Mixed Subtype Research Articles

Prevalence and risk factors associated with psoriatic arthritis among patients with psoriasis.

Psoriatic arthritis is a chronic, autoimmune inflammatory arthritis that occurs with psoriasis and has profound impact on patients' physical and psychological well-being. This study aims to determine the prevalence and risk factors associated with psoriatic arthritis among patients with psoriasis. A single-center, cross-sectional study was conducted over a 12-month period at the Dermatology Clinic, Hospital Pulau Pinang, Malaysia involving all consecutive psoriasis patients. CASPAR (ClASsification of Psoriatic ARthritis) criteria were used to diagnose psoriatic arthritis. A total of 360 patients with psoriasis were recruited, of whom 107 (29.7%) had psoriatic arthritis. Psoriatic arthritis patients had equal gender distribution and the mean age of arthritis onset was 40.7 ± 12.8 years. Psoriasis preceded arthritis in 81.3% of patients (n = 87) with a mean latency interval of 10.5 years. Polyarthropathy was the predominant subtype affecting 46.8% (n = 50) of patients, followed by oligoarthropathy (22.4%, n = 24), axial joint disease (5.6%, n = 6), predominant distal interphalangeal joint disease (2.8%, n = 3), and mixed subtype (22.4%, n = 24). Enthesitis and dactylitis occurred in 12.1% (n = 13) and 20.6% (n = 22) of arthritis patients, respectively, and deformity was present in 37.4% (n = 40). Psoriatic arthritis was significantly associated with being an ever smoker (adjusted odds ratio [aOR] 0.41; 95% confidence interval [CI] 0.18-0.91, p = .029), genital psoriasis (aOR 2.25; 95% CI 1.17-4.33, p = .015), and increased erythrocyte sedimentation rate (ESR) (aOR 1.02; 95% CI 1.01-1.04, p = .005) and C-reactive protein [CRP] (aOR 1.04; 95% CI 1.00-1.08, p = .040). Our study showed a high prevalence of psoriatic arthritis among the psoriasis cohort. Genital involvement, and increased ESR and CRP were associated with psoriatic arthritis among patients with psoriasis.

MR Imaging Findings and Texture Analysis of Pure and Mixed Mucinous Breast Carcinoma

Purpose: To evaluate the ability of magnetic resonance imaging (MRI) findings and texture features to differentiate between pure and mixed subtypes of mucinous breast carcinoma.Methods: This retrospective study included 136 patients who were surgically diagnosed with mucinous breast carcinoma and underwent pre-treatment breast MRI between January 2008 and December 2020. All clinicopathological and MRI features were reviewed. For texture analysis, regions of interest of the tumors were drawn manually on T2-weighted images and first-subtraction T1-weighted images. Texture feature extraction and analysis were conducted using open-source 3D slicer software. Univariate and multivariate analyses were used to identify significant MRI findings and texture features to differentiate between the two subtypes. To evaluate the diagnostic performance of the texture features, a receiver operating characteristic curve analysis was conducted.Results: Among the MRI findings, very high signal intensity on T2-weighted images was significantly associated with pure mucinous breast carcinoma (odds ratio=5.23, <i>p</i>=0.001). The homogeneity and skewness texture features from T2-weighted imaging showed statistically significant differences between pure and mixed subtypes, and the areas under the receiver operating curve were 0.749 and 0.815, respectively.Conclusion: Signal intensity and texture features on T2- weighted images derived from breast MRI can assist in the differential diagnosis of pure and mixed types of mucinous breast carcinoma.

A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantification.

Gastric cancer is a highly heterogeneous malignant tumor of the digestive system. Anti-HER2 treatment can inhibit downstream signaling pathways and improve clinical treatment and outcomes in patients with HER2 protein overexpression. Currently, two standard methods for evaluating HER2 expression status are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). However, these low-throughput assays often produce discordant or equivocal results. In this study, we presented a new HER2 protein detection method based on mass spectrometry selected reaction monitoring (MS-SRM) and validated the method. We conducted a retrospective study on 118 formalin-fixed paraffin-embedded (FFPE) tissues from patients with advanced gastric adenocarcinoma in northern China, and we compared the MS-SRM results with those from IHC and correlated them with FISH. We established and validated the upper and lower detection limits (300-700 amol/μg) for abnormal HER2 protein expression in advanced gastric cancer. We also found that, among samples with mixed Lauren subtypes, those with a high level of HER2 expression had typical intestinal type features in pathology. This study demonstrated that the MS-SRM method can overcome the limitations and deficiencies of IHC, directly quantify the expression of HER2 protein in tumor cells and be used as a supplement to IHC. It has the potential to be used as a companion diagnosis for new drugs used to treat advanced gastric cancer. Large-scale clinical validation is required.

