Acute Pancreatitis during and after Pregnancy: A Review.

During pregnancy and in the post-partum period, several diseases may arise or become exacerbated. Acute pancreatitis is an inflammatory disease with an increasing incidence in Western countries. The incidence of acute pancreatitis during pregnancy is not different with respect to the general population, but this incidence increases in the first 2 years after delivery. Biliary sludge and stones are the most frequent aetiologies, followed by hypertriglyceridemia. Taking care of the mother and foetus through a potentially severe disease requires a team consisting of an obstetrician, a gastroenterologist, an anaesthesiologist, and a surgeon. It is necessary to monitor the health of the foetus/child and the mother during pregnancy, childbirth, and puerperium. The management of this care depends on the systemic and local complications, the severity of the acute pancreatitis, and the trimester of pregnancy. Some diagnostic tools and many drugs are not safe for foetuses, while interventional endoscopy and surgery have limitations and can only be used after an accurate evaluation of benefit/risk ratios. Despite these limitations, maternal mortality due to acute pancreatitis is low during pregnancy, mainly thanks to multidisciplinary approaches for these patients. A careful diet to prevent obesity, alcohol abstinence, routine serum triglyceride control, and breastfeeding for at least three months may prevent acute pancreatitis during and after pregnancy.

Imaging and molecular features of adenomyosis after menopause.

OBJECTIVES: To explore the imaging features and the molecular characterization of adenomyosis after menopause. STUDY DESIGN: An observational cross-sectional study was performed in a group of postmenopausal patients undergoing a transvaginal ultrasound (TVUS) (n = 468). Among those presenting the US criteria for adenomyosis, also confirmed by magnetic resonance imaging (MRI), previous menstrual symptoms, gynecological and obstetric history were reviewed. In a subgroup undergoing hysterectomy, uterine specimens were analyzed by histology and expression of genes implicated in the epithelial-mesenchymal transition, inflammation and fibrosis, including the sphingosine-1-phosphate (S1P) pathway, was evaluated and compared to matched non-menopausal adenomyosis specimens. MAIN OUTCOME MEASURES: Direct and indirect US features of adenomyosis according to Morphological Uterus Sonographic Assessment at TVUS. Molecular characterization of postmenopausal versus pre-menopausal adenomyosis samples. RESULTS: According to TVUS and MRI, adenomyosis was identified in 49 patients (10.4 %). On US, diffuse adenomyosis was the most common phenotype, whereas internal adenomyosis with diffuse pattern and asymmetric type was the most prevalent on MRI. Molecular analysis showed that adenomyosis lesions express markers of epithelial-mesenchymal transition, inflammation and fibrosis also in postmenopausal women. By comparing the results with those from pre-menopausal samples, the expression of α smooth muscle actin (αSMA), a marker of fibrosis, was significantly greater after menopause, and altered S1P catabolism and signaling were observed. CONCLUSIONS: Adenomyosis may be identified in postmenopausal women by imaging, either TVUS or MRI, and fibrosis is one of the key features on molecular analysis.

Sphingosine 1-phosphate signaling axis mediates neuropeptide S-induced invasive phenotype of endometriotic cells.

Endometriosis is a chronic gynecological syndrome characterized by endometrial cell invasion of the extra-uterine milieu, pelvic pain and infertility. Treatment relies on either symptomatic drugs or hormonal therapies, even though the mechanism involved in the onset of endometriosis is yet to be elucidated. The signaling of sphingolipid sphingosine 1-phosphate (S1P) is profoundly dysregulated in endometriosis. Indeed, sphingosine kinase (SK)1, one of the two isoenzymes responsible for S1P biosynthesis, and S1P1, S1P3 and S1P5, three of its five specific receptors, are more highly expressed in endometriotic lesions compared to healthy endometrium. Recently, missense coding variants of the gene encoding the receptor 1 for neuropeptide S (NPS) have been robustly associated with endometriosis in humans. This study aimed to characterize the biological effect of NPS in endometriotic epithelial cells and the possible involvement of the S1P signaling axis in its action. NPS was found to potently induce cell invasion and actin cytoskeletal remodeling. Of note, the NPS-induced invasive phenotype was dependent on SK1 and SK2 as well as on S1P1 and S1P3, given that the biological action of the neuropeptide was fully prevented when one of the two biosynthetic enzymes or one of the two selective receptors was inhibited or silenced. Furthermore, the RhoA/Rho kinase pathway, downstream to S1P receptor signaling, was found to be critically implicated in invasion and cytoskeletal remodeling elicited by NPS. These findings provide new information to the understanding of the molecular mechanisms implicated in endometriosis pathogenesis, establishing the rationale for non-hormonal therapeutic targets for its treatment.

