An extremelyinteresting piece of data regarding the disease is that in up to 50% of cases thedisease manifests as a result of a mutation in the NF1 gene inindividuals with no known family histor(1).Neurofibromatosis type 1 (NF1), or von Recklinghausen disease, is one of the most commongenetic diseases, with an estimated incidence of 1:2,500 to 1:3,000 people, regardlessof gender or ethnicity(2): six or morecafé-au-lait spots; axillary or inguinal ephelides; two or more cutaneousneurofibromas of any type or one plexiform neurofibroma; two or more pigmented irishamartomas (Lisch nodules); a specific skeletal lesion (sphenoid wing dysplasia or longbone dysplasia); an optic nerve glioma; and at least one first-degree relative affectedby the disease.Among patients with NF1, the clinical presentation of the disease varies greatly. Thediagnosis is made on the basis of the presence of at least two of the following sevencriteriaNF1 gene is a tumor suppressor gene that is located on the long armof chromosome 17. Regular follow-up of patients with NF1 is recommended because of theincreased risk of neoplasms, such as optic nerve gliomas, glioblastomas, malignanttumors of peripheral nerves, pheochromocytomas, gastrointestinal stromal tumors, andcarcinoid tumors of the duodenum, as well as breast cancer, leukemia, andrhabdomyosarcoma(1). Patientswith NF1 can present with thoracic involvement, including intrathoracic neurogenictumors, meningoceles, kyphoscoliosis, rib deformities, cutaneous or subcutaneousneurofibromas of the chest wall, bullous lung disease, and interstitial lungdisease.The (6), published inthe previous issue of Radiologia Brasileira, revisits the topic in adidactic way, through a retrospective analysis of 14 patients with NF1 and diffusepulmonary involvement. The authors evaluated six male patients and eight femalepatients. The sample included only one child. In 11 patients, the presence or absence ofrespiratory complaints at the time of chest computed tomography was recorded. Of thosepatients, five had some type of symptom, the most common being cough and dyspnea, andthree of those five patients were smokers.The article "Neurofibromatosis type 1: evaluation by chest computed tomography", by AlvesJúnior et al.7, 8,9, 10, 11,12). Among the pulmonaryfindings on computed tomography scans of the chest, Alves Júnior et al.(6) found, in descending order, cysts (in92.9% of patients), emphysema (in 57.1%), and subpleural bullae (in 42.9%), typically incombination and bilateral. Cutaneous or subcutaneous neurofibromas in the chest wallwere also identified in 85.7% of the patients.A number of recent studies in the radiology literature of Brazil have highlighted theimportance of imaging methods in the assessment of the chest, cysts and bullae being the most common such abnormalities. Itis also noteworthy that pulmonary involvement in NF1 occurs late in the evolution of thedisease, typically when patients are in the third or fourth decade of life.Among patients with NF1, smokers and nonsmokers can both present with pulmonaryabnormalities((6) included only one child. The reading of this articleshould be required for thoracic and general radiologists, because the recognition ofpulmonary impairment in NF1 can play a fundamental role in the follow-up of thesepatients. In that study, approximately 45.4% of the patients for whom respiratorysymptoms were recorded had some respiratory complaint, although three of them weresmokers.The patient sample evaluated by Alves Júnior et al.Finally, further studies are needed in order to correlate pulmonary tomography findingswith the evolution of respiratory function in patients with NF1. Such studies could alsodetermine the impact that those findings have on survival.


Adolescent myopia has become a major public health problem in Asian countries and even the world. Due to its unstable prognosis and numerous complications, it has caused serious social and economic burden. As a common treatment in Asia, Chinese medicine has been shown to be effective in controlling the development of myopia, but its evidence-based medical evidence is not sufficient. Therefore, the purpose of this study is to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of adolescent myopia through network meta-analysis, and to provide evidence for clinical and scientific research.We searched seven databases for randomized controlled trials of TCM decoction for adolescent myopia, including PubMed, the Cochrane Library, EMbase, China National Knowledge Infrastructure, China Biological Medicine, Chinese Scientific Journals Database, and wan-fang databases, from the date of the establishment of each database to January 31, 2022. The network meta-analysis will be implemented through Aggregate Data Drug Information System 1.16.8 and Stata 13.0 software. Primary outcomes include distant vision, intraocular pressure, and diopter. Mean differences or odds ratios will be used for statistical analysis. We will ensure the reliability of the results through node-split model and heterogeneity analysis. In addition, the Cochrane Collaboration's tool and Grading of Recommendations Assessment, Development and Evaluation system will be used for the methodological quality and the evidence quality.This study will provide reliable evidence for the clinical selection of TCM decoction in the treatment of adolescent myopia.The results of this study will evaluate the efficacy and safety of TCM decoction in the treatment of adolescent myopia, and provide decision-making references for future clinical and scientific research.This study did not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal.DOI 10.17605/OSF.IO/VXQUP. Myopia is also one of the main causes of visual impairment and has caused serious social and economic burden. Now, in China, the number of myopia patients remains high and continues to increase. Complications caused by excessive axial elongation caused by myopia, such as myopia macular, glaucoma, choroidal neovascularization, acquer cracks, etc., seriously affect the prognosis of myopia, which can lead to irreversible visual damage and heavy economy burden.,6 In fact, in China, myopia macular degeneration is one of the main causes of low vision in adults and the second leading cause of blindness.,8Currently, myopia has become a major global public health problem in Asian countries.–11 However, long-term use can cause photosensitivity and rebound effects after drug withdrawal due to concentration-dependent side effects, so higher concentrations of atropine drops are still not widely used.Numerous studies have shown that low-dose (0.01%) atropine is effective in reducing the increase in myopia in adolescents, and topical atropine drops have been used for 150 years to relieve myopia. However, there are many types of traditional Chinese medicine (TCM) decoctions in clinical application, and there is no interactive comparison between them. Therefore, the purpose of this study is to evaluate the efficacy and safety of different TCM decoctions in the treatment of adolescent myopia through network meta-analysis (NMA), and to provide reference and evidence for clinical application.At present, a large number of classic Chinese medicine decoctions have been used in clinical treatment of adolescent myopia, and they have been made into different dosage forms at the same time, with good effects.22.1https://osf.io/vxqup), registration number: DOI 10.17605/OSF.IO/VXQUP. This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines.The NMA protocol has been registered on the Open Science Framework platform , Intervention (I), Comparator (C), Outcome (O), and Study Design (S).2.3.1All participants included in this study will meet the following criteria:(a)be 18 years of age or younger;(b)in this study, myopia will be defined as: equivalent spherical lens ≤-1.00 diopter after dilated eye examination;(c)not accompanied by any organic diseases of organs or eye diseases;(d)those who have participated in any surgery or treatment related to vision correction will not be included.2.3.2The treatment group was treated with TCM alone or integrated traditional Chinese and Western medicine, while the control group was treated with conventional western medicine or placebo or waiting for treatment. TCM treatment mainly selects the relevant dosage forms of TCM, not limited to decoction, pill, injection, etc.2.3.32.3.3.1Distant vision;Intraocular pressure;Diopter;2.3.3.2Interpupillary distance and axis of eyeball;Adverse reaction.2.3.4This study is a systematic review with NMA of randomized controlled trials (RCTs) on TCM decoction for the adolescent myopia. All relevant RCTs using TCM decoction for the adolescent myopia will be included. Quasi-RCTs will be excluded such as those allocating by medical record number. The specific participants, interventions, comparators, and outcomes criteria are as follows.2.4Computer retrieval of published RCTs of TCM decoction for the adolescent myopia is conducted in PubMed, the Cochrane Library issue 1, 2022), EMbase, China National Knowledge Infrastructure, China Biological Medicine, Chinese Scientific Journals Database (VIP), and wan-fang databases. The time limit of document retrieval is from the establishment of each database to January 31, 2022. The language is limited to English and Chinese. In addition, inclusive literature from the field and references from previous evaluations will be manually retrieved to find other potentially relevant articles. Search terms mainly include: “Myopia,” “Nearsightedness,” “Adolescent myopia,” “Traditional Chinese Medicine,” “Injection,” “Pill,” “Decoction,” “Powder,” “Eye ointment,” etc. Taking PubMed as an example, the initial retrieval strategy is shown in Table , 2022, E2.5As shown in Figure 2.6:Methodological quality will be assessed based on the bias tool (ROB) in Cochrane Handbook 5.1.0. Two trained researchers Yonghua L and Xianglin J will independently evaluate the risk of bias of the included studies. In case of dispute, submit to the third researcher Xingying L for arbitration. Cochrane bias risk assessment tool will be used to assess the risk of RCTs being included in NMA, 7 items are included(a)random sequence generation, allocation concealment possibility;(b)blinding of participants and personnel;(c)blinding of outcome assessment;(d)incomplete outcome data;(e)selective reporting;(f)other bias.Based on the above 7 items, the included studies will be classified into three grades: low risk of bias, high risk of bias, and unclear risk of bias.2.72.7.1 Iteration operations were performed according to the following preset model parameters: 4 chains were used for simulation analysis, with initial value of 2.5, a step size of 10, annealing times of 20,000, and 50,000 simulation iteration times. Aggregate Data Drug Information System software is used to draw network evidence diagrams of different outcome indicators, and odds ratio or standardized mean differences is used for statistical analysis, both with 95% credible intervals. According to the results of the NMA, rank probability plot of various TCM decoction is generated and sorted by dominance, with Rank1 being the optimal sort.This study uses Aggregate Data Drug Information System 1.16.8 for NMA, and uses Markov Chain-Monte Carlo algorithm to make Bayesian inference.2.7.2P > .5), the consistency model was used for analysis. On the contrary, inconsistent model is adopted for analysis. If the consistency model is adopted, then the stability of the results is verified by the inconsistency model: when the inconsistency factors including 0, at the same time inconsistency standard deviation including 1 says the result of inconsistency model is more stable and reliable. At the same time, the pre-set parameters are used for iterative operation, and the convergence degree of iteration is judged by the potential scale reduced factor (PSRF). When the PSRF value is close to or equal to 1 (1 ≤ PSRF ≤ 1.05), the convergence is complete, indicating good stability of the model and reliable analysis results. If the PSRF is not in this range (1 ≤ PSRF ≤ 1.05), the iteration will continue manually until the PSRF value reaches the range standard.In this study, node-split model was used to analyze the consistency of data. When the statistical difference was compared directly and indirectly , the quality classification for the four level of evidence: high, medium, low, and very low.To grade evidence quality and understand the current situation of evidence rating thereby analyzing possible problems, The Grading of Recommendations Assessment, Development and Evaluation instrument will be used to assess the quality of evidence in the NMA.2.7.9There was no patient or public involvement in the preparation of this protocol.3Myopia has gradually become one of the leading eye diseases in the world. Studies have shown that TCM treatment with TCM decoction can effectively slow down the occurrence and development of myopia. Therefore, we hope to understand the efficacy and safety of various TCM decoction in the treatment of adolescent myopia through this study. Due to the diversity of clinical medication and to avoid large heterogeneity in the study, we could not include all categories of TCM decoction. There is a potential risk of bias. We will further optimize and deepen the research scheme according to actual needs. We will promptly disclose the reasons and timing of any changes that may be made.All the authors have approved the publication of the protocol.Conceptualization: Xiurong Tian, Zhongli Sun, Penglong Yu.Data curation: Xiurong Tian, Zhongli Sun, Yonghua Li.Formal analysis: Xiurong Tian, Zhongli Sun.Funding acquisition: Yonghua Li.Methodology: Yonghua Li, Xianglin Jiang, Xingying Li.Project administration: Xiurong Tian, Zhongli Sun, Yonghua Li.Writing – original draft: Xiurong Tian, Zhongli Sun.Writing – review & editing: Xiurong Tian, Zhongli Sun, Yonghua Li, Xianglin Jiang, Xingying Li, Penglong Yu.