Evaluation of the Blood-Brain Barrier, Demyelination, and Neurodegeneration in Paramagnetic Rim Lesions in Multiple Sclerosis on 7 Tesla MRI.

Paramagnetic rim lesions (PRLs) are associated with chronic inflammation in multiple sclerosis (MS). 7-Tesla (7T) magnetic resonance imaging (MRI) can evaluate the integrity of the blood-brain barrier (BBB) in addition to the tissue myelination status and cell loss. To use MRI metrics to investigate underlying physiology and clinical importance of PRLs. Prospective. Thirty-six participants (mean-age 47, 23 females, 13 males) of mixed MS subtypes. 7T, MP2RAGE, MULTI-ECHO 3D-GRE, FLAIR. Lesion heterogeneity; longitudinal changes in lesion counts; comparison of T1, R2*, and χ; association between baseline lesion types and disease progression (2-3 annual MRI visits with additional years of annual clinical follow-up). Two-sample t-test, Wilcoxon Rank-Sum test, Pearson's chi-square test, two-group comparison with linear-mixed-effect model, mixed-effect ANOVA, logistic regression. P-values <0.05 were considered significant. A total of 58.3% of participants had at least one PRL at baseline. Higher male proportion in PRL+ group was found. Average change in PRL count was 0.20 (SD = 2.82) for PRLs and 0.00 (SD = 0.82) for mottled lesions. Mean and median pre-/post-contrast T1 were longer in PRL+ than in PRL-. No differences in mean χ were seen for lesions grouped by PRL (P = 0.310, pre-contrast; 0.086, post-contrast) or PRL/M presence (P = 0.234, pre-contrast; 0.163, post-contrast). Median χ were less negative in PRL+ and PRL/M+ than in PRL- and PRL/M-. Mean and median pre-/post-contrast R2* were slower in PRL+ compared to PRL-. Mean and median pre-/post-contrast R2* were slower in PRL/M+ than in PRL/M-. PRL presence at baseline was associated with confirmed EDSS Plus progression (OR 3.75 [1.22-7.59]) and PRL/M+ at baseline with confirmed EDSS Plus progression (OR 3.63 [1.14-7.43]). Evidence of BBB breakdown in PRLs was not seen. Quantitative metrics confirmed prior results suggesting greater demyelination, cell loss, and possibly disruption of tissue anisotropy in PRLs. 2 TECHNICAL EFFICACY: Stage 2.

Coagulation profiles in patients with sepsis/septic shock identify mixed hypo-hypercoagulation patterns based on rotational thromboelastometry: A prospective observational study

IntroductionSepsis-induced hemostatic disturbances are common and are associated with poor outcomes. Additionally, conventional coagulation tests (CCTs) overdiagnose hypocoagulation and cannot detect hypercoagulation and hyperfibrinolysis. The aim of this study was to describe the coagulation profiles of patients with sepsis/septic shock using rotational thromboelastometry (ROTEM) and to compare coagulation states between sepsis and septic shock groups and between surviving and non-surviving groups. Materials and methodsThis prospective, observational, single-center study was conducted in the intensive care unit (ICU) of the University Medical Center Ho Chi Minh City, from 6/2020–12/2021. Patients aged ≥18 years with sepsis or septic shock according to the Sepsis-3 criteria were included. ROTEM and CCTs were concurrently performed within the first 24 h of ICU admission. ResultsIn total, 161 patients were enrolled. Based on ROTEM, 72.7 % of patients with sepsis/septic shock had coagulation disorders, including 25.5 % hypercoagulation, 54.7 % hypocoagulation, 13.6 % mixed hypo-hypercoagulation patterns, and 18.6 % hyperfibrinolysis. A common mixed disorder subtype was characterized by prolonged initial clotting time (CT) with subsequently increased clot firmness. Fibrinogen levels and maximum clot formation (MCF)-fibtem were strongly correlated (rho = 0.73, p < 0.05). Hypocoagulation was observed more in the septic shock group than in the sepsis group. Compared to survivors, non-survivors had more prolonged CT-extem. ConclusionsROTEM could identify hypocoagulability, hypercoagulability, mixed hypo-hypercoagulability patterns, and hyperfibrinolysis in patients with sepsis/septic shock. Elevated MCF-fibtem and elevated fibrinogen levels were notably common and strongly correlated. The septic shock group had more hypocoagulation than the sepsis group. Lastly, non-survivors had more prolonged CT-extem than survivors.