Development of a multi-component gastroretentive expandable drug delivery system (GREDDS) for personalized administration of metformin.

OBJECTIVES: Efficacy and compliance of type II diabetes treatment would greatly benefit from dosage forms providing controlled release of metformin in the upper gastrointestinal tract. In this respect, the feasibility of a new system ensuring stomach-retention and personalized release of this drug at its absorption window for multiple days was investigated. METHODS: The system proposed comprised of a drug-containing core and a viscoelastic umbrella-like skeleton, which were manufactured by melt-casting and 3D printing. Prototypes, alone or upon assembly and insertion into commercially-available capsules, were characterized for key parameters: thermo-mechanical properties, accelerated stability, degradation, drug release, deployment performance, and resistance to simulated gastric contractions. RESULTS: Each part of the system was successfully manufactured using purposely-selected materials and the performance of final prototypes matched the desired one. This included: i) easy folding of the skeleton against the core in the collapsed administered shape, ii) rapid recovery of the cumbersome configuration at the target site, even upon storage, and iii) prolonged release of metformin. CONCLUSIONS: Composition, geometry, and performance of the system developed in this work were deemed acceptable for stomach-retention and prolonged as well as customizable release of metformin in its absorption window, laying promising bases for further development steps.

Sphingosine-1-phosphate receptor 3 is a non-hormonal target to counteract endometriosis-associated fibrosis.

OBJECTIVE: To study the molecular mechanisms responsible for fibrosis in endometriosis by investigating whether the protein expression levels of sphingosine-1-phosphate receptor 3 (S1PR3), one of the five specific receptors of the bioactive sphingolipid sphingosine-1-phosphate (S1P), correlate with fibrosis extent in endometriotic lesions and which are the cellular mechanisms involved in this process. DESIGN: Case-control laboratory study and cultured endometriotic cells. SETTING: University research institute and university hospital. PATIENT(S): A total of 33 women, with and without endometriosis, were included in the study. INTERVENTIONS(S): Endometriotic lesions were obtained from women with endometriosis (ovarian endometrioma, n = 8; deep infiltrating endometriosis, n = 15; [urological n = 5, gastrointestinal n = 6, and posterior n = 4]) and control endometrium from healthy women, n = 10, by means of laparoscopic and hysteroscopic surgery. The expression of S1PR3 was evaluated using immunohistochemistry and the extent of fibrosis was assessed using Masson's trichrome staining. Human-cultured epithelial endometriotic 12Z cells were used to evaluate the mechanisms involved in the profibrotic effect of S1PR3 activation. MAIN OUTCOME MEASURE(S): The expression of S1PR3 in endometriotic lesions is positively correlated with endometriosis-associated fibrosis. In addition, S1P induced epithelial-mesenchymal transition (EMT) and fibrosis in epithelial endometriotic cells. Using RNA interference and pharmacological approaches, the profibrotic effect of S1P was shown to rely on S1PR3, thus unveiling the molecular mechanism implicated in the profibrotic action of the bioactive sphingolipid. RESULT(S): The protein expression levels of S1PR3 were significantly augmented in the glandular sections of endometrioma and deep infiltrating endometriosis of different localizations with respect to the control endometrium and positively correlated with the extent of fibrosis. Sphingosine-1-phosphate was shown to have a crucial role in the onset of fibrosis in epithelial endometriotic cells, stimulating the expression of EMT and fibrotic markers. Genetic approaches have highlighted that S1PR3 mediates the fibrotic effect of S1P. Downstream of S1PR3, ezrin and extracellular-signal-regulated kinases 1 and 2 signaling were found to be critically implicated in the EMT and fibrosis elicited by S1P. CONCLUSION(S): Sphingosine-1-phosphate receptor 3 may represent a possible innovative pharmacological target for endometriosis.

