Orthostatic hypotension,an often-neglected problem in community-dwelling older people:discrepancies between studies and real life

Orthostatic hypotension (OH)is a common condition in older persons.According to the 2011criteria,OH is defined by a sustained reduction of systolic blood pressure of 20 mmHg or a 10mmHg-fall of diastolic blood pressure,[1] Its prevalence increases with age and according to a recent systematic review the pooled prevalence in community dwelling older people is 22.2%.[2]Although OH is largely explained by concurrent clinical conditions (in particular, hypertension,diabetes,malnutrition,vascular encephalopa- thy,anemia,Parkinson's disease)[3],aging per se determines a series of physiological dysfunctions potentially representing its biological substratum (e.g.,reduction in barore- flex-mediated cardiovascular function,altered salt and water balance at renal level,impaired cardiac diastolic filling).It is also noteworthy that age-related changes in pharmacokinetic and pharmacodynamic mechanisms of drugs (especially in the context of polypharmacy)also increase the risk of OH.

Differential expression of genes involved in the epigenetic regulation of cell identity in normal human mammary cell commitment and differentiation

The establishment and maintenance of mammary epithelial cell identity depends on the activity of a group of proteins, collectively called maintenance proteins, that act as epigenetic regulators of gene transcription through DNA methylation, histone modification, and chromatin remodeling. Increasing evidence indicates that dysregulation of these crucial proteins may disrupt epithelial cell integrity and trigger breast tumor initiation. Therefore, we explored in silico the expression pattern of a panel of 369 genes known to be involved in the establishment and maintenance of epithelial cell identity and mammary gland remodeling in cell subpopulations isolated from normal human mammary tissue and selectively enriched in their content of bipotent progenitors, committed luminal progenitors, and differentiated myoepithelial or differentiated luminal cells. The results indicated that, compared to bipotent cells, differentiated myoepithelial and luminal subpopulations were both characterized by the differential expression of 4 genes involved in cell identity maintenance: CBX6 and PCGF2, encoding proteins belonging to the Polycomb group, and SMARCD3 and SMARCE1, encoding proteins belonging to the Trithorax group. In addition to these common genes, the myoepithelial phenotype was associated with the differential expression of HDAC1, which encodes histone deacetylase 1, whereas the luminal phenotype was associated with the differential expression of SMARCA4 and HAT1, which encode a Trithorax protein and histone acetylase 1, respectively. The luminal compartment was further characterized by the overexpression of ALDH1A3 and GATA3, and the down-regulation of NOTCH4 and CCNB1, with the latter suggesting a block in cell cycle progression at the G2 phase. In contrast, myoepithelial differentiation was associated with the overexpression of MYC and the down-regulation of CCNE1, with the latter suggesting a block in cell cycle progression at the G1 phase.

Orthostatic hypertension and adverse clinical outcomes in adults and older people

Orthostatic hypertension(OHT)is a condition characterized by an increase in blood pressure after assuming the standing position.[1]Nowadays no consensus definition exists,thus OHT prevalence varies among studies(4%-20.3%).

Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation

BACKGROUND Polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless,long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also unclear.AIM To investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation.METHODS This single-centre observational study with a median follow up of 57(31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasmaquantitative polymerized chain reaction. Patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment,rejection, renal function, urologic complications, opportunistic infections, newonset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and nephropathy.RESULTS BK-viremia was detected in 9.5% recipients. Initial viral load was high(≥ 10000 copies/mL) in 66.7% and low(< 10000 copies/mL) in 33.3% of these patients.Polyomavirus-associated nephropathy was diagnosed in 6.5% of the study population. Patients with high initial viral load were more likely to experience sustained viremia(95% vs 25%, P < 0.00001), nephropathy(92.5% vs 15%, P <0.00001), and polyomavirus-related graft loss(27.5% vs 0%, P = 0.0108) than recipients with low initial viral load. Comparison between recipients with or without BK-viremia showed that the proportion of patients with Afro-Caribbean ethnicity(33.3% vs 16.5%, P = 0.0024), panel-reactive antibody ≥ 50%(30% vs14.6%, P = 0.0047), human leukocyte antigen(HLA) mismatching > 4(26.7% vs13.4%, P = 0.0110), and rejection within thirty days of transplant(21.7% vs 9.5%; P= 0.0073) was higher in the viremic group. Five-year patient and overall graft survival rates for patients with or without BK-viremia were similar. However,viremic recipients showed higher 5-year crude cumulative(22.5% vs 12.2%, P =0.0270) and 30-d-event-censored(22.5% vs 7.1%, P = 0.001) incidences of graft failure than control. In the viremic group we also observed higher proportions of recipients with 5-year estimated glomerular filtration rate < 30 mL/min than the group without viremia: 45% vs 27%(P = 0.0064). Urologic complications were comparable between the two groups. Response to treatment was complete in55%, partial in 26.7%, and absent in 18.3% patients. The nephropathy group showed higher 5-year crude cumulative and 30-d-event-censored incidences of graft failure than control: 29.1% vs 12.1%(P = 0.008) and 29.1% vs 7.2%(P <0.001), respectively. Our multivariable model demonstrated that Afro-Caribbean ethnicity, panel-reactive antibody > 50%, HLA mismatching > 4, and rejection were independent risk factors for BK-virus viremia whereas cytomegalovirus prophylaxis was protective.CONCLUSION Current treatment of BK-virus infection offers sub-optimal results. Initial viremia is a valuable parameter to detect patients at increased risk of nephropathy. Panelreactive antibody > 50% and Afro-Caribbean ethnicity are independent predictors of BK-virus infection whereas cytomegalovirus prophylaxis has a protective effect.

