Hepatocellular Carcinoma in 2021: An Exhaustive Update.

Primary liver cancer is a challenging global health concern with an estimated more than a million persons to be affected annually by the year 2025. The commonest type is hepatocellular carcinoma (HCC), which has been increasing in incidence the world over, mostly due to chronic viral hepatitis B infection. In the last decade, paradigm changes in the etiology, understanding of molecular biology, and pathogenesis, including the role of gut microbiota; medical and surgical treatments, and outcome trends are notable. The application of omics-based technology has helped us unlock the molecular and immune landscape of HCC, through which novel targets for drug treatment such as immune-checkpoint inhibitors have been identified. Novel tools for the surveillance and diagnosis of HCC include protein-, genomics-, and composite algorithm-based clinical/biomarker panels. Magnetic resonance imaging-based novel techniques have improved HCC diagnosis through ancillary features that enhance classical criteria while positron emission tomography has shown value in prognostication. Identification of the role of gut microbiota in the causation and progression of HCC has opened areas for novel therapeutic research. A select group of patients still benefit from modified surgical and early interventional radiology treatments. Improvements in radiotherapy protocols, identification of parameters of futility among radiological interventions, and the emergence of novel first-line systemic therapies that include a combination of antiangiogenic and immune-checkpoint inhibitors have seen a paradigm change in progression-free and overall survival. The current review is aimed at providing exhaustive updates on the etiology, molecular biology, biomarker diagnosis, imaging, and recommended treatment options in patients with HCC.

Stabilized zirconia ceramics for dental applications.

The research is aiming to obtain at room temperature a new ceramic material containing partially stabilized zirconia with different oxides after sintering used for dental and other technological purposes. Our research proposes a new method based on the use of stabilized zirconia with other oxides to obtain optimized dental material with a lower cost price and / or improved properties to allow wider use of these products to an increased number of patients in dental offices. X-ray diffraction, SEM analysis. FTIR spectroscopy, UVVis and density measurements were accomplished for the three ceramic systems. The correlation between the microstructure and the spectroscopic properties of zirconium stabilized by FTIR spectroscopy, UV-Vis helps understanding the mechanisms associated with the formation of high (tetragonal and / or cubic) temperature zirconia. Along with the simple, less costly preparation method and high purity of the ceramic products our study offers a highly desirable product for technological applications.

A systematic approach on the frequency of cleft lip/palate in pediatric patients with leukemia.

PURPOSE: The purpose of this study was to reveal the frequency between cleft lip/palate and leukemia in pediatric patients by a systematic analysis of the current literature. MATERIALS AND METHODS: Electronic search on three database (PubMed, Web of Science, Cochrane) was carried out using the following keywords: cleft lip, cleft palate, facial cleft, oral cleft, orofacial cleft, leukemia, acute myeloid leukemia, acute lymphocytic leukemia, lymphoma. Studies published until March 2020 reporting an association between leukemia and cleft lip/palate (CL/P) were included in our research. RESULTS: Five articles (2 case-controls, 3 cohorts), met the inclusion criteria. Case-control studies involved 268 patients with acute lymphocytic leukemia (ALL) and 177 patients with acute myeloid leukemia (AML), of which 9 patients had CL/P. The cohorts studies involved 10 patients with ALL, of which 6 patients with CL/P, 2 patients with cleft palate and 1 patient with cleft lip and palate. CONCLUSION: This research was able to indicate a limited evidence of the association between CL/P and leukemia. In order to draw a clear conclusion, studies with larger cohorts are needed to establish this correlation.

