An Automated Radiosynthesis of [68Ga]Ga-FAPI-46 for Routine Clinical Use.

[68Ga]Ga-FAPI-46 is a promising new tracer for the imaging of fibroblast activation protein (FAP) by positron emission tomography (PET). Labeled FAP inhibitors (FAPIs) have demonstrated uptake in various types of cancers, including breast, lung, prostate, pancreatic and colorectal cancer. FAPI-PET also possesses a practical advantage over FDG-PET as fasting and resting are not required. [68Ga]Ga-FAPI-46 exhibits enhanced pharmacokinetic properties, improved tumor retention, and higher contrast images than the earlier presented [68Ga]Ga-FAPI-02 and [68Ga]Ga-FAPI-04. Although a manual synthesis protocol for [68Ga]Ga-FAPI-46 was initially described, in recent years, automated methods using different commercial synthesizers have been reported. In this work, we describe the development of the automated synthesis of [68Ga]Ga-FAPI-46 using the iPHASE MultiSyn synthesizer for clinical applications. Initially, optimization of the reaction time and comparison of the performance of four different solid phase extraction (SPE) cartridges for final product purification were investigated. Then, the development and validation of the production of 0.6-1.7 GBq of [68Ga]Ga-FAPI-46 were conducted using these optimized parameters. The product was synthesized in 89.8 ± 4.8% decay corrected yield (n = 6) over 25 min. The final product met all recommended quality control specifications and was stable up to 3 h post synthesis.

Is motor-driven insertion of orthodontic miniscrews more advantageous than manual insertion? A micro-CT evaluation of bone miniscrew contact surface area and cortical microcracks in rabbits.

AIM: This in vitro study aimed to evaluate and compare the bone-miniscrew contact surface area (BMC) and the cortical bone microcracks (CM) resulting from manual (hand-driven) and automated (motor-driven) orthodontic miniscrew (OM) insertion methods. METHODS: Thirty-three OM were inserted in the femurs of nine New Zealand rabbits using manual (n = 16) and automated (n = 17) insertions. After euthanizing the rabbits, bone blocks, each including one OM, were sawed. Micro-CT scanning was performed, and data analysis included reconstruction, binarization and quantification of morphometric parameters of BMC and the number and length of CM. Means and standard deviations for complete BMC, complete BMC proportion, cortical BMC, cortical BMC proportion, and length and number of CM were calculated. Mixed model analysis was used to adjust for more than one sample/CM per animal. A paired t-test was used to compare the number of CM between the two groups. RESULTS: Compared to the automated insertion, manually inserted miniscrews had significantly lower complete BMC (7.54 ± 1.80 mm2 vs. 11.99 ± 3.64 mm2), cortical BMC (5.91 ± 1.48 mm2 vs. 8.48 ± 1.90 mm2) and cortical BMC proportion (79.44 ± 5.84% vs. 87.94 ± 3.66%). However, it was not statistically significant in complete BMC proportion (p = .052). The automated insertion also resulted in a significantly lower mean number of CM than the manual method (p = .012). However, the length of the cracks was shorter in the manual group but with no significant difference (p = 0.256). CONCLUSION: Motor-driven OM insertion results in superior BMC and reduction in the number of CM, which may lead to better miniscrew stability.

Utility of diffusion tensor imaging in differentiating benign from malignant thyroid nodules.

Purpose: To assess diffusion tensor imaging (DTI) in differentiating benign from malignant thyroid nodules. Methods: A retrospective analysis was done on 55 patients with thyroid nodules who had undergone DTI. The fraction anisotropy (FA) and mean diffusivity (MD) of the thyroid nodules were measured using region of interest (ROI) by two observers. The final diagnosis was malignant and benign, as proved by pathological examination. Results: The mean MD of benign thyroid nodules (1.84 ± 0.42 and 1.90 ± 0.37 × 10-3mm2/s) was significantly higher (p < .001) than malignant nodules (0.95 ± 0.46 and 0.97 ± 0.41 × 10-3mm2/s) as scored by both observers. The cut-off values of 1.45 and 1.50 × 10-3mm2/s were used to differentiate malignant from benign thyroid nodules with the areas under the curve (AUC) of 0.926 and 0.937, respectively. The mean FA of benign thyroid nodules (0.23 ± 0.07 and 0.24 ± 0.08) was significantly lower (p < .001) than malignant nodules (0.48 ± 0.21 and 0.49 ± 0.18). The FA cut-off value of ≤0.32 and 0.33 was used for differentiating malignant from benign thyroid nodules with an AUC of 0.877 and 0.881, respectively. A combination of MD and FA values was used to differentiate benign from malignant thyroid nodules with an AUC of 0.932 and an accuracy of 87%. There was an excellent agreement between both observers for FA and MD (K = 0.939, 0.929). Conclusion: The DTI is a non-invasive, non-contrast imaging tool that can differentiate benign from malignant thyroid nodules.

