Addressing corneal opacity after herpes zoster infection.

A 15-year-old boy was referred for corneal opacity evaluation. The patient had a previous herpes zoster virus (HZV) infection-varicella-zoster virus (VZV)-with ocular manifestation 1 year ago. After the infection, he developed a central corneal scar and decreased corrected distance visual acuity (CDVA) in the right eye. The slitlamp examination showed the right eye with central corneal opacity (involving anterior stroma), lacuna area between the haze, fluorescein negative, and no vascularization near the scar (Figure 1JOURNAL/jcrs/04.03/02158034-202406000-00019/figure1/v/2024-07-10T174224Z/r/image-tiff). The patient had been treated with oral valacyclovir and topical corticosteroids without any improvement of visual acuity or changes in opacity within the 1-year follow-up. His CDVA was 20/200 (-4.50 -0.75 × 25) in the right eye and counting fingers (-4.00) in the left eye. Intraocular pressure was 12 mm Hg in both eyes. Fundoscopy was normal in the right eye, but he had a macular scar in the left eye (diagnosed when he was 7 years). The left eye had no cornea signs. The patient has no comorbidity or previous surgeries. Considering this case, a corneal central scar in a 15-year-old boy, legally single eye only, and assuming it is an opacity in the anterior stroma, would you consider surgery for this patient? If so, which would you choose: Would you consider an excimer laser treatment of his ametropia while partially removing his opacity, a phototherapeutic keratectomy (PTK), or a PTK followed by a topography-guided treatment, femtosecond laser-assisted anterior lamellar keratoplasty (FALK), or deep anterior lamellar keratoplasty (DALK) or penetrating keratoplasty (depending on the scar depth)? Would you consider prophylactic acyclovir during and after surgery? Would you consider any other surgical step to prevent delayed corneal healing-persistent epithelial defect? Before the surgical approach, would you consider treating this patient with topical losartan (a transforming growth factor [TGF]-ß signaling inhibitor)? Would you first perform the surgery (which one) and then start the medication? Furthermore, if so, how long would you treat this patient? Would you consider treatment with another medication?

Evaluation of macular integrity, after retinal detachment surgery, using MAIA microperimetry.

BACKGROUND AND OBJECTIVE: To describe visual function, macular integrity, and fixation stability using MAIA microperimetry (macular integrity assessment) after retinal detachment surgery. Evaluate if there are statistically significant differences between surgical approaches. MATERIALS AND METHODS: A prospective, comparative, interventional study was conducted, recruiting a total of 21 patients with rhegmatogenous retinal detachment and macula-off. Eleven patients underwent surgery using pars plana vitrectomy (PPV), and 10 patients underwent scleral buckle surgery. Clinical examinations and optical coherence tomography (OCT) were performed post-surgery. MAIA microperimetry was conducted at 6 months. RESULTS: Best-corrected visual acuity (BCVA) and the number of letters read improved over time in the operated eye but did not reach the level of the control eye (p = 0.001). No significant differences were found between the two surgical approaches in BCVA (p = 0.230) or the number of letters read (p = 0.608). Macular integrity in the operated eye did not match that of the control eye in both procedures (p = 0.05). No differences were detected between the two surgeries, either in macular integrity (p = 0.512) or fixation stability (p = 0.835). CONCLUSIONS: Following retinal detachment surgery, a decrease in BCVA and the number of letters read occurs, which does not reach the level of the control eye. No significant differences were observed between the two surgical approaches. Macular integrity in the operated eye does not match that of the control eye.

Risk-based lung cancer screening performance in a universal healthcare setting.

