Minor Subgroup Research Articles

Design, synthesis, biological evaluation and molecular docking of alkoxyaurones as potent pancreatic lipase inhibitors

Aurones are a minor subgroup of flavonoids. Unlike other subgroups such as chalcones, flavones, and isoflavones, aurones have not been extensively explored as pancreatic lipase inhibitors. In this work, we studied the pancreatic lipase inhibitory potency of synthetic aurone derivatives. Thirty-six compounds belonging to four series (4,6-dihydroxyaurone, 6-hydroxyaurone, 4,6-dialkoxyaurone, and 6-alkoxyaurone) were designed and synthesized. Their in vitro inhibitory activities were determined by spectrophotometric assay in comparison with quercetin and orlistat. Alkoxyaurone derivatives with long-chain (6–10 carbons) alkoxy substituents showed greater potency. Of them, 4,6-dialkoxyaurone 8 displayed the highest activity against pancreatic lipase (IC50 of 1.945 ± 0.520 µM) relative to quercetin (IC50 of 86.98 ± 3.859 µM) and orlistat (IC50 of 0.0334 ± 0.0015 µM). Fluorescence quenching measurement confirmed the affinity of alkoxyaurone derivatives to pancreatic lipase. Kinetic study showed that 8 inhibited lipase through a competitive mechanism (Ki of 1.288 ± 0.282 µM). Molecular docking results clarified the role of long-chain substituents on ring A in interacting with the hydrophobic pockets and pushing the inhibitor molecule closer to the catalytic triad. The findings in this study may contribute to the development of better pancreatic lipase inhibitors with aurone structure.

Characterizing Sjögren-Associated Fatigue: A Distinct Phenotype from ME/CFS.

Fatigue is the most commonly reported and debilitating extraglandular symptom of primary Sjögren's syndrome (pSS). Fatigue and exertional intolerance are hallmark symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We aimed to characterize fatigue and further symptoms among pSS patients and to determine whether there is a symptom overlap in pSS and ME/CFS. In 19 patients with pSS, we assessed pSS symptom severity and disease activity via questionnaires as well as the Canadian Consensus Criteria (CCC) for ME/CFS. Hand grip strength (HGS) and levels of α1-, α2-, β1-, β2-, M3- and M4-receptor-autoantibodies were measured. A subgroup of pSS patients exhibited severe fatigue and had higher severity of pain (p = 0.045), depression (p = 0.021) and sleep disturbances (p = 0.020) compared to those with less fatigue. Four of eighteen pSS patients fulfilled the CCC. HGS parameters strongly correlated with fatigue severity (p < 0.05), but strength fully recovered one hour after exertion in contrast to ME/CFS. Levels of β1-, β2- and M4-receptor-autoantibodies were elevated and correlated significantly with disease activity assessed by the ESSDAI (p < 0.05), but not fatigue severity. Only a minor subgroup of pSS patients fulfills the CCC, and post exertional malaise (PEM) is atypical, as it is primarily triggered by mental/emotional but not physical exertion. HGS assessment is an objective measure to assess overall fatigue severity.

Video Consultations and Safety App Targeting Pregnant Women Exposed to Intimate Partner Violence in Denmark and Spain: Nested Cohort Intervention Study (STOP Study).

