analysis. Both neutropenic and non-neutropenic groups were compared according to their incidence densities based on times in days of overall hospitalization, total antibiotic use and hospitalization until diagnosis. The antibiotics used in neutropenic patients were piperacillin-tazobactam (41.9%), imipenem (25.7%), cefepime (17.5%), ciprofloxacin (2.7%) and others (12.2%) and in non-neutropenic patients were ampicillin-sulbactam (29.3%), ciprofloxacin (18.7%), ceftriaxone (14.6%) and others (30.7%). C. difficile toxin A positivity rates in neutropenic and non-neutropenic groups were found as 13.5% (10/74) and 14.7% (11/75), respectively, with a total rate of 14.1% (21/149). The positivity rate of toxin A/B was 24.3% (n= 18) for neutropenic, and 21.3% (n= 16) for non-neutropenic patients, with a total rate of 22.8% (n= 34). There was no statistically significant difference between the groups by means of toxin A or toxin A/B positivity rates (p > 0.05). Thirteen (38.2%) of 34 toxin A/B positive patients yielded negative results with toxin A detection test. Our results revealed that infection in the neutropenic patients developed much earlier than that in the non-neutropenic group by comparing durations of hospitalization and antibotic use which were shorter for toxin positive individuals (p < 0.01 and p < 0.001, respectively). In the control group, implementation of sulbactam-ampicillin or amoxicillin-clavulanate was determined as a risk factor. In addition to duration of hospitalization, use of antibiotics was evaluated as a risk factor for C. difficile associated colitis, especially in the neutropenic group. According to these results, it is possible to point out that antibiotic-associated colitis develops relatively earlier in neutropenic patients and is more frequently C. difficile toxin positive. In this context, appropriate control measures should therefore be kept in mind.