Role of PTX3 and complement modulation in the tumor microenvironment

Pentraxin-3(PTX3),the prototype of long pentraxins,seems to influence complement system(CS)modulation.PTX3 and CS sustain carcinogenesis,enriching tumor microenvironment(TME)with pro-inflammatory molecules promoting angiogenesis in prostate cancer(PC)and renal cell carcinoma(RCC).Furthermore,cancer cells overexpress complement regulatory proteins,such as CD46,CD55 and CD59,which negatively affect complement pathways for support cancer cells survival.This viewpoint aims to elucidate the ambivalent role of PTX3 and the CS in the context of tumor microenvironment(TME).

Allograft artery mycotic aneurysm after kidney transplantation: A case report and review of literature

BACKGROUND Allograft artery mycotic aneurysm(MA)represents a rare but life-threatening complication of kidney transplantation.Graftectomy is widely considered the safest option.Due to the rarity of the disease and the substantial risk of fatal consequences,experience with conservative strategies is limited.To date,only a few reports on surgical repair have been published.We describe a case of true MA successfully managed by aneurysm resection and arterial re-anastomosis.CASE SUMMARY An 18-year-old gentleman,on post-operative day 70 after deceased donor kidney transplantation,presented with malaise,low urinary output,and worsening renal function.Screening organ preservation fluid cultures,collected at the time of surgery,were positive for Candida albicans.Doppler ultrasound and contrastenhanced computer tomography showed a 4-cm-sized,saccular aneurysm of the iuxta-anastomotic segment of the allograft artery,suspicious for MA.The lesion was wide-necked and extended to the distal bifurcation of the main arterial branch,thus preventing endovascular stenting and embolization.After multidisciplinary discussion,the patient underwent surgical exploration,aneurysm excision,and re-anastomosis between the stump of the allograft artery and the internal iliac artery.The procedure was uneventful.Histology and microbiology evaluation of the surgical specimen confirmed the diagnosis of MA caused by Candida infection.Three years after the operation,the patient is doing very well with excellent allograft function and no signs of recurrent disease.CONCLUSION Surgical repair represents a feasible option in carefully selected patients with allograft artery MA.Anti-fungal prophylaxis is advised when preservation fluid cultures are positive.

Estimation of the Piecewise Exponential Model by Bayesian P-Splines via Gibbs Sampling: Robustness and Reliability of Posterior Estimates

