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The limited data on post-operative analgesia management after laparoscopic cholecystectomy in the paediatric population make it difficult for clinicians to manage pain in this group. Administration of a modified thoracoabdominal nerve block through a perichondrial approach (M-TAPA) has recently been identified as a technique providing effective analgesia on the anterior and lateral thoracoabdominal wall. Unlike thoracoabdominal nerve block through the perichondrial approach block, the local anaesthetic (LA) with M-TAPA block provides effective post-operative analgesia in abdominal surgery by affecting T5-T12 dermatomes, just like when applied to the lower part of the perichondrium. As far as we know, all patients in previous case reports were adults, and we did not come across any study on the effectiveness of M-TAPA in paediatric patients. We present our case who did not need any additional analgesic during the post-operative 24 h after an M-TAPA block was administered before paediatric laparoscopic cholecystectomy.

Resumo Fundamento Embora tenha havido melhorias significativas no tratamento da insuficiência cardíaca (IC) nas últimas décadas, seu prognóstico permanece desfavorável. Embora existam muitos biomarcadores que podem ajudar a prever o prognóstico de pacientes com IC, há necessidade de biomarcadores mais simples, menos dispendiosos e mais facilmente disponíveis. Objetivo Avaliar o valor preditivo do valor pan-imune-inflamatório (PIV, do inglês pan-immune-inflammation value) em pacientes com IC agudamente descompensada. Métodos Analisamos 409 pacientes com IC com fração de ejeção reduzida internados por IC aguda descompensada. Os pacientes foram divididos em 3 grupos de acordo com os tercis de PIV: tercil 1 (PIV < 357,25), tercil 2 (PIV ≥ 357,25 e < 834,55) e tercil 3 (PIV ≥ 834,55). Foram considerados estatisticamente significativos valores de p < 0,05. Curvas de Kaplan-Meier e modelos de regressão de riscos proporcionais de Cox foram utilizados para avaliar a associação entre PIV e mortalidade por todas as causas. O desfecho primário foi mortalidade por todas as causas em 5 anos, e o desfecho secundário compreendeu a mortalidade por todas as causas intra-hospitalar em 30 dias, em 180 dias e em 1 ano Resultados Mostramos que valores mais elevados de PIV estavam associados a desfechos primários e secundários. A curva de Kaplan-Meier mostrou que pacientes com valores mais elevados de PIV apresentaram risco aumentado de mortalidade por todas as causas em curto e longo prazo (log-rank p < 0,001). Na análise multivariada, o PIV foi identificado como um preditor independente de mortalidade por todas as causas em longo prazo em pacientes com IC aguda descompensada, e observamos um aumento de 1,96 vezes no risco de um evento (razão de chances: 1,96; intervalo de confiança de 95%: 1,330 a 2,908; p = 0,001). Conclusões Nosso estudo mostrou que o novo biomarcador PIV pode ser usado como preditor de prognóstico em pacientes com IC aguda descompensada.

Abstract Postoperative pulmonary complications (PPCs) arise from a complex interplay of patient, surgical, and anesthesia-related factors. Despite their significant impact, there are currently no standardized guidelines recommending a comprehensive preoperative approach to assessing patients with PPC risk factors. Preoperative pulmonary evaluation (PPE) plays a pivotal role in identifying underlying patient conditions, undiagnosed diseases and optimal treatments. PPE involves systematic identification of patient, surgical, and anesthesia-related risk factors. Severe PPCs include atelectasis, pneumonia, respiratory failure, pulmonary embolism, and worsening chronic lung disease. Surgical urgency, type, duration, approach of the surgical procedure, and comorbidities influence PPC rates, with cardiac, thoracic, abdominal, and vascular surgeries being particularly vulnerable. Patient-related risk factors encompass non-pulmonary and pulmonary factors. Aging populations increase surgical demand, with advanced age and frailty predicting higher morbidity and mortality risks. Conditions like congestive heart failure, obesity, obstructive sleep apnea, and smoking heighten PPC risks. Asthma, chronic obstructive pulmonary disease, interstitial lung diseases, pulmonary hypertension, previous pulmonary thromboembolism, acute respiratory infections, and COVID-19 impact pulmonary risk profiles. Surgery and anesthesia-related risk factors include the site of surgery, operation time, and emergency surgery. Surgery near the diaphragm elevates PPC risk, while longer operation times correlate with increased PPC incidence. Emergency surgeries pose challenges in risk assessment. Anesthetic techniques influence outcomes, with regional anesthesia often preferable. Neuromuscular blocking agents impact PPCs, and protective ventilation strategies can mitigate complications. As current literature lacks a comprehensive approach to PPE, in this review, we present a comprehensive approach to preoperative pulmonary approach to surgical patients to help in risk stratification, further optimization, as well as shared decision making between the surgeon and the patients and their family prior to consenting for a major surgical procedure. Graphical Abstract

Summary: Characterizing the effect of combination therapies is vital for treating diseases like cancer. We introduce correlated drug action (CDA), a baseline model for the study of drug combinations in both cell cultures and patient populations, which assumes that the efficacy of drugs in a combination may be correlated. We apply temporal CDA (tCDA) to clinical trial data, and demonstrate the utility of this approach in identifying possible synergistic combinations and others that can be explained in terms of monotherapies. Using MCF7 cell line data, we assess combinations with dose CDA (dCDA), a model that generalizes other proposed models (e.g., Bliss response-additivity, the dose equivalence principle), and introduce Excess over CDA (EOCDA), a new metric for identifying possible synergistic combinations in cell culture.

Assigning medical codes for patients is essential for healthcare organizations, not only for billing purposes but also for maintaining accurate records of patients' medical histories and analyzing the outputs of certain procedures. Due to the abundance of disease codes, it can be laborious and time-consuming for medical specialists to manually assign these codes to each procedure. To address this problem, we discuss the automatic prediction of ICD-9 codes, the most popular and widely accepted system of medical coding. We introduce a two-stream deep learning framework specifically designed to analyze multi-modal data. This framework is applied to the extensive and publicly available MIMIC-III dataset, enabling us to leverage both numerical and text-based data for improved ICD-9 code prediction.Our system uses text representation models to understand the text-based medical records; the Gated Recurrent Unit (GRU) to model the numerical health records; and fuses these two streams to automatically predict the ICD-9 codes used in the intensive care unit. We discuss the preprocessing and classification methods and demonstrate that our proposed two-stream model outperforms other state-of-the-art studies in the literature.