Globally, lung cancer is the leading cause of cancer death. Previous trials demonstrated that low-dose computed tomography lung cancer screening of high-risk individuals can reduce lung cancer mortality by 20% or more. Lung cancer screening has been approved by major guidelines in the United States, and over 4,000 sites offer screening. Adoption of lung screening outside the United States has, until recently, been slow. Between June 2017 and May 2019, the Ontario Lung Cancer Screening Pilot successfully recruited 7,768 individuals at high risk identified by using the PLCOm2012noRace lung cancer risk prediction model. In total, 4,451 participants were successfully screened, retained and provided with high-quality follow-up, including appropriate treatment. In the Ontario Lung Cancer Screening Pilot, the lung cancer detection rate and the proportion of early-stage cancers were 2.4% and 79.2%, respectively; serious harms were infrequent; and sensitivity to detect lung cancers was 95.3% or more. With abnormal scans defined as ones leading to diagnostic investigation, specificity was 95.5% (positive predictive value, 35.1%), and adherence to annual recall and early surveillance scans and clinical investigations were high (>85%). The Ontario Lung Cancer Screening Pilot provides insights into how a risk-based organized lung screening program can be implemented in a large, diverse, populous geographic area within a universal healthcare system.

Visual outcomes of combined use of implantable collamer lens implantation and laser corneal visual correction for myopia over -18.00 diopters.

PURPOSE: To explore visual outcomes in patients with extreme myopia receiving an implantable collamer lens (ICL) at -18.00 diopters (D), with central port, followed by bioptics by laser vision correction (laser in situ keratomileusis [LASIK] or photorefractive keratectomy [PRK]) to address residual myopia or myopic astigmatism. SETTING: Clínica Baviera (Aier Eye Hospital Group), Bilbao, Spain. DESIGN: Retrospective analysis of cases. METHODS: The study assessed uncorrected distance visual acuity, corrected distance visual acuity (CDVA), predictability, safety, efficacy, and patient satisfaction after implantation of the ICL and bioptics. The model implanted was V4c and EVO, with a correction of -18.00 D. Bioptics were performed at least 3 months after implantation, and patients were followed up for at least 3 months after LASIK or PRK. RESULTS: The analysis included 125 eyes from 90 patients. Of these, 51.2% underwent LASIK and 48.8% PRK. Mean time from implantation to bioptics was 5.9 ± 9.4 months. Patients were followed up for a mean of 40.2 ± 37.9 months after bioptics. Median manifest refractive spherical equivalent was -2.89 D before bioptics and -0.49 D after. Median CDVA was 0.18 logMAR before bioptics and 0.17 after. The mean safety and efficacy indices were 2.22 ± 1.88 and 2.06 ± 1.85, respectively. CONCLUSIONS: Visual outcomes and safety indices after ICL implantation and subsequent LASIK or PRK in patients with extreme myopia are excellent.

Phacoemulsification with implantation of a trifocal intraocular lens in eyes with asteroid hyalosis and synchysis scintillans.

PURPOSE: To compare the visual outcomes in both eyes of patients who undergo phacoemulsification and trifocal intraocular lens (IOL) implantation and have asteroid hyalosis (AH) or synchysis scintillans (SS) in only one eye. METHODS: A retrospective comparative case series was performed. We evaluated uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), predictability, safety, efficacy, and satisfaction after implantation of the same model of trifocal IOL in both eyes (PhysIOL FineVision Pod-F and Micro-F and Rayner RayOne Trifocal). RESULTS: A total of 164 eyes of 82 patients (41 females, 50%) met the inclusion criteria. There were no statistically significant differences in sphere, cylinder, spherical equivalent, UDVA, UIVA, or UNVA between the groups. Postoperative CDVA was slightly better in the control group (logMAR 0.03) than in the AH/SS group (logMAR 0.04) (P: 0.014). There were no statistically significant differences in predictability, safety index, or efficacy index between the groups. Overall subjective satisfaction was good (98.2%). CONCLUSIONS: Visual outcomes and satisfaction are good after implantation of trifocal IOLs in eyes with AH or SS. Therefore, trifocal IOLs should not be ruled out in these patients when no other vitreoretinal disorder is present.

Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma.

