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Objective: Türkiye is the leading country that has been applying the MPOWER criteria of the World Health Organization for years. However, the prevalence of smoking among nurses appears to be high, according to the literature. Therefore, we aimed to determine the prevalence, addiction levels, and dynamics of tobacco smoking among nurses in Türkiye., Method: In this descriptive cross-sectional study, a questionnaire (prepared in cooperation with the "World Health Organization") and the Fagerström Test for Nicotine Dependence were administered to 529 nurses working at a tertiary-care university hospital in 2020. Logistic regression was performed to determine factors predicting smoking., Results: The prevalence of smoking among nurses was 32.7% (n = 173). The mean Fagerström test score indicated a "low dependence" level (score: 3 ± 2.6). Both results were higher for males. A relationship was found between trying smoking cigarette and hookah. Of the "current smokers" group, 102 (60.4%) stated that they wanted to quit smoking. Only 21 (27.6%) of the nurses who have tried to quit smoking thus far have received professional help., Conclusion: The prevalence of smoking among nurses working at a tertiary-care university hospital was relatively low compared to that among nurses in Türkiye. While females are normally expected to smoke less, the high prevalence of smoking among nurses (most of them female) raises the question of the professional basis of this situation. However, the low rate of receiving professional help reveals the lack of promotion and accessibility of smoking cessation outpatient clinics in the faculty environment. Finally, the perception that hookah is an alternative tobacco product leads to cigarette smoking. The good news was that nurses had a low dependency rate., (© 2024. The Author(s).)

Objective: Urinary tract infections (UTIs) due to extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae are among the leading causes of morbidity and mortality in older adults. Identifying associated factors for ESBL production may contribute to more appropriate empirical treatment., Materials and Methods: This was a prospective observational study. Hospitalized patients of age > 65 with community-onset or hospital-acquired upper UTI due to E. coli or Klebsiella pneumoniae were included. A multivariate analysis was performed., Results: A total of 97 patients were included. ESBL prevalence among UTIs with E. coli or Klebsiella pneumoniae was 69.1% ( n  = 67). CRP values at the time of UTI diagnosis were found to be significantly higher in the ESBL-producing group ( p  = 0.004). The multivariate analysis revealed that male gender (OR: 2.72, CI: 1.02-7.25), prior recurrent UTI (OR: 3.14, CI: 1.21-8.14), and the development of secondary bacteremia (OR: 4.95, CI: 1.03-23.89) were major associated factors for UTI in older adults due to ESBL-producing E. coli and Klebsiella pneumoniae., Conclusion: Severe UTI in older men with a history of recurrent UTI may be a warning to the clinician for ESBL production in the setting of high ESBL prevalence. Carbapenems may be prioritized in the empirical treatment of patients with known risk factors for ESBL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alkan, Balkan, Surme, Bayramlar, Kaya, Karaali, Mete, Aygun, Tabak and Saltoglu.)

Introduction: We aimed to evaluate the prevalence and clinical outcomes of COVID-19 in healthcare workers (HCWs) in the pre-vaccination and post-vaccination periods. In addition, we determined factors associated with the development of COVID-19 after vaccination., Methodology: In this analytical cross-sectional epidemiological study, HCWs who were vaccinated between January 14, 2021, and March 21, 2021, were included. HCWs were followed up for 105 days after the 2 doses of CoronaVac. Pre-vaccination and post-vaccination periods were compared., Results: A total of 1,000 HCWs were included, 576 patients (57.6%) were male, and the mean age was 33.2 ± 9.6 years. In the last 3 months during the pre-vaccination period, 187 patients had COVID-19, and the cumulative incidence of COVID-19 was 18.7%. Six of these patients were hospitalized. Severe disease was observed in three patients. In the first 3 months post-vaccination period, COVID-19 was detected in 50 patients, and the cumulative incidence of the disease was determined to be 6.1%. Hospitalization and severe disease were not detected. Age (p = 0.29), sex (OR = 1.5, p = 0.16), smoking (OR = 1.29, p = 0.43), and underlying diseases (OR = 1.6, p = 0.26) were not associated with post-vaccination COVID-19. A history of COVID-19 significantly reduced the likelihood of the development of post-vaccination COVID-19 in multivariate analysis (p = 0.002, OR = 0.16, 95% CI = 0.05-0.51)., Conclusions: CoronaVac significantly reduces the risk of SARS-CoV-2 infection and alleviates the severity of COVID-19 in the early period. Additionally, HCWs who have been infected and vaccinated with CoronaVac are less likely to be reinfected with COVID-19., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Yusuf Emre Ozdemir, Aysegul Inci Sezen, Serkan Surme, Sevtap Senoglu, Zuhal Yesilbag, Meryem Sahin Ozdemir, Osman Faruk Bayramlar, Emine Ilay Duman, Nomin Bold, Habip Gedik, Kadriye Kart Yasar.)

