Efficacy of complementary treatment with autologous platelet concentrates and/or mesenchymal stem cells in chemical osteonecrosis of the jaw. Systematic review of the literature.

The aim of this systematic review was to establish the current status of the subject and find out what scientific evidence we have on the use of autologous plasma concentrates (APCs) and mesenchymal stem cells (MSCs) as complementary therapies at the management of Medication-related Osteonecrosis of the jaw (MRONJ). We performed a literature search of articles published between December 2019 to January 2020 in electronic databases, in accordance to PRISMA system. The variables analyzed were: the number of patients, age, sex, medical history, origin of MRONJ, imaging studies, treatment performed, and evolution of MRONJ. The articles included in the review were grouped into two groups (Group A "Therapy with APCs" and Group B "Therapy with APCs and MSCs"). Newcastle-Ottawa scale (NOS) was used to assess the quality of the articles. Fisher's exact test was used to evaluate eventual differences between groups. Of the 306 patients who were included, 297 belonged to Group A and 9 to Group B. In our sample, women predominated against men and no significant differences in age were observed. Osteoporosis was the most frequent underlying disease in both groups. The most common origin of MRONJ was oral surgery in group A. Conservative surgery was performed in all patients, but complementary treatment was applied in different ways in each group. The resolution of the pathology was achieved in 90% of cases in both groups without significant differences between them. The mean score of the reviewed studies at NOS was 4. There are currently no published scientific data that can sufficiently support the use of APCs and MSCs for the treatment of established MRONJs.

Mediastinitis of odontogenic origin. A serious complication with 80 years of history.

We performed a systematic review of the literature about descending necrotising mediastinitis (DNM) of odontogenic origin. In parallel, a retrospective review of this pathology was carried out in an Oral and Maxillofacial Surgery Service of a reference hospital for a population of 1,100,000 inhabitants. The main objectives were to determine changes in mortality and prevalence of this serious complication. The systematic review included 51 articles with 89 patients and our study comprised seven patients. The period of time with the highest number of cases was between 2000-2009 (38 patients). The percentage of mortality observed was 20.2% in diffuse DNM and 4.9% in localised DNM. Thirty-one patients with DNM in our review were admitted for more than 41 days. Despite evidence of a decrease in DNM cases, publications have increased over the years, but it does not appear to be due to an increase in those of odontogenic origin. The survival of DNM has improved since 1998 and remained stable since then. Despite the low prevalence of this disease, multicentre control studies are needed to achieve better evidence about this entity.

Medication-related osteonecrosis of the jaw. Implant presence-triggered osteonecrosis: Case series and literature review.

PURPOSE: The aim of this study was to review the characteristics of 'implant presence-triggered osteonecrosis' (IPTO) in the literature and identify possible differences between IPTOs and 'implant surgery-triggered osteonecrosis' (ISTO). MATERIALS AND METHODS: Reviews using PubMed and the Cochrane Database of Systematic Reviews were performed from 2009-2018; the focus was on medication-related osteonecrosis of the jaw (MRONJ) and dental implants. In addition, the hospital records of all patients presented in our department with IPTO were retrospectively reviewed. In both studies, the following data were collected: the number of patients with ISTO or IPTO, age, gender, location, stage of MRONJ, number of implants involved in MRONJ, the elapsed time between the placement of the implants and the development of MRONJ, applied treatment and the presence of mandibular fractures and progress. RESULTS: The literature review provided 111 articles. Nine of the articles were selected for bibliographic review. The number of osteonecrosis cases was significantly higher in the IPTO group (74 cases) compared with the ISTO group (27 cases). The duration of the anti-resorptive treatment (oral and intravenous) was also longer in the IPTO group. In our centre, seven patients with IPTO were chosen; however, no patients with ISTO were selected. The significant differences between the patients in our series and the information collected in the literature for the IPTO group were the time of ingestion of alendronate, the elapsed time from the placement of the implants to the development of the MRONJ and the number of implants linked to the development of a complication. CONCLUSIONS: The use of antiresorptives causes osteonecrosis in patients with implants that are subjected to functional loading, and this occurs at a higher frequency than what is observed after implant placement surgery.

