Efficacy and safety of Ixekizumab vs. low-dose IL-2 vs. Colchicine vs. standard of care in the treatment of patients hospitalized with moderate-to-critical COVID-19: A pilot randomized clinical trial (STRUCK: Survival Trial Using Cytokine Inhibitors).

BACKGROUND: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. METHODS: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the "per protocol" population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization's (WHO) seven-category ordinal scale by day 28. RESULTS: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. CONCLUSIONS: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

Efficacy and safety of Ixekizumab vs. low-dose IL-2 vs. Colchicine vs. standard of care in the treatment of patients hospitalized with moderate-to-critical COVID-19: A pilot randomized clinical trial (STRUCK: Survival Trial Using Cytokine Inhibitors)

ABSTRACT Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the "per protocol" population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization's (WHO) seven-category ordinal scale by day 28. Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

Sensitive LC-MS/MS Methods for Amphotericin B Analysis in Cerebrospinal Fluid, Plasma, Plasma Ultrafiltrate, and Urine: Application to Clinical Pharmacokinetics.

Neurocryptococcosis, a meningoencephalitis caused by Cryptococcus spp, is treated with amphotericin B (AmB) combined with fluconazole. The integrity of the brain-blood barrier and the composition of the cerebrospinal fluid (CSF) may change due to infectious and/or inflammatory diseases such as neurocryptococcosis allowing for the penetration of AmB into the central nervous system. The present study aimed to develop LC-MS/MS methods capable of quantifying AmB in CSF at any given time of the treatment in addition to plasma, plasma ultrafiltrate, with sensitivity compatible with the low concentrations of AmB reported in the CSF. The methods were successfully validated in the four matrices (25 µl, 5-1,000 ng ml-1 for plasma or urine; 100 µl, 0.625-250 ng ml-1 for plasma ultrafiltrate; 100 µl, 0.1-250 ng ml-1 for CSF) using protein precipitation. The methods were applied to investigate the pharmacokinetics of AmB following infusions of 100 mg every 24 h for 16 days administered as a lipid complex throughout the treatment of a neurocryptococcosis male patient. The methods allowed for a detailed description of the pharmacokinetic parameters in the assessed patient in the beginning (4th day) and end of the treatment with AmB (16th day), with total clearances of 7.21 and 4.25 L h-1, hepatic clearances of 7.15 and 4.22 L h-1, volumes of distribution of 302.94 and 206.89 L, and unbound fractions in plasma ranging from 2.26 to 3.25%. AmB was quantified in two CSF samples collected throughout the treatment with concentrations of 12.26 and 18.45 ng ml-1 on the 8th and 15th days of the treatment, respectively. The total concentration of AmB in plasma was 31 and 20 times higher than in CSF. The unbound concentration in plasma accounted for 77 and 44% of the respective concentrations in CSF. In conclusion, the present study described the most complete and sensitive method for AmB analysis in plasma, plasma ultrafiltrate, urine, and CSF applied to a clinical pharmacokinetic study following the administration of the drug as a lipid complex in one patient with neurocryptococcosis. The method can be applied to investigate the pharmacokinetics of AmB in CSF at any given time of the treatment.

Cryptococcosis by Cryptococcus neoformans/Cryptococcus gattii Species Complexes in non-HIV-Infected Patients in Southeastern Brazil.

INTRODUCTION: The clinical manifestations of cryptococcosis are usually associated with the infecting agents Cryptococcus neoformans (CN) and C. gattii (CG) species complexes and the host. In this study, non-HIV-infected patients, at a university hospital in southeastern Brazil, had epidemiological and clinical data associated with cryptococcal disease and isolated Cryptococcus species: CN - 24 patients and CG - 12 patients. METHODS: The comparison was comprised of demographic data, predisposing factors, clinical and laboratory manifestations, and outcomes of cryptococcosis patients treated between 2000 and 2016. Immunocompetent and immunosuppressed patients were also compared, irrespective of the infecting species. Cryptococcus spp. were genotyped by PCR-RFLP analysis of the URA5 gene. RESULTS: Infections by the CN species complex (100% VNI genotype) were associated with drug immunosuppression and fungemia, and patients infected with the CG species complex (83% VG II and 17% VGI genotypes) had more evident environmental exposure and higher humoral response. CN and CG affected patients with or without comorbidities. CONCLUSIONS: Diabetes mellitus, other chronic non-infectious diseases, and alcoholism were likely predisposing factors for infection by both CN and CG species. Immunocompetent patients, independent of the infecting Cryptococcus species complexes, showed a higher occurrence of meningitis and a trend toward less fungal dissemination and longer survival than immunosuppressed hosts.

