High Risk For Development Research Articles

Occupational stress in healthcare workers during a COVID-19 pandemic

Healthcare workers experience overwhelming occupational and psycho-emotional stress during COVID-19 pandemic. Occupational stress leads to emotional burnout, can cause anxiety, depression and other psychopathological symptoms, influencing the quality of medical care. Existing situation necessitates to define risk factors, influencing occupational stress in healthcare workers in order to develop ways and methods to overcome it. Aim of the study was to identify socio-psychological factors associated with occupational stress in healthcare workers during the COVID-19 epidemic in Ukraine. Using a specially designed questionnaire, an online survey of 1,100 medical workers was conducted in all regions of Ukraine. Questioning was carried out over three weeks from 30.03.2020 to 21.04.2020, during the period of quarantine. The majority of respondents were female medical workers (79.9%). Age of respondents: up to 30 years – 179 (16.2%), from 31 to 60 – 824 (75.0%), over 60 – 97 (8.8%), among them doctors – 695 (63.1%) 236 nurses (21.5%), more than a third are general practitioners. Direct care for patients with COVID-19 was provided by 170 (15.5%) medical personnel. The analysis of the results of the questionnaire enabled to determine the peculiarities of medical worker`s response to the situation in connection with COVID-19 and highlight the emotional and behavioral factors associated with stress that are significant for most respondents. The study answered the questions regarding the perceived risk associated with the spread, contamination and death related to coronavirus. The most significant factors affecting the occurrence of stress in medical workers are identified. Along with this, factors contributing to stress coping have been identified as well. For subsequent statistical processing, all respondents were divided into two groups depending on the severity of the anxiety/fear. Comparison of these groups by socio-demographic indicators was done using the test χ2. There were no statistically significant differences between groups in all socio-demographic indicators, except for age. That is, only the age factor affected the severity of anxiety/fear among healthcare workers due to COVID-19 (p<0.05). Comparative analysis to assess the severity of stress in groups was performed using the Mann-Whitney U test. Healthcare workers with severe anxiety/fear have a high risk for development of occupational stress during a COVID-19 pandemic (p<0.01). In conclusion, the need for the development and implementation of methods for the prevention of occupational stress in medical workers in the current epidemic situation is substantiated.

Novel PTCH1 and concurrent TP53 mutations in four patients with numerous non-syndromic basal cell carcinomas: The paradigm of oncogenic synergy.

There has been a significant increase in basal cell carcinoma (BCC) incidence, the most common cancer in humans and the age of presentation with the first diagnosis of BCC has decreased in past decades. In this study, we investigated the possibility of genetic markers that can lead to earlier and closer observation of patients at high risk for development of multiple BCCs. The overall goal is to decrease the morbidity and the economic burden of diagnosis and treatment of recurring and/or advanced BCCs. Four patients with numerous BCCs, some of them exceptionally large, were included in this study. A sample of representative BCCs, normal non-sun-exposed skin and blood samples were obtained from each patient. Whole-exome sequencing of DNA was conducted on all samples, and a series of bioinformatics filtering was performed to identify potentially pathogenic sequence variants. The analysis of the data resulted in detection of oncogenic mutations in PTCH1, two of which being novel, and concurrent mutations in TP53 in BCC tumours of all four patients. Such mutations may explain the numerous and postexcision recurring nature of the BCCs of exceptionally large size observed in all these patients, and they can be suggested to serve as a genetic marker for high-risk patients for early detection, prognostication and close follow-up.

Role of the <i>GRIN1</i> gene polymorphism in the formation of post-traumatic epilepsy