Background: We aimed to explore the prevalence of prolonged symptoms, pulmonary impairments and residual disease on chest tomography (CT) in COVID-19 patients at 6 months after acute illness. Methods: In this prospective, single-center study, hospitalized patients with radiologically and laboratory-confirmed COVID-19 were included. Results: A high proportion of the 116 patients reported persistent symptoms (n = 54; 46.6%). On follow-up CT, 33 patients (28.4%) demonstrated residual disease. Multivariate analyses revealed that only neutrophil-to-lymphocyte ratio was an independent predictor for residual disease. Conclusion: Hospitalized patients with mild/moderate COVID-19 still had persistent symptoms and were prone to develop long-term pulmonary sequelae on chest CT. However, it did not have a significant effect on long-term pulmonary functions.

Background: In this study, we presented two cases of late diagnosed complicated oculoglandular tularemia and reviewed the clinical features of oculoglandular tularemia in cases reported in the last ten years., Method: Tularemia was diagnosed when serum microagglutination test (MAT) was ≥ 1/160 titer or when there was at least a four-fold increase in MAT titers measured over a two-week interval. We searched the oculoglandular tularemia cases reported in the last 10 years in the PubMed and Google Academic engines., Results: Case 1 (19 M) and case 2 (15 M) had complaints of fever and burning in the eye. In both cases, the diagnosis of tularemia was delayed. Lymph node suppuration developed in both cases. A total of 19 cases of tularemia were found within the search. In the cases of oculoglandular tularemia reported in the last 10 years, submandibular and preauricular lymphadenopathy were most common after ocular findings and fever. The mean time to diagnosis was 41 ± 94 days, and the complication rate was 31.5%., Conclusion: Tularemia should definitely be considered in cases of fever and ocular findings, especially in endemic areas. In non-endemic areas, a good anamnesis and clinical suspicion can help diagnose the disease early and reduce the complication rate., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Optimal component placement, equalization of leg lengths, and recreation of offset are important surgical objectives during total hip arthroplasty (THA). Historically, many surgeons have aimed for the Lewinnek's " safe zone," which is defined as 30°-50° of abduction and 5°-25° of anteversion. Methods for optimizing cup position include anatomic landmarks, room landmarks, acetabular cup coverage, and ischial or pubis palpation. Malposition of the acetabular component after total hip arthroplasty (THA) is related to dislocation of the prosthetic femoral head, increased polyethylene liner wear, and limited range of motion. The orientation of the acetabular component comprises inclination and anteversion. Although the inclination of the acetabular component can be easily measured on plain radiographs, the calculation of the anteversion is difficult. This study evaluates the effect of intra-operative fluoroscopy on component position, mainly anteversion and inclination of the acetabular cup, during a total hip arthroplasty., Methods: 106 hips undergoing total hip arthroplasty were assessed, and the decision to use fluoroscopy assistance was randomized based on a simple randomization technique. A total of 48 patients were operated on with fluoroscopy assistance and 58 patients without fluoroscopy assistance. All patients were evaluated postoperatively for version of component on anteroposterior radiographs of the hip using the method of Liaw et al. and for inclination of component on anteroposterior radiographs using the method of Woo and Morrey., Results: The mean version for the non-fluoroscopy (NF) group was 15.62° and the mean inclination was 44.22°, with 15.5% (9 out of 58) of the patients who did not fit into Lewinnek's safe zone for version and 25.9% (15 out of 58) of the patients who were outliers for inclination of the acetabular cup position. The mean version for the fluoroscopy group (F) was 11.80° and the mean inclination was 47.05°, with 0% (0 out of 48) of the patients who did not fit into Lewinnek's safe zone for version and 12.5% (6 out of 48) of the patients who were outliers for inclination of the acetabular cup position., Conclusion: While the mean version and inclination of the acetabular component were comparable for both groups, outliers for version and inclination were far more common in the group of patients who underwent surgery without intra-operative fluoroscopic assistance. Therefore, intra-operative fluoroscopy imaging confirms appropriate inclination (abduction) and version of acetabular cup position according to Lewinnek's safe zone and prevents undesirable component position during a total hip arthroplasty while adding a maximum of 5 min to the operative time., Competing Interests: Conflict of InterestThe authors declare that there is no conflict of interest relevant to this article., (© Indian Orthopaedics Association 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: This study was designed to investigate the effectiveness of CoronaVac in preventing COVID-19 in healthcare workers (HCWs) during the Alpha variant-dominant period. Materials & methods: Follow-up was initiated 14 days after the second dose for double-dose vaccinated HCWs and on 25 February 2021, for the unvaccinated group. The incidence rate ratio was calculated to estimate the unadjusted effectiveness. Cox regression was used to adjust the effectiveness of CoronaVac. Results & Conclusion: The adjusted effectiveness of CoronaVac against COVID-19 was 65% (95% CI: 50-75%). Compared with the results of the phase III trial conducted in Turkey, a lower effectiveness of CoronaVac against COVID-19 was detected in this real-life study. This finding suggests that mass vaccination and booster doses are needed.