Cryptococcosis by Cryptococcus neoformans/Cryptococcus gattii Species Complexes in non-HIV-Infected Patients in Southeastern Brazil

Abstract INTRODUCTION: The clinical manifestations of cryptococcosis are usually associated with the infecting agents Cryptococcus neoformans (CN) and C. gattii (CG) species complexes and the host. In this study, non-HIV-infected patients, at a university hospital in southeastern Brazil, had epidemiological and clinical data associated with cryptococcal disease and isolated Cryptococcus species: CN - 24 patients and CG - 12 patients. METHODS: The comparison was comprised of demographic data, predisposing factors, clinical and laboratory manifestations, and outcomes of cryptococcosis patients treated between 2000 and 2016. Immunocompetent and immunosuppressed patients were also compared, irrespective of the infecting species. Cryptococcus spp. were genotyped by PCR-RFLP analysis of the URA5 gene. RESULTS: Infections by the CN species complex (100% VNI genotype) were associated with drug immunosuppression and fungemia, and patients infected with the CG species complex (83% VG II and 17% VGI genotypes) had more evident environmental exposure and higher humoral response. CN and CG affected patients with or without comorbidities. CONCLUSIONS: Diabetes mellitus, other chronic non-infectious diseases, and alcoholism were likely predisposing factors for infection by both CN and CG species. Immunocompetent patients, independent of the infecting Cryptococcus species complexes, showed a higher occurrence of meningitis and a trend toward less fungal dissemination and longer survival than immunosuppressed hosts.

Minimum concentration of Amphotericin B in serum according to the formulation, dose, and daily or prolonged intermittent therapeutic regimen.

INTRODUCTION: The therapeutic efficacy of daily amphotericin B infusion is related to its maximum concentration in blood; however, trough levels may be useful in intermittent regimens of this antifungal drug. METHODS: : High performance liquid chromatography (HPLC) was used to determine the minimum concentration (Cmin) of amphotericin B in the serum of patients receiving deoxycholate (D-Amph) or liposomal amphotericin B (L-AmB) for the treatment of cryptococcal meningitis (n=28), histoplasmosis (n=8), paracoccidioidomycosis (n=1), and leishmaniasis (n=1). RESULTS: Daily use of D-Amph 30 to 50 mg or L-AmB 50 mg resulted in a similar Cmin, but a significant increase ocurred with L-AmB 100 mg/day. The geometric mean Cmin tended to decrease with a reduction in the dose and frequency of intermittent L-AmB infusions: 357 ng/mL (100 mg 4 to 5 times/week) > 263 ng/mL (50 mg 4 to 5 times/week) > 227 ng/mL (50 mg 1 to 3 times/week). The impact on Cmin was variable in patients whose dose or therapeutic scheme was changed, especially when administered the intermittent infusion of amphotericin B. The mean Cmin for each L-AmB schedule of intermittent therapy was equal or higher than the minimum inhibitory concentration of amphotericin B against Cryptococcus isolates from 10/12 patients. The Cmin of amphotericin B in patients with cryptococcal meningitis was comparable between those that survived or died. CONCLUSIONS: By evaluating the Cmin of amphotericin B, we demonstrated the therapeutic potential of its intermittent use including in the consolidation phase of neurocryptococcosis treatment, despite the great variability in serum levels among patients.

Minimum concentration of Amphotericin B in serum according to the formulation, dose, and daily or prolonged intermittent therapeutic regimen

Abstract INTRODUCTION: The therapeutic efficacy of daily amphotericin B infusion is related to its maximum concentration in blood; however, trough levels may be useful in intermittent regimens of this antifungal drug. METHODS : High performance liquid chromatography (HPLC) was used to determine the minimum concentration (Cmin) of amphotericin B in the serum of patients receiving deoxycholate (D-Amph) or liposomal amphotericin B (L-AmB) for the treatment of cryptococcal meningitis (n=28), histoplasmosis (n=8), paracoccidioidomycosis (n=1), and leishmaniasis (n=1). RESULTS: Daily use of D-Amph 30 to 50 mg or L-AmB 50 mg resulted in a similar Cmin, but a significant increase ocurred with L-AmB 100 mg/day. The geometric mean Cmin tended to decrease with a reduction in the dose and frequency of intermittent L-AmB infusions: 357 ng/mL (100 mg 4 to 5 times/week) > 263 ng/mL (50 mg 4 to 5 times/week) > 227 ng/mL (50 mg 1 to 3 times/week). The impact on Cmin was variable in patients whose dose or therapeutic scheme was changed, especially when administered the intermittent infusion of amphotericin B. The mean Cmin for each L-AmB schedule of intermittent therapy was equal or higher than the minimum inhibitory concentration of amphotericin B against Cryptococcus isolates from 10/12 patients. The Cmin of amphotericin B in patients with cryptococcal meningitis was comparable between those that survived or died. CONCLUSIONS: By evaluating the Cmin of amphotericin B, we demonstrated the therapeutic potential of its intermittent use including in the consolidation phase of neurocryptococcosis treatment, despite the great variability in serum levels among patients.