Disclosing Early Excited State Relaxation Events in Prototypical Linear Carbon Chains.

One-dimensional (1D) linear nanostructures comprising sp-hybridized carbon atoms, as derivatives of the prototypical allotrope known as carbyne, are predicted to possess outstanding mechanical, thermal, and electronic properties. Despite recent advances in their synthesis, their chemical and physical properties are still poorly understood. Here, we investigate the photophysics of a prototypical polyyne (i.e., 1D chain with alternating single and triple carbon bonds) as the simplest model of finite carbon wire and as a prototype of sp-carbon-based chains. We perform transient absorption experiments with high temporal resolution (<30 fs) on monodispersed hydrogen-capped hexayne H─(C≡C)6─H synthesized by laser ablation in liquid. With the support of computational studies based on ground state density functional theory (DFT) and excited state time-dependent (TD)-DFT calculations, we provide a comprehensive description of the excited state relaxation processes at early times following photoexcitation. We show that the internal conversion from a bright high-energy singlet excited state to a low-lying singlet dark state is ultrafast and takes place with a 200 fs time constant, followed by thermalization on the picosecond time scale and decay of the low-energy singlet state with hundreds of picoseconds time constant. We also show that the time scale of these processes does not depend on the end groups capping the sp-carbon chain. The understanding of the primary photoinduced events in polyynes is of key importance both for fundamental knowledge and for potential optoelectronic and light-harvesting applications of low-dimensional nanostructured carbon-based materials.

Towards compact laser-driven accelerators: exploring the potential of advanced double-layer targets.

The interest in compact, cost-effective, and versatile accelerators is increasing for many applications of great societal relevance, ranging from nuclear medicine to agriculture, pollution control, and cultural heritage conservation. For instance, Particle Induced X-ray Emission (PIXE) is a non-destructive material characterization technique applied to environmental analysis that requires MeV-energy ions. In this context, superintense laser-driven ion sources represent a promising alternative to conventional accelerators. In particular, the optimization of the laser-target coupling by acting on target properties results in an enhancement of ion current and energy with reduced requirements on the laser system. Among the advanced target concepts that have been explored, one appealing option is given by double-layer targets (DLTs), where a very low-density layer, which acts as an enhanced laser absorber, is grown to a thin solid foil. Here we present some of the most recent results concerning the production with deposition techniques of advanced DLTs for laser-driven particle acceleration. We assess the potential of these targets for laser-driven ion acceleration with particle-in-cell simulations, as well as their application to PIXE analysis of aerosol samples with Monte Carlo simulations. Our investigation reports that MeV protons, accelerated with a ∼20 TW compact laser and optimized DLTs, can allow performing PIXE with comparable performances to conventional sources. We conclude that compact DLT-based laser-driven accelerators can be relevant for environmental monitoring.

Epigenetics, endometriosis and sex steroid receptors: An update on the epigenetic regulatory mechanisms of estrogen and progesterone receptors in patients with endometriosis.

Endometriosis is a benign gynecological disease affecting ∼10% of reproductive-aged women and is defined as the presence of endometrial glands and stroma outside the uterine cavity. Endometriosis can cause a variety of health problems, from pelvic discomfort to catamenial pneumothorax, but it's mainly linked with severe and chronic pelvic pain, dysmenorrhea, and deep dyspareunia, as well as reproductive issues. The pathogenesis of endometriosis involves an endocrine dysfunction, with estrogen dependency and progesterone resistance, and inflammatory mechanism activation, together with impaired cell proliferation and neuroangiogenesis. The present chapter aims to discuss the main epigenetic mechanisms related to estrogen receptors (ERs) and progesterone receptors (PRs) in patients with endometriosis. There are numerous epigenetic mechanisms participating in endometriosis, regulating the expression of the genes encoding these receptors both indirectly, through the regulation of transcription factors, and directly, through DNA methylation, histone modifications, micro RNAs and long noncoding RNAs. This represents an open field of investigation, which may lead to important clinical implications such as the development of epigenetic drugs for the treatment of endometriosis and the identification of specific and early biomarkers for the disease.