Summary: The Centers for Disease Control and Prevention promoted the Test-to-Stay (TTS) program to facilitate in-person instruction in K-12 schools during COVID-19. This program delineates guidelines for schools to regularly test students and staff to minimize risks of infection transmission. TTS enrollment can be implemented via two different consent models: opt-in, in which students do not test regularly by default, and the opposite, opt-out model. We study the impacts of the two enrollment approaches on testing and positivity rates with data from 259 schools in Illinois. Our results indicate that after controlling for other covariates, schools following the opt-out model are associated with 84% higher testing rate and 30% lower positivity rate. If all schools adopted the opt-out model, 20% of the total lost school days could have been saved. The lower positivity rate among the opt-out group is largely explained by the higher testing rate in these schools, a manifestation of status quo bias.

Objectives:The aims of this study were to describe the clinical presentation and treatment modalities of acute retinal necrosis (ARN) and to evaluate complications and clinical outcomes according to the extent of retinal involvement at initial presentation.Materials and Methods:The medical records of 52 patients diagnosed with ARN were reviewed and 48 were included in the study. Patients were categorized into two groups according to the extent of retinitis at presentation: retinal involvement of 1-2 quadrants (Group A) or 3-4 quadrants (Group B).Results:The mean age of the 14 women and 34 men at presentation was 51.3±13.6 years (range: 27-78). There were 40 unilateral and 8 bilateral cases. There were 11 eyes (19.6%) in Group A and 45 eyes (80.4%) in Group B. Eleven patients (22.9%) had a history of herpes simplex virus/varicella-zoster virus infection. One patient in Group A and 11 patients in Group B had received local or systemic corticosteroid therapy without concomitant antiviral treatment before referral. The median follow-up period was 29 months (range: 1-209) in Group A and 8.5 months (range: 0.75-209) in Group B. Mean visual acuity (VA) at presentation was 0.42±0.55 LogMAR (range: 0-2.0) in Group A and 1.28±0.95 LogMAR (range: 0-2.9) in Group B (p

الملخص: يعتبر التسرب المجاور للصمام من المضاعفات الخطيرة لجراحة الصمام الاصطناعي. يمكن استخدام الطرق الجراحية وطرق القسطرة في العلاج. من النادر أن تنفصل أجهزة الإغلاق من مكانها وتتجول في غرف القلب. يمكن استخدام طرق القسطرة مرة أخرى، ولكن إذا كانت إعادة الاستخدام هذه بسبب زيادة في التسرب المجاور للصمام، فإن العلاج الجراحي يكون أكثر ملاءمة. نقدم هنا حالة تم علاجها بنجاح مع جهاز إغلاق يمر بحرية عبر التسرب المجاور للصمام من البطين إلى الأذين، بعد استبدال أربعة صمامات جراحية وإغلاق جهازين عبر القسطرة، بسبب التهاب الشغاف العدوائي. Abstract: Paravalvular leakage (PVL) is a serious complication of prosthetic valve surgery. Surgical and transcatheter methods can be used for treatment. It is rare for closure devices to detach and free float in cardiac chambers. Transcatheter methods can be reused, but surgical treatment is more appropriate if this reuse is due to an increase in PVL. Here, we present a successfully operated case with a closure device freely passing through the PVL from the ventricle to the atrium, after four surgical valve replacements and two transcatheter device closures, owing to infective endocarditis.

Microneedles (MNs) are micrometer-sized arrays that can penetrate the skin in a minimally invasive manner; these devices offer tremendous potential for the transdermal delivery of therapeutic molecules. Although there are many conventional techniques for manufacturing MNs, most of them are complicated and can only fabricate MNs with specific geometries, which restricts the ability to adjust the performance of the MNs. Herein, we present the fabrication of gelatin methacryloyl (GelMA) MN arrays using the vat photopolymerization 3D printing technique. This technique allows for the fabrication of high-resolution and smooth surface MNs with desired geometries. The existence of methacryloyl groups bonded to the GelMA was verified by 1H NMR and FTIR analysis. To examine the effects of varying needle heights (1000, 750, and 500 µm) and exposure times (30, 50, and 70 s) on GelMA MNs, the height, tip radius, and angle of the needles were measured; their morphological and mechanical properties were also characterized. It was observed that as the exposure time increased, the height of the MNs increased; moreover, sharper tips were obtained and tip angles decreased. In addition, GelMA MNs exhibited good mechanical performance with no breakage up to 0.3 mm displacement. These results indicate that 3D printed GelMA MNs have great potential for transdermal delivery of various therapeutics.

The utilization of externally bonded carbon fiber-reinforced polymers (CFRPs) and glass fiber-reinforced polymers (GFRPs) for reinforcing and retrofitting components has garnered considerable interest recently, as such composites provide beneficial properties, including a high modulus of elasticity, high strength, and low weight. This work conducts a finite element analysis, verified through laboratory experiments on 14 reinforced concrete (RC) beams. The primary focus is the final load of these components, considering varying CFRP orientations relative to the loading direction. In this research, the performances of control beams and RC beams are compared to assess the effectiveness and efficiency of different strengthening methods. The results demonstrated that bonding CFRP sheets with V-shaped end anchorages on the tension side was highly effective in improving the flexural capacity of RC beams in the weaker concrete strength group. This strengthening method resulted in a substantial increase in strength (of around 29.8%) in the higher concrete strength group. In addition, utilizing V-shaped end anchorages to bond CFRP sheets on the tension side proved to be a highly efficient technique for improving flexural strength. Conversely, bonding inclined CFRP strips to the sides of RC beams was highly effective at enhancing the shear capacity of the beams. These outcomes convincingly demonstrate the effectiveness of FRP for the reinforcement of structural components. The specimens strengthened with inclined strips exhibited enhanced shear and deformation capacity compared to those strengthened with vertical strips.