Introduction: NMDA receptors are involved in the pathogenesis of seizures, as it subunit is coded for by the GRIN1 gene. Different GRIN1 mutations are known in patients with different forms of epilepsy and encephalopathy. However, no data are available on the participation of the GRIN1 gene and its polymorphisms in the development of post-traumatic epilepsy (PTE). Aim: To determine the influence of single-nucleotide rs1126442 polymorphism of GRIN1 on the risk of PTE formation. Materials and methods: A total of 140 patients were examined, which included 69 patients with PTE and 71 patients with genetic epilepsy. All patients underwent a comprehensive examination, with evaluation of history, neurological status, electroencephalography (EEG) and neuroimaging results, and genotyping of blood samples by real-time polymerase chain reaction. The control sample for genetic examination was venous blood from 60 healthy individuals. Results: Focal seizures with transition to bilateral and tonicclonic seizures were predominant in the PTE group. Neuroimaging revealed dystrophic, cystic, and cystogliotic alterations and signs of external hydrocephaly. EEG recorded interictal and ictal epileptiform activity and slowing of theta waves. Genotyping by rs1126442 polymorphism of GRIN1 revealed predominance of heterozygous G/A and homozygous A/A genotypes in patients with PTE in the codominant (odds ratio (OD)=3.43; 95% confidence index (CI) 1.567.55; p=0.0047), dominant (OR=3.24; 95% CI 1.576.68; p=0.0011), and superdominant (OR=2.90; 95% CI 1.366.22; p=0.0048) inheritance models. The carriage of heterozygous G/A rs1126442 genotype of GRIN1 was associated with an epileptiform activity in the EEG of all patients with epilepsy (OR=2.40; 95% CI 1.115.20; p=0.024). Conclusion: The carriage of heterozygous G/A genotype and homozygous A/A rs 1126442 genotype of GRIN1 in the dominant and codominant inheritance models is associated with a high risk of development of epilepsy after craniocerebral trauma. The carriage of heterozygous G/A rs 1126442 genotype of GRIN1 is associated with an epileptiform activity in EEG.

Women and ethnoracial minorities with poor cardiovascular health measures associated with a higher risk of developing mood disorder

BackgroundMood disorders (MDS) are a type of mental health illness that effects millions of people in the United States. Early prediction of MDS can give providers greater opportunity to treat these disorders. We hypothesized that longitudinal cardiovascular health (CVH) measurements would be informative for MDS prediction.MethodsTo test this hypothesis, the American Heart Association’s Guideline Advantage (TGA) dataset was used, which contained longitudinal EHR from 70 outpatient clinics. The statistical analysis and machine learning models were employed to identify the associations of the MDS and the longitudinal CVH metrics and other confounding factors.ResultsPatients diagnosed with MDS consistently had a higher proportion of poor CVH compared to patients without MDS, with the largest difference between groups for Body mass index (BMI) and Smoking. Race and gender were associated with status of CVH metrics. Approximate 46% female patients with MDS had a poor hemoglobin A1C compared to 44% of those without MDS; 62% of those with MDS had poor BMI compared to 47% of those without MDS; 59% of those with MDS had poor blood pressure (BP) compared to 43% of those without MDS; and 43% of those with MDS were current smokers compared to 17% of those without MDS.ConclusionsWomen and ethnoracial minorities with poor cardiovascular health measures were associated with a higher risk of development of MDS, which indicated the high utility for using routine medical records data collected in care to improve detection and treatment for MDS among patients with poor CVH.

Extensive bilateral diffuse infiltrates and deterioration of lung following infection with severe acute respiratory syndrome coronavirus 2 in a pregnant woman: a case report

IntroductionSevere acute respiratory syndrome coronavirus 2 is the third member of the coronavirus family to cause global concern in the twenty-first century. Pregnant women are particularly at higher risk of developing severe viral pneumonia, possibly because of a partial immune suppression during their pregnancy. Under such critical and rapidly evolving circumstances, these poor findings might be helpful for the treatment of infected pregnant women with the 2019 novel coronavirus.Case presentationIn this study, we report the case of a 33-year-old Asian pregnant woman at 25 gestational weeks with coronavirus disease 2019 who developed severe complications, including hypoxemia, acute respiratory distress syndrome, pulmonary infiltration, and bilateral pleural effusion. She died 1 month after admission to the hospital.ConclusionPregnant populations are especially at higher risk of viral pneumonia development caused by severe acute respiratory syndrome coronavirus 2. Further research on the prevention and treatment of the new coronavirus is necessary.