A retrospective, multi-center cohort study evaluating the severity- related effects of cerebrolysin treatment on clinical outcomes in traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and disability for which there is currently no effective drug therapy available. Because drugs targeting a single TBI pathological pathway have failed to show clinical efficacy to date, pleiotropic agents with effects on multiple mechanisms of secondary brain damage could represent an effective option to improve brain recovery and clinical outcome in TBI patients. In this multicenter retrospective study, we investigated severity-related efficacy and safety of the add-on therapy with two concentrations (20 ml/day or 30 ml/day) of Cerebrolysin (EVER Neuro Pharma, Austria) in TBI patients. Adjunctive treatment with Cerrebrolysin started within 48 hours after TBI and clinical outcomes were ranked according to the Glasgow Outcome Scale and the Modified Rankin Disability Score at 10 and 30 days post-TBI. Analyses of efficacy were performed separately for subgroups of patients with mild, moderate or severe TBI according to Glasgow Coma Scale scores at admission. Compared to standard medical care alone (control group), both doses of Cerebrolysin were associated with improved clinical outcome scores at 10 days post-TBI in mild patients and at 10 and 30 days in moderate and severe cases. A dose-dependent effect of Cerebrolysin on TBI recovery was supported by the dose-related differences and the significant correlations with treatment duration observed for outcome measures. The safety and tolerability of Cerebrolysin in TBI patients was very good. In conclusion, the results of this large retrospective study revealed that early Cerebrolysin treatment is safe and is associated to improved TBI outcome.

Real-time analysis of the effects of toxic, therapeutic and sub-therapeutic concentrations of digitoxin on lung cancer cells.

Digitoxin belongs to a naturally occurring class of cardiac glycosides (CG); digitoxin is clinically approved for heart failure and known for its anti-cancer effects against non-small lung cancer cells (NSCLC). However, concerns associated with its narrow therapeutic index and its concentration-dependent mechanism of action are rising. Thus, before digitoxin implementation in designing and developing safer and more effective CG-based anti-cancer therapies, its pharmacological and safety profiles need to be fully elucidated. In this research we used a combinatorial approach to evaluate the anti-cancer mechanisms of digitoxin in real-time. Our approach employed a non-invasive electric cell impedance sensing technique as a proxy to monitor NSCLC behavior post-exposure to toxic, therapeutic and sub-therapeutic concentrations of the drug. By developing structure-function combinatorial relations we showed that digitoxin targets cancer cells in a time and dose-dependant manner by activating pro-apoptotic and anti-proliferative signaling cascades that results in strengthening cellular adhesion and sequestration of key regulatory proliferation protein from the nucleus.

In vivo behavior of surface modified Ti6Al7Nb alloys used in selective laser melting for custom-made implants. A preliminary study.

The objectives of this study were to test the biocompatibility and to evaluate the osseointegration of Titanium-Aluminum-Niobium (Ti6Al7Nb) alloy used in the manufacturing of personalized implants with selective laser melting (SLM) technology and to compare the growth viability of osteoblastic-like cells on different Ti6Al7Nb alloy samples (plain, coated with hydroxyapatite or SiO2-TiO2) implanted into the cranial bone of Wistar rats. In terms of biocompatibility, the cone-beam computer-tomography head scans taken at the moment of sacrifice of each group (one, two and three months) showed no implant displacement, no osteolysis and no liquid collection around the implants. At one month, around all types of implants new bone formation was noticed, although around the plain Ti6Al7Nb implant a large amount of powder debris was present. Still, no inflammatory reaction was seen. At two months, the distance between the implants and the calvarial bone margins diminished. A thin layer of fibrous tissue was noticed around the Ti6Al7Nb implant coated with hydroxyapatite but no bone contact was achieved. In the group sacrificed at three months there was still no bone contact, but noticeable were the SiO2-TiO2. In the group sacrificed at three months SiO2-TiO2 particles detached from the implant and completely integrated in the tissue were noticeable. All results suggested that the Ti6Al7Nb alloy with or without infiltration is well biologically tolerated.

Single-walled carbon nanotube-induced mitotic disruption.

