Preliminary Report for the Development of a Multiparameter Protocol for the Identification of Sinusoidal Obstruction Syndrome including Abdominal Ultrasound before and after Allogeneic Stem Cell Transplantation

Sinusoidal obstruction syndrome (SOS) is a rare complication after allogeneic hematopoietic stem cell transplantation (alloHSCT) caused by endothelial dysfunction. Previous definitions and diagnostic criteria for the presence of SOS include bilirubinemia, hepatomegaly and weight gain, but histological evaluation is still the only way to prove the diagnosis of SOS. However, biopsy remains an invasive technique and is therefore undesirable in the alloHSCT scenario. Hence, a non-invasive diagnostic strategy is critical. Besides thorough clinical assessment and laboratory values, ultrasound examination remains part of the diagnostic workflow in clinical routine. Previous studies defined sonographic abnormalities, which are associated with the occurrence of SOS, but a standardized protocol to perform reliable abdominal ultrasound has not been finally defined. In this study, we evaluated a multi-parameter protocol including laboratory values as well as ultrasound examination pre- and post-alloHSCT. The application of this protocol was feasible in clinical practice and achieved a high inter- and intra-rater reliability. In our population, no case of SOS was identifiable and, in line with previous studies, no changes known to be associated with SOS were detected by ultrasound examination in our cohort. Additionally, we investigated subgroups of patients partly fulfilling SOS diagnostic criteria analyzing correlations between the fulfilled criteria and aberrances in ultrasound measurements pre- and post-alloHSCT. Although statistical examination may be limited by a small sample size and missing SOS cases, hyperbilirubinemia, thrombocytopenia and weight gain showed only a coincidence with selected, enlarged liver dimensions in few patients. This may underline the fact that hepatomegaly occurs as an unspecific finding after alloHSCT. Our protocol, including the ultrasound examination pre- and post-alloHSCT and laboratory parameters, may help to rule out SOS early, but validation in a greater population and different transplantation centers is required to warrant broader appliance. Nevertheless, we aim to contribute to an elaborate and standardized work-flow in peri-alloHSCT patient care.

Deconstructing a Syndrome: Genomic Insights into PCOS Causal Mechanisms and Classification

Polycystic ovary syndrome (PCOS) is among the most common disorders of reproductive-age women, affecting up to 15% worldwide, depending on the diagnostic criteria. PCOS is characterized by a constellation of interrelated reproductive abnormalities including disordered gonadotropin secretion, increased androgen production, chronic anovulation, and polycystic ovarian morphology. It is frequently associated with insulin resistance and obesity. These reproductive and metabolic derangements cause major morbidities across the lifespan, including anovulatory infertility and type 2 diabetes (T2D). Despite decades of investigative effort, the etiology of PCOS remains unknown. Familial clustering of PCOS cases has indicated a genetic contribution to PCOS. There are rare Mendelian forms of PCOS associated with extreme phenotypes, but PCOS typically follows a non-Mendelian pattern of inheritance consistent with a complex genetic architecture, analogous to T2D and obesity, that reflects the interaction of susceptibility genes and environmental factors. Genomic studies of PCOS have provided important insights into disease pathways and have indicated that current diagnostic criteria do not capture underlying differences in biology associated with different forms of PCOS. We provide a state-of-the-science review of genetic analyses of PCOS, including an overview of genomic methodologies aimed at a general audience of non-geneticists and clinicians. Applications in PCOS will be discussed, including strengths and limitations of each study. The contributions of environmental factors, including developmental origins, will be reviewed. Insights into the pathogenesis and genetic architecture of PCOS will be summarized. Future directions for PCOS genetic studies will be outlined.

Aerobic Vaginitis Diagnosis Criteria Combining Gram Stain with Clinical Features: An Establishment and Prospective Validation Study

Wet-mount microscopy aerobic vaginitis (AV) diagnostic criteria need phase-contrast microscopy and keen microscopists, and the preservation of saline smears is less common in clinical practice. This research work developed new AV diagnostic criteria that combine Gram stain with clinical features. We enrolled 325 AV patients and 325 controls as a study population to develop new AV diagnostic criteria. Then, an independent group, which included 500 women, was used as a validation population. AV-related microscopic findings on Gram-stained and wet-mount smears from the same participants were compared. The accuracy of bacterial indicators from the two methods was verified by bacterial 16S rRNA V4 sequencing (n = 240). Logistic regression was used to analyse AV-related clinical features. The screened clinical features were combined with Gram-stain microscopic indicators to establish new AV diagnostic criteria. There were no significant differences in the leukocyte counts or the parabasal epitheliocytes (PBC) proportion between the Gram-stain and wet-mount methods (400×). Gram stain (1000×) satisfied the ability to identify bacteria as verified by 16S rRNA sequencing but failed to identify toxic leukocytes. The new criteria included: Lactobacillary grades (LBG) and background flora (Gram stain, 1000×), leukocytes count and PBC proportion (Gram stain, 400×), and clinical features (vaginal pH > 4.5, vagina hyperemia, and yellow discharge). These criteria satisfied the accuracy and reliability for AV diagnosis (Se = 86.79%, Sp = 95.97%, and Kendall’s W value = 0.899) in perspective validation. In summary, we proposed an alternative and valuable AV diagnostic criteria based on the Gram stain, which can make it possible to diagnose common vaginitis like AV, BV, VVC, and mixed infections on the same smear and can be available for artificial intelligence diagnosis in the future.

Relationship of Inflammatory Markers and Metabolic Syndrome in Postmenopausal Women

The increased deposition of visceral fat in the postmenopause period increases the production of inflammatory cytokines and the release of tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), and decrease in IL-10. This study investigated the relationship between inflammatory biomarkers and metabolic syndrome (MS) in postmenopausal women considering different diagnostic criteria. We conducted a cross-sectional observational study based on STROBE. Data were collected regarding the diagnostic criteria for MS (International Diabetes Federation; NCEP (International Diabetes Federation (IDF), National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III), and Harmonized criteria), body composition, comorbidities, time without menstruation, values of IL-6, IL-10, and TNF-α. ANOVA, Kruskal–Wallis, Levene tests, ROC, and odds ratio were performed to analyze the data. The results showed no significant difference between the methods and no interaction between the method and the presence of MS. However, for the values of WC, body fat percentage, TNF-α, and IL-10/TNF-α ratio, a significant effect of MS was observed. In subjects with MS, lower values of body fat percentage and TNF-α and higher values of the IL-10/TNF-α ratio were also observed. The higher IL-10/TNF-α ratio in the MS group is related to the greater anti-inflationary action of IL-10. The IL-10/TNF-α ratio showed significant accuracy to discriminate patients with MS according to the NCEP-ATP III criteria.

Metabolic Obesity in People with Normal Body Weight (MONW)—Review of Diagnostic Criteria

Disorders of metabolic obesity with normal body weight (MONW) are widely recognized risk factors for the development of cardiovascular diseases and type 2 diabetes. Despite this, MONW is not diagnosed in clinical practice. There is no consensus on the definition of MONW, and measuring the degree of insulin resistance or obesity among apparently healthy, non-obese patients is not widely applicable. The awareness of the relationship between metabolic disorders such as MONW and a higher risk of mortality from cardiovascular causes and other related diseases prompts the need for action to be taken aimed at creating appropriate diagnostic models that will allow for the effective detection of those with metabolic abnormalities among people with normal body weight. Such actions are decisive in the prevention and treatment of diseases. Therefore, the purpose of this article is to review the MONW diagnostic criteria used over the years.