Correlation and Level of Agreement between the Ocular Surface Disease Index and the Symptom Assessment in Dry Eye Questionnaires: A Survey-Based Study

Purpose The Ocular Surface Disease Index (OSDI) is the most frequently used dry eye disease (DED) questionnaire, and the Symptom Assessment iN Dry Eye (SANDE) is the simplest and quickest to apply. We analyze the correlation and level of agreement between these two questionnaires in a large DED heterogeneous population to evaluate their performance and potential interchangeability. Methods Prospective, multicenter longitudinal survey-based study performed on patients diagnosed with DED by 99 ophthalmologists from 20/32 Mexican states. Questionnaires were applied in two consecutive visits to analyze the correlation between OSDI and SANDE to evaluate patients with DED clinically. Level of agreement was evaluated with Bland-Altman analysis, and internal consistency of instruments was evaluated individually and combined with Cronbach’s alpha index. Results 3421 patients studied: 1996 (58.3%) women and 1425 (41.7%) men, aged 49.5 ± 15.4 years; 995 (29.1%) patients had aqueous-deficient, 1086 (31.7%) evaporative, and 1340 (39.2%) mixed DED subtypes. Normalized baseline scores were 53.7 (OSDI) and 54.1 (SANDE). After 36.3 ± 24.4 days between visits, scores were reduced to 25.2 (OSDI) and 21.8 (SANDE) points (p < .001). A positive correlation between questionnaires was found at baseline (R = 0.592; p < .001), follow-up (R = 0.543; p < .001) and change between visits (R = 0.630; p < .001). Using both questionnaires together improved the overall reliability of symptom evaluation at baseline (α = 0.7), follow-up (α = 0.7), and both (α = 0.7), compared to individual application (OSDI α = 0.5, SANDE α = 0.6)—the same improvements applied to all DED subtypes. Bland-Altman analysis revealed a differential bias of -0.41% at baseline and +3.6% at follow-up visits between OSDI and SANDE. Conclusions We validated the correlation (high precision) between questionnaires in a large-scale population, demonstrating improved reliability (high accuracy) in evaluating DED when used together, challenging their interchangeable use. These results open a venue to improve recommendations toward a more precise and accurate diagnostic and therapeutic evaluation of DED by using OSDI and SANDE concurrently.

The mixed subtype has a worse prognosis than other histological subtypes: a retrospective analysis of 217 patients with metaplastic breast cancer

ObjectiveMetaplastic breast cancer (MpBC) is an aggressive subtype of all breast cancer. We aimed to investigate the clinicopathological features, treatments and prognoses of MpBC patients.MethodsWe collected the data from MpBC patients diagnosed at Tianjin Medical University Cancer Hospital from 2010 to 2017. Kaplan Meier curves and Cox regression model were used to evaluating clinical outcomes and prognostic factors. After removing baseline differences by propensity score matching (PSM), we analyzed the prognosis between MpBC patients and invasive ductal carcinomas of no special type (IDC-NST) patients.ResultsA total of 217 MpBC patients were subsumed. Of all histological subtypes, 45.1% were mixed subtypes, followed by with mesenchymal differentiation (27.2%), pure squamous (15.2%) and pure spindle (12.4%) subtypes. 69.6% of MpBC were triple-negative, 25.3% and 6.5% were HR-positive and HER2-positive. MpBC patients had worse survival compared to IDC-NST patients, with 5-year RFS of 73.8 and 83.6% (HR = 1.177 95%CI (1.171–2.676) P = 0.0068), and 5-year BCSS of 79.0% and 89.7% (HR = 2.187 95%CI (1.357–3.523) P = 0.0013). In the multivariate COX model, AJCC stage, mixed subtype and chemotherapy were independent prognostic factors. Mixed MpBC is more aggressive than pure and with heterologous mesenchymal differentiation subtypes. And whether squamous or spindle MpBC, mixed forms have shorter outcomes than pure forms.ConclusionsMpBCs are associated with poorer prognoses than IDC-NSTs. They are heterogeneous with different clinicopathological features and clinical outcomes between histological subtypes. Pure and with heterologous mesenchymal differentiation subtypes have more survival benefits than the mixed subtype.

