Myocarditis post-SARS-CoV-2 vaccination: a systematic review.

Variable clinical criteria taken by medical professionals across the world for myocarditis following coronavirus disease 2019 (COVID-19) vaccination along with wide variation in treatment necessitates understanding and reviewing the same. A systematic review was conducted to elucidate the clinical findings, laboratory parameters, treatment and outcomes of individuals with myocarditis after COVID-19 vaccination after registering with PROSPERO. Electronic databases including MEDLINE, EMBASE, PubMed, LitCovid, Scopus, ScienceDirect, Cochrane Library, Google Scholar and Web of Science were searched. A total of 85 articles encompassing 2184 patients were analysed. It was a predominantly male (73.4%) and young population (mean age: 25.5 ± 14.2 years) with most having taken an mRNA-based vaccine (99.4%). The mean duration from vaccination to symptom onset was 4.01 ± 6.99 days. Chest pain (90.1%), dyspnoea (25.7%) and fever (11.9%) were the most common symptoms. Only 2.3% had comorbidities. CRP was elevated in 83.3% and cardiac troponin in 97.6% patients. An abnormal ECG was reported in 979/1313 (74.6%) patients with ST-segment elevation being most common (34.9%). Echocardiographic data were available for 1243 patients (56.9%), of whom 288 (23.2%) had reduced left ventricular ejection fraction. Non-steroidal antiinflammatory drugs (76.5%), steroids (14.1%) followed by colchicine (7.3%) were used for treatment. Only 6 patients died among 1317 of whom data were available. Myocarditis following COVID-19 vaccination is often mild, seen more commonly in young healthy males and is followed by rapid recovery with conservative treatment. The emergence of this adverse event calls for harmonizing case definitions and definite treatment guidelines, which require wider research.

Hyperintense Optic Nerve due to Diffusion Restriction: Diffusion-Weighted Imaging in Traumatic Optic Neuropathy.

BACKGROUND AND PURPOSE: Abnormal signal intensity of the optic nerve due to diffusion restriction may be seen in traumatic optic neuropathy. In addition to evaluating optic nerve hyperintensity on diffusion-weighted imaging, we compared the group differences of ADC values between the injured and uninjured contralateral nerve and identified the relation between measured ADC values and admission visual acuity. MATERIALS AND METHODS: We retrospectively evaluated 29 patients with traumatic optic neuropathy who underwent MR imaging with DWI. Uninjured contralateral optic nerves were used as controls. Two attending radiologists, blinded to the side of injury, independently reviewed the DWI for the presence of signal-intensity abnormality and obtained ADC values after manually selecting the ROI. RESULTS: Hyperintensity of the optic nerve was demonstrated in 8 of the 29 patients, with a sensitivity of 27.6% (95% CI, 12.8-47.2) and a specificity of 100% (95% CI, 87.9-100). ADC values were obtained in 25 patients. The mean ADC in the posterior segment of the injured nerve was significantly lower than that in the contralateral uninjured nerve (Welch ANOVA, F = 9.7, P = .003). There was a moderate-to-strong correlation between low ADC values and poor visual acuity in 10 patients in whom visual acuity could be obtained at admission (R = 0.7, P = .02). Patients with optic nerve hyperintensity presented with worse visual acuity. CONCLUSIONS: Hyperintensity of the optic nerve due to diffusion restriction can serve as a specific imaging marker of traumatic optic neuropathy. When paired with reduced ADC values, this finding may be an important surrogate for visual acuity.

Under-report and underdiagnosis of chronic respiratory diseases in an African country.