Intimate partner violence (IPV) during pregnancy is a public health issue with wide-ranging consequences for both the mother and fetus, and interventions are needed. Therefore, the Stop Intimate Partner Violence in Pregnancy (STOP) cohort was established with the overall aim to identify pregnant women exposed to IPV through digital screening and offer women screening positive for IPV a digital supportive intervention. The aim of this study was to (1) introduce the design and profile of the STOP cohort study, (2) assess the feasibility of implementing digital IPV screening among pregnant women, and (3) assess the feasibility of implementing a digital supportive intervention targeting pregnant women exposed to IPV. Pregnant women attending antenatal care in the Region of Southern Denmark and in Andalucía, Spain were offered digital screening for IPV using validated scales (Abuse Assessment Screen and Women Abuse Screening Tool). Women who screened positive were eligible to receive a digital supportive intervention. The intervention consisted of 3-6 video consultations with an IPV counselor and a safety planning app. In Denmark, IPV counselors were antenatal care midwives trained by a psychologist specialized in IPV, whereas in Spain, the counselor was a psychologist. Data collection started in February 2021 and was completed in October 2022. Across Denmark and Spain, a total of 19,442 pregnant women were invited for IPV screening and 16,068 women (82.65%) completed the screening. More women in Spain screened positive for exposure to IPV (350/2055, 17.03%) than in Denmark (1195/14,013, 8.53%). Among the women who screened positive, only 31.39% (485/1545) were eligible to receive the intervention with only 104 (21.4%) of these women ultimately receiving it. Digital screening for IPV among pregnant women is feasible in an antenatal care context in Denmark and Spain; however, a digital supportive intervention during pregnancy appears to have limited feasibility as only a minor subgroup of women who screened positive for eligibility received the intervention. More research is needed on how to best support pregnant women exposed to IPV if universal IPV screening is to be implemented in antenatal care.

Assessing the Efficacy of Mechanical Thrombectomy in Patients with an NIHSS &lt; 6 Presenting with Proximal Middle Cerebral Artery Vessel Occlusion as Compared to Best Medical Management

Minor acute ischemic stroke (AIS) patients-defined by an NIHSS score < 6-presenting with proximal middle cerebral artery large vessel occlusions (MCA-LVO) is a subgroup for which treatment is still debated. Although these patients present with minor symptoms initially, studies have shown that several patients afflicted with MCA-LVO in this subgroup experience cognitive and functional decline. Although mechanical thrombectomy (MT) is the standard of care for patients with an NIHSS score of 6 or higher, treatment in the minor stroke subgroup is still being explored. The purpose of this preliminary study is to report our center's experience in evaluating the potential benefit of mechanical thrombectomy (MT) in minor stroke patients when compared to medical management (MM). We performed a retrospective study with two comprehensive stroke centers within our hospital enterprise of consecutive patients presenting with minor AIS secondary to MCA-LVO (defined as M1 or proximal M2 segments of MCA). We subsequently evaluated patients who received MT versus those who received MM. Between January 2017 and July 2021, we identified 46 AIS patients (11 treated with MT and 35 treated with MM) who presented with an NIHSS score < 6 secondary to MCA-LVO (47.8% 22/46 female, mean age 62.3 years, range 49-75 years). MT was associated with a significantly lower mRS at 90 days (median: 1.0 [IQR 0.0-2.0] versus 3.0 [IQR 1.0-4.0], p = <0.001), a favorable NIHSS shift (-4.0 [IQR -10.0--2.0] versus 0.0 [IQR -2.0-1.0], p = 0.002), favorable NIHSS shift dichotomization (5/11, 45.5% versus 3/35, 8.6%, p = 0.003) and favorable mRS dichotomization (7/11, 63.6% versus 14/35, 40.0%, p = 0.024). In our center's preliminary experience, for AIS patients presenting with an NIHSS score < 6 secondary to MCA-LVO, MT may be associated with improved clinical outcomes when compared to MM only.

Inherited metabolic disorders in a cohort of Egyptian children

BackgroundInborn errors of metabolism (IEMs) represent a special challenge in pediatric practice. Despite the unquestionable clinical significance of newborn screening, it just offers a snapshot of an extremely minor subgroup of metabolic disorders. So, it is crucial to use multiple techniques for accurate diagnosis of a wider spectrum of IEMs early in infancy to prevent overwhelming irreversible neurological complications in a cohort of high-risk Egyptian pediatrics. This study included four thousand and eighty suspected IEMs patients. They were referred to the Chromatography Unit, Clinical Biochemistry and Molecular Diagnostics Laboratories, National Liver Institute (NLI) for laboratory assessment in the period from March 2016 to November 2020. Separation of amino acids and acylcarnitines using tandem mass spectrometry (LC/MS) and organic acids using gas chromatography mass spectrometry (GC/MS) was done.ResultsThree hundred and twenty (320/4080, 7.8%) patients were diagnosed with IEMs. The following disorders were identified: organic acidopathies—200 (62.5%) including methylmalonic acidemia (MMA) (48/320, 15%), glutaric academia (GA) (40/320, 12, 5%), propionic acidemia (PA), (32/320, 10%), isovaleric acidemia (IVA) (40/320, 12.5%), methylcrotonyl glyceinuria (16/320, 5%), and orotic acidemia (24/320, 7.5%); amino acidopathies—80 (25%) including maple syrup urine disease (MSUD) (32/320, 10%), phenylketonuria (24/320, 7.5%), homocystinuria (16/320, 5%), and nonketotic hyperglycinemia (8/320, 2.5%) in addition to fatty acid disorders (FAO): 24 (7.5%) and lactic academia (LA), 16 (5%).ConclusionEarly detection of IEMs by rapid non-invasive techniques. LC/MS and GC/MS. is a crucial process for early diagnosis of different types of IEMs to install therapeutic clue in a group of high-risk Egyptian pediatrics for proper treatment and better outcome