Epidermal necrolysis: SCORTEN performance in AIDS and non-AIDS patients.

BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis are life-threatening blistering drug reactions with high incidence of ocular sequela. The term 'Epidermal Necrolysis' has been recently used to better describe the full spectrum of the disease that includes Stevens-Johnson syndrome and toxic epidermal necrolysis at opposite ends, which differ by the extent of body surface area with epidermal detachment. SCORTEN is a mortality prognosis score for 'Epidermal Necrolysis' cases that still needed validation in acquired immunodeficiency syndrome. OBJECTIVE: To evaluate the SCORTEN performance in acquired immunodeficiency syndrome, and the differences in outcomes between acquired immunodeficiency syndrome and non- acquired immunodeficiency syndrome cohorts. METHODS: Retrospective cohort study of AIDS and non-AIDS 'Epidermal Necrolysis' cases admitted to a Brazilian reference center from 1990-2014. RESULTS: Five deaths (16.7%) occurred as a consequence of EN in 30 AIDS patients, and seven (17.9%) in 39 non-AIDS patients, relative risk (RR) .92 (p=1.0). SCORTEN showed great performance, with an Area Under the Receiver Operating Curve (AUC) (ROC) of 0.90 with a 95% confidence interval ranging from .81 to .99. The performance of SCORTEN was better among non- AIDS patients than AIDS patients: AUC non- acquired immunodeficiency syndrome =0.99 (CI 05% 0.96-1.00), AUC acquired immunodeficiency syndrome = 0.74 (CI 95% 0.53-0.95), p=.02. STUDY LIMITATIONS: Heterogeneity of cases, wide variation of systemic corticosteroid doses when used. CONCLUSION: SCORTEN is valid for the Brazilian population, including among those patients with acquired immunodeficiency syndrome, and, as such, its use is recommended for aiding treatment choice in this subgroup of patients.

Epidermal necrolysis: SCORTEN performance in AIDS and non-AIDS patients

Abstract: Background: Stevens-Johnson syndrome and toxic epidermal necrolysis are life-threatening blistering drug reactions with high incidence of ocular sequela. The term 'Epidermal Necrolysis' has been recently used to better describe the full spectrum of the disease that includes Stevens-Johnson syndrome and toxic epidermal necrolysis at opposite ends, which differ by the extent of body surface area with epidermal detachment. SCORTEN is a mortality prognosis score for 'Epidermal Necrolysis' cases that still needed validation in acquired immunodeficiency syndrome. Objective: To evaluate the SCORTEN performance in acquired immunodeficiency syndrome, and the differences in outcomes between acquired immunodeficiency syndrome and non- acquired immunodeficiency syndrome cohorts. Methods: Retrospective cohort study of AIDS and non-AIDS 'Epidermal Necrolysis' cases admitted to a Brazilian reference center from 1990-2014. Results: Five deaths (16.7%) occurred as a consequence of EN in 30 AIDS patients, and seven (17.9%) in 39 non-AIDS patients, relative risk (RR) .92 (p=1.0). SCORTEN showed great performance, with an Area Under the Receiver Operating Curve (AUC) (ROC) of 0.90 with a 95% confidence interval ranging from .81 to .99. The performance of SCORTEN was better among non- AIDS patients than AIDS patients: AUC non- acquired immunodeficiency syndrome =0.99 (CI 05% 0.96-1.00), AUC acquired immunodeficiency syndrome = 0.74 (CI 95% 0.53-0.95), p=.02. Study Limitations: Heterogeneity of cases, wide variation of systemic corticosteroid doses when used. Conclusion: SCORTEN is valid for the Brazilian population, including among those patients with acquired immunodeficiency syndrome, and, as such, its use is recommended for aiding treatment choice in this subgroup of patients.

Effects of drying and storage conditions on the stability of TSH in blood spots.