Liver cancer, specifically hepatocellular carcinoma (HCC), is the sixth most common cancer and the third leading cause of cancer mortality worldwide. The development of effective systemic therapies, particularly those involving immune-checkpoint inhibitors (ICIs), has substantially improved the outcomes of patients with advanced-stage HCC. Approximately 30% of patients are diagnosed with early stage disease and currently receive potentially curative therapies, such as resection, liver transplantation or local ablation, which result in median overall survival durations beyond 60 months. Nonetheless, up to 70% of these patients will have disease recurrence within 5 years of resection or local ablation. To date, the results of randomized clinical trials testing adjuvant therapy in patients with HCC have been negative. This major unmet need has been addressed with the IMbrave 050 trial, demonstrating a recurrence-free survival benefit in patients with a high risk of relapse after resection or local ablation who received adjuvant atezolizumab plus bevacizumab. In parallel, studies testing neoadjuvant ICIs alone or in combination in patients with early stage disease have also reported efficacy. In this Review, we provide a comprehensive overview of the current approaches to manage patients with early stage HCC. We also describe the tumour immune microenvironment and the mechanisms of action of ICIs and cancer vaccines in this setting. Finally, we summarize the available evidence from phase II/III trials of neoadjuvant and adjuvant approaches and discuss emerging clinical trials, identification of biomarkers and clinical trial design considerations for future studies.

Economic impact of inflammatory bowel disease in Catalonia: a population-based analysis.

Background: Inflammatory bowel disease (IBD) has a major economic impact on healthcare costs. Objectives: The aim of this study was to evaluate the current healthcare expenditure associated with IBD in a population-wide study in Catalonia. Design: Retrospective observational study. Methods: All patients with IBD included in the Catalan Health Surveillance System (CHSS) were considered eligible. The CHSS compiles data on more than 7 million individuals in 2020 (34,823 with IBD). Data on the use of healthcare resources and its economic impact were extracted applying the International Classification of Diseases, 10th revision, Clinical Modification codes (ICD-10-CM codes). Health expenditure, comorbidities, and hospitalization were calculated according to the standard costs of each service provided by the Department of Health of the Catalan government. The data on the IBD population were compared with non-IBD population adjusted for age, sex, and income level. IBD costs were recorded separately for Crohn's disease (CD) and ulcerative colitis (UC). Results: Prevalence of comorbidities was higher in patients with IBD than in those without. The risk of hospitalization was twice as high in the IBD population. The overall healthcare expenditure on IBD patients amounted to 164M€. The pharmacy cost represents the 60%. The average annual per capita expenditure on IBD patients was more than 3.4-fold higher (IBD 4200€, non-IBD 1200€). Average costs of UC were 3400€ and 5700€ for CD. Conclusion: The risk of comorbidities was twice as high in patients with IBD and their use of healthcare resources was also higher than that of their non-IBD counterparts. Per capita healthcare expenditure was approximately 3.4 times higher in the population with IBD. Trial registration: The study was not previously registered.

Economic impact of inflammatory bowel disease in Catalonia The manuscript includes data of the most recent epidemiologic data about the high economic impact of IBD in Catalonia.

Critical Appraisal of Guideline Recommendations on Systemic Therapies for Advanced Hepatocellular Carcinoma: A Review.

