The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort.

Background and objectives: Although several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. Methods: Patients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. Results: We retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (ß [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (ß [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (ß [95% CI]: 0.84 [0.02-1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). Conclusion: Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.

The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients.

The COVID-19-related death rate varies between countries and is affected by various risk factors. This multicenter registry study was designed to evaluate the mortality rate and the related risk factors in Turkey. We retrospectively evaluated 1500 adults with COVID-19 from 26 centers who were hospitalized between March 11 and July 31, 2020. In the study group, 1041 and 459 cases were diagnosed as definite and highly probable cases, respectively. There were 993 PCR-positive cases (66.2%). Among all cases, 1144 (76.3%) were diagnosed with non-severe pneumonia, whereas 212 (14.1%) had severe pneumonia. Death occurred in 67 patients, corresponding to a mortality rate of 4.5% (95% CI:3.5-5.6). The univariate analysis demonstrated that various factors, including male sex, age ≥65 years and the presence of dyspnea or confusion, malignity, chronic obstructive lung disease, interstitial lung disease, immunosuppressive conditions, severe pneumonia, multiorgan dysfunction, and sepsis, were positively associated with mortality. Favipiravir, hydroxychloroquine and azithromycin were not associated with survival. Following multivariate analysis, male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were found to be independent risk factors for mortality. Among the biomarkers, procalcitonin levels on the 3rd-5th days of admission showed the strongest associations with mortality (OR: 6.18; 1.6-23.93). This study demonstrated that the mortality rate in hospitalized patients in the early phase of the COVID-19 pandemic was a serious threat and that those patients with male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were at increased risk of mortality; therefore, such patients should be closely monitored.

Value of caffeic acid phenethyl ester pretreatment in experimental sepsis model in rats.

BACKGROUND AND AIM: The aim of this study was to determine the actions of caffeic acid phenethyl ester (CAPE) on the changes of endothelin-1 (ET-1) level, tumor necrosis factor- (TNF-) alpha, and oxidative stress parameters such as superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in experimental sepsis model in rats. MATERIALS AND METHODS: Twenty-four rats were randomly divided into three experimental groups: sham (group 1), sepsis (group 2), and sepsis + CAPE (group 3), n = 8 each. CAPE was administered (10 µmol/kg) intraperitoneally to group 3 before sepsis induction. Serum ET-1, serum TNF-alpha, tissue SOD activity, and tissue MDA levels were measured in all groups. RESULTS: Pretreatment with CAPE decreased ET-1, TNF-alpha, and MDA levels in sepsis induced rats. Additionally SOD activities were higher in rats pretreated with CAPE after sepsis induction. CONCLUSION: Our results demonstrate that CAPE may have a beneficial effect on ET and TNF-alpha levels and oxidative stress parameters induced by sepsis in experimental rat models. Therefore treatment with CAPE can be used to avoid devastating effects of sepsis.

Comparison of colistin monotherapy and non-colistin combinations in the treatment of multi-drug resistant Acinetobacter spp. bloodstream infections: a multicenter retrospective analysis.

OBJECTIVES: To compare the efficacy of colistin (COL) monotherapy versus non-COL based combinations in the treatment of bloodstream infections (BSIs) due to multidrug resistant Acinetobacter spp.(MDR-A). MATERIALS AND METHODS: Retrospective data of 107 MDR-A BSI cases from 27 tertiary centers in Turkey were included. PRIMARY END-POINT: 14-day mortality. SECONDARY END-POINTS: Microbial eradication and clinical improvement. RESULTS: Thirty-six patients in the COL monotherapy (CM) group and 71 in the non-COL based combinations (NCC) group were included in the study. Mean age was 59.98 ± 20 years (range: 18-89) and 50.5% were male. Median duration of follow-up was 40 days (range: 9-297). The 14-day survival rates were 52.8% in CM and 47.23% in NCC group (P = 0.36). Microbiological eradication was achieved in 69% of CM and 83% of NCC group (P = 0.13). Treatment failure was detected in 22.9% of cases in both CM and NCC groups. Univariate analysis revealed that mean age (P = 0.001), Charlson comorbidity index (P = 0.03), duration of hospital stay before MDR-A BSI (P = 0.04), Pitt bacteremia score (P = 0.043) and Acute Physiology and Chronic Health Evaluation II score (P = 0.05) were significant in terms of 14-day mortality. Advanced age (P = 0.01) and duration of hospital stay before MDR-A BSI (P = 0.04) were independently associated with 14-day mortality in multivariate analysis. CONCLUSION: No significant difference was detected between CM and non-COL based combinations in the treatment of MDR-A BSIs in terms of efficacy and 14-day mortality.