OBJECTIVE: To evaluate the influence of sample drying and storage temperature on TSH stability in neonatal screening. SUBJECTS AND METHODS: Blood samples from 29 adult volunteers as a surrogate for neonatal blood (10 with normal TSH, 9 with overt hypothyroid and 10 with subclinical hypothyroidism) were spotted on filter paper and dried at 22°C or 35°C for 3 hours. The samples were then stored at 22°C, -4°C, or -20°C, and TSH measurements were performed at day 0 (D0), D7, D30, D60, D180, and D360 of storage. RESULTS: The drying temperature did not interfere with TSH measurement on D0. TSH values remained stable up to D30 when stored at 22°C and were stable up to D60 when stored in a refrigerator or freezer. Samples stored at 22°C had a greater decrease in TSH values than samples stored in a refrigerator or a freezer. CONCLUSIONS: Freezer storage is not advantageous compared to storage in the refrigerator. At the end of one year, if confirmation of the initial result is required, a reduction of TSH concentrations should be taken into account.

Effects of drying and storage conditions on the stability of TSH in blood spots

ABSTRACT Objective To evaluate the influence of sample drying and storage temperature on TSH stability in neonatal screening. Subjects and methods Blood samples from 29 adult volunteers as a surrogate for neonatal blood (10 with normal TSH, 9 with overt hypothyroid and 10 with subclinical hypothyroidism) were spotted on filter paper and dried at 22°C or 35°C for 3 hours. The samples were then stored at 22°C, -4°C, or -20°C, and TSH measurements were performed at day 0 (D0), D7, D30, D60, D180, and D360 of storage. Results The drying temperature did not interfere with TSH measurement on D0. TSH values remained stable up to D30 when stored at 22°C and were stable up to D60 when stored in a refrigerator or freezer. Samples stored at 22°C had a greater decrease in TSH values than samples stored in a refrigerator or a freezer. Conclusions Freezer storage is not advantageous compared to storage in the refrigerator. At the end of one year, if confirmation of the initial result is required, a reduction of TSH concentrations should be taken into account.

Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

ABSTRACT Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400-800 mg.

Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections.

Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400-800mg.

Secular trends in Klebsiella pneumoniae isolated in a tertiary-care hospital: increasing prevalence and accelerated decline in antimicrobial susceptibility.

UNLABELLED: INTRODUCTION Klebsiella pneumoniae has become an increasingly important etiologic agent of nosocomial infections in recent years. This is mainly due to the expression of virulence factors and development of resistance to several antimicrobial drugs. METHODS This retrospective study examines data obtained from the microbiology laboratory of a Brazilian tertiary-care hospital. To assess temporal trends in prevalence and antimicrobial susceptibility, K. pneumoniae isolates were analyzed from 2000 to 2013. The relative frequencies of K. pneumoniae isolation were calculated among all Gram-negative bacilli isolated in each period analyzed. Susceptibility tests were performed using automated systems. RESULTS: From 2000-2006, K. pneumonia isolates comprised 10.7% of isolated Gram-negative bacilli (455/4260). From 2007-2013, this percentage was 18.1% (965/5331). Strictly considering isolates from bloodstream infections, the relative annual prevalence of K. pneumoniae increased from 14-17% to 27-32% during the same periods. A progressive decrease in K. pneumoniae susceptibility to all antimicrobial agents assessed was detected. Partial resistance was also observed to antimicrobial drugs that have been used more recently, such as colistin and tigecycline. CONCLUSIONS Our study indicates that K. pneumoniae has become a major pathogen among hospitalized patients and confirms its recent trend of increasing antimicrobial resistance.

Secular trends in Klebsiella pneumoniae isolated in a tertiary-care hospital: increasing prevalence and accelerated decline in antimicrobial susceptibility

Abstract: INTRODUCTION Klebsiella pneumoniae has become an increasingly important etiologic agent of nosocomial infections in recent years. This is mainly due to the expression of virulence factors and development of resistance to several antimicrobial drugs. METHODS This retrospective study examines data obtained from the microbiology laboratory of a Brazilian tertiary-care hospital. To assess temporal trends in prevalence and antimicrobial susceptibility, K. pneumoniae isolates were analyzed from 2000 to 2013. The relative frequencies of K. pneumoniae isolation were calculated among all Gram-negative bacilli isolated in each period analyzed. Susceptibility tests were performed using automated systems. RESULTS: From 2000-2006, K. pneumonia isolates comprised 10.7% of isolated Gram-negative bacilli (455/4260). From 2007-2013, this percentage was 18.1% (965/5331). Strictly considering isolates from bloodstream infections, the relative annual prevalence of K. pneumoniae increased from 14-17% to 27-32% during the same periods. A progressive decrease in K. pneumoniae susceptibility to all antimicrobial agents assessed was detected. Partial resistance was also observed to antimicrobial drugs that have been used more recently, such as colistin and tigecycline. CONCLUSIONS Our study indicates that K. pneumoniae has become a major pathogen among hospitalized patients and confirms its recent trend of increasing antimicrobial resistance.