Over the past decades, primate populations have been declining. Four years ago, >60% of species were listed as threatened. As the rate of loss accelerates and new IUCN assessments are being published, we used IUCN Red List assessments and peer-reviewed literature published within the last 5 yr to evaluate the status of primates globally, by region and by taxonomic group. We also examined the main factors affecting a species’ conservation status to determine if we could predict the status of understudied species. We found that 65% of species are in the top three IUCN Red List categories . Globally, the main threats to primates are Biological Resource Use, including Hunting & Logging, and Agriculture. The impact of these threats varied by region and taxon. Our model showed that Malagasy and Asian primates, and those affected by Agriculture, Human Disturbance, and Climate Change were more likely to be considered at risk of extinction. The model’s predictive probability, however, was low. Our literature analysis showed that some threats, especially climate change and disease, affected more species than indicated by the IUCN Red List. As we move into the next decade, we must continue tackling hunting and agricultural expansion but also be vigilant about emerging threats. We must also aim to regularly test the effectiveness of mitigation strategies, evaluating their long-term adoption and their impact on primates; as well as to increase communication between researchers and applied conservationists to ensure IUCN assessments include current and emerging threats.The online version contains supplementary material available at 10.1007/s10764-021-00242-2. Within the four geographical areas where primates are found, i.e., the Americas, Africa, Asia, and Madagascar, 36%, 37%, 73%, and 87% of primate species were threatened, respectively, although their conservation status within each country varied greatly  having been extirpated from this region in the past decade  from Critically Endangered to Endangered —most of which are examined in detail in this special issue—jeopardize primate existence, as many countries struggle to balance economic development with biodiversity protection , a Critically Endangered Afro-Eurasian monkey with fewer than 2000 individuals remaining  in Madagascar, with a diet that consists almost exclusively of bamboo , an opportunistic omnivore that exhibits greater dietary flexibility, changing its primary food resource in response to ecological unpredictability  report on the current conservation status of the world’s primates; 2) analyze the main threats to primates as reported in the IUCN Red List by region  and by taxonomic group ; and 3) model the most important factors influencing a species’ IUCN conservation status to help inform the development of conservation strategies for poorly known species. Finally, because the current primate IUCN Red List is based on assessments that took place between 2013 and 2019, as well as some from as far back as 2008, we also 4) compare threats identified in the current IUCN Red List assessments with those appearing in recent  scientific publications, to identify emerging threats that may need further attention.On July 9, 2020, we extracted information on all primate species recorded on the IUCN Red List website ; the region ; the countries of the species’ extant geographical range excluding “extant introduced,” “possibly extinct,” and “extinct” and the IUCN Level 1 and Level 2 conservation threats . In total, we identified 95 specific keywords from the literature review, which we organized into 12 predefined, higher-level categories: Urbanisation & Road Development; Commercial Agriculture; Small-Holder Agriculture; Energy Production & Mining; Logging, Wood Harvesting, & Gathering of Terrestrial Plants; Commercial Hunting; Subsistence Hunting; Pet Trade; Civil Unrest; Genes; Diseases; and Climate Change & Severe Weather . We deemed the 10% cutoff appropriate, as beyond 10% most articles were not relevant to the present study, despite containing the search terms. Out of the 899 articles that came up in the combined search results, many (55.7%) articles had been selected more than once. After excluding duplicates, the total number of articles reviewed was 398. For each article, we read its title, abstract, and keywords, and when needed the whole article and extracted the following information: article title, first author’s name, year of publication, scientific and common name of the species and subspecies studied, country, region, and the type(s) of aforementioned threats affecting each primate species, including those threats based on anecdotal evidence or those cited in the publication but for which no reference was provided. We combined entries for subspecies with their respective species’ entry. In total, we extracted information for 287 species from the peer-reviewed literature.We collected a total of 8977 articles across the 12 predefined, threat categories. Given that the data we needed from this primary search required manual extraction, it was not feasible to sample the total search. Therefore, after each Google Scholar search, we sampled only 10% of all articles retrieved for each search term  across regions and across primate taxonomic groups. We also examined the distribution of specific type of threats (Level 2) for those Level 1 threats that were most prevalent. Taxonomic groups included family, subfamily, and in the case of the subfamily Cercopithecinae, tribe , as in many cases using the family taxonomic grouping would merge subfamilies with markedly different biology and ecology . In the case of Cercopithecinae, we used tribes to capture differences in the ecology, biology, and distribution that exists between Cercopithecini  and Papionini .To examine which factors were most predictive in determining a species’ IUCN Red List conservation status, we performed an ordinal logistic regression Agresti, . The resThe model initially included all predictor variables. To improve the predictive power of the model, we removed variables with the lowest explanatory power using a backward stepwise procedure  were threatened with extinction, meaning they fall within the top three categories of the IUCN Red List . In particular, 100 species (20.4%) were Vulnerable, 136 (27.7%) were Endangered, and 83 (16.9%) were classified as Critically Endangered. In contrast, 118 species (24.0%) were classified as Least Concern and 32 (6.5%) as Near Threatened. There was not enough information to assess the status of 22 species (4.5%), which were classified as Data Deficient.N = 103 species, or 96.3%) and Asia  had the largest proportion of threatened species  were classified as either Least Concern or Near Threatened , Indriinae (N = 19 species), Daubentoniidae (N = 1 species), Homininae (N = 4 species), Hylobatidae (N = 20 species), Lemuridae (N = 21 species), and Lepilemuridae (N = 26 species) were considered threatened. In contrast, for Callicebinae (N = 30 species), Pitheciinae (N = 24 species), Callitrichinae (N = 49 species), and Galagidae (N = 19 species) only between 10.5% and 33.3% of their species were considered threatened . More specifically, all species within Atelinae , Energy Production , Natural System Modifications , and Transportation and Service Corridors . When we examined the specific Level 2 activities within these two threats, we found that the most prevalent Biological Resource Use activity was Hunting , followed closely by Logging . The most prevalent Agricultural Level 2 activity was Non-Timber Crop Production, affecting on average 368 (92.0%) of the species, followed by Livestock Production, which affected 135 species (33.8%)  and 392 (79.8%) species, respectively (Table %) Table .N = 110 species, or 67.9%) and Agriculture  were the most prevalent threats. The number of species impacted by these threats in the Americas, however, was lower compared to the other three regions. Similarly, in Madagascar, the impact of Development, Transport, and Human Intrusion was much lower than in other regions, affecting only 5 (4.7%), 1 (0.1%), and 0 species, respectively. Finally, in Africa Human Intrusion  and Climate Change  affected a relatively large proportion of species compared to a mean of 4.8 ± SD 3.9% (range: 0.0–9.5) and 3.7 ± SD 2.1 (range: 1.9%–6.5%) of species in the other three regions . This threat was particularly prevalent in Africa, Asia, and Madagascar, where it affected 280 (85.1%) species Table , Fig. 2.Within the Biological Resource Use Level 1 threat category, in Africa, Asia, and Madagascar, Hunting was the main activity, affecting 252 (76.6%) of the species, while it was less common in the Americas, where hunting affected 75 (46.3%) species Table , Fig. 2.When examining the distribution of Level 1 IUCN threats across primate taxonomic groups, we found that at least 3 different threat types affected all 23 groups: 7 were affected by 3–6 threat types , 13 by 7–9 threat types  and 3 by 10 or more  , Cheirogaleinae , Galagidae , and Saimiriinae . Similarly, Cebinae , Galagidae  and Pitheciinae (N = 4 species or 16.7%) were relatively less affected by Annual and Perennial Non-Timber Crop Production, the most prevalent Agricultural activity affecting primates globally , showed that among the 12 Level 1 IUCN threat types, those that had the largest influence on determining a species’ conservation status were Human Intrusion & Disturbance, followed by Agriculture & Aquaculture and Climate Change & Severe Weather Table . In partThe predictive probability of the ordinal logistic regression model based on the type and number of threats was poor, however, as the confusion matrix showed a predictive accuracy of only 41.2% Table . The modN = 168 species, or 58.5%); Hunting ; Commercial & Small-Holder Agriculture ; Urbanisation & Road Development ; and Logging, Wood Harvesting, & Gathering of Terrestrial Plants  , Pet Trade , and Diseases .Papers published between January 1, 2015 and July 1, 2020 revealed that the threats that affected the largest proportion of species were those related to habitat destruction, including Habitat Degradation (%) Table . In addi%) Table , such asN = 56) of the species studied  and Africa  having the largest proportion of species affected , 9 by 7–9 threats , and 8 by 10–12 threats . Among them, Cebinae, Hylobatidae, Cheirogaleinae, and Lemuridae had between 3 and 5 more threats in the recent publications than indicated in the IUCN Red List. In contrast, Tarsiidae and Pitheciinae had 6 and 3 threat types fewer in the literature review compared to the IUCN Red List, respectively.et al., et al., et al., Our results confirmed that the majority of primate species are currently threatened and require urgent conservation attention. The IUCN Red List showed that the two main threats to primates worldwide are Biological Resource Use (including Hunting and Logging) and Agriculture. Although the IUCN Red List does not distinguish between small and large-scale commodity-driven agriculture, it is the latter that seems to pose the main threats to primate populations, given that it creates permanent forest clearings and networks of roads and railways and make intensive use of pesticides  and larger-bodied (≥ 10kg) primates are facing a greater variety of threats compared to smaller-bodied primates. This is probably due to the many intrinsic factors that increase their risk of extinction, including attractiveness to hunters both for meat and for trophies, the need for more food resources, and longer life histories, such as later age at first birth, which can slow the pace of population growth  has evaluated the effectiveness of mitigation interventions focused on primates. Although there is a significant lack of such evidence in primatology , Agriculture, and Climate Change & Severe Weather had the largest impact on determining a species conservation status. Region also had an impact in the model, as a species from Madagascar or Asia is almost 5 or 3 times more likely to be considered at higher risk of extinction compared to species from other regions, respectively. Perhaps appropriately, increasing the number of countries in which a species is found, and therefore the species’ distribution range, decreases the odds of having a higher conservation status.Tarsius lariang), native to Indonesia, is classified as Data Deficient, and affected by four different threats, including Agriculture , found in Ethiopia, Sudan, and South Sudan , endemic to Brazil . Interestingly, a model to predict extinction risk in primates and carnivores by examining factors including range size and slow life histories explained nearly 50% of the variation  populations ESM 2(PDF 203 kb)ESM 3(PDF 163 kb)