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BACKGROUND p53 mutation and Rb over-expression have been extensively studied in oral squamous cell carcinoma (OSCC) but their clinical relevance with respect to excision margins is still controversial. The purpose of the study was to determine the expression of molecular markers (p53& Rb) for predicting early locoregional recurrence in oral cancer. METHODS Histopathological specimens of 93 patients of oral cavity squamous cell carcinoma were subjected to p53 mutation and Rb protein testing in tumour and at the closest negative margin on H &E using immunohistochemistry. The expression of p53 and Rb in tumour tissue and at excision margin was correlated with clinicopathologic parameters recurrence and survival over a 2 year follow up period. RESULTS p53 mutation expression in tumour tissue was associated with increased recurrence (22.5 % versus 11.3 % P = 0.13) and mortality (17.5 % versus 5.6 % P = 0.056). p53 expression at margins is also associated with higher recurrence and mortality. Rb overexpression in tumour tissue is not significantly associated with recurrence (15 % and 16.4 %). Rb overexpression at margins had higher recurrence (40 %; P = 0.627) and higher mortality (60 %) in comparison to Rb negative cases (16.4 %versus 6.8 % respectively). CONCLUSIONS Clinical and routine histopathological assessments of margins remain the standard method of prognosticating and planning adjuvant treatment. Determination of molecular positive margins using p53 & Rb in oral cancer may aid in identifying patients at high risk of development of recurrence despite negative pathological margins. KEYWORDS Rb, Margin, P53, Recurrence.

Analysis of adherence to therapy and compliance of outpatient treatment with the EURO FORTA system in elderly and senile polymorbid patients with CHF

Abstract Introduction Chronic heart failure (CHF) is one of the main reasons for hospitalization in the elderly. Various scales and algorithms have been proposed to combat polypharmacy. Purpose To assess adherence to therapy and compliance of outpatient treatment with the EURO FORTA system. Methods The study included 313 patients admitted to the city center for the treatment of CHF from February 1, 2019 to October 1, 2020 at the age of 75±8.22 years. In all patients, the Charlson comorbidity index and the number of diseases (1–2, 3–5, >5) were calculated. Outpatient treatment was assessed according to the EURO FORTA system (2018) in patients (over 65 years old – n=274, over 60 years old and ≥6 drugs – n=39) with CHF depending on the level of polymorbidity, age, sex, CHF variant and its severity. Heart failure was diagnosed in 66.77% of patients with preserved ejection fraction (EF), in 19.81% – with intermediate, in 13.42% - with low. Results Depending on the class of drugs according to the EURO FORTA system, 5 groups of patients were identified: 1st (received only class A drugs) – 3.51% of patients; 2nd (A, B)-22.36%; 3rd (A, B and C)-17.25%; 4th (A, B, C and D) – 27.17%; 5th – not taking medications on an outpatient basis 29.71%. In almost all groups at the outpatient stage, patients with>5 diseases (pmg=0.020) prevailed (45.46–70.59%). At the outpatient stage in groups 1, 3 and 4 there were more patients with stage IIB CHF (63.64%, 51.86% and 47.06%) pmg=0.041, and in groups 2 and 5 – patients with stage IIA (58, 57% and 48.39%). Class C: digoxin (n=4, patients with atrial fibrillation (AF) and CHF), amiodarone (n=3, patients with AF), moxonidine (n=1, patient with hypertension), betablockers 3 years after myocardial infarction (MI) (n=2), spironolactone (n=23, CHF). Reception of spironolactone on an outpatient basis was associated with a high risk of developing acute kidney injury (AKI) p=0.01, AKI in CKD p=0.042, and AF p=0.03. Class D: non-steroidal anti-inflammatory drugs (NSAIDs) (n=68), aspirin for AF (n=2), class I-III antiarrhythmics (except amiodarone) (n=8), glibenclamide (n=1), nondihydropyridine calcium antagonists (n=2, patients with hypertension), dihydropyridine antagonists (n=1, with ischemic heart disease 3 years after MI). Taking NSAIDs on an outpatient basis was associated with a high risk of AKI development p=0.033, as well as anemia p=0.036, including grade 3 and 4 anemia (WHO) p=0.042. Conclusion Every second patient with CHF had more than 5 diseases. Every third person did not take drug therapy at the outpatient stage. The frequency of taking drugs of classes C and D was higher in polymorbid patients. With a more severe course of CHF, patients more often took class D drugs. Among class D were NSAIDs (80%) and class I-III antiarrhythmics (except amiodarone) (9.4%) prevailed. The use of spironolactone on an outpatient basis was associated with a high risk of AKI and AF, and NSAIDs-with AKI and anemia. Funding Acknowledgement Type of funding sources: None.