ObjectiveThe Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score and the Geriatric Nutrition Risk Index (GNRI) are used as prognostic factors in different types of cancers. In this study we analyzed the prognostic value of the HALP Score and the GNRI calculated prior to first-line treatment in patients diagnosed with de novo metastatic non-small cell lung cancer (mNSCLC).Materials and methodsDe novo mNSCLC patients were retrospectively evaluated from January 2016 to December 2019. Patients with Driver’s mutation, severe comorbidities, active infection, or insufficient organ function, and those receiving anti-inflammatory treatment were excluded from the study. Optimal cut-off points for the HALP score and the GNRI were calculated with the receiver operating characteristic (ROC) curve analysis. Predictive factors for overall survival (OS) were assessed with univariate and multivariate Cox proportional hazard analyses, and OS was studied with the Kaplan–Meier analysis.ResultsThe study included 401 patients in total. In the ROC curve analysis, the cut-off points were found 23.24 (AUC = 0.928; 95% CI: 0.901–0.955, p < 0.001) for HALP, and 53.60 (AUC = 0.932; 95% CI: 0.908–0.955, p < 0.001) for GNRI. Groups with lower HALP scores and lower GNRI had significantly shorter OS compared to those with higher HALP scores and GNRIs. Univariate analysis showed that male gender, smoking, high ECOG score, low HALP score and low GNRI were associated with worse survival rates. Multivariate analysis showed that low HALP score (HR = 2.988, 95% CI: 2.065–4.324, p < 0.001); low GNRI score (HR = 2.901, 95% CI: 2.045–4.114, p < 0.001) and smoking history (HR = 1.447, 95% CI: 1.046–2.001, p = 0.025) were independent factors associated with worse OS rates.ConclusionOur study showed the HALP score and the GNRI to be of prognostic value as simple, cost-effective, and useful markers that predict OS in de novo mNSCLC patients.

Aim:Despite advances in-stent technology, in-stent restenosis (ISR) is still a major problem following percutaneous coronary intervention (PCI) and its reasons have not been fully revealed. In the presented study, we investigated the effect of admission blood glucose (ABG), fasting blood glucose (FBG) and glycated hemoglobin A1c (HbA1c) levels on coronary ISR patients with ST-elevation myocardial infarction (STEMI) who underwent primary PCI in five-year follow-up.Methods:From 2.900 patients who underwent coronary stent implantation for STEMI from January 2008 through December 2012 were retrospectively analyzed through the hospital digital recording system. Of these, 264 patients who underwent control coronary angiography during the five-year follow-up were included in the study. Patients were divided into two main group ISR and non-ISR; were divided into two subgroups diabetic and non-diabetic groups were compared with HbA1c, ABG, FBG and angiographic parameters.Results:There were 127 patients in the ISR group (diabetic: 36 non-diabetic: 91) and 137 patients in the non-ISR group (diabetic: 43 non-diabetic: 94). Regardless of the patients diabetes status, no significant difference was found between the groups with and without ISR in terms of HbA1c, FBG and ABG. A significant relationship was found between the baseline HbA1c value and having ISR only in the diabetic subgroup (p=0.01).Conclusion:This study results showed that in diabetic STEMI patients who underwent primary PCI, higher HbA1c levels were associated with higher ISR rates, but not with FBG and ABG levels.

Aim:ST segment elevated myocardial infarction (STEMI) is regarded as a type of acute coronary syndrome. However, the mortality of STEMI patients is substantial. Asymmetric dimethylarginine (ADMA) is the major inhibitor of nitric oxide biosynthesis in humans. Studies have shown that increased ADMA levels are associated with endothelial dysfunction and increased atherogenesis. It is aimed to show the relationship between ADMA and prognosis of STEMI.Materials and Methods:The study population was 45 (40 male, 5 female) patients with a diagnosis of STEMI, who underwent primary percutaneous coronary intervention (PCI). Demographic data, blood tests, medical history, data related to interventions, in-hospital and out-hospital follow-up of the patients were recorded. Ten cc of blood samples were collected following sheat application. ADMA levels were studied by ELISA kit.Results:The follow-up period was 42.837±14.343 months. The mean age was 52.4±7.8. Only significant relation was observed between ADMA levels and heart rate (p=0.025). Other relations with demographic data, risk factors for STEMI, follow-up events such as major adverse cardiovascular events, heart failure, target vessel revascularization, reinfarction, ongoing myocardial ischemia, in-hospital events, intervention artery, type of intervention, Pre-TIMI, ejection fraction, use of tirofiban, anterior or inferior MI were not statistically significant (p>0.05). Although, a positive relation was observed between ADMA levels and chronic heart failure, it was not significant.Conclusion:Although, there was a relation with heart failure, the only significant relation was found between ADMA levels and heart rate. Further studies with greater number of participants should be performed for drawing strict conclusions.

The structural pounding caused by an earthquake may damage structures and lead to their collapse. This study is focused on the pounding between two adjacent asymmetric structures with different dynamic properties resting on the surface of an elastic half-space. An exploration of the relationship between the effects of the seismic analysis with the impact response to the torsional pounding between adjacent buildings under different SSI effects has been presented. In this paper, the authors have proposed a procedure for analyzing the response for adjacent buildings subjected to the pounding effects, considering systems with multiple degrees of freedom and modal equations of motion with four types of soil. All the calculations have been performed based on the fourth-order Runge–Kutta method. The novelty of the present study is related to the fact that the rigorous and approximate methods are used to examine the effects of pounding and SSI simultaneously. As a result, these two methods have been thoroughly investigated for both effects and the results have been compared. The results show that the approximate method produces results that are slightly different from those obtained by the rigorous direct integration method in the case of small SSI effects due to an increase in the pounding force. The efficiency of the method is also validated using numerical examples.

Resistance to first line treatment is a major hurdle in cancer treatment, that can be overcome with drug combinations. Here, the authors provide a large drug combination screen across cancer cell lines to benchmark crowdsourced methods and to computationally predict drug synergies.

