Pharmacokinetic characterization of favipiravir in patients with COVID-19.

This prospective observational study describes the pharmacokinetic characteristics of favipiravir in adult patients hospitalized for mild to moderate COVID-19 with a positive RT-PCR test. Favipiravir was administered for 5 days, with a loading dose of 3200 mg and a maintenance dose of 1200 mg/day. Serial blood samples were collected on Day 2 and Day 4 of the therapy. Laboratory findings of the patients (n = 21) and in-hospital mortality were recorded. Favipiravir concentrations exhibited substantial variability and a significant decrease during the treatment of COVID-19. The median favipiravir trough concentration (C0-trough ) on Day 2 was 21.26 (interquartile range [IQR], 8.37-30.78) µg/mL, whereas it decreased significantly to 1.61 (IQR, 0.00-6.41) µg/mL on Day 4, the area under the concentration-time curve decreased by 68.5%. Day 2 C0-trough of female patients was higher than male patients. Our findings indicate that favipiravir concentrations show significant variability during the treatment of COVID-19 and therapeutic drug monitoring may be necessary to maintain targeted concentrations.

First known COVID-19 case and contact tracing efforts in Istanbul, Turkey

Background/aim: COVID-19 has now become a global pandemic. Understanding the routes of transmission is vital in the mitigation and suppression of the disease. Istanbul has become one of the disease's epicenters. This study aims to describe the first COVID-19 case and contact tracing efforts around it in Istanbul. Materials and methods: The descriptive study was conducted in Istanbul, Turkey. The first COVID-19 cases and those associated with them were investigated with contact tracing, and primary and secondary cases were described. Results: The source case was an individual who returned to Turkey from international travel at the beginning of March and tested PCR (­). The index case is the brother of the source case and is considered the first PCR (+) case diagnosed in Istanbul. Contact tracing revealed 23 PCR (+) cases, 14 of which resulted in hospitalization and three deaths. Conclusions: This study described cases of the first COVID-19 cluster in Istanbul. Moreover, contact tracing was used in this first cluster. This contributed to contact tracing algorithms in Turkey.

Characteristics of leptospirosis with systemic inflammatory response syndrome: a multicenter study.

BACKGROUND: Leptospirosis is a common zoonotic infection in the world. In patients with leptospirosis, in case of presence of Systemic Inflammatory Response Syndrome (SIRS), clinical and laboratory findings can be mistaken for sepsis due to other causes of infection. The purpose of this study is to assess the clinical and laboratory parameters of patients with leptospirosis in terms of the presence of SIRS and to examine the association of these with mortality. METHODS: One hundred fifty-seven patients were included in the study. The patients were classified according to the presence or absence of SIRS and divided into SIRS (+) and SIRS (-). Patient files were retrospectively evaluated. Clinical features and laboratory data were compared, and risk factors associated with mortality were determined. RESULTS: SIRS (+) was found in 70 % (n = 110) of patients who had signs on admission. Comparison of the clinical symptoms and findings of organ systems in the SIRS (+) and SIRS (-) showed that abdominal pain and vomiting were significantly more common in the SIRS (+) than in the SIRS (-) (p = 0.025 and p = 0.046, respectively). BUN and serum creatinine levels were significantly higher in the SIRS (+) than in the SIRS (-) (p = 0.002 and p < 0.001, respectively). In follow-up posterior-anterior chest radiography, pathological findings improved in 58.8 % (n = 40) of patients in the SIRS (+) and 27.3 % (n = 9) of patients in the SIRS (-) (p = 0.003). The mortality rate of the SIRS (+) and SIRS (-) was not significantly different (p = 0.868). CONCLUSION: In patients with positive SIRS findings, while examining the etiology of sepsis, leptospirosis should come to mind especially in endemic areas for differential diagnosis. Early initiation of antibiotic and supportive therapy can be lifesaving in these patients.