Exploring Blastocystis genetic diversity in rural schoolchildren from Colombia using next-generation amplicon sequencing reveals significant associations between contact with animals and infection risk

Blastocystis is a common intestinal protist with a global distribution in humans and many other animals. Yet, the status of Blastocystis as a pathogen, the risk factors associated with its transmission, and its zoonotic potential remain ill-defined. Here, we explored subtype (ST) diversity and potential risk factors for Blastocystis infection in 98 children from Apulo, Colombia. Samples were screened for Blastocystis via PCR, and ST identification was performed through next-generation amplicon sequencing (NGS). Associations between the presence of Blastocystis and individual STs and sociodemographic variables were assessed via logistic regression analyses. Seventy-one samples (72.4%) were Blastocystis-positive, and NGS revealed the presence of five STs (ST1-ST5). ST1, ST2, and ST3 were common and observed in nearly equal proportions (~ 40%), while samples with ST4 (1.4%) and ST5 (5.6%) were comparatively rare. The presence of mixed STs in the same sample was also common (28.2%). Comparisons among children within the same household identified that shared ST profiles were common, but diversity within family units was also observed. Logistic regression analyses returned significant associations between the presence of Blastocystis, individual subtypes, or mixed subtypes for several variables. Intriguingly, the presence of animals was one of the most common significant associations. Taken together, these data represent an important step forward in understanding both the potential routes and risk factors that may influence Blastocystis transmission and will be useful in shaping future studies which seek to clarify the relationships between STs, pathogenicity, and zoonotic transmission.

Updated Parkinson's disease motor subtypes classification and correlation to CSF HVA and 5-HIAA levels (P3-11.005)

<h3>Objective:</h3> To update a motor subtypes classification using the MDS-UPDRS and determine if CSF neurotransmitter profiles (HVA and 5-HIAA) are different between MDS-UPDRS subtypes in a cohort from the Parkinson9s Progression Marker Initiative (PPMI). <h3>Background:</h3> Schiess <i>et al</i> designed a UPDRS motor classification of Parkinson9s Disease (PD) that has been widely used, but in the last decade, the field has moved towards the use of the MDS-UPDRS. <h3>Design/Methods:</h3> UPDRS and MDS-UPDRS scores were collected for 20 PD patients. Akinetic-rigid (AR), Tremor-dominant (TD), and Mixed (MX) subtypes were calculated using a UPDRS formula, and a new ratio was developed for MDS-UPDRS. This new formula was subsequently applied to 95 PD patients from the PPMI dataset, and subtyping was correlated to neurotransmitter levels. Data were analyzed using receiver operating characteristic models and ANOVA. <h3>Results:</h3> Compared to previous UPDRS classifications, the new MDS-UPDRS AR/TD ratios produced significantly different areas under the curves (AUC). The optimal sensitivity and specificity cutoff scores were ≥0.82 for TD, ≤0.71 for AR classifications and Mixed &gt;0.71 and &lt;0.82. Analysis of variance showed significant differences in 5-HIAA levels between the HC and AR group. Logistic models utilizing neurotransmitter levels and MDS-UPDRS motor scores showed significant AUCs for MDS-UPDRS classifications. <h3>Conclusions:</h3> This MDS-UPDRS motor subtype classification system provides a method to transition from the original UPDRS to the newer MDS-UPDRS and offers a reliable and quantifiable tool for monitoring disease progression that is supported by neurotransmitter levels. <b>Disclosure:</b> Dr. Suescun has nothing to disclose. Dr. Adams has stock in Medtronic. Dr. Block has nothing to disclose. Dr. Tharp has nothing to disclose. The institution of Prof. Ellmore has received research support from NIMH. Dr. Schiess has nothing to disclose.

Abstract 4212: Comparison of thirty-year population-based incidence rates of invasive lobular vs ductal vs mixed breast carcinoma in Ontario, Canada