Impact of the 2008 economic crisis on the burden of hepatitis B and C diseases in Southern European countries.

BACKGROUND: The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may have affected ongoing efforts to eliminate viral hepatitis. This study was conducted to investigate the impact of the economic crisis on the burden of HBV and HCV disease. METHODS: Global Burden of Diseases 2019 data were used to analyse the rates of epidemiological metrics of HBV and HCV acute and chronic infections in SWE and WE. Time series modelling was performed to quantify the impact of healthcare expenditure on the time trend of HBV and HCV disease burden in 2000-2019. RESULTS: Declining trends in incidence and prevalence rates of acute HBV (aHBV) and chronic HBV were observed in SWE and WE, with the pace of decline being slower in the post-austerity period (2010-2019) and mortality due to HBV stabilised in SWE. Acute HCV (aHCV) metrics and chronic HCV incidence and mortality showed a stable trend in SWE and WE, whereas the prevalence of chronic HCV showed an oscillating trend, decreasing in WE in 2010-2019 (p < 0.001). Liver cancer due to both hepatitis infections showed a stagnant burden over time. An inverse association was observed between health expenditure and metrics of both acute and chronic HBV and HCV. CONCLUSIONS: Epidemiological metrics for HBV and HCV showed a slower pace of decline in the post-austerity period with better improvement for HBV, a stabilisation of mortality and a stagnant burden for liver cancer due to both hepatitis infections. The economic crisis of 2008 had a negative impact on the burden of hepatitis B and C. Elimination of HBV and HCV by 2030 will be a major challenge in the SWE countries.

Engineered biochar combined clay for microplastic biodegradation during pig manure composting.

This study pursued to regulate bacterial community succession pattern and expedited biodegradation of microplastics (MP) during pig manure (PM) composting employing walnut shell biochar (WSB) and montmorillonite (M). The WSB with concentration of 0%, 2.5%, 5%, 7.5%, 10% and 12% along with 10% M participated into PM for 42 days compost to search the optimal solution. The results confirmed the most prosperous bacterial phylum consisted of Firmicutes (3.02%-91.80%), Proteobacteria (2.08%-48.54%), Chloroflexi (0-44.62%) and Bacteroidetes (0.85%-40.93%). The addition of biochar has dramatically arranged bacterial community at different stages of composting. Energy Dispersive Spectrometer (EDS) revealed that carbon element in MPs decreased since the chemical bond fracture, under the intervention of high-temperature composting and WSB, the carbon content of MPs was maximum reduced by 20.25%. Fourier transform infrared spectrum indicated that CC, C-O, C-H and -COOH abundance of MPs in 10% and 12% dose biochar addition sharply reduced, interestingly, explicating WSB and composting made MP biodegradable. This experiment possesses affirmatory practical meaning for elimination of potential hazards by composting.

Approaches to embryonic neurodevelopment: from neural cell to neural tube formation through mathematical models.

