Control of intraabdominal hemorrhage and shock: a comparison of fluid resuscitation, MAST, and balloon occlusion

Our study examined the efficacy of four treatment modalities in controlling hemorrhage and achieving hemodynamic stabilization in hemorrhagic shock: intravenous fluid replacement (IV); military antishock trousers used concomitantly with fluids (MAST); balloon occlusion at the level of the diaphragm with concomitant fluid replacement (balloon); and a combination of MAST inflation, balloon occlusion, and fluid resuscitation (MAST and balloon). Twenty-eight mongrel dogs were anesthetized, and the spleen was exposed and completely crushed. The abdomen was closed, and treatment was initiated and continued for four hours or until the dog died. For all conditions the hematocrit dropped during the course of the experiment; balloon occlusion was effective at slowing this drop (P less than .0001), but MAST had no statistically significant effect. Animals with balloons bled more slowly into the abdominal cavity than did animals in the other two groups (P less than .0001). MAST also were effective at slowing the bleeding (P less than .05). Of the balloon and the MAST and balloon dogs, all except one survived the entire four hours; this difference between balloon and nonballoon dogs is significant (P = .002). MAST did not have a statistically significant effect on survival. Perfusion pressure (PP) declined during the course of the experiment, and the balloon was effective at slowing this decline (P less than .0001); none of the other comparisons was statistically significant.     

Interplay between interferon-mediated innate immunity and porcine reproductive and respiratory syndrome virus

Innate immunity is the first line of defense against viral infection, and in turn, viruses have evolved to evade host immune surveillance. As a result, viruses may persist in host and develop chronic infections. Type I interferons (IFN-α/β) are among the most potent antiviral cytokines triggered by viral infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of pigs that is characterized by negligible induction of type I IFNs and viral persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT pathways are two major signaling pathways, and recent studies indicate that PRRS virus is armed to modulate type I IFN responses during infection. This review describes the viral strategies for modulation of type I IFN responses. At least three non-structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N nucleocapsid protein) have been identified and characterized to play roles in the IFN suppression and NF-κB pathways. Nsp's are early proteins while N is a late protein, suggesting that additional signaling pathways may be involved in addition to the IFN pathway. The understanding of molecular bases for virus-mediated modulation of host innate immune signaling will help us design new generation vaccines and control PRRS.     

A Call to Action to Enhance Filovirus Disease Outbreak Preparedness and Response

The frequency and magnitude of recognized and declared filovirus-disease outbreaks have increased in recent years, while pathogenic filoviruses are potentially ubiquitous throughout sub-Saharan Africa. Meanwhile, the efficiency and effectiveness of filovirus-disease outbreak preparedness and response efforts are currently limited by inherent challenges and persistent shortcomings. This paper delineates some of these challenges and shortcomings and provides a proposal for enhancing future filovirus-disease outbreak preparedness and response. The proposal serves as a call for prompt action by the organizations that comprise filovirus-disease outbreak response teams, namely, Ministries of Health of outbreak-prone countries, the World Health Organization, Médecins Sans Frontières, the Centers for Disease Control and Prevention—Atlanta, and others.     

Disease Pandemics and Major Epidemics Arising From New Encounters between Indigenous Viruses and Introduced Crops

Virus disease pandemics and epidemics that occur in the world’s staple food crops pose a major threat to global food security, especially in developing countries with tropical or subtropical climates. Moreover, this threat is escalating rapidly due to increasing difficulties in controlling virus diseases as climate change accelerates and the need to feed the burgeoning global population escalates. One of the main causes of these pandemics and epidemics is the introduction to a new continent of food crops domesticated elsewhere, and their subsequent invasion by damaging virus diseases they never encountered before. This review focusses on providing historical and up-to-date information about pandemics and major epidemics initiated by spillover of indigenous viruses from infected alternative hosts into introduced crops. This spillover requires new encounters at the managed and natural vegetation interface. The principal virus disease pandemic examples described are two (cassava mosaic, cassava brown streak) that threaten food security in sub-Saharan Africa (SSA), and one (tomato yellow leaf curl) doing so globally. A further example describes a virus disease pandemic threatening a major plantation crop producing a vital food export for West Africa (cacao swollen shoot). Also described are two examples of major virus disease epidemics that threaten SSA’s food security (rice yellow mottle, groundnut rosette). In addition, brief accounts are provided of two major maize virus disease epidemics (maize streak in SSA, maize rough dwarf in Mediterranean and Middle Eastern regions), a major rice disease epidemic (rice hoja blanca in the Americas), and damaging tomato tospovirus and begomovirus disease epidemics of tomato that impair food security in different world regions. For each pandemic or major epidemic, the factors involved in driving its initial emergence, and its subsequent increase in importance and geographical distribution, are explained. Finally, clarification is provided over what needs to be done globally to achieve effective management of severe virus disease pandemics and epidemics initiated by spillover events.     