Importance: The combination of immune checkpoint inhibitors with antiangiogenic agents has revolutionized the treatment landscape of advanced hepatocellular carcinoma (HCC). However, due to rapid publication of new studies that attained their predefined primary end points, a lack of robust cross-trial comparison of first-line therapies, and diverging clinical guidelines, no clear-cut treatment flowchart and sequence of therapies are available. This critical analysis of the recommendations for the management of advanced HCC from the main scientific societies in the US and Europe adopted an integrated approach to provide information on the clinical benefit (overall survival and progression-free survival) and safety profile of these therapies using the European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) score and an ad hoc network meta-analysis. Observations: There is a major consensus among guidelines that atezolizumab plus bevacizumab has a primacy as the recommended first-line treatment of choice in advanced HCC. On progression after immunotherapy-containing regimens and for patients with contraindications for immunotherapies, most guidelines maintain the established treatment hierarchy, recommending lenvatinib or sorafenib as the preferred options, followed by either regorafenib, cabozantinib, or ramucirumab. Thus far, the first-line immune-based regimen of tremelimumab plus durvalumab has been integrated only in the American Association for the Study of Liver Diseases guidance document and the latest National Comprehensive Cancer Network guidelines and has particular utility for patients with a high risk of gastrointestinal bleeding. Overall, in the first-line setting, both atezolizumab plus bevacizumab and sintilimab plus IBI305 (a bevacizumab biosimilar) and durvalumab plus tremelimumab received the highest ESMO-MCBS score of 5, indicating a substantial magnitude of clinical benefit. In a network meta-analysis, no significant differences in overall survival were found among the various combination regimens. However, the newly reported combination of camrelizumab plus rivoceranib was associated with a significantly higher risk of treatment-related adverse events compared with atezolizumab plus bevacizumab (relative risk, 1.59; 95% CI, 1.25-2.03; P < .001). Conclusions and Relevance: This narrative review found that atezolizumab plus bevacizumab is regarded as the primary standard of care for advanced HCC in the first-line setting. These findings from integrating the recommendations from scientific societies' guidelines for managing advanced HCC along with new data from cross-trial comparisons may aid clinicians in decision-making and guide them through a rapidly evolving and complex treatment landscape.

Molecular portraits of patients with intrahepatic cholangiocarcinoma who diverge as rapid progressors or long survivors on chemotherapy.

OBJECTIVE: Cytotoxic agents are the cornerstone of treatment for patients with advanced intrahepatic cholangiocarcinoma (iCCA), despite heterogeneous benefit. We hypothesised that the pretreatment molecular profiles of diagnostic biopsies can predict patient benefit from chemotherapy and define molecular bases of innate chemoresistance. DESIGN: We identified a cohort of advanced iCCA patients with comparable baseline characteristics who diverged as extreme outliers on chemotherapy (survival <6 m in rapid progressors, RP; survival >23 m in long survivors, LS). Diagnostic biopsies were characterised by digital pathology, then subjected to whole-transcriptome profiling of bulk and geospatially macrodissected tissue regions. Spatial transcriptomics of tumour-infiltrating myeloid cells was performed using targeted digital spatial profiling (GeoMx). Transcriptome signatures were evaluated in multiple cohorts of resected cancers. Signatures were also characterised using in vitro cell lines, in vivo mouse models and single cell RNA-sequencing data. RESULTS: Pretreatment transcriptome profiles differentiated patients who would become RPs or LSs on chemotherapy. Biologically, this signature originated from altered tumour-myeloid dynamics, implicating tumour-induced immune tolerogenicity with poor response to chemotherapy. The central role of the liver microenviroment was confrmed by the association of the RPLS transcriptome signature with clinical outcome in iCCA but not extrahepatic CCA, and in liver metastasis from colorectal cancer, but not in the matched primary bowel tumours. CONCLUSIONS: The RPLS signature could be a novel metric of chemotherapy outcome in iCCA. Further development and validation of this transcriptomic signature is warranted to develop precision chemotherapy strategies in these settings.

Comparison of Patients With Emmetropia and Presbyopia and Different Accommodation Who Undergo Unilateral or Bilateral Implantation of a Trifocal IOL.