Implementing placental-growth-factor (PLGF) measurements in suspected pre-eclampsia----Challenges in clinical practice

ObjectivesAs a part of NHS’ Innovation and Technology Payment programme (ITP), pregnant women were offered Placental Growth Factor (PLGF)-based testing to help rule out pre-eclampsia (PET) – a serious condition that affects approximately 2.3% of the female population. The study was aimed to evaluate the implementation of PLGF-based testing at United Lincolnshire Trust Hospitals (ULHT). Study DesignThe soluble FMS like Tyrosine kinase 1/placental growth factor (sFlt-1/PLGF) ratio test was launched at ULHT on 8th October 2020. The project involved a review of an electronic maternity database (MEDWAY) for all women who had sFLT-1/PLGF ratio test performed at ULHT over a 5-month period (October 2020-February 2021). The sFlt-1/PLGF ratio was recorded alongside clinical outcome. Women were classified as low, moderate, and high risk for development of PET if the sFlt-1/PLGF ratio was ≤ 38, 39–84 and ≥ 85 respectively. Reasons for admission were further investigated and adherence to the sFLT-1/PLGF protocol was monitored to evaluate staff performance. Data was then statistically analysed with χ2 and T-test for categorical and continuous variables respectively. Finally, sensitivity and specificity of the sFLT-1/PLGF was assessed with an ROC curve. ResultsA total of 236 women had sFlt-1/PLGF ratio test performed in a five-month period. A two-time point analysis (a “during implementation” and “post implementation phase”) showed a significant decrease in the admission rates in the post-implementation phase in low-risk group (28.5% during implementation vs 11.3% post-implementation, P < 0.05). Further analysis showed greater staff adherence to the sFLT-1/PLGF protocol in the post-implementation period. The high-risk group demonstrated shorter time from test to delivery, earlier gestational age at delivery and lower birth weight (P < 0.05). ConclusionsThe study outcomes resulted in a successful submission of a business case. Successful triage of low-risk women at the point where historically admissions were considered reduced clinical workload and enabled better utilisation of resources by allowing focussed care on high-risk women for an optimal maternal and perinatal outcome.

Transcription Factor 7-Like-2 (TCF7L2) rs7903146 (C/T) Polymorphism in Patients with Type 2 Diabetes Mellitus

Abstract Background Type 2 diabetes mellitus (T2DM) is a heterogeneous group of metabolic disorders characterized by the incapability of pancreatic beta cells to increase insulin secretion to compensate for insulin resistance in the peripheral tissues. T2DM is a multi-factorial disease including several environmental factors with the presence of genetic predisposition. The transcription factor 7-like-2 gene (TCF7L2) rs7903146 (C/T) polymorphism is one of the most susceptible genes to T2DM discovered to date, with contribution to the disease through the Wnt/β –catenin signaling pathway affecting pancreatic islet development, expression of several genes involved in insulin granules exocytosis and the incretin glucagon-like peptide 1 (GLP-1) gene. Aim of the Work In this study we aimed to investigate the potential association of the transcription factor 7-like-2 (TCF7L2) rs7903146 (C/T) gene polymorphism in patients with type 2 diabetes mellitus. Patients and Methods The study was a case- control study conducted on 70 T2DM patients recruited from the endocrinology clinic at Ain Shams University Hospitals, and 30 non diabetic healthy controls matched with the patients in age and sex. All subjects underwent full history taking, thorough clinical examination, routine laboratory investigations including haemoglobin A1c (HbA1c), lipid profile; total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) and determination of TCF7L2 gene polymorphism by real-time quantitative polymerase chain reaction (RT-PCR). Results The minor T allele of the rs7903146(C/T) SNP was associated with high risk of development of T2DM with an OR of 1.35 (95% CI: 0.68-2.6), the heterozygous genotype (CT) with an OR 1.16 (95% CI: 0.49-2.7) and the homozygous mutant genotype (TT) with OR of 3.16 (95% CI: 0.15-6.31), however, they were statistically insignificant (p-value &amp;gt;0.05). Conclusion Our study did not confirm the presence of significant association between the TCF7L2 rs7903146(C/T) polymorphism and T2DM, however, it pointed to the possibility of presence of high risk of development of T2DM in patients with TT genotype. Further studies with higher sample size are needed to clarify the association.

SECONDARY BACTERIAL INFECTION WITH MULTIDRUG-RESISTANT PATHOGENS WAS COMMON IN INTUBATED CRITICALLY ILL PATIENTS WITH COVID-19: WHAT ARE PREDICTORS FOR POOR OUTCOMES?