MicroRNA Signatures in the Upper Urinary Tract Urothelial Carcinoma Scenario: Ready for the Game Changer?

Upper urinary tract urothelial carcinoma (UTUC) represents a minor subgroup of malignancies arising in the urothelium of the renal pelvis or ureter. The estimated annual incidence is around 2 cases per 100,000 people, with a mean age at diagnosis of 73 years. UTUC is more frequently diagnosed in an invasive or metastatic stage. However, even though the incidence of UTUC is not high, UTUC tends to be aggressive and rapidly progressing with a poor prognosis in some patients. A significant challenge in UTUC is ensuring accurate and timely diagnosis, which is complicated by the non-specific nature of symptoms seen at the onset of disease. Moreover, there is a lack of biomarkers capable of identifying the early presence of the malignancy and guide-tailored medical treatment. However, the growing understanding of the molecular biology underlying UTUC has led to the discovery of promising new biomarkers. Among these biomarkers, there is a class of small non-coding RNA biomarkers known as microRNAs (miRNAs) that are particularly promising. In this review, we will analyze the main characteristics of UTUC and focus on microRNAs as possible novel tools that could enter clinical practice in order to optimize the current diagnostic and prognostic algorithm.

Major and minor subgroup profile of blood in patients receiving multiple transfusions and donors.

It was aimed to profile the blood subgroups of our region and to reveal the prevalence of auto/alloimmune sensitization in patients who had to undergo multiple erythrocyte transfusions and to establish the sensitization profile by screening major and minor subgroups. In this study, the distribution of ABO and Rh system major subgroups was studied in 100 donor blood. As the patient group, 50 patients who received three or more red blood cell transfusions were included. In addition to this group, Kell, Lewis, Duffy blood group systems were studied. According to the ABO system, 35% of the donors were in O, 33% in A, 17% in AB, and 15% in B. According to the Rh system, 75% is Dvi positive. Rh system is 99% e positive and 33% E positive in major subgroups and Kell1 positivity is 8%. In the patient group, 22% D(-) was determined compared to Rh blood group. Among the major subgroups of Rh, C was 68%, E was 14%, c was 76%, and e positivity was found to be 100%. The Kell1 negativity rate is 96%. The highest negativity was found in 86% Lea antigen in Lewis system, in 36% S antigen in MNS system, 34% Fyb antigen in Duffy system, and 24% Jka antigen in Kidd system. When inappropriate blood is given for any antigen, a double population is formed. The double negativities we detected in our study occurred as follows according to blood group systems: E 18%, C 12%, c 8%, Cw 2%, Kell 1 2%, M 8%, N 4%, S 18%, s 6%, Fya 8%, Jka 6%, Jkb 22%. Indirect Agglutination Test (IAT) was negative in all patients. IAT negativity in all patient groups suggests that we do not develop alloimmunization, but the high rates of double population suggest a high risk of alloimmunization.

Survival analysis between laparoscopic and open hepatectomy for hepatocellular carcinoma: a meta-analysis based on reconstructed time-to-event data.

