Analysing features of home-based workout during COVID-19 pandemic: a systematic review.

OBJECTIVE: Since the beginning of the COVID-19 pandemic, a decrease in physical activity (PA) related to home confinement has been reported worldwide. However, some individuals were able to engage in physical activities at home. Thus, in a perspective of public health, it may be useful to analyse the available evidence regarding PA adopted during home restrictions, in order to identify possible strategies to help people stay active even during emergency situations. The aim of this review was to analyse how healthy individuals spontaneously exercised at home in the course of the pandemic, in order to detect possible factors associated with this behaviour. STUDY DESIGN: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. METHODS: The protocol was registered in PROSPERO, an international prospective register of systematic reviews, with the registration number CRD42023394673. A literature search was conducted in PubMed, Scopus, and Web of Science. Cross-sectional studies published in English from the inception of each database to February 06th 2023 and focused on healthy individuals practicing spontaneous PA/exercise at home during the pandemic were considered eligible. The quality assessment was performed using the adapted Newcastle-Ottawa Quality Assessment Scale. Bibliographic information, sample size, study paricipant/population with age, gender, ethnicity, socioeconomic status, education, smart workers or not, anthropometric parameters, characteristics of at home exercises, athletic status and sedentariness, associated health-related effects, and main findings were synthetised. RESULTS: From 504 articles, 19 were included. Notwithstanding the differences in the studies examined, the majority of them reported that previous PA level was associated with exercise in such challenging conditions. Furthermore, technologies aimed at supporting exercise were shown to be a useful resource. CONCLUSIONS: Being habitually active and using digital supports may be associated with a positive attitude towards exercise at home during isolation. This suggests that in emergency situations, exercise should be promoted, also through digital media, especially among those groups who are usually less engaged in PA. Further analyses of longitudinal studies are needed to confirm these findings.

Comorbidity and in-hospital mortality in peritoneal dialysis patients: data of the Emilia Romagna region of Italy.

OBJECTIVE: Kidney failure increases in-hospital mortality (IHM); however, comorbidity is crucial for predicting mortality in dialysis patients. Our aim was to evaluate the impact of comorbidity, assessed by modified Elixhauser index (mEI), Charlson Comorbidity Index (CCI), and age-adjusted CCI, on IHM in a cohort of peritoneal dialysis patients admitted to hospitals of the Emilia Romagna region (ERR) of Italy. PATIENTS AND METHODS: All hospital admissions of peritoneal dialysis patients recorded between 2007 and 2021 in the ERR database were analyzed. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) was used for detecting diagnoses and procedures, and the inclusion criterion was code 5498. Comorbidity burden was evaluated by three different scores, and hemodialysis (HD) treatment need was considered. IHM was our outcome. RESULTS: During the 15 years of the study, 3,242 hospitalized peritoneal dialysis patients (62.7% males) were evaluated. Mean age was 62.8±20.6 years, 9.6% underwent HD, and IHM was 5.9% (n=192). IHM mortality was stable throughout the study period. Deceased subjects were older, were hospitalized longer, had a higher comorbidity burden, and had a higher percentage of HD treatment needs than survivors. Age, male sex, comorbidity burden, and HD treatment were predictors of IHM. Receiver operating characteristics (ROC) analysis confirmed the impact of comorbidity burden on IHM, especially when age was considered. CONCLUSIONS: We conclude that in male, elderly hospitalized peritoneal dialysis patients with failing dialysis technique, comorbidity burden should be considered being a predictor of IHM.

Spatial, temporal and network analyses provide insights into the dynamics of the bacterial communities associated with two species of Caribbean octocorals and indicate possible key taxa.