Introduction: Although vaccines are the safest and most effective means to prevent and control infectious diseases, the increasing rate of vaccine hesitancy and refusal (VHR) has become a worldwide concern. We aimed to find opinions of parents on vaccinating their children and contribute to available literature in order to support the fight against vaccine refusal by investigating the reasons for VHR on a global scale., Methodology: In this international cross-sectional multicenter study conducted by the Infectious Diseases International Research Initiative (ID-IRI), a questionnaire consisting of 20 questions was used to determine parents' attitudes towards vaccination of their children., Results: Four thousand and twenty-nine (4,029) parents were included in the study and 2,863 (78.1%) were females. The overall VHR rate of the parents was found to be 13.7%. Nineteen-point three percent (19.3%) of the parents did not fully comply with the vaccination programs. The VHR rate was higher in high-income (HI) countries. Our study has shown that parents with disabled children and immunocompromised children, with low education levels, and those who use social media networks as sources of information for childhood immunizations had higher VHR rates (p < 0.05 for all)., Conclusions: Seemingly all factors leading to VHR are related to training of the community and the sources of training. Thus, it is necessary to develop strategies at a global level and provide reliable knowledge to combat VHR., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Yakup Cag, Mohammad Emad al Madadha, Handan Ankarali, Yasemin Cag, Kubra Demir Onder, Aysegul Seremet-Keskin, Filiz Kizilates, Rok Civljak, Ghaydaa Shehata, Handan Alay, Sevil Alkan-Ceviker, Fatma Yilmaz-Karadag, Meliha Cagla-Sonmezer, Manar Ezzelarab Ramadan, Dumitru Irina Magdelena, Ljiljana Betica Radic, Jurica Arapovic, Fatma Kesmez-Can, Nagwa Mostafa El-Sayed, Oladapo Babatunde Campbell, Gulden Eser-Karlidag, Reham Khedr, Mehmet Emirhan Isik, Michael Mihailov Petrov, Roxana Cernat, Umran Erturk, Yesim Uygun-Kizmaz, Eva Huljev, Fatma Amer, Mehmet Resat Ceylan, Andrea Marino, Gulnur Kul, Tuba Damar-Cakirca, Yara Mohsen Khalaf, Arzu Cennet Isik, Olumuyiwa Elijah Ariyo, Ismail Necati Hakyemez, Rezaul Karim Ripon, Abdorrahim Afkhamzadeh, Emine Kubra Dindar-Demiray, Osasona Oluwadamilola Gideon, Maya Belitova, Mustafa Altindis, Rehab El-Sokkary, Recep Tekin, Mohammed Ahmed Garout, Joanna Zajkowska, Farhan Fazal, Muhammed Bekcibasi, Mirsada Hukic, Summiya Nizamuddin, Serkan Surme, Ricardo Fernandez, Amani El-Kholy, Nasim Akhtar, Saadia Ijaz, Andrea Cortegiani, Meliha Meric-Koc, Hakan Hasman, Agah Victor Maduka, Jehan Ali ElKholy, Sema Sari, Mumtaz Ali Khan, Yasemin Akin, Sukran Kose, Hakan Erdem.)