Carbon nanotubes were among the earliest products of nanotechnology and have many potential applications in medicine, electronics, and manufacturing. The low density, small size, and biological persistence of carbon nanotubes create challenges for exposure control and monitoring and make respiratory exposures to workers likely. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to 24, 48 and 96 µg/cm(2) single-walled carbon nanotubes (SWCNT). To investigate mitotic spindle aberrations at concentrations anticipated in exposed workers, primary and immortalized human airway epithelial cells were exposed to SWCNT for 24-72 h at doses equivalent to 20 weeks of exposure at the Permissible Exposure Limit for particulates not otherwise regulated. We have now demonstrated fragmented centrosomes, disrupted mitotic spindles and aneuploid chromosome number at those doses. The data further demonstrated multipolar mitotic spindles comprised 95% of the disrupted mitoses. The increased multipolar mitotic spindles were associated with an increased number of cells in the G2 phase of mitosis, indicating a mitotic checkpoint response. Nanotubes were observed in association with mitotic spindle microtubules, the centrosomes and condensed chromatin in cells exposed to 0.024, 0.24, 2.4 and 24 µg/cm(2) SWCNT. Three-dimensional reconstructions showed carbon nanotubes within the centrosome structure. The lower doses did not cause cytotoxicity or reduction in colony formation after 24h; however, after three days, significant cytotoxicity was observed in the SWCNT-exposed cells. Colony formation assays showed an increased proliferation seven days after exposure. Our results show significant disruption of the mitotic spindle by SWCNT at occupationally relevant doses. The increased proliferation that was observed in carbon nanotube-exposed cells indicates a greater potential to pass the genetic damage to daughter cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is an early event in the progression of many cancers, suggesting that it may play a role in both tumorigenesis and tumor progression. These results suggest caution should be used in the handling and processing of carbon nanotubes.

The effect of distraction rate on bone histological and histomorphometrical properties in an ovine mandible model.

UNLABELLED: Lengthening the mandible by distraction osteogenesis (DO) is nowadays a well-recognized technique in maxillofacial surgery. This study compared two different distraction rates and evaluated histological and histomorphometrical properties of the distracted bone in an experimental ovine mandible model with the goal of elaborating a universally accepted distraction protocol. STUDY DESIGN: Tissue blocks of regenerated bone were harvested from twelve young adult sheep. DO was performed on the mandibular midline after five days of latency period. The sheep were divided into two groups. The first group underwent activation of 0.8 mm÷day during 12 days resulting in 9.6 mm of new bone while the second group followed a geometric rate pattern of 0.2 mm - three days, 0.4 mm - three days, 0.8 mm - three days and 1.6 mm - three days resulting in 9 mm of new bone. The regenerated bone was histologically and histomorphometrically analyzed after 30, 45 and 60 days of consolidation. The relative osteoid volume (OV÷TTV) was significantly increased in the geometric rate distraction group (p=0.015) comparing with linear distraction group while the relative bone volume (BV÷TTV) was significantly increased in the linear distraction group (p=0.019) compared to the geometric distraction group.

Severe compartment syndrome following fibula harvesting for mandible reconstruction.

There are many reports of the use of free fibular flap for mandible reconstruction, but donor site morbidity is not uncommon. The authors present the case of a 52-year-old man who underwent mandible reconstruction with free fibular flap. After surgery, he developed severe compartment syndrome involving all four-calf compartments. Debridement of the necrotic areas was followed by posterior nerve neurolysis and soft tissue coverage with free latissimus dorsi and anterior serratus muscle flaps. The postoperative period was uneventful and the patient remained with diminished plantar sensation 1 year later. Compartment syndrome after fibula harvesting is a possibility and should be recognized as soon as possible in order to limit extensive damage to the calf muscles and nerves.

[The etiological aspects of acute abdominal pain in children]. / Aspecte etiologice ale durerii abdominale acute la copil.

