Nevin Manimala

J Urol. 2022 Nov 14:101097JU0000000000003049. doi: 10.1097/JU.0000000000003049. Online ahead of print.

ABSTRACT

PURPOSE: Adrenal 11-oxygenated androgens may support cancer progression in men with prostate cancer (PCa) owing to their abundance and androgenic potential. We hypothesized that preoperative circulating levels of 11-oxygenated androgens influence clinical outcomes in men with newly diagnosed localized PCa.

MATERIAL AND METHODS: We studied 1793 treatment-naïve patients and 155 patients who received preoperative treatment with 5α-reductase inhibitors (5-ARIs) in the prospective PROCURE cohort for which preoperative plasma samples were obtained prior to radical prostatectomy (RP). Adrenal 11-oxygenated precursors, potent 11-oxygenated androgens and their metabolites (n=7) were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Circulating levels were evaluated in relation to prognostic factors, disease-free survival (DFS), and metastasis-free survival (MFS), using multivariable Cox proportional hazards models.

RESULTS: At a median follow-up time of 93.8 months after surgery, 583 patients experienced biochemical recurrence, 104 developed metastatic disease and 168 diseased. Higher levels of 11-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT) were observed in men with prostatic specific antigen (PSA) >20 ng/ml and positive nodal status (P<.05). In multivariable analyses, no significant association between 11-oxygenated androgens and DFS was observed. Adrenal 11β-hydroxyandrostenedione (11OHA4), the predominant androgenic 11KT, and its metabolite 11-ketoandrosterone (11KAST), modeled as quartiles, were associated with MFS (P=.06, .03, and 0.008, respectively). A significant accumulation of 11-oxygenated androgen precursors and bioactive androgens, but reduced metabolite levels, was observed in 5-ARIs patients (P<.001).

CONCLUSIONS: Preoperative circulating 11-oxygenated androgen levels are associated with MFS in men with localized PCa undergoing RP and are affected by 5-ARI treatment.

PMID:36373402 | DOI:10.1097/JU.0000000000003049

J Appl Biomater Funct Mater. 2022 Jan-Dec;20:22808000221125870. doi: 10.1177/22808000221125870.

ABSTRACT

The nanoparticles are frequently used in biomedical science for the treatment of diseases like cancer and these nanoparticles are injected in blood which is transported in the cardiovascular system on the principle of peristalsis. This study elaborates the effects of Lorentz force and joule heating on the peristaltic flow of copper and iron oxide suspended blood based nanofluid in a complex wavy non-uniform curved channel. The Brinkman model is utilized for the temperature dependent viscosity and thermal conductivity. The problem is formulated using the fundamental laws in terms of coupled partial differential equations which are simplified using the creeping flow phenomenon. The graphical results for velocity, temperature, streamlines, and axial pressure are simulated numerically. The concluded observations deduce that the solid volume fraction of nanoparticles reduces the velocity and enhance the pressure gradient and accumulation of trapping bolus in the upper half of the curved channel is noticed for temperature dependent viscosity.

PMID:36373397 | DOI:10.1177/22808000221125870

Scand J Gastroenterol. 2022 Nov 14:1-8. doi: 10.1080/00365521.2022.2143724. Online ahead of print.

ABSTRACT

BACKGROUND: The role of laparoscopy in the treatment of intrahepatic cholangiocarcinoma (ICC) remains unclear. This multicenter study examined the outcomes of laparoscopic liver resection for ICC.

METHODS: Patients with ICC who had undergone laparoscopic or open liver resection between 2012 and 2019 at four European expert centers were included in the study. Laparoscopic and open approaches were compared in terms of surgical and oncological outcomes. Propensity score matching was used for minimizing treatment selection bias and adjusting for confounders (age, ASA grade, tumor size, location, number of tumors and underlying liver disease).

RESULTS: Of 136 patients, 50 (36.7%) underwent laparoscopic resection, whereas 86 (63.3%) had open surgery. Median tumor size was larger (73.6 vs 55.1 mm, p = 0.01) and the incidence of bi-lobar tumors was higher (36.6 vs 6%, p < 0.01) in patients undergoing open surgery. After propensity score matching baseline characteristics were comparable although open surgery was associated with a larger fraction of major liver resections (74 vs 38%, p < 0.01), lymphadenectomy (60 vs 20%, p < 0.01) and longer operative time (294 vs 209 min, p < 0.01). Tumor characteristics were similar. Laparoscopic resection resulted in less complications (30 vs 52%, p = 0.025), fewer reoperations (4 vs 16%, p = 0.046) and shorter hospital stay (5 vs 8 days, p < 0.01). No differences were found in terms of recurrence, recurrence-free and overall survival.

