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  • Extracorporeal Membrane Oxygenation (ECMO)—A Lifesaving Technology. Review and Single-center Experience

    Objective: Extracorporeal membrane oxygenation is used to bypass the cardiopulmonary system in a severe heart or/and lung failure, mainly in intractable conditions where all other therapy options fail or are unfeasible. Extracorporeal membrane oxygenation (ECMO) is a well-established therapeutic option in such circumstances for neonatal, pediatric, and adult patients. Managing a patient with ECMO requires dedicated and specific management. The importance and necessity of this essential technology in life-threatening cardio-respiratory rescue prompted Rambam Health Care Campus to implement it and make it available as a service to the population in northern Israel. This article includes a brief review of extracorporeal life support and a report of our single-center experience since the establishment of the service. Methods: The ECMO unit was established in 2014 under the responsibility of the Cardiac Surgery Department. The ECMO service was initiated by a well-planned program with consideration of all aspects including economics, education and training, the specialist team and equipment needed, strategies for medication, and ethical challenges. Results: Between February 2014 and May 2018, 65 patients were treated with ECMO; 43 patients received veno-arterial ECMO for cardiac support (66%), while 22 received veno-venous ECMO for respiratory support (34%). The in-hospital mortality was 56%. Conclusions: Extracorporeal membrane oxygenation is an effective therapy that is constantly growing in use and provides a therapy that can replace previous options. To establish such a service requires a planned program and concerted effort. Our single-center experience presented a good learning curve and showed the feasibility as well as the efficacy of the ECMO procedure in life-threatening conditions.
  • Letter to the Editor: Delayed Presentation of Non-COVID-19 Patients During the COVID-19 Pandemic Is Not Limited to Children

    TO THE EDITOR We read with interest the report by Yeshayahu about four minors who were diagnosed late with non-COVID-19 diseases during the COVID-19 pandemic (Rambam Maimonides Med J 2021;12:e0017. doi: 10.5041/RMMJ.10431 ). We would like to emphasize that, firstly, such delays are not limited to minors, and secondly, that also in minors should we distinguish the administrative and the physiological meanings of the term “child” and hence distinguish administratively defined “chil¬dren” who bodily are already mature from those young patients who bodily are indeed still children.
  • Response to Letter to the Editor: Delayed Presentation of Non-COVID-19 Patients During the COVID-19 Pandemic Is Not Limited to Children

    TO THE EDITOR I read with interest the letter by Klaus Rose et al. regarding the article about delayed diagnosis of severe medical conditions during the coronavirus disease 2019 (COVID-19) pandemic.1 The author stressed the importance of recognizing that delayed presentation of patients, during the COVID-19 pandemic, was not limited to the pediatric population. I agree with this important point, and the article does not claim otherwise. The presented cases are pediatric, given that they took place in a pediatric department, but it is reasonable to assume that adults have faced the same challenges.
  • Human Papilloma Virus and Cancer Stem Cell markers in Oral Epithelial Dysplasia—An Immunohistochemical Study

    Objectives: To study the correlation between the putative cancer stem cell (CSC) markers aldehyde dehydrogenase 1 (ALDH1), cluster of differentiation 44 (CD44), sex-determining region Y-box 2 (SOX2), and octamer-binding protein 4 (OCT4) and human papilloma virus (HPV) infection using p16, the surrogate marker of HPV in oral epithelial dysplasia (OED) and normal mucosa. Methods: Five sections each from 40 histopathologically diagnosed cases of different grades of OED and 10 cases of normal oral mucosa without dysplasia were immunohistochemically stained with p16, ALDH1, CD44, SOX2, and OCT4, respectively. Results: Expression of ALDH1 and SOX2 was significantly increased in OED cases, whereas CD44 and OCT4 expression was increased in normal mucosa. P16-positive OED cases showed upregulation of ALDH1 and OCT4 expression as compared to p16-negative cases, while CD44 and SOX2 expression was downregulated in p16-positive OED cases; however, the results were not statistically significant. Conclusion: The present study indicated a suggestive link between p16 and cancer stem cell marker expression in HPV-associated OED, and that p16 has a significant role in CSC progression in OED. This is the first study to evaluate the expression of putative CSC markers in HPV-associated OED. However, low study numbers are a potential limiting factor in this study.
  • Response to Letter to the Editor: “First Admission Neutrophil–Lymphocyte Ratio May Indicate Acute Prognosis of Ischemic Stroke”