[Notice of first NDM-1 expressing isolates in Turkey and the use of modified Hodge test]. / Ülkemizden NDM-1 salgilayan ilk izolatlarin bildirimi ve modifi ye Hodge test kullanimi

We read the article entitled "Investigation of the presence of New Delhi metallo- beta-lactamase-1 (NDM-1) by PCR in carbapenem-resistant gram-negative isolates" by Yanik et al. [Mikrobiyol Bul 2013; 47(2):382], with a great interest. Today, gram-negative enteric bacteria expressing NDM-1 are spreading rapidly all over the world and this is of great concern when increasing carbapenem resistance is considered. Yanik et al. reported that there were no NDM-1 positive isolates in their study involving a part of Turkey. It is well-known that the most sensitive indicator related to carbapenem resistance is ertapenem resistance [Perçin et al. Mikrobiyol Bul 2012; 46(4):546]. In their study Yanik et al. used imipenem, meropenem or doripenem instead of ertapenem resistance for screening carbapenem resistance. Thus, carbapenem-resistant strains might be unnoticed in their study. They also used Modified Hodge Test (MHT) for the investigation of carbapenem resistance in the second stage of their study. MHT is known to have a low sensitivity as a screening test for NDM-1 positive strains. To increase its sensitivity, ZnSO4 should be added to the culture medium [Girlich et al. J Clin Microbiol 2012; 50(2):477]. However, this issue was not specified in Yanik et al's study. Thus, this may be another possible cause of failure to detect NDM-1 expressing strains. Yanik et al. reported in their study that NDM-1-producing isolates were not detected in Turkey. However, very recently, four NDM-1 isolates which were not associated with importation from abroad, were reported in a study from Turkey [Alp et al. J Hosp Infect 2013; 84(2):178] and this was the first report of domestic NDM-1 secreting strains in Turkey. In conclusion, there is a need in our country to a carbapenem group antibiotic investigate the presence of NDM-1 positive strains. The use of ertapenem for screening carbapenem resistance and also adding ZnSO4 to MHT for the detection of NDM-1 strains are of great importance.

[Tuberculosis and tularemia as part of the differential diagnosis in cervical lymphadenitis]. / Servikal lenfadenitlerin etiyolojisinde tüberküloz ve tularemi ayirici tanisi

We have read with interest the recently published article entitled "Investigation of the presence of Mycobacterium tuberculosis in the lymph node aspirates of the suspected tularemia lymphadenitis cases" by Albayrak et al. published in Mikrobiyol Bul 2014; 48(1): 129-34. They concluded that tuberculous lymphadenitis (TCL) should be kept in mind in suspected tularemia cases and those patients should also be investigated simultaneously for the presence of TCL. With reference to data provided by the Ministry of Health in Turkey, the number of reported cases of pulmonary tuberculosis in comparison to previous years is currently on decline whereas a gradual increase in extra-pulmonary (specifically cervical TCL) cases has been observed. Besides, as one of the most common causes of cervical lymphadenitis, we are witnessing a marked increase in granulomatous infections which have been part of the evaluated cases of oropharyngeal tularemia in Turkey. In fact, differentiation of the two types of lymphadenitis can be confusing on the basis of clinical and histopathological findings. Thus, investigating the presence of M.tuberculosis in cervical lymph node aspirates of tularemia suspected cases is a vital contribution, specifically in a geographical region that is considered endemic for both diseases. We would therefore like to note the importance of this study and thank the authors for their comprehensive contribution. Contrary to what is noted in the study, cervical lymphadenitis due to acute tonsillopharyngitis unresponsive to penicillin and its derivatives, has been regarded as cervical TCL due to their histopathological appearance and have been treated unnecessarily with long-term antituberculous drugs. There are some publications from Turkey indicating the detection of Francisella tularensis antibodies and nucleic acids in the patients who were histologically diagnosed as TCL. In situations where the exact etiology of cervical lymphadenitis is not determined, treatment is delayed, disease duration is prolonged and patients are forced into visiting multiple physicians and hospitals. In this case uneccessary protocols such as lymph node excision and various surgical procedures are performed to rule out the presence of commonly encountered malignancies like lymphoma. On the other hand, lymph node suppuration is more commonly seen among these group of patients. As a conclusion, tularemia and TCL should be kept in mind as different endemic entities in widespread geographical regions such as Turkey. In particular, early serological and microbiological investigations should be performed for early diagnosis and appropriate treatment in such patients.

Piperacillin/tazobactam-induced neutropenia, thrombocytopenia, and fever during treatment of a diabetic foot infection.

Piperacillin/tazobactam (PTZ) is frequently used in patients with diabetic foot infections. Herein, we report a patient who developed severe neutropenia, thrombocytopenia, and fever while receiving PTZ for a diabetic foot infection. We recommend vigilance when long-term PTZ use is planned in patients with diabetic foot infections.