Laparoscopic hepatectomy (LH) has been widely used in the treatment of hepatocellular carcinoma (HCC). It is generally believed that the long-term outcomes of LH are not inferior to open hepatectomy (OH). However, the quality of evidence is low. The purpose of this study was to reconstruct time-to-event data for meta-analysis based on Kaplan-Meier curves from propensity-score matched studies and compare survival rates following LH and OH for hepatocellular carcinoma. All published propensity-score matched studies reported in English that compared LH and OH for hepatocellular carcinoma with Kaplan-Meier curves were screened. Patients' survival information was reconstructed with the aid of a computer vision program. Different models (fixed-effects model for two-stage survival analysis and Cox regression for one-stage survival analysis) were performed for sensitivity analysis. In addition to the primary meta-analysis, two specific subgroup analyses were performed on patients by types of resection, cirrhosis status. Time-to-event data were extracted from 45 propensity-score matched studies (N = 8905). According to the time-to-event data and the reconstructed Kaplan-Meier curves, the cumulative overall survival rate was 49.0% and 50.9% in the LH and OH cohorts, respectively, a log-rank test did not demonstrate statistical significance (p > 0.05). The cumulative recurrence-free survival (RFS) probability was both close to 0.0%. The median RFS time was 49.1 (95% CI 46.1 ~ 51.7) and 44.3 (95% CI 41 ~ 46.1) months. The difference in disease status was statistically significant by the Log-rank test (p < 0.05). Using the random-effects model of two-stage analysis, the minor hepatectomy subgroup (HR = 1.32, 95% CI [1.09, 1.55], I2 = 6.2%, p = 0.383) and the shared fragile model of one-stage analysis (HR = 1.44 95% CI [1.23, 1.69], p < 0.001) suggested that LH could significantly prolong RFS of patients compared with OH. This result was consistent with sensitivity analysis using different models. This study was the first reconstructed time-to-event data based on a high-quality propensity-score matching study to compare the survival outcomes of LH and OH in the treatment of HCC. Results suggested that LH can improve RFS in patients with HCC undergoing minor hepatectomy and may also benefit long-term RFS in overall patients.

Laparotomic versus robotic surgery in elderly patients with endometrial cancer: A systematic review and meta-analysis.

BackgroundAlthough robotics has been shown to improve outcomes in some high‐difficulty surgical category patients, it is unclear if such an approach may improve outcomes in elderly patients with endometrial carcinoma (EC).ObjectiveTo compare robotic and laparotomic surgery in the treatment and staging of elderly EC patients.Materials and methodsA systematic review and meta‐analysis was performed assessing the risk of overall, intra‐operative, and peri‐operative complications associated with the surgical approach (laparotomic vs robotic) for elderly patients with EC by relative risk (RR). Pooled means ± standard deviation of length of stay were compared with the unpaired t test. Subgroup analyses for overall complications were performed based on different age cut‐offs (>70, >65, and >75 years) and severity of complications (minor and major). A value of P less than 0.05 was considered significant.ResultsFive studies with 7629 EC patients were included. Pooled RR for robotic compared with laparotomic surgery was 0.40 (P < 0.001) for overall, 0.46 (P = 0.18) for intra‐operative, and 0.43 (P < 0.001) for peri‐operative complications. Pooled difference between means ± standard deviation of length of stay for robotic versus laparotomic surgery was −3.34 (P < 0.001). At subgroup analyses, pooled RR of overall complications for robotic surgery versus laparotomic surgery was 0.34 (P < 0.001) in the >70 years, 0.51 (P < 0.01) in the >65 years, 0.20 (P = 0.12) in the >75 years groups. Pooled RR was 0.50 (P = 0.1) in the minor complications subgroup, and 0.42 (P = 0.002) in the major complications subgroup.ConclusionRobotics might be a viable alternative to the laparotomic approach for EC in elderly patients because it significantly decreases the risk of overall and peri‐operative complications (mainly major complications), and the length of stay when compared with laparotomy. The decrease in risk of overall complications is greater with increasing patient age.

Ultrasound-guided dextrose solution perimysium dissection for posterior shoulder myofascial pain.

