Follicular thyroid carcinoma: Differences in clinical relevance between minimally invasive and widely invasive tumors

Evidence on the biological behavior and clinical courses of minimally invasive and widely invasive follicular thyroid carcinoma (MI-FTC, WI-FTC) is still debatable. The current study was conducted to identify differences between MI and WI tumors and those prognostic parameters influencing late outcome such as local recurrence and survival

Autosomal-dominant myopia associated to a novel P4HA2 missense variant and defective collagen hydroxylation

We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole-exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations.We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole-exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations

Lower urinary tract symptoms and mental health during COVID-19 pandemic

Objective: Coronaviruses (CoVs) are a group of RNA viruses involved in several human diseases affecting respiratory, enteric, hepatic, and neurological systems. COVID-19 was identified in 2020 and was named SARS-CoV-2. To limit worldwide contagion, many countries instituted a lockdown, which conducted to disruption of routine life. In fact, pandemic was associated with several stresses among population, such as loss of employment, deaths of family members, friends, or colleagues, financial insecurity, and isolation. This led to long-lasting psychosocial effects as anxiety and depression, increasing the prevalence of stress and traumarelated disorders in the population. The aim of this study was to investigate the correlation between lower urinary tracts symptoms (LUTS) and stress/depressive symptoms during COVID-19 pandemic. Materials and methods: An anonymous cross-sectional webbased survey (comprehending anthropometric data, education level, occupation status, smoking and alcohol habits, current therapies, quarantine and COVID-19 infection status) was conducted from March to May 2020 in Italy. LUTS were examined through National Institute of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and Genitourinary Pain Index (GUPI). Hamilton Depression Rating Scale (HDRS) was utilized to evaluate depressive and anxiety symptoms. Non-parametric Kruskal-Wallis H Test was used for statistical analysis. Results: A total of 356 out of 461 subjects fully completed the survey, with a response rate of 77.2%. Data showed that subjects involved in economic difficulties, quarantine measures or with increased HDRS reported a significative statistic worsened urinary symptoms (H(3) = 11.731, p = 0.008), quality of life, (H(3) = 10.301, p = 0.016), total NIH-CPSI/GUPI score (H(3) = 42.150, p = 0.000), and quality of life (H(3) = 48.638, p = 0.000). Conclusions: COVID-19 pandemic provoked several alterations in everyday life. Although general lockdown, quarantine and social distancing have been necessary to prevent virus spreading, this had long term effects on all population in terms of mental and physical health. NIH-CPSI and GUPI scores increased linearly with stress and anxiety levels measured at HDRS, confirming worse LUTS in subjects who suffered anxiety and stress from COVID-19 pandemic

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains

Postoperative Management of Zygomatic Arch Fractures: In-House Rapid Prototyping System for the Manufacture of Protective Facial Shields

Zygomatic fractures account for 10% to 15% of all facial fractures. The surgical management of isolated zygomatic arch fractures usually requires open reduction treatment without fixation through an intraoral access. Therefore, the main problem in the non-fixed treatment of zygomatic arch fractures is related to the difficulty in obtaining a stable reduction for a period long enough to guarantee the physiological bone healing process. We propose an innovative "in-house" rapid prototyping (RP) protocol for the 3D-zygoma mask manufacture of a patient-specific protective device to apply after zygomatic arch fracture reduction. Our study includes 16 consecutive patients who underwent surgical open reduction for an isolated zygoma fracture without fixation between January 2017 and February 2018. The patients received regular postoperative checks at weeks 1 and 2. Before the device was removed, a multiple choice questionnaire was administered to measure the degree of wearability of the mask. The estimated cost of the production is around &OV0556;5 per case and the construction time is around 90 minutes. Based on the encouraging results, obtained in our experience, we hope that other studies can be conducted to confirm our procedure and improve its functionality in the field of facial trauma

Multiscale analysis of materials with anisotropic microstructure as micropolar continua

Multiscale procedures are often adopted for the continuum modeling of materials composed of a specific micro-structure. Generally, in mechanics of materials only two-scales are linked. In this work the original (fine) micro-scale description, thought as a composite material made of matrix and fibers/particles/crystals which can interact among them, and a scale-dependent continuum (coarse) macro-scale are linked via an energy equivalence criterion. In particular the multiscale strategy is proposed for deriving the constitutive relations of anisotropic composites with periodic microstructure and allows us to reduce the typically high computational cost of fully microscopic numerical analyses. At the microscopic level the material is described as a lattice system while at the macroscopic level the continuum is a micropolar continuum, whose material particles are endowed with orientation besides position. The derived constitutive relations account for shape, texture and orientation of inclusions as well as internal scale parameters, which account for size effects even in the elastic regime in the presence of geometrical and/or load singularities. Applications of this procedure concern polycrystals, wherein an important descriptor of the underlying microstructure gives the orientation of the crystal lattice of each grain, fiber reinforced composites, as well as masonry-like materials. In order to investigate the effects of micropolar constants in the presence of material non central symmetries, some numerical finite element simulations, with elements specifically formulated for micropolar media, are presented. The performed simulations, which extend several parametric analyses earlier performed [1], involve two-dimensional media, in the linear framework, subjected to compression loads distributed in a small portion of the medium

Identification of sixteen novel candidate genes for late onset Parkinson’s disease

Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis of PD. Methods The study includes a discovery stage based on the analysis of whole exome data from 26 dominant late onset PD families, a validation analysis performed on 1542 independent PD patients and 706 controls from different cohorts and the assessment of polygenic variants load in the Italian cohort (394 unrelated patients and 203 controls). Results Family-based approach identified 28 disrupting variants in 26 candidate genes for PD including PARK2, PINK1, DJ-1(PARK7), LRRK2, HTRA2, FBXO7, EIF4G1, DNAJC6, DNAJC13, SNCAIP, AIMP2, CHMP1A, GIPC1, HMOX2, HSPA8, IMMT, KIF21B, KIF24, MAN2C1, RHOT2, SLC25A39, SPTBN1, TMEM175, TOMM22, TVP23A and ZSCAN21. Sixteen of them have not been associated to PD before, were expressed in mesencephalon and were involved in pathways potentially deregulated in PD. Mutation analysis in independent cohorts disclosed a significant excess of highly deleterious variants in cases (p = 0.0001), supporting their role in PD. Moreover, we demonstrated that the co-inheritance of multiple rare variants (≥ 2) in the 26 genes may predict PD occurrence in about 20% of patients, both familial and sporadic cases, with high specificity (> 93%; p = 4.4 × 10− 5). Moreover, our data highlight the fact that the genetic landmarks of late onset PD does not systematically differ between sporadic and familial forms, especially in the case of small nuclear families and underline the importance of rare variants in the genetics of sporadic PD. Furthermore, patients carrying multiple rare variants showed higher risk of manifesting dyskinesia induced by levodopa treatment. Conclusions Besides confirming the extreme genetic heterogeneity of PD, these data provide novel insights into the genetic of the disease and may be relevant for its prediction, diagnosis and treatment

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Systematic review and meta-analysis on the impact of thrombolytic therapy in liver transplantation following donation after circulatory death

Aim: The livers from DCD (donation after cardiac death) donations are often envisaged as a possible option to bridge the gap between the availability and increasing demand of organs for liver transplantation. However, DCD livers possess a heightened risk for complications and represent a formidable management challenge. The aim of this study was to evaluate the effects of thrombolytic flush in DCD liver transplantation. Methods: An extensive search of the literature database was made on MEDLINE, EMBASE, Cochrane, Crossref, Scopus databases, and clinical trial registry on 20 September 2018 to assess the role of thrombolytic tissue plasminogen activator (tPA) flush in DCD liver transplantation. Results: A total of four studies with 249 patients in the tPA group and 178 patients in the non-tPA group were included. The pooled data revealed a significant decrease in ischemic-type biliary lesions (ITBLs) (P = 0.04), re-transplantation rate (P = 0.0001), and no increased requirement of blood transfusion (P = 0.16) with a better one year graft survival (P = 0.02). Conclusions: To recapitulate, tPA in DCD liver transplantation decreased the incidence of ITBLs, re-transplantation and markedly improved 1-year graft survival, without any increased risk for blood transfusion, hence it has potential to expand the boundaries of DCD liver transplantation

The role of normothermic perfusion In liver transplant (TRaNsIT Study): a systematic review of preliminary studies

Introduction: The success of liver transplantation has been limited by unavailability of suitable donor livers. The current organ preservation technique i.e static cold storage (SCS) is not suitable for marginal organs. Alternatively, normothermic machine perfusion (NMP) promises to recreate the physiological environment and thus provide better organ preservation. The objective of this systematic review, is to provide an overview on the safety, benefits and other potential useful parameters of NMP device. Material and Methods: We searched the current literature following registration in with the International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42018086034 for prospective trials comparing the role of NMP device to SCS in liver transplant by searching the PubMed, EMBASE, Cochrane, BIOSIS, Crossref, Scopus databases and clinical trial registry. Results: The literature search identified five prospective clinical trials (four early phase single institutional and single randomized multi-institutional) comparing 187 donor liver on NMP device to 275 donor livers on SCS. The primary outcome of interest was to assess the safety and graft survival at day 30 after transplant following NMP of the donor liver. Secondary outcomes included were early allograft dysfunction (EAD) in the first seven days; serum measures of liver functions as (bilirubin, aspartate aminotransferase (AST), alanine amino transferase(ALT), alkaline phosphatase (ALP), international normalized ratio (INR) on days 1–7; major complications as defined by a Clavien-Dindo score ≥3; patient & graft survival and biliary complications at six months. The peaked median AST level between day 1-7 in the five trials was from 417-1252 U/L (range 84-15009 U/L) while on NMP and 839-1474 U/L (range 153-8786 U/L) in SCS group. The median bilirubin level on day 7 was ranged from 25-79 μmol/L (range 8-344 μmol/l) and 30- 47.53 μmol/l (range 9-340 μmol/l) in NMP and SCS groups respectively. There was no reported PNF in either groups in the three trials. There was inter trial variability in EAD which ranged from 15-56% in NMP group while 23-30 in SCS group. Biliary complications in form of 6 months’ biliary stricture were observed in NMP group ranged from 0-20%. None of the three trials reported any machine failure, although inadvertent events of catheter occlusion (four events) in hepatic vein and bile duct or unrecognized twist in portal vein (single event) were reported. Conclusion: This review outlines that NMP not only demonstrated safety and efficacy but also provides the favourable environment of organ preservation, repair, and viability assessment to donor liver with low rate of complication as PNF, EAD and biliary complication following transplantation, however further studies are needed to broaden our horizon