Barrett's Esophagus: Where Do We Stand?

Barrett''s esophagus (BE) is a precursor for esophageal adenocarcinoma, which has an increased incidence rate over the last few decades. Its importance stems from the poor five-year survival of esophageal adenocarcinoma and current data that suggest a survival benefit when surveillance programs are implemented. In this review, we will cover the pathophysiology and natural history of BE and the different endoscopic findings. The prevalence of BE in different geographic areas and the incidence of high-grade dysplasia and adenocarcinoma in this patient population is reviewed. Recent recommendation for screening and surveillance of BE has been covered in this review as well as the efficacy of nonconventional imaging modalities and endoscopic ablation therapies.     

The Technology Transfer from Europe to China in the 17th–18th Centuries: Non-Invasive On-Site XRF and Raman Analyses of Chinese Qing Dynasty Enameled Masterpieces Made Using European Ingredients/Recipes

Two masterpieces of the Qing Dynasty (1644–1912 CE), one in gilded brass (incense burner) decorated with cloisonné enamels stylistically attributed to the end of the Kangxi Emperor’s reign, the other in gold (ewer offered by Napoleon III to the Empress as a birthday present), decorated with both cloisonné and painted enamels bearing the mark of the Qianlong Emperor, were non-invasively studied by optical microscopy, Raman microspectroscopy and X-ray microfluorescence spectroscopy (point measurements and mapping) implemented on-site with mobile instruments. The elemental compositions of the metal substrates and enamels are compared. XRF point measurements and mappings support the identification of the coloring phases and elements obtained by Raman microspectroscopy. Attention was paid to the white (opacifier), blue, yellow, green, and red areas. The demonstration of arsenic-based phases (e.g., lead arsenate apatite) in the blue areas of the ewer, free of manganese, proves the use of cobalt imported from Europe. The high level of potassium confirms the use of smalt as the cobalt source. On the other hand, the significant manganese level indicates the use of Asian cobalt ores for the enamels of the incense burner. The very limited use of the lead pyrochlore pigment (European Naples yellow recipes) in the yellow and soft green cloisonné enamels of the Kangxi incense burner, as well as the use of traditional Chinese recipes for other colors (white, turquoise, dark green, red), reinforces the pioneering character of this object in technical terms at the 17th–18th century turn. The low level of lead in the cloisonné enamels of the incense burner may also be related to the use of European recipes. On the contrary, the Qianlong ewer displays all the enameling techniques imported from Europe to obtain a painted decoration of exceptional quality with the use of complex lead pyrochlore pigments, with or without addition of zinc, as well as cassiterite opacifier.     

Formoterol Delivered via the Dry Powder Aerolizer® Inhaler Versus Albuterol MDI and Placebo in Mild-to-Moderate Asthma: A Randomized, Double-Blind, Double-Dummy Trial

The objectives of this study were to compare the efficacy and tolerability of twice-daily formoterol dry powder 12 µg and 24 µg (Foradil) delivered via Aerolizer inhaler with four times daily albuterol (salbutamol) 180 µg delivered via metered dose inhaler (MDI) and placebo. A total of 554 adolescents and adults (ages 12-75 years) with mild-to-moderate asthma were randomized to this 12-week, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study. Twelve-hour spirometry measurements were taken at weeks 0, 4, 8, and 12. A total of 484 patients completed the study (122, 116, 127, and 119 given formoterol 12 µg, formoterol 24 µg, albuterol, and placebo, respectively). For the primary efficacy variable, the forced expiratory volume in 1 second (FEV₁), both formoterol 12 µg and 24 µg were statistically superior to placebo at all time points on all test days (p ≤ 0.017) and to albuterol at most time points on all test days (p ≤ 0.001). The onset of improvement in FEV₁ was rapid, with 15% increase within 5 min in 57%, 71%, and 65% of formoterol 12 µg, formoterol 24 µg, and albuterol patients, respectively. Formoterol was also superior to placebo and albuterol in terms of secondary efficacy variables: FEV₁ area under the curve, percentage of predicted FEV₁, forced vital capacity and forced expiratory flow, asthma symptom scores, and peak expiratory flows. In conclusion, both formoterol doses were superior to placebo in all lung function measurements. Overall, compared with albuterol, both formoterol doses produced superior bronchodilation. Formoterol and albuterol were safe and well-tolerated.     