The development of the human central nervous system initiates in the early embryonic period until long after delivery. It has been shown that several neurological and neuropsychiatric diseases originate from prenatal incidents. Mathematical models offer a direct way to understand neurodevelopmental processes better. Mathematical modelling of neurodevelopment during the embryonic period is challenging in terms of how to 'Approach', how to initiate modelling and how to propose the appropriate equations that fit the underlying dynamics of neurodevelopment during the embryonic period while including the variety of elements that are built-in naturally during the process of neurodevelopment. It is imperative to answer where and how to start modelling; in other words, what is the appropriate 'Approach'? Therefore, one objective of this study was to tackle the mathematical issue broadly from different aspects and approaches. The approaches were divided into three embryonic categories: cell division, neural tube growth and neural plate growth. We concluded that the neural plate growth approach provides a suitable platform for simulation of brain formation/neurodevelopment compared to cell division and neural tube growth. We devised a novel equation and designed algorithms that include geometrical and topological algorithms that could fit most of the necessary elements of the neurodevelopmental process during the embryonic period. Hence, the proposed equations and defined mathematical structure would be a platform to generate an artificial neural network that autonomously grows and develops.

Vicinal diaryl pyrazole with tetrazole/urea scaffolds as selective angiotensin converting enzyme-1/cyclooxygenase-2 inhibitors: Design, synthesis, anti-hypertensive, anti-fibrotic, and anti-inflammatory.

As a hybrid weapon, two novel series of pyrazoles, 16a-f and 17a-f, targeting both COX-2 and ACE-1-N-domain, were created and their anti-inflammatory, anti-hypertensive, and anti-fibrotic properties were evaluated. In vitro, 17b and 17f showed COX-2 selectivity (SI = 534.22 and 491.90, respectively) compared to celecoxib (SI = 326.66) and NF-κB (IC50 1.87 and 2.03 µM, respectively). 17b (IC50 0.078 µM) and 17 f (IC50 0.094 µM) inhibited ACE-1 comparable to perindopril (PER) (IC50 0.048 µM). In vivo, 17b decreased systolic blood pressure by 18.6%, 17b and 17f increased serum NO levels by 345.8%, and 183.2%, respectively, increased eNOS expression by 0.97 and 0.52 folds, respectively and reduced NF-κB-p65 and P38-MAPK expression by -0.62, -0.22, -0.53, and -0.24 folds, respectively compared to  l-NAME (-0.34, -0.45 folds decline in NF-κB-p65 and P38-MAPK, respectively). 17b reduced ANG-II expression which significantly reversed the cardiac histological changes induced by L-NAME.

Prevalent Parental Practice Toward Drug Storage and Disposal.

Introduction The environment, healthcare services, and public safety can all be directly impacted by improper drug storage and disposal practices. It is unknown whether parents store drugs at home in accordance with recommended storage guidelines, despite the fact that storage conditions are strictly regulated and monitored at every stage of the drug supply chain prior to drug dispensing. Therefore, it is crucial to dispose of medications properly and store them at home to avoid the consequences. Aim The purpose of this study was to evaluate the drug storage safety measures used by parents to prevent unintentional drug poisoning in children. Methodology A structured questionnaire was used to conduct a cross-sectional, interview-based study on home medication storage, attitudes, and disposal practices between October 2023 and January 2024. We recruited parents who visited primary healthcare centers or pediatric clinics using a convenience sampling technique. Results All of the 353 returned questionnaires were valid for data entry and analysis. The mean age of the parents was 35.1 ± 11.9 years old and more than half of them 229 (64.9%) have bachelor's degrees. The majority of drugs (271, 88.6%) were stored in the fridge, followed by bedrooms (26.8%). The medication classes that were stored the most frequently were analgesics (92.2%) and antihistamines (62.1%). The majority of parents (214, 69.9%) kept medications above adult eye level, even though only 28% did not keep them in safe and secure locations like locked drawers or boxes. Eighty percent (80%) disposed of unwanted medicines by throwing them in the trash, and only 10 (2.8%) returned them to the pharmacy.  Conclusions Drug storage at home encourages self-medication, which has a number of negative effects. Over time, there has been an increase in the use of medications due to a rise in people's health-seeking awareness and behavior on a global scale. Therefore, this study may be used as a guide by national policy-makers for pharmaceutical disposal and storage management. Moreover, it might help in raising public awareness of the importance of pharmacists in the society and the safe handling and storage of medications at home.

Giant Ganglioneuroma of the Lumbar Spine: A Rare Cause of Radiculopathy.