    We have carefully read and evaluated the letter writ¬ten by Drs Mungmunpuntipantip and Wiwanitkit regarding our article published in the July issue of Rambam Maimonides Medical Journal.
  • Factors Associated with Catch-up Growth in Term, Asymmetrical Small-for-Gestational Age Infants in the First Year of Life

    Introduction: Catch-up growth (CUG) in small-for-gestational age (SGA) infants is essential for their overall development. Knowledge about the factors influencing CUG might be critical in their effective management. Hence this study was performed with the aim of identifying factors that may influence CUG in SGA infants. Methods: Asymmetrical SGA infants born at term were included in the study as per defined criteria, and their demographic details were recorded. Anthropometric data, feeding practice details, and intercurrent illnesses data were collected on follow-up at 6 weeks, 6 months, and 12–15 months of age. Catch-up growth weight was defined as improvement of weight to the normal range of -2 to +2 weight-for-age Z score (WAZ). Analysis was carried out using SPSS Expand 17 software. Chi-square test was used to find association between variables. Logistic regression analysis was used to measure effect. A P value of less than 0.05 was taken as significant. Results: Out of 324 SGA infants born at term, 119 completed 12–15-month follow-up, of which 69.7% had achieved CUG weight. Exclusive breastfeeding >4 months, continued breastfeeding until 12–15 months, and absence of diarrheal episodes were positively associated with CUG. Pregnancy-induced hypertension, gestational diabetes, and maternal overweight/obesity were negatively associated with CUG. Maternal education status, conception age, gravida status, mode of delivery, vitamin D and iron supplementation, and intercurrent respiratory infections were not associated with CUG. On multivariate analysis, continued breastfeeding and absence of diarrheal episodes were independent factors associated with CUG. Conclusion: Breastfeeding practice, especially continued breastfeeding, and the absence of diarrheal illness are the key determinants for achieving CUG weight in term SGA infants, particularly in settings where resources are limited.
  • Eosinophil Cell Count Predicts Mortality in the Intensive Care Unit after Return of Spontaneous Circulation

    Background: Eosinophils constitute 1%–5% of peripheral blood leukocytes, less in the presence of acute infections (referred to as eosinopenia). Studies indicate that eosinopenia can be used as a prognostic predictor for chronic obstructive pulmonary disease exacerbation, sepsis, or acute myocardial infarction disease. There are only a few studies about predicting mortality in emergency departments and intensive care units (ICUs). Prognostic studies about patients in ICUs are generally carried out using different scoring systems. We aimed to analyze if the eosinophil count can estimate the prognosis among non-traumatic patients who underwent cardiopulmonary resuscitation and were hospitalized in ICU thereafter. Methods: The data were evaluated of 865 non-traumatic adult patients (>18 years of age) who were admitted with cardiopulmonary arrest or developed cardiopulmonary arrest during clinical follow-ups. Admission venous blood sample tests, complete blood count, and biochemical laboratory results were recorded. Arterial blood gas results were also evaluated. The mean results of the recorded laboratory results were compared between the surviving and non-surviving patients groups. Results: There was a significant difference between the two groups in regard to platelet, eosinophil count, pH, PaO2, SaO2, and HCO3- (P<0.001 for all). In the multiple linear regression analysis, eosinophil counts were found to be an independent factor (odds ratio=0.03, 95% confidence interval 0.33–0.56, P<0.001) associated with the mortality after cardiopulmonary resuscitation. Conclusion: Because admission eosinophil counts can be measured easily, they are inexpensive biomarkers that can be used for predicting the prognosis among the patients who have return of spontaneous circulation and are treated in ICUs.
  • Can Endoscopic Appearance, Selective Cytology, and Pathological Sampling During Ureteroscopy Accurately Predict Tumor Grade of Upper-Tract Urothelial Carcinoma?