Despite the current decline of scleractinian coral populations, octocorals are thriving on reefs in the Caribbean Sea and western North Atlantic Ocean. These cnidarians are holobiont entities, interacting with a diverse array of microorganisms. Few studies have investigated the spatial and temporal stability of the bacterial communities associated with octocoral species and information regarding the co-occurrence and potential interactions between specific members of these bacterial communities remain sparse. To address this knowledge gap, this study investigated the stability of the bacterial assemblages associated with two common Caribbean octocoral species, Eunicea flexuosa and Antillogorgia americana, across time and geographical locations and performed network analyses to investigate potential bacterial interactions. Results demonstrated that general inferences regarding the spatial and temporal stability of octocoral-associated bacterial communities should not be made, as host-specific characteristics may influence these factors. In addition, network analyses revealed differences in the complexity of the interactions between bacteria among the octocoral species analyzed, while highlighting the presence of genera known to produce bioactive secondary metabolites in both octocorals that may play fundamental roles in structuring the octocoral-associated bacteriome. Supplementary Information: The online version contains supplementary material available at 10.1007/s13199-023-00923-x.

Sex-related differences and chronobiology of ST-elevation myocardial infarction: findings from a single hub center in Italy.

OBJECTIVE: Type I acute myocardial infarction (AMI) is a life-threatening condition. Time of event and rescue procedures, and sex-specific differences may play a crucial role. We aimed to investigate chronobiological patterns and sex-specific differences in a cohort of AMI patients referred to a single hub center in Italy. PATIENTS AND METHODS: We considered all patients consecutively admitted for AMI (STEMI) to the Hospital of the Heart, in Massa, Tuscany (a region of Italy), between 2006 to 2018, who underwent interventional procedures. Sex, age, time of hospital admission, outcome (discharged alive/deceased), main comorbidities, and time between symptom onset and emergency medical service (EMS) activation, were analyzed. Chronobiologic analysis was applied according to hour of day, month, and season of the year. RESULTS: Overall 2,522 patients (mean age 64.6±13.1 years, 73% males) were considered. In-hospital death (IHM) occurred in 96 subjects (3.8%). At univariate analysis, deceased subjects were more likely to be female, older, with longer wait for EMS activation and with interventional procedures during night-time. The multivariate analysis identified female sex, age, history of ischemic heart disease, and night-time interventional procedure as independently associated factors to IHM. Chronobiologic analysis showed a pattern with a main morning peak for total sample, males, and females (p=0.00027; p=0.0006); p=0.0121, respectively). Events showed a higher peak in summer, with no differences by sex, but IHM was higher in winter. Females showed a higher delay for EMS activation, compared to males (p<0.001), but with no effects on prognosis. On the contrary, males with a delay showed higher mortality. CONCLUSIONS: Great effort should be spent to reduce patient-related delays in interventional procedures, being this issue crucial in both sexes.

Targeted screening and quantification of synthetic cathinones and metabolites in hair by UHPLC-HRMS.

OBJECTIVE: Synthetic cathinones (SCs) are new psychoactive substances with sympathomimetic effects, which emerged into the illegal drug market to replace controlled stimulants. Since every year more powerful and toxic substances enter the illicit market, there is the need for analytical methodologies able to detect these new compounds in conventional and non-conventional biological matrices. We sought to develop and validate a targeted screening and quantification method for thirty-two parent SCs and two metabolites in hair samples by ultra-high-performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-HRMS). MATERIALS AND METHODS: 20 mg hair samples were soaked in 250 µL of 2 mM ammonium formate, methanol and acetonitrile mixture (50/25/25, v/v/v) and incubated overnight at 40°C. After incubation, the samples were evaporated to dryness under nitrogen stream and reconstituted with 100 µL of mobile phase mix (A:B, 80:20) and 10 µL were injected into UHPLC-HRMS. A Q ExactiveTM Focus Orbitrap Mass spectrometer with full scan and targeted data-dependent MS/MS scan acquisition was used for the screening and quantitation analysis. RESULTS: The assay was linear from 5 to 500 pg/mg hair for all the analytes under investigation. Intra-day and inter-day precision were always < 15% and matrix effect and analytical recovery were always within acceptable criteria (±25% and >50%, respectively). The developed method was applied to authentic hair samples from SCs consumers. The most prevalent found SCs were 3,4-Methylenedioxy-α-Pyrrolidinohexanophenone with a concentration range of 6.0-1,000.0 pg/mg along with α-Pyrrolidinohexiophenone (54.0 and 554.0 pg/mg, respectively), 3-Methylmetcathinone (556.0 and 5,000.0 pg/mg) and 4-Methylethcathinone (11.5 and 448.0 pg/mg) CONCLUSIONS: The developed method showed good selectivity, specificity, an easy and low-cost sample preparation and an analysis time compatible with a high throughput laboratory.