Objective: Heart failure (HF) is an important health issue of the 21st century and the prevalence in Turkey has been reported as 2.9%. A national profile, frequency data, characteristics of different phenotypes, and risk factors have not yet been well established. The Snapshot Evaluation of Heart Failure Patients in Turkey (SELFIE-TR) was an analysis of a representative sample of HF patients from Turkey. Methods: A total of 23 centers with at least 2 cardiologists from the 12 NUTS-1 regions of Turkey were invited to participate in the research. The contributing centers shared the data of a consecutive enrollment of HF patients, as confirmed by an investigator, on a pre-selected day of each week for the month of October or November of 2015. Results: The mean age of the entire cohort was 63.3+-13.3 years (male/female ratio: 751/303, 71.3%/28.7%). There were 712 acute HF patients and 342 chronic HF patients. The total number of HF patients with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction, and heart failure with preserved ejection fraction was 801 (75%), 176 (16.7%), and 77 (7.3%), respectively. The patients with chronic HF were younger than those with acute HF (61.1+-13.3 years vs 67.9+-12.1 years; p

Background: Pilonidal disease is a common condition that usually affects young men. The disease presents with pain, cysts, abscesses, pits, sinus tracts, retained hairs and draining in the sacrococcygeal area. Various surgical techniques have been described in the treatment of pilonidal disease. Modified Limberg flap is a commonly used procedure, however, studies which compared the outcomes of modified Limberg flap technique have reported different results. Diverse geometric rhomboid excisions in shape and size, and varied lateralization distance can lead to differences in healing time, complication and recurrence rates. Standardization of the modified Limberg flap technique can help to compare the end results of the surgical intervention more accurately. Therefore, we developed an acetate template to draw a sketch map of Limberg/modified Limberg flap preoperatively, in order to standardize the procedure. Materials and Methods: A Limberg/modified Limberg flap template was prepared by using an online drawing program. Rhomboid flaps with four different sizes were drawn. The template was printed onto an acetate sheet. With the help of a sewing needle, pin holes were performed on the acetate template. The borders of the rhomboid excision and the Limberg/modified Limberg flap were defined with the acetate template and drawn on the gluteal region by using a water resistant multi-purpose pen. The surgeon decided which rhomboid flap size to choose according to the dispersion of the pilonial sinus openings. All pilonidal pits and abscess orifices stayed within the resected area. The size of modified Limberg flap was standardized by the help of the acetate template. Results: This study included 10 male patients with pilonidal disease between the ages of 20 to 35. The mean disease duration of the patients was 4.2 years. All the patients underwent modified Limberg flap surgery using an acetate template. The follow-up period was three months. We observed surgical site infection only in one patient within seven days, postoperatively. Conclusions: We suggest that using a standardized template while performing a modified Limberg flap procedure for the treatment of pilonidal disease may help to evaluate and compare the outcomes of this surgical procedure more accurately.

Cancer testis antigens (CTAs) are an extensive gene family with a unique expression pattern restricted to germ cells, but aberrantly reactivated in cancer tissues. Studies indicate that the expression (or re-expression) of CTAs within the MAGE-A family is common in hepatocellular carcinoma (HCC). However, no systematic characterization has yet been reported. The aim of this study is to perform a comprehensive profile of CTA de-regulation in HCC and experimentally evaluate the role of MAGEA3 as a driver of HCC progression. The transcriptomic analysis of 44 multi-regionally sampled HCCs from 12 patients identified high intra-tumor heterogeneity of CTAs. In addition, a subset of CTAs was significantly overexpressed in histologically poorly differentiated regions. Further analysis of CTAs in larger patient cohorts revealed high CTA expression related to worse overall survival and several other markers of poor prognosis. Functional analysis of MAGEA3 was performed in human HCC cell lines by gene silencing and in a genetic mouse model by overexpression of MAGEA3 in the liver. Knockdown of MAGEA3 decreased cell proliferation, colony formation and increased apoptosis. MAGEA3 overexpression was associated with more aggressive tumors in vivo. In conclusion MAGEA3 enhances tumor progression and should be considered as a novel therapeutic target in HCC.

Background: Assistive automatic seizure detection can empower human annotators to shorten patient monitoring data review times. We present a proof-of-concept for a seizure detection system that is sensitive, automated, patient-specific, and tunable to maximise sensitivity while minimizing human annotation times. The system uses custom data preparation methods, deep learning analytics and electroencephalography (EEG) data. Methods: Scalp EEG data of 365 patients containing 171,745 s ictal and 2,185,864 s interictal samples obtained from clinical monitoring systems were analysed as part of a crowdsourced artificial intelligence (AI) challenge. Participants were tasked to develop an ictal/interictal classifier with high sensitivity and low false alarm rates. We built a challenge platform that prevented participants from downloading or directly accessing the data while allowing crowdsourced model development. Findings: The automatic detection system achieved tunable sensitivities between 75.00% and 91.60% allowing a reduction in the amount of raw EEG data to be reviewed by a human annotator by factors between 142x, and 22x respectively. The algorithm enables instantaneous reviewer-managed optimization of the balance between sensitivity and the amount of raw EEG data to be reviewed. Interpretation: This study demonstrates the utility of deep learning for patient-specific seizure detection in EEG data. Furthermore, deep learning in combination with a human reviewer can provide the basis for an assistive data labelling system lowering the time of manual review while maintaining human expert annotation performance. Funding: IBM employed all IBM Research authors. Temple University employed all Temple University authors. The Icahn School of Medicine at Mount Sinai employed Eren Ahsen. The corresponding authors Stefan Harrer and Gustavo Stolovitzky declare that they had full access to all the data in the study and that they had final responsibility for the decision to submit for publication.

Abstract The limited data on post-operative analgesia management after laparoscopic cholecystectomy in the paediatric population make it difficult for clinicians to manage pain in this group. Administration of a modified thoracoabdominal nerve block through a perichondrial approach (M-TAPA) has recently been identified as a technique providing effective analgesia on the anterior and lateral thoracoabdominal wall. Unlike thoracoabdominal nerve block through the perichondrial approach block, the local anaesthetic (LA) with M-TAPA block provides effective post-operative analgesia in abdominal surgery by affecting T5-T12 dermatomes, just like when applied to the lower part of the perichondrium. As far as we know, all patients in previous case reports were adults, and we did not come across any study on the effectiveness of M-TAPA in paediatric patients. We present our case who did not need any additional analgesic during the post-operative 24 h after an M-TAPA block was administered before paediatric laparoscopic cholecystectomy. Keywords: Cholecystectomy, laparoscopic surgery, modified thoracoabdominal nerve block through a perichondrial approach block, paediatric, Author(s): Volkan Ozen (corresponding author) [1]; Mehmet Eren Acik [2]; Nurten Ozen [3] INTRODUCTION Cholecystectomy performed with the laparoscopic approach has beneficial effects such as requiring a minimal surgical incision, [...]

