The Deterioration of Sarcopenia Post-Transarterial Radioembolization with Holmium-166 Serves as a Predictor for Disease Progression at 3 Months in Patients with Advanced Hepatocellular Carcinoma: A Pilot Study.

PURPOSE: The aim of this pilot study is to explore the relationship between changes in sarcopenia before and after one to three months of Transarterial Radioembolization (TARE) treatment with Holmium-166 (166Ho) and its effect on the rate of local response. Our primary objective is to assess whether the worsening of sarcopenia can function as an early indicator of a subgroup of patients at increased risk of disease progression in cases of hepatocellular carcinoma (HCC). METHODS: A single-center retrospective analysis was performed on 25 patients with HCC who underwent 166Ho-TARE. Sarcopenia status was defined according to the measurement of the psoas muscle index (PMI) at baseline, one month, and three months after TARE. Radiological response according to mRECIST criteria was assessed and patients were grouped into responders and non-responders. The loco-regional response rate was evaluated for all patients before and after treatment, and was compared with sarcopenia status to identify any potential correlation. RESULTS: A total of 20 patients were analyzed. According to the sarcopenia status at 1 month and 3 months, two groups were defined as follows: patients in which the deltaPMI was stable or increased (No-Sarcopenia group; n = 12) vs. patients in which the deltaPMI decreased (Sarcopenia group; n = 8). Three months after TARE, a significant difference in sarcopenia status was noted (p = 0.041) between the responders and non-responders, with the non-responder group showing a decrease in the sarcopenia values with a median deltaPMI of -0.57, compared to a median deltaPMI of 0.12 in the responder group. Therefore, deltaPMI measured three months post-TARE can be considered as a predictive biomarker for the local response rate (p = 0.028). Lastly, a minor deltaPMI variation (>-0.293) was found to be indicative of positive treatment outcomes (p = 0.0001). CONCLUSION: The decline in sarcopenia three months post-TARE with Holmium-166 is a reliable predictor of worse loco-regional response rate, as evaluated radiologically, in patients with HCC. Sarcopenia measurement has the potential to be a valuable assessment tool in the management of HCC patients undergoing TARE. However, further prospective and randomized studies involving larger cohorts are necessary to confirm and validate these findings.

Endovascular treatments of acute pulmonary embolism in the post-fibrinolytic era: an up-to-date review.

Pulmonary embolism (PE) is a significant contributor to global cardiovascular-related mortality that mainly depends on the severity of the event. The treatment approach for intermediate and high-risk PE remains a topic of debate due to the fine balance between hemodynamic deterioration and bleeding risk. The initial treatment choice for intermediate-risk PE with hemodynamic deterioration and high-risk PE is historically systemic thrombolysis, but this approach is not always effective and carries a notable risk of severe bleeding. For such patients, various interventional treatments have been introduced to clinical practice, including catheter-directed lysis (CDL), ultrasound-assisted CDL, pharmacomechanical CDL, and aspiration thrombectomy. However, the optimal treatment approach remains uncertain. Encouraging outcomes have been presented assessing the novel endovascular treatments, in terms of reducing right ventricular dysfunction and improving hemodynamic stability, opening the possibility of using these devices to prevent hemodynamic instability in less severe cases. However, ongoing randomized trials that assess the efficacy and the association with mortality, especially for aspiration devices, have not yet published their final results. This article aims to offer a comprehensive update of the available catheter-directed therapies for PE, with a focus on novel mechanical thrombectomy techniques, assessing their safety and efficacy, after comparison to the conventional treatment. CRITICAL RELEVANCE STATEMENT: This is a comprehensive review of the indications of use, techniques, and clinical outcomes of the most novel endovascular devices for the treatment of pulmonary embolism. KEY POINTS: Mechanical thrombectomy is an effective tool for patients with PE. Aspiration devices prevent hemodynamic deterioration. Catheter directed therapy reduces bleeding complications.

Histology profiling of lung tumors: tru-cut versus full-core system for CT-guided biopsies.