A radiographic study of dorsovolar wrist axes and a database of angular measurements on axial computed tomography images.

OBJECTIVES: This study aims to identify the most accurate dorsovolar principal axis of the distal radius and carpus identified on axial computed tomography (CT) sections and to establish normative data for angular measurements among these axes. PATIENTS AND METHODS: Between December 2019 and December 2021, normal axial CT images of wrists of a total of 42 individuals (25 males, 17 females; mean age: 31±8.4 years; range, 18 to 45 years) were retrospectively analyzed. Eight axes were identified on axial CT images: four distal radial axes (the volar cortical, medial cortical, central, and sigmoid notch axes) and four carpal axes (the scapholunate, lunotriquetral, capitohamate, and pisotrapezial axes). Twenty-two angular parameters were measured with reference to four principal axes (the volar cortical, medial cortical, central, and pisotrapezial axes). RESULTS: The mean sigmoid notch rotation (version) angles relative to the four principal axes were 8±5° (range, -2° to 18°), 6±5° (range, -2° to 13°), 1±5° (range, -8° to 14°), and 4±4° (range, -3° to 15°), respectively. The mean scapholunate rotation angles were -13±5° (range, -27° to -6°), -15±6° (range, -29° to -8°), -21±5° (range, -30° to -11°), and -8±5° (range, -28° to -6°), respectively. Among four principal axes, the volar cortical and medial cortical axes were nearly collinear with both of relatively fixed carpal axes. The four principal axes showed angular differences between 2° and 8° with each other. There was no significant difference between men and women for all measurements. CONCLUSION: The axial CT sections can be used to describe the various angulations between the normal wrist axes such as the sigmoid notch and scapholunate joint rotation angles. Despite slight differences among the four principal axes, the volar cortical and medial cortical axes are more consistent with the relatively fixed carpal axes.

What is the clinical and functional effect of performing suspension arthroplasty with abductor pollicis longus tendon slip to carpometacarpal joint osteoarthritis of the thumb?

OBJECTIVES: This study aims to investigate the clinical, radiological, and functional results of trapeziectomy, ligament reconstruction and suspensionplasty surgery with abductor pollicis longus (APL) tendon slip autograft to thumb carpometacarpal (CMC) osteoarthritis. PATIENTS AND METHODS: Between January 2011 and June 2017, a total of 25 hands of 25 patients (4 males, 21 females; mean age: 63.6±5.8 years; range, 54 to 76 years) were included. All patients underwent trapeziectomy and ligament reconstruction and suspensionplasty procedure due to the diagnosis of thumb CMC joint osteoarthritis. The patients were administered the Patient-Rated Wrist Evaluation Questionnaire (PRWE), Quick Disabilities of the Arm, Shoulder, and Hand (Q-DASH), and Visual Analog Scale (VAS). Scaphometacarpal distance (SMD), Kapandji opposition score, thumb range of motion (ROM), grip strength, tip pinch, lateral pinch, and palmer pinch values were measured for both hands. The values calculated for the operated and contralateral hands of the patients were compared. RESULTS: The ROM measurements, Kapandji opposition scores, and pinch values of the operated hands of the patients were found to be statistically significant lower compared to the contralateral hands (p<0.001, p<0.001, p=0.002; respectively). The grip strength values were similar for both hands (p=0.147). The median SMD in the operated hand was found to be 7.5 mm and 12.1 mm in the contralateral hand (p<0.001). CONCLUSION: The ROM, strength and functional results were reached a satisfactory level, particularly in the patients with a follow-up period of ≥36 months. In patients with thumb CMC joint osteoarthritis, ligament reconstruction and suspensionplasty using APL tendon slip are considered to be a useful and preferable surgical technique modification.

Radiographic assessment of bone tunnels after anterior cruciate ligament reconstruction: A comparison of hamstring tendon and bone-patellar tendon-bone autografting technique.