Our ability to discover effective drug combinations is limited, in part by insufficient understanding of how the transcriptional response of two monotherapies results in that of their combination. We analyzed matched time course RNAseq profiling of cells treated with single drugs and their combinations and found that the transcriptional signature of the synergistic combination was unique relative to that of either constituent monotherapy. The sequential activation of transcription factors in time in the gene regulatory network was implicated. The nature of this transcriptional cascade suggests that drug synergy may ensue when the transcriptional responses elicited by two unrelated individual drugs are correlated. We used these results as the basis of a simple prediction algorithm attaining an AUROC of 0.77 in the prediction of synergistic drug combinations in an independent dataset.

The response to respiratory virus exposure can currently not be predicted by pre- or early post-exposure molecular signatures. Here, the authors conduct a community-based analysis of blood gene expression from healthy individuals exposed to respiratory viruses and provide predictive models and biological insight into the physiological response.

Familial Mediterranean fever (FMF) is one of the most common autoinflammatory diseases. FMF is a disease that characterized by recurrent fever, transient and self-limiting polyserositis, responds well to the treatment of colchicine. In 95% of patients, the first attack occurs with severe abdominal pain. The first attack frequency that starts with pleuritic chest pain, pleural effusion and fever are lower than 10%. Ninety percent of the cases are younger than 20 years old. After 40 years old, it is rarely diagnosed (1.25%). In this case report; we wanted to present an FMF case diagnosed after 40 years old in the context of the patient's clinical follow-up, treatment, and literature, since it is very rare to diagnose in this age group, and unexpected complications can occur.

An inguinal hernia repair operation is a common procedure in general surgery. However, several other conditions such as inguinal lymphadenopathy, groin lipoma, spermatic-cord lipoma and sarcoma may have similar clinical findings with inguinal hernia. Preoperative diagnosis is crucial to make the appropriate treatment plan. An accurate preoperative diagnosis prevents both unnecessary operations and surgical complications. Radiological imaging techniques such as ultrasonography, computed tomography and magnetic resonance imaging should be considered in the differential diagnosis of inguinal masses. Hereby, we present a 41-year-old Caucasian male patient with a giant lipoma in the right groin which mimicked an inguinal hernia. Preoperative ultrasound imaging helped us to make an initial diagnosis of lipoma which was subsequently confirmed by histopathological examination.

Abstract Background Metastasis via pelvic and/or para-aortic lymph nodes is a major risk factor for endometrial cancer. Lymph-node resection ameliorates risk but is associated with significant co-morbidities. Incidence in patients with stage I disease is 4–22% but no mechanism exists to accurately predict it. Therefore, national guidelines for primary staging surgery include pelvic and para-aortic lymph node dissection for all patients whose tumor exceeds 2cm in diameter. We sought to identify a robust molecular signature that can accurately classify risk of lymph node metastasis in endometrial cancer patients. 86 tumors matched for age and race, and evenly distributed between lymph node-positive and lymph node-negative cases, were selected as a training cohort. Genomic micro-RNA expression was profiled for each sample to serve as the predictive feature matrix. An independent set of 28 tumor samples was collected and similarly characterized to serve as a test cohort. Results A feature selection algorithm was designed for applications where the number of samples is far smaller than the number of measured features per sample. A predictive miRNA expression signature was developed using this algorithm, which was then used to predict the metastatic status of the independent test cohort. A weighted classifier, using 18 micro-RNAs, achieved 100% accuracy on the training cohort. When applied to the testing cohort, the classifier correctly predicted 90% of node-positive cases, and 80% of node-negative cases (FDR = 6.25%). Conclusion Results indicate that the evaluation of the quantitative sparse-feature classifier proposed here in clinical trials may lead to significant improvement in the prediction of lymphatic metastases in endometrial cancer patients.

Background: The classification of pulmonary stenosis (PS) severity based on the transpulmonary pressure gradient, which is affected by flow rate. Case Report: We report the first case of a pregnant patient with atrial septal defect (ASD) and pulmonary stenosis that was misclassified by conventional echocardiographic methods. Most importantly, three-dimensional transoesophageal echocardiographic assessment of pulmonary stenosis changed the entire treatment strategy. Conclusion: The planimetric calculation of the pulmonary valve (PV) opening area using three-dimensional transoesophageal echocardiographic may be helpful, especially in encounters with specialized conditions such as ASD and/or pregnancy, which can cause inaccurate recordings of the transvalvular peak gradient

Congenital nevus is a melanocytic proliferation that is present at birth. When the diameter of a congenital melanocytic nevus is 20 cm or greater, it is called giant congenital melanocytic nevus. A giant congenital melanocytic nevus harbors the risk of malignant transformation. Moreover, the risk of malignant transformation increases with increasing lesion size. Furthermore, various abnormalities like scoliosis, spina bifida, atrophy and asymmetry of extremities can coexist with congenital nevi. Hereby, we present a 4-year-old Caucasian female child with a giant congenital melanocytic nevus on her trunk associated with postural asymmetry. The lesion depicted here had a characteristic clinical appearance, however the surface of the nevus had verrucous and hairy areas despite the patient’s young age. The patient was evaluated for clinical signs of possible malignant changes, and regular dermatoscopic follow-up was recommended.

Background: Development of contrast-induced acute kidney injury (CI-AKI) in patients with ST-elevation myocardial infarction (STEMI) treated via primary percutaneous coronary intervention (PCI) is a major cause of morbidity and mortality worldwide. The neutrophil-to-lymphocyte ratio (NLR), which is a marker of inflammation, has been demonstrated to be associated with the development of major adverse cardiovascular outcomes in many studies. From this point of view, in this study, we aimed to evaluate the predictive value of the NLR as regards the occurrence of CI-AKI in patients with STEMI undergoing primary PCI. Methods: This study was conducted at Dr. Siyami Ersek Training and Research Hospital from May 2008 to June 2016. A total of 2000 patients with STEMI treated via primary PCI were enrolled in the study. The NLR was calculated as the ratio of the number of neutrophils to the number of lymphocytes. All venous blood samples were obtained within 8 hours after admission. CI-AKI was the primary end point of the study. Then, the relationship between CI-AKI and the NLR was assessed. Results: CI-AKI was detected in 148 (7.4%) patients. The patients who developed CI-AKI had a significantly higher NLR than those who did not (7.08±4.43 vs. 6.18±3.98; P=0.011). In the multivariate logistic regression analyses, the NLR remained a significant independent predictor of CI-AKI (OR: 1.78, 95% CI: 1.21–2.61, and P=0.003). Conclusion: The NLR may be a significant independent predictor of CI-AKI in patients with STEMI treated via primary PCI and higher NLR values could be independently associated with a greater risk for CI-AKI.