Pathologic Findings at Risk Reducing Surgery in BRCA and Non-BRCA Mutation Carriers: A Single-Center Experience.

Risk-reducing surgery (RRS) is recommended in BRCA-mutated carriers because of their increased risk of developing ovarian cancer, while its role is still discussed for women harboring mutations in non-BRCA homologous repair genes. The aim of this study was to retrospectively evaluate the occurrence of pathological findings in a high-risk population undergoing RRS in San Matteo Hospital, Pavia between 2012 and 2022, and correlate their genetic and clinical outcomes, comparing them with a control group. The final cohort of 190 patients included 85 BRCA1, 63 BRCA2, 11 CHEK2, 7 PALB2, 4 ATM, 1 ERCC5, 1 RAD51C, 1 CDH1, 1 MEN1, 1 MLH1 gene mutation carriers and 15 patients with no known mutation but with strong familial risk. Occult invasive serous carcinoma (HGSC) and serous tubal intraepithelial carcinoma (STIC) were diagnosed in 12 (6.3%) women, all of them BRCA carriers. No neoplastic lesion was diagnosed in the non-BRCA group, in women with familial risk, or in the control group. Oral contraceptive use and age ≤45 at surgery were both found to be favorable factors. While p53 signature and serous tubal intraepithelial lesion (STIL) were also seen in the control group and in non-BRCA carriers, STIC and HGSC were only found in BRCA1/2 mutation carriers.

Tunable physics through coordination chemistry: formation on oxide surface of Ti and Al chelates with 3-hydroxyflavone capable of electron injection and light emission.

The optoelectronic features of 3-hydroxyflavone (3HF) self-assembled on the surface of an n-type semiconducting metal oxide (TiO2) and an insulator (Al2O3) are herein investigated. 3HF molecules use the coordinatively unsaturated metal ions present on the oxide surface to form metal complexes, which exhibit different behaviors upon light irradiation, depending on the nature of the metal ion. Specifically, we show that the photoluminescence of the surface species can be modulated according to the chemical properties of the complex (i.e. the binding metal ion), resulting in solid-state emitters in a high quantum yield (about 15%). Furthermore, photoinduced charge injection can be promoted or inhibited, providing a multifunctional hybrid system.

Hormonal drugs for the treatment of endometriosis.

In the past, the primary approach for the treatment of endometriosis was represented by surgery; however, after the introduction of non-invasive diagnosis of endometriosis with the development of imaging technologies, medical treatment became the preferred approach, particularly in young patients. Hormonal drugs, by blocking menstruation, are the most effective for the treatment of endometriosis-related pain, independently of phenotype (ovarian, deep, or superficial endometriosis). Gonadotropin-releasing hormone analogs and oral antagonists act on hypothalamus-pituitary-ovary axis inducing iatrogenic menopause, thus reducing dysmenorrhea and all pain symptoms. The side effects, such as hot flushes and bone loss, may be reduced by an add-back therapy. However, the cost in terms of women's health remains high in view of a long-term treatment. Progestins are considered the first-line treatment, highly effective, and with reduced side effects. In addition to the well-known and largely used Norethisterone acetate and Medroxyprogesterone acetate, recently Dienogest has become one of the most used drugs in all endometriosis phenotypes for long-term treatment. Besides, Intrauterine levornogestrel or subcutaneous etonogestrel are valid alternative for long-term treatment.