In the elderly (≥70 years old) primary operable  database between January 2010 and December 2015. Kaplan–Meier curves were used to show the survival patterns in the different subgroups. Multivariate Cox analysis was used to identify independent risk factors in the 3-, 5-, and 7- year overall survival (OS) and cancer-specific survival (CSS) in this subpopulation. The predictive model was further developed and validated for clinical use.1c: HR = 1.83; T2: HR = 2.78; T3: HR = 4.93), positive N stage , receiving radiation therapy (HR = 0.66), and receiving adjuvant chemotherapy (HR = 0.61) were the independent prognostic factors for OS, and a similar prognostic pattern was also determined in CSS. Besides, two nomograms for predicting the 3-, 5-, and 7-year OS and CSS in this population were developed with a favorable concordance index of 0.716 and 0.746, respectively.Between 2010 and 2015 years, a total of 4,761 elderly primary operable TNBC patients were enrolled for the study, with a mean age of 76 years and a median follow-up of 56 months. The multivariate Cox analysis showed that age (increased per year: hazard ratio (HR) = 1.05), race , differentiation grade , larger tumor size (TThe results highlight that both radiation and adjuvant chemotherapy are significantly associated with favorable long-term OS and CSS probability in elderly primary operable TNBC patients. Based on the determined independent prognostic factors, the novel nomograms could assist the oncologists to make individualized clinical decisions for the subpopulation at different risks. Nowadays, breast cancer has become the most frequently diagnosed malignancy and one of the leading causes of cancer-specific death in industrialized countries, with a female predominance –4. NearlTriple-negative breast cancer (TNBC) accounts for 10%–15% of all breast cancer cases, which lack estrogen and progesterone receptors and express low levels of human epidermal growth factor 2 (Her-2) and therefore do not respond to hormonal or anti-HER2 therapies. Compelling evidence has demonstrated that TNBC frequently implies more aggressive biology and shows a worse prognosis that requires optimal treatment to reduce the future risk of recurrence and mortality , 12. ForRegarding this special subpopulation, however, there are limited data to make appropriate recommendations for those ≥70 years of age. Recently, many well-designed trials and comprehensive reviews demonstrated that adjuvant chemotherapy and radiotherapy are effective at reducing TNBC recurrences and associated with better cancer-specific survival (CSS) and OS in early-stage or younger TNBC patients , 15–19. Hereby, the purpose of this study is to explore the impact of radiation therapy or chemotherapy after surgery on the long-term OS and CSS in the setting of elderly primary operable TNBC patients. Besides, we also aim to explore the independent prognostic factors for OS and CSS in this subpopulation and further establish a utility nomogram for oncologists to make tailored clinical decisions.As an observational retrospective cohort study, patients’ clinical information was extracted from one national cancer database , which covered approximately 28% of the US population and is grouped in various races and ethnicities. In 2010, SEER registries began collecting Her-2 receptor status for breast cancer cases . Thus, t1-3N0-1M0. The excluding criteria were as follows: 1) patients with T4  primary site; 2) no regional nodes examined; and 3) lost to follow-up or incomplete medical records. The flow diagram was presented in the study (TNBC was defined by the absence of estrogen receptor α (ERα), progesterone receptor (PR), and Her-2. The age cutoff for breast cancer in the elderly was assigned based on what has been used in previous studies –28. Patihe study Figure 1via the “R” program.To perform the multivariate Cox regression analysis, the sample size in this study should be at least 10 times the number of independent variables in the equation. Thus, after excluding the unqualified cases, there were 4,761 elderly female patients with primary operable TNBC enrolled in this study. Moreover, for predicting 3-, 5-, and 7- year OS and CSS probability, the original cohort was randomly divided into a training group and validating cohort at a ratio of 7:3 Data analysis from this database is considered to be non-human subjects by the Office for Human Research Protection as part of the US Department of Health and Human Services because patient data were anonymized and publicly available. For these reasons, the need for ethics approval was omitted by the Mianyang Central Hospital Ethics Committee.1mi: >0 and ≤1 mm, T1a: >1 and ≤5 mm, T1b: >5 and ≤10 mm, T1c: >10 and ≤20 mm, T2: >20 and ≤50 mm; T3: >50 mm), lymph node stage , primary surgical extension , postoperative radiation record (performed or not), and chemotherapy recode (performed or not). The OS and CSS probability were calculated in months . The age at diagnosis was used as a continuous variable.Variables were extracted based on their associations with the prognosis outcomes of interest. Namely, the following clinicopathological features were collected and transformed into categorical variables: race , laterality (right and left origin of primary), stage , grade , tumor location , histological subtype , primary tumor stage . Harrell’s C-index , calibration curve, and Kaplan–Meier analysis were constructed and plotted based on the results  derived from the multivariate Cox regression analysis  C-index  and the In total, from the SEER database between 2010 and 2015 years, 4,761 elderly primary operable TNBC patients were enrolled in this study with a mean age of 76.85 years at diagnosis and a median follow-up time of 56 months (range: 1–107 months). White race played a majority population in the present study , whereas Asian or Pacific Islander and American Indian/Alaska Native only accounted for 3.4% of the whole population (340 cases). Based on the TNM stage classification, nearly half of the study population in the present study was at the IA stage . The patients were subsequently randomized divided into training  and validating  cohorts for further Cox analysis and nomogram construction as well validation. The specific demographic and clinical characteristics of the elderly primary operable TNBC patients are shown in Among the whole study population, approximately 47.4%  of patients were not elected to receive radiation therapy and a similar result was found in the chemotherapy record . The KM curves presented that receiving radiation therapy could benefit the OS , positive N stage , and radical surgical extension  were the potential risk factors in impairing the long-term OS probability. On the contrary, Asian/Pacific Islander and American Indian/Alaska Native race , receiving radiation therapy , and receiving chemotherapy  were favorable prognostic factors for OS  = 1.08, 95% confident interval (CI): 1.07–1.09; p ≤ 0.001), worse differentiation grade , larger tumor size , positive N stage , receiving radiation therapy , and receiving chemotherapy  were the independent prognostic factors for OS , Asian/Pacific Islander and American Indian/Alaska Native race , differentiation grade , larger tumor size , positive N stage , and radical surgical extension  were the potential risk factor in impairing the long-term CSS. By contrast, Asian/Pacific Islander and American Indian/Alaska Native race  and receiving radiation therapy  were favorable prognostic factors for CSS , worse differentiation grade , larger tumor size , positive N stage , receiving chemotherapy , and radiation therapy  were the independent prognostic factors for CSS , Asian/Pacific Islander and American Indian/Alaska Native race , differentiation grade , larger tumor size , and the AUC of the 3-, 5-, and 7- year time-dependent ROC reached 0.720, 0.740, and 0.750, respectively . Notably, the KM curves showed that OS but not CSS benefits from the addition of adjuvant chemotherapy to surgery. Based on literature review , 34 and On the other hand, based on existing evidence, the value of adjuvant radiotherapy in elderly TNBC patients also remains in conflict. One earlier meta-analysis  showed that adjuvant radiotherapy was not likely to benefit the OS of the elderly population but women with late-stage disease and younger patients . Moreovemi and N1macro . It is suggested that Nmi was equally essential to assigning patients for more active treatment modalities. Moreover, recent studies have demonstrated that age at diagnosis and heterogeneous health backgrounds were significantly associated with the clinical decision-making for this population  patient after radiation without chemotherapy was met in the outpatient room. The physicians could calculate the 3-, 5-, and 7-year OS  and CSS  probability. The C-index derived from the training and validating cohorts supported that the two nomograms we developed had promising predicting value in clinical use. Moreover, the calibration curves and DCA graphically highlighted the accuracy and clinical utility of the model. The calculation outcome will help oncologists to choose adjuvant treatment regimens.Based on the prognostic factors we determined, we further established an individualized predicting model for quantitatively analyzing the long-term OS and CSS probability for elderly primary operable TNBC patients. For example, one 75-year-old black TNBC (TReviewing recently published literature, our study partially confirmed their results and took it a step further , 18, 26.Nevertheless, this observational study has some limitations which need to be mentioned. First, this is a retrospective study in which selection bias inevitably exists. Second, while ten pivotal variables were enrolled for analysis, some information regarding important confounders including but not limited to Ki-67 index  and 21-GIn conclusion, our results highlight that receiving adjuvant chemotherapy and radiotherapy could be favorable prognostic factors for elderly primary operable TNBC patients after local surgery. Besides, age, race, differentiation grade, T stage, and N stage were identified as the independent prognostic indicators for predicting the long-term survival of this population. The two novel nomograms could help physicians to evaluate the survival probability and make tailored clinical decisions in elderly TNBC patients. Nevertheless, these findings need to be further validated and explored in future studies.The original contributions presented in the study are included in the article/All authors contributed to the conception and design of the study. ZT and YJ organized the database. YM, ZT, XZ, WX, and LZ performed the statistical analysis. All authors wrote the first draft of the manuscript. All authors wrote sections of the manuscript. All authors contributed to the manuscript revision and read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Healthy lifestyles should be encouraged in the workplace through the occupational health teams of the companies. The objective of the present study was to