In the investigation of disease dynamics, the effect of covariates on the hazard function is a major topic. Some recent smoothed estimation methods have been proposed, both frequentist and Bayesian, based on the relationship between penalized splines and mixed models theory. These approaches are also motivated by the possibility of using automatic procedures for determining the optimal amount of smoothing. However, estimation algorithms involve an analytically intractable hazard function, and thus require ad-hoc software routines. We propose a more user-friendly alternative, consisting in regularized estimation of piecewise exponential models by Bayesian P-splines. A further facilitation is that widespread Bayesian software, such as WinBUGS, can be used. The aim is assessing the robustness of this approach with respect to different prior functions and penalties. A large dataset from breast cancer patients, where results from validated clinical studies are available, is used as a benchmark to evaluate the reliability of the estimates. A second dataset from a small case series of sarcoma patients is used for evaluating the performances of the PE model as a tool for exploratory analysis. Concerning breast cancer data, the estimates are robust with respect to priors and penalties, and consistent with clinical knowledge. Concerning soft tissue sarcoma data, the estimates of the hazard function are sensitive with respect to the prior for the smoothing parameter, whereas the estimates of regression coefficients are robust. In conclusion, Gibbs sampling results an efficient computational strategy. The issue of the sensitivity with respect to the priors concerns only the estimates of the hazard function, and seems more likely to occur when non-large case series are investigated, calling for tailored solutions.

Advancing immunosuppression in liver transplantation: A narrative review

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation(LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solidorgan transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

Survey of international experts on research priorities to improve care for healthy ageing

INTRODUCTION The United Nations(UN)Decade of Healthy Ageing(2021–2030),coordinated by the World Health Organization(WHO),1 is a global collaborative initiative aimed at improving the lives of older people,their families and the communities.23 The Action Areas 3(ie,‘deliver person-centred,integrated care and primary health services responsive to older people’)and 4(ie,‘provide access to long-term care(LTC)for older people who need it’)of the Decade’s work programme focus on reorienting health and care systems to promote‘ageing in place’and the delivery of personalised interventions in a seamless continuum of care.

Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease

Background Klotho proteins （α- and β） are membrane-based circulating proteins that regulate cell metabolism, as well as the lifespan modulating activity of Fibroblast Growth Factors （FGFs）. Recent data has shown that higher plasma circulating Klotho levels reduce cardio- vascular risk, suggesting Klotho has a protective role in cardiovascular diseases. However, although so far it has been identified in various organs, it is unknown whether cardiomyocytes express Klotho and FGFs, and whether high cardiovascular risk could affect cardiac expres- sion ofKlotho, FGFs and other molecules. Methods We selected 20 patients with an estimated 10-year high atherosclerotic cardiovascular disease and 10 age-matched control subjects with an estimated 10-year low risk undergone cardiac surgery for reasons other than coronary artery by-pass. In myocardial biopsies, we evaluated by immuno-histochemistry whether Klotho and FGFs were expressed in cardiomyo- cytes, and whether higher cardiovascular risk influenced the expression of other molecules involved in endoplasmic reticulum stress, oxida- tive stress, inflammation and fibrosis. Results Only cardiomyocytes of patients with a higher cardiovascular risk showed lower expression of Klotho, but higher expressions of FGFs. Furthermore, higher cardiovascular risk was associated with increased expression of oxidative and endoplasmic reticular stress, inflammation and fibrosis. Conclusions This study showed for the first time that Klotho proteins are ex- pressed in human cardiomyocytes and that cardiac expression of Klotho is down-regulated in higher cardiovascular risk patients, while expression of stress-related molecules were significantly increased.

Systematic review of ablative therapy for the treatment of renal allograft neoplasms

BACKGROUND To date,there are no guidelines on the treatment of solid neoplasms in the transplanted kidney.Historically,allograft nephrectomy has been considered the only reasonable option.More recently,nephron-sparing surgery (NSS) and ablative therapy (AT) have been proposed as alternative procedures in selected cases.AIM To review outcomes of AT for the treatment of renal allograft tumours.METHODS We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 Checklist.PubMed was searched in March 2019 without time restrictions for all papers reporting on radiofrequency ablation (RFA),cryoablation (CA),microwave ablation (MWA),high-intensity focused ultrasound (HIFU),and irreversible electroporation (IRE) of solid tumours of the kidney allograft.Only original manuscripts describing actual cases and edited in English were considered.All relevant articles were accessed in full text.Additional searches included all pertinent references.Selected studies were also assessed for methodological quality using a tool based on a modification of the Newcastle Ottawa scale.Data on recipient characteristics,transplant characteristics,disease characteristics,treatment protocols,and treatment outcomes were extracted and analysed.Given the nature and the quality of the studies available (mostly retrospective case reports and small retrospective uncontrolled case series),a descriptive summary was provided.RESULTS Twenty-eight relevant studies were selected describing a total of 100 AT procedures in 92 patients.Recipient age at diagnosis ranged from 21 to 71 years whereas time from transplant to diagnosis ranged from 0.1 to 312 mo.Most of the neoplasms were asymptomatic and diagnosed incidentally during imaging carried out for screening purposes or for other clinical reasons.Preferred diagnostic modality was Doppler-ultrasound scan followed by computed tomography scan,and magnetic resonance imaging.Main tumour types were: papillary renal cell carcinoma (RCC) and clear cell RCC.Maximal tumour diameter ranged from 5 to 55 mm.The vast majority of neoplasms were T1a N0 M0 with only 2 lesions staged T1b N0 M0.Neoplasms were managed by RFA (n = 78),CA (n = 15),MWA (n = 3),HIFU (n = 3),and IRE (n = 1).Overall,3 episodes of primary treatment failure were reported.A single case of recurrence was identified.Follow-up ranged from 1 to 81 mo.No cancer-related deaths were observed.Complication rate was extremely low (mostly < 10%).Graft function remained stable in the majority of recipients.Due to the limited sample size,no clear benefit of a single procedure over the other ones could be demonstrated.CONCLUSION AT for renal allograft neoplasms represents a promising alternative to radical nephrectomy and NSS in carefully selected patients.Properly designed clinical trials are needed to validate this therapeutic approach.