Medication-related osteonecrosis of the jaw: A survey of knowledge, attitudes, and practices among dentists in the principality of Asturias (Spain).

INTRODUCTION: The objective of this study was to investigate the knowledge and capabilities of dentists and dental students in their last year of study in regard to risk factors of medication-related osteonecrosis of the jaw (MRONJ) in Spain. MATERIAL AND METHOD: We conducted a cross-sectional study consisting of a questionnaire survey in Asturias, Spain. The study was divided into three groups: dentists who worked for the public dental health care system (n=32), dentists who worked exclusively as private health care practitioners (n=136), and dental students in their last year (year five) of study (n=38). The quantitative differences in the scores obtained in the resolution of clinical cases between students and dentists were evaluated. Differences between dentists were evaluated depending on number of years in practice, activity (private or public care), and area of specialty. The study tracked the possible differences in the general knowledge of MRONJ among dentists and students and the participants' adherence to the dental clinic guidelines regarding the MRONJ. RESULTS: Students from year five reached a higher score than those dentists with private practice activity (P=0.01). Significant differences between the students and the public health care dentists were not recognized, nor between the latter and the private health care dentists. The lowest percentage of correct answers among participants was related to implant surgery in patients treated with oral aminobisphosphonates. The dentists with more than 20 years of professional experience obtained significantly lower-than-average scores in the resolution of the clinical cases based on clinical guidelines (P=0.01). We did not observe any differences in the average test scores obtained by dentists dependent on their area of expertise. CONCLUSIONS: Knowledge of side effects of antiresorptive drugs decreases with years of professional practice. Training efforts on MRONJ should focus especially on those dentists who practice privately, who have over 20 years of professional experience, and who perform implant surgery on patients at risk of MRONJ.

A retrospective comparison of VLBW outcomes before and after implementing new delivery room guidelines at a regional tertiary care center.

OBJECTIVE: To evaluate the impact of implemented protocol changes on delivery room interventions and very low birth weight (VLBW) health outcomes. STUDY DESIGN: Retrospective study comparing birth characteristics, interventions and health outcomes of VLBW infants born in a tertiary care center before (calendar years 2008 to 2009) and after (calendar years 2012 to 2013) implementing new protocols using Chi-square analyses. RESULT: Four hundred and nine were born before and 303 after changes were implemented. Postimplementation infants had more use of antenatal steroids (P=0.02), gestational age ⩽24 weeks (P=0.03) and birth weights between 501 and 750 g (P=0.04) and less oxygen administration (P=0.002), face mask ventilation (P=0.0001), surfactant use (P=0.0001), chest compressions (P=0.0001), intubation (P=0.002), epinephrine use (P=0.011), hypothermia (P=0.0001) and discharges home on supplemental oxygen (P=0.05). CONCLUSION: Changes creating a new delivery team, adopting new delivery practice guidelines and updating delivery room equipment resulted in positive outcomes for delivery room practices and patient outcomes.

Thermal defense of extremely low gestational age newborns during resuscitation: exothermic mattresses vs polyethylene wrap.

OBJECTIVE: The purpose of this study was to assess the effectiveness of thermal warming mattresses compared with wrapping in a polyethylene sheet during resuscitation in extremely low gestational age newborns (ELGANs) in preventing admission hypothermia in the neonatal intensive care unit. STUDY DESIGN: Patients delivered between 24 and 28 weeks gestation and ≤1250 g were eligible for this prospective, randomized study. In the delivery room, the resuscitation team opened a sealed opaque envelope for treatment group assignment to either the wrap or the sodium acetate mattress group. Resuscitation followed protocols recommended by the Neonatal Resuscitation Program. The primary outcome for this study was comparison of axillary temperatures recorded at the time of neonatal intensive care unit admission between the two groups. RESULT: Thirty-nine patients were enrolled in the study. The mattress group's mean admission temperature was 36.5±0.67, whereas the plastic wrap group's was 36.1±0.66 (P=0.0445). CONCLUSION: Thermal mattresses improved admission temperature for ELGANs over plastic wrap. Although both plastic wrap and thermal mattresses improve the thermal status of ELGANs, all current interventions fall short of truly protecting all these vulnerable patients from thermal stress.

Long-term complications and survival of patients after orthotopic liver transplantation.

