Pre-existing Pathological Conditions Research Articles

Fatal diving accidents in Genoa (North-West Italy) from 1968 to 2021: Forensic approach and literature review

Scuba diving is one of the most common and practised water sport activities in Genoa, especially in the more recent years. Although scuba diving is generally considered a safe activity, this does not exclude the possibility of serious or fatal accidents from happening.This retrospective study investigates the case history of deaths resulting from diving accidents recorded by the Municipal Morgue of Genoa over a period of 53 years, specifically from 1968 to 2021.Of the total 52 deaths covered by the study, 48 were male with an age range of 16–71 years. In 25 of these subjects, pre-existing pathological conditions of a cardiovascular nature, not recognised at the time of death, were reported. Out of the total deaths studied, 9 subjects died following a diving accident related to free diving, while 43 subjects died from scuba or rebreather diving. Among the latter subjects, the cause of death was attributed to drowning in 17 cases, arterial gas embolism (AGE) from pulmonary over-distension in 11 cases, cardio-circulatory arrest (CA) favoured by pre-existing and non-existing heart disease known prior to the death in 10 cases, decompression sickness (DCS) in 2 cases, a combination of DCS and AGE in 2 cases and oxygen intoxication in 1 case.Twelve of the fatal accidents occurred in the marine area near the village of Arenzano, where the shipwreck of the oil tanker, the “Haven”, sank in 1991 and is today the largest shipwreck explored by divers in the Mediterranean Sea.In all cases of diving deaths, a multi-disciplinary approach is important: in particular, the role of the forensic pathologist is essential in order to accurately reconstruct the dynamics of the accident, thus identifying the predisposing or triggering factors that led to death, and defining the cause of it.

Relação entre a pandemia da COVID-19 e os resultados de mortes de causas externas – o antes e o durante

ntroduction: Deaths from external causes are those that result from an exogenous and harmful action to the individual, or that worsen a preexisting pathological condition, so that there is a cause and effect relationship between aggression and death. These deaths are directly related to human activities, as well as existing environmental phenomena in the world, such as the pandemic that started in December 2019, as a result of covid-19, a disease caused by the SARS-CoV-2 virus. Objectives: This study aimed to analyze a possible change in the profile of deaths from external causes based on cadaveric reports from the Instituto Médico Legal Estácio de Lima, in Maceió/AL in a pre-pandemic period (2018 and 2019) and with the pandemic in force (2020 and 2021). Material and method: This was a documentary, epidemiological, descriptive, and analytical study through sampling. The research analyzed a sample of 1824 cadaveric reports from the IML Estácio de Lima archive from 2018 to 2021. Results: Comparing the period 2018-2019, without a pandemic, with the years 2020-2021 in which the pandemic was in progress, the percentage of deaths from external causes increased from 87.83% to 90.13%. The predominant gender was male, ranging from 82.24% to 87.5% of the cases. Homicides increased from 48.46% in the 2018/2019 biennium to 45.94% in the 2020/2021 biennium. Suicides decreased by 0.88%. Deaths from undetermined causes rose from 3.73% in the first biennium analyzed, to 10.42% in the pandemic period. Mechanical energy had the highest prevalence in all years, with the blunt punch instrument being the most prevalent in the years 2018, 2019 and 2020 and the blunt instrument in the year 2021. Discussion: The covid-19 pandemic has had an impact on deaths from external causes in its modalities and variables, in addition to generating changes in the forensic activities of the IML Estácio de Lima, leading to a greater number of deaths from undetermined causes, probably due to the limitations arising from the covid-19 pandemic, such as protocols created to prevent the spread of the virus to those involved in the necroscopic expertise. Conclusion: The covid-19 pandemic changed the social context, human activities and, consequently, the profile of deaths from external causes, due to changes aimed at containing cases of the disease.