Breastfeeding in Prevention of Postpartum Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) caused by gallstones has an increased rate of incidence in young women in the 2 years postpartum. Middle-aged women with longer periods of breastfeeding have less hospitalization for gallbladder disease. AIM: To investigate whether breastfeeding or other variables may be associated with AP. METHODS: We conducted a population-based case-control study among all Sicilian women of childbearing age, and we identified all women who delivered (2013-2016) and had AP within 2 years postpartum. We reviewed their medical records, and for each case we matched four women of the same age (± 5 years), without AP. Univariate and multivariate logistic regression was used to estimate the odds ratios (OR) with their confidence intervals (CI) to assess associations between AP and clinical determinants. RESULTS: In the 74 women with AP and 298 controls at univariate analysis, > 6 months oral contraception history (p < 0.01; OR 3.30; 95% CI 1.33-8.16), previous biliary disease (p < 0.001; OR 5.90; 95% CI 1.98-17.57) and smoking (p = 0.035; OR 2.04; 95% CI 1.04-4.0) were predictors of AP; amenorrhea ≥ 3 months (p < 0.001; OR 0.34; 95% CI 0.19-0.59) and breastfeeding ≥ 3 months (p < 0.001; OR 0.07; 95% CI 0.03-0.14) were protective. At multivariate analysis, previous biliary disease (p = 0.011; OR 5.49; 95% CI 1.48-20.38) and breastfeeding ≥ 3 months (p < 0.001; OR 0.06; CI 95% 0.03-0.14) were associated with AP. CONCLUSIONS: Women who breastfeed for at least 3 months and do not have a history of biliary disorders have reduced risk of developing AP in the 2 years after delivery.

Hormonal treatments for endometriosis: The endocrine background.

Endometriosis is a benign uterine disorder characterized by menstrual pain and infertility, deeply affecting women's health. It is a chronic disease and requires a long term management. Hormonal drugs are currently the most used for the medical treatment and are based on the endocrine pathogenetic aspects. Estrogen-dependency and progesterone-resistance are the key events which cause the ectopic implantation of endometrial cells, decreasing apoptosis and increasing oxidative stress, inflammation and neuroangiogenesis. Endometriotic cells express AMH, TGF-related growth factors (inhibin, activin, follistatin) CRH and stress related peptides. Endocrine and inflammatory changes explain pain and infertility, and the systemic comorbidities described in these patients, such as autoimmune (thyroiditis, arthritis, allergies), inflammatory (gastrointestinal/urinary diseases) and mental health disorders.The hormonal treatment of endometriosis aims to block of menstruation through an inhibition of hypothalamus-pituitary-ovary axis or by causing a pseudodecidualization with consequent amenorrhea, impairing the progression of endometriotic implants. GnRH agonists and antagonists are effective on endometriosis by acting on pituitary-ovarian function. Progestins are mostly used for long term treatments (dienogest, NETA, MPA) and act on multiple sites of action. Combined oral contraceptives are also used for reducing endometriosis symptoms by inhibiting ovarian function. Clinical trials are currently going on selective progesterone receptor modulators, selective estrogen receptor modulators and aromatase inhibitors. Nowadays, all these hormonal drugs are considered the first-line treatment for women with endometriosis to improve their symptoms, to postpone surgery or to prevent post-surgical disease recurrence. This review aims to provide a comprehensive state-of-the-art on the current and future hormonal treatments for endometriosis, exploring the endocrine background of the disease.

Optical and Magneto-Optical Properties of Donor-Bound Excitons in Vacancy-Engineered Colloidal Nanocrystals.

Controlled insertion of electronic states within the band gap of semiconductor nanocrystals (NCs) is a powerful tool for tuning their physical properties. One compelling example is II-VI NCs incorporating heterovalent coinage metals in which hole capture produces acceptor-bound excitons. To date, the opposite donor-bound exciton scheme has not been realized because of the unavailability of suitable donor dopants. Here, we produce a model system for donor-bound excitons in CdSeS NCs engineered with sulfur vacancies (VS) that introduce a donor state below the conduction band (CB), resulting in long-lived intragap luminescence. VS-localized electrons are almost unaffected by trapping, and suppression of thermal quenching boosts the emission efficiency to 85%. Magneto-optical measurements indicate that the VS are not magnetically coupled to the NC bands and that the polarization properties are determined by the spin of the valence-band photohole, whose spin flip is massively slowed down due to suppressed exchange interaction with the donor-localized electron.