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: The aim of this study was to determine the risk factors for poor outcomes in intubated, critically ill patients with COVID-19 with multi-drug-resistant pathogens associated secondary bacterial pneumonia. METHODS: This study was restrospective, observational study of 109 crtitcally ill intubated patients with COVID-19 at the intensive care unit(ICU) university hospital from 01 of July to 30 December 2021. RESULTS: In 53 of 109 intubated patients (48.0%) have identified the secondary bacterial infection after 48 hours of intubation and common risk factors associated with invasive mechanical ventilation in patients were:age(p<0.001);lack of use of high nasal cannula(p<0.004);high level of D-dimer(p<0.002);lymphopenia(p<0.001);and low albumin level (p<0.003).Multi-drug-resistant (MDR)pathogens were identified in 37 of 53 patients with ventilator-associated pneumonia(71.0%). In patients with VAP mixed ground glasses/consolidative radiological pattern was common compared to intubated but non-VAP patients(p<0.001).However, in patients with MDR pathogen associated VAP local lung complications such as pleural effusions and lung destructions were commonest compared to non-MDR pathogen associated VAP(p<0.001 and <0.0001;respectively).Among MDR pathogens commonest were:Acinotebacter baumanii(37.0%);Pseudomonas aeruginosa(29.0%) and MRSA(18.0%).MDR pathogen related to VAP in patients was associated with more high median SOFA score (p<0.001) and severe sepsis and septic shock was higher compared to non-MDR VAP patients( OR 4.67 [0.98-8.94]95%CI;p<0.01) and patients with MDR VAP were more resistant to the ventilatory support and their median PaO2/FiO2 was 132(89-194) which was significantly lower compared to non-MDR VAP patients(171[120-254];p<0.001).Serum lactete level, serun creatinine level(acute kidney failure), and serum D-dimer level were significantly higher compared to non-MDR VAP patients(p<0.001 for all three data respectively).Overall mortality rate among intubated patients was 58.0%(64 of 109), however, secondary bacterial infection was associated with higher mortality rate compared to non-VAP patients(73.0% vs 44.0%;p<0.05).MDR pathogen related to VAP patients were characterized with higher in -hopspital mortality compared to non-MDR pathogen related to VAP patients(81.0%vs 52.0%;p<0.05) CONCLUSIONS: Intubated and critically ill patients with COVID-19 are at high risk for development of ventilator -associated pneumonia and commonly such pneumonias are associated with MDR pathogens.Secondary MDR pathogen associated infection in intubated patients commonly is associated with severe sepsis and septick shock, kidney failure and among local lung complications with pleural effusions and lung destructions.MDR pathogents in such patients associated with increased risk of in-hospital mortality. CLINICAL IMPLICATIONS: Critical care physicians, respiratory therapist, nurses, pulmonologists, intensivist DISCLOSURES: no disclosure on file for Pari Khoshbanyani;No relevant relationships by Alizaman Sadigov, source=Web Response no disclosure on file for Bayram Tagiyev;

The impact of constant antibiotic prophylaxis in children affected by spinal dysraphism performing clean intermittent catheterization: a 2-year monocentric retrospective analysis

IntroductionSpinal dysraphism (SD) is a general term used to refer to developmental abnormalities of the spine that involves many clinical conditions including myelomeningocele (MMC). In these patients, neurogenic bladder (NB) is a common and predisposing factor for renal damage; the most frequently used approach to manage this situation is based on clean intermittent catheterization (CIC) and anticholinergic drugs. Urinary tract infections (UTIs) are a significant concern for these patients, and antibiotic prophylaxis is frequently used even if it is still a debated topic of literature. The purpose of this paper is to investigate the role and the real effectiveness of antibiotic prophylaxis in the reduction of incidence of UTIs in patients with spina bifida performing CIC.MethodsWe collected data of all patients performing CIC, who did their last follow-up visit in the period between January 2019 and January 2021, followed at the children multidisciplinary Spina Bifida Center of A. Gemelli Hospital in Rome. Data collected included age at referral, gender, type of SD lesion, serum creatinine and cystatin C levels, the use of anticholinergic medications, antibiotic prophylaxis and type of prophylaxis (oral/endovesical), age of starting prophylaxis with its duration/adherence, number of CIC/day and its duration, episodes of UTIs in the 2 years prior to the last follow-up, and presence and grade of vesical-ureteric reflux (VUR) on cystourethrogram.ResultsA total of 121 patients with SD performing CIC was included in the study; 66 (54%) presented ≥ 1 episode of UTIs in the last two years and 55 (46%) none. During the study period, 85 (70%) patients received antibiotic prophylaxis (ABP group) and 36 (30%) did not (NABP group): no statistically significative difference in terms of UTI development was observed between the two groups (p = 0.17). We also evaluated compliance to the therapy; 71 patients (59%) took antibiotic prophylaxis constantly (CABP group) and 50 (41%) did not do antibiotic prophylaxis constantly or did not do antibiotic prophylaxis at all (NCABP group): we observed a statistically significative difference in terms of UTIs with a 2.2 times higher risk of development at least one episode of UTIs in NCABP group.ConclusionIn conclusion, antibiotic prophylaxis performed constantly, without interruption, is associated with a lower risk of developing urinary tract infections and consequently to develop renal failure in adulthood.