Pathogenetic correlation of severe sepsis and multiple organ dysfunction syndrome provoked by multiple infections in perinatal period of women

Introduction. Despite significant advances in diagnosis, medical management and antimicrobial therapy, sepsis in the puerperium remains an important cause of maternal morbidity and mortality. The abnormalities associated with the clinical syndrome of sepsis result from a nonspecific innate inflammatory response. This is due to the fact that sepsis represents a systemic inflammatory response syndrome (SIRS) to infection or injury; therefore, it can rapidly progress to septic shock and death despite aggressive treatment. Severe sepsis with MODS has a mortality rate of 20– 40%, rising to around 60% if septicemic shock develops. Symptoms of sepsis may be less distinctive than in the non-pregnant population and are not necessarily present in all cases; therefore, a high index of suspicion is necessary. The major pathogens causing sepsis in the puerperium are: group A streptococcus (GAS), also known as Streptococcus pyogenes, Escherichia coli, Staphylococcus aureus, Streptococcus pneumonia, methicillin-resistant S. aureus (MRSA), Clostridium septicum, Morganella morganii and antibiotic-resistant Stenotrophomonas Moltrophilia. Multiple risk factors for maternal sepsis have been identified: obesity, impaired glucose tolerance/diabetes, impaired immunity/immunosuppressant medication, anemia, vaginal discharge, history of pelvic infection, amniocentesis and other invasive procedures, cervical cerclage, prolonged spontaneous rupture of membranes, caesarean section, wound hematomas, retained products of conception, GAS infection, vaginal trauma. Material and methods. Presentation of case report using the following key-words: „infection”, „systemic inflammatory response syndrome (SIRS)”, „severe sepsis”, „septic shock”, „multiorgan dysfunction syndrome (MODS)”. Results. We present a case of perinatal infections complicated with MODS. Conclusions. The presence of pelvic hematomas triggers the sepsis caused by multiple infections in perinatal period and can significantly increase the morbidity related to bleeding, infection, surgery and blood product transfusion. The clinical situation may worsen in the presence of pre-existing pathological conditions before pregnancy.

The Role and Implications of Epicardial Fat in Coronary Atherosclerotic Disease

The current minireview aims to assess the implications of epicardial fat secretory function in the development of coronary artery disease. The epicardial adipose tissue (EAT) is a visceral fat depot that has been described as a cardiovascular risk factor. In addition to its mechanical protection role and physiological secretory function, it seems that various secretion products of the epicardial fat are responsible for metabolic disturbances at the level of the cardiac muscle when in association with pre-existing pathological conditions, such as metabolic syndrome. There is a pathological reduction in sarcomere shortening, abnormal cytosolic Ca2+ fluxes, reduced expression of sarcoplasmic endoplasmic reticulum ATPase 2a and decreased insulin-mediated Akt-Ser473-phosphorylation in association with abnormal levels of epicardial fat tissue. Activin A, angiopoietin-2, and CD14-positive monocytes selectively accumulate in the diseased myocardium, resulting in reduced cardiomyocyte contractile function. At the same time, it is believed that these alterations in secretory products directly decrease the myocyte function via molecular changes, thus contributing to the development of coronary disease when certain comorbidities are associated.

Acute Esophageal Necrosis (Black Esophagus): An Autopsy Case Series

Introduction: Acute esophageal necrosis (AEN), also known as black esophagus and acute necrotizing esophagitis, is a rare pathologic finding of unknown etiology. It was first characterized as diffuse, circumferential black discoloration of the esophageal mucosa that affects predominantly the distal esophagus with sharp transition to normal-appearing mucosa at the gastroesophageal junction. Case frequency of AEN remains low and mainly found incidentally, with up to 0.2% in autopsy and endoscopy studies. Men are 4 times more commonly affected and overall mortality is approximately 32%. Methods: Black esophagus was incidentally found during ten forensic autopsy cases. Complete autopsies with photographs, histological examination, and toxicological analysis were performed. Case background information was reviewed. A review of literature was done, with research criteria including previous case reports, diagnosis, and autopsy, endoscopic, and microscopic findings of AEN. Results: Nine of ten deceased were male, with an age range of 26 to 67 years old. The most common preexisting pathological condition was chronic alcohol consumption, seen in six of ten cases, and in eight cases, the death occurred suddenly at home. “Classic” black esophagus was only seen in four cases. Upper gastrointestinal hemorrhage due to acute necrotizing esophagitis was established as the immediate cause of death in six of ten cases. Discussion: This case series demonstrates ten cases of AEN with variation in appearance, yet diagnosis supported by histology, ancillary testing, and case information. The case frequency was higher than previously reported, 0.7%, suggesting that the prevalence of AEN may be underestimated, especially in forensic death investigations.