To assess the efficacy and safety of perimysium dissection for posterior shoulder myofascial pain. This retrospective single-arm study was performed at a medical center between April 2016 and August 2017. Fifty-seven participants with refractory chronic posterior shoulder pain of myofascial origin underwent ultrasound (US)-guided perimysium dissection with hypertonic dextrose solution. Visual analog scale (VAS) scores and complication rate were evaluated before treatment and 4 weeks after treatment. US-guided perimysium dissection with dextrose solution resulted in excellent treatment efficacy and safety. Nineteen participants (33.3%) were free of pain after treatment, and 32 (56.1%) had >50% improvement in pain score. Forty-nine participants had complete VAS records. Overall mean pre- and posttreatment VAS scores were 7.18 ± 1.60 and 1.91 ± 2.04 (mean difference -5.27, 95% CI -5.99 to -4.55, p < 0.0001), respectively, including 7.26 ± 1.44 and 1.84 ± 1.98 (mean difference -5.43, 95% CI -6.33 to -4.52, p < 0.0001) for those with infraspinatus myofascial pain, and 7.00 ± 1.96 and 2.07 ± 2.26 (mean difference -4.93, 95% CI -6.23 to -3.62, p < 0.0001) for those in the teres minor subgroup. No complications were reported in any of the participants. One participant received retreatment for teres minor myofascial pain. US-guided perimysium dissection is an easy, safe, and effective injection method to manage posterior myofascial shoulder pain.

MBRS-46. CHARTING NEOPLASTIC AND IMMUNE CELL HETEROGENEITY IN HUMAN AND GEM MODELS OF MEDULLOBLASTOMA USING scRNAseq

We explored cellular heterogeneity in medulloblastoma using single-cell RNA sequencing (scRNAseq), immunohistochemistry and deconvolution of bulk transcriptomic data. Over 45,000 cells from 31 patients from all main subgroups of medulloblastoma (2 WNT, 10 SHH, 9 GP3, 11 GP4 and 1 GP3/4) were clustered using Harmony alignment to identify conserved subpopulations. Each subgroup contained subpopulations exhibiting mitotic, undifferentiated and neuronal differentiated transcript profiles, corroborating other recent medulloblastoma scRNAseq studies. The magnitude of our present study builds on the findings of existing studies, providing further characterization of conserved neoplastic subpopulations, including identification of a photoreceptor-differentiated subpopulation that was predominantly, but not exclusively, found in GP3 medulloblastoma. Deconvolution of MAGIC transcriptomic cohort data showed that neoplastic subpopulations are associated with major and minor subgroup subdivisions, for example, photoreceptor subpopulation cells are more abundant in GP3-alpha. In both GP3 and GP4, higher proportions of undifferentiated subpopulations is associated with shorter survival and conversely, differentiated subpopulation is associated with longer survival. This scRNAseq dataset also afforded unique insights into the immune landscape of medulloblastoma, and revealed an M2-polarized myeloid subpopulation that was restricted to SHH medulloblastoma. Additionally, we performed scRNAseq on 16,000 cells from genetically engineered mouse (GEM) models of GP3 and SHH medulloblastoma. These models showed a level of fidelity with corresponding human subgroup-specific neoplastic and immune subpopulations. Collectively, our findings advance our understanding of the neoplastic and immune landscape of the main medulloblastoma subgroups in both humans and GEM models.

Growth patterns and cardiovascular abnormalities in SGA fetuses: 2. Normal growth and progressive growth restriction