CONCLUSION: Laparoscopic resection seems to be associated with improved short-term and with similar long-term outcomes compared with open surgery in patients with ICC. However, possible selection criteria for laparoscopic surgery are yet to be defined.

PMID:36373379 | DOI:10.1080/00365521.2022.2143724

Eur J Transl Myol. 2022 Nov 8. doi: 10.4081/ejtm.2022.10836. Online ahead of print.

ABSTRACT

Acute pain after surgery can cause harmful effects. There are many ways to treat pain after surgery. Bier block technique is also a type of intravenous regional anesthesia that is suitable for short and minor surgeries of the arm, wrist, and fingers, so this study aims to compare the analgesic effect of Ketorolac in intravenous injection and when the lidocaine is added to Bier block. In surgery, traumatic injuries to the upper limbs. This study was a clinical trial, randomized and double-blind. The target population was candidates for upper limb orthopedic surgery. The patients selected based on the entry and exit criteria were randomly assigned to one of the 3 study groups. The intensity of pain, the amount of morphine consumed through the intravenous PCA pump, the incidence of side effects of morphine and ketorolac, as well as the overall patient satisfaction regarding the anesthesia method and pain control were compared between the groups. Data analysis, both descriptive and analytical, was done using SPSS statistical software version 21. The three studied groups were identical and had no differences in terms of quantitative and qualitative demographic variables. The median tourniquet closing time is different between the control group and the intravenous ketorolac and topical ketorolac groups with P=0.002 and P=0.001, respectively. There was no significant difference between the three groups in terms of the time of the first request to receive painkillers after deflating the tourniquet, but the amount of morphine received between the groups was significantly different (P=0.02). Comparison of pain intensity based on NRS, considering Taking the measurement repetition times indicated the significance of the effect of pain intensity between the groups (P=0.001). In terms of overall satisfaction with the quality of analgesia and anesthesia method, no significant difference was observed between the three study groups. In terms of the occurrence of complications related to the use of ketorolac, no complications were observed in any of the groups receiving this drug. In general, by conducting this study, it can be said that the administration of Ketorolac reduces the intensity of postoperative pain in the recovery room and transfer to the inpatient ward, and reduces the amount of morphine received by patients, but the time of the first request for pain relief by the patient It does not significantly delay and does not affect the overall satisfaction of patients with the quality of analgesia during and after the operation and their satisfaction with the anesthesia method they received.

PMID:36373375 | DOI:10.4081/ejtm.2022.10836

J Alzheimers Dis. 2022 Nov 8. doi: 10.3233/JAD-220604. Online ahead of print.

ABSTRACT

BACKGROUND: Discrete choice experiments (DCEs) may facilitate persons with dementia and informal caregivers to state care preferences. DCEs can be cognitively challenging for persons with dementia.

OBJECTIVE: This study aims to design a dementia friendly dyadic DCE that enables persons with dementia and informal caregivers to provide input individually and jointly, by testing the number of attributes and choice tasks persons with dementia can complete and providing insight in their DCE decision-making process.

METHODS: This study included three DCE rounds: 1) persons with dementia, 2) informal caregivers, and 3) persons with dementia and informal caregivers together. A flexible DCE design was employed, with increasing choice task complexity to explore cognitive limitations in decision-making. Summary statistics and bivariate comparisons were calculated. A qualitative think-aloud approach was used to gain insight in the DCE decision-making processes. Transcripts were analyzed using thematic analysis.

RESULTS: Fifteen person with dementia, 15 informal caregiver, and 14 dyadic DCEs were conducted. In the individual DCE, persons with dementia completed six choice tasks (median), and 80% could complete a choice task with least three attributes. In the dyadic DCE persons with dementia completed eight choice tasks (median) and could handle slightly more attributes. Qualitative results included themes of core components in DCE decision-making such as: understanding the choice task, attribute and level perception, option attractiveness evaluation, decision rule selection, and preference adaptation.