Biomarkers of Glyco-Metabolic Control in Hemodialysis Patients: Glycated Hemoglobin vs. Glycated Albumin.

Background and Objectives: Glycated hemoglobin (HbA1c) dosage is considered the gold standard in glycol-metabolic monitoring, but it presents limits, which can underestimate the glycemia trend. In this regard, it was introduced the glycated albumin (GA). The aim of the study is to verify the predictivity of the GA compared to HbA1c in identifying glyco-metabolic alterations in non-diabetic and diabetic hemodialysis (HD) patients. Materials and Methods: For this purpose, we conducted a multicenter study involving one analysis laboratory and six dialysis centers in the Lazio region (Rome, Italy). Both diabetic and non-diabetic HD patients represent the study population, and the protocol included five time points. Results: The analyzed data highlighted the ability of GA to predict changes in glycemic metabolism in HD patients, and GA values are not significantly influenced, like HbA1c, by dialysis therapy itself and by comorbidities of the uremic state, such as normochromic and normocytic anemia. Thus, GA seems to reflect early glyco-metabolic alterations, both in patients with a previous diagnosis of diabetes and in subjects without diabetes mellitus. As part of this study, we analyzed two HD patients (one diabetic and one non-diabetic) in which GA was more predictive of glycol-metabolic alterations compared to HbA1c. Our study confirms the need to compare classical biomarkers used for the monitoring of glyco-metabolic alterations with new ones, likely more reliable and effective in specific subgroups of patients in which the classic biomarkers can be influenced by the preexisting pathological conditions. Conclusions: In conclusion, our evidence highlights that in uremic patients, GA shows a better ability to predict glyco-metabolic alterations allowing both an earlier diagnosis of DM and a prompt modulation of the hypoglycemic therapy, thus improving the clinical management of these patients.

Neues zu Hypertonie und Diabetes

Hypertonie und Diabetes treten oft gemeinsam auf und erhöhen die kardiovaskuläre Mortalität. Beide Erkrankungen sind bei COVID-19-Patienten (COVID-19: „coronavirus disease 2019“) mit schweren Verläufen gehäuft anzutreffen. Hinsichtlich der Kausalität für COVID-19 ist die Datenlage widersprüchlich. Sicher ist ein Surrogateffekt, da meiste ältere COVID-19-Patienten einen schweren Verlauf aufgrund der Vorschäden aufweisen. Hemmer des Renin-Angiotensin-Aldosteron-Systems (RAAS-Blocker) erhöhen nicht die Wahrscheinlichkeit der positiven SARS-CoV-2-Testung (SARS-CoV-2: „severe acute respiratory syndrome coronavirus 2“). Sie haben keinen Einfluss auf die Schwere des Verlaufs und die Mortalität und sollten daher unter COVID-19 nicht pausiert/abgesetzt werden. Die renale Denervierung erfreut sich einer Renaissance, nachdem sich die Studiendesigns und Technologien stark weiterentwickelt haben. Bei den SGLT-2-Hemmern (SGLT-2: „sodium glucose linked transporter 2“) ist der Wissenszuwachs enorm. In den ersten beiden großen randomisierten kontrollierten Studien mit primären renalen Endpunkten verzögerten sie die Progression der chronischen Niereninsuffizienz (CKD) bis zum Dialysebeginn deutlich um zusätzliche ca. 12–13 Jahre. Sie sind prinzipiell bei Typ‑2- sowie Typ-1-Diabetes und auch bei herzinsuffizienten Patienten mit und ohne Diabetes einsetzbar und reduzieren den systolischen Blutdruck. Der nichtsteroidale Mineralokortikoidrezeptorantagonist (MRA) Finerenon wirkt bei Typ‑2-Diabetes reno- und kardioprotektiv bezüglich kardiovaskulärer Mortalität und Niereninsuffizienz. Wie bei den klassischen MRA kann es auch hier zur Hyperkaliämie in höheren CKD-Bereichen kommen. Größere Vergleichsstudien zu den klassischen MRA liegen nicht vor. Die Zulassung in Deutschland steht noch aus.