Background: The aim was to explore a novel risk score to predict mortality in hospitalized patients with COVID-19 pneumonia. Methods: This was a retrospective, multicenter study. Results: A total of 1013 patients with COVID-19 were included. The mean age was 60.5 ± 14.4 years, and 581 (57.4%) patients were male. In-hospital death occurred in 124 (12.2%) patients. Multivariate analysis revealed peripheral capillary oxygen saturation (SpO2), albumin, D-dimer and age as independent predictors. The mortality score model was given the acronym SAD-60, representing S pO2, A lbumin, D -dimer, age ≥60 years. The SAD-60 score (0.776) had the highest area under the curve compared with CURB-65 (0.753), NEWS2 (0.686) and qSOFA (0.628) scores. Conclusion: The SAD-60 score has a promising predictive capacity for mortality in hospitalized patients with COVID-19.

Introduction: This article reports a case of surgical repair of traumatic rupture of tibialis posterior (TP) tendon in a young healthy male after alleged history of grinder (heavy machine) injury over the foot, with the help of a suture anchor and running whip stitch followed by immobilization in a below knee slab postoperatively. The acute rupture of the TP tendon (TPT), compared to an acute rupture of the Achilles tendon, is a quite uncommon disease to be diagnosed in the emergency department setting. In most cases symptoms related to a TP dysfunction, like weakness, pain along the course of the tendon, swelling in the region of the medial malleolus, and the partial or complete loss of the medial arch with a flatfoot deformity precede the complete rupture of the tendon., Case Report: A 32-year-old healthy male presented to the outpatient clinic with a history of pain and swelling in the right foot for 10 months after alleged history of sustaining a grinder (heavy machine) injury to the medial aspect of the right foot 10 months ago. Anteroposterior and oblique radiographs of the right foot suggestive of no skeletal pathology and patient was managed conservatively with analgesic, anti-inflammatory, and compression bandaging. A magnetic resource imaging of the right foot was advised after no relief of symptoms and was suggestive of high-grade tear of the distal tibialis posterior tendon from the level of medial malleolus to its insertion. Surgical repair of the TPT was planned with a suture anchor placed in the navicular bone. The procedure was carried out under spinal anesthesia and there were no complications in the intraoperative or post-operative period. Patient was given a below knee slab with the foot in inversion postoperatively which was revised into a below knee cast with foot in inversion. Six-week post-operative follow-up, cast was removed and physiotherapy was started for the patient that included Active Ankle ROM and Gait Training, patient had a Modified Olerud and Molander Score of 45/100. Six-month post-operative follow-up, patient was relieved of chronic pain and was able walk and stand on his toes without pain and showed significant improvement in gait with Modified Olerud and Molander Score 90/100., Conclusion: The TPT is the main dynamic stabilizer of the medial longitudinal arch of the foot. With appropriate surgical technique, adequate post-operative immobilization followed by physiotherapy surgical repair of the TPT helped alleviate the chronic pain experienced by the patient during weight bearing activities., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Introduction: We aimed to determine the indicators for poor long-term outcome in older adults with community-acquired pneumonia (CAP)., Methodology: Patients with CAP requiring hospitalization were included in this retrospective study. The long-term mortality was defined as all-cause 1-year mortality following hospital admission., Results: A total of 145 patients with CAP were recorded. The median age was 70 (18-103), of whom 94 (65%) were ≥ 65 years old and 86 (59.5%) were male. Long-term mortality rates following CAP requiring hospitalization were substantially high in both the younger (n = 16, 31.4%) and older adults (n=43, 45.7%). In univariate analysis, the Pneumonia Severity Index (PSI) (p = 0.007), mechanical ventilation (p > 0.001), mental status changes (p = 0.018) as well as the modified Charlson Comorbidity Index (p=0.001), presence of malignancy (p < 0.001) and hospital readmission (p < 0.001) were associated with long-term mortality in the older group. Our results revealed that the need for mechanical ventilation (OR = 47.61 CI = 5.38-500.0, p = 0.001) and hospital readmission (OR = 15.87 CI = 5.26-47.61, p < 0.001) were major independent predictors of 1-year mortality., Conclusions: Clinicians should consider the lethal possibilities of CAP even after hospital discharge. The need for mechanical ventilation and hospital readmission may predict long-term mortality. Therefore, the patients who have these predictors should be closely monitored., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Serkan Surme, Ilker Inanc Balkan, Osman Faruk Bayramlar, Ritvan Kara Ali, Bilgul Mete, Fehmi Tabak, Nese Saltoglu.)