Эпидемиологические аспекты сахарного диабета в г. Ташкенте на основании данных регистра

Цель исследования — анализ эпидемиологических аспектов сахарного диабета (СД) 1-го и 2-го типов в г. Ташкенте. Материалы и методы. Анализ регистра СД проведен на основании карт-регистров в г. Ташкенте. Для этого была использована унифицированная карта национального регистра, разработанная сотрудниками центра с учетом рекомендаций Европейской ассоциации по изучению СД и опыта других стран. В г. Ташкенте зарегистрировано 16 356 больных, их данные были введены в специализированную компьютерную программу и обработаны соответствующим образом. Проанализировано течение болезни и лечение состоящих на учете больных, среди которых 1225 страдали СД 1-го типа, 15 131 — СД 2-го типа. Результаты. В городе на учете состоит 1225 пациентов с СД 1-го типа, что составляет 7,5 % всей популяции с СД. Средний уровень гликемии натощак составил 10,9 ммоль/л при СД 1-го типа и 8,8 ммоль/л — при СД 2-го типа. Определение общего холестерина (ОХС) проведено лишь у 3144 (20,8 %) больных, из них у 2380 (91,4 %) уровень ОХС был более 4,8 ммоль/л. Содержание триглицеридов определяли всего у 507 (3,34 %) больных, из них у 374 (91,9 %) их уровень был более 1,7 ммоль/л. Выводы. Подавляющее большинство пациентов с СД находится в состоянии декомпенсации по показателям контроля гликемии. На сегодняшний день оказание лечебно-профилактической помощи больным СД в Ташкенте не соответствует современным критериям, в силу чего высок риск развития и прогрессирования как сердечно-сосудистых заболеваний, так и хронических микрососудистых диабетических осложнений.

Classification and Reliability of Lumbar Facet Cysts Grading Scales

The presence of symptomatic lumbar facet cysts has been associated with segmental instability. Given this association, decompression versus decompression with fusion is a frequently debated topic. Multiple grading scales have been devised to identify patients at high risk for development of cyst recurrence; however, there exists no external evaluation of these scales. A retrospective review of 54 patients undergoing initial treatment for lumbar synovial cysts at a single institution over the past 12 years was conducted. Surgical treatment consisted of decompression with cystectomy without fusion. Patients were assessed and classified according to the NeuroSpine Surgery Research Group (NSURG) and Rosenstock Classification systems. Five neurosurgeons reviewed the preoperative magnetic resonance images, and results were classified. Interrater reliability was assessed using both Gwet's AC1 coefficient and Krippendorff's alpha. A 1-way analysis of variance was used to evaluate predictive ability of both classification systems. In total, of the 54 patients who underwent decompression, 7 had cyst recurrence. Overall cyst recurrence was most common in NSURG grade 2 cysts (3/12, 25%) followed by grade 1 cysts (4/27, 14.8%). Of the NSURG grade 3 and 4 patients, none had cyst recurrence. In the Rosenstock grades the most common recurrence was in grade 3 cysts (1/4, 25%) followed by grade 1 cysts (5/26, 19.2%). Interrater reliability demonstrated good reproducibility on Gwet's AC1 and Krippendorff's alpha on both grading scales. Neither score was predictive of cyst recurrence (P > 0.05). The Rosenstock and NeuroSpine scores demonstrate good overall interrater reliability but are inconsistent in their ability to predict recurrence of lumbar facet cysts.

Acute Liver Failure: Indian Perspective.

Acute Liver Failure: Indian Perspective.