Abstract Purpose: We calculated crude, age-adjusted and age-specific incidence rates for invasive lobular, ductal and mixed ductal-lobular breast carcinoma from 1990 to 2020 in the province of Ontario, Canada. We further examined incidence relationships between clinical stage, age at diagnosis and time. Methods: We used population-based administrative healthcare datasets from the Institute of Clinical Evaluative Sciences (ICES Ontario), including the Ontario Cancer Registry, to identify all women diagnosed with breast cancer between 1990 and 2020. We calculated crude, age-adjusted and age-specific incidence rates for invasive lobular (ILC), ductal (IDC) and mixed ductal-lobular (IDC-ILC) breast carcinoma. Incidence rates were adjusted to the 2011 Canadian female standard population. We further examined the incidence relationships between clinical stage and age at diagnosis over time. Results: From 1990 to 2020, the 5-year crude incidence rates of ILC increased from 53.1 to 73.4 per 100,000 (+38%), while IDC increased from 501 to 746.5 per 100,000 (+49%). The crude incidence of mixed IDC-ILC peaked at 45 per 100,000 between 2005 and 2009 and is currently 29 per 100,000. The age-adjusted 5-year incidence rate of ILC has slightly increased from 64 to 70 per 100,000 (+9%) while that of IDC has increased from 598 to 726 per 100,000 (+21%). The age-adjusted 5-year incidence of mixed IDC-ILC peaked at 47 per 100.000 between 2005 and 2009 and has declined to 29 per 100,000. Age-specific 5-year incidence rates for ILC has decreased over time in women &amp;lt; 40 years of age and increased in women over the age of 65. In contrast, age-specific 5-year incidence rates for IDC have remained stable in women over 75. For mixed IDC-ILC, age-specific 5-year incidence rates have increased over time in all age categories. Among women with ILC, there is a greater proportion of women under the age of 50 diagnosed with stage III disease (30%) compared with women diagnosed over the age of 50 (16%). Women between the ages of 50 and 74 have higher rates of being diagnosed at stage I (43%) compared with 35% and 31% for women diagnosed between the ages of 40-49 and over 75, respectively. Conclusions: The incidence of invasive lobular breast carcinoma in increasing, particularly in women over the age 65. Consequently, the burden of lobular breast carcinoma is expected to increase, as the proportion of women over the age of 65 is expected to rise exponentially in the foreseeable future, highlighting a need for further study of this not uncommon breast cancer subtype. While representing a smaller proportion of breast cancer diagnoses, the incidence of mixed invasive ductal-lobular subtype is increasing in all age groups. Citation Format: David Wai Lim, Vasily Giannakeas, Steven Narod, Kelly A. Metcalfe. Comparison of thirty-year population-based incidence rates of invasive lobular vs ductal vs mixed breast carcinoma in Ontario, Canada. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4212.

Abstract 768: Immunohistochemistry analysis of the molecular subtypes of muscle invasive bladder cancer in association with prognosis

Abstract Background: Bladder cancer (BC) is one of the most common cancers worldwide. Muscle invasion BC (MIBC) has a poor prognosis and is usually in an advanced stage. Recently, whole genome sequencing research in BC has pointed out the molecular subtypes of BC which presented correlate with the patient outcome as well as clinical behavior. There are differences between the stratification’s subtypes determined by several research teams. However, the central of these stratifications are classified the BC into the basal BC type and the luminal BC type. We aim to use the immunohistochemical surrogated markers for basal and luminal BC subtypes to discriminate the molecular subtypes of BC and their association with the clinicopathologic features of BC. Method: We performed IHCs for surrogated basal makers (CK5/6 and CD44), and surrogated luminal makers (CK20 and Gata3) in 130 MIBC patients. IHCs classified the MICB into the fourth group including basal type (positive with CK5/6 and/or CD44 and negative both of CK20 and Gata3), luminal type (negative both of CK5/6 and CD44 and positive with CK20 and/or Gata3), null type (negative for all fourth markers) and mixed type (expressed both basal and luminal markers), respectively. We investigated the relationship between the molecular subtypes and the clinicopathological significance of MIBC patients. Furthermore, we analyzed the association of molecular subtypes with the overall survival of MIBC patients. We also analyzed the IMVigor210 cohort and the TCGA-BLCA cohort to validate our results. We investigated the chemo reagents (cisplatin, and 5-Fu) resistance of the BC cell lines which molecular subtypes classified by IHCs. Results: We figured out that the basal subtype and luminal subtype presented 35.28% and 29.23% of MIBC respectively. The null subtype accounted for 18.47% of MIBC. The basal subtype was associated with T stage (p=0.035), squamous differentiation (p=0.0002), stage (p=0.035), and tumor infiltrated lymphocytes (TILs) (p=0.047). There were no significantly different between the overall survival of the basal and mixed subtype of MIBC and the luminal and null subtype MIBC (Log-rank test, p=0.090). Interestingly, we explored that the MIBC without intensive TILs - basal subtype presented the worst prognosis in comparison with other molecular subtypes (Log-rank test, p=0.012). The mRNA basal subtype also presented poor prognosis in BC without immune activities in BLCA (p=0.037) or in IMVigor210 (p=0.0005). Furthermore, the basal cell lines presented lower IC50 than luminal cell lines when treated the cells with cisplatin. Conclusion: Our results pointed out that the molecular subtypes of MIBC were associated with the progression of MIBC. The MIBC patients without intensive TILs - basal subtype have the worst outcome. Suggesting that stratification of molecular subtypes of MIBC by IHCs are appealing option for clinical implementation. Citation Format: QuocThang Pham, Anh Toan Do, Ngoc Minh Tam Nguyen, Phuc Nguyen Nguyen, Thi Phuong Thao Doan, Thi Thanh Tam Bui, Quoc Dat Ngo. Immunohistochemistry analysis of the molecular subtypes of muscle invasive bladder cancer in association with prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 768.