CONCLUSION: Persons with dementia can use simple DCE designs. The dyadic DCE was promising for dyads to identify overlapping and discrepant care preferences while reaching consensus.

PMID:36373319 | DOI:10.3233/JAD-220604

Ann Med. 2022 Dec;54(1):2921-2928. doi: 10.1080/07853890.2022.2129090.

ABSTRACT

BACKGROUND: The burden of Sickle cell anaemia (SCA) is huge in Sub Sahara Africa as it affects 1-2% of the population. HbSS impacts negatively on the quality of life of the sufferers. The clinical manifestations start between 3 and 5 months of life as a result of reduction in foetal hemoglobin.

OBJECTIVES: This study describes the clinical and laboratory characteristics of HbSS patients at presentation in steady state, vaso-occlusive and hemolytic crises states.

MATERIAL AND METHOD: This was a cross sectional, analytical study. Ninety HbSS participants were divided into three groups; steady state, hemolytic and vaso-occlusive crises with 30 individuals in each group. The survey contained sections on bio-data and past medical history obtained from the patients’ notes and results of laboratory tests. Data were analysed using SPSS version 23.0. Results were considered statistically significant if p < 0.05.

RESULTS: Ninety participants were analysed in this study. The mean age of the participants was 29.4 ± 8.9 years. Only one-third of the participants were diagnosed within the first year of age. Forty-seven (52.2%) participants have steady state haematocrit in the range of 21-25%. All the participants experienced bone pain in a year, about 25% of these participants had more than three episodes of pain per year. There was a statistically significant difference in the mean values of PCV (p < .001), WBC (p < .001), platelet (p = .008), ANC (p < .001), ALC (p < .001), AMC (p < .001), reticulocyte count and ISC % among the different categories.

CONCLUSION: This study established the fact that only a minority of the SCD patients are diagnosed in the first year of life and vaso-occlusive crisis is the most frequent reason for hospital presentation. We therefore recommend the institutionalisation by government policy, neonatal screening programme in Nigeria.KEY MESSAGESThe study highlight delay in early diagnosis of SCA due to unavailability of neonatal diagnosis program in our setting.Bone pain remains the major cause of presentation for SCA and most patients presented after a day of onset of pain to the hospital.

PMID:36371797 | DOI:10.1080/07853890.2022.2129090

J Clin Lab Anal. 2022 Nov 13:e24749. doi: 10.1002/jcla.24749. Online ahead of print.

ABSTRACT

INTRODUCTION: Viral infections are often accompanied by reactive thrombocytosis, that is, increased activity of platelets, which is especially common in infants and children.

OBJECTIVE: This study aimed to test the diagnostic properties of platelet indices, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW), in children with beta corona virus 2 (SARS-CoV-2) infection.

METHODS: The study included 232 patients below the age of 18 admitted to the coronavirus disease (COVID-19) isolation wards at the Institute for Child and Youth Health Care of Vojvodina. PCT, MPV and PDW values on the day of admission were recorded. In total, 245 controls were selected from those treated for SARS-CoV-2 negative respiratory infections. Descriptive and inferential statistical analyses were performed.

RESULTS: MPV and PDW were found important as independent predictors for COVID-19 in children. Furthermore, the joint effect of MPV and PDW for predicting COVID-19 was confirmed. The parameters showed better sensitivity than specificity.

CONCLUSION: Our study showed that PCT is not clinically significant, while MPV and PDW have diagnostic value in predicting COVID-19 in children. In perspective, these parameters could be implemented in the various learning algorithms in order to achieve earlier diagnosis and treatment.

PMID:36371787 | DOI:10.1002/jcla.24749

Metabolomics. 2022 Nov 13;18(11):92. doi: 10.1007/s11306-022-01949-w.

ABSTRACT

INTRODUCTION: PKCδ is ubiquitously expressed in mammalian cells and its dysregulation plays a key role in the onset of several incurable diseases and metabolic disorders. However, much remains unknown about the metabolic pathways and disturbances induced by PKC deficiency, as well as the metabolic mechanisms involved.

OBJECTIVES: This study aims to use metabolomics to further characterize the function of PKC from a metabolomics standpoint, by comparing the full serum metabolic profiles of PKC deficient mice to those of wild-type mice.