PURPOSE: To compare visual outcomes and satisfaction in patients with emmetropia, presbyopia, and greater or lesser residual accommodation who undergo unilateral or bilateral implantation of a trifocal diffractive intraocular lens (IOL). METHODS: A multicenter, multisurgeon study was performed to evaluate outcomes in patients with emmetropia and presbyopia who underwent refractive lens exchange followed by implantation of a FineVision trifocal IOL (PhysIOL). The inclusion criteria were as follows: emmetropia, sphere -0.25 to +0.50 diopters (D), cylinder less than 0.75 D, and manifest refractive spherical equivalent (MRSE) of -0.25 to +0.25 D. All patients also had to have an uncorrected distance visual acuity (UDVA) of Snellen 0.9 or better in each eye. The sample was divided into different clusters based on two variables: eyes operated on (monocular or binocular) and age either younger than 55 years or 55 years or older. Thus, four possible groups were created. Visual and refractive performance, patient satisfaction, and spectacle independence were assessed. RESULTS: A total of 690 eyes from 431 patients were evaluated. There was no difference in postoperative uncorrected (UDVA) and corrected (CDVA) distance visual acuity between the groups. Binocular uncorrected near vision (UNVA) was better in patients who underwent surgery on both eyes regardless of age (median [interquartile range]: 0.00 [0.00; 0.10] vs 0.10 [0.00; 0.10] logMAR; P < .001). Binocular uncorrected intermediate vision (UIVA) was better in patients who underwent surgery on both eyes aged younger than 55 years than in those who underwent surgery in one eye aged 55 years or older (median [interquartile range]: 0.18 [0.10; 0.18] vs 0.30 [0.18; 0.30] logMAR; P < .001). The efficacy and safety indexes were 0.98 ± 0.09 and 1.01 ± 0.06, respectively. A total of 93.3% of eyes were within the 0.50 D range in postoperative MRSE. Visual dysphotopsia was worse in patients with both eyes operated on, although the differences were not statistically significant. CONCLUSIONS: The study shows that after refractive lens exchange, patients with emmetropia and presbyopia who received a trifocal IOL in one or both eyes achieved good UNVA, UIVA, and UDVA. Regarding near binocular visual acuity, results were better for patients who underwent surgery on both eyes than for those who underwent surgery on one eye. Regarding binocular intermediate visual acuity, patients aged younger than 55 years with both lenses replaced had better results than those 55 years or older with only one lens replaced. However, no significant differences were observed in UDVA or patient satisfaction. [J Refract Surg. 2023;39(12):817-824.].

Visual and refractive outcomes after implantation of two models of trifocal intraocular lenses in eyes with previous corneal ablation to treat hyperopia.

BACKGROUND: To assess whether a trifocal intraocular lens (IOL) with neutral spherical aberration (SA) provides better visual and refractive outcomes than a trifocal IOL with negative SA after hyperopic corneal laser ablation. METHODS: This is a retrospective comparative study. Patients were classified according to the IOL implanted after cataract or clear lens phacoemulsification [group 1, PhysIOL FineVision Pod-F (negative SA); group 2, Rayner RayOne Trifocal (neutral SA)]. We evaluated uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), predictability, safety, efficacy, and satisfaction. RESULTS: 198 eyes of 119 patients met the inclusion criteria. Group 1 comprised 120 eyes and group 2 comprised 78 eyes. At completion, the refractive and predictability results were significantly better in group 1 than in group 2 for manifest refraction spherical equivalent (MRSE) (P < 0.001). Differences were not significant for UDVA (P = 0.647), CDVA (P = 0.343), UIVA (P = 0.059), UNVA (P = 0.382), binocular UIVA (P = 0.157), or binocular UNVA (P = 0.527). Safety and efficacy indices in refractive lens exchange (RLE) eyes were 0.96 and 0.91, and 0.89 and 0.93 in groups 1 and 2, respectively (P = 0.254 and 0.168). Patient satisfaction was similar in both groups (P > 0.05, all items). CONCLUSION: In eyes previously treated with hyperopic corneal ablation, implantation of a trifocal IOL with neutral SA provided better efficacy and safety outcomes but worse predictability outcomes than those obtained with a trifocal model with negative SA.

Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial.

