A Case of Stevens–Johnson Syndrome in Recurrent Late-Stage Ovarian Cancer Patient after Management of Chronic Pain with Elastomeric Pump

(1) Background. Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, characterized by extensive necrosis and detachment of the epidermis. (2) Case presentation. We present a case of a 46-year-old patient with late-stage high-grade serous ovarian cancer who was primarily treated with neoadjuvant chemotherapy and interval debulking, which was followed by adjuvant chemotherapy. At first recurrence, she was again treated with chemotherapy, and due to severe abdominal pain, an elastomeric pump containing analgesics, anti-inflammatories, and ondansetron was administered. In the same month, she was admitted to the hospital due to severe dysphagia, and in the following days she developed haemorrhagic vesiculobullous lesions on the facial skin and trunk. Stevens–Johnson syndrome was confirmed and ondansetron as a plausible leading cause was discontinued. Despite multimodal treatment, her condition deteriorated, and she died. (3) Discussion and conclusion. Although gynaecologists rarely encounter Stevens–Johnson syndrome, high mortality of the disease should ensure a low threshold for diagnosing and treating this disease.     

Machine Learning for Predicting Cognitive Diseases: Methods,Data Sources and Risk Factors

Machine learning and data mining approaches are being successfully applied to different fields of life sciences for the past 20 years. Medicine is one of the most suitable application domains for these techniques since they help model diagnostic information based on causal and/or statistical data and therefore reveal hidden dependencies between symptoms and illnesses. In this paper we give a detailed overview of the recent machine learning research and its applications for predicting cognitive diseases, especially the Alzheimer’s disease, mild cognitive impairment and the Parkinson’s disease. We survey different state-of-the-art methodological approaches, data sources and public data, and provide their comparative analysis. We conclude by identifying the open problems within the field that include an early detection of the cognitive diseases and inclusion of machine learning tools into diagnostic practice and therapy planning.     

Identification of Novel Diagnostic Biomarkers in Breast Cancer Using Targeted Metabolomic Profiling

IntroductionBreast cancer (BC) is the most common cancer in women, with a high disease burden, especially in the advanced disease stages. Our study investigated the metabolomic profile of breast cancer patients’ serum with the aim of identifying novel diagnostic biomarkers that could be used, especially for early disease detection.Materials and MethodsUsing targeted metabolomic serum profiling based on high-performance liquid chromatography mass spectrometry, women with BC (n = 39) and a control group (n = 21) were examined for 232 endogenous metabolites.ResultsThe top performing biomarkers included acylcarnitines (ACs) and 9,12-linoleic acid. A combined panel of the top 4 biomarkers achieved 83% sensitivity and 81% specificity, with an area under the curve (AUC) of 0.839 (95% confidence interval, 0.811-0.867). Individual markers also provided significant predictive values: AC 12:0, sensitivity of 72%, specificity of 67%, and AUC of 0.71; AC 14:2, sensitivity of 74%, specificity of 71%, and AUC of 0.73; AC 14:0: sensitivity of 67%, specificity of 81%, and AUC of 0.73; and 9,12-linoleic acid, sensitivity of 69%, specificity of 67%, and AUC of 0.71. The individual markers, however, did not reach the high sensitivity and specificity of the 4-biomarker combination.ConclusionUsing mass spectrometry-targeted metabolomic profiling, ACs and 9,12-linoleic acid were identified as potential diagnostic biomarkers for breast cancer. Additionally, these identified metabolites could provide additional insight into cancer cell metabolism.     

Identification of new impurities of enalapril maleate on oxidation in the presence of magnesium monoperoxyphthalate

Stress stability testing and forced degradation were used to determine the stability of enalapril maleate (EM) and to find a degradation pathway for the drug. The degradation impurities, formed under different stressed conditions, were investigated by HPLC and UPLC–MS methods. HPLC analysis showed several degradation impurities of which several were already determined, but on oxidation in the presence of magnesium monoperoxyphthalate (MMPP) several impurities of EM were observed which were not yet characterized. The HPLC methods for determination of EM were validated. The linearity of HPLC method was established in the concentration range between 0.5 and 10 μg/mL with correlation coefficient greater than 0.99. The LOD of EM was 0.2 μg/mL and LOQ was 0.5 μg/mL. The validated HPLC method was used to determine the degradation impurities in samples after stress stability testing and forced degradation of EM. In order to identify new degradation impurities of EM after forced degradation UPLC–MS/MSⁿ, Orbitrap has been used. It was found that new impurities are oxidation products: (S)-1-((S)-2-((S)-1-ethoxy-4-(o,m,p-hydroxyphenyl)-1-oxobutan-2-ylamino)propanoyl)pyrrolidine-2-carboxylic acid, (2S)-1-((2S)-2-((2S)-1-ethoxy-4-hydroxy-1-oxo-4-phenylbutan-2-ylamino)propanoyl)pyrrolidine-2-carboxylic acid. (S)-2-(3-phenylpropylamino)-1-(pyrrolidin-1-yl)propan-1-one was identified as a new degradation impurity.     