Background: Ganglioneuroma (GN) is a rare, benign tumor that originates from neural crest cells and can potentially affect any anatomical site within the sympathetic nervous system. Typically, GNs are more frequently reported in children and young adults, with a slightly higher prevalence in females. We are reporting a rare case of a giant lumbar spine ganglioneuroma by outlining the clinical presentation, radiological finding, management, and outcome. Case Description. A 37-year-old female presented with low back pain radiating to the right lower limb for few years. Neurological examination revealed bilateral lower limb hyperreflexia (+3). Lumbar spine CT and MRI revealed a right paravertebral soft tissue lesion with heterogeneous signal intensity and enhancement at L1 to L3. The patient underwent complete resection of the lesion via a retroperitoneal approach. The surgery was uneventful. The histopathological sections were suggestive of mature ganglioneuroma. She was discharged in stable condition with follow-up at neurosurgery clinic. Conclusion: Giant ganglioneuromas are rare, benign tumors of sympathetic neurons. Complete surgical resection is the most effective therapeutic option for ganglioneuroma to avoid recurrence. Given the benign nature of ganglioneuroma, chemotherapy and radiotherapy tend to have a limited role following surgical resection.

Hope on the Horizon: Promising Therapies for Steatotic Liver Disease.

Steatotic liver disease (SLD) is a highly prevalent chronic liver disease with significant challenges for global health. The pathophysiology of SLD involves an interplay among genetic, endocrine, and metabolic factors. Successful management of SLD entails accurate diagnosis and disease monitoring through noninvasive methods such as advanced imaging techniques and biomarkers. Many emerging pharmacotherapies for SLD are now in the pipeline, which target different pathways like collagen turnover, fibrogenesis, inflammation, and metabolism. The recent approval of resmetirom for noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) has been a milestone in addressing the unmet medical need for an efficacious SLD treatment. Finally, the potential of personalized medicine approaches and interdisciplinary cooperation in improving patient outcomes and reducing disease burden should be strongly pursued. SIGNIFICANCE STATEMENT: The healthcare burden due to steatotic liver disease (SLD) is enormous. This perspective sheds light on the recent advances in understanding the pathophysiology and diagnosis of SLD as well as promising drug development approaches.

A Mechanically Resilient Soft Hydrogel Improves Drug Delivery for Treating Post-Traumatic Osteoarthritis in Physically Active Joints.

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in early post-traumatic osteoarthritis (PTOA) when symptoms are minimal and patients are physically active. DMOAD delivery systems therefore must withstand repeated mechanical loading without affecting the drug release kinetics. Although soft materials are preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt drug release. Here, we report a mechanically resilient soft hydrogel that rapidly self-heals under conditions resembling human running while maintaining sustained release of the cathepsin-K inhibitor L-006235 used as a proof-of-concept DMOAD. Notably, this hydrogel outperformed a previously reported hydrogel designed for intra-articular drug delivery, used as a control in our study, which neither recovered nor maintained drug release under mechanical loading. Upon injection into mouse knee joints, the hydrogel showed consistent release kinetics of the encapsulated agent in both treadmill-running and non-running mice. In a mouse model of aggressive PTOA exacerbated by treadmill running, L-006235 hydrogel markedly reduced cartilage degeneration. To our knowledge, this is the first hydrogel proven to withstand human running conditions and enable sustained DMOAD delivery in physically active joints, and the first study demonstrating reduced disease progression in a severe PTOA model under rigorous physical activity, highlighting the hydrogel's potential for PTOA treatment in active patients.

Clinical validation of a cell-free DNA fragmentome assay for augmentation of lung cancer early detection.

Lung cancer screening via annual low-dose computed tomography (LDCT) has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by an LDCT. Changes in genome-wide cell-free DNA (cfDNA) fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples, and then validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer, and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a five-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths.

Foodborne botulism outbreak with potential new management options.