Objective: The goal of this study was to develop a national database of patients hospitalized in Turkey with acute heart failure (AHF) using evaluations of diagnostic and therapeutic approaches. Methods: Patient data was collected using an Internet-based survey. Total of 588 patients were enrolled from 36 participating medical centers from across the country. Results: Mean age was 62+-13 years and 38% of the patients were female. Ratio of de novo AHF to study cohort was 24%. Coronary heart disease and hypertension were found in 61% and 53% of the patients, respectively. Valvular heart disease was underlying cause in 46% of heart failure patients. Most frequent factor associated with decompensation was noncompliance with treatment, observed in 34% of patients. Systolic blood pressure was 125+-28 mmHg and heart rate was 93+-22 beats/minute in the cohort. Most common findings on physical examination were inspiratory fine crackles (84%), peripheral edema (64%), and cold extremities in 34%. Mean ejection fraction (EF) measured at admission was 33+-13%. Preserved EF (≥%40) was present in 20% of patients. At admission, 60%, 46%, and 40% of patients were using angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, or aldosterone antagonist, respectively. Death, stroke, and myocardial infarction were reported with frequency of 3.4%, 1.6%, and 2%, respectively, as in-hospital events. Conclusion: Compared to some other research data collected around the world, AHF patients in Turkey were younger, more frequently had valvular heart disease as underlying cause, and were more noncompliant with medical treatment, but overall mortality was lower. Drugs shown to reduce mortality, and which also form the backbone of guideline-directed medical therapy, are still used inadequately.

Heart failure is a progressive disease. A considerable number of patients eventually reach an advanced or terminal phase, in spite of developments in diagnostic procedure, alternative treatments that can slow progression, management, and follow-up. In addition to palliative care of patients in the terminal phase, accurate recognition of advanced disease is vital in the determination of therapeutic options. Overall management of patients with heart failure requires the collaboration of professionals from multiple disciplines. Still, patients with advanced heart failure should be managed by a 'heart team,' as indicated by guidelines; communication and collaboration among cardiologists, cardiovascular surgeons, and other medical staff responsible for patient care is necessary. While our country has physicians experienced in the management of patients with advanced heart failure, these professionals are not distributed evenly across the country, and equitable access to therapeutic options is not provided. Hence, progress has yet to be made regarding appropriate referrals and patient circulation. The aims of the present consensus report are to strengthen the connection between certified, experienced centers and those that care for patients irrespective of disease phase and healthcare staff, as well as to raise awareness and provide information regarding conditions in Turkey.

Abstract Objective: Transcatheter aortic valve implantation has recently been used in the treatment of severe aortic valve stenosis, particularly in patients with high mortality and morbidity rates for open surgery. The purpose of this study was to compare quality of life in patients over 70 years of age undergoing surgical or transcatheter aortic valve implantation, before the procedure and in the early post-procedural period. Methods: Seventy-nine patients were included in the study, 38 (48.1%) male and 41 (51.9%) female. Mean age of patients was 74.3±5.2 (70-91) years. The surgical aortic valve replacement group consisted of 51 (64.6%) patients and the transcatheter aortic valve replacement group of 28 (35.4%). Quality of life data before the procedure and at the 3rd month postoperatively in patients aged 70 years and older undergoing surgical or transcatheter aortic valve implantation were assessed using the 36-item Short Form Health Survey form. Results: Positive increases in physical task difficulty (13.2±9.8vs. 5.1±7.3) (P=0.001), emotional task difficulty (14.4±11.9 vs.8.5±6.4) (P=0.035), and mental health (0.4±10.4 vs. 9.6±15.1) (P=0.001; P

Tinea incognito is a dermatophyte infection with altered clinical appearance which is usually caused by the use of immunosuppressive agents such as topical corticosteroids. Hereby, we present a 59-year-old Caucasian male patient with tinea manuum on the dorsum of his left hand. The lesion was formerly misdiagnosed as psoriasis vulgaris and treated with topical corticosteroids. However, the symptoms were worsened. Moreover, new papules and pustules appeared within the lesion. The past medical history was remarkable for psoriasis vulgaris and he had an erythematous and squamous plaque on his lower back resembling psoriasis vulgaris. In order to reach a definitive diagnosis, the skin lesion on the dorsum of the patient’s left hand was examined by light microscopy after the application of 10% potassium hydroxide solution. Detection of septate hyphae confirmed dermatophytosis. The lesion was completely healed with oral terbinafine 250 mg daily for four weeks. Dermatophyte infections in early stages may be misdiagnosed as psoriasis vulgaris and thus, prolonged use of corticosteroids can lead to tinea incognito. Therefore, cutaneous lesions unresponsive to topical corticosteroid treatment should be evaluated with microscopic examination and fungal culture to confirm a suspected dermatophyte infection. Past medical history can provide useful information but a complete dermatological examination should be performed before the final diagnosis is made.

Background: Seborrheic dermatitis is an inflammatory skin disease that affects 1–3% of the general population. The Malassezia species has been implicated as the main causative agent; however, the bacterial flora of the skin may also play role in the etiopathogenesis. Therefore, we investigated the most common bacterial agent of the skin flora of patients with seborrheic dermatitis. Materials and Methods: Fifty-one patients with seborrheic dermatitis and 50 healthy individuals are included in this study. Sterile cotton swabs were rubbed on the scalp of the participants for bacterial culture. Colonial morphology was identified with gram stain and catalase test. Results: Staphylococcus aureus was isolated from 25 (49%) patients with seborrheic dermatitis and 10 (20%) healthy individuals within the control group. Coagulase-negative staphylococci were isolated from 24 (47.1%) patients with seborrheic dermatitis and 17 (34%) healthy individuals within the control group. Diphtheroids were present in 2 (3.9%) patients and 1 (2%) subject within the control group. Gram-negative bacilli were present only in 1 (2%) patient. Hemolytic streptococci and bacilli were identified in 1 (2%) subject from each group. Colonization of coagulase-negative staphylococci, diphtheroids, gram-negative bacilli, hemolytic streptococci, and bacillus did not differ between patients and healthy controls. However, S. aureus colonization was significantly more common in patients with seborrheic dermatitis than in healthy controls. Conclusion: Within this study we revealed that S. aureus colonization was significantly higher among the patients. Therefore, we propose that, in addition to the Malassezia species, S. aureus may play a role in the etiopathogenesis of seborrheic dermatitis.