Occurrence and accumulation of pharmaceutical products in water and biota of urban lowland rivers.

We evaluated the distribution of eleven groups of pharmaceutically active compounds (PhACs) in surface waters and biota of different trophic levels, in five sites of two lowland urban rivers in Argentine. Twenty-nine out of 39 PhACs and two metabolites were detected in at least one water sample (2-9622 ng/L), eleven detected in biofilms (1-179 ng/g d.w.) and eight in the macrophyte Lemna gibba (4-112 ng/g d.w). The two more polluted sites had a similar distribution of the main groups of compounds. In surface waters, the largest concentrations were for the analgesic acetaminophen (9622 ng/L), the antibiotic sulfamethoxazole (326 ng/L), the antihypertensive valsartan (963 ng/L), the ß-blocking agent atenolol (427 ng/L), the diuretic hydrochlorothiazide (445 ng/L) and the psychiatric drug carbamazepine (99 ng/L). The antibiotic ciprofloxacin exhibited the highest concentration in the biofilm (179 ng/g d.w.) and in the macrophyte L. gibba (112 ng/g d.w.) Several compounds were detected in the water but not in the biota (e.g., codeine and bezafibrate), and others (e.g., azithromycin and citalopram) were found in the biota but not in the surface water. Significant bioaccumulation factors (>1000 L/kg d.w.) were obtained for venlafaxine and ciprofloxacin in biofilm. Our results show that PhACs may accumulate in several biological compartments. Within an environmental compartment, similar PhACs profile and concentrations were found in different sites receiving urban pollution. Among different compartments, biofilms may be the most suitable biota matrix to monitor the immediate reception of PhACs in the biota. Our results indicate that the presence of PhACs in urban rivers and their accumulation in the biota could be incorporated as symptoms of the urban stream syndrome.

Nurses, sleep disturbances, desynchronization of circadian rhythms, and performance: a dangerous liaison? A narrative mini-review.

OBJECTIVE: Nursing is a high-stress occupation, and recent research of circadian rhythm desynchronization has focused on its consequences for nurses' health. Moreover, shiftwork, sleep disturbances, nightmares, and health issues are closely related to individual circadian preferences ('chronotype'). The aim of this narrative mini-review was to check the available literature to collect findings on the interrelationships among these aspects, as well as to determine the possible consequences for performance. MATERIALS AND METHODS: We explored the PubMed, EMBASE and Google Scholar electronic databases using the search terms 'Nursing', 'Stress', 'Sleep disturbances', 'Nightmares', 'Circadian rhythm', 'Desynchronization', 'Chronotype', 'Performance', and 'Sex/Gender'. Due to the wide heterogeneity of studies, with most including only some of these terms, we proceeded to single data extractions after analyzing the studies case by case and decided to conduct a narrative mini-review. RESULTS: Shift work, due to the regular alterations of the daily light profile, disrupts the normal circadian sleep-wake cycle and is associated with impaired health among rotational shift workers, with nurses on the frontline. Circadian desynchronization may be associated with adverse effects on nurses' health and may be a risk factor for stress, metabolic disorders, and sleep disturbances, including nightmares, and stress operates in a bidirectional fashion. Chronotype plays a crucial role as well, since the asynchrony between one's chronotype and social working hours (social jetlag) may generate problems, since the time-of-day and optimal performance are strongly connected. CONCLUSIONS: Circadian rhythms, chronotype, sleep, health, and working performance are strongly connected. The assessment of chronotype could represent a tool to identify health care personnel at higher risk of circadian disruption, allowing for mitigation of work-related stress and sleep disturbances, and reducing the risk of making working errors.