PURPOSE: We aimed to compare the diagnostic yield and procedure-related complications of two different types of systems for percutaneous CT-guided lung biopsy. MATERIAL AND METHODS: All patients with a lung lesion who underwent a CT-guided lung biopsy at our institution, between January 2019 and 2021, were retrospectively analyzed. The inclusion criteria were: (a) Procedures performed using either a fully automated tru-cut or a semi-automated full-core biopsy needle, (b) CT images demonstrating the position of the needles within the lesion, (c) histopathological result of the biopsy and (d) clinical follow-up for at least 12 months and\or surgical histopathological results. A total of 400 biopsy fulfilling the inclusion criteria were selected and enrolled in the study. RESULTS: Overall technical success was 100% and diagnostic accuracy was 84%. Tru-cut needles showed a significantly higher diagnostic accuracy when compared to full-core needles (91% vs. 77%, p = 0.0004) and a lower rate of pneumothorax (31% vs. 41%, p = 0.047). Due to the statistically significant different of nodules size between the two groups, we reiterated the statistical analysis splitting our population around the 20 mm cut-off for nodule size. We still observed a significant difference in diagnostic accuracy between tru-cut and full-core needles favoring the former for both smaller and larger lesions (81% vs. 71%, p = 0.025; and 92% vs. 81%; p = 0.01, respectively). CONCLUSION: Our results demonstrated that the use of automated tru-cut needles is associated with higher histopathological diagnostic accuracy compared to semi-automated full-core needles for CTLB.

Iterative Reconstruction: State-of-the-Art and Future Perspectives.

ABSTRACT: Image reconstruction processing in computed tomography (CT) has evolved tremendously since its creation, succeeding at optimizing radiation dose while maintaining adequate image quality. Computed tomography vendors have developed and implemented various technical advances, such as automatic noise reduction filters, automatic exposure control, and refined imaging reconstruction algorithms.Focusing on imaging reconstruction, filtered back-projection has represented the standard reconstruction algorithm for over 3 decades, obtaining adequate image quality at standard radiation dose exposures. To overcome filtered back-projection reconstruction flaws in low-dose CT data sets, advanced iterative reconstruction algorithms consisting of either backward projection or both backward and forward projections have been developed, with the goal to enable low-dose CT acquisitions with high image quality. Iterative reconstruction techniques play a key role in routine workflow implementation (eg, screening protocols, vascular and pediatric applications), in quantitative CT imaging applications, and in dose exposure limitation in oncologic patients.Therefore, this review aims to provide an overview of the technical principles and the main clinical application of iterative reconstruction algorithms, focusing on the strengths and weaknesses, in addition to integrating future perspectives in the new era of artificial intelligence.

Digital tomosynthesis spot view in architectural distortions: outcomes in management and radiation dose.

PURPOSE: To evaluate if digital breast tomosynthesis spot compression view (DBT-SCV) could be an additional projection to confirm or deny architectural distortions (ADs) detected by digital breast tomosynthesis (DBT) while assessing the average glandular radiation dose. METHODS: This is a retrospective cohort study enrolling 8864 DBT exams, of which only cases detecting primary AD and with BI-RADS 2-5 score were considered. Seventy-one AD cases examined with DBT-SCV, US and MRI were evaluated for correlation in terms of BI-RADS score; variables among exams were assessed for inter-relationships. RESULTS: Of all ADs identified at DBT, biopsy yielded malignancy in only 38%. PPV in identifying malignancy of ADs was higher for DBT-SCV than DBT (p < 0.05); the NPV of DBT-SCV was 94%. The difference between DBT and DBT-SCV in the detection of benign ADs was statistically significant (p < 0.05). AD without US or MRI confirmation was less likely to represent malignancy (p < 0.05). In detecting malignant cases of ADs, both DBT and DBT-SCV were strongly correlated with US and RM (Kappa > 0.90). In identifying benign cases of ADs, DBT-SCV was poorly/moderately correlated with US and RM (Kappa 0.25 and 0.66); DBT was negatively correlated with US and MRI. CONCLUSION: DBT-SCV could be useful to better characterize AD firstly identified by DBT, keeping dose levels within the reference limits. If AD is detected by DBT without an US or MRI correlate, that is not confirmed by DBT-SCV, a "wait and see" approach can be applied to reduce unnecessary biopsy.

Easy Scheme Outlining the Various Morphological and Vascular Abnormalities of the Lymph Node Structure Associated with Recent COVID-19 Vaccination, Each with a Different Clinical/Diagnostic Management.