Bilateral Ovarian Malakoplakia: Case Report and Review of the Literature With Clinical and Diagnostic Considerations.

Malakoplakia is a rare condition in which histiocytic cells accumulate within different organs and tissues, sometimes mimicking neoplasia. Gynecologic involvement is extremely rare and therefore may cause relevant diagnostic confusion for both clinicians and pathologists. In this paper, we described the seventh case of ovarian malakoplakia, and we reviewed the literature to compare it with the previously reported ones. Moreover, we investigated the histologic and molecular differential diagnosis of malakoplakia, with special attention to other histiocytic disorders of gynecologic interest. Finally, we discussed the most relevant points with regard to possible pathogenesis and management. Malakoplakia often represents a forgotten entity that should be remembered preoperatively, when approaching a possible gynecologic neoplasia. Moreover, it is of remarkable importance to differentiate malakoplakia from multisystem histiocytosis involving gynecologic organs. All this would prevent misdiagnosis and overtreatment of such a rare but benign condition.

Photobiomodulation and Miescher's cheilitis granulomatosa: case report.

BACKGROUND: Miescher's cheilitis granulomatosa (MCG) is a rare chronic inflammatory disease and is known as the monosymptomatic clinical form of Melkersson-Rosenthal syndrome (MRS). It is characterised by swelling of one or both lips and more frequently affects the upper lip. Histopathological findings show the presence of numerous inflammatory infiltrates and granuloma formations. Pharmacological treatments and surgery have provided results that are positive yet insufficiently stable in the long term. The clinical case described is of a 68-year-old female patient with a diagnosis of MCG of the upper lip. CASE PRESENTATION: The patient was diagnosed and treated at the Oral Medicine and Oral Pathology outpatient clinic of Maxillofacial and Odontostomatology Unit, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico. The patient was recommended localised treatments of photobiomodulation (PBM) using a diode laser with a 635 nm and 980 nm dual-wavelength (λ) approach, a 600-micron fibre, and a handpiece with a 1-cm-diameter lens at 300 mW. Three treatments a week were administered for four weeks for a total of 12 treatment sessions (T 1-T 12). After that, the patient had a long follow-up period of about 2 years. The therapeutic results were clear from the initial stages of treatment. There was an immediate, gradual, and consistent reduction in labial swelling. A reduction in the size of the lip by about 35% at T 10-T 12 was observed, returning the size and volume of the upper lip within the normal clinical range. The painful symptoms subsided after the seventh treatment (T 7). The histopathological check at 3 months and the follow-up in particular confirmed the disease was in remission with satisfactorily stable treatment results. Moreover, the patient did not use any other treatments on the area from the early laser treatments through to the end of the follow-up period. CONCLUSIONS: Our experience describes a clinical case of MCG treated with PBM and effectively resolved with a reduction of the lip swelling. The real success of the treatment emerged over time, showing that the tissue healing was stable. In absence of any collateral phenomena, this confirms the effective and documented therapeutic potential of PBM for chronic inflammatory infiltrates.

Utility of neutrophil-to-lymphocyte ratio to identify long-term survivors among HCC patients treated with sorafenib.