AIM: The study of the etiological aspects of acute abdominal pain in children, in order to perceive the clinical-etiological correlations and the disorders distribution related to age, gender and the origin of the patients. MATERIAL AND METHODS: The criteria for including patients were age (between 0 and 18 years) and the presence of acute abdominal pain before or during the consultation with the physician. The research on acute abdominal pain in children was performed on the level of the Surgery and Pediatrics II clinical departments of the "Sf. Ioan" Children's Emergency Clinical Hospital in Galati, between 01.01.2009 - 01.01.2011. The clinical study performed on the patients registered in the studied groups focused on the identification, the evaluation of the symptoms of acute abdominal pain in children, diagnosing and treating it. The criteria for excluding patients were an age older than 18 years or the absence of acute abdominal pain as a symptom before or during the examination. The statistical analysis used the descriptive and analytical methods. The data was centralized and statistically processed in M.S.EXCEL and S.P.S.S. databases. RESULTS: The patients with acute abdominal pain represent a percentage of 92.9% (2358 cases) of the total number of patients who suffer from abdominal pain (N=2537). The highest frequency of cases is represented by acute appendicitis (1056 cases - 44.8%). In the 5-18 years age group, acute appendicitis, mesenteric lymphadenitis, ovarian follicular cysts, acute pyelenophritis and salpingitis are predominant. In the 0-4 years age group gastroenteritis, acute pharyngitis, reactive hepatitis and lower digestive bleeding are predominant. CONCLUSIONS: In females, acute appendicitis, gastroenteritis, gastroduodenitis and cystitis are predominant, whereas in males, peritonitis, sepsis through E. coli, the contusion of the abdominal wall and acute pharyngitis are predominant.

The influence of expansion on intraoperative bone blood flow in multisegmental maxillary osteotomies: an experimental study.

The aim of the presented study was to investigate the effect of maxillary expansion in multisegmental Le Fort I osteotomies on bone blood flow. Five sheep underwent a three-piece total maxillary osteotomy. Bone blood flow was measured intraoperatively by laser Doppler flowmetry in the premaxilla, the lateral segments and the mandible before osteotomy, after osteotomy and segmentation as well as after 4mm, 8mm and 12mm expansion with a Hyrax screw. A significant reduction in blood flow was seen after osteotomy and segmentation with a factor of 3.10 and between 4mm and 8mm expansion with a factor of 1.81. No significant differences could be found between 0mm and 4mm widening or between 8mm and 12mm widening. These results suggest that expansion of more than 4mm in multisegmental osteotomies enhances the risk of avascular sequelae. As greater maxillary widening has been carried out in many cases without avascular complications, further research on additional factors, influencing the recovery of perfusion, is needed.

[Treatment of arterio-venous high-flow vascular malformations of the mandible]. / Tratamentul malformatiilor vasculare arterio-venoase de flux înalt ale mandibulei.

Arterio-venous vascular malformations (AVM) rarely occur in craniofacial bones. The most frequent location has been reported in the mandible. The first clinical evidence of the lesions can be a fatal hemorrhage, occurring spontaneously or subsequent to dental therapy. Lack of knowledge about these lesions among specialists dealing with the oral and maxillofacial regions can lead to fatal complications. The study presents the successful multidisciplinary management of two cases of mandibular AVM using embolization, sclerotherapy and bone reconstruction, a major challenge owing to the substantial risk of morbidity, recurrence by recanalization and revascularization, neurologic deficits and mortality. There were no complications over a follow-up period of 12 years.

[A combined surgical-orthodontic approach of a class II/1 malocclusion. A case report]. / Tratamentul combinat chirurgical-ortodontic la un pacient cu o anomalie Angle clasa II/1. Prezentare de caz.

This case report highlights the possibility of a non extraction orthodontic treatment, surgically assisted, in a Class II Division 1 malocclusions in order to reduce maxillary protrusion prior to the surgical advancement of the mandible for the correction of the skeletal deficiency. The combined orthodontic-surgical approach optimizes the profile while allowing the settling of a Angle Class I occlusion at the end of the entire treatment sequence.