Background: We aimed to compare the clinical, laboratory and radiological findings of confirmed COVID-19 and unconfirmed patients. Methods: This was a single-center, retrospective study. Results: Overall, 620 patients (338 confirmed COVID-19 and 282 unconfirmed) were included. Confirmed COVID-19 patients had higher percentages of close contact with a confirmed or probable case. In univariate analysis, the presence of myalgia and dyspnea, decreased leukocyte, neutrophil and platelet counts were best predictors for SARS-CoV-2 RT-PCR positivity. Multivariate analyses revealed that only platelet count was an independent predictor for SARS-CoV-2 RT-PCR positivity. Conclusion: Routine complete blood count may be helpful for distinguishing COVID-19 from other respiratory illnesses at an early stage, while PCR testing is unique for the diagnosis of COVID-19.

Objective: We aimed to determine Hepatitis B virus (HBV) prevalence, immune status, and the prevalence of antibody response in people living with HIV/AIDS (PLWHA) in Istanbul, Turkey., Methods: The study includes PLWHA aged 18 years and older who were followed-up for at least 6 months from 1997 to 2018., Results: Of the 653 patients with PLWHA, 99 (15.2%) were both antiHBc-IgG and antiHBs positive, 120 (18.3%) were antiHBc-IgG positive/antiHBs negative. HBsAg was positive in 40 (6.1%) patients. HBsAg positive coinfection (≤40 years 4.6% vs. >40 years 21.7%, p<0.001) and antiHBc-IgG positivity/antiHBs negativity (≤40 years 14.0% vs. >40 years 26.5, p<0.001) were higher in PLWHA older than 40 years. The prevalence of HIV/HBV coinfection reached a peak level of 22.2% in 2004, and it decreased to 3.3% in 2018. The prevalence of immunization before HIV diagnosis was low (15.6%). The prevalence of antibody response (anti-HBs>10 IU/L) after immunization for HBV was 50%. A higher protective response was associated with CD4+≥350 cell/mm3 (59.3%, p=0.014)., Conclusion: HBV coexistence in PLWHA remains an imperatively important problem. The most conclusive methods in solving this problem are to prevent transmission by immunization and control measures. Also, HBV screening should in no manner be neglected in PLWHA., (© 2021 Zerdali E et al.)

We aimed to determine the predictors of intensive care unit (ICU) admission or death in patients with coronavirus disease 2019 (COVID-19) pneumonia. This retrospective, single-center study included patients aged ≥18 years who were diagnosed with COVID-19 pneumonia (laboratory and radiologically confirmed) between March 9 and April 8, 2020. The composite endpoint was ICU admission or in-hospital mortality. Univariate and multivariate logistic regression analyses were performed to evaluate the factors associated with the composite endpoint. A total of 336 patients with COVID-19 pneumonia were evaluated. The median age was 54 years (interquartile range: 21), and 187 (55.7%) were men. Fifty-one (15.2%) patients were admitted to the ICU. In-hospital mortality occurred in 33 patients (9.8%). In the univariate analysis, 17 parameters were associated with the composite endpoint, and procalcitonin had the highest odds ratio (odds ratio [OR] = 36.568, confidence interval [CI] = 5.145-259.915). Our results revealed that body temperature (OR = 1.489, CI = 1.023-2.167, P = 0.037), peripheral capillary oxygen saturation (SpO2) (OR = 0.835, CI = 0.773-0.901, P < 0.001), and consolidation (> 25%) on chest computed tomography (OR = 3.170, CI = 1.218-8.252, P = 0.018) at admission were independent predictors. As a result, increased body temperature, decreased SpO2, a high level of procalcitonin, and degree of consolidation on chest computed tomography may predict a poor prognosis and have utility in the management of patients.