evaluate the adherence to a lifestyle intervention carried out in university employees during the COVID-19 pandemic and its impact on health-related quality of life (HrQoL). A randomized controlled trial following the CONSORT guidelines was performed, consisting of three supervised interventions lasting for 18 weeks: an educational intervention on healthy habits, a nutritional intervention, and a telematic aerobic and strength exercise intervention. Lifestyle and HrQoL were analyzed six months post-intervention to assess adherence. Twenty-three middle-aged participants completed the study. The intervention group significantly improved their lifestyle according to the Health Promoting Lifestyle Profile II questionnaire, especially in the categories of Health Responsibility, Physical Activity, and Nutrition, with a large effect size. Sitting time was reduced by 2.5 h per day, with a moderate effect size. Regarding HrQoL, the intervention group showed a clinically significant improvement in the Physical Component Summary. Despite the lockdown and the mobility restrictions caused by the COVID-19 pandemic, this intervention performed on university employees achieved adherence to a healthier lifestyle and improved their HrQoL, which is of great clinical relevance. The COVID-19 pandemic has affected and overwhelmed our healthcare systems and our lifestyles in an unprecedented way. Consequently and pending a massive and effective vaccination, social distance and mobility restrictions are the main preventive measures to stop the transmission of SARS-CoV-2 ,4,5,6, aIncreased sedentary behavior predisposes to developing metabolic, cardiovascular, pulmonary, neurological, musculoskeletal, psychological, and oncological diseases . PossiblEvery hour of sedentary behavior a day affects our health ,12,13, eIf the decrease in PA (38%) and the increase in sedentary behavior (28.6%), reported by Ammar et al. , were maPA, through epigenetic modulation , influenObservational and epidemiological studies associate adherence to the Mediterranean diet with a protective effect against cardiometabolic diseases ,29,30. HHealthy lifestyles should be encouraged in all age groups since health risk factors develop from childhood. The work environment covers an age group with risk factors, but generally without declared disease, where it is easy for the occupational health teams of the companies to act due to the high number of hours spent in the workplace. In this respect, the WHO global action plan on workers’ health establishes that lifestyle interventions should be carried out within the workplace .Exercise interventions carried out in the work environment consisting of supervised aerobic and strength exercise, lasting at least four months and at least two weekly sessions, achieve a clinically significant decrease in fat mass and an increased muscle mass ,37,38,39According to a recent meta-analysis, interventions carried out in the workplace to increase PA levels achieve increases of 210 metabolic equivalent tasks (METS)-min per week . RegardiMost of the studies that provide nutrition and exercise interventions in the obese population successfully achieve their objectives but fail to maintain adherence to the new habits, losing effectiveness in the long term, generally after six months . The samNo randomized clinical trial has been found reporting a telematic intervention at the workplace that manages to increase PA levels ,50 and tObjective: The objective of the present study was to evaluate the adherence to a lifestyle exercise and nutrition intervention carried out in university employees during the COVID-19 pandemic, and its impact on health-related quality of life (HrQoL).A randomized controlled trial with a parallel group design consisting of an intervention arm and a control arm was developed following the CONSORT guidelines.Participants were recruited by nonprobabilistic convenience sampling from the occupational medical service of the Universidad Europea in December 2019. An informative meeting of the program was held, after which people interested in participating in the study filled out the questionnaires Global Physical Activity Questionnaire (GPAQ), University of Rhode Island Change Assessment Scale (URICA) and Mediterranean Diet Adherence Score (MEDAS), to see if they met the inclusion criteria.The inclusion criteria to participate in the study were the following: (1) Working-age adults; (2) Failure to comply with 2010 WHO physical exercise recommendations ; (3) ScoThe exclusion criteria were: (1) Having a diagnosed chronic disease that the medical service considers as a contraindication to physical exercise; (2) Having musculoskeletal injuries that make it impossible to perform physical exercise.n needed to cover our objective was 22 subjects, so we sampled 24 subjects to compensate for a probable 10% loss of sample.To calculate the sample size, we used data from a pilot study with a mixed design of two repeated measures and two groups. The primary variable was the effect on lifestyle using the Health Promoting Lifestyle Profile II (HPLP II), with an alpha error of 0.05 and a beta error of 0.2. Using the G-Power v.3.1 software , the resulting Before randomization, the sample was matched by BMI and age, taking the median as a reference to achieve a homogeneous distribution in both groups. Subsequently, the randomization of the participants was carried out with the random function of Microsoft Office Excel , being assigned to the control group (CG) or the intervention group (IG). All the participants read and signed the corresponding, specific, informed consent form before being part of this investigation. Then, a code was assigned to each participant. The correspondence table between the personal identification data and the code was kept exclusively by the lead researcher and was kept separate from the rest of the study data. There was no blinding for the participants, the therapists, the evaluators, or the researcher who analyzed the statistical data.The HPLP II questionnaire was filled out to analyze the lifestyle. It consists of 52 items that are answered as N (never), A (sometimes), M (frequently), and R (routinely). It consists of 6 categories: Nutrition (9 items), Physical activity (8 items), Health responsibility (9 items), Stress management (8 items), Interpersonal relationships (9 items), and Spiritual growth (9 items) ,55. The Adherence to the Mediterranean diet was assessed through the MEDAS questionnaire to complement the analysis of the lifestyle. The MEDAS consists of 14 items, of which each adds 0 or 1 point. A score ≥ 10 is considered high adherence, a score of 8–9 is considered medium adherence, and a score ≤ 7 is considered low adherence. High adherence to the Mediterranean diet is considered a strong protector against cardiovascular diseases . In addiTo evaluate another component of lifestyle, PA levels and sedentary behavior were analyzed using the questionnaire GPAQ ,58. The To assess HrQoL, the participants filled out the Short Form 36 Health Survey Questionnaire v2 (SF-36) . It consThe eight sections are regrouped into two main components: Physical Component Summary and Mental Component Summary. A 4-point increase in one of these two components, after an intervention, is considered clinically relevant, in a healthy adult population .2) was calculated.Height  and weight  were measured. Then, by dividing the weight in kg by the height in meters squared, the body mass index . Finally, a 10-min cool down was performed, consisting of flexibility exercises.The nutrition intervention was directed and supervised in person by two nutritionists per participant, and the physical exercise intervention was telematically supervised in real-time by two trainers for each participant.Once the physical exercise intervention ended, the IG received some PA and nutrition recommendations to maintain their new healthy habits for six months. The objective was to measure long-term adherence to the program .Throughout this process, the CG continued with its ordinary activities without monitoring.The nutritional intervention was carried out at the facilities of the Universidad Europea de Madrid, during the employees’ workday. The physical exercise intervention was carried out using a telematics platform, as the subjects were at home to the COVID-19 lockdown. The initial assessments (T1) were performed before starting the interventions, and the final assessments (T2) were performed six months after the end of the interventions.p < 0.05. Eta partial squared (η2p) was used as a measure of effect size [All the results were analyzed by protocol and intention-to-treat analysis (ITT). The distribution and normality of the data were analyzed with the Shappiro–Wilk and Levene tests and with P-P and Q-Q plots. Data are expressed as mean ± SD. The independent T test and the Mann–Whitney U-test were used to compare the differences between both groups (CG and IG) before the intervention, with the aim of evaluating the homogeneity of the groups. A two-way analysis of variance (ANOVA) with repeated measures was conducted, to determine the effects of the intervention. To assess the effects of the intervention and minimize the risk of type I error, only interactions between time groups were considered. The level of statistical significance was set at ect size , consideect size . All stan = 12) and CG (n = 12). There was one dropout in the IG so the final analysis was performed on 12 CG and 11 IG subjects, as is shown in the flow diagram  did not meet the inclusion criteria. The remaining 24 subjects were randomly assigned into two groups, IG , and in the categories of Health Responsibility , Physical Activity  and Nutrition , with a large effect size for these four variables. Regarding Adherence to the Mediterranean diet, both groups progressed from low adherence (MEDAS score ≤ 7) to medium adherence (MEDAS score 8–9), with no significant differences between groups (txgp = 0.16). Regarding PA levels, both groups showed an increase, progressing from low to moderate levels [txgp = 0.52). Finally, the number of hours sitting decreased 2.5 h in the IG, although without significance in the time x group interaction (txgp = 0.09)  .txgp = 0.60, 2pη = 0.01), Role Physical , Bodily Pain , General Health , Vitality , Social Functioning , Mental Health , Role Emotional , Physical Component Summary , and Mental Component Summary . The effect size was large for Vitality, and Moderate for the Role Physical, General Health, and the Physical Component Summary  but not in the Mental Component Summary (<4 points) . However Summary .txgp = 0.17) and BMI (txgp = 0.16) did not change after the intervention.Bodyweight . Furthermore, the number of hours sitting per day and the PA levels did not show a significant variation between groups. However, the IG group showed a reduction in the daily sitting time but not the CG. Possibly, the exceptional situation of the COVID-19 lockdown, the mobility restrictions, and the novel context of teleworking influenced these results. In addition, the fact that both groups analyzed were in a state of predisposition to change, according to the study’s inclusion criteria, could have caused the CG to make changes in their lifestyle, not finding significant differences regarding HrQoL.According to a recent systematic review, many studies report an increase in the PA levels after a telematic intervention, but very few assess the adherence to these habits six months later, without achieving beneficial results . RegardiTo date, there are no lifestyle interventions during the COVID-19 pandemic in the workplace described in the literature, as there is only one observational study . We provThe participants of this study were middle-aged university employees with adequate body weight and without diagnosed associated diseases. They had an improvable health-promoting lifestyle