BACKGROUND: Systemic therapies have improved the management of hepatocellular carcinoma, but there is still a need to further enhance overall survival in first-line advanced stages. This study aimed to evaluate the addition of pembrolizumab to lenvatinib versus lenvatinib plus placebo in the first-line setting for unresectable hepatocellular carcinoma. METHODS: In this global, randomised, double-blind, phase 3 study (LEAP-002), patients aged 18 years or older with unresectable hepatocellular carcinoma, Child Pugh class A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no previous systemic treatment were enrolled at 172 global sites. Patients were randomly assigned (1:1) with a central interactive voice-response system (block size of 4) to receive lenvatinib (bodyweight <60 kg, 8 mg/day; bodyweight ≥60 kg, 12 mg/day) plus pembrolizumab (200 mg every 3 weeks) or lenvatinib plus placebo. Randomisation was stratified by geographical region, macrovascular portal vein invasion or extrahepatic spread or both, α-fetoprotein concentration, and Eastern Cooperative Oncology Group performance status. Dual primary endpoints were overall survival (superiority threshold at final overall survival analysis, one-sided p=0·019; final analysis to occur after 532 events) and progression-free survival (superiority threshold one-sided p=0·002; final analysis to occur after 571 events) in the intention-to-treat population. Results from the final analysis are reported. This study is registered with ClinicalTrials.gov, NCT03713593, and is active but not recruiting. FINDINGS: Between Jan 17, 2019, and April 28, 2020, of 1309 patients assessed, 794 were randomly assigned to lenvatinib plus pembrolizumab (n=395) or lenvatinib plus placebo (n=399). Median age was 66·0 years (IQR 57·0-72·0), 644 (81%) of 794 were male, 150 (19%) were female, 345 (43%) were Asian, 345 (43%) were White, 22 (3%) were multiple races, 21 (3%) were American Indian or Alaska Native, 21 (3%) were Native Hawaiian or other Pacific Islander, 13 (2%) were Black or African American, and 46 (6%) did not have available race data. Median follow up as of data cutoff for the final analysis (June 21, 2022) was 32·1 months (IQR 29·4-35·3). Median overall survival was 21·2 months (95% CI 19·0-23·6; 252 [64%] of 395 died) with lenvatinib plus pembrolizumab versus 19·0 months (17·2-21·7; 282 [71%] of 399 died) with lenvatinib plus placebo (hazard ratio [HR] 0·84; 95% CI 0·71-1·00; stratified log-rank p=0·023). As of data cutoff for the progression-free survival final analysis (April 5, 2021), median progression-free survival was 8·2 months (95% CI 6·4-8·4; 270 events occurred [42 deaths; 228 progressions]) with lenvatinib plus pembrolizumab versus 8·0 months (6·3-8·2; 301 events occurred [36 deaths; 265 progressions]) with lenvatinib plus placebo (HR 0·87; 95% CI 0·73-1·02; stratified log-rank p=0·047). The most common treatment-related grade 3-4 adverse events were hypertension (69 [17%] of 395 patients in the lenvatinib plus pembrolizumab group vs 68 [17%] of 395 patients) in the lenvatinib plus placebo group), increased aspartate aminotransferase (27 [7%] vs 17 [4%]), and diarrhoea (25 [6%] vs 15 [4%]). Treatment-related deaths occurred in four (1%) patients in the lenvatinib plus pembrolizumab group (due to gastrointestinal haemorrhage and hepatorenal syndrome [n=1 each] and hepatic encephalopathy [n=2]) and in three (1%) patients in the lenvatinib plus placebo group (due to gastrointestinal haemorrhage, hepatorenal syndrome, and cerebrovascular accident [n=1 each]). INTERPRETATION: In earlier studies, the addition of pembrolizumab to lenvatinib as first-line therapy for advanced hepatocellular carcinoma has shown promising clinical activity; however, lenvatinib plus pembrolizumab did not meet prespecified significance for improved overall survival and progression-free survival versus lenvatinib plus placebo. Our findings do not support a change in clinical practice. FUNDING: Eisai US, and Merck Sharp & Dohme, a subsidiary of Merck.