Oral health problems in high-performance athletes at 2019 Pan American Games in Lima: a descriptive study

IntroductionDental care is provided for high-performance athletes at national and international sports events. Elite athletes may seek care for sports-related injuries and pre-existing oral diseases. Previous studies indicate an association between oral health problems and negative performance impacts in elite athletes.ObjectivesTo determine the prevalence of the most common oral pathologies in high-performance athletes during the emergency dental care performed at the Lima 2019 Pan American Games (JPL-19).MethodologyAll reports of athletes (≥18 years old, of both sexes, from 41 countries) who received emergency dental care at Pan American Villas during the JPL-19 were included. Injuries and types of oral diseases were classified according to the Injury and Disease Surveillance System proposed by the International Olympic Committee.ResultsOf the 6680 participating athletes, 76 (1.14%) presented as dental emergencies, 90.8% (69/76) of the athletes seen presented pre-existing oral pathological conditions, the most frequent were periodontal diseases (34%, 26/76) and dental caries (29%, 22/76). Among the sports with the most cases, there were 22 (29%) in athletics, 6 (8%) in soccer, and 6 (8%) in taekwondo. The most frequent dental emergencies came from Peru, Puerto Rico, Bahamas, Grenada, and Venezuela.ConclusionsPre-existing oral diseases were more frequent than sports-related accidents. The most prevalent diseases were periodontal disease and dental caries disease. It is necessary to implement new care strategies for athletes, based on prevention, before and during sports competitions.

Correlation study between anatomopathological data and levels of blood morphine concentrations in heroin-related deaths.

Heroin-related mortality is a complex phenomenon involving several factors that make an individual more susceptible to opioid toxicity. Among these, pre-existing pathological conditions play an important role. The current paper reviewed 51 autopsied cases performed over the last 30years, each subject ("frequent heroin user") having taken heroin intravenously alone before death. For each case, total blood morphine concentration determined by gas chromatography-mass spectrometry (GC-MS) was obtained from the archives. For histopathological evaluation we examined microscopic sections of the heart, lung, brain, liver and kidney, and for each organ a score table with a numerical value from 1 to 5, as an indicator of increasing severity, was drawn up. Finally, we created a scoring system based on the Injury Severity Score (ISS), generated by the sum of the squares of the three highest organ scores. We investigated the relationship between total blood morphine value (mg/l) and pathological score by inserting the two variables in a linear regression model: Score=a+b·Morphinemia (p-value <0.001). The results demonstrated a statistically significant correlation between the two variables: individuals with low total blood morphine values tended to have a higher pathological score. Our study provides useful assessment tools for forensic practice, confirming the need to combine two important disciplines in drug death investigation: forensic pathology and toxicology.