Throughout this recent ongoing SARS-CoV-2 pandemic, the European Society of Breast Imaging have surely contributed in improving the management of unilateral axillary adenopathy appearance homolaterally to the side of vaccine inoculation. After considering the patient's COVID-19 history of vaccination, our group produced a day-to-day scheme that evaluates meticulously the probability of mammary malignancy, according to the lymph node characteristics including vascular abnormalities. It comprises of a UN (ultrasound node) score ranging from 2 to 5, that increases with the suspicion of malignancy. In this setting and in view of the additional incoming COVID-19 boost-dose vaccinations, we believe our model could be of great utility to radiologist when assessing patients whom do not have a straight forward diagnosis, in order to reduce breast cancer missed diagnosis, avoid delaying vaccinations, reduce rescheduling of breast imaging examinations and lastly avoid unnecessary lymph node biopsies.

Automated Identification of Coronary Arteries in Assisting Inexperienced Readers: Comparison between Two Commercial Vendors.

Background: to assess the performance and speed of two commercially available advanced cardiac software packages in the automated identification of coronary vessels as an aiding tool for inexperienced readers. Methods: Hundred and sixty patients undergoing coronary CT angiography (CCTA) were prospectively enrolled from February until September 2021 and randomized in two groups, each one composed by 80 patients. Patients in group 1 were scanned on Revolution EVO CT Scanner (GE Healthcare), while patients in group 2 had the CCTA performed on Brilliance iCT (Philips Healthcare); each examination was evaluated on the respective vendor proprietary advanced cardiac software (software 1 and 2, respectively). Two inexperienced readers in cardiac imaging verified the software performance in the automated identification of the three major coronary vessels: (RCA, LCx, and LAD) and in the number of identified coronary segments. Time of analysis was also recorded. Results: software 1 correctly and automatically nominated 202/240 (84.2%) of the three main coronary vessels, while software 2 correctly identified 191/240 (79.6%) (p = 0.191). Software 1 achieved greater performances in recognizing the LCx (81.2% versus 67.5%; p = 0.048), while no differences have been reported in detecting the RCA (p = 0.679), and the LAD (p = 0.618). On a per-segment analysis, software 1 outperformed software 2, automatically detecting 942/1062 (88.7%) coronary segments, while software 2 detected 797/1078 (73.9%) (p < 0.001). Average reconstruction and detection time was of 13.8 s for software 1 and 21.9 s for software 2 (p < 0.001). Conclusions: automated cardiac software packages are a reliable and time-saving tool for inexperienced reader. Software 1 outperforms software 2 and might therefore better assist inexperienced CCTA readers in automated identification of the three main vessels and coronaries segments, with a consistent time saving of the reading session.

Personalized Nutrition in the Management of Female Infertility: New Insights on Chronic Low-Grade Inflammation.

Increasing evidence on the significance of nutrition in reproduction is emerging from both animal and human studies, suggesting a mutual association between nutrition and female fertility. Different "fertile" dietary patterns have been studied; however, in humans, conflicting results or weak correlations are often reported, probably because of the individual variations in genome, proteome, metabolome, and microbiome and the extent of exposure to different environmental conditions. In this scenario, "precision nutrition", namely personalized dietary patterns based on deep phenotyping and on metabolomics, microbiome, and nutrigenetics of each case, might be more efficient for infertile patients than applying a generic nutritional approach. In this review, we report on new insights into the nutritional management of infertile patients, discussing the main nutrigenetic, nutrigenomic, and microbiomic aspects that should be investigated to achieve effective personalized nutritional interventions. Specifically, we will focus on the management of low-grade chronic inflammation, which is associated with several infertility-related diseases.

Circulating irisin levels in functional hypothalamic amenorrhea: a new bone damage index? A pilot study.