INTRODUCTION: The survival rates among patients after orthotopic liver transplantation (OLT) has increased to 83% and 75% at 1 and 5 years, respectively. However, these patients are at increased risk of long-term complications. OBJECTIVE: To identify long-term complications and survivals among patients after OLT. METHODS: From September 1999 to July 2009 we evaluated long-term complications among 78 consecutive patients after OLT including 46 males. RESULTS: Complications de novo after OLT were metabolic (n = 38; 67%), infections (n = 13; 23%), recurrent liver disease (n = 12; 21%), osteopenia/osteoporosis (n = 10; 18%), acute/chronic rejection (n = 8; 14%), renal failure (n = 2; 4%) and Kaposi's sarcoma (n = 1). Their overall survival at 118 months was 55%. CONCLUSIONS: The most common long-term complications after OLT were metabolic, infections, and disease recurrence.

Moving from experience to evidence: changes in US Neonatal Resuscitation Program based on International Liaison Committee on Resuscitation Review.

The Neonatal Workgroup of the International Liaison Committee on Resuscitation recently made available their rigorous review of the scientific evidence base for selected neonatal resuscitation issues. The Neonatal Resuscitation Program guidelines have been recently revised based on that review and published as the Textbook of Neonatal Resuscitation, 5th edn. This review article highlights pertinent changes in recommendations, including revisions in: oxygen use; CO(2) detectors for confirmation of intubation; management of the infant born through meconium-stained amniotic fluid; initial ventilation devices and strategies; thermal protection of very small preterm infants; medications, including doses and routes of delivery; postresuscitation therapies for consideration and ethical issues in initiation and discontinuation of resuscitation. Journal of Perinatology (2008) 28, S35-S40; doi:10.1038/jp.2008.48.

The monocyte-derived chemokine is released in the bronchoalveolar lavage fluid of steady-state asthmatics.

Infiltration of the airways by T helper type 2 (Th2) lymphocytes is a well-recognized feature of bronchial asthma. Monocyte-derived chemokine (MDC) is a potent attractant which activates Th2 lymphocytes via the chemokine receptor CCR4. We have investigated both leukocyte recruitment and MDC release into the airways of asthmatic patients. Differential cell counts in bronchoalveolar lavage (BAL) fluid showed that numbers of lymphocytes and eosinophils were elevated in asthmatics compared with normal subjects (median, 6.1 vs. 1.0 x 10(3)/ml, P < 0.005 and 1.4 vs. 0.24 x 10(3)/ml, P = 0.001, respectively). By enzyme-linked immunosorbent assay it was demonstrated that MDC concentrations were significantly elevated in BAL fluid from asthmatics compared with normals (medians 282 pg/ml, range 190-780 pg/ml vs. median 29 pg/ml range 17-82 pg/ml, P < 0.001). Interestingly, there was a significant correlation between MDC levels and the bronchoconstrictive response to methacholine [PC20 forced expiratory volume (FEV)1, r = -0.78, P = 0.001], suggesting that MDC may be involved in the severity of the disease. By immunohistochemistry, MDC was localized predominantly to the bronchial epithelium in bronchial biopsies derived from stable asthmatics. Moreover, primary human airway epithelial cells were found to release MDC upon cytokine stimulation. These findings suggest that MDC may play a major role in the pathogenesis of bronchial asthma.

Tuberculosis and other infectious diseases in the adolescent immigrant.

Adolescent medicine physicians are frequently the initial contact for adolescents newly arriving in the U.S. and it is important that they recognize the needs of their patients. The adolescent immigrant may be encountered in a school-based health setting, private practice, community health center, or other health care settings. This article begins with a review of the categories of immigrants comprising the adolescent population. It gives an extensive review of tuberculosis among Mexican-American adolescents, detailing history, epidemiology, diagnosis, social factors, and treatment modalities. It further delineates the impact of Mexican tuberculosis control strategies on the practice of medicine in the U.S., and outlines preventive, diagnostic, and therapeutic strategies that should be followed in the adolescent immigrant. This article also reviews viral hepatitis in its multiple forms and its impact on the adolescent immigrant. It concludes by delineating prevention practices required for the adolescent immigrant and summarizes the interventions an initial contact physician should undertake upon encountering such adolescents.

