Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights

ObjectivesThe aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI).BackgroundThe pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood.MethodsPatients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used.ResultsIn total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p < 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post–percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99).ConclusionsSmoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850)     

Converting modified health assessment questionnaire (HAQ), multidimensional HAQ,and HAQII scores into original HAQ scores using models developed with a large cohort of rheumatoid arthritis patients

Objective

The Stanford Health Assessment Questionnaire Disability Index (HAQ) is the gold standard functional status questionnaire in rheumatology, but it is lengthy. Three shorter versions, the modified HAQ (MHAQ), the Multidimensional HAQ (MDHAQ), and the HAQII are often used in outcomes research as HAQ substitutes. We developed conversion formulas between these modified versions and the original HAQ.

Methods

Analysis was limited to the comparison of rheumatoid arthritis (RA) patients at a random observation when the HAQ was recorded in conjunction with the MHAQ (n = 29,596), the MDHAQ (n = 13,665), or the HAQII (n = 15,823). Development models were randomly limited to 80% of the data (development sample) and the remaining 20% was used for model validation.

Results

Two conversion formulas were developed for each of the MHAQ, the MDHAQ, and the HAQII: a short model and a long model inclusive of questions common to both the modified measures and the original HAQ. Short models explained 81–83%, and long models 82–86%, of the variance. Predicted HAQ values of zero were assigned to all cases with an MDHAQ or HAQII score of zero, with remaining cases used for model estimation. Bland‐Altman plots demonstrated good concordance between actual and predicted values for each measure. The validation sample closely approximated the results from the development sample (0.005 ≤ ΔR² ≤ 0.009) for each measure.

Conclusion

We have developed and validated highly accurate conversion formulas from the MHAQ, MDHAQ, and HAQII to the original HAQ in a large sample of RA patients. The developed models are useful for conversion of measures in the research setting. Because of substantial variability at the individual patient level, application of the formulas to individual patients is inadvisable.     

Immune history shapes specificity of pandemic H1N1 influenza antibody responses

Human antibody responses against the 2009 pandemic H1N1 (pH1N1) virus are predominantly directed against conserved epitopes in the stalk and receptor-binding domain of the hemagglutinin (HA) protein. This is in stark contrast to pH1N1 antibody responses generated in ferrets, which are focused on the variable Sa antigenic site of HA. Here, we show that most humans born between 1983 and 1996 elicited pH1N1 antibody responses that are directed against an epitope near the HA receptor–binding domain. Importantly, most individuals born before 1983 or after 1996 did not elicit pH1N1 antibodies to this HA epitope. The HAs of most seasonal H1N1 (sH1N1) viruses that circulated between 1983 and 1996 possess a critical K133 amino acid in this HA epitope, whereas this amino acid is either mutated or deleted in most sH1N1 viruses circulating before 1983 or after 1996. We sequentially infected ferrets with a 1991 sH1N1 virus and then a pH1N1 virus. Sera isolated from these animals were directed against the HA epitope involving amino acid K133. These data suggest that the specificity of pH1N1 antibody responses can be shifted to epitopes near the HA receptor–binding domain after sequential infections with sH1N1 and pH1N1 viruses that share homology in this region.Most influenza pandemics occur when a new subtype of virus enters the human population. Once introduced into the human population, influenza viruses typically accumulate mutations in the hemagglutinin (HA) and neuraminidase (NA) glycoproteins, a process called antigenic drift. An H1N1 influenza virus strain caused a pandemic in 2009 (Smith et al., 2009) even though H1N1 viruses have circulated in humans from 1918 to 1957 and then again from 1977 to 2009. The 2009 pandemic H1N1 (pH1N1) strain is antigenically distinct from recently circulating seasonal H1N1 (sH1N1) strains and is more closely related to older sH1N1 strains (Garten et al., 2009; Manicassamy et al., 2010; Skountzou et al., 2010).Sera isolated from influenza-infected ferrets are currently used for surveillance of antigenically drifted influenza strains (Stöhr et al., 2012). Anti-pH1N1 antibody responses elicited in ferrets are focused on the highly variable Sa antigenic site of HA (Chen et al., 2010). Conversely, the majority of monoclonal antibodies derived from humans infected or vaccinated with pH1N1 are directed against conserved regions of the HA stalk and receptor binding domain (Li et al., 2012; O’Donnell et al., 2012; Wrammert et al., 2011). Most of these monoclonal antibodies possess many somatic mutations and bind to sH1N1 viruses efficiently, which is consistent with the idea that these antibody responses were likely originally primed by sH1N1 infection and were later recalled during pH1N1 infection/vaccination (Settembre et al., 2011; Wrammert et al., 2011; Li et al., 2012; O’Donnell et al., 2012; Qiu et al., 2012). Understanding the precise events that promote the development of these cross-reactive antibody repertoires will aid in developing a universal influenza vaccine that targets conserved areas of HA.Here, we compared the specificity of pH1N1 antibody responses elicited in different aged humans. We find that most individuals born between 1983 and 1996 elicit pH1N1 antibody responses that are dominated against an epitope near the HA receptor–binding domain. Most sH1N1 viruses that circulated between 1983 and 1996 share homology with the pH1N1 virus in this region of HA. Antibody responses dominated against this HA epitope were induced after sequential infection of ferrets with a 1991 sH1N1 virus and a pH1N1 virus. Most humans born before 1983 or after 1996 did not mount anti-pH1N1 antibody responses against this HA region. Importantly, most sH1N1 viruses that circulated before 1983 or after 1996 have an amino acid mutation or deletion in this HA epitope.     