METHODS: The serum metabolomes of PKCδ knock-out mice were compared to that of a wild-type strain using a GCxGC-TOFMS metabolomics research approach and various univariate and multivariate statistical analyses.

RESULTS: Thirty-seven serum metabolite markers best describing the difference between PKCδ knock-out and wild-type mice were identified based on a PCA power value > 0.9, a t-test p-value < 0.05, or an effect size > 1. XERp prediction was also done to accurately select the metabolite markers within the 2 sample groups. Of the metabolite markers identified, 78.4% (29/37) were elevated and 48.65% of these markers were fatty acids (18/37). It is clear that a total loss of PKCδ functionality results in an inhibition of glycolysis, the TCA cycle, and steroid synthesis, accompanied by upregulation of the pentose phosphate pathway, fatty acids oxidation, cholesterol transport/storage, single carbon and sulphur-containing amino acid synthesis, branched-chain amino acids (BCAA), ketogenesis, and an increased cell signalling via N-acetylglucosamine.

CONCLUSION: The charaterization of the dysregulated serum metabolites in this study, may represent an additional tool for the early detection and screening of PKCδ-deficiencies or abnormalities.

PMID:36371785 | DOI:10.1007/s11306-022-01949-w

Hum Brain Mapp. 2022 Nov 13. doi: 10.1002/hbm.26112. Online ahead of print.

ABSTRACT

In this manuscript, we consider the problem of relating functional connectivity measurements viewed as statistical distributions to outcomes. We demonstrate the utility of using the distribution of connectivity on a study of resting-state functional magnetic resonance imaging association with an intervention. The method uses the estimated density of connectivity between nodes of interest as a functional covariate. Moreover, we demonstrate the utility of the procedure in an instance where connectivity is naturally considered an outcome by reversing the predictor/response relationship using case/control methodology. The method utilizes the density quantile, the density evaluated at empirical quantiles, instead of the empirical density directly. This improved the performance of the method by highlighting tail behavior, though we emphasize that by being flexible and non-parametric, the technique can detect effects related to the central portion of the density. To demonstrate the method in an application, we consider 47 primary progressive aphasia patients with various levels of language abilities. These patients were randomly assigned to two treatment arms, transcranial direct-current stimulation and language therapy versus sham (language therapy only), in a clinical trial. We use the method to analyze the effect of direct stimulation on functional connectivity. As such, we estimate the density of correlations among the regions of interest and study the difference in the density post-intervention between treatment arms. We discover that it is the tail of the density, rather than the mean or lower order moments of the distribution, that demonstrates a significant impact in the classification. The new approach has several benefits. Among them, it drastically reduces the number of multiple comparisons compared with edge-wise analysis. In addition, it allows for the investigation of the impact of functional connectivity on the outcomes where the connectivity is not geometrically localized.

PMID:36371779 | DOI:10.1002/hbm.26112

Eur Spine J. 2022 Nov 13. doi: 10.1007/s00586-022-07451-0. Online ahead of print.

ABSTRACT

PURPOSE: The goal of this study was to provide recent data on incidence of spinal cord injuries (SCI) in Germany.

METHODS: The source of information was data collected via the mandatory submission of ICD-10 GM Codes by German public hospitals after patient discharge. Data from 2013 to 2020 were retrieved from the databases of the Federal Bureau of Statistics. ICD-10 Codes for acute SCI were identified. Statistical analysis was performed using Jamovi and Excel.

RESULTS: A total of 10,360 patients were reported, of whom 58.7% suffered from a cervical, 30.8% a thoracic and 10.4% a lumbar lesion. Two peaks in incidence were observed at approximately 30 and 70 years old. A population-size-adjusted overall incidence of 15.73 (SD 0.77) per million per year was calculated. We calculated the incidences in several subpopulations and discovered significantly higher incidences among males and among those over the age of 60. We discovered that differences in age groups mainly concerned injuries of the upper spine, with the incidence in the lumbar spine being similar among age groups. In addition, we found that while the probability of suffering from SCI increases with age, the relative risk of suffering from a complete injury decreases.

CONCLUSIONS: This study closes a long-lasting gap in epidemiological data regarding SCI in Germany, specifically by updating the incidence rates. We found that incidence depends on age, gender and type of lesion. We also provide some new angles for future research, especially considering the relative reduction in complete injuries among the elderly.

PMID:36371751 | DOI:10.1007/s00586-022-07451-0