Smell and taste dysfunction during the COVID-19 pandemic: an infodemiological analysis.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause smell and taste dysfunction. We aimed to investigate the general community's interest in smell dysfunction (SD) and taste dysfunction (TD) using Google Trends to compare results with more common symptoms associated with SARS-CoV-2 infection, such as fever and cough. MATERIALS AND METHODS: Relative Search Volumes (RSVs) for the English terms "Smell", "Taste", "Fever" and "Cough", filtered by the category "Health", were collected from 2018 through 2020. Moreover, RSVs using synonyms of "Taste" and "Smell" in 5 European languages were analyzed. RESULTS: The worldwide mean RSVs for "Fever", "Cough", "Smell", and "Taste" during 2020 were 49%, 34%, 8% and 9%, respectively. RSVs associated with the search terms "Fever" and "Cough" showed a peak between February and March 2020, as did "Smell" and "Taste". Even though RSVs were much lower, they were highly correlated (r=0.890). RSVs obtained from "Smell" and "Taste" in five European languages (German, English, French, Italian and Spanish) had similar temporal trends. CONCLUSIONS: Our findings show the level of the general population's interest for early symptoms, suggesting that their interest in SARS-CoV-2 infection symptoms, such as SD and TD, was scarce but peaked during the pandemic outbreak.

Combining robotics with enhanced serotonin-driven cortical plasticity improves post-stroke motor recovery.

Despite recent progresses in robotic rehabilitation technologies, their efficacy for post-stroke motor recovery is still limited. Such limitations might stem from the insufficient enhancement of plasticity mechanisms, crucial for functional recovery. Here, we designed a clinically relevant strategy that combines robotic rehabilitation with chemogenetic stimulation of serotonin release to boost plasticity. These two approaches acted synergistically to enhance post-stroke motor performance. Indeed, mice treated with our combined therapy showed substantial functional gains that persisted beyond the treatment period and generalized to non-trained tasks. Motor recovery was associated with a reduction in electrophysiological and neuroanatomical markers of GABAergic neurotransmission, suggesting disinhibition in perilesional areas. To unveil the translational potentialities of our approach, we specifically targeted the serotonin 1A receptor by delivering Buspirone, a clinically approved drug, in stroke mice undergoing robotic rehabilitation. Administration of Buspirone restored motor impairments similarly to what observed with chemogenetic stimulation, showing the immediate translational potential of this combined approach to significantly improve motor recovery after stroke.

SARS-CoV-2 infection and H1N1 vaccination: does a relationship between the two factors really exist? A retrospective analysis of a territorial cohort in Ferrara, Italy.

OBJECTIVE: SARS-CoV-2 has been compared with other strains of coronaviruses, SARS-CoV and MERS-CoV, and with the flu viruses: all of them manifest themselves with respiratory symptoms and, although their genetic patterns are similar, the spread of SARS-CoV-2 infection has quickly reached global dimensions, demonstrating that SARS-CoV-2 is a virus with greater spreading capacity, albeit less lethal. Compared with influenza viruses, coronaviruses have a longer incubation period and the patients with coronaviruses' syndromes develop more severe diseases requiring frequent hospitalizations and intensive care admissions. The aim was to explore the relationships between seasonal influenza vaccination and coronavirus infection and to understand whether this hypothetic role by the flu vaccines modifies SARS-CoV-2 infection's outcomes. PATIENTS AND METHODS: In this retrospective, multicenter study, we enrolled 952 patients diagnosed with SARS-CoV-2 infection; 448 were admitted to our two main hospitals in Ferrara territory, while the remaining 504 were isolated at home. We compared the group of patients who had been vaccinated for influenza in the previous 12 months to that of unvaccinated patients. RESULTS: Significant differences were found for both the need for hospitalization and 30-day mortality between vaccinated and unvaccinated patients. We found age to be the only independent risk factor for a worse 30-day prognosis, while gender, influenza vaccinations and age itself were independent risk factors for undergoing hospitalization. CONCLUSIONS: In our groups of patients, we found a relationship between seasonal influenza vaccinations and SARS-CoV-2 infection. Age seems to be the main risk factor for short-term mortality in COVID-19 inpatients, while the influenza vaccination is, together with gender and age itself, a determining factor in predicting the need for hospitalization.

Sleep, dreams, nightmares, and sex-related differences: a narrative review.