OBJECTIVES: To shed some light on a potential therapeutic modality that may facilitate resolution of botulism symptoms, namely 3,4-diaminopyridine (3,4-DAP). METHODS: In Riyadh, Saudi Arabia, we recently encountered a foodborne botulism outbreak that, luckily, was discovered early. In Prince Sultan Military Medical city, we admitted, during a period of approximately 3 weeks, 15 probable cases, 2 of which were excluded due to more likely alternative diagnoses. We report in this case series 13 highly suspected cases of botulism that we encountered during the outbreak. RESULTS: A total of 12 out of 13 patients required intensive care unit (ICU) admission, one of which required intubation. Symptoms included cranial nerve palsies, gastrointestinal symptoms, limb and respiratory muscle weakness. Patients showed clinical improvement when received botulinum antitoxin and 3,4-DAP if given early in the course of the disease. CONCLUSION: Early admisntration of 3,4-DAP may facilitate recovery and prevent disease progression. Larger prospective trials should be carried out to confirm that.

Ameliorative effect of licorice extract against the detrimental effect of glyphosate-based pesticide: Toxicity and health.

This study sheds the light on the potential of licorice (Glycyrrhiza glabra) root aqueous extract as a cornerstone for mitigating and detoxifying the residues of the widely used agricultural Glyphosate-based pesticides (GBPs). This study examined the GBPs toxic effects on kidney, liver, thyroid functions, and apoptosis using 50 adult male albino rats. All rats were divided into 5 groups, with 10 each. Control: served as untreated rats. GBP: rats were treated with 1 mL glyphosate solution 24 % orally for three weeks. The glyphosate-treated rats were gavaged with licorice root aqueous extractsolution (100, 200, and 300 mg/mLdistilled water, respectively) daily for three weeks. Licorice root aqueous extract solution (300 mg/mL distilled water) yielded notable reductions in liver, kidney enzymes, albumin, and AFP levels within the serum. Immunological tests, including immunohistochemical evaluations of caspase-3 and TNF-α expressions revealed a dose-dependent attenuation of apoptosis and inflammation with licorice intervention. This will provide a valuable perspective for agricultural practices future and paving the way for a more sustainable approach for using GBPs in animal agriculture industries.

Unlocking the secrets of apple harvests: Advanced stratification techniques in the Himalayan region.

This study focuses on standardizing sampling techniques and comparing various methods of sample allocation to effectively estimate apple area and production in the Himalayan region of India. We investigate different stratification tools,in formulating a sampling plan using information gathered from select orchardists in the locale during the 2016-17 period, it becomes essential to explore diverse methodologies to define the most suitable stratum boundaries, ascertain the requisite number of strata, and identify the optimal sample size. The stratification process, underpinned by the "Area under Apple" variable, which demonstrates a pronounced association with apple production, assumes a central role in this endeavor Several methods are utilized to construct strata, such as equalizing strata totals, cumulative equalization, equalization of ½{r(x) + f(x)} and equalization of f ( x ) . We assess their efficiencies in estimating total apple production in the study district. The combination of the "Cum f ( x ) " of Neyman allocation demonstrates the lowest variance and the highest efficiency within a range of 2-4 strata, coupled with an increase in sample size from 10 to 40. Consequently, it can be inferred that the "Cum f ( x ) " method, particularly with L > 2, is preferable for estimating apple production in the Himalayan region of India.

Intermittent Fasting Regulates Metabolic Homeostasis and Improves Cardiovascular Health.

Obesity is a leading cause of morbidity and mortality globally. While the prevalence of obesity has been increasing, the incidence of its related complications including dyslipidemia and cardiovascular disease (CVD) has also been rising. Recent research has focused on modalities aimed at reducing obesity. Several modalities have been suggested including behavioral and dietary changes, medications, and bariatric surgery. These modalities differ in their effectiveness and invasiveness, with dietary changes gaining more interest due to their minimal risks compared to other modalities. Specifically, intermittent fasting (IF) has been gaining interest in the past decade. IF is characterized by cycles of alternating fasting and eating windows, with several different forms practiced. IF has been shown to reduce weight and alleviate obesity-related complications. Our review of clinical and experimental studies explores the effects of IF on the lipid profile, white adipose tissue (WAT) dynamics, and the gut microbiome. Notably, IF corrects dyslipidemia, reduces WAT accumulation, and decreases inflammation, which reduces CVD and obesity. This comprehensive analysis details the protective metabolic role of IF, advocating for its integration into public health practices.

Thymoquinone attenuates diabetes-induced hepatic damage in rat via regulation of oxidative/nitrosative stress, apoptosis, and inflammatory cascade with molecular docking approach.