Objectives To characterize growth processes and their associated cardiovascular abnormalities in SGA fetuses with normal growth and progressive growth restriction patterns as defined by Individualized Growth Assessment (IGA). Methods A SGA cohort (EFW and BW < 10th percentile) was derived from the PORTO study that included 47 fetuses with normal growth outcome (SGA Normal) and 34 fetuses with progressive growth restriction (SGA Growth Restricted, Pattern 1). Composite fetal size parameters were used to quantify growth pathology at individual third trimester time points (individual composite Prenatal Growth Assessment Score {icPGAS}) and calculated cumulatively during the third trimester (Fetal Growth Pathology Score 1{FGPS1}). Paired Doppler evaluations of the umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and myocardial performance index (MPI) were used to detect cardiovascular anomalies. Outcome variables were birth age and birth weight. Results Ranking fetuses with respect to the severity of the 3rd trimester growth pathology (–FGPS1) revealed three subgroups in each of these two groups. In SGA Normal, no (51%), minimal (19%) or minor (30%) growth abnormalities were present. Although vascular flow abnormalities occurred without growth abnormalities (UA: 38%; MCA: 35%), they increased with minor growth disturbances (UA: 64%; MCA: 50%). All fetuses delivered at term and in only 7 cases (minor growth abnormalities subgroup) were the neonates abnormally small based on IGA criteria. In SGA Growth Restricted, Pattern 1, the progression of growth restriction was slow (47%), moderate (21%) and rapid (32%). Corresponding median –FGPS1 values were −1.34%, −2.67% and −4.88%, respectively. The median age of onset was 33.6, 29.7 and 29.7 weeks in these three subgroups. UA abnormalities occurred infrequently in the first two subgroups but were found in all cases of rapidly progressing pathology. Similar results were found for the MCA and DV + MPI Doppler parameters (rapid progression: MCA = 50%; DV + MPI = 50%). Premature delivery occurred less frequently with slow progression but was nearly 100% in the moderately and rapidly progressive subgroups. Conclusions Negative FGPS1 growth restriction patterns can be used to classify SGA fetuses. Subgroups, based on ranked –FGPS1 values in both SGA Normal and SGA Growth Restricted Pattern 1 groups had marked differences in cardiovascular abnormalities and neonatal outcomes. The characteristics of these two groups are consistent with small, normally growing fetuses and fetuses with “early” growth restriction, respectively.

Fundamental Questions about ??T Cells

γδT cells is a minor subgroup of T lymphocytes expressing γδ-T Cell Receptor (TCR), with many subsets, dominated by Vδ2 and Vδ1. γδT cells recognize antigens independently of the context of MHC class I, MHC class II, or CD1 presenting molecules. However, this recognition requires the expression of the transmembrane Butyrophilin proteins by the presenting cells. Their activation is controlled by many surface receptors, namely, co-stimulatory receptors, cytokines receptors, NK receptors and inhibitory receptors. Once activated, γδT cells polarize into Th1, Th2, Th17, follicular T helper or Treg cells. They can play direct anti infectious and antitumor roles through perforin-granzyme molecules, FasL and Tumor-necrosis-factor Related Apoptosis Inducing Ligand (TRAIL), antibody-dependent cellular cytotoxicity and by IFN-γ and TNF-α cytokine’s release. They also exert an indirect antitumor activity by cooperating with B cells, dendritic cells, αβT cells and NK cells. Additionally, γδT cells can infiltrate solid cancers and display a selective cytolytic activity. Conversely, γδT cells might promote cancer progression either directly through IL17 and/or VEGF, or indirectly by impairing other antitumor immune cell activities. Given its complex functions, γδT cell-based immunotherapy seems efficient and well tolerated, yet needs to overcome many obstacles including those related to the tumor environment.

ТРАНС-ГЕРМАНСЬКІ ОСОБЛИВОСТІ ПРЕТЕРИТО-ПРЕЗЕНТНИХ ДІЄСЛІВ

This article contains systematic and detailed analysis of morphological and semantic parameters of Germanic preterite-present verbs, dividing them into major and minor subgroups. The development of both preterite-present subgroups and their steady transformation into the modal verbs is a specific feature of all Germanic languages. Since the modal verbs of the Modern Germanic languages are morphologically defective, it is commonly assumed that preterite-present verbs of the old Germanic languages lost some of their morphological features in the process of turning into modal verbs. The semantic aspects of this process are rather obscure. All Germanic languages were losing some preterite-present verbs in the process of transformation from the Gothic language, which had fourteen preterite-present verbs. In OE there were twelve preterite-present verbs. Six of them survived in NE. The morphological description focuses on the finite and non-finite forms of the preterite-present verbs, which belong to the minor subgroup. The detailed description helps to see the origin and development of the minor subgroup in the new light. The description encompasses the data of classical Indo-European languages and Old Germanic languages. The authors emphasize the expediency of turning to the theory of preterite/strong verb origin, the verbs in question may be regarded as inter-group, hybrid units. In order to gain insight into the origin of the Germanic languages it is necessary to look into the history of the Gothic and West Germanic and North Germanic languages. The authors find it useful to compare common and different phenomena, highlighting individual specific processes taking place in the process of development of the Germanic languages. These languages are analyzed on different stages of their development, but inline with the view that the languages co-operated and coexisted in the same area. The data given in the article are used to analyze the problem implementing comparative grammar tools. The authors were particularly careful to take all grammatical forms into consideration while working with the lexical units from the ancient sources. Some additional information was taken from Greek, Latin and Sanskrit to produce reliable and consistent comparison of the German language with the rest of Indo-European languages.