Epithelial cell identity in hyperplastic precursors of breast cancer

Introduction:In the adult human breast,hyperplastic enlarged lobular unit(HELU) and atypical ductal hyperplasia(ADH) are two common abnormalities that frequently coexist with ductal carcinoma in situ(DCIS).For this reason,they have been proposed as the early steps in a biological continuum toward breast cancer.Methods:We investigated in silico the expression of 369 genes experimentally recognized as involved in establishing and maintaining epithelial cell identity and mammary gland remodeling,in HELUs or ADHs with respect to the corresponding patient-matched normal tissue.Results:Despite the common luminal origin,HELUs and ADHs proved to be characterized by distinct gene profiles that overlap for 5 genes only.While HELUs were associated with the overexpression of progesterone receptor(PGR),ADHs were characterized by the overexpression of estrogen receptor 1(ESR1) coupled with the overexpression of some proliferation-associated genes.Conclusions:This unexpected finding contradicts the notion that in differentiated luminal cells the expression of estrogen receptor(ER) is dissociated from cell proliferation and suggests that the establishing of an ER-dependent signaling is able to sustain cell proliferation in an autocrine manner as an early event in tumor initiation.Although clinical evidence indicates that only a fraction of HELUs and ADHs evolve to invasive cancer,present findings warn that exposure to synthetic progestins,frequently administered as hormone-replacement therapy,and estrogens,when abnormally produced by adipose cells and persistently present in the stroma surrounding the mammary gland,may cause these hyperplastic lesions.

Treatment options for localised renal cell carcinoma of the transplanted kidney

Currently,there is no consensus among the transplant community about the treatment of renal cell carcinoma(RCC)of the transplanted kidney.Until recently,graftectomy was universally considered the golden standard,regardless of the characteristics of the neoplasm.Due to the encouraging results observed in native kidneys,conservative options such as nephron-sparing surgery(NSS)(enucleation and partial nephrectomy)and ablative therapy(radiofrequency ablation,cryoablation,microwave ablation,high-intensity focused ultrasound,and irreversible electroporation)have been progressively used in carefully selected recipients with early-stage allograft RCC.Available reports show excellent patient survival,optimal oncological outcome,and preserved renal function with acceptable complication rates.Nevertheless,the rarity and the heterogeneity of the disease,the number of options available,and the lack of long-term follow-up data do not allow to adequately define treatment-specific advantages and limitations.The role of active surveillance and immunosuppression management remain also debated.In order to offer a better insight into this difficult topic and to help clinicians choose the best therapy for their patients,we performed and extensive review of the literature.We focused on epidemiology,clinical presentation,diagnostic work up,staging strategies,tumour characteristics,treatment modalities,and follow-up protocols.Our research confirms that both NSS and focal ablation represent a valuable alternative to graftectomy for kidney transplant recipients with American Joint Committee on Cancer stage T1aN0M0 RCC.Data on T1bN0M0 lesions are scarce but suggest extra caution.Properly designed multi-centre prospective clinical trials are warranted.