Diabetes mellitus (DM) is a complex metabolic condition that causes organ dysfunction. The current experiment sought to determine the effect of thymoquinone (TQ) on hyperglycemia, hyperlipidemia, oxidative/nitrosative stress, inflammation, and apoptosis in diabetic rats prompted by streptozotocin (STZ) (55 mg/kg body weight i/p). The animals were allocated into control, TQ (50 mg/kg B.W. orally administered for 4 succeeding weeks), Diabetic, and Diabetic + TQ groups. This study confirmed that TQ preserves the levels of insulin, fasting blood glucose, HOMA ß-cell indices, HbA1c %, body weight, and lipid profile substantially relative to the DC group. Furthermore, hepatic antioxidant (CAT, GSH, and T-SOD) values were reduced. Conversely, the enzymatic activity of liver functions (AST, ALT, ALP, cytochrome P450, and hepatic glucose-6-phosphatase), lipid peroxidation (MDA), pro-inflammatory cytokines (IL-1ß, TNF-α, and IL-6), nitric oxide (NO) and inflammatory marker (CRP) enhanced with STZ administration, which is substantially restored after TQ treatment. Relative to the diabetic rats, TQ reestablished the hepatic architectural changes and collagen fibers. Additionally, TQ downregulated the intensity of the immunohistochemical staining of pro-apoptotic marker (caspase-3), p53, and tumor necrosis factor-alpha (TNF-α) proteins in hepatic tissues. Furthermore, TQ displayed abilities to interact and inhibit the binding site of caspase-3, interleukin-6 receptor, interleukin-1 receptor type 1, TNF receptor superfamily member 1A, and TNF receptor superfamily member 1B in rats following the molecular docking modeling. All these data re-establish the liver functions, antioxidant enzymes, anti-inflammatory markers, and anti-apoptotic proteins impacts of TQ in STZ-induced DM rats. Founded on these outcomes, the experiment proposes that TQ is a novel natural supplement with various clinical applications, including managing DM, which in turn is recommended to play a pivotal role in preventing the progression of diabetes mellitus.

An effective and economic estimation of population mean in stratified random sampling using a linear cost function.

Improvement in the estimation of population mean has been an area of interest in sampling theory. So many estimators have been suggested for elevated estimation of the population mean in stratified random sampling, but there is still a gap for more closely estimating the population mean. In this paper, the authors propose a ratio-product-cum-exponential-cum-logarithmic type estimator for the enhanced estimation of population mean by implying one auxiliary variable in stratified random sampling using conventional ratio, exponential ratio, and logarithmic ratio type estimators. The suggested estimator is a generalization of ratio, exponential ratio, and logarithmic ratio type estimators, and therefore these are special cases of the proposed estimator. The proposed estimator's bias and MSE are determined and compared with those of influential estimators, with the linear cost function being used to investigate and compare alternatives. Use Cramer's rule to determine the optimal value of the proposed estimator. The proposed estimator is more effective than other existing estimators, according to theoretical observations. For various applications, we suggest using a proposed estimator with the minimal MSE, which is verified by a numerical example, to have practical applicability of theoretical conclusions in real life.

How severity and classification of pulmonary hypertension affect pregnancy outcomes: a systematic review and timeline.

Women with pulmonary hypertension (PH) have increased mortality during pregnancy and the peripartum period. An increasing number of publications suggest improvements in maternal outcomes, so we conducted a systematic review focusing on disease severity and maternal survival. After screening 9097 potential studies from 1967 to 2021, we identified 66 relevant publications. Outcomes improved continuously over time and mortality fell from 11.6% in studies published before 2015 to 8.2% in studies published after 2015. Mortality was lower in patients with mild disease (0.8%) than in those with Eisenmenger syndrome (26.2%) or idiopathic pulmonary arterial hypertension (7.4-24.0%). One major drawback of the published studies is that they define severity using echocardiographic-estimated pulmonary artery pressures, without considering more contemporary parameters. This systematic review provides new insights for preconception counseling on pregnancy risks related to PH and suggests that PH classification and severity should be carefully considered in determining an individual's pregnancy-associated risk.