Mixed Autoimmune Hemolytic Anemia in a 2-Year-Old Girl

Immune hemolytic anemia is diagnosed when it exhibits the clinical symptoms and laboratory findings of hemolytic anemia, such as pallor, jaundice, anemia, high indirect bilirubin, increased reticulocyte count, and a positive direct antiglobulin test. Depending on the type of antigenic stimulation, this condition can be divided into three distinct subtypes: (1) autoimmune hemolytic anemia (AIHA), (2) alloimmune hemolysis, and (3) drug-induced hemolysis. In addition, the thermal amplitude of autoantibodies is used to categorize AIHA as either a warm (most common), cold, or mixed (rare) subtype. Mixed autoimmune hemolytic anemia is diagnosed when both warm and cold autoantibodies are present. Here, we report a case of a mixed AIHA in a 2-year-old girl who responded well to corticosteroids. Due to the rarity of the condition and the lack of rigorous diagnostic criteria, it is crucial to report this case.

Clinicopathologic Features and Genetic Alterations in Mixed-Type Ampullary Carcinoma

Mixed-type ampullary carcinoma is a subtype that combines intestinal-type (I-type) and pancreatobiliary-type (PB-type) lesions, but few studies have examined its clinicopathologic features and genetic alterations. The differences in genetic alterations between mixed type and other subtypes, as well as the genetic differences between I-type and PB-type lesions in the mixed type, remain unclear. In this study, we compared the clinicopathologic features and prognosis of 110 ampullary carcinomas classified by hematoxylin and eosin and immunohistochemical staining as follows: 63 PB-type, 35 I-type, and 12 mixed-type carcinomas. A comparative analysis of genetic mutations by targeted sequencing of 24 genes was also performed in 3 I-type cases, 9 PB-type cases, and I and PB-type lesions of 6 mixed-type cases. The mixed subtype had a poorer prognosis than the other subtypes, and there was also a similar tendency in the adjuvant group (n = 22). A total of 49 genetic mutations were detected in all 18 lesions for which genetic alteration was analyzed. No genetic mutations specific to the mixed type were found, and it was not possible to determine genetically whether the mixed type had originally been I or PB type. However, 5 of 6 cases had mutations common to both I and PB-type lesions, and additional mutations were found only in either I or PB-type lesions. In support of this, the mixed type more frequently exhibited genetic heterogeneity intratumorally than the other subtypes. Mixed-type tumors are histologically, immunohistochemically, and genetically heterogeneous, and this heterogeneity is associated with poor prognosis and may affect treatment resistance.

KRAS mutations and endometriosis burden of disease.