OBJECTIVES: This study aims to compare the postoperative change of femoral and tibial tunnel widths after hamstring tendon (HT) and bone-patellar tendon-bone (BPTB) autografting in primary anterior cruciate ligament (ACL) reconstruction surgery with the anteromedial portal technique. PATIENTS AND METHODS: This case-control and retrospective study included 39 patients (36 males, 3 females; mean age 30.1±7.9; range, 17 to 44 years) who underwent primary ACL reconstruction surgery with either BPTB autografting method (BPTB group, n=18) or HT autografting method (HT group, n=21) between March 2014 and December 2016. Femoral fixation was achieved with bioabsorbable screw in BPTB group and endobutton in HT group. Tibial fixation was achieved with bioabsorbable interference screw in both groups. Femoral and tibial tunnel widths of groups were compared on digital radiographs. RESULTS: When we compared the baseline values with the second-year results, the mean of femoral tunnel widths were significantly lower on radiographs at the second-year evaluation in both groups (p<0.001 for all). However, the means of tibial tunnel widths were significantly lower only in the BPTB group (p<0.001 for BPTB group and p=0.616 for HT group). Change levels of anteroposterior and lateral widths were more prominent in BPTB group than HT group (p<0.001 for all). CONCLUSION: Changes in tunnel widths show us superior ossification in BPTB grafting. This can be explained by superior bone-to-bone healing. As a result of radiological evaluation, we think that BPTB grafting can be more strong and durable.

Radiologic Evaluation of the Effect of Distal Tibiofibular Joint Anatomy on Arthroscopically Proven Ankle Instability.

BACKGROUND: Ankle sprains occur frequently in both athletes and the general population. The social and economic consequences can be significant. In an effort to understand the injury, dynamic and static structures around the ankle have been investigated in detail, but anatomical factors predisposing to lateral ankle instability have not been fully clarified. The aim of this study was to radiologically investigate the relationship between bony variations of the distal tibiofibular joint and arthroscopically proven ankle instability. METHODS: Fifty patients with arthroscopically proven ankle instability and 50 patients without instability were included in this study. Measurements were obtained from a magnetic resonance imaging (MRI) section 1 cm proximal to the tibiotalar joint; distal tibiofibular joint anterior facet length (a), posterior facet length (b), angle between the anterior and posterior facets (c), fibular notch depth (d), tibia thickness (e), and fibula thickness (f) was measured. RESULTS: It was found that instability was more frequent when the length of a (P < .001) and e (P < .001) were shorter. In addition, when value of a/b and e/f were evaluated, it was observed that the number of individuals who had instability increased as the ratio became smaller (P < .016-.020, respectively). Pearson correlation analysis indicated strong negative correlation between the values of a-e and instability (r = -0.348, P < .001, and r = -0.328, P = .001; respectively). CONCLUSION: Lateral ankle sprains are common, and a clear understanding of the relevant structures and clinical function of the ankle complex should extend beyond the talocrural joint. This study demonstrated that the presence of narrow anterior facet (a) and thinner tibia (e) were strongly correlated with lateral ankle instability. LEVEL OF EVIDENCE: Level III, retrospective case control study.

Surgical treatment of supplementary motor area lesions.

Different portions of the SMA appear to be engaged by different types of neurological functions. It is important to identify the functional activation of SMA in terms of planning the surgical strategy. Our unpublished data from M.D. Anderson suggest that resection of the site of SMA activation based on fMRI is an important parameter for predicting the postoperative neurological deficit. Also, protecting the functional SMA during tumor resection may prevent post-operative deficit. Adjunctive non-invasive intraoperative monitoring techniques such as phase reversal of somatosensory evoked potentials, motor evoked potentials monitoring and subcortical stimulation are very important to identify the eloquent cortical brain areas during tumor resection. Delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation may also provide improved preservation of eloquent regions during the surgery. Use of preoperative imaging studies including fMRI, diffusion tensor MRI, intraoperative monitoring techniques and awake craniotomies together in suitable cases may minimize the incidence and severity of the SMA syndrome.

Wartime infections and tragedies at the beginning of the 20th century in the Eastern part of Turkey.

In the early 20th century, Europe and the Ottoman Empire as a whole experienced a large number of epidemic diseases, and several wars. During World War I (WW1) a general mobilization of the medical services under Ottoman Empire rule was enacted. However, shortages of food and water, unfavourable weather and poor sanitary conditions resulted in numerous diseases at the battle fronts. Indeed, during the Ottoman-Russian war on the Eastern Front, the Turks suffered massive loss of life. This article therefore emphasises that during WW1, such loss of life in the Ottoman Army on the Eastern Front, which was one of the key fronts of the war, was mainly due to epidemic diseases rather than battles.