PURPOSE: Patients with functional hypothalamic amenorrhea (FHA) could commonly have bone damage, often preceded by metabolic alterations due to a relative energy deficit state. To date, there are no markers capable of predicting osteopenia before it is manifested on DXA. Irisin is a myokine that promotes the differentiation of osteoblastic cells and appears to be inversely correlated with the incidence of bone fragility and fractures in postmenopausal women. The aim of this study was to measure irisin levels in FHA patients and to correlate it with bone density parameters. METHODS: Thirty-two patients with FHA and 19 matched controls underwent the same clinical and laboratory evaluation. RESULTS: Irisin and body mass index (BMI) were significantly lower in the case group than in healthy controls (2.03 ± 0.12 vs. 2.42 ± 0.09 p < 0.05 and 19.43 ± 2.26 vs. 22.72 ± 0.67 p < 0.05, respectively). Additionally, total body mass density (BMD g/cm2) was significantly lower in the case group than in the healthy controls (1.09 ± 0.08 vs. 1.14 ± 0.05, p < 0.05), without signs of osteopenia. CONCLUSIONS: The FHA group showed lower irisin levels associated with significantly reduced BMD parameters that did not reach the severity of osteopenia. Therefore, we could speculate that irisin could predict DXA results in assessing modifications of body composition parameters. Future research is warranted to study these parameters in a larger population to confirm our results, so that irisin could be used as a predictor and screening method for bone deprivation. Furthermore, irisin is strictly related to energy metabolism and could be an indirect marker of nutritional status in FHA patients, identifying earlier states of energy deficit.

Severe male factor in in vitro fertilization: definition, prevalence, and treatment. An update.

Infertility affects 10%-15% of couples worldwide. Of all infertility cases, 20%-70% are due to male factors. In the past, men with severe male factor (SMF) were considered sterile. Nevertheless, the development of intracytoplasmic sperm injection (ICSI) drastically modified this scenario. The advances in assisted reproductive technology (ART), specifically regarding surgical sperm retrieval procedures, allowed the efficacious treatment of these conditions. Yet, before undergoing ICSI, male factor infertility requires careful evaluation of clinical and lifestyle behavior together with medical treatment. Epidemiologically speaking, women whose male partner is azoospermic tend to be younger and with a better ovarian reserve. These couples, in fact, are proposed ART earlier in their life, and for this reason, their ovarian response after stimulation is generally good. Furthermore, in younger couples, azoospermia can be partially compensated by the efficient ovarian response, resulting in an acceptable fertility rate following in vitro fertilization (IVF) techniques. Conversely, when azoospermia is associated with a reduced ovarian reserve and/or advanced maternal age, the treatment becomes more challenging, with a consequent reduction in IVF outcomes. Nonetheless, azoospermia seems to impair neither the euploidy rate at the blastocyst stage nor the implantation of euploid blastocysts. Based on the current knowledge, the assessment of male infertility factors should involve: (1) evaluation - to diagnose and quantify seminologic alterations; (2) potentiality - to determine the real possibilities to improve sperm parameters and/or retrieve spermatozoa; (3) time - to consider the available "treatment window", based on maternal age and ovarian reserve. This review represents an update of the definition, prevalence, causes, and treatment of SMF in a modern ART clinic.

Maternal body mass index associates with blastocyst euploidy and live birth rates: the tip of an iceberg?

RESEARCH QUESTION: Does maternal preconceptional body mass index (BMI) associate with mean blastocyst euploidy rate (m-ER) per patient and live birth rate (LBR) after vitrified-warmed euploid single embryo transfer (SET)? DESIGN: Observational study conducted between April 2013 and March 2020 at a private IVF clinic, involving 1811 Caucasian women undergoing trophectoderm biopsy and comprehensive chromosome testing. The outcomes of 1125 first vitrified-warmed euploid SET were also analysed. Patients were clustered as normal weight (BMI 18.5-25; n = 1392 performing 859 SET), underweight (BMI <18.5; n = 160 performing 112 SET) and overweight (BMI >25; n = 259 performing 154 SET). m-ER per patient was the primary outcome. The secondary outcomes were all clinical outcomes per euploid SET. All data were adjusted for confounders through regression analyses. RESULTS: The m-ER per patient decreases as maternal BMI increases from 17 up to 22-23 before reaching a plateau. A linear regression adjusted for maternal age confirmed this moderate association (unstandardized coefficient B: -0.6%, 95% confidence interval [CI]: -1.1 to -0.1%, P = 0.02). All clinical outcomes were similar between normal weight and underweight women. Overweight women, instead, showed higher miscarriage rate per clinical pregnancy (n = 20/75, 26.7% versus n = 67/461, 14.5%; odds ratio [OR] adjusted for blastocyst quality and day of full blastulation: 2.0, 95% CI: 1.1-3.6, P = 0.01) and lower LBR per SET (n = 55/154, 35.7% versus n = 388/859, 45.2%; OR adjusted for blastocyst quality and day of full blastulation: 0.67, 95% CI: 0.46-0.96, P = 0.03). CONCLUSION: These data indicate a need for future research on more sensitive metrics to assess body fat mass and distribution, as well as on the mechanisms leading to lipotoxicity, thereby impairing embryo competence and/or endometrial receptivity. Overweight women should be informed of their higher risk for miscarriage and, whenever possible, encouraged to lose weight, especially before transfer.