Usefulness and limitations of polymerase chain reaction in the etiologic diagnosis of neurotoxoplasmosis in immunocompromised patients.

The objective of the present study was to assess the performance and the best indication of the polymerase chain reaction (PCR) for the detection of Toxoplasmosis gondii DNA in cerebrospinal fluid (CSF) from patients with suspected neurotoxoplasmosis. CSF samples were collected from 79 patients for amplification of the T. gondii genome (gene B1) by two PCR techniques (nested and real time). Twenty-seven of the 79 patients were classified as probable cases of neurotoxoplasmosis on the basis of clinical criteria, neuroimaging and therapeutic response. PCR showed high sensitivity (86.6%) when performed in CSF samples which were collected up to the seventh day of specific toxoplasmosis treatment. There was no positive test after 1 week of treatment. These results suggest the usefulness of PCR for the diagnosis of cerebral toxoplasmosis, and support the first week as the window for the best performance of toxoplasmosis PCR in CSF.

Hematological particularities and co-infections in injected drug users with AIDS

HIV patients infected through injected drug use have poorer prognosis than other groups. We evaluated the hematological alterations and rates of co-infections in injected drug use patients with AIDS. Injected drug use patients were younger, predominantly of male gender, and presented lower CD4, total lymphocyte, and platelet counts, but not neutrophil count, than control group. Injected drug use patients had a higher rate of hepatitis C and mycobacteria infection. Furthermore, all injected drug use patients with hemoglobin <10.0 g dL-1 and lymphocyte <1000 µL-1 had CD4 count lower than 100 µL-1. In conclusion, HIV-infected injected drug use patients constitute a special group of patients, and hemoglobin concentration and lymphocyte count can be used as surrogate markers for disease severity.

Hematological particularities and co-infections in injected drug users with AIDS.

HIV patients infected through injected drug use have poorer prognosis than other groups. We evaluated the hematological alterations and rates of co-infections in injected drug use patients with AIDS. Injected drug use patients were younger, predominantly of male gender, and presented lower CD4, total lymphocyte, and platelet counts, but not neutrophil count, than control group. Injected drug use patients had a higher rate of hepatitis C and mycobacteria infection. Furthermore, all injected drug use patients with hemoglobin <10.0 g dL(-1) and lymphocyte <1000µL(-1) had CD4 count lower than 100µL(-1). In conclusion, HIV-infected injected drug use patients constitute a special group of patients, and hemoglobin concentration and lymphocyte count can be used as surrogate markers for disease severity.

Evaluation of cardiac involvement during dengue viral infection.

BACKGROUND: Dengue is a disease whose clinical manifestations range from asymptomatic infections to a severe disease. There have been some previous reports of myocardial involvement in dengue, but this association has not been completely established. METHODS: From January to July of 2011, patients hospitalized with dengue, confirmed through dengue nonstructural protein 1 and/or immunoglobulin M detection, were included in this study and troponin I and N terminal fragment of B-type natriuretic peptide levels were determined. Patients with abnormal biomarkers underwent echocardiography and when any abnormality was detected, they underwent cardiac magnetic resonance imaging. RESULTS: Eighty-one patients were evaluated and 12 patients (15%) presented with elevated biomarker levels. Compared to controls, they had higher leukocyte (P < .001) and platelet counts (P = .005); higher C-reactive protein (P = .02), and a lower viral load (P = .03). There was no difference according to clinical dengue classification; dengue hemorrhagic fever/dengue shock syndrome severity; duration of symptoms; or prevalence of secondary infection between the 2 groups. Two patients died secondary to cardiogenic shock before imaging studies. Necroscopic findings were compatible to myocarditis in both, and immunohistochemistry for dengue virus showed increased staining on mononuclear cells located in the myocardial tissue. Of the 10 patients who underwent echocardiography, depressed left ventricular ejection fraction (LVEF) was identified in 1, left ventricular segmental abnormalities with preserved LVEF in 2, and an important pericardial effusion with tamponade in another. Cardiac involvement was confirmed by CMR in these 4 patients. CONCLUSIONS: Dengue viruses were shown to cause cardiac disease with clinical manifestations ranging from mild elevation of biomarkers to myocarditis and/or pericarditis.