Routine diagnosis of intestinal tuberculosis and Crohn’s disease in Southern India

AIM:To investigate whether routinely measured clinical variables could aid in differentiating intestinal tuberculosis(ITB)from Crohn’s disease(CD).METHODS:ITB and CD patients were prospectively included at four South Indian medical centres from October 2009 to July 2012.Routine investigations included case history,physical examination,blood biochemistry,ileocolonoscopy and histopathological examination of biopsies.Patients were followed-up after 2 and 6 mo of treatment.The diagnosis of ITB or CD was re-evaluated after 2 mo of antituberculous chemotherapy or immune suppressive therapy respectively,based on improvement in signs,symptoms and laboratory variables.This study was considered to be an exploratory analysis.Clinical,endoscopic and histopathological features recorded at the time of inclusion were subject to univariate analyses.Disease variables with sufficient number of recordings and P<0.05 were entered into logistic regression models,adjusted for known confounders.Finally,we calculated the odds ratios with respective confidence intervals for variables associated with either ITB or CD.RESULTS:This study included 38 ITB and 37 CD patients.Overall,ITB patients had the lowest body mass index(19.6 vs 22.7,P=0.01)and more commonly reported weight loss(73%vs 38%,P<0.01),watery diarrhoea(64%vs 33%,P=0.01)and rural domicile(58%vs 35%,P<0.05).Endoscopy typically showed mucosal nodularity(17/31 vs 2/37,P<0.01)and histopathology more frequently showed granulomas(10/30vs 2/35,P<0.01).The CD patients more frequently reported malaise(87%vs 64%,P=0.03),nausea(84%vs 56%,P=0.01),pain in the right lower abdominal quadrant on examination(90%vs 54%,P<0.01)and urban domicile(65%vs 42%,P<0.05).In CD,endoscopy typically showed involvement of multiple intestinal segments(27/37 vs 9/31,P<0.01).Using logistic regression analysis we found weight loss and nodularity of the mucosa were independently associated with ITB,with adjusted odds ratios of 8.6(95%CI:2.1-35.6)and 18.9(95%CI:3.5-102.8)respectively.Right lower abdominal quadrant pain on examination and involvement of≥3 intestinal segments were independently associated with CD with adjusted odds ratios of 10.1(95%CI:2.0-51.3)and 5.9(95%CI:1.7-20.6),respectively.CONCLUSION:Weight loss and mucosal nodularity were associated with ITB.Abdominal pain and excessive intestinal involvement were associated with CD.ITB and CD were equally common.     

Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014

In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures.     

Liver enzymes,metabolomics and genome-wide association studies:From systems biology to the personalized medicine

For several decades,serum levels of alanine(ALT) and aspartate(AST) aminotransferases have been regarded as markers of liver injury,including a wide range of etiologies from viral hepatitis to fatty liver.The increasing worldwide prevalence of metabolic syndrome and cardiovascular disease revealed that transaminases are strong predictors of type 2 diabetes,coronary heart disease,atherothrombotic risk profile,and overall risk of metabolic disease.Therefore,it is plausible to suggest that aminotransferases are surrogate biomarkers of "liver metabolic functioning" beyond the classical concept of liver cellular damage,as their enzymatic activity might actually reflect key aspects of the physiology and pathophysiology of the liver function.In this study,we summarize the background information and recent findings on the biological role of ALT and AST,and review the knowledge gained from the application of genome-wide approaches and "omics" technologies that uncovered new concepts on the role of aminotransferases in human diseases and systemic regulation of metabolic functions.Prediction of biomolecular interactions between the candidate genes recently discovered to be associated with plasma concentrations of liver enzymes showed interesting interconnectivity nodes,which suggest that regulation of aminotransferase activity is a complex and highly regulated trait.Finally,links between aminotransferase genes and metabolites are explored to understand the genetic contributions to the metabolic diversity.     