Treatment of Nigella sativa in experimental sepsis model in rats.

This experimental study was designed to determine effects of Nigella sativa oil (NSO) on endothelin-1 (ET-1) level and oxidative stress parameters, superoxide dismutase (SOD) and malondialdehyde (MDA) in a rat sepsis model. Twenty four adult Wistar albino rats were divided randomly into three groups: sham group (group 1), sepsis group (group 2), sepsis group pretreated with NSO (group 3). Serum ET-1, tissue SOD and tissue MDA levels were measured in all groups. Compared to group 1, ET-1 and MDA levels were higher in group 2. ET-1 and MDA levels in NSO pretreated group 3 were lower with respect to group 2 (p<0.03, and p<0.02, respectively). Additionally, SOD levels in group 3 were found to be higher than group 2 (p<0.02). Based on our results, it can be concluded that NSO may have a positive impact on ET-1 levels and oxidative stress induced by sepsis in experimental rat models.

Antioxidant effects of curcumin in spinal cord injury in rats.

BACKGROUND: This experimental study was performed to investigate the benefit of curcumin via its antioxidant effect on spinal cord injury (SCI) in rats. METHODS: Twenty-four adult Wistar albino rats were randomized into three groups. SCI was performed by the weight-drop model. Group 1 underwent laminectomy followed by SCI and received no medication. Group 2 underwent laminectomy followed by SCI and received curcumin (200 mg/kg/day orally). Group 3 underwent laminectomy followed by SCI and received methylprednisolone (30 mg/kg intraperitoneally). Twenty-four hours later, blood samples were obtained from all rats; serum superoxide dismutase (SOD) and malondialdehyde (MDA) levels were determined, and the obtained results were compared. RESULTS: SOD level in the curcumin group was higher than in the control group (p < 0.000) and methylprednisolone group (p < 0.012). MDA level in the curcumin group was lower than in the control group (p < 0.042). Similarly, the MDA level in the methylprednisolone group was lower than in the control group (p < 0.001). CONCLUSION: The results of the present study show that curcumin effectively protects the spinal cord tissues against oxidative damage.

A forgotten but important risk factor for infective endocarditis in patients with prosthetic valve: pedicure.

We report a case of infective endocarditis developing after pedicure in a 36-y-old female. Methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis was diagnosed. Even aggressive therapy was ineffective. To our knowledge, we report the first case of infective endocarditis secondary to pedicure in the literature.

Incidence and etiology of thrombocytosis in an adult Turkish population.

The aim of the study was to determine the incidence and etiology of thrombocytosis in an adult Turkish population. The medical records of 2000 patients were reviewed retrospectively to determine (i) the etiology of elevated platelet counts, (ii) additional laboratory parameters (i.e., complete blood counts), and (iii) the presence of thromboembolic complications. Within 5 years, 174 678 platelet counts had been performed for 124,340 patients. Of the 124,340 patients, 2000 (1.6%; mean age, 55.2 +/- 17.4 years; range 16-94 years; male-to-female ratio, 3.6:1 [1570:430]) had one or more platelet counts of 500 x 10(3)/mm3 or higher during the study period. Secondary thrombocytosis was the most frequent cause of an elevated platelet count and occurred in 1934 cases (96.7%). Infection was the most common cause of secondary thrombocytosis, occurring in 1001 patients (50.1%). Compared with secondary thrombocytosis, primary thrombocytosis was significantly associated with a higher rate of thromboembolic complications. It is concluded that a high platelet count may have both diagnostic and therapeutic implications. Secondary thrombocytosis is a common finding and mostly secondary to infection. Primary thrombocytosis has a higher risk for thromboembolic events than does secondary thrombocytosis.