A Postmortem Portrait of the Coronavirus Disease 2019 (COVID-19) Pandemic: A Large Multi-institutional Autopsy Survey Study

This study represents the largest compilation to date of clinical and postmortem data from decedents with coronavirus disease 2019 (COVID-19). It will augment previously published small series of autopsy case reports, refine clinicopathologic considerations, and improve the accuracy of future vital statistical reporting. To accurately reflect the preexisting diseases and pathologic conditions of decedents with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection through autopsy. Comprehensive data from 135 autopsy evaluations of COVID-19-positive decedents is presented, including histologic assessment. Postmortem examinations were performed by 36 pathologists at 19 medical centers or forensic institutions in the United States and Brazil. Data from each autopsy were collected through the online submission of multiple-choice and open-ended survey responses. Patients dying of or with COVID-19 had an average of 8.89 pathologic conditions documented at autopsy, spanning a combination of prior chronic disease and acute conditions acquired during hospitalization. Virtually all decedents were cited as having more than 1 preexisting condition, encompassing an average of 2.88 such diseases each. Clinical conditions during terminal hospitalization were cited 395 times for the 135 autopsied decedents and predominantly encompassed acute failure of multiple organ systems and/or impaired coagulation. Myocarditis was rarely cited. Cause-of-death statements in both autopsy reports and death certificates may not encompass the severity or spectrum of comorbid conditions in those dying of or with COVID-19. If supported by additional research, this finding may have implications for public health decisions and reporting moving forward through the pandemic.

Long-Term Ligature-Induced Periodontitis Exacerbates Development of Bisphosphonate-Related Osteonecrosis of the Jaw in Mice.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a detrimental intraoral lesion that occurs in patients with long-term or high-dose use of anti-resorptive agents such as bisphosphonates. Tooth extraction is a known risk factor for BRONJ, and such intervention is often performed to eliminate existing pathological inflammatory conditions. Previously, we determined that ligature-induced periodontitis (LIP) is a risk factor for the development of osteonecrosis in mice, but it remains unclear whether the chronicity of LIP followed by extraction influences osteonecrosis development. In this study, we assess the effect of short-term and long-term LIP (ligature placed for 3 weeks [S-LIP] or 10 weeks [L-LIP], respectively) on osteonecrosis development in mice receiving 250 μg/kg/week zoledronic acid (ZOL). When compared to S-LIP, L-LIP caused 70% (p≤ 0.0014) more bone loss without altering microbe composition. In the presence of ZOL, bone loss mediated by LIP was prevented and bone necrosis was induced. When the ligated tooth was extracted, histologic hallmarks of osteonecrosis including empty lacunae and necrotic bone were increased by 88% (p= 0.0374) and 114% (p= 0.0457), respectively, in L-LIP compared to S-LIP. We also observed significant increases in serum platelet factor 4 (PF4) and macrophage inflammatory factor 1 γ (MIP1γ) in mice that received ZOL treatment and had tooth extractions compared to controls, which may be systemic markers of inflammation-associated osteonecrosis development. Additionally, CD3+ T cells were identified as the major immune population in both health and disease, and we observed a 116% (p= 0.0402) increase in CD3+IL23R+ T cells in L-LIP compared to S-LIP lesions following extraction. Taken together, our study reveals that extracting a periodontally compromised tooth increases the formation of necrotic bone compared to extracting a periodontally healthy tooth and that osteonecrosis may be associated with the duration of the preexisting pathological inflammatory conditions. © 2022 American Society for Bone and Mineral Research (ASBMR).

Removal of Pre-Existing Periodontal Inflammatory Condition before Tooth Extraction Ameliorates Medication-Related Osteonecrosis of the Jaw–Like Lesion in Mice