OBJECTIVE: The aim of this study was to review the available findings on sex-related differences for sleep disorders, dreams and nightmares. MATERIALS AND METHODS: We explored the PubMed, EMBASE and Google Scholar electronic databases, with regards to the searching terms 'sleep', 'dreams', and 'nightmares' associated with 'sex' and/or 'gender'. Moreover, other supplementary terms for the searching strategy were 'chronobiology', and 'circadian rhythm'. Due to the relative paucity of studies including separate analysis by sex, and especially to their wide heterogeneity, we decided to proceed with a narrative review, highlighting the sex-related findings of each topic into apposite boxes. RESULTS: On one hand, sleep disorders seem to be more frequent in women. On the other hand, sex-related differences exist for either dreams or nightmares. As for the former, differences make reference to dream content (men: physical aggression, women family themes), self-reported perspective (men dream in third person, women in first person), dream sharing (more frequent in women), lucid dreaming (women more realistic, men more controlled), and daydreaming (young men more frequently have sexual themes). Nightmares are more frequent in women too, and they are often associated with sleep disorders and even with psychiatric disorders, such as depression and/or anxiety. In women, a strong association has been shown between nightmares and evening circadian preference. CONCLUSIONS: For many years, and for many reasons, laboratory experiments have been conducted mainly, if not exclusively, on male animals. Thus, a novel effort towards a new governance of scientific and research activities with a gender-specific perspective has been claimed for all areas of medicine, and more research on sex-differences is strongly needed also on this topic.

Infodemiology of renal diseases: a novel opportunity to investigate public global interest.

OBJECTIVE: The aim of this study was to investigate the global community interest about renal diseases through relative search volumes (RSVs) of Google Trends (GT). MATERIALS AND METHODS: The online interest for the search terms hematuria (H), proteinuria (P), chronic kidney disease (CKD) and dialysis (D) was measured by evaluating RSVs from 2010 to 2019. All countries listed in GT were analysed and those presenting RSVs related to all search terms were considered following geographical position. RESULTS: Mean values of RSVs for D, CKD, H and P were 80±9%, 11±2%, 17±2% and 11±1%, respectively. D is the search term most frequently typed in English-speaking countries. On the other hand, in Latin Countries, the interest for P and H was higher than D. Searching for D, CKD and H are highly correlated whilst correlation coefficients between RSVs for D, CKD, and H with P are lower. Since 2010, the interest for renal diseases maintained stable. CONCLUSIONS: GT is a reliable tool in evaluating global interest for renal diseases in different geographical areas and temporal patterns. Although infodemiology represents a method for investigating the dissemination of information at a global level, our results suggest the need for increasing general population's interest for renal diseases especially, and move from simple interest to global awareness in the view of prevention strategies.

Infodemiology of solid organ transplantation: relationship to the Global Observatory on Donation and Transplantation data.

OBJECTIVE: Although transplantation medicine has been continuously improving, its impact on the general population needs to be evaluated. This study describes the global community interest in solid organ transplantation (SOT) using Google Trends, comparing relative search volumes (RSVs) and data from the World Health Organization (WHO) Global Observatory on Donation and Transplantation (GODT) regarding SOT activity all around the world. MATERIALS AND METHODS: The online interest for the search terms "kidney transplantation", "liver transplantation", "heart transplantation" and "lung transplantation" was measured, evaluating RSVs and the number of worldwide SOT recorded in the GODT website from 2008 to 2018. RESULTS: The mean values of RSVs were 51.7±16.8 for liver transplantation, 39.8±9.6 for kidney transplantation, 22.4±7.4 for heart transplantation and 15.4±5.2 for lung transplantation, and these values gradually reduced during the study period. Anglo Saxon countries had the highest interest for SOT, and the mean values of RSVs per year and annual numbers of SOT were inversely correlated. CONCLUSIONS: Despite the apparent interest and awareness, we found that public interest in SOT is decreasing. Access to information is crucial for improving understanding of transplantation and motivation to donate. Health care professionals could take advantage by using the internet, and evaluation of RSVs could represent valuable feedback.

Prediction of in-hospital mortality of patients with SARS-CoV-2 infection by comorbidity indexes: an Italian internal medicine single center study.