BACKGROUND: Chronic respiratory diseases (CRD) are greatly underestimated. The aim of this study was to assess the burden associated with reported CRD and chronic obstructive pulmonary disease, as defined on the basis of various standardized criteria, by estimating their point prevalence in a sample of individuals attending the Primary Health Care (PHC) level and Emergency Room (ER) Departments in Cape Verde (CV) archipelago. The second aim of the study was to identify factors related to airways obstruction and reported CRD in this population. METHODS: A cross-sectional study was carried out in CV during 2 weeks. Outpatients aged more than 20 years seeking care at PHC level and ER answered a standardized questionnaire and were subjected to spirometry, independently of their complaint. Two criteria for airways obstruction were taken into account: forced expiratory volume (FEV(1)) <80% of the predicted value and FEV(1)/forced vital capacity (FVC) ratio <0.70. RESULTS: A total of 274 individuals with a satisfactory spirometry were included. 22% of the individuals had a FEV(1) < 80%. Individuals older than 46 years had a higher risk of having airways obstruction. Asthma diagnosis (11%) had a clear association with airways obstruction. Smoking was a risk factor for a lower FEV(1). Working in a dust place and cooking using an open fire were both related to chronic bronchitis and asthma diagnosis. CONCLUSION: Under-report and underdiagnosis of chronic respiratory conditions seem to be a reality in CV just as in other parts of the world. To improve diagnosis, our results reinforce the need of performing a spirometry.

GenoMycDB: a database for comparative analysis of mycobacterial genes and genomes

Several databases and computational tools have been created with the aim of organizing, integrating and analyzing the wealth of information generated by large-scale sequencing projects of mycobacterial genomes and those of other organisms. However, with very few exceptions, these databases and tools do not allow for massive and/or dynamic comparison of these data. GenoMycDB (http://www.dbbm.fiocruz.br/GenoMycDB) is a relational database built for large-scale comparative analyses of completely sequenced mycobacterial genomes, based on their predicted protein content. Its central structure is composed of the results obtained after pair-wise sequence alignments among all the predicted proteins coded by the genomes of six mycobacteria: Mycobacterium tuberculosis (strains H37Rv and CDC1551), M. bovis AF2122/97, M. avium subsp. paratuberculosis K10, M. leprae TN, and M. smegmatis MC2 155. The database stores the computed similarity parameters of every aligned pair, providing for each protein sequence the predicted subcellular localization, the assigned cluster of orthologous groups, the features of the corresponding gene, and links to several important databases. Tables containing pairs or groups of potential homologs between selected species/strains can be produced dynamically by user-defined criteria, based on one or multiple sequence similarity parameters. In addition, searches can be restricted according to the predicted subcellular localization of the protein, the DNA strand of the corresponding gene and/or the description of the protein. Massive data search and/or retrieval are available, and different ways of exporting the result are offered. GenoMycDB provides an on-line resource for the functional classification of mycobacterial proteins as well as for the analysis of genome structure, organization, and evolution.

Nondominant right coronary artery occlusion and ventricular tachyarrythmias.

It is usually considered that occlusion of a nondominant right coronary artery is not associated with significant consequences. We report two cases of nondominant right coronary artery occlusion that presented with sudden cardiac death. Timely intervention resulted in complete resolution of the ventricular arrhythmias. This highlights the need for greater vigilance in the recognition and treatment of these lesions.

Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin).

BACKGROUND: Trastuzumab (Herceptin), an anti-HER2/neu receptor monoclonal antibody that inhibits growth of ErbB2-overexpressing breast cancer, is used to treat such cancers. Development of resistance to trastuzumab, however, is common. We investigated whether insulin-like growth factor-I (IGF-I), which activates cell survival signals, interferes with the growth-inhibitory action of trastuzumab. METHODS: MCF-7/HER2-18 and SKBR3 human breast cancer models were used to assess cell proliferation, colony formation in soft agar, and cell cycle parameters. Throughout, we used trastuzumab at a dose of 10 microg/mL and IGF-I at a dose of 40 ng/mL. All statistical tests were two-sided. RESULTS: Trastuzumab inhibited the growth of MCF-7/HER2-18 cells, which overexpress HER2/neu receptors and express IGF-I receptors (IGF-IRs), only when IGF-IR signaling was minimized. For example, in 1% fetal bovine serum (FBS), trastuzumab reduced cell proliferation by 42% (P =.002); however, in 10% FBS or IGF-I, trastuzumab had no effect on proliferation. In SKBR3 cells, which overexpress HER2/neu receptor but express few IGF-IRs, trastuzumab reduced proliferation by 42% (P =.008) regardless of IGF-I concentration. When SKBR3 cells were genetically altered to overexpress IGF-IRs and cultured with IGF-I, trastuzumab had no effect on proliferation. However, the addition of IGF-binding protein-3, which decreased IGF-IR signaling, restored trastuzumab-induced growth inhibition. CONCLUSIONS: In breast cancer cell models that overexpress HER2/neu, an increased level of IGF-IR signaling appears to interfere with the action of trastuzumab. Thus, strategies that target IGF-IR signaling may prevent or delay development of resistance to trastuzumab.