Oocyte competence is independent of the ovulation trigger adopted: a large observational study in a setting that entails vitrified-warmed single euploid blastocyst transfer.

PURPOSE: To assess whether the GnRH-agonist or urinary-hCG ovulation triggers affect oocyte competence in a setting entailing vitrified-warmed euploid blastocyst transfer. METHODS: Observational study (April 2013-July 2018) including 2104 patients (1015 and 1089 in the GnRH-a and u-hCG group, respectively) collecting ≥1 cumulus-oocyte-complex (COC) and undergoing ICSI with ejaculated sperm, blastocyst culture, trophectoderm biopsy, comprehensive-chromosome-testing, and vitrified-warmed transfers at a private clinic. The primary outcome measure was the euploid-blastocyst-rate per inseminated oocytes. The secondary outcome measure was the maturation-rate per COCs. Also, the live-birth-rate (LBR) per transfer and the cumulative-live-birth-delivery-rate (CLBdR) among completed cycles were investigated. All data were adjusted for confounders. RESULTS: The generalized-linear-model adjusted for maternal age highlighted no difference in the mean euploid-blastocyst-rate per inseminated oocytes in either group. The LBR per transfer was similar: 44% (n=403/915) and 46% (n=280/608) in GnRH-a and hCG, respectively. On the other hand, a difference was reported regarding the CLBdR per oocyte retrieval among completed cycles, with 42% (n=374/898) and 25% (n=258/1034) in the GnRh-a and u-hCG groups, respectively. Nevertheless, this variance was due to a lower maternal age and higher number of inseminated oocytes in the GnRH-a group, and not imputable to the ovulation trigger itself (multivariate-OR=1.3, 95%CI: 0.9-1.6, adjusted p-value=0.1). CONCLUSION: GnRH-a trigger is a valid alternative to u-hCG in freeze-all cycles, not only for patients at high risk for OHSS. Such strategy might increase the safety and flexibility of controlled-ovarian-stimulation with no impact on oocyte competence and IVF efficacy.

The Impact of Unbalanced Maternal Nutritional Intakes on Oocyte Mitochondrial Activity: Implications for Reproductive Function.

Accumulating evidence on the effect of nutrition on reproduction is emerging from both animal and human studies. A healthy dietary pattern and nutrient supplementation, especially during the peri-conceptional period, might be helpful to achieve a live birth, although the mechanisms implicated are not fully understood. The endocrine system and the ooplasmic organelles apparatus, in particular the mitochondria, are clearly key elements during oogenesis and subsequent embryo development, and their proper functioning is associated with nutrition, even beyond maternal aging. Several studies in animal models have reported various adverse effects on mitochondria caused by unbalanced dietary intakes such as high fat diet, high fat high sugar diet, and low protein diet. The alterations produced might include mitochondrial intracellular distribution, content, structure, biogenesis, and functioning. This review summarizes the key role of mitochondria in female reproduction and the effects of different dietary macronutrient compositions on oocyte mitochondrial activity with their possible short-, medium-, and long-term effects.

DuoStim - a reproducible strategy to obtain more oocytes and competent embryos in a short time-frame aimed at fertility preservation and IVF purposes. A systematic review.