High-dose thoracic radiation therapy for non-small cell lung cancer: a novel grading scale of radiation-induced lung injury for symptomatic radiation pneumonitis

BackgroundSymptomatic radiation pneumonitis (RP) may be a serious complication after thoracic radiation therapy (RT) for non-small cell lung cancer (NSCLC). This prospective observational study sought to evaluate the utility of a novel radiation-induced lung injury (RILI) grading scale (RGS) for the prediction of RP.Materials and methodsData of 41 patients with NSCLC treated with thoracic RT of 60–66 Gy were analysed. CT scans were scheduled before RT, one month post-RT, and every three months thereafter for one year. Symptomatic RP was defined as Common Terminology Criteria for Adverse Events grade ≥ 2. RGS grading ranged from 0 to 3. The inter-observer variability of the RGS was assessed by four senior radiologists. CT scans performed 28 ± 10 days after RT were used to analyse the predictive value of the RGS. The change in the RGS severity was correlated to dosimetric parameters.ResultsThe CT obtained one month post-RT showed RILI in 36 (88%) of patients (RGS grade 0 [5 patients], 1 [25 patients], 2 [6 patients], and 3 [5 patients]). The inter-observer agreement of the RGS grading was high (Kendall’s W coefficient of concordance = 0.80, p < 0.01). Patients with RGS grades 2–3 had a significantly higher risk for development of RP (relative risk (RR): 2.4, 95% CI 1.6–3.7, p < 0.01) and RP symptoms within 8 weeks after RT (RR: 4.8, 95% CI 1.3–17.6, p < 0.01) compared to RGS grades 0–1. The specificity and sensitivity of the RGS grades 2–3 in predicting symptomatic RP was 100% (95% CI 80.5–100%) and 45.4% (95% CI 24.4–67.8%), respectively. Increase in RGS severity correlated to mean lung dose and the percentage of the total lung volume receiving 5 Gy.ConclusionsThe RGS is a simple radiologic tool associated with symptomatic RP. A validation study is warranted.

Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.

Change in Blood and Benign Breast Biomarkers in Women Undergoing a Weight-Loss Intervention Randomized to High-Dose ω-3 Fatty Acids versus Placebo.

The inflammation-resolving and insulin-sensitizing properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids have potential to augment effects of weight loss on breast cancer risk. In a feasibility study, 46 peri/postmenopausal women at increased risk for breast cancer with a body mass index (BMI) of 28 kg/m2 or greater were randomized to 3.25 g/day combined EPA and DHA (ω-3-FA) or placebo concomitantly with initiation of a weight-loss intervention. Forty-five women started the intervention. Study discontinuation for women randomized to ω-3-FA and initiating the weight-loss intervention was 9% at 6 months and thus satisfied our main endpoint, which was feasibility. Between baseline and 6 months significant change (P < 0.05) was observed in 12 of 25 serum metabolic markers associated with breast cancer risk for women randomized to ω-3-FA, but only four for those randomized to placebo. Weight loss (median of 10% for trial initiators and 12% for the 42 completing 6 months) had a significant impact on biomarker modulation. Median loss was similar for placebo (-11%) and ω-3-FA (-13%). No significant change between ω-3-FA and placebo was observed for individual biomarkers, likely due to sample size and effect of weight loss. Women randomized to ω-3-FA exhibiting more than 10% weight loss at 6 months showed greatest biomarker improvement including 6- and 12-month serum adiponectin, insulin, omentin, and C-reactive protein (CRP), and 12-month tissue adiponectin. Given the importance of a favorable adipokine profile in countering the prooncogenic effects of obesity, further evaluation of high-dose ω-3-FA during a weight-loss intervention in obese high-risk women should be considered. PREVENTION RELEVANCE: This study examines biomarkers of response that may be modulated by omega-3 fatty acids when combined with a weight-loss intervention. While focused on obese, postmenopausal women at high risk for development of breast cancer, the findings are applicable to other cancers studied in clinical prevention trials.

The promise of precision medicine in autism

Autism spectrum disorder (ASD) is a clinically and etiologically diverse developmental condition characterized by diminished social interactions, impaired communication, and repetitive and/or restrictive behaviors. Recent advances in ASD genetics pave the way for implementation of precision medicine in clinical management of autism.