Diagnostic Performance of p16/Ki-67 Dual Immunostaining at Different Number of Positive Cells in Cervical Smears in Women Referred for Colposcopy

BackgroundThe aim of the study was to evaluate the diagnostic accuracy of p16/Ki-67 dual immunostaining (p16/ Ki-67 DS) in cervical cytology and the number of positive p16/Ki-67 cells to diagnose high grade cervical intraepithelial neoplasia (CIN2+) in colposcopy population.Subjects and methodsWe performed an analysis on a subset cohort of 174 women enrolled within a large-scale randomised controlled human papillomavirus (HPV) self-sampling project organised as part of the population-based Cervical Cancer Screening Programme ZORA in Slovenia. This subset cohort of patients was invited to the colposcopy clinic, underwent p16/Ki-67 DS cervical cytology and had the number of p16/Ki-67 positive cells determined.ResultsAmong analysed women, 42/174 (24.1%) had histologically confirmed CIN2+. The risk for CIN2+ was increasing with the number of positive cells (p < 0.001). The sensitivity of p16/Ki-67 DS for detection of CIN2+ was 88.1%, specificity was 65.2%, positive predictive value was 44.6% and negative predictive value was 94.5%.ConclusionsDual p16/Ki-67 immunostaining for the detection of CIN2+ has shown high sensitivity and high negative predictive value in our study, which is comparable to available published data. The number of p16/Ki-67 positive cells was significantly associated with the probability of CIN2+ detection. We observed a statistically significant and clinically relevant increase in specificity if the cut-off for a positive test was shifted from one cell to three cells.Key words: cervical cytology, high-grade dysplasia, p16/Ki-67 immunostaining     

Human papillomavirus infection in patients with residual or recurrent cervical intraepithelial neoplasia

AIMS AND BACKGROUND: The main purpose of this longitudinal study was to evaluate the frequency of HPV infection in patients with residual or recurrent CIN. METHODS: 797 consecutive patients with CIN, treated with conization, were included. In 38 patients with residual or recurrent CIN in whom reconization was performed, infection with high-risk HPV types was analyzed. RESULTS: Reconization was performed in 4.8% of patients. Before reconization, 21 patients (55.3%) were infected with high-risk HPV and 17 patients (44.7%) were HPV negative. Among the HPV-negative patients, two (11.8%) had CIN 1, five (29.4%) CIN 2, nine (52.9%) CIN 3 and one patient (5.9%) had microinvasive cancer of the uterine cervix. The difference in frequency of infection with high-risk HPV was not significant (chi-square 0.372; P > 0.05). CONCLUSIONS: On the basis of the study results it is not possible to recommend the HPV test as the only method of detection of residual or recurrent CIN after conization.     

Rationality,practice variation and person‐centred health policy: a threshold hypothesis

Variation in practice of medicine is one of the major health policy issues of today. Ultimately, it is related to physicians' decision making. Similar patients with similar likelihood of having disease are often managed by different doctors differently: some doctors may elect to observe the patient, others decide to act based on diagnostic testing and yet others may elect to treat without testing. We explain these differences in practice by differences in disease probability thresholds at which physicians decide to act: contextual social and clinical factors and emotions such as regret affect the threshold by influencing the way doctors integrate objective data related to treatment and testing. However, depending on a theoretical construct each of the physician's behaviour can be considered rational. In fact, we showed that the current regulatory policies lead to predictably low thresholds for most decisions in contemporary practice. As a result, we may expect continuing motivation for overuse of treatment and diagnostic tests. We argue that rationality should take into account both formal principles of rationality and human intuitions about good decisions along the lines of Rawls' ‘reflective equilibrium/considered judgment’. In turn, this can help define a threshold model that is empirically testable.