Ewing's sarcoma: a trial of adjuvant chemotherapy and sequential half-body irradiation

The results of a pilot study using adjuvant chemotherapy and sequential half-body irradiation (HBI) for nonmetastatic Ewing's sarcoma are presented. Seventeen patients received Cyclophosphamide, Vincristine, and Adriamycin (8 cycles), followed by sequential radiation treatment of the upper (500 cGy) and lower (600 cGy) half body. Survival at 3 years was 49%. These results are contrasted with those for 18 concurrently treated patients who received standard adjuvant therapy. Overall 5-year survival and relapse-free survival for these 35 consecutive patients was 61 and 53%. The pilot protocol was given on an out-patient basis with limited and acceptable acute toxicology. Further study is necessary to determine the value of the pilot protocol.     

Subclinical endophthalmitis following a rooster attack

Ocular injury resulting from rooster attacks is rarely reported in the literature. Sadly, the target of these attacks is most often children younger than 3 years old, whose naiveté of the aggressive, territorial behavior of birds can place them at risk. Acute sequelae of these attacks can result in a lifetime of visual impairment. The possibility of a subacute or occult infection is an unusual occurrence that must always be considered. In an effort to prevent future attacks and ocular casualties, we present a case of a 12-month-old boy who suffered an open globe following a rooster attack. The open globe was emergently repaired. One week later, a white cataract was noticed on examination in the absence of systemic or ocular signs of inflammation. Traumatic endophthalmitis and lenticular abscess were suspected during examination under anesthesia. Vitrectomy, lensectomy, and injection of intravitreal antibiotics were performed. Culture of lenticular and vitreous aspirates grew alpha-streptococcus. Alpha-streptococcal endophthalmitis can result from ocular injuries caused by rooster pecking. The infection may present insidiously and without typical ocular or systemic symptoms or signs. Management is challenging and may require surgery.     

Biaxial flexure testing of calcium phosphate bioceramics for use in tissue engineering

This study analyzes data from 206 CaP specimens (68 HA, 70 BCP, and 68 beta-TCP) fractured via biaxial flexure testing. Specimens were divided into four groups: (a) Group I, dry; (b) Group II, wet (day 0, immersion time approximately 5-10 s); (c) Group III, after immersion in media for 21 days (day 21); and (d) Group IV, after culturing osteoblasts (OBs) on the surface for 21 days (day 21 with cells). X-ray diffraction verified the presence of minor second phases in HA and beta-TCP while BCP was a biphasic mixture of HA and beta-TCP with minor phases present. The statistical significance (p < 0.05) of differences in the measured biaxial flexure fracture strength, S, between groups was assessed via one-way ANOVA with Tukey's test. Also, a two-parameter Weibull analysis assessed the mechanical reliability of each group. Osteoblasts increase the biaxial flexure fracture strength in a statistically significant way compared to both the HA discs in Groups II and III. Scanning electron microscope examination revealed grain boundary grooving on the sintered surfaces and with thermal expansion anisotropy, likely leads to the observed rapid strength decline upon exposure to media found in Groups II, III and IV.     