Thromboembolism in ALL Patients 1-45 Years Treated According to the NOPHO-ALL 2008 Protocol

Background. Thromboembolism (TE) contributes to treatment-related morbidity and mortality in Philadelphia-chromosome negative acute lymphoblastic leukemia (ALL) with a reported incidence ranging 4.2-36.7%. No common recommendations for preemptive antithrombotic prophylaxis exist, and identification of ALL patients at high risk of TE, who may benefit from such prophylaxis, is highly warranted.Methods. We included patients 1-45 years of age diagnosed with either BCP- or T-ALL and treated according to NOPHO-ALL 2008 protocol in Denmark, Sweden, Norway, Finland, Estonia, Lithauania, or Iceland 7/2008-2/2016. Patient demographics, clinical characteristics, ALL biology, therapy, and TE events were prospectively reported to the common Nordic/Baltic ALL database at 3-months intervals throughout the study. Further details on the TE events, incl. treatment and outcome, were subsequently retrospectively collected through questionnaires. End of follow-up for all patients was April 1st 2017. Of 93 children 1-18.1 yrs of age diagnosed with symptomatic TE in this study, 58 have previously been reported (Tuckuviene, J Thromb Haemost, 2016). In case of TE low molecular weight heparin without truncation of asparaginase is recommended.Results . A total of 1637 patients with no record of TE and 139 ALL patients diagnosed with first-time TE were included, of whom 90% (N=125) were symptomatic. 102 patients had BCP-ALL (73%) and 37 T-ALL (27%). Male:female ratio 1.7:1. TE patients had a median age of 16y (IQR 6-21); 32% 1-9.9y (N=45), 33% 10-17.9y (N=46), and 35% 18-45y (N=48). 3y cumulative TE incidence was 7.9% (95% confidence interval (CI), 6.6-9.1); 3.9% 1-9.9y (95% CI, 2.7-4.9), 15.6% 10-17.9y (95% CI, 11.5-19.6) and 16.9% 18-45y (95% CI, 12.3-21.2). Time interval between diagnosis of ALL and TE ranged 2-799 days (median 80, IQR 49-127), and 46% of these (N=64) occurred during induction/consolidation 1. 17 patients (12%) had TE at ≥2 sites. 36 cases were cerebral sinus venous thrombosis (26%), 31 cases pulmonary embolism (22%), 54 cases otherwise supra-diaphragmatic (39%), and 36 cases infra-diaphragmatic (26%). 93% were of venous origin. A central venous line was present at the site of thrombosis in 45 patients with symptomatic TE (36%) and in 11 patients with asymptomatic TE (79%). 113 of 139 cases occurred within ≤6 weeks from asparaginase administration, and this treatment was truncated in 24% (N=34) due to TE event. Diagnosis of TE was not associated with increased hazard for mortality or relapse compared to the patients without TE (P 0.29 and 0.15). Risk of TE was significantly increased with presence of mediastinal mass at ALL diagnosis (def: ≥1/3 of thorax width at 5th thoracic vertebra level) (adjusted TE-specific HR 1.89, P 0.005 (95% CI, 1.21-2.96)), age 10-17.9y (adjusted TE-specific HR 4.16, P <0.0001 (95% CI 2.76-6.28)), and age 18-45y (adjusted TE-specific HR 4.53, P <0.0001 (95% CI, 2.98-6.91)) (Cox proportional hazards model with sex, immunophenotype, CNS status (CNS1-3), (WBC < or > 100K, mediastinal mass, 3 age groups, induction therapy with dexamethasone (T-ALL a/o WBC>100K), and treatment group. In regression model using age groups 1-5.9y, 6-14.9y, 15-20.9y and 21-45y (division into quartiles by TE events) the TE hazard was significantly increased for all 3 older age groups; 6-14.9y (adjusted HR 1.74, P 0.03 (95% CI, 1.07-2.84)), 15-20.9y (adjusted HR 6.38, P <0.0001 (95% CI, 4.00-10.2)), and 21-45y (adjusted HR 4.43, P <0.0001 (95% CI, 2.73-7.20)). The HR of presence of mediastinal mass remained unchanged (adjusted HR 1.92, P 0.004 (95% CI, 1.23-3.00)).Conclusion . Patients with a mediastinal mass a/o age ≥6-10 yrs at ALL diagnosis constitute a group at high risk for development of TE during chemotherapy with ASP, and routine antithrombotic prophylaxis should be considered for this high risk group. DisclosuresNo relevant conflicts of interest to declare.