The clinical phenotype of somatic mutations in endometriosis is unknown. The objective was to determine whether somatic KRAS mutations were associated with greater disease burden in endometriosis (i.e. more severe subtypes and higher stage). This prospective longitudinal cohort study included 122 subjects undergoing endometriosis surgery at a tertiary referral center between 2013 and 2017, with 5-9 years of follow-up. Somatic activating KRAS codon 12 mutations were detected in endometriosis lesions using droplet digital PCR. KRAS mutation status for each subject was coded as present (KRAS mutation in at least one endometriosis sample in a subject) or absent. Standardized clinical phenotyping for each subject was carried out via linkage to a prospective registry. Primary outcome was anatomic disease burden, based on distribution of subtypes (deep infiltrating endometriosis, ovarian endometrioma, and superficial peritoneal endometriosis) and surgical staging (Stages I-IV). Secondary outcomes were markers of surgical difficulty, demographics, pain scores, and risk of re-operation. KRAS mutation presence was higher in subjects with deep infiltrating endometriosis or endometrioma lesions only (57.9%; 11/19) and subjects with mixed subtypes (60.6%; 40/66), compared with those with superficial endometriosis only (35.1%; 13/37) (p=0.04). KRAS mutation was present in 27.6% (8/29) of Stage I cases, in comparison to 65.0% (13/20) of Stage II, 63.0% (17/27) of Stage III, and 58.1% (25/43) of Stage IV cases (p=0.02). KRAS mutation was also associated with greater surgical difficulty (ureterolysis) (relative risk [RR]=1.47, 95% CI: 1.02-2.11) and non-Caucasian ethnicity (RR=0.64, 95% CI: 0.47-0.89). Pain severities did not differ based on KRAS mutation status, at either baseline or follow-up. Re-operation rates were low overall, occurring in 17.2% with KRAS mutation compared with 10.3% without (RR=1.66, 95% CI: 0.66-4.21). In conclusion, KRAS mutations were associated with greater anatomic severity of endometriosis, resulting in increased surgical difficulty. Somatic cancer-driver mutations may inform a future molecular classification of endometriosis.

A review and analysis of cryptosporidiosis outbreaks in New Zealand.

Cryptosporidium is a leading global cause of diarrhoea with many reported outbreaks related to water and zoonotic transmission. This study summarizes data from Public Health Surveillance reports since 2010 in New Zealand to describe exposures associated with human diarrhoea outbreaks caused by Cryptosporidium. We investigate the species and subtypes of cases involved in some of the outbreaks to elucidate transmission routes and the predominant aetiological agents of cryptosporidiosis. For the period 2010–2017, 318 cryptosporidiosis outbreaks were reported in New Zealand resulting in 1634 cases and 20 hospitalizations. The most important mode of transmission was person-to-person (primary infections and secondary or close contacts infections), relating to 260 outbreaks and 1320 cases, followed by 113 outbreaks associated with animals, resulting in 436 human cases. From 2018 to 2021, there were 37 cryptosporidiosis outbreaks associated with 324 cases. We identified the subtypes by using polymerase chain reaction targeting the gp60 gene and the likelihood of mixed subtype infections with the Tracking of Indels by DEcomposition (TIDE) algorithm. Subtype families Ib and Ig of Cryptosporidium hominis and IIa and IId of Cryptosporidium parvum were found among cases; however, C. hominis subtypes occurred in 8 of the 11 outbreaks reviewed where molecular data were available. Examination of the chromatograms showed no mixed subtype infections in the samples assessed. Subtyping data need to be routinely incorporated into national surveillance programmes to better understand the epidemiology, sources, transmission and extent of cryptosporidiosis outbreaks in New Zealand. Our study highlights the value of integrating epidemiological information and molecular typing to investigate and manage clusters of cryptosporidiosis cases.

Molecular characterization of Blastocystis subtypes in symptomatic patients from the southern region of Syria.

Blastocystis sp. is an enteric protist found in humans and a wide range of animal hosts. Genetic variations were established among the 38 different subtypes detected so far, 14 of which are commonly found in human and animal hosts. The aim of the present study is to estimate the prevalence of the common Blastocystis subtypes and evaluate the possible correlation with several variables (gender, age, symptoms, domestic animals…), among patients from the southern region of Syria. Fecal samples were collected from individuals suffering from gastrointestinal complaints. Microscopic examination along with genotype analyses using seven pairs of subtype-specific primers was performed. Our results revealed the presence of Blastocystis sp. in 46 isolates out of the 60 samples microscopically studied (76.7%); single infection was detected in 24 isolates whereas co-infection with other protozoa was identified in 22 ones. Molecular detection targeting the SSU rRNA gene revealed a 100% positive presence of Blastocystis sp. in all the samples. Genotyping results detected the presence of five different subtypes (ST1-ST5) with varying proportions. However, ST1 was the dominant subtype observed (66.7%). Mixed subtype infections were found in 9 isolates (15%). Three samples remained undefined, nonetheless. Our statistical results showed no significant correlation between Blastocystis STs infection and the different studied variables. In conclusion, this study provides the first genetic characterization of Blastocystis subtypes prevalence in patients from the southern region of Syria. ST1 distribution was highly predominant. Further molecular studies are needed to estimate the prevalence of Blastocystis sp. infection in other regions in Syria and to understand the epidemiology and sources of transmission to humans.