Enhanced MYCN expression and lsochromosome 17q in pineoblastoma cell lines

We have established two cell lines, PER-452 and PER-453, from an 8-month-old girl with an extensive pineoblastoma. Characterization of these lines revealed that the proto-oncogenes MYC and MYCN were not amplified, but both cell lines showed MYCN expression comparable to a cell line with 200-fold MYCN amplification. Both cell lines contained an i( 17q). These results support the concept that pineoblastomas belong to a larger group of primitive neuroectodermal tumors of the central nervous system. These two cell lines provide a unique opportunity to investigate the molecular genetic mechanisms underlying these neoplasms further. Genes Chrom Cancer 9:129-135 (1994).© 1994 Wiley-Liss, Inc.     

Primitive Neuroectodermal Tumors of the Central Nervous System

Controversial issues relating to the pathobiology and classification of central nervous system primitive neuroectodermal tumors (PNETs) have plagued neuropathologists for more than 70 years. Hypotheses advanced in the mid-1920's have remained as fixed concepts in contemporary literature, largely consequent to repetitious support by a small number of neuropathologists despite a growing body of information discrediting these ideas from neuroembryologists, oncologists, neuroscien-tists and pathologists.
Attention has largely focused upon PNETs arising in the cerebellum (commonly known as medul-loblastomas [MBs]), because about 80% of central nervous system (CNS) PNETs originate in this site. It has been asserted that the 20% which do not are biologically different, although most individuals agree that the histological features of PNETs that occur in different sites throughout the CNS are indistinguishable from those growing in the cerebellum.
The historical aspects of this controversy are examined in the face of evidence that there is, in fact, a unique class of CNS tumors which should appropriately be regarded as primitive neuroectodermal in nature. Specifically, a number of different approaches to the problem have yielded data supporting this hypothesis. These approaches include the identification of patterns of expression among a variety of cellular antigens (demonstrated by the use of immunopathological techniques), molecular analyses of cell lines derived from these tumors, experimental production of PNETs and molecular genetic analyses.
Differences of opinion among surgeons, oncologists and radiotherapists are typically resolved by conducting cooperative studies of patients with these tumors who are diagnosed and treated at multiple centers.     

Limitations of the criteria used to diagnose histologic endometritis in epidemiologic pelvic inflammatory disease research

While endometrial neutrophils and plasma cells are criteria used to diagnose histologic endometritis in epidemiologic pelvic inflammatory disease (PID) research, plasma cell misidentification and nonspecificity may limit the accuracy of these criteria. Herein, we examined: (1) the identification of endometrial plasma cells with conventional methyl green pyronin-based methodology versus plasma cell-specific (CD138) immunostaining, (2) the prevalence of endometrial plasma cells among women at low risk for PID, and (3) endometrial leukocyte subpopulations among women diagnosed with acute or chronic histologic endometritis by conventional criteria. We observed an absence of CD138⁺ cells in 25% of endometrial biopsies in which plasma cells had been identified by conventional methodology, while additional immunohistochemical analyses revealed indistinguishable inflammatory infiltrates among women diagnosed with acute or chronic endometritis by conventional criteria. Among women considered at lower risk for PID development, flow cytometric analyses detected plasma cells in 30% of endometrial biopsy specimens, suggesting that these cells, even when accurately identified, only nonspecifically identify upper genital tract inflammatory processes. Combined, our findings underscore the limitations of the criteria used to diagnose histologic endometritis in PID-related research and suggest that satisfactory understanding of PID pathogenesis, treatment, and prevention is hindered by continued use of these criteria.