Intestinal ischemic manifestations of SARS-CoV-2:Results from the ABDOCOVID multicentre study

BACKGROUND Intestinal ischemia has been described in case reports of patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)disease(coronavirus disease 19,COVID-19).AIM To define the clinical and histological,characteristics,as well as the outcome of ischemic gastrointestinal manifestations of SARS-CoV-2 infection.METHODS A structured retrospective collection was promoted among three tertiary referral centres during the first wave of the pandemic in northern Italy.Clinical,radiological,endoscopic and histological data of patients hospitalized for COVID-19 between March 1st and May 30th were reviewed.The diagnosis was established by consecutive analysis of all abdominal computed tomography(CT)scans performed.RESULTS Among 2929 patients,21(0.7%)showed gastrointestinal ischemic manifestations either as presenting symptom or during hospitalization.Abdominal CT showed bowel distention in 6 patients while signs of colitis/enteritis in 12.Three patients presented thrombosis of main abdominal veins.Endoscopy,when feasible,confirmed the diagnosis(6 patients).Surgical resection was necessary in 4/21 patients.Histological tissue examination showed distinctive features of endothelial inflammation in the small bowel and colon.Median hospital stay was 9 d with a mortality rate of 39%.CONCLUSION Gastrointestinal ischemia represents a rare manifestation of COVID-19.A high index of suspicion should lead to investigate this complication by CT scan,in the attempt to reduce its high mortality rate.Histology shows atypical feature of ischemia with important endotheliitis,probably linked to thrombotic microangiopathies.

Evaluation of Xpert MTB/RIF Ultra for Diagnosis of Extrapulmonary Tuberculosis: A Retrospective Analysis in a Low-Tuberculosis Prevalence Setting

Background: Extrapulmonary tuberculosis (EPTB) remains difficult to diagnose because the clinical specimens to be examined are often paucibacillary and obtained with difficulty from inaccessible sites. An updated Xpert® MTB/RIF Ultra (Ultra) test has been designed and licensed to improve sensitivity in the detection of Mycobacterium tuberculosis complex. The aim of the present study is to evaluate the performance of Ultra assay for the clinical diagnosis of EPTB in a low tuberculosis prevalence country. Methods: A retrospective analysis was performed at “A. O dei Colli” of Naples on consecutive extrapulmonary specimens for EPTB across a three-year period. All different types of extrapulmonary specimens were tested for EPTB by smear microscopy, culture and Ultra assay in accordance with relevant guidelines. Results: A total of 606 EPTB samples, 561 culture negative EPTB and 45 culture positive EPTB were included. Using culture as reference standard, the overall sensitivities and specificities of Ultra assay were 95.6% (95% CI 84.8 - 99.5) and 97.5% (95% CI 95.8 - 98.6) respectively. Sensitivity and specificity of Ultra for individual category of specimens were also performed. Conclusion: In a low-tuberculosis prevalence setting, Ultra assay confirms to have a good performance in the diagnosis of EPTB for all different extrapulmonary samples.

Minimally invasive valve surgery:pushing boundaries over the eighty

BACKGROUND Mean age of patients with valves diseases is significantly increasing,and,in the near future,cardiac surgeons will have to deal with a considerable number of patients aged more than 80 years.The remarkable results gained by the minimally invasive approach have encouraged its application in more complex and fragile patients,such as older people.This study aimed to identify the rate of early mortality and major complications,and independent predictors for mid-term mortality in octogenarians undergoing minimally invasive valve surgery.METHODS Octogenarian patients undergoing right mini-thoracotomy mitral and/or tricuspid valve surgery between 2006 and2020 were included.Primary endpoint was to identify independent predictors for mid-term mortality,and secondary endpoints were operative morality,stroke,independent predictors for early composite outcome,and quality of life at follow-up.RESULTS Analysis was performed on 130 patients.Stroke occurred in one patient(0.8%),while operative mortality was 6%(eight patients).One-year and five-year survival were 86% and 64%,respectively.Logistic regression identified age and creatinine level as independent predictors of mid-term mortality,survival analysis showed that age ≥ 84 years and creatinine level ≥ 1.22 mg/dL were the cut-off points for worst prognosis.Female gender and hypertension were found to be independent predictors of early composite outcome.CONCLUSIONS Results of the present study show that age alone should not be considered a contraindication for minimally invasive valve surgery.Identifying patients who are most likely to have survival and functional benefits after surgery is decisive to achieve optimal health outcomes and prevent futile procedures.