score , low PA The IG achieved a significant improvement regarding diet, analyzed with the HPLP II questionnaire, with a large effect size. It implied the acquisition of healthy habits such as “following a diet low in saturated fat”, “limiting the consumption of sugars and sweets”, “eating 2–4 servings of fruit and 3–5 servings of vegetables a day”, or “limiting the salt intake”. However, when analyzing adherence to the Mediterranean diet using the MEDAS questionnaire, both groups increased their adherence to this diet, as did the general population in many countries during the COVID-19 pandemic ,8, progrThe IG achieved a significant improvement in their lifestyle in terms of PA, measured with the HPLP II questionnaire, with a large effect size in the time x group interaction. This improvement involved the acquisition of habits such as “follow an exercise program”, “perform vigorous PA for at least 20 min 3 times a week”, or “perform light to moderate-intensity PA for at least 30–45 min 5 times a week”. However, when performing a quantitative analysis of the PA levels expressed in weekly METS-min through the GPAQ questionnaire , both gr2pη = 0.13). These results were not statistically significant, possibly due to the size of the sample. Other studies performed in the workplace have reported significant reductions post-intervention regarding sedentary behavior, but without assessing long-term adherence [In previous studies carried out during the COVID-19 pandemic, there have been reported increases of 23.8–28.6% in the number of hours sitting per day . Yet, indherence . Bodyweidherence .Regarding HrQoL, the IG showed an improvement trend in all the variables, being clinically relevant in the Physical Component Summary (>4 points), with a moderate effect size, but not in the Mental Component Summary . This coAccording to the Transtheoretical Model of Behavior change (TMBC) , the optHowever, adherence to the lifestyle changes achieved in this study is an effective primary prevention strategy for preventing NCDs . One of We believe that lifestyle programs or interventions should be promoted in the workplace, especially during the COVID-19 pandemic, as the general population has reduced its PA levels. Perhaps, for greater benefits, exercise programs should be of a longer duration ,37,38,39Regarding the limitations of the study, the researcher who analyzed the statistical data was not blinded, and we did not control the caloric intake of the subjects.Despite the lockdown and the mobility restrictions caused by the COVID-19 pandemic, this supervised physical exercise and nutrition intervention performed on university employees achieved adherence to a healthier lifestyle . The par


Sexual and gender minorities (SGM) may experience stigma, discrimination and show higher prevalence of behavioural risk factors than heterosexual counterparts. In Italy, the information on SGM is scarce and outdated. The present cross-sectional study aims to provide a more up-to-date estimate of the SGM proportion in young adults and to assess differences in the adoption of risk behaviours compared to their heterosexual counterparts. The study involved university students aged 18–25. Information on socio-demographic and behavioural characteristics were collected. The effect of sexual orientation on risk behaviours was assessed with a multinomial single-step logistic regression analysis. A total of 9988 participants were included. Overall, 518 students (5.2%) self-identified as SGM. While lesbians showed significantly higher odds of only non-regular use of protective barriers (AOR: 11.16), bisexuals showed higher odds for frequent drinking (AOR: 2.67), smoking (AOR: 1.85), multiple sexual partnerships (AOR: 1.78) and non-regular use of protective barriers (AOR: 1.90) compared with heterosexual women. Gay men showed higher odds of multiple sexual partnerships compared with heterosexual males (AOR: 5.52). SGM accounted for 5.2% of the sample, slightly more than the proportion found in the general population, but substantially in line with similarly aged populations abroad. Our findings confirm that unhealthy risk behaviours are more frequent among LGBTQ+, in particular among bisexual women. Rather than targeting specific subpopulations, our study aims to show the need for health promotion interventions that aim at the empowerment of all students regardless of sexual orientation, being aware that SGMs can benefit to a relatively greater extent. Recent literature estimates that the proportion of sexual and gender minorities (SGM) stands at around 3.8% in the general population . In ItalHowever, the proportion of SGM is not immutable in time and space. The age and the education of the interviewed population, the place, the cultural context and even the year in which the survey was conducted should be considered. Changes, although seemingly secular, could take place in a relatively short period of time ,12,13,14SGM often experience stigma and discrimination, conditions associated with psychological distress that frequently result in health risk behaviours . SeveralIn Italy, the information on SGM is scarce and latest demographic data in this regard date back to the 2011 census. In addition, the prevalence of risk behaviours in LGBTQ+ young adults has not been previously estimated. The present study aims to provide a more up-to-date estimate of the proportion of SGM in young adults and to assess the probability of the adoption of health risk behaviours in SGM compared to their heterosexual counterparts.The study was conducted from October 2015 to June 2016 at the University of Padova and the University of Verona, Italy. Participants were eligible if they were 18–25 years old and enrolled in one of the two universities. The participation was on a completely free and voluntary basis and no form of compensation was offered. Members of the research group visited the sampled classrooms and all students in attendance were invited to complete the questionnaire. Participants were given oral information about the purpose of the study, and reassurance on its confidentiality and their anonymity. A written questionnaire was administered to each participant.The questionnaire investigated the following socio-demographic and behavioural factors: age (entered as a continuous variable); nationality (citizenship); degree course; gender identity; sexual orientation ; involvement in a relationship; alcohol consumption; smoking habit; number of sexual partners within the previous 24 months; age at the sexual onset; use of condoms (or other protective barriers). Degree courses attended by participants were classified as follows: (a) healthcare professions, (b) sciences, (c) humanities, (d) engineering, (e) law and economics, (f) psychology, (g) medicine and dentistry. Participants with an alcohol consumption of 6 or more days a week were coded as ‘frequent drinker’. In the subsequent analyses, a sexual onset at the age of 14 or earlier was considered as ‘early sexual onset’ and a number of three or more sexual partners in the previous 24 months was coded as ‘multiple sexual partnership’. Pretesting of the questionnaire was conducted; findings from the pilot study and subsequent changes were described in detail elsewhere .p < 0.05 (two-sided) and confidence intervals (CIs) were set at 95%. Statistical analyses were performed using IBM® SPSS Statistics® version 23. Items and data in this study were collected, analysed and presented according to criteria from the STROBE Statement for cross-sectional studies. Written informed consent was obtained and collected separately from the questionnaire in order to ensure the anonymity of the data. The study protocol was approved by the ethics committee of the Padua Provincial Authority on 30 July 2015 (ID: 3404/U16/15) [Descriptive analyses, using absolute and relative frequencies, were performed. Chi-squared tests were conducted to compare the different groups on baseline characteristics. The effect of sexual orientation on the adoption of risk behaviours was assessed with a multinomial single-step logistic regression analysis adjusting for age, nationality, degree course, involvement in a relationship, alcohol consumption, smoking habit, number of sexual partners within the previous 24 months, sexual onset, and use of condoms (or other protective barriers). Statistical significance for all tests was set at /U16/15) .Out of 11,096 candidates, 10,135 students agreed to be included in the study (response rate: 91.3%). After checking for completeness and failure to adhere to inclusion criteria, 9988 questionnaires were included in the study .The mean age of participants was 20.5 years (SD: 1.81), and the median age was 20.0 years. Participants with Italian citizenship comprised 97.4% of the sample. Students committed to a stable relationship constituted 44.8% of the total participants. Overall, 518 students (5.2%) self-identified as SGM. Among cisgender males, 2.59% declared themselves as MSM, while 2.02% declared themselves as bisexual. Among cisgender females, 1.28% declared as WSW, while 4.21% declared as bisexual. Transgender individuals accounted for 0.12% of the sample. Fully detailed socio-demographic characteristics of the study population are shown in While no statistical differences in the pattern of alcohol consumption were found among males, a higher proportion of bisexual women used to drink alcohol more than 6 days a week , or 2–5 days a week , as shown in In a similar manner, while among males, smoking habits did not show significant differences among the three subgroups, the proportion of non-smokers was lower in bisexuals (48.4%) and WSW (59.5%) compared with heterosexual women (73.9%). Speaking of the number of sexual partners, the proportion of bisexual women that had three or more partners in the past two years (26.3%) was more than twice that of heterosexuals (11.1%) and lesbians (12.5%); among males, the proportion was 18.7% among heterosexuals, 32.4% among bisexuals, and 49.4% among MSM. An early sexual onset was reported by 12.0% of bisexual women, while the proportion was lower in heterosexuals and lesbians . Among gay men, the proportion of those who had an early sexual onset was slightly higher than their heterosexual counterparts (5.9 vs. 4.9%), while the proportion of those who declared a sexual onset after the age of 19 was almost double (31.8 vs. 16.0%). No significant differences were noted regarding the use of condoms among males, while the proportion of WSW who declared regular use of condoms (19.0%) was lower than both hetero- and bisexuals .Results from the logistic regression are reported in Overall, SGM accounted for 5.2% of the study population. Considering the data from the latest national census in 2011, which reported a proportion of 3.2% in the age range of 18–25, our findings show a higher proportion of SGM ,29. Our Regarding the prevalence of risk behaviours, the main finding of our study is that while, among males, no significant differences were noted between SGM and their heterosexual counterparts , among women, bisexuality was significantly associated with frequent alcohol drinking and smoking, multiple sexual partnerships, and non-regular use of condoms or other protective barriers; in contrast, lesbians did not show higher odds for any of the risk factors investigated compared to heterosexual females, with the exception of a non-regular use of condoms or other protective barriers.Most of the students in the sample used to drink alcohol once a week or less and were non-smokers regardless their gender identity or sexual orientation. However, while, among males, there were no significant differences, bisexual women reported a significantly higher alcohol consumption compared with heterosexual females and lesbians, and their odds were more than twice as high ; almost the same applied to smoking . In our sample, gay and