Aspirin responsive platelet thrombophilia in essential thrombocythemia and polycythemia vera

Essential thrombocythemia (ET) and polycythemia vera (PV) frequently present with erythromelalgia and acrocyanotic complications, migraine-like microvascular cerebral and ocular transient ischemic attacks (MIAs) and/or acute coronary disease. The spectrum of MIAs in ET range from poorly localized symptoms of transient unsteadiness, dysarthria and scintillating scotoma to focal symptoms of transient monocular blindness, transient mono- or hemiparesis or both. The attacks all have a sudden onset, occur sequentially rather than simultaneously, last for a few seconds to several minutes and are usually associated with a dull, pulsatile or migraine-like headache. Increased hematocrit and blood viscosity in PV patients aggravate the microvascular ischemic syndrome of thrombocythemia to major arterial and venous thrombotic complications. Phlebotomy to correct hematocrit to normal in PV significantly reduces major arterial and venous thrombotic complications, but fails to prevent the platelet-mediated erythromelalgia and MIAs. Complete long-term relief of the erythromelalgic microvascular disturbances, MIAs and major thrombosis in ET and PV patients can be obtained with low dose aspirin and platelet reduction to normal, but not with anticoagulation. Skin punch biopsies from the erythromelalgic area show fibromuscular intimal proliferation of arterioles complicated by occlusive platelet-rich thrombi leading to acrocyanotic ischemia. Symptomatic ET patients with erythromelalgic microvascular disturbances have shortened platelet survival, increased platelet activation markers β-thromboglobulin (β-TG), platelet factor 4 (PF4) and thrombomoduline (TM), increased urinary thromboxane B2 (TXB2) excretion, and no activation of the coagulation markers thrombin fragments F1+2 and fibrin degradation products. Inhibition of platelet cyclooxygenase (COX1) by aspirin is followed by the disappearance and no recurrence of microvascular disturbances, increase in platelet number, correction of the shortened platelet survival times to normal, and reduction of increased plasma levels of β-TG, PF4, TM and urinary TXB2 excretion to normal. These results indicate that platelet-mediated fibromuscular intimal proliferation and platelet-rich thrombi in the peripheral, cerebral and coronary end-arterial microvasculature are responsible for the erythromelalgic ischemic complications, MIAs and splanchnic vein thrombosis. Baseline platelet P-selectin levels and arachidonic acid induced COX1 mediated platelet activation showed a highly significant increase of platelet P-selectin expression (not seen in ADP and collagen stimulated platelets), which was significantly higher in JAK2^V617F mutated compared to JAK2 wild type ET.     

Antiviral Activity of 4'-thioIDU and Thymidine Analogs against Orthopoxviruses

The search for effective therapies for orthopoxvirus infections has identified diverse classes of molecules with antiviral activity. Pyrimidine analogs, such as 5-iodo-2'-deoxyuridine (idoxuridine, IDU) were among the first compounds identified with antiviral activity against a number of orthopoxviruses and have been reported to be active both in vitro and in animal models of infection. More recently, additional analogs have been reported to have improved antiviral activity against orthopoxviruses including several derivatives of deoxyuridine with large substituents in the 5 position, as well as analogs with modifications in the deoxyribose moiety including (north)-methanocarbathymidine, and 5-iodo-4'-thio-2'-deoxyuridine (4'-thioIDU). The latter molecule has proven to have good antiviral activity against the orthopoxviruses both in vitro and in vivo and has the potential to be an effective therapy in humans.     

Use of fab fragments of digoxin-specific antibodies in the therapy of massive digoxin poisoning

A case of massive digoxin ingestion with multiple arrhythmias, consisting of high grade A-V block and ventricular ectopy not responsive to lidocaine, is described. The arrhythmias ceased following administration of digoxin-specific Fab fragments. The patient improved and was transferred to the psychiatric unit.     