Aim: We aimed to determine the prognostic values of the National Early Warning Score 2 (NEWS2) and laboratory parameters during the first week of COVID-19. Materials & methods: All adult patients who were hospitalized for confirmed COVID-19 between 11 March and 11 May 2020 were retrospectively included. Results: Overall, 611 patients were included. Our results showed that NEWS2, procalcitonin, neutrophil/lymphocyte ratio and albumin at D0, D3, D5 and D7 were the best predictors for clinical deterioration defined as a composite of ICU admission during hospitalization or in-hospital death. Procalcitonin had the highest odds ratio for clinical deterioration on all days. Conclusion: This study provides a list of several laboratory parameters correlated with NEWS2 and potential predictors for clinical deterioration in patients with COVID-19.

Light-activated biointerfaces provide a non-genetic route for effective control of neural activity. InP quantum dots (QDs) have a high potential for such biomedical applications due to their uniquely tunable electronic properties, photostability, toxic-heavy-metal-free content, heterostructuring, and solution-processing ability. However, the effect of QD nanostructure and biointerface architecture on the photoelectrical cellular interfacing remained unexplored. Here, we unravel the control of the photoelectrical response of InP QD-based biointerfaces via nanoengineering from QD to device-level. At QD level, thin ZnS shell growth (∼0.65 nm) enhances the current level of biointerfaces over an order of magnitude with respect to only InP core QDs. At device-level, band alignment engineering allows for the bidirectional photoelectrochemical current generation, which enables light-induced temporally precise and rapidly reversible action potential generation and hyperpolarization on primary hippocampal neurons. Our findings show that nanoengineering QD-based biointerfaces hold great promise for next-generation neurostimulation devices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Karatum, Aria, Eren, Yildiz, Melikov, Srivastava, Surme, Dogru, Bahmani Jalali, Ulgut, Sahin, Kavakli and Nizamoglu.)

Ntroduction: Anticoagulant treatment approach in patients with COVID-19 is not well studied and not standardized. We aimed to compare the effects of standard prophylactic and pre-emptive therapeutic Low-Molecular-weight Heparin (LMWH) treatment approaches on mortality in patients with COVID-19., Patients and Methods: This retrospective and single-centre study includes patients aged ≥ 18 years, who were diagnosed with COVID-19 and treated with LMWH during the hospital stay. Therapeutic dose of LMWH was defined as 1 mg/kg subcutaneously twice daily and prophylactic dose of LMWH was defined as 40 mg subcutaneously once daily., Results: Among the 336 patients diagnosed with COVID-19 pneumonia, 115 patients, who received LMWH were included in the study. The mean age was 58.6 ± 13.3 and 58 (50.4 %) of the patients were male. Sixty-nine (60 %) of the patients were treated with prophylactic and 46 (40 %) therapeutic LMWH.In-hospital mortality was not different between patients treated therapeutic LMWH and prophylactic LMWH by the multivariate regression analysis (OR=2.187, 95% CI 0.484-9.880, p=0.309) and the propensity score modelling (OR=1.586, 95% CI 0.400-6.289, p=0.512.)CONCLUSION: Clinicians should consider the potential risks and benefits of standard prophylactic and pre-emptive therapeutic LMWH. Therefore, anticoagulant therapy should be individualized in patients with COVID-19 (Tab. 3, Ref. 28).

Mammalian circadian clocks are driven by transcription/translation feedback loops composed of positive transcriptional activators (BMAL1 and CLOCK) and negative repressors (CRYPTOCHROMEs (CRYs) and PERIODs (PERs)). CRYs, in complex with PERs, bind to the BMAL1/CLOCK complex and repress E-box-driven transcription of clock-associated genes. There are two individual CRYs, with CRY1 exhibiting higher affinity to the BMAL1/CLOCK complex than CRY2. It is known that this differential binding is regulated by a dynamic serine-rich loop adjacent to the secondary pocket of both CRYs, but the underlying features controlling loop dynamics are not known. Here we report that allosteric regulation of the serine-rich loop is mediated by Arg-293 of CRY1, identified as a rare CRY1 SNP in the Ensembl and 1000 Genomes databases. The p.Arg293His CRY1 variant caused a shortened circadian period in a Cry1 -/- Cry2 -/- double knockout mouse embryonic fibroblast cell line. Moreover, the variant displayed reduced repressor activity on BMAL1/CLOCK driven transcription, which is explained by reduced affinity to BMAL1/CLOCK in the absence of PER2 compared with CRY1. Molecular dynamics simulations revealed that the p.Arg293His CRY1 variant altered a communication pathway between Arg-293 and the serine loop by reducing its dynamicity. Collectively, this study provides direct evidence that allosterism in CRY1 is critical for the regulation of circadian rhythm., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Gul et al.)