Objective: The objective of this study was to retrospectively analyze the clinical course and postoperative long-term survival of patients diagnosed with isolated left main coronary artery (LMCA) stenosis after surgical revascularization. Methods: A total of 38 patients (27 males, 11 females) who were diagnosed with isolated LMCA stenosis and underwent surgical revascularization were enrolled in the study. Isolated LMCA stenosis was classified into 2 groups: ostial stenosis and nonostial stenosis. Coronary events were defined as death of cardiac origin, the need for a new myocardial revascularization procedure, or the occurrence of myocardial infarction in the course of follow-up. The postoperative assessment period included short- and long-term follow-up. The study endpoint was defined as all-cause mortality. Results: Among the 38 patients who participated in the study, 25 suffered from ostial LMCA stenosis. The early postoperative mortality rate before hospital discharge was 2.6%. Median duration of postoperative long-term follow-up was 73.43 months (range: 0.17–187.23). Median duration of long-term follow-up free from coronary events or percutaneous coronary interventions was 73.43 months. Postoperative 2-year survival rate was 97.4%, and 5-year survival rate was 92.1%. The postoperative survival period and period free of coronary events of patients with isolated ostial LMCA stenosis did not differ significantly from those of patients with nonostial stenosis (p=0.801, p=0.970, respectively). Conclusion: Postoperative short- and long-term prognosis of isolated LMCA stenosis appears good in terms of mortality and coronary event symptoms.

Rical kitaplarında hadis senetlerindeki şahıslar ele alınmakta ve rical ilmi isnat ile başlamaktadır. bu sebeple makale öneceelikle isnat ilmi ile ilgili bilgi vermektedir. Daha sonra hadis ilminde çok önemli bir yeri olan rical ilminin tarihsel gelişimi, ilk rical kitapları, bu kitaplarda şahısların tertip ediliş şekilleri, biyografilerin sunuluşu ve rical kitaplarının hadis ve diğer İslami ilimlere nasıl hizmet ettiği üzerinde durulmuştur. Makalede, rical ilminin, kimlik bilgileri, tabakat bilgileri, belirli kitapların ve bölgelerin ricali, cerh ve tadil, mucem-meşyehat olmak üzere beş ana grupta toplanabileceğini belirterek bu bölümler hakkında bilgi verilmektedir.

OBJECTIVE: In heart failure (HF) patients, functional capacity has been demonstrated to be a marker of poor prognosis, independent of left ventricular ejection fraction (EF). Lymphocyte count is currently recognized in certain risk stratification scores for chronic HF, and severe HF is associated with lymphocytopenia. However, no data exists on the association between lymphocyte count and functional capacity in patients with stable HF. This study aimed to assess the relationship between lymphocyte count and New York Heart Association (NYHA) functional capacity in systolic HF outpatients. METHODS: The Turkish Research Team-HF (TREAT-HF) is a network which undertakes multi-center observational studies in HF. Data on 392 HF reduced ejection fraction (HFREF) patients from 8 HF centers are presented here. The patients were divided into two groups and compared: Group 1 comprised stable HFREF patients with mild symptoms (NYHA Class I-II), while Group 2 consisted of patients with NYHA Class III-IV symptoms. RESULTS: Patient mean age was 60+-14 years. Lymphocyte count was lower in patients with NYHA functional classes III and IV than in patients with NYHA functional classes I and II, (0.9 [0.6–1.5] x1000 versus 1.5 [0.7–2.2] x1000, p

Objective: In order to define the current characteristics of infective endocarditis (IE) in Turkey, we evaluated IE cases over a 14-year period in a tertiary referral hospital. Methods: All adult patients who were hospitalized in our hospital with a diagnosis of IE between 2000 and 2013 were included in the study. Modified Duke criteria were used for diagnosis. The Chi-square test, Student's t-test, Mann–Whitney U-test, Cox and logistic regression analysis were used for the statistical analysis. Results: There were 325 IE cases during the study period. The mean age of the patients was 47 years. Causative microorganisms were identified in 253 patients (77.8%) and included staphylococci (36%), streptococci (19%), enterococci (7%), and Brucella spp (5%). A streptococcal aetiology was associated with younger age (1.2 mg/dl (OR 2.15). Older age (>50 year) (OR 3.93), patients with perivalvular abscess (OR 9.18), being on dialysis (OR 6.22), and late prosthetic valve endocarditis (OR 3.15) were independent risk factors for enterococcal IE. Independent risk factors for mortality in IE cases were the following: being on dialysis (hazard ratio (HR) 4.13), presence of coronary artery heart disease (HR 2.09), central nervous system emboli (HR 2.33), and congestive heart failure (HR 2.15). Higher haemoglobin (HR 0.87) and platelet (HR 0.996) levels and surgical interventions for IE (HR 0. 33) were found to be protective factors against mortality. Conclusions: In Turkey, IE occurs in relatively young patients and Brucella spp should always be taken into consideration as a cause of this infection. We should first consider streptococci as the causative agents of IE in young patients, those with CRHD or congenital heart valve disease, and cases of community-acquired IE. Staphylococci should be considered first in the case of pacemaker lead IE, when there are high levels of creatinine, and in cases of healthcare-associated IE. Enterococci could be the most probable causative agent of IE particularly in patients aged >50 years, those on dialysis, those with late prosthetic valve IE, and those with a perivalvular abscess. The early diagnosis and treatment of IE before complications develop is crucial because the mortality rate is high among cases with serious complications. The prevention of bacteraemia with the measures available among chronic haemodialysis patients should be a priority because of the higher mortality rate of subsequent IE among this group of patients.