    Objective: This study examined the reliability of the various parameters obtained in diagnostic ureteroscopy for upper-tract urothelial carcinoma (UTUC) in predicting the degree of differentiation in the final pathological report after radical nephroureterectomy (RNU). Methods: We conducted a retrospective review of patients undergoing RNU at a single tertiary hospital between 2000 and 2020. Only patients who underwent preoperative diagnostic ureteroscopy (URS) were included. The results of urine selective cytology, endoscopic appearance of the tumor, and biopsy taken during ureteroscopy were compared to the final pathological report. Results: In total, 111 patients underwent RNU. A preliminary URS was performed in 54. According to endoscopic appearance, 40% of the “solid”-looking tumors were high grade (HG), while 52% of those with a papillary appearance were low grade (LG). Positive cytology predicted HG tumors in 86% of cases. However, 42% of patients with negative cytology had HG disease. The biopsies acquired during URS showed that HG disease findings matched the final pathology in 75% of cases. However, 25% of patients noted as being HG, based on URS biopsies, were noted to have LG disease based on nephroureterectomy biopsies. Full analyses revealed that 40% of the cases diagnosed as LG based on the URS biopsies actually had HG disease. Conclusions: Direct tumor observation of papillary lesions, negative cytology, and biopsies indicating LG disease are of low predictive value for classifying the actual degree of tumor differentiation. No single test can accurately rule out HG disease. In light of the rising use of neo-adjuvant chemotherapy in UTUC, a reliable predictive model should be developed that accurately discriminates between HG and LG disease.
  • COVID-19 and Preeclampsia: Overlapping Features in Pregnancy

    Coronavirus disease 2019 (COVID-19) is a global respiratory disease with unique features that have placed all medical professionals in an alarming situation. Preeclampsia is a hypertensive disorder of pregnancy affecting 8%–10% of India’s pregnant population. Assuming that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells through the angiotensin-converting enzyme 2 (ACE2) receptor, the resulting symptoms are due to vasoconstriction, caused by disturbances in the renin–angiotensin system (RAS). Other features of preeclampsia include endothelial dysfunction due to placental ischemia, leading to imbalances in angiogenic and antiangiogenic factors which result in increased blood pressure, proteinuria, altered hepatic enzymes, renal failure, and thrombocytopenia, amongst others. The increased prevalence of preeclampsia that was seen among mothers with SARS-CoV-2 infection might be due to misdiagnosis, as COVID-19 and preeclampsia have coincidental medical features. The major similarities of SARS-CoV-2-infected and preeclamptic women are a rise in pro-inflammatory cytokines, and increased serum ferritin and thrombocytopenia. Therefore, differential diagnosis might be difficult in pregnant women with COVID-19 who present with hypertension and proteinuria, thrombocytopenia, or elevated liver enzymes. The most promising markers for earlier diagnosis of preeclampsia is soluble endoglin (sEng), pregnancy-associated plasma protein-A (PAPP-A), soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF). Due to placental hypoxia, sFlt-1 will be overproduced, thus inhibiting PlGF, and this alteration will be observed in the circulation five weeks or more before the onset of symptoms. The sFlt-1/PlGF ratio may also be modified via infectious states, but unregulated levels of those mediators are related to placental insufficiency. Hence, pregnant women with COVID-19 may develop a preeclampsia-like syndrome that might be differentiated properly by angiogenic markers to avoid unnecessary interventions and induced preterm labor.
  • Nailfold Videocapillaroscopy in Connective Tissue Diseases with Raynaud’s Phenomenon in an Indian Population

    Introduction: Microvasculopathy is characterized by progressive structural and functional damage to the microvessels and plays a key role in the pathogenesis of various connective tissue diseases (CTD). Nailfold videocapillaroscopy is an optimal and validated method for analysis of microvascular abnormalities and is able to differentiate secondary Raynaud’s phenomenon (RP) of CTD from primary RP and healthy subjects. Aim: To assess and analyze nailfold capillaroscopic findings in Indian subjects with secondary Raynaud and to compare with findings in healthy subjects. Methods: A total of 62 study participants including cases and controls underwent nailfold videocapil-laroscopy. Capillary loop length, capillary width, capillary density, presence/absence of tortuosity, giant loops, neoangiogenesis, microhemorrhages, and avascular areas were the parameters studied. Results: All the quantitative and qualitative parameters studied were significantly associated with second¬ary RP. Mean loop length in cases of connective tissue diseases was significantly less than in the controls (225.74 µm versus 282.97 µm) (P=0.002). Capillary density was also reduced significantly in the cases as compared to the controls (4.6 versus 7.39/mm) (P<0.01), whereas it was markedly decreased in systemic sclerosis (SSc) and mixed connective tissue diseases (MCTD), and near normal in systemic lupus erythematosus (SLE). Tortuosity was the most frequent (77.4%) qualitative parameter. Scleroderma pattern was found in 62.5% of patients with SSc and in 60% with MCTD. Non-specific pattern was found in 80% of SLE cases and 50% of dermatomyositis cases. Conclusion: Both quantitative and qualitative capillaroscopic changes are significantly associated with secondary RP. Scleroderma pattern was predominant in SSc and MCTD, whereas non-specific pattern was predominantly found in SLE and dermatomyositis.