Altered Tryptophan-Kynurenine Pathway in Delirium: A Review of the Current Literature.

Delirium, a common form of acute brain dysfunction, is associated with increased morbidity and mortality, especially in older patients. The underlying pathophysiology of delirium is not clearly understood, but acute systemic inflammation is known to drive delirium in cases of acute illnesses, such as sepsis, trauma, and surgery. Based on psychomotor presentations, delirium has three main subtypes, such as hypoactive, hyperactive, and mixed subtype. There are similarities in the initial presentation of delirium with depression and dementia, especially in the hypoactive subtype. Hence, patients with hypoactive delirium are frequently misdiagnosed. The altered kynurenine pathway (KP) is a promising molecular pathway implicated in the pathogenesis of delirium. The KP is highly regulated in the immune system and influences neurological functions. The activation of indoleamine 2,3-dioxygenase, and specific KP neuroactive metabolites, such as quinolinic acid and kynurenic acid, could play a role in the event of delirium. Here, we collectively describe the roles of the KP and speculate on its relevance in delirium.

A Genome-Wide Association Study to Identify Novel Candidate Genes Related to Low-Nitrogen Tolerance in Cucumber (Cucumis sativus L.).

Cucumber is one of the most important vegetables, and nitrogen is essential for the growth and fruit production of cucumbers. It is crucial to develop cultivars with nitrogen limitation tolerance or high nitrogen efficiency for green and efficient development in cucumber industry. To reveal the genetic basis of cucumber response to nitrogen starvation, a genome-wide association study (GWAS) was conducted on a collection of a genetically diverse population of cucumber (Cucumis sativus L.) comprising 88 inbred and DH accessions including the North China type, the Eurasian type, the Japanese and South China type mixed subtype, and the South China type subtype. Phenotypic evaluation of six traits under control (14 mM) and treatment (3.5 mM) N conditions depicted the presence of broad natural variation in the studied population. The GWAS results showed that there were significant differences in the population for nitrogen limitation treatment. Nine significant loci were identified corresponding to six LD blocks, three of which overlapped. Sixteen genes were selected by GO annotation associated with nitrogen. Five low-nitrogen stress tolerance genes were finally identified by gene haplotype analysis: CsaV3_3G003630 (CsNRPD1), CsaV3_3G002970 (CsNRT1.1), CsaV3_4G030260 (CsSnRK2.5), CsaV3_4G026940, and CsaV3_3G011820 (CsNPF5.2). Taken together, the experimental data and identification of candidate genes presented in this study offer valuable insights and serve as a useful reference for the genetic enhancement of nitrogen limitation tolerance in cucumbers.

Congenital Mesoblastic Nephroma: A Case Report.

case reports; congenital mesoblastic nephroma; kidney neoplasms; nephrectomy.

Recurrence Following Globe Sparing Excision for Basal Cell Carcinoma with Anterior Orbital Invasion.

Globe-sparing excision for periocular basal cell carcinoma (BCC) with orbital invasion has evident benefits, but the ensuing morbidity and characteristics of recurrence are not well elucidated. This study aims to describe the extent of visual morbidity following globe-sparing excision, and the clinicoradiological characteristics of tumor recurrence. Multicentre retrospective case series. Eight patients were identified for inclusion in this series. Time to recurrence following globe-sparing excision ranged from 3 to 12 years. Seven patients (87.5%) presented with recurrent disease originating from the medial canthus. Clinical features at presentation included contracture ( n =4, 50.0%), upper lid ptosis ( n =3, 37.5%), a palpable mass ( n =2, 25.0%), and hypoesthesia ( n =2, 25.0%). Radiologically, tumor recurrence was predominantly characterized by isointense signals on T1 and T2-weighted sequences ( n =5, 62.5%) with moderate contrast enhancement. The most common histologic subtype in recurrent tumors was a mixed nodular and infiltrative growth pattern ( n =5, 62.5%). Perineural invasion was a feature in four (50%) cases. Salvage therapy in the form of exenteration was performed in seven cases. Vismodegib and adjuvant radiotherapy were provided for one case with surgically unresectable tumor recurrence. Globe-sparing excision for invasive periocular BCC can be complicated by late recurrence that develops rapidly despite silent neuroimaging for years. Early clinical signs are subtle. High-risk features predictive of recurrence include medial canthus location, mixed histological subtypes, and perineural invasion. Patients with such characteristics require lifelong clinical and imaging surveillance following globe-sparing excision.