Antimicrobial stewardship is of major importance in patients with febrile neutropenia (FN). In this study, we aimed to investigate the trends in resistance and the relationship with mortality rates in patients with FN. The single-center surveillance data of inpatients with FN and diagnosed as microbiologically confirmed bloodstream infections (BSIs) between 2006 and 2016 were reviewed retrospectively. A total of 950 episodes in 552 patients with BSIs were analyzed. Of whom, 55.9% were male, the median age was 43 years, and 35.6% had acute myeloid leukemia. In total, 1016 microorganisms were isolated from blood cultures. Gram-negatives accounted for 42.4% (n = 403) of the episodes. Among Gram-negatives, Enterobacteriaceae accounted for 346 (86%) (E. coli, n = 197; 34% extended-spectrum β-lactamases (ESBL) producers, and Klebsiella spp., n = 120; 48.3% ESBL producers). Also, 24 (20.0%) of Klebsiella spp. had carbapenemase activity. There were 6 (5.0%) colistin-resistant Klebsiella spp. Thirteen (26.5%) of Pseudomonas spp. and 17 (60.7%) of Acinetobacter spp. had carbapenemase activity. There were 2 (5.6%) colistin-resistant Acinetobacter spp. The 30-day mortality rates were 12.0%, 21.5%, 34.6%, and 29.0% in BSIs due to Gram-positive, Gram-negative bacterial, fungal, and polymicrobial etiology respectively (p = 0.001). BSIs with ESBL-producing (p = 0.001) isolates, carbapenem (p < 0.001), and colistin-resistant isolates (p < 0.001) were associated with increased mortality risk. The tremendous rise in resistance rates among Gram-negatives is dreadfully related to increasing mortality and leads to sharp shifts toward extreme restrictions of unnecessary antibiotic uses. Antimicrobial stewardship in patients with FN requires vigilance and tailoring of treatment upon local surveillance data.

Objectives: We described the clinical outcomes of the diabetic patients who had foot infections with multidrug resistant organisms., Methods: We included the patients with diabetic foot infections (DFI) from 19 centers, between May 2011 and December 2015. Infection was defined according to IDSA DFI guidelines. Patients with severe infection, complicated moderate infection were hospitalized. The patients were followed-up for 6 months after discharge., Results: In total, 791 patients with DFI were included, 531(67%) were male, median age was 62 (19-90). Severe infection was diagnosed in 85 (11%) patients. Osteomyelitis was diagnosed in 291(36.8%) patients. 536 microorganisms were isolated, the most common microorganisms were S. aureus (20%), P. aeruginosa (19%) and E. coli (12%). Methicillin resistance (MR) rate among Staphylococcus aureus isolates was 31%. Multidrug resistant bacteria were detected in 21% of P. aeruginosa isolates. ESBL (+) Gram negative bacteria (GNB) was detected in 38% of E. coli and Klebsiella isolates. Sixty three patients (8%) were re-hospitalized. Of the 791 patiens, 127 (16%) had major amputation, and 24 (3%) patients died. In multivariate analysis, significant predictors for fatality were; dialysis (OR: 8.3, CI: 1.82-38.15, p=0.006), isolation of Klebsiella spp. (OR:7.7, CI: 1.24-47.96, p=0.028), and chronic heart failure (OR: 3, CI: 1.01-9.04, p=0.05). MR Staphylococcus was detected in 21% of the rehospitalized patients, as the most common microorganism (p<0.001)., Conclusion: Among rehospitalized patients, methicillin resistant Staphylococcus infections was detected as the most common agent, and Klebsiella spp. infections were found to be significantly associated with fatality., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)