OBJECTIVE: Clinical outcomes in patients hospitalized for severe acute respiratory syndrome due to coronavirus (SARS-CoV-2) infection seems to be closely related with burden of comorbidities. A comorbidity score could help in clinical stratification of patients admitted to internal medicine units. Our aim was to assess a novel modified Elixhauser index (mEi) and the Charlson Comorbidity Index (CCI) for predicting in-hospital mortality (IHM) in internal medicine patients with SARS-CoV-2 infection. PATIENTS AND METHODS: This single-center retrospective study enrolled all consecutive patients discharged from internal medicine unit with confirmed SARS-CoV-2 infection. Both the mEi and CCI were easily calculated from administrative data. Comorbidity scores were tested using receiver operating characteristic (ROC) analysis, and the respective area under the curve (AUC). RESULTS: The total sample consisted of 151 individuals, and 30 (19.9%) died during their hospital stay. Deceased subjects were older (82.8±10.8 vs. 63.3±18.1 years; p<0.001) and had a higher burden of comorbidities: the mEi and CCI were 29.9±11 vs. 8.8±9.2 and 4.6±2.6 vs. 1.2±2 (p<0.001), respectively. Only the mEi was independently associated with IHM (OR 1.173), and ROC curves analysis showed that the AUCs were 0.863 and 0.918 for the CCI and for mEi, respectively. CONCLUSIONS: In patients admitted to internal medicine wards with SARS-CoV-2 infection, the mEi showed a better performance in predicting IHM than CCI.

Morning vs. evening administration of antiviral therapy in COVID-19 patients. A preliminary retrospective study in Ferrara, Italy.

OBJECTIVE: At the end of 2019, the Novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), spread rapidly from China to the whole world. Circadian rhythms can play crucial role in the complex interplay between viruses and organisms, and temporized schedules (chronotherapy) have been positively tested in several medical diseases. We aimed to compare the possible effects of a morning vs. evening antiviral administration in COVID patients. PATIENTS AND METHODS: We retrospectively evaluated all patients admitted to COVID internal medicine units with confirmed SARS-CoV-2 infection, and treated with darunavir-ritonavir (single daily dose, for seven days). Age, sex, length of stay (LOS), pharmacological treatment, and timing of antiviral administration (morning or evening), were recorded. Outcome indicators were death or LOS, and laboratory parameters, e.g., variations in C-reactive protein (CRP) levels, ratio of arterial oxygen partial pressure (PaO2, mmHg) to fractional inspired oxygen (FiO2) (PaO2/FiO2), and leucocyte count. RESULTS: The total sample consisted of 151 patients, 33 (21.8%) of whom were selected for antiviral treatment. The mean age was 61.8±18.3 years, 17 (51.5%) were male, and the mean LOS was 13.4±8.6 days. Nine patients (27.3%) had their antiviral administration in the morning, and 24 (72.7%) had antiviral administration in the evening. No fatalities occurred. Despite the extremely limited sample size, morning group subjects showed a significant difference in CRP variation, compared to that in evening group subjects (-65.82±33.26 vs. 83.32±304.89, respectively, p<0.032). No significant differences were found for other parameters. CONCLUSIONS: This report is the first study evaluating temporized morning vs. evening antiviral administration in SARS-CoV-2 patients. The morning regimen was associated with a significant reduction in CRP values. Further confirmations with larger and multicenter samples of patients could reveal novel potentially useful insights.

Chronobiology of acute pancreatitis in a single Italian centre.

OBJECTIVE: Seasonal variation may occur in many different diseases hence influencing awareness in clinical practice. This study aimed to establish seasonal variations of acute pancreatitis by using a validated chronobiological analysis. PATIENTS AND METHODS: All cases of acute pancreatitis consecutively observed in fifteen years, i.e., from January 2003 to December 2017, at St. Anna University Hospital of Ferrara, Italy, were included in this study. Accurate statistical and logistic regression analyses were applied to our database. RESULTS: A total number of 1883 consecutive cases of acute pancreatitis were observed. A significant peak was identified in the summer period (p=0.014). Patient stratification, according to age, showed that elderly people had an increased incidence of acute pancreatitis in autumn and summer (being the biliary stone disease the main cause, p=0.011) vs. other seasons (p=0.003). Mortality occurred more prominently in males vs. females, although the latter gender was more prone to acute pancreatitis (p=0.017). CONCLUSIONS: In a single centre of Northern East of Italy, we demonstrated that acute pancreatitis had a clear seasonal variation with a prominent incidence during summer. Various associated factors could contribute to this chronobiological pattern, including gender, age, and biliary stone disease.