Comparison of FIB-4 Index and Child-Pugh Score in Predicting the Outcome of Hepatic Resection for Hepatocellular Carcinoma

Background and AimsThe Child-Pugh (CP) score is a widely used method to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the fibrosis index (FIB-4) has been demonstrated to be closely associated with liver fibrosis and cirrhosis. This study aimed to compare the capability of FIB-4 index with CP score in predicting the outcomes for HCC patients after hepatectomy. MethodsA total of 495 HCC patients who underwent hepatectomy were enrolled. The performance of the FIB-4 index in predicting postoperative liver failure (PHLF) and overall survival was compared with that of the CP score. ResultsOf them, 9.3% (46/495) patients developed PHLF. The area under the receiver operating characteristic (ROC) curve of the FIB-4 index for predicting PHLF was greater than that of the CP score (0.744 versus 0.621; P = 0.044). The optimal cutoff value of the FIB-4 index for predicting PHLF was 4.16. Multivariable analyses revealed that the FIB-4 index was an independent predictor of PHLF regardless of the hepatectomy subgroups, but the CP grade was only a significant predictor of PHLF in the minor hepatectomy subgroup. The FIB-4 index (4.16) stratified patients into two distinct overall survival cohorts (P = 0.006). The FIB-4 index also classified patients with the Barcelona Clinical Liver Cancer (BCLC) stages 0 and A into two distinct overall survival cohorts (P = 0.001 and P = 0.034, respectively). ConclusionThe FIB-4 index may be a better predictor of PHLF and overall survival in HCC patients with hepatectomy than CP score.

Patient-reported complications related to colonoscopy: a prospective feasibility study of an email-based survey

Objective: This prospective pilot study assessed the feasibility of electronic email-based questionnaires about patient-reported complications after colonoscopy.Material and methods: A newly internally validated questionnaire on patient-reported complications related to colonoscopy was conducted as an online survey.Results: Out of 200 patients (mean age 65 years), 83% completed the first questionnaire immediately after the procedure, 77% completed the second follow-up questionnaire after 24 h at home, and 70% the third one after 30 d. Forty-four percent of the patients reported minor adverse events after 24 h, and 23% at the follow-up after 30 d. The rate of sick leave in the 30-d period after the colonoscopy was 6%.Conclusions: This study shows that email-based questionnaires give a high response rate independent of age or gender, but that the response rate declines with time after colonoscopy. Minor adverse events are underestimated, and colonoscopy could lead to sick leave in a minor subgroup of patients.

A Comparative Study of Albumin-Bilirubin Score with Child-Pugh Score, Model for End-Stage Liver Disease Score and Indocyanine Green R15 in Predicting Posthepatectomy Liver Failure for Hepatocellular Carcinoma Patients

Background: The albumin-bilirubin (ALBI) grade is a newly proposed model for assessing the hepatic function. This study aimed to compare the value of the ALBI score with Child-Pugh score, model for end-stage liver disease (MELD) score and indocyanine green (ICG) R15 in predicting posthepatectomy liver failure (PHLF). Methods: Patients undergoing curative resection for hepatocellular carcinoma (HCC) between January 2014 and June 2017 were enrolled. The values of the Child-Pugh score, MELD score, ICG R15 and ALBI score in predicting PHLF were evaluated. Results: A total of 473 HCC patients were enrolled. The ALBI score was identified as an independent predictor of PHLF. The AUCs for the Child-Pugh score, MELD score, ICG R15 and ALBI score in predicting PHLF were 0.665, 0.649, 0.668, and 0.745 respectively. Multivariable analyses revealed that the ALBI score was an independent predictor of PHLF regardless of the hepatectomy subgroups, but the Child-Pugh score and MELD score were not significant predictors of PHLF both in major and minor hepatectomy subgroups, and ICG R15 was only a significant predictor of PHLF in minor hepatectomy subgroup. Conclusion: The ALBI score showed superior predictive value of PHLF over Child-Pugh score, MELD score and ICG R15. We propose to use the ALBI score to evaluate surgical risk for HCC patients undergoing hepatic resection.