Recent evidence suggests that follicular development occurs in a wave-like model during the ovarian cycle, where up to three cohorts of follicles are recruited to complete folliculogenesis. This understanding overtakes the previous dogma stating that follicles grow only during the follicular phase of the menstrual cycle. Therefore, in in vitro fertilization (IVF), novel protocols regarding ovarian stimulation have been theorized based on the use of gonadotrophins to prompt the growth of antral follicles at any stage of the menstrual cycle. These unconventional protocols for ovarian stimulation aim at a more efficient management of poor-prognosis patients, otherwise exposed to conflicting outcomes after conventional approaches. DuoStim appears among these unconventional stimulation protocols as one of the most promising. It combines two consecutive stimulations in the follicular and luteal phases of the same ovarian cycle, aimed at increasing the number of oocytes retrieved and embryos produced in the short time-frame. This protocol has been suggested for the treatment of all conditions requiring a maximal and urgent exploitation of the ovarian reserve, such as oncological patients and poor responders at an advanced maternal age. At present, data from independent studies have outlined the consistency and reproducibility of this approach, which might also reduce the drop-out between consecutive failed IVF cycles in poor-prognosis patients. However, the protocol must be standardized, and more robust studies and cost-benefit analyses are needed to highlight the true clinical pros and cons deriving from DuoStim implementation in IVF.

Double stimulation in the same ovarian cycle (DuoStim) is an intriguing strategy to improve oocyte yield and the number of competent embryos in a short timeframe.

Proper ovarian stimulation regimens are crucial for any patient undergoing in-vitro fertilization (IVF). However, maximizing the oocyte yield in advanced maternal age patients with poor or suboptimal response is still a challenge. In fact, no standard treatment has been outlined yet to manage these women. Across the last years, an improved efficiency of the IVF units via blastocyst culture, vitrification and reliable embryo selection approaches paved the way to the investigation of novel unconventional stimulation protocols, like double stimulation in a single ovarian cycle (DuoStim). DuoStim, by conjugating follicular phase stimulation (FPS) and luteal phase stimulation (LPS) in the same ovarian cycle, allows to maximize the number of oocytes obtained in a short timeframe, a precious outcome when we aim at shortening time to pregnancy. In this regard, LPS seems to contribute to conventional stimulation with more oocytes with a comparable competence as FPS, retrieved per ovarian cycle. Although any stimulation protocol which exploits anovulatory waves of follicular growth needs a thorough investigation, no evidence has been produced to question the safety of DuoStim, which to date represents the most intriguing strategy to treat poor prognosis in IVF.

Impact of Maternal Age on Oocyte and Embryo Competence.

The overall success of human reproduction, either spontaneously or after IVF, is highly dependent upon maternal age. The main reasons for age-related infertility include reduced ovarian reserve and decreased oocyte/embryo competence due to aging insults, especially concerning an increased incidence of aneuploidies and possibly decreased mitochondrial activity. Age-related chromosomal abnormalities mainly arise because of meiotic impairments during oogenesis, following flawed chromosome segregation patterns such as non-disjunction, premature separation of sister chromatids, or the recent reverse segregation. In this review, we briefly discuss the main mechanisms putatively impaired by aging in the oocytes and the deriving embryos. We also report the main strategies proposed to improve the management of advanced maternal age women in IVF: fertility preservation through oocyte cryopreservation to prevent aging; optimization of the ovarian stimulation and enhancement of embryo selection to limit its effects; and oocyte donation to circumvent its consequences.

What is new in the management of poor ovarian response in IVF?

PURPOSE OF REVIEW: The management and treatment of patients with poor ovarian response is still a controversial issue in IVF. Increasing evidences demonstrate that the number of oocytes retrieved after a controlled ovarian stimulation (COS) greatly influences the clinical outcome in terms of cumulative live birth per started cycle. For this reason, any COS should aim to optimize the number of oocytes according to the ovarian reserve of the patient. The aim of this review is to provide an overview of new strategies proposed to manage poor responders according to the novel POSEIDON classification. RECENT FINDINGS: Gonadotrophins cannot compensate for the absence of follicles in the ovary, therefore, COS in poor responders may benefit from the exploitation of multiple follicular waves within a single ovarian cycle, for instance, through luteal phase stimulation or double stimulation (follicular plus luteal) in the same ovarian cycle (DuoStim) protocols. SUMMARY: Many strategies have been proposed to manage poor responder patients, however, a consensus upon which is the most beneficial has not been yet reached. DuoStim is the most promising approach to increase the number of oocytes collected in a single ovarian cycle; however, more embryological and clinical data is required, as well as an analysis of its cost-effectiveness.