Sorafenib is the first multikinase inhibitor demonstrating a survival benefit for patients suffering from advanced hepatocellular carcinoma (HCC). However, 1 issue remains open: what is the factor able to predict which patients will be long survivors?In the present study, we harnessed the potential of conditional survival, aiming at estimating the probability that a patient receiving sorafenib survives for more than 3 years.The present multicentric study was conducted on a cohort of 438 HCC patients. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities at 3 years.The 3-year conditional survival of patients without disease progression highlights that NLR and ECOG are the factors that most accurately predict the probability of long survival. The 3-year conditional survival of patients with disease progression showed a medium effect size for HCV status, alpha-fetoprotein and NLR at all time-points. Macro-vascular portal vein invasion, extra hepatic disease, and BCLC we have a large effect size at 6 months and a medium effect size at 12 and 24 months.Our findings support the use of baseline NLR for the identification of patients with a higher probability of long-survival. NLR should be used as a stratification factor in the forthcoming clinical trials on the drugs for the advanced HCC now in pipeline.

Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients.

BACKGROUND & AIMS: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. METHODS: We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAAs. DAA-untreated patients from the ITA.LI.CA. cohort (n = 328) served as controls. After propensity score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared. RESULTS: In the DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in the DAA group compared to the No DAA group (hazard ratio [HR] 0.39; 95% CI0.17-0.91; p = 0.03). HCC recurrence was not significantly different between the DAA and No DAA groups (HR0.70; 95% CI0.44-1.13; p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in the DAA group compared with the No DAA group (HR0.32; 95% CI0.13-0.84; p = 0.02). In the DAA group, sustained virologic response was a significant predictor of OS (HR 0.02; 95% CI 0.00-0.19; p <0.001), HCC recurrence (HR 0.25; 95% CI 0.11-0.57; p <0.001) and hepatic decompensation (HR 0.12; 95% CI 0.02-0.38; p = 0.02). CONCLUSIONS: In patients with HCV-related cirrhosis who had been successfully treated for early HCC, DAAs significantly improved OS compared with No DAA treatment. LAY SUMMARY: We aimed to determine whether direct-acting antivirals (DAAs) significantly improve overall survival in patients with hepatitis C virus-related compensated cirrhosis and a first diagnosis of hepatocellular carcinoma (HCC) which has been successfully treated with curative resection or ablation. Using propensity-score matched patients, we found that DAAs improved overall survival and reduced the risk of hepatic decompensation. However, the risk of HCC recurrence was not significantly reduced.

Quantized Electronic Doping towards Atomically Controlled "Charge-Engineered" Semiconductor Nanocrystals.

"Charge engineering" of semiconductor nanocrystals (NCs) through so-called electronic impurity doping is a long-standing challenge in colloidal chemistry and holds promise for ground-breaking advancements in many optoelectronic, photonic, and spin-based nanotechnologies. To date, our knowledge is limited to a few paradigmatic studies on a small number of model compounds and doping conditions, with important electronic dopants still unexplored in nanoscale systems. Equally importantly, fine-tuning of charge engineered NCs is hampered by the statistical limitations of traditional approaches. The resulting intrinsic doping inhomogeneity restricts fundamental studies to statistically averaged behaviors and complicates the realization of advanced device concepts based on their advantageous functionalities. Here we aim to address these issues by realizing the first example of II-VI NCs electronically doped with an exact number of heterovalent gold atoms, a known p-type acceptor impurity in bulk chalcogenides. Single-dopant accuracy across entire NC ensembles is obtained through a novel non-injection synthesis employing ligand-exchanged gold clusters as "quantized" dopant sources to seed the nucleation of CdSe NCs in organic media. Structural, spectroscopic, and magneto-optical investigations trace a comprehensive picture of the physical processes resulting from the exact doping level of the NCs. Gold atoms, doped here for the first time into II-VI NCs, are found to incorporate as nonmagnetic Au+ species activating intense size-tunable intragap photoluminescence and artificially offsetting the hole occupancy of valence band states. Fundamentally, the transient conversion of Au+ to paramagnetic Au2+ (5d9 configuration) under optical excitation results in strong photoinduced magnetism and diluted magnetic semiconductor behavior revealing the contribution of individual paramagnetic impurities to the macroscopic magnetism of the NCs. Altogether, our results demonstrate a new chemical approach toward NCs with physical functionalities tailored to the single impurity level and offer a versatile platform for future investigations and device exploitation of individual and collective impurity processes in quantum confined structures.