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but detrimental intraoral lesion that predominantly occurs in patients with long-term use of antiresorptive agents, such as bisphosphonate and denosumab, a human anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody (Ab). Surgical intervention, such as tooth extraction, is a known risk factor for MRONJ, which is often performed to eliminate preexiting pathologic inflammatory conditions, such as periodontal diseases. Nonetheless, it remains unknown whether pre-existing periodontal disease condition exacerbates, or removal of such condition ameliorates, MRONJ development after tooth extraction. In this study, we combined the ligature-induced periodontitis and the tooth extraction mouse models under the administration of zoledronic acid (ZOL) or anti-RANKL Ab, and provide experimental evidence that a pre-existing pathologic inflammatory condition exacerbates MRONJ development after tooth extraction in mice. Under ZOL administration, tooth extraction alone induced ONJ lesions; however, extraction of a ligature-placed tooth further exacerbated ONJ development. When the ligature was removed and theinflammatory condition was deescalated, ONJ development was ameliorated. Anti-RANKL Ab administration resulted in similar outcomes. Interestingly, unlike ZOL-administered mice, anti-RANKL Ab-administered mice exhibited complete absence of osteoclasts, suggesting that physical presence of osteoclasts is not directly involved in ONJ development. Collectively, our study demonstrated that periodontal disease is a functionally linked risk factor that predisposes ONJ development after tooth extraction in the presence of bisphosphonate and denosumab.

New non-invasive indexes of arterial stiffness are significantly correlated with severity and complexity of coronary atherosclerosis

ABSTRACTBackground: Endothelial dysfunction and increased arterial stiffness gradually develop before the manifestation of catastrophic cardiovascular events. Therefore, detection and assessment of vascular function are required to address pre-existing pathological conditions. However, the currently available diagnostic devices and methods are insufficient due to variability among investigators and the time-consuming nature of manual procedures. Methods: Recently, novel devices were developed for the detection of both arterial stiffness and endothelial dysfunction in a single blood pressure measurement using a cuff-oscillometric technique (AVE-1500, Shisei Datum, Japan). API (arterial pressure volume index) is defined as the reciprocal of the slope of the tangent of the brachial artery pressure-volume curve, and AVI (arterial velocity pulse index) is defined as the ratio of the difference between the ejection and reflection waves. In the present study, we performed retrospective, cross-sectional analyses of subjects (n = 102; mean age = 70.5 ± 10.4 years) with detailed coronary angiographic examinations and clinical background parameters. Results: After adjusting for various variables using multiple linear regression analyses, we found that API, but not AVI, was significantly correlated with coronary artery severity and complexity scores. Conclusions: We propose that API may be a new vascular index useful for monitoring and assessing the severity and complexity of atherosclerosis in subjects with coronary artery disease and for evaluating atherosclerotic diseases.

Mechanical Asphyxia with Ascaris lumbricoides - A Forensic Case Report

Ascaris lumbricoides is a nematode (roundworm), a parasite which inhabits the intestines of humans. This organism is responsible for the infective disease named ascariasis (a type of helminthiasis) which is prevalent in deprived areas where there is often a combination of poor sanitation and a host made vulnerable by iron-deficiency anaemia, malnutrition or impairment of growth. We present a violent death case; A child aged two, who died of mechanical asphyxia that followed airway obstruction by worms of the species Ascaris lumbricoides. Death was considered a forensic case because it occurred suddenly and the child was not known with pre-existing pathological conditions. We examined this case according to the information received from the criminalistics team correlated with the macroscopic autopsy findings and histopathological examinations with results being consistent and which indicated the diagnosis of death aforementioned. The literature cites such deaths which occurred consecutively to trauma or post general anesthesia, but in this situation a possible previous injury was infirmed by necropsy and according to the criminalistics team data the child never suffered a general anesthesia, which makes us consider this particular case as a rarely seen one.

Preexisting Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced Bisphosphonate-related Osteonecrosis of the Jaw Lesions in Mice