Duración de la erupción dental prefuncional temporal y permanente en la población de Villa Clara / Duration of temporary and permanent prefunctional tooth eruption in Villa Clara population

Introducción: En Cuba ha sido poco estudiado el tiempo que demora el diente, desde que aflora a la cavidad bucal hasta que alcanza el plano oclusal. Objetivo: Determinar la duración de la erupción clínica prefuncional temporal y permanente en la población de Villa Clara. Métodos: Se realizó un estudio epidemiológico descriptivo entre los años 2014 a 2018. Mediante un muestreo polietápico aleatorio simple se obtuvo una muestra de 2 584 niños y adolescentes (520 entre tres meses y cuatro años para la dentición temporal, y 2 064 entre cuatro y 14 años para la permanente), nacidos en la provincia, sin alteraciones del crecimiento general y craneofacial; se observó el brote; se calcularon por medio de la regresión de probit, las edades medias para los dientes brotados sin contacto oclusal y las que habían alcanzado la oclusión. La duración de la erupción clínica prefuncional fue calculada restando las medianas de ambas variables. Resultados: En los dientes temporales demoró más la erupción clínica prefuncional en los 1ros molares (superiores, 0,63; inferiores, 0,62); en los permanentes, en los incisivos centrales inferiores de hombres y mujeres, 1 y 1,07, respectivamente. Conclusiones: La erupción clínica prefuncional para los dientes permanentes osciló entre cuatro meses y un año; para los temporales, entre cuatro y siete meses con diferencias dentarias. Se elaboró una tabla de duración de la erupción clínica prefuncional de los dientes temporales y permanentes ajustada a la población villaclareña.

Introduction: the time the tooth takes to emerge from the oral cavity until it reaches the occlusal plane has been little studied in Cuba. Objective: to determine the duration of temporary and permanent prefunctional clinical tooth eruption in Villa Clara population. Methods: a descriptive and epidemiological study was carried out from 2014 to 2018. A sample of 2,584 children and adolescents who were born in the province without alterations in general and craniofacial growth was obtained through simple random multistage sampling (520 between three months and four years for temporary dentition and 2,064 between four and 14 years for permanent one); the outbreak was observed; the mean ages for teeth eruption without occlusal contact and those that had reached occlusion were calculated by means of probit regression. The duration of the prefunctional clinical eruption was calculated by subtracting the medians of both variables. Results: prefunctional clinical eruption took longer in temporary (upper, 0.63 and lower, 0.62) 1st molars, as well as in permanent lower central incisors of men and women (1 and 1.07, respectively). Conclusions: prefunctional clinical eruption for permanent teeth ranged from four months to one year and for temporary ones between four and seven months presenting dental differences. A table of the duration of the prefunctional clinical eruption of temporary and permanent teeth was created according to Villa Clara population.

Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy.

Hepatocellular carcinoma (HCC) mortality rates are increasing globally, and particularly in the Western world. Cirrhosis remains the predominant risk factor for HCC. However, epidemiological shifts in the incidence of HCC from patients with virus-related liver disease to those with non-viral aetiologies, including alcohol-associated and metabolic dysfunction-associated steatotic liver disease, have important implications for prevention, surveillance and treatment. Hepatitis B vaccination and antiviral therapy for hepatitis B and C are effective for primary prevention of virus-related HCCs, but chemoprevention strategies for non-viral liver disease remain an unmet need. Emerging data suggest associations between aspirin, statins, metformin and coffee and reduced HCC incidence, although none has been proved to be causally related. Secondary prevention of HCC via semi-annual surveillance is associated with improvements in early detection and thus reduced mortality; however, current tools, including abdominal ultrasonography, have suboptimal sensitivity for the detection of early stage HCC, particularly in patients with obesity and/or non-viral liver disease. Promising blood-based or imaging-based surveillance strategies are emerging, although these approaches require further validation before adoption in clinical practice. In the interim, efforts should be focused on maximizing use of the existing surveillance tools given their prevalent underuse globally. Remarkable advances have been made in the treatment of HCC, including expanded eligibility for surgical therapies, improved patient selection for locoregional treatments and increased systemic treatment options, including immune-checkpoint inhibitors. In this Review, we discuss trends in the epidemiology of HCC and their implications for screening, prevention and therapy.