[Antibiotic resistance rates of Shigella species isolated from stool cultures in the years 1999-2003]. / Diski kültürlerinden 1999-2003 yillari arasinda izole edilen Shigella türleri ve antibiyotiklere direnç oranlari.

In this study, species distribution, seasonal isolation rates and antibiotic susceptibilitiy patterns of 115 Shigella spp, isolated from 5396 stool samples in our microbiology laboratory between 1999 and 2003, were investigated. Of the isolates, 96 (83.5%) were S. sonnei, 15 (13%) were S. flexneri, 3 (2.6%) were S. dysenteriae and 1 (1.9%) was S. boydii. Maximum isolation rates were observed at summer and fall seasons, especially in August, September and November (24%, 40%, 17%, respectively). The resistance rates against trimetoprime-sulphametoxasole and ampicillin were 79.1% and 19.1%, respectively. The rate of co-resistance against these two drugs was 12.2 percent. No isolate was found to be resistant to ciprofloxacin. Only one S. sonnei isolate had extended spectrum beta-lactamase detected by double-disk synergy test. In conclusion, ciprofloxacin is the drug of choice for empirical treatment of shigellosis. However, to avoid the loss of this choice, ampicillin which still has an high effectivity rate, should be preferred for the treatment of shigellosis with the guidence of antibiogram results. On the other hand, emergence of ESBL production among Shigella spp. after Salmonella spp. should warn us about the unexpected results of inappropriate antibiotic therapy.

[Short communication: prevalence of extended spectrum beta-lactamases in gram negative rods: data of 2001-2004 period]. / Kisa bildiri: gram negatif çomaklarda genis spektrumlu beta-laktamaz sikligi: 2001-2004 yili verileri.

This study was undertaken to determine the prevalence of extended spectrum beta-lactamase (ESBL) production by Gram negative rods (GNRs) isolated from various clinical specimens (3.240 urine, 336 pus, 277 feces, 83 blood, 38 sputum) sent to our hospital laboratory, between 2001-2004. Of isolated bacteria 71.4% were identified as Escherichia coli, 11.1% were Klebsiella spp, 4.2% were Salmonella spp, 3.7% were Pseudomonas spp, 3.5% were Proteus spp, 2.9% were Shigella spp, 2.3% were Enterobacter spp, 0.5% were Acinetobacter spp, 0.12% of each Serratia spp, and Stenotrophomonas maltophilia, 0.1% were Citrobacter spp, and one of each Providencia spp and Pantoeae spp. (0.02%). ESBL production were screened by using the double disk synergy test. Of a total of 3.974 isolates, 269 (6.8%) were found to be ESBL producers. Klebsiella spp had the highest rate (14.3%) which was followed by Enterobacter spp (8.6%) and E.coli (6.7%). All of the S.maltophilia isolates were resistant to carbapenems. One of the Shigella spp was found to be an ESBL producer, being the first case from Turkey and the fifth from the world. There was statistically significant difference in distribution of ESBL producing isolates between hospitalized (16%) and non-hospitalized patients (5%) (p<0.01). A significant increase in ESBL production rates (from 3.8% in 2001 to 10.6% in 2004) was observed over time (p<0.05). The increasing trend (about 300% in four years) in ESBL production rates, should be considered as an indicator for expansion propensity and speed of the threat against the effective treatment of infections, and possible preventive strategies should be established.

Fatal lactic acidosis due to leukemic transformation in a patient with non-Hodgkin's lymphoma: case report.

Lactic acidosis (LA) associated with hematologic malignancies is uncommon, life-threatening, and generally occurs in adults. Its pathogenesis is poorly understood. This is a case report of LA due to leukemic transformation that occurred in a patient with non-Hodgkin's lymphoma (NHL). A 24-year-old man with NHL was admitted to the hospital with dyspnea. Venous blood gas analysis revealed metabolic acidosis (pH 7.05; HCO3 6 mEq/L; BE 22 mmol/L; anion gap 28 mEq/L); the patient had an elevated plasma lactate concentration (12 mmol/L) and low glucose concentration (38 mg/dL). There was no reason other than leukemia-such as infection, circulatory failure, or drug use-for the development of severe LA. This case report shows that in patients with NHL, leukemic transformation may give rise to LA.