IntroductionSurgical interventions such as tooth extraction increase the chances of developing osteonecrosis of the jaw in patients receiving bisphosphonates (BPs) for the treatment of bone-related diseases. Tooth extraction is often performed to eliminate preexisting pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related osteonecrosis of the jaw (BRONJ) development after tooth extraction is not clearly defined. Here, we examined the effects of periapical periodontitis on tooth extraction–induced BRONJ development in mice. MethodsPeriapical periodontitis was induced by exposing the pulp of the maxillary first molar for 3 weeks in C57/BL6 mice that were intravenously administered with BPs. The same tooth was extracted, and after an 3 additional weeks, the mice were harvested for histologic, histomorphometric, and histochemical staining analyses. ResultsPulp exposure induced periapical radiolucency as shown by increased inflammatory cells, tartrate-resistant acid phosphatase–positive osteoclasts, and bone resorption. When BPs were administered, pulp exposure did not induce apical bone resorption despite the presence of inflammatory cells and tartrate-resistant acid phosphatase–positive osteoclasts. Although tooth extraction alone induced BRONJ lesions, pulp exposure further increased tooth extraction-induced BRONJ development as shown by the presence of more bone necrosis. ConclusionsOur study demonstrates that a preexisting pathological inflammatory condition such as periapical periodontitis is a predisposing factor that may exacerbate BRONJ development after tooth extraction. Our study further provides a clinical implication wherein periapical periodontitis should be controlled before performing tooth extraction in BP users in order to reduce the risk of developing BRONJ.

Forensic medical characteristic of the causes behind sudden death in the young subjects

The objective of the present study was to analyze the causes of sudden death in the general population and in the fraction of the young subjects (below 39 years of age). The results of the original retrospective study were obtained in the course of forensic medical autopsies of the subjects aged below 39 years that had been carried out during a period of 10 years. It was shown that one of the causes behind sudden death among the young subjects is cardiovascular disorders associated with the pre-existing pathological condition in the form of connective tissue dysplasia. The principal mechanism underlying sudden death among the young subjects has an arrhythmogenic nature. The development of terminal symptoms is promoted by a number of provocative factors including sporting activities, physical loading, psychoemotional stress, and alcohol consumption.

Phenytoin versus Levetiracetam for Prevention of Early Posttraumatic Seizures: A Prospective Comparative Study

Background Antiepileptic drugs are routinely given for the prevention of early posttraumatic seizures (EPTS) occurring within the first 7 days after traumatic brain injury. The objective of this study was to compare phenytoin with levetiracetam in their effectiveness for prophylaxis for EPTS. Method This single-blinded, prospective randomized study included 100 consecutive admitted patients at our center during a 3-month period from February 1, 2014, to April 30, 2014. Patients with preexisting seizure disorders and pathological brain conditions were excluded from the study. The patients were alternately assigned to a group receiving phenytoin (group P) or a group receiving levetiracetam (group L). Group P patients received phenytoin intravenously at 18 mg/kg as a loading dose followed by a maintenance dose of 5 mg/kg with phenytoin level monitoring. Group L patients received levetiracetam at a dose of 20 mg/kg loading dose and 20 mg/kg/d maintenance dose. A comparative study was done for the occurrence of EPTS and adverse effects in the two groups. Results One patient in group L ( n = 50) and four patients in group P ( n = 50) developed EPTS after initiating treatment, but this was not statistically significant ( p = 0.362 with odds ratio, OR = 0.24 [95% confidence interval, CI: 0.03–2.17]). There was no statistically significant difference between the two groups in the incidence of drug adverse effects ( p = 0.617 with OR = 0.32 [95% CI: 0.03–3.18]). Adverse effects such as poor glycemic control, ataxia, nystagmus, or giddiness were seen in three patients in group P. One patient in group L had sinus bradycardia. Toxic serum drug levels (> 20 µg/mL) were observed in 6 of 50 (12%) patients of group P. Conclusion There was no significant difference in the occurrence of their adverse effects, but the adverse effects because of the phenytoin were more troublesome. Levetiracetam had a better safety profile than phenytoin and it was equally efficacious for the prevention of EPTS.

Oral inflammation and bacteremia: implications for chronic and acute systemic diseases involving major organs.