Incidence of Myelotoxicity and Other Adverse Effects Related to Thiopurine Starting in Patients with Inflammatory Bowel Disease: Retrospective Observational Study in a Third-Level Hospital.

BACKGROUND AND OBJECTIVES: Thiopurines are an effective treatment for the maintenance of remission in inflammatory bowel disease (IBD). They can present adverse effects (AEs), with myelotoxicity being the most relevant. This study aims to determine the incidence of AEs related to the starting of thiopurines in our centre. METHODOLOGY: Retrospective study. The AEs in patients that were started on thiopurines between January 2016 and June 2020 were registered, with a two-year follow-up. The mean and standard deviation were used to describe the quantitative variables, and percentages and confidence intervals were used for the qualitative variables. The statistical significance was set at a p-value < 0.05. RESULTS: 98 patients were included, with 64 AEs detected in 48 patients (49%). Most of the AEs appeared in the first 6 months. The most relevant were: 21 neutropenia (21.4%), 19 hypertransaminasemia (19.4%), 13 digestive intolerances (13.2%), 6 acute pancreatitis (6.12%), 3 phototoxicity (3%), and 2 unknown origin fevers (2%). In 29 patients (29.4%) the treatment had to be suspended due to AEs. In 11 cases (11.2%), azathioprine (AZA) was switched to 6-mercaptopurine (6 MP) as 5 showed tolerance and 6 patients needed suspension due to AEs. Eight patients required hospital admission, but none of them needed intensive care unit admission. There were no fatal adverse effects. CONCLUSIONS: Thiopurines are a safe drug with few AEs, especially after the first months of treatment. These results suggest that periodic analytic follow-up may not be necessary after the initial period of treatment.

Element Depletion Due to Missing Boundary Fluorescence in Electron Probe Microanalysis: The Case of Ni in Olivine.

Secondary fluorescence (SF) is known to be a potential source of error in electron probe microanalysis (EPMA) when analyzing for a trace or minor element near a phase boundary. This often overlooked effect leads to a concentration enhancement whenever the neighboring phase contains a high concentration of the analyzed element. Here we show that SF may also lead to a concentration decrease, which can be mistakenly interpreted as a depletion. To examine this issue, we compare Ni profiles measured on well-characterized, homogeneous olivine [(Mg,Fe)2SiO4] grains embedded in basaltic glass, with semi-analytical calculations and numerical simulations of SF across phase boundaries. We find that the Ni content consistently decreases with decreasing distance to the interface or grain radius, deviating from the expected concentration by ∼2-5% at 10 µm from the interface. This decrease is explained by the lower bremsstrahlung fluorescence emitted from the sample as compared to that emitted from the standard. The analytical error due to boundary fluorescence affecting other elements of petrologic importance in olivine is discussed.

Assessing the Accuracy of Mass Attenuation Coefficients for Soft X-ray EPMA.

The use of soft X-rays in electron probe microanalysis (EPMA) has gained renewed interest over the past decades due to the advent of new detector technologies. Because X-ray absorption is the dominant correction for soft X-rays, a reliable set of mass attenuation coefficients (MACs) is needed for accurate composition determination. Although several MAC tabulations cover the soft X-ray range, the accuracy of such tabulations below 1 keV is not firmly established. In this study, we assess the accuracy of MAC tabulations in the soft X-ray region by comparing tabulated values for Be, B, C, N, O, and F Kα X-rays with experimental data available in the literature. We find that the 1993 semi-empirical MAC compilation of Henke et al. [(1993). Low-energy X-ray interaction coefficients: Photoabsorption, scattering, transmission and reflection at E=50-30000 eV, Z=1-92. Atom Data Nucl Data Tables54, 181-342] and the more recent theoretical MAC calculations of Sabbatucci and Salvat [(2016). Theory and calculation of the atomic photoeffect. Rad Phys Chem121, 122-140] perform slightly better than the rest of the considered tabulations. The Sabbatucci-Salvat dataset also provides the best agreement with the few existing experimental measurements for Al L2,3M X-rays.