[Use of laser-therapy for treatment of oral and maxillofacial hemangioma]. / Utilizarea laserterapiei pentru tratamentul hemangioamelor orale si maxilofaciale.

UNLABELLED: Laser-therapy opened new perspectives for the treatment of vascular lesions of the maxillofacial regions. MATERIAL AND METHOD: The study evaluated the results of diode laser percutaneous coagulation of oral and maxillofacial hemangioma. A group of 12 patients with sonographically certified hemangioma was treated using percutaneous coagulation with a diode laser. RESULTS: The results showed good and rapid healing, without any complications. All patients presented size reduction of the lesions, a favorable esthetic appearance and no morbidity. There were no complications over a follow-up period of 3 years. The study recommends diode laser-therapy as a valuable treatment option for hemangioma in correctly selected indications.

Cellular motors for molecular manufacturing.

Cells are composed of macromolecular structures of various sizes that act individually or collectively to maintain their viability and perform their function within the organism. This review focuses on one structure, the microtubule, and one of the motor proteins that move along it, conventional kinesin (kinesin 1). Recent work on the cellular functions of kinesins, such as the organization of microtubules during cellular division and the movement of the organelles and vesicles, offers insights into how biological motors might prove useful for organizing structures in engineered environments.

Effect of calcium tablets on interpretation of lumbar spine DXA scans.

Undissolved calcium (Ca) tablets in the gastrointestinal tract at the time of a dual-energy X-ray absorptiometry (DXA) scan could conceivably affect the accuracy of the lumbar spine bone mineral density (BMD) determination. We studied phantoms and volunteers to determine the effect of Ca tablets overlying bone, Ca tablets in the soft-tissue field, and Ca tablets overlapping both bone and soft tissue. For L1-4, a 500-mg Ca tablet taped to the phantom surface or the skin of volunteers resulted in

[Algorithms for adding and subtracting noise levels]. / Algoritmi de (DES)compunere utili în audiologie când exista mai multe surse de zgomot.

Nowadays 7% of Europe's workers suffer from work related hearing difficulties and noise induced hearing loss is among the most commonly reported occupational diseases in the E.U. In this situation the occupational health physician has to evaluate the noise level especially in industrial environment in order to help the patients and the employers to prevent the noise irreversible health damages. This material presents two simple algorithms to be used to calculate the resulting noise level when composing noise sources. Personal contributions.

[Specific effects upon hearing due to occupational noise]. / Efectele otice specifice ale expunerii la zgomot profesional.

Every day, millions of employees are exposed to noise at work and at the risks this can entail. While the noise is most obviously in industries such as manufacturing and construction, it can also be an issue in a wide range of other working environments. One in five workers have to raise their voice to be heard for at least half of the time when they are at work. This paper shortly presents the physical aspects of the noise and its dangerous local level effects on the human body.

Rydberg state ionization by half-cycle-pulse excitation: strong kicks create slow electrons.

The asymptotic velocity distribution of electrons ionized in half-cycle-pulse excitation of high Rydberg states (n=34), placed in a static electric field, is studied using electron velocity-map imaging. At weak half-cycle pulse strengths, the electrons escape over the saddle point in the potential. For strong half-cycle pulses, the electrons are emitted in the direction of the field kick. The much slower and less intense half cycle of opposite polarity, which necessarily follows the main half-cycle pulse, strongly affects the momentum distribution and reduces the excess energy of the electrons significantly.

Therapeutical aspects of the plasmocytoma localized at the level of head and neck.

The authors present a study on 7 cases of extramedullary plasmocytoma localized in E.N.T. area, hospitalized and solved in the E.N.T. Department of the the "Sf. Spiridon" Universitary Hospital, in the last 15 years, between 1983-1997. We insist on the last solved case, presenting a double isolated localization, a laryngeal and a rhinosinusal one. We consider that the most indicated treatment in the isolated extramedullary plasmocytoma, is the radiosurgical therapy with a good rate of survival.