Familial multiple lipomatosis and familial multiple angiolipomatosis are both rare and autosomal-dominantly inherited diseases. Familial multiple lipomatosis is characterized by multiple lipomas on the trunk and extremities, while familial multiple angiolipomatosis presents with multiple angiolipomas. Hereby, we present a 50-year-old Caucasian male patient with both multiple lipomas and angiolipomas on his trunk, arms and thighs with a family history of similar subcutaneous lesions. As multiple lipomas and angiolipomas coexist in the same patient, we suggest that this condition should be nominated as a distinct entity rather than a traditional familial multiple lipomatosis case.

Sebaceous carcinoma is an uncommon malign tumor arising from sebaceous glands. Sebaceous carcinoma typically occurs on the eyelid as a slow growing, pink-yellow, painless subcutaneous papule or nodule. Although it is rare, sebaceous carcinoma can also be seen on head, neck, trunk, extremities, breasts, oral mucosa and external genitalia. Sebaceous carcinoma is a locally aggressive tumor, moreover it can metastasize to regional lymph nodes and distant organs. Hereby, we report a 91-year-old Caucasian female with sebaceous carcinoma on the forehead. The extraocular 1,9 cm large sebaceous carcinoma on the forehead was removed surgically with wide local excision under local anesthesia.

Objective: Trauma is one of the most important reasons of death in the pediatric age group. The aim of this study is to analyze the relation between the trauma type, trauma time, and the way of arrival to the hospital and to examine the causes of traumatic etiology and outcomes in the 0-6 age group (pre-primary) of trauma cases in our state.Material and Methods: Trauma cases in the 0-6 age group (pre-primary) who were admitted to the Cumhuriyet University Medical School Emergency Department between May 2009-May 2011 were evaluated.Results: In our study period, 799 children aged 0-6 were admitted to our emergency service; 55.8% of these patients were male. Most patients were mainly referred to the ER in July, August, and September, and the highest value was detected in July. Falls were first and motor vehicle accidents were second in frequency among the causes of injury.Conclusion: Consequently, traumas are showing an increase, especially in summer time, and it is observed that children are disregarded during farm works, and because of this, trauma numbers are being increased between the ages of 0-6 years.

Objectives: The genetic risk factors that contribute to the risk of developing aortic dissection (AD) have been studied. We assessed the association of endothelial nitric oxide synthase (eNOS) gene polymorphism with AD. Study design: Patients who underwent surgery with the diagnosis of AD and survived after the operation in our center between May 2007 and June 2011 were recruited retrospectively. The eNOS intron 4a/b polymorphism was determined by polymerase chain reaction (PCR) using oligonucleotide primers (sense: 5'-AGGCCCTATGGTAGTGCCTTT-3'; antisense: 5'-TCTCTTAGTGCTGTGGTCAC-3') that flank the region of the 27 bp VNTR in intron 4. Results: Thirty-nine patients (88%) had type A AD, while the remainder (12%) had type B AD. The distribution of eNOS4 a/b gene polymorphism differed significantly from the control group, with higher frequencies of eNOS 4a/a and 4a/b genotypes in the AD group (χ2=7.16, p=0.03). Conclusion: In this study, the distribution of eNOS genotypes differed between the AD and control groups; however, this polymorphism was not found to be an independent factor for the development of AD.

Orf is a viral zoonotic skin disorder which is also called ecthyma contagiosum. The disease primarily affects sheep and goats, however it can be transmitted to humans through close contact with infected animals. Orf presents with characteristic skin lesions and the diagnosis of orf is usually made based on its clinical features. Hereby, we present a 21-year-old female patient with orf disease with a characteristic clinical lesion on her hand.

Hypertensive emergency usually appears in older patients with previous recurrent episodes, and is among the most frequent admissions to emergency departments. A 29-year-old woman was referred to our clinic with the diagnosis of hypertensive emergency. The patient complained of severe headache, dyspnea, palpitation, diaphoresis, and confusion due to hypertensive encephalopathy. Her blood pressure was 250/150 mmHg on admission. At the referral hospital, the patient had undergone cranial CT because of her confused state and this excluded acute cerebral hemorrhage. Also at that hospital, thoracoabdominal CT for differential diagnosis depicted an adrenal mass with a necrotic core. After admission to our clinic, initial control of excessive blood pressure was not achieved despite high dose intravenous nitrate therapy. Thereafter intravenous esmolol treatment was initiated simultaneously with oral alpha blocker therapy in order to counterbalance the unopposed alpha adrenergic activity with beta blocker therapy. After 12 hours, sudden onset of hypotension developed and deepened despite IV saline, inotropic and vasopressor agents such as IV dopamine, noradrenaline and adrenaline. The patient died at the 24th hour due to hemodynamic collapse as a result of hyperadrenergic state due to possible pheochromocytoma crisis. This case is an exceptional example of hypertensive emergency secondary to fulminant pheochromocytoma crisis failing to respond to intensive antihypertensive treatment, and in which patient death was unavoidable due to uncontrolled excessive adrenergic activity which led to profound cardiogenic shock.

Objectives: The relationship between markers of myocardial ischemia and severity of coronary artery disease (CAD) has been investigated in several studies. In this study, we examined the relationship between severity of CAD and heart-type fatty acid-binding protein (H-FABP), a new marker of ischemia in patients with non-ST-segment elevation acute coronary syndrome (ACS). Study design: This prospective study comprised 49 patients who were referred to the emergency room with a diagnosis of non-ST elevation myocardial infarction. Troponins, creatine kinase-MB, lactate dehydrogenase, and aspartate aminotransferase levels were measured quantitatively, while blood H-FABP levels were measured qualitatively in the 4th- 8th hour from the onset of symptoms. All patients underwent coronary angiography within 72 hours after admission. Clinical and coronary angiographic characteristics of patients with positive and negative values of H-FABP were compared. Gensini and SYNTAX scores were used to determine the severity of CAD. Results: There were no statistically significant differences in mean age, gender distribution, risk factors for CAD, ischemic changes on ECG, or Gensini and SYNTAX scores between the H-FABP-negative and -positive groups (p>0.05). The duration of chest pain in the H-FABP-positive group was significantly longer than in the negative group (p