Diagnostic performance of COVID‐19 serological assays during early infection: A systematic review and meta‐analysis of 11 516 samples

ObjectiveThe use of coronavirus disease 2019 (COVID‐19) serological testing to diagnose acute infection or determine population seroprevalence relies on understanding assay accuracy during early infection. We aimed to evaluate the diagnostic performance of serological testing in COVID‐19 by providing summary sensitivity and specificity estimates with time from symptom onset.MethodsA systematic search of Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed was performed up to May 13, 2020. All English language, original peer‐reviewed publications reporting the diagnostic performance of serological testing vis‐à‐vis virologically confirmed SARS‐CoV‐2 infection were included.ResultsOur search yielded 599 unique publications. A total of 39 publications reporting 11 516 samples from 8872 human participants met eligibility criteria for inclusion in our study. Pooled percentages of IgM and IgG seroconversion by Day 7, 14, 21, 28 and after Day 28 were 37.5%, 73.3%, 81.3%, 72.3% and 73.3%, and 35.4%, 80.6%, 93.3%, 84.4% and 98.9%, respectively. By Day 21, summary estimate of IgM sensitivity was 0.872 (95% CI: 0.784‐0.928) and specificity 0.973 (95% CI: 0.938‐0.988), while IgG sensitivity was 0.913 (95% CI: 0.823‐0.959) and specificity 0.960 (95% CI: 0.919‐0.980). On meta‐regression, IgM and IgG test accuracy was significantly higher at Day 14 using enzyme‐linked immunosorbent assay (ELISA) compared to other methods.ConclusionsSerological assays offer imperfect sensitivity for the diagnosis of acute SARS‐CoV‐2 infection. Estimates of population seroprevalence during or shortly after an outbreak will need to adjust for the delay between infection, symptom onset and seroconversion.     

Comparison of intravenous and oral routes of theophylline loading in acute asthma

In a prospective, randomized clinical trial, 19 patients with an acute exacerbation of asthma were given a loading dose of aminophylline by the IV (n = 10) or oral route (n = 9) of administration following treatment with epinephrine. Plasma concentrations of theophylline were measured prior to giving the loading dose, and one, two, three, and 24 to 48 hours later. Therapeutic effectiveness was evaluated by analyzing spirometric measurements prior to giving the loading dose, and one, three, and 24 to 48 hours later. Side effects also were recorded. In the IV group, the mean peak plasma theophylline concentration was 15.1 micrograms/mL one hour after loading, and in the oral group the mean peak serum theophylline concentration was 14.2 micrograms/mL three hours after loading. There was no correlation between theophylline concentrations and normalized change in spirometric values. There was no significant difference in spirometric values between the IV and oral groups. Nausea was slightly more common in the IV group. We conclude that there is no therapeutic advantage to giving a loading dose of aminophylline by the IV route rather than orally in patients with mild-to-moderate exacerbation of asthma initially treated with epinephrine.     

A comparison of stapled and handsewn anastomoses in patients undergoing resection for Dukes' B and C colorectal cancer

This study was to assess the effect of stapled colorectal anastomoses on local recurrence, disease-free survival, and survival following curative resection for Dukes' B and C adenocarcinoma. Data were derived from two randomized prospective trials of the National Surgical Adjuvant Breast and Bowel Project designed to evaluate the efficacy of adjuvant therapy in colorectal cancer. Of 1111 patients with colonic anastomoses, 255 were stapled mechanically. There were no significant differences in disease-free survival, survival, or local tumor recurrence among patients subjected to stapled or handsewn anastomoses. Of the 181 patients undergoing anterior resection for rectal cancer, 82 anastomoses were fashioned with staples. No significant disadvantage in disease-free survival, survival, or local recurrence could be attributed to use of the mechanical stapling devices. Twelve percent of patients undergoing stapled rectal anastomoses developed a local recurrence as a first sign of treatment failure compared with 19 percent for the handsewn group. No significant differences in the length of distal margins were detectable. The average time on study was 41 months. The use of stapled anastomoses for carcinoma of the colon or rectum is not associated with an adverse effect on long-term outcome. Read at the meeting of the American Society of Colon and Rectal Surgeons, San Diego, California, May 5 to 10, 1985. Supported by USPHS NIH-U10-34212 and an American Cancer Society Grant RC-13.