bisexual men did not show higher odds of smoking compared with heterosexual males. This leaves the debate open, as there are studies reporting a similar result ,30 but aMultiple sexual partnerships were reported by 1 in 4 26.3%) bisexual women and almost 1 in 2 gay men (49.2%), with an AOR of 1.78 (95%CI: 1.21–2.61) and 5.52 (95%CI: 3.26–9.35), respectively, compared with their heterosexual counterparts. Again, our findings partially challenge previous results by dissecting the SGM into subgroups: thus, although we confirm the tendency to have multiple sexual partners in gay men and bisexual females, our results align lesbian women and bisexual men to their heterosexual counterparts [.3% bisexWith regard to the use of condoms or other protective barriers in SGM, an interesting finding comes from a comparison with an US national survey on college students by Eisenberg and colleagues: in our sample, bisexuality among females was associated with a non-regular use of condoms , while no significant difference was noted in the US survey; conversely, in the US survey, MSM showed significantly higher odds for non-regular use of condoms , while, in our sample, gay men did not show a significant difference with heterosexual males in terms of the use of condoms . MoreoveSome participants may have had concerns in self-identifying as non-heterosexuals and may have provided answers perceived as being correct according to social norms. A social desirability bias may more easily affect face-to-face interviews; however, also in self-administered anonymous questionnaires, the presence of a social desirability bias cannot be excluded . In addiIn conclusion, the proportion of SGM among young adults in our sample stood at around 5.2%, substantially higher than in the Italian general population, but in line with similar-aged populations, as reported in studies conducted abroad. Italy does not seem to be an exception in the proportion of gay/lesbian and bisexual individuals in females  and males , as well as the proportion of transgender individuals (0.1%). Compared with their heterosexual counterparts, SGM individuals showed higher odds of risk behaviours but the burden was not equally distributed within the SGM: whereas, in males, no overall significant differences were noted according to sexual orientation , bisexuality in females was associated with a higher risk for frequent alcohol drinking, smoking, multiple sexual partnerships and non-regular use of condoms or other protective barriers. Compared to the past, the regular use of condoms in gay men is particularly high.Our research shows that SGM university students are at higher risk of adopting unhealthy behaviours in Italy and supports the use of easy-to-implement and proven effective public health interventions to actively increase the empowerment of university students such as short seminars, short counselling activities and well-planned communication campaigns. For example, studies on raising awareness of condom use among university women have shown the importance of conveying information appropriately and one of the most efficient ways is through health education websites that are certified and reliable, such as the university website; similarly, short online seminars or self-assessment questionnaires followed by a tailored risk assessment feedback have been shown to be effective in uncovering and preventing alcohol abuse ,45,46. H


Gestational diabetes mellitus (GDM) is defined as an impairment of glucose tolerance, manifested by hyperglycemia, which occurs at any stage of pregnancy. GDM is more common in the third trimester of pregnancy and usually disappears after birth. It was hypothesized that the glycemic status of the mother can modulate liver development and growth early during the pregnancy. The simplest modality to monitor the evolution of GDM employs noninvasive techniques. In this category, routinely obstetrical ultrasound (OUS) examinations (simple or 2D/3D) can be employed for specific fetal measurements, such as fetal liver length (FLL) or volume (FLV). FLL and FLV may emerge as possible predictors of GDM as they positively relate to the maternal glycated hemoglobin (HbA1c) levels and to the results of the oral glucose tolerance test. The aim of this review is to offer insight into the relationship between GDM and fetal nutritional status. Risk factors for GDM and the short- and long-term outcomes of GDM pregnancies are also discussed, as well as the significance of different dietary patterns. Moreover, the review aims to fill one gap in the literature, investigating whether fetal liver growth can be used as a predictor of GDM evolution. To conclude, although studies pointed out a connection between fetal indices and GDM as useful tools in the early detection of GDM (before 23 weeks of gestation), additional research is needed to properly manage GDM and offspring health. Gestational diabetes mellitus (GDM) is a relatively common pregnancy pathological condition that was recently defined by the American Diabetes Association (ADA) as hyperglycemia, with no obvious cause, first appearing or discovered during the pregnancy’s second or third trimester ,2,3,4,5.Maternal obesity has emerged as a public health threat and a worrying elevation in its prevalence has been registered worldwide. It is well known that obesity contributes to the development of GDM and of cardiovascular disease (CVD) both in pregnant and nonpregnant females ,10. DuriA relatively recent meta-analysis of 40 studies involving a total of 177,063 subjects displayed that the prevalence of GDM in Europe is 5.4% . The incThe pathophysiology of GDM is not fully understood, but the latest studies point out that in GDM there is an elevated insulin requirement and a progressive peripheral resistance to the action of this hormone, most often present but not expressed before the pregnancy. Various circulating cytokines, e.g., interleukin 6 (IL−6) or tumor necrosis factor-alpha , seem to be culprits in exacerbating insulin resistance in pregnancy .The standard diagnostic method for GDM is the oral glucose tolerance test (OGTT) 75 g). Thus, all pregnant women should be subjected to this test at 24–28 weeks of gestation, although a recent study showed that GDM diagnosed at 24–28 weeks of gestation has already impacted the fetus but only in older and obese women, suggesting the necessity of screening before this period  g. Thus,. AlthougAlthough the above tests have an undeniable diagnostic value, new noninvasive diagnostic methods, e.g., ultrasonography, have emerged as useful tools in identifying patients at risk of developing GDM. Thus, Perovic et al. (2012) highlighted the advantages of an ultrasound GDM screening score as a predictor of GDM development by screening pregnant females who were at least in the week 24 of gestation and who harbored risk factors for GDM. The ultrasound GDM screening score proposed by the aforementioned researchers exhibited a specificity and a sensitivity of over 89% and took into consideration several relevant parameters, i.e., subcutaneous fetal adipose tissue, the immature appearance of the placenta, and the placental thickness . MoreoveBehavioral changes such as diet modification and increased physical activity are often used in the first-line treatment of GDM ,42. If gThe development of GDM can occur under the influence of several factors, as previously described. However, certain dietary patterns before and during the pregnancy might play roles in its development as well. Although the attention of many researchers has been focused on several macro- and (or) micronutrients, we believe a broader approach would be more suitable for women at risk of GDM. Thus, in the future, special attention should be given to dietary patterns. One discusses here some of the most recent conclusions of the studies in the field.A study by Shin et al. (2015) of 253 pregnant women included in the National Health and Nutrition Examination Survey (NHANES) concluded that there is a direct link between “a high consumption of refined grains, fat, added sugars and low intake of fruits and vegetables” and the risk to develop GDM during pregnancy. However, it also underlines the need for future prospective and cohort studies that should be correlated with the degree of physical activity . SedaghaThere also seems to be a connection between the diet and the microbiome of pregnant females suffering from GDM, with the microbiome viewed as another culprit in enhancing insulin resistance and a proinflammatory state in GDM . MoreoveDesulfovibrio, Rothia, and Collinsella can be detected in higher amounts in GDM pregnancies [Prevotella, Parabacteroides distasonis, and Ruminococcaceae in pregnant females suffering from GDM [Bacteroides and Lactobacillus, which are components of the normal, “healthy” microbiome [For example, in terms of phylum, Actinobacteria seem to be more represented in pregnant women with GDM. In addition, in terms of the genus, gnancies . Anotherfrom GDM . In muricrobiome . Interescrobiome .Vitamin D supplementation seems to reduce the risk of GDM and displays a negative association with the values of the glycemia and of the homeostasis model of assessment for insulin resistance index (HOMA-IR). Moreover, vitamin D supplementation in GDM can alleviate glycemia, HOMA-IR, lipid, glutathione, and C-reactive protein levels . In addiEarly diagnosis and treatment are mandatory in GDM as there are a number of severe complications that can occur in both the fetus and the mother. These include preeclampsia, premature birth, polyhydramnios, macrosomia, postnatal hypoglycemia, and jaundice, neonatal respiratory distress syndrome, and an increased risk of developing birth defects, the latter occurring in up to 10% of diabetic pregnancies ,5,68. PrMaternal hyperglycemia causes diabetic embryopathy, which represents multiple impairments in embryogenesis and diabetic fetopathy, translated as complications in fetal development . MaternaThe anabolic action of insulin is manifested at the fetal level by increasing the tissue production of amino acids and glucose while increasing the transplacental gradient for glucose and resulting in excessive intake . MoreoveFetal hyperinsulinism, in turn, causes stimulation of glycogen accumulation in the liver, increased lipid synthesis with the accumulation of subcutaneous adipose tissue, and disproportionate growth of insulin-sensitive tissues, namely, the liver tissue, muscle tissue including the myocardium, and the subcutaneous adipose tissue . The fetFetal macrosomia in pregnancies complicated with GDM has a special feature, namely, that excess fat is deposited in the abdomen and scapular girdle, disproportionate to the cephalic extremity, leading to visceromegaly, with its onset after 24 weeks of gestation without any influence on the skeletal development of the fetus. Biometrically, macrosomic newborns from diabetic pregnant women with poor glycemic control are characterized by increased abdominal circumference, increased biacromial ratio, decreased skull–shoulder ratio, body fat deposition, and hypertrophic skin fold at the level of the upper extremities. Other features of macrosomic offspring born to pregnancies complicated with diabetes with poor glycemic control are the presence of cushingoid facies and the occurrence of skin jaundice .The main risk factors for GDM and the main consequences of untreated GDM on the mother and offspring are represented in p < 0.02) [Prospective randomized controlled studies to track the effects of maternal nutritional factors on the fetal liver are limited due to ethical implications. Thus, on human subjects, these effects can be followed only in retrospective studies. However, in the literature, there are data collected from animal studies that may show the possible effects of the maternal diet on fetal liver fat. A study on guinea pigs found that feeding the