Activation of phosphatidylinositol 3-kinase is sufficient for cell cycle entry and promotes cellular changes characteristic of oncogenic transformation.

Using a new inducible form of phosphatidylinositol 3-kinase (PI 3-kinase) we have found that PI 3-kinase activation has the following effects on cell growth and proliferation. (i) Activation of PI 3-kinase was sufficient to promote entry into S phase of the cell cycle within several hours. This was shown by activation of cyclin-dependent kinase 4 (Cdk4) and Cdk2 and by the induction of DNA synthesis. (ii) PI 3-kinase activation alone was not, however, sufficient to provide for progression through the entire cell cycle. Instead, prolonged activation of PI 3-kinase in the absence of serum stimulation resulted in apoptosis. It is possible that the cells undergo apoptosis because the PI 3-kinase-induced entry into the cell cycle is abnormal. For example, we found that the cyclin E-Cdk2 complex, which normally disappears after entry into S phase of the cell cycle, fails to be downregulated following induction by PI 3-kinase. (iii) Finally, we found that prolonged activation of PI 3-kinase in the presence of serum resulted in cellular changes that resemble those associated with oncogenic transformation. The cells reached high densities, were irregular and refractile in appearance, and formed colonies in soft agar. In contrast, neither PI 3-kinase nor serum stimulation alone could induce these changes. Our results suggest that activation of PI 3-kinase promotes anchorage-independent cell growth and entry into the cell cycle but does not abrogate the growth factor requirement for cell proliferation.

Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways.

Phosphatidylinositol (PI) 3-kinase is a cytoplasmic signaling molecule recruited to the membrane by activated growth factor receptors. The p85 subunit of PI 3-kinase links the catalytic p110 subunit to activated growth factor receptors and is required for enzymatic activity of p110. In this report, we describe the effects of expressing novel forms of p110 that are targeted to the membrane by either N-terminal myristoylation or C-terminal farnesylation. The expression of membrane-localized p110 is sufficient to trigger downstream responses characteristic of growth factor action, including the stimulation of pp70 S6 kinase, Akt/Rac, and Jun N-terminal kinase (JNK). These responses can also be triggered by expression of a form of p110 (p110*) that is cytosolic but exhibits a high specific activity. Finally, targeting of pl10* to the membrane results in maximal activation of downstream responses. Our data demonstrate that either membrane-targeted forms of p110 or a form of p110 with high specific activity can act as constitutively active PI 3-kinases and induce PI 3-kinase-dependent responses in the absence of growth factor stimulation. The results also show that PI 3-kinase activation is sufficient to stimulate several kinases that appear to function in different signaling pathways.

Profile of HIV disease in an American border city.

A previous study on patterns of migration of HIV-infected persons suggested that most patients in a rural setting in eastern Tennessee acquired their disease in an urban area, typically during a period of prolonged residence. Disease and disability were the most common reasons for returning to their hometown. We studied our urban, border-city HIV clinic population to see whether similar patterns of migration were discernible. Fifty-one of the 103 patients studied lived outside the El Paso/Juarez area when they contracted HIV infection. The major reason cited for returning home was a desire to return to family (25%). Those who returned and those who had never left showed no statistically significant difference in age, race, or risk factors. This study suggests that migration of HIV-infected patients back to their hometown does not appear to be an exclusively rural phenomenon.

Current issues in Texas neonatology.

Since almost 10% of the births in the United States occur in Texas, issues that affect neonatal care in Texas are important for both the state and the nation. Although overall statistics are similar for the state and nation, closer examination reveals a need for improvement in specific areas, namely prenatal care, black and Hispanic mortality, and low birth-weight rates. Lay midwifery regulation has been an important concern in Texas. Surfactant use and education to prevent birth asphyxia have had a positive impact on perinatal health, contributing to public health efforts to improve perinatal outcome.

[Primary liver cancer. Its epidemiological, clinical and biochemical characteristics]. / Cáncer hepático primario. Características epidemiológicas, clínicas y bioquímicas.