Gingivitis and periodontitis are both highly prevalent gum diseases characterized by an accumulation of a polymicrobial biofilm (dental plaque) around teeth and inflammation in adjacent soft tissues. During dental procedures, even tooth brushing, these bacteria and their components, such as endotoxin, can easily disseminate into the systemic circulation through minor or major gingival injuries. Particularly in immuno-compromised subjects or patients with preexisting pathologic conditions, bacteremia may lead to bacterial infection of distant organs, which may cause immunological reactions. Oral bacteria and endotoxins have been found in sepsis, infective endocarditis, lung infection, liver disease and many other potentially lethal disorders. This article presents a review of the possible pathologic consequences of bacteremia originating in the oral cavity and points out the most commonly affected organs as well as preventive and treatment measures. At the present time, plaque control by subjects and/or dental professionals is one of the most effective means to prevent the onset and progression of oral bacteremia-induced systemic diseases.

Molecular mechanisms underlying chemical liver injury

The liver is necessary for survival. Its strategic localisation, blood flow and prominent role in the metabolism of xenobiotics render this organ particularly susceptible to injury by chemicals to which we are ubiquitously exposed. The pathogenesis of most chemical-induced liver injuries is initiated by the metabolic conversion of chemicals into reactive intermediate species, such as electrophilic compounds or free radicals, which can potentially alter the structure and function of cellular macromolecules. Many reactive intermediate species can produce oxidative stress, which can be equally detrimental to the cell. When protective defences are overwhelmed by excess toxicant insult, the effects of reactive intermediate species lead to deregulation of cell signalling pathways and dysfunction of biomolecules, leading to failure of target organelles and eventual cell death. A myriad of genetic factors determine the susceptibility of specific individuals to chemical-induced liver injury. Environmental factors, lifestyle choices and pre-existing pathological conditions also have roles in the pathogenesis of chemical liver injury. Research aimed at elucidating the molecular mechanism of the pathogenesis of chemical-induced liver diseases is fundamental for preventing or devising new modalities of treatment for liver injury by chemicals.

Encephalopathy in a dialysis patient treated with lanthanum carbonate (LC).

Sir, Dr Fraile et al. [1] report the interesting case of a dialysis patient who was treated with lanthanum carbonate (LC; 2000 mg daily for 8 months increased to 3500 mg daily for the subsequent 10 months) and developed acute confusional syndrome. Conduct disorders and delirious ideas were also observed. The neurological examination was normal and the electroencephalogram tracing, as well as brain Computed Tomography scan, was also referred as normal. After removing LC from therapy, the patient improved in 72 h. Interestingly, Dr Fraile assessed LC concentration in cerebrospinal fluid (CSF) and in serum and the levels were very high (33.85 and 49 μg/L, respectively). The LC serum and CSF levels were measured also 10 weeks after the admittance and were found surprisingly undetectable. Of interest, the CSF protein levels that was >100 mg/dL in two occasions. The authors speculate on the fact that high-serum levels of free LC could be a consequence of reduced serum protein (serum albumin was 2.3 g/dL at admittance) and that blood–brain barrier (BBB) could be also altered by LC itself or by pre-existing pathological conditions. In their final conclusions, the AA are rising the hypothesis that LC might potentially damage and cross and the BBB thus increasing the risk of neurological side effects in dialysis patients. The authors also claim that no brain deposit of LC or cognitive disorders have been described so far in patients treated with LC, forgetting, however, the important contribution by Altmann et al. [2] who showed—in a prospective randomized multicenter study—that cognitive function deteriorates in haemodialysis patients over a 2-year time period and that LC, as a phosphate binder, does not adversely affect cognitive function compared with standard therapy. This study confirms previous studies performed in animals, exposed to large doses of LC, in which it has been shown that Lanthanum ions cannot pass between the tight junctions of the BBB [3]. Moreover, additional contributions confirmed the safety of LC therapy in dialysed patients followed for up to 6 years [4]. In sum, it is not surprising that a deranged BBB could allow a high LC concentration in CSF in this patient. The real surprise is that this patient also had likely a concomitant increased intestinal permeability, combined with a severe liver cirrhosis, a typical condition in which LC should never be administered.