mother during pregnancy a Western diet is associated with a lower overall fetal fat level but with an increase in fetal liver fat ( < 0.02) . In thei < 0.02) . Further < 0.02) .Fetal growth and fetal liver development are influenced by the nutrient intakes of the fetus. The glucose tolerance of the mother and fetus and the insulin/insulin-like growth factor axis act as mediators of the relationship ,84.Fetal screening by ultrasound examination 2D, 3/4D) performed between 18 and 23 weeks of gestation is a noninvasive, effective, fast, and relatively inexpensive method of monitoring fetal development that can replace the OGTT as a diagnostic method for GDM D perform. The evaGiven the direct relationship between GDM and various parameters related to fetal growth, particularly liver indices, which can be assessed by ultrasound, we wanted to evaluate the effectiveness of OUS as a method of diagnosis and monitoring complicated pregnancies with GDM.Thus, we computed a search in PubMed/MEDLINE, Clarivate Analytics Web of Science, SCOPUS, and ScienceDirect for articles published up to 1 April 2021 that evaluated the relationship of fetal liver indices with GDM. For inclusion in this review, we selected the articles published in English, French, Italian, and Romanian (the languages spoken by the authors) with full texts that could be accessed and presented relevant information on OUS parameters useful in the evaluation of GDM. The exclusion criteria were (1) articles with full texts in another language than the aforementioned ones; (2) articles whose full-texts could not be accessed; (3) case reports, letters to the editor, reviews, or abstracts presented at various scientific conferences. The keywords and word combinations employed were “fetal liver”, “obstetrical ultrasound”, “gestational diabetes”, “pregnancy”, “gestational diabetes mellitus”, “midtrimester ultrasound”, “fetal liver length measurement”, “fetal growth”, “fetal liver blood flow”, “umbilical venous volume flow”, and the results are systematized in the following paragraphs and in p < 0.001 for all time points). At each time point, the authors registered significantly higher FLL values (p < 0.001) [p < 0.02). Despite this finding, there were no differences regarding fetal liver or other ultrasonographic measurements at any time point during gestation between type I and type 2 patients. All of these in utero measurements were maintained postpartum, with the liver of newborns from diabetic mothers weighing 179% of control values at delivery [Roberts et al. (1994) analyzed a group of 104 pregnant women, diabetic or at risk to develop GDM , each of them performing an OUS at 18, 28, and 36 weeks of gestation. The waist circumference, the length of the femur, and the FLL were notably elevated in pregnancy versus reference values (< 0.001) . Moreovedelivery .p < 0.01) [Mirghani et al. (2006) performed an elaborate OUS on a group of 123 pregnant women, 19 (15.4%) with GDM, and 104 (84.6%) healthy, based on the World Health Organization criteria. The ultrasound included, besides standard fetal biometry measurements and detailed anomaly scans, some specific evaluations of body composition, e.g., the Wharton’s jelly area, length of the right lobe of the liver, placental thickness, subcutaneous fat layer, and cardiac muscle. Of these, in women diagnosed with GDM, the FLL was the only measurement significantly elevated ( < 0.01) .In the cross-sectional study of Boito et al. (2007), a group of 32 pregnant insulin-dependent diabetes mellitus (IDDM) females was compared to an equal control group of pregnant females with a normal status of health. As in the previous study, the authors examined in addition to common biometry measurements, such as fetal abdominal circumference or FLV, a series of particular indices, including liver volume/estimated fetal weight ratio, ultrasonically estimated fetal weight, umbilical venous volume flow per kilogram fetal weight or umbilical artery pulsatility index, using Doppler and B mode ultrasound . The finp = 0.03) and 36  weeks, respectively [Regarding the importance of the correct treatment, Dubé et al. (2011) analyzed a group of 27 pregnant women and divided them according to the OGTT results based on the guidelines of the Canadian Diabetes Association (CDA): 17 females had GDM (study group), and 10 females had normal glucose tolerance (NGT) (control group). The study found no differences in fetal weight or FLV in the GDM (managed according to the CDA guidelines) versus the NGT group. Thus, integrative management of GDM with a focus on stricter control of blood glucose levels may contribute to a normal weight at birth and a normal FLV. Moreover, the birth weight was associated with the FLV at 32 . FLL correlated positively with the blood glucose levels during the OGTT (p < 0.001)  in GDM subjects, yet this correlation was not found in healthy patients (p > 0.05) [p < 0.001) and not with the parity. FLL was significantly associated with the presence of GDM , and there was an independent association of FLL with the presence of GDM independently of BMI or parity. Using receiver operating characteristic curves, the authors decided a FLL cutoff value of 39 mm as a predictor of GDM  [Perovic et al. (2014) analyzed a group of 331 women at high risk of developing GDM, detecting a final GDM prevalence of 25.7%. There were significant differences only in terms of the BMI and the second parity . GDM females, as opposed to healthy pregnant females, registered notably elevated fetal liver indices ( > 0.05) . Further= 90.9%) .the control group (p < 0.01) [p > 0.05) and GDM groups . On the other hand, although the birth weight was significantly elevated in the GDM group, the authors found a significant positive birth weight—FLV correlation in the GDM subjects (p < 0.05) [In a prospective study conducted by Ilhan et al. (2018), which enrolled 97 pregnant females, the study group was split based on the OGTT results: 64 healthy and 33 GDM-complicated pregnancies. The OUS included standard fetal biometric measurements and FLV. Despite no significant differences in terms of standard fetal biometric measurements and EFW , FLV was notably elevated in the GDM versus p < 0.001)), with the FLL in the GDM group being 1.6 times higher than in the non-GDM group  and having a high specificity (95.9%) and negative predictive value of 95.9% [In another prospective study, Showman et al. (2019) recruited 120 pregnant women aged 21–37 years at high risk for GDM. A routine OUS was performed at 23 weeks of gestation and followed up at 24 weeks by the OGTT, which detected an overall incidence of GDM of 19.2%. History of previous GDM and a first-degree family history of diabetes were the most important risk factors for GDM . There wp < 0.001) and again at 37 weeks of gestation . Furthermore, when the authors compared the subjects within the case group, FLL was higher among those with PGD than those with GDM at 28 weeks  and again at 37 weeks . At 28 weeks, screening by FLL measurement exhibited a sensitivity of 100% and a specificity of 92% in predicting the occurrence of diabetes in pregnancy. In the end, there was a strong positive association of the FLL and the HbA1c (r = 0.83), AFI (r = 0.86), expected fetal birth weight (r = 0.82), abdominal circumference (r = 0.82), and neonatal birth weight (r = 0.80) [3 ↗ 14.36 cm3 ↗ 20.77 cm3 at 18–21, 22–25, and 26–30 weeks of gestation, respectively), accelerated by approximately 20%/gestation week when compared with normal values [To assess the presence of dissimilarities between the ultrasonographic parameters of mothers with pre-GDM  or GDM, Gharib et al. (2019) divided 60 pregnant females (age 20–39) into two groups, based on the HbA1c and glycemia: healthy pregnant females as controls (n = 30) and pregnant females with PGD or GDM (n = 30) . FLL was = 0.80) . This fil values .Some animal and human studies showed that an increased hepatic flow from the umbilical vein results in elevated cell proliferation in different essential organs, such as the liver, heart, and kidneys. Fetal growth is regulated by the distribution of the nutrient-rich umbilical venous blood to the liver . MoreoveIn the prospective cohort study of Opheim et al. (2019), the impact of maternal nutritional conditions during fetal life over the long-term health of the newborn was explored. The consequences of regular maternal meals and of prepregnancy BMI on the fetal liver blood flow were assessed. Doppler OUS was employed in 137 healthy women at 18 and 20 weeks of gestation and several indices were evaluated, e.g., the umbilical vein flow (mL/min) or the mean left portal vein flow velocity . Surprisp = 0.004). Thus, the levels of corticotrophin-releasing hormone predicted approximately 10.5% of the blood flow to the liver of the fetus [Overall, the analyzed research papers point out a possible connection between fetal liver indices and GDM; however, the base of evidence is too small to conclude that these parameters can serve as predictors of GDM in pregnancy. Consequently, further research is needed to clarify the relationship between fetal liver indices and GDM and, if our hypothesis is confirmed, to delineate cutoff values for the variables that could predict the development of GDM ,91,92,93he fetus . This cahe fetus .The main results of this subsection are summarized in p < 0.001) in terms of FLV: 41.46 ± 6.56 cm3 versus 33.67 ± 6.42 cm3 [p < 0.001) [p < 0.001 and Mirghan et al. (2006), particularly 36 (32–37) mm vs. 31 (30–33 mm, p < 0.001 [Most authors who compared fetal liver measurements obtained by OUS found significant differences between the values measured in women with GDM versus healthy counterparts ( < 0.001 ,69. At tly 36 32– mm vs. 3Currently, nutritional and lifestyle interventions have been recognized as the cornerstone of therapy for females diagnosed early with GDM. These approaches have emerged as attractive strategies with benefits that extend beyond pregnancy, being particularly helpful in decreasing the risk of CVD or T2DM ,97,98. IThe caloric restriction remains a foundational strategy in preventing ponderal gain, controlling glycemia values, and preventing macrosomia in the offspring born to GDM mothers . A stricPhysical activity has shown multiple benefits, such as improving blood glucose control, reducing weight, insulin resistance, and cardiovascular risk. Thus, regular physical exercise might play an important role in GDM prevention ,100,101.Given all the above, we conclude that an early diagnosis of GDM is crucial due to its potential complications, i.e., preeclampsia, birth defects, and possible development of CVD and T2DM later in the life of the newborn. Screening all pregnancies with an OGTT may not always be feasible due to several drawbacks. Since a midtrimester OUS is already a standard, future studies should investigate its feasibility and utility in the prediction, early diagnosis, and follow-up of GDM and, additionally, in estimating the birth weight prenatally. Measuring different fetal liver indices is an easy technique and could emerge as a reliable method to assess GDM pregnancies. Further research should clarify whether common measurement parameters, i.e., FLL and FLV, could be strong predictors of GDM and to which extent they positively relate to maternal HbA1c levels. In addition, other indirect indicators, such as fetal liver blood flow, have been shown to be strongly connected to the glycemia of the GDM female in the first trimester of pregnancy. Finally, these studies highlighted the crucial role of a proper multidisciplinary approach to GDM treatment during pregnancy and maternal nutritional status, as the enhanced growth of the fetal liver can be modulated by controlling the mother’s glycemia even in the late stages of pregnancy. Soon, medical nutrition therapy should also be integrated into the management of pregnancies at risk for GDM.