Is sibship composition a risk factor for childhood asthma? Systematic review and meta‑analysis

Background Following the“hygiene hypothesis”,the role of sibship composition in asthma and wheezing has been extensively studied,but the fndings are inconsistent.For the frst time,this systematic review and meta-analysis synthesized evidences from studies investigating the association of sibship size and birth order with risk of asthma and wheezing.Methods Fifteen databases were searched to identify eligible studies.Study selection and data extraction were performed independently by pairs of reviewers.Meta-analysis with robust variance estimation(RVE)was used to produce pooled risk ratio(RR)efect estimates from comparable numerical data.Results From 17,466 identifed records,158 reports of 134 studies(>3 million subjects)were included.Any wheezing in the last≤1.5 years occurred more frequently in infants with≥1 sibling[pooled RR 1.10,95%confdence interval(CI)1.02–1.19]and≥1 older sibling(pooled RR 1.16,95%CI 1.04–1.29).The pooled efect sizes for asthma were overall statistically nonsignifcant,although having≥1 older sibling was marginally protective for subjects aged≥6 years(pooled RR 0.93,95%CI 0.88–0.99).The efect estimates weakened in studies published after 2000 compared with earlier studies.Conclusions Being second-born or later and having at least one sibling is associated with a slightly increased risk of temporary wheezing in infancy.In contrast,being second-born or later is associated with marginal protection against asthma.These associations appear to have weakened since the turn of the millennium,possibly due to lifestyle changes and socioeconomic development.

New low-cost magnifying device for temporal bone laboratory

Temporal bone dissection has important role in educating and training oto and skull base surgeons.Mounting of a temporal bone laboratory is expensive.A dedicated magnifying system,such as a surgical microscope or an endoscopic equipment,represents one of the most significant costs.The aim of this study is to test and demonstrate the utility of a commercial USB as a low-cost solution to equip the laboratory with a good magnifying system and illumination.

Clinical significance of erectile dysfunction developing after acute coronary event： exception to the rule or confirmation of the artery size hypothesis？

Erectile dysfunction （ED） has been found to frequently precedes the onset of coronary artery disease （CAD）, representing an early marker of subclinical vascular disease, included CAD. Its recognition is, therefore, a ＂window opportunity＂ to prevent a coronary event by aggressive treatment of cardiovascular risk factors. The artery size hypothesis （ASH） has been proposed as a putative mechanism to explain the relationship between ED and CAD. Since atherosclerosis is a systemic disorder all major vascular beds should be affected to the same extent. However, symptoms at different points in the system rarely become evident at the same time. This is likely the result of smaller vessels （i.e. the penile artery） being able to less well tolerate the same amount of plaque when compared with larger ones （i.e. the coronary artery）. If true, ED will develop before CAD. We present a case in which ED developed after a coronary event yet before a coronary recurrence potentially representing a late marker of vascular progression. Reasons for this unusual sequence are discussed as they might still fit the ASH.

Old-fashioned and newly discovered biomarkers:the future of NAFLD-related HCC screening and monitoring

Nonalcoholic fatty liver disease(NAFLD)is the major contributor to the global burden of chronic liver diseases and ranges from simple and reversible steatosis to nonalcoholic steatohepatitis(NASH),which may progress into cirrhosis and hepatocellular carcinoma(HCC).HCC represents the most common liver cancer,and it is a leading cause of death worldwide with an increasing trend for the future.Due to late diagnosis,non-responsiveness to systemic therapy,and high cancer heterogeneity,the treatment of this malignancy is challenging.To date,liver biopsy and ultrasound(US)are the gold standard procedures for HCC diagnosis and surveillance,although they are not suitable for mass screening.Therefore,it is impelling to find new,less invasive diagnostic strategies able to detect HCC at an early stage as well as monitor tumor progression and recurrence.Common and rare inherited variations that boost the switching from NASH to liver cancer may help to predict tumor onset.Furthermore,epigenetic changes which reflect intertumoral heterogeneity occur early in tumorigenesis and are highly stable under pathologic conditions.The severity of hepatic injuries can be detected through the analysis of cell circulating tumor DNAs(ctDNAs),microRNAs(miRNAs),and noncoding RNAs(ncRNAs),which are involved in several pathological processes that feature cancer,including cell growth,survival,and differentiation,thus representing appealing biomarkers for HCC.Therefore,this review discusses the current options for HCC surveillance,focusing on the role of genetic and epigenetic biomarkers as new strategies to refine HCC management.