Epidemiological, clinical, biochemical and topographic features of primary hepatic cancer (PHC) were reviewed retrospective and prospectively in this study. This review consisted of 76 patients from 1971 to 1990. Forty nine males and 27 females. The mean age was 66.1 +/- 11.7 years. Hepatocellular carcinoma (HC) was the most frequent histological type (84.1%), followed by cholangiocarcinoma (87.7%). Mixed carcinoma and hepatoblastoma were 4.3 and 2.9% respectively. The prevalence af PHC among 1485 autopsies was 0.74%. The most frequent sites af metastasis were the lungs (66%) and portal vein (50%). Hepatocellular carcinoma was associated to cirrhosis in 80% of the cases. A syndrome including asthenia, weight loss, hepatomegaly and cholestasis was identified in most of the patients, and alkaline phosphatase was the most frequently disturbed laboratory test. 60% of tumors were bilateral and none of the solitary tumors had less than 5 cms in diameter. 20% of HC showed normal serum levels of AFP (< 20 ng/ml). 40% had at least one of the markers of B virus hepatitis in serum.

Immunologic analysis of the cloned platelet thrombin receptor activation mechanism: evidence supporting receptor cleavage, release of the N-terminal peptide, and insertion of the tethered ligand into a protected environment.

The recently cloned functional thrombin receptor is thought to be activated by thrombin cleavage of the bond between R41 and S42, followed by the insertion of the new N-terminal region ("tethered ligand") into an unknown site in the receptor. Antibodies to peptides at or near the cleavage site have been reported to inhibit thrombin-induced platelet activation to varying extents, but the precise mechanism(s) of their inhibition is unknown. We have produced: (1) a polyclonal antibody in rabbits to a peptide containing amino acids 34 to 52 (anti-TR34-52); enzyme-linked immunosorbent assays (ELISA) indicate that anti-TR34-52 contains antibodies to regions on both sides of the thrombin cleavage site; (2) two murine monoclonal antibodies (MoAbs) to a peptide containing amino acids 29 to 68; one antibody reacts primarily with residues N-terminal to the thrombin cleavage site, and the other reacts primarily with residues C-terminal to the cleavage site; and (3) a polyclonal rabbit antibody to a peptide containing amino acids 83 to 94 (anti-TR83-94). Anti-TR34-52 binds to platelets as judged by flow cytometry, and pretreating platelets with a thrombin receptor peptide ligand does not lead to loss of antibody reactivity, suggesting that platelet activation does not initiate redistribution or internalization of surface thrombin receptors. In contrast, pretreating platelets with thrombin leads to complete loss of anti-TR34-52 binding. Similarly, the binding of both MoAbs to platelets is dramatically reduced by pretreatment with thrombin. However, the binding of anti-TR83-94 is not decreased by thrombin activation, confirming that the receptor is not internalized. Anti-TR34-52 profoundly inhibits low dose thrombin-induced platelet shape change and aggregation, but the inhibition can be overcome with higher thrombin doses. However, anti-TR34-52 does not inhibit platelet aggregation induced by tethered ligand peptides. The TR34-52 peptide is a thrombin substrate, with cleavage occurring at the R41-S42 bond as judged by high performance liquid chromatography (HPLC) and platelet aggregation analysis. Anti-TR34-52 prevented cleavage of the TR34-52 peptide, suggesting that the antibody prevents platelet activation, at least in part, by preventing cleavage of the thrombin receptor. These data, although indirect, provide additional support for a thrombin activation mechanism involving thrombin cleavage of the receptor; in addition, they provide new evidence indicating that receptor cleavage is followed by loss of the N-terminal peptide, and insertion of the tethered ligand into a protected domain.

Chemical and nutritional evaluation of two amaranth (Amaranthus cruentus)-based infant formulas.

The objective of this study was to calculate, prepare and evaluate the Protein Efficiency Ratio (P.E.R.) and Net Protein Utilization (N.P.U.) of two infant formulas made with amaranth (Amaranthus cruentus). Both formulas were formulated to match a previously developed and tested soy-oats infant formula. No significant differences were found between the three formulas with respect to corrected Protein Efficiency Ratio (P.E.R.) and Net Protein Utilization (N.P.U.) values. Only the product made with the 1-R fraction of amaranth was found to have a significantly lower P.E.R. than casein.