A significant dysfunction of another organ is usually considered an absolute contraindication for lung transplantation, unless multiorgan transplantation is indicated and practical, as is the case of combined lung-kidney transplantation. Few cases of combined lung-kidney transplantation have been described in the literature; however, it is known that, in certain cases, it is the only way to offer an opportunity to selected patients with renal and lung dysfunction. The authors are not aware of any previously published case of a patient receiving both extracorporeal membrane oxygenation and continuous venovenous hemodiafiltration as a bridge for combined kidney-lung transplantation.The authors present the first case of combined lung-kidney transplantation performed in Portugal. At the time of admission, she weighed 52 kg was 165 cm tall and had Forced Expiratory Volume in 1 second (FEV1) of 720 cc (21%) and Total Lung Capacity (TLC) of 3650 cc (79%). She was also hypoxemic, requiring oxygen support therapy. The patient entered the list for lung transplantation in February 2017, with low priority, due to her clinical and functional stability. For better understanding, we perform a timeline , with exocrine pancreatic insufficiency and pansinusitis. She has been monitored as a pre-transplantation consultation since June 2016, with extensive cystic bronchiectasis  with Psetimeline .Table 1TPseudomonas aeruginosa infection. Due to worsening respiratory failure, it was necessary to start venovenous extracorporeal membrane oxygenation (VV-ECMO). After failure of weaning from mechanical ventilation, the patient underwent tracheostomy, maintaining invasive mechanical ventilation, awake-ECMO and CVVHDF. The absence of improvement in renal function granted formal indication for combined lung-kidney transplantation (CLKT).To investigate the appearance of nephrotic proteinuria in February 2018, she underwent a renal biopsy that revealed deposits of amyloid A, and the diagnosis of AA amyloidosis (or secondary amyloidosis) was established. In October 2018, the patient was admitted to the Intensive Care Unit (ICU) for dehydration secondary to diarrhea, with subsequent acute renal failure and oligoanuria requiring continuous venovenous hemodiafiltration (CVVHDF). At the ICU, she developed a respiratory infection  and septDuring the 32 days of ICU stay, 27 of them under “awake-ECMO,” the patient suffered hemothorax and hemopericardium secondary to anticoagulation, which evolved to cardiac arrest that was successfully reversed. Physical rehabilitation was limited at this point, and only in-bed mobilization exercises were feasible.2 of 512 mmHg with FiO2 of 1.0 and a positive end-expiratory pressure of 5 cmH2O for 5 min. Tracheobronchial aspirate cultures were negative. The donor explants were performed in a multiorgan context without complications, and the lungs were preserved in Perfadex®.On the 33rd day of the ICU stay, the patient was underwent CLKT. The donor was a 69-year-old woman, weighing 60 kg and measuring 171 cm, with no relevant medical history. She had a predicted TLC of 4050 cc. Her last arterial blood gas analysis had pOA sequential double-lung transplant was performed under venoarterial ECMO. It was very laborious because of the existence of bilateral empyema, which led to extrapleural pneumectomy with profuse hemorrhage, due to the patient's hypocoagulant status. In total, one prothrombin complex, 15 red cell concentrates, five platelet concentrates and four fresh frozen plasma units were required to support the patient. Ischemic times were 6 h 18 min for right lung and 8 h 13 min for left lung. After lung transplantation, kidney transplantation was performed, with an ischemic time of 11 h 57 min and no major complications noted, and good perfusion was observed after implantation.The immediate post-transplant period was complicated by multifactorial shock, requiring the restart of CVVHDF, high-dose vasopressor support , VV-ECMO and intensive fluid therapy.Immunosuppression included induction with 20 mg basiliximab on day 0 and day 4 of transplantation and maintenance therapy with tacrolimus, which was started during surgery (target blood levels around 10 ng/mL in the first 6 months and 6 ng/mL afterwards), mofetil mycophenolate and steroids. Corticosteroid therapy was started during the transplant, at the unclamping of each pulmonary artery, initially with methylprednisolone 500 mg I.V., continuing with the following weaning schedule: 125 mg tid on day 1, 125 mg bid on day 2, and 125 mg qd on day 3, with weaning of 10 mg per day down to a daily dose of 0.5 mg/kg/day prednisolone for the first month after transplant and progressive weaning down to 0.1 mg/kg/day after the first month.Candida albicans and C. dubliniensis  and to previous isolations of A. fumigatus. Prophylaxis with inhaled colistin and prophylactic therapy for cytomegalovirus with ganciclovir  were also carried out.She was started on empirical antibiotics with meropenem, as well as anidulafungin directed at There was slow improvement and complicated ventilatory weaning due to marked sarcopenia, which also motivated the assessment of renal function based on serum cystatin C rather than creatinine levels, estimating a glomerular filtration rate of 25–35 mL/min. The patient was subsequently submitted to amputation of the left forearm, fourth and fifth toes of the left foot and distal phalanx of the fifth toe of the right foot due to irreversible ischemia, owing to the high aminergic support in the pre-operative, intra-operative and post-operative periods. In the first five days post-transplantation, rehabilitation exercises aimed to improve orthostatic positioning and passive limb mobilization.The discontinuation of VV-ECMO was only possible on day 5 post-transplant, while continuous dialysis was suspended on day 7 post-transplant. After this, she showed progress in the physical rehabilitation program, and started resistance training with light weights, postural re-education and transfer to chair. Spontaneous ventilation was achieved on day 50, supplemental oxygen therapy was suspended on day 60 and tracheostomy was removed on day 130 post-transplant.Klebsiella oxytoca isolated from a renal graft; 21 days of ceftazidime-avibactam and intravenous colistine, respectively, directed at Pandoraea and P. aeruginosa isolated in pleural fluid; fluconazole directed at C. parapsilosis in urine; and 15 days of cotrimoxazole and ceftriaxone to treat K. pneumoniae sepsis of urinary origin.During her stay in the Transplant Unit, the patient also underwent multiple cycles of antibiotics for nosocomial infections, in addition to those previously described, namely 7 days of tigecycline directed at Transfer to the Pulmonology ward took place on the 23rd day post-transplant. Serial renal Doppler ultrasonography was performed, which showed renal artery stenosis requiring stent placement (day 158 post-transplant).At the ward, it was possible to start an intensive rehabilitation program and occupational therapywith progressive gain of autonomy. The patient continued to perform resistance training with light weights, stretching and started to walk in the corridor. Only after the first 20 days in the ward, she did undergo respiratory and physical rehabilitation in the gym, where she started to do resistance training with progressively heavier weights, chest wall mobility and chest expansion exercises and walking on treadmill, with progressively higher speed settings. No additional complications, renal, pulmonary or otherwise, were identified.The patient was discharged from the hospital 186 days after the transplant and after 224 days of hospitalization, with FEV1 of 1790 cc (54%), FVC 2030 cc (52%) and DLCO 56% (KCO 84%), creatinine 2.31 mg/dL, blood urea nitrogen 100 mg/dL, and cystatin C 2.64 mg/L, with an estimated GFR of 22 mL/min.She maintains follow-up on the kidney and lung transplant services. Twenty-four months after CLKT, the patient wears a forearm prosthesis. She denies any major complaints and presents with FEV1 2520 cc (74%), FVC 3420 cc (85%), creatinine 1.4 mg/dL, and blood urea nitrogen 38 mg/dL, with an estimated GFR of 50 mL/min.2The hospital of Santa Marta, in Lisbon, has been the lung transplantation center of reference in Portugal since 1991, when the first combined heart-lung transplant was performed. It was only in 2001 that the first isolated lung transplantation took place. Twenty-one lung transplants were performed before 2008, when the team was reorganized and new protocols were elaborated. Since then, more than 300 lung transplantation have been performed, but, to date, no CLKT has never been carried out.In Portugal, cystic fibrosis is only the third leading cause of lung transplantation , and worThe combined transplantation of solid organs has evolved in recent years, however, with few studies carried out .Regarding the CLKT, particular attention should be paid to the type and dose of immunosuppression used in order to reduce the nephrotoxic effects and the risk of infection as to not compromise the viability of the pulmonary and renal grafts, especially taking into account the use of calcineurin-inhibiting drugs. In this case, it was tacrolimus, and the main indication for kidney transplantation in lung transplant patients is the nephrotoxicity caused by this type of immunosuppressant . On the The authors would like to highlight the extreme complexity of the patient and the extreme severity of her clinical condition at the time of the transplant and in the following weeks that she was hospitalized. In fact, it was the first time in our center that a patient has undergone a transplant and has been on VV-ECMO, CCVDHF and invasive mechanical ventilation concurrently and for so long. The recipient's youth, as well as the good conditions of the pulmonary graft, together with an experienced multidisciplinary team, certainly helped in the successful outcome of this case.In conclusion, CLKT may be indicated in carefully selected lung transplantation candidates with end-stage renal disease, as long as it is possible to proceed with kidney transplantation, ideally at the same operative time.All authors report no conflict of interest.