Mutation of serine/threonine protein kinase 36 (STK36) causes primary ciliary dyskinesia with a central pair defect.

Primary ciliary dyskinesia (PCD) is a genetic condition of impaired ciliary beating, characterized by chronic infections of the upper and lower airways and progressive lung failure. Defects of the outer dynein arms are the most common cause of PCD. In about half of the affected individuals, PCD occurs with situs inversus (Kartagener syndrome). A minor PCD subgroup including defects of the radial spokes (RS) and central pair (CP) is hallmarked by the absence of laterality defects, subtle beating abnormalities, and unequivocally apparent ultrastructural defects of the ciliary axoneme, making their diagnosis challenging. We identified homozygous loss-of-function mutations in STK36 in one PCD-affected individual with situs solitus. Transmission electron microscopy analysis demonstrates that STK36 is required for cilia orientation in human respiratory epithelial cells, with a probable localization of STK36 between the RS and CP. STK36 screening can now be included for this rare and difficult to diagnose PCD subgroup.

Clinical significance of psychotic-like experiences in children and adolescents.

Psychotic-like experiences (PLEs) are subtle, subclinical hallucinations and delusions which are quite common in general population. In children and youth prevalence rate is probably age-dependent with higher rate in younger population. PLEs are suggested to be a form of extended psychosis phenotype. Similar demographic, genetic and environmental risk factors observed for PLEs and schizophrenia support this hypothesis. Other mental health problems associated with PLEs include depression, suicidality, low functioning and psychiatric comorbidity. PLEs may be a risk factor for psychosis, but probably only for a minor subgroup of population. It is possible however, that PLEs are a risk factor for different psychiatric disorders. In the majority of children and adolescents PLEs disappear over time. PLEs are supposed to be a heterogenic phenomenon with different subtypes: associated with psychosis risk, associated with other psychiatric disorders and being within the normal range of experiences. Due to lack of widely acknowledged PLEs definition and because of substantial diversity of research methodology interpretation of the previous research should be made with caution.

Molecular subtypes of colorectal cancers determined by PCR-based analysis.

Tumor tissue consists of a heterogeneous cell population. The allelic imbalance (AI) ratio, determined in isolated tumor glands, is a good index of tumor heterogeneity. However, associations of the patterns of AI and microsatellite instability (MSI) development, observed in most cases of colorectal cancer (CRC), with tumor progression have not been reported previously. In this study, we examined whether CRC genetic profiles stratified by a combination of the AI ratio and MSI facilitate categorization of CRC, and whether these genetic profiles are associated with specific molecular alterations in CRC. A crypt isolation method was used to isolate DNA from tumors and normal glands obtained from 147 sporadic CRCs. AI and MSI statuses were determined using PCR‐based microsatellite analysis and stratified based on AI ratio and MSI status. DNA methylation status (high methylation, intermediate methylation and low methylation status and mutations in KRAS,BRAF, and TP53 were examined. In addition, mucin markers were immunostained. Based on this analysis, four subgroups were categorized. Subgroup 1 was characterized by a high MSI status and BRAF mutation; subgroup 2 was closely associated with a high AI ratio, which accumulated during the early phases of colorectal carcinogenesis, and TP53 mutation; subgroup 3 was associated with a low AI ratio, seen during the later phases of colorectal carcinogenesis, and KRAS mutation; and subgroup 4 was defined as a minor subgroup. These results confirmed that classification of distinct molecular profiles provides important insights into colorectal carcinogenesis.