Sex and acute oesophageal variceal bleeding-related in-hospital mortality: a 15-year retrospective study.

OBJECTIVE: The relationship between in-hospital mortality (IHM) and acute oesophageal variceal bleeding (AOEVB) has not been fully assessed. The aim of this study was to establish the association between sex and mortality for patients hospitalized with AOEVB. PATIENTS AND METHODS: We analyzed hospitalizations from the Italian Health Ministry database by identifying all patients discharged with AOEVB from January 2001 to December 2015. A total of 144,943 hospitalizations were for oesophageal varices, but only 24,570 emergency admissions with AOEVB coded as the primary or secondary diagnosis were included for analysis. Factors independently associated with IHM were evaluated by multilevel logistic regression. RESULTS: Approximately half of the population was aged ≥ 65 years, and nearly 10% was diagnosed with hepatocellular carcinoma. Overall, the IHM was 11.8%, with 12.1% in males and 11.3% in females, increasing from 9.2% among subjects aged < 55 years to 18.9% among those aged ≥ 85 years. The crude risk of death was slightly higher among females; however, when age and clinical presentation were considered, female sex was associated with reduced mortality. For liver disease, the risk of death in women was lower only in those with non-alcoholic liver disease (odds ratio= 0.77, 0.66-0.89), but it was similar to that in men for unspecified, cancer and alcoholic liver disease. The risk declined over time and was increased in patients with multiple comorbidities. CONCLUSIONS: AOEVB-related IHM decreased from 2001-2005 to 2011-2015. Factors affecting mortality included liver disease, age, sex, development of hepatocellular carcinoma and comorbidities.

The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0-2.5 µM) of OCA were added to culture media and, after 3-10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 µM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients.

Neoplasms and renal transplantation: impact of gender, comorbidity and age on in-hospital mortality. A retrospective study in the region Emilia-Romagna of Italy.

OBJECTIVE: The aim of this retrospective study was to investigate the relationship between cancer, non-immunologic comorbidity, estimated by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codification, gender and in-hospital mortality (IHM) in a large sample of renal transplant recipients (RTRs) living in the region Emilia-Romagna (RER) of Italy. PATIENTS AND METHODS: We evaluated IHM in RTRs admitted between 2000 and 2013 recorded in the RER database. By using ICD-9-CM codes, the Elixhauser index (EI) was calculated, and cancers were identified and classified as skin cancers (SC), solid organ cancers (SOC) and post-transplant lymphoproliferative disorders (PTLD). IHM was the dependent variable of the multivariate models, while age, gender, EI corrected removing the effect of malignancies (cEI), and different types of cancer were the independent ones. RESULTS: During the examined period, a total of 9,063 admissions in 3,648 RTRs were recorded, of whom 117 died (3.2%). The mean age was 52.9±13.1 years. Cancers were reported in 580 admissions (6.4%), and mean cEI was 3.5±3.4. Deceased RTRs were older, had a higher prevalence of PTLD and SOC, and had a higher cEI than survivors. IHM was independently associated with (in decreasing order) PTLD (OR 12.431, 95%CI 5.834-26.489, p<0.001), SOC (OR 6.804, 95%CI 4.323-10.707, p<0.001), female gender (OR 1.633, 95%CI 1.057-2.523, p=0.006), cEI (OR 1.106, 95%CI 1.068-1.145, p<0.001), and age (OR 1.049, 95%CI 1.031-1.068, p<0.001) CONCLUSIONS: Cancer, in particular SOC and PTLD, is strongly associated with IHM in RTRs. On the other hand, rather surprisingly, female gender exhibited a stronger association with IHM than other more expected factors, such as comorbidity and age.