Successful use of eptifibatide as an adjunct to coronary stenting in a patient with abciximab-associated acute profound thrombocytopenia.

A 72-year-old male who was given abciximab for unstable angina developed acute profound thrombocytopenia with a platelet count nadir of 6,000/mm3. He was treated with steroids and platelet transfusion. Four days later, he underwent coronary angioplasty after pretreatment with eptifibatide without development of thrombocytopenia. This suggests that the development of thrombocytopenia with abciximab is not necessarily a contraindication to subsequent use of glycoprotein (GP) IIb/IIIa receptor antagonists. Eptifibatide may be an appropriate consideration in high-risk patients who would benefit from a GP IIb/IIIa receptor antagonist, in spite of acute profound thrombocytopenia due to abciximab therapy.

Anabolic effects of rhIGF-I/IGFBP-3 in vivo are influenced by thyroid status.

BACKGROUND: There are close interrelationships between hormones that regulate bone formation and protein biosynthesis. For example, growth hormone and thyroid hormones can influence plasma levels of insulin-like growth factor-I (IGF-I). A patient's status regarding hormones other than IGF-I may thus indirectly modify the efficacy of IGF-I treatment. The aim of the current study was to determine if a statistical method could be used to identify key endocrine variables controlling an individual's response to IGF-I treatment. DESIGN: Biochemical profiles from the somatotropic, thyroid and adrenal axes were determined on two separate occasions in two different study cohorts. Each cohort was divided into four groups: placebo, low, medium and high dose of recombinant human IGF-I/IGF binding protein-3 (rhIGF-I/IGFBP-3). The relative changes in collagen C-terminal peptide (CICP) levels were explained as a function of the basal endocrine profile of each treated individual. This relationship was further examined in an experimental rat model, where undernourished rats were rendered hypothyroid by propylthiouracil and subsequently treated with rhIGF-I/IGFBP-3. RESULTS: The results of our statistical analysis in both cohorts indicated that each subject's response to rhIGF-I/IGFBP-3 administration was controlled in part by the individual's thyroid status prior to drug administration (r = 0.78 for both cohorts). The results from the animal study revealed that IGF-I treatment stimulated muscle protein synthesis by 35 +/- 9% (P = 0.05) in euthyroid rats but not in hypothyroid rats. CONCLUSION: The relationship between endocrine axes is not simple. An improved understanding of the interactions between neuroendocrine systems may facilitate the design of efficient drug regimens in the treatment of diseases such as osteoporosis and muscle wasting.

Acute profound thrombocytopenia without bleeding complications after re-administration of abciximab.

Abciximab (c7E3) is the Fab fragment of the chimeric (murine/human) monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor, which is the final common pathway for platelet aggregation. Abciximab has been widely used for patients undergoing angioplasty who are at high risk for ischemic complications. Severe thrombocytopenia (defined as platelet count < 50,000 platelet/mm3) has been observed in both first-time administration and re-administration of abciximab. Platelet transfusion as treatment for the reversal of thrombocytopenia is ubiquitously accepted. Intravenous corticosteroid as an adjunctive therapy is being explored. We previously reported our experience with platelet transfusion combined with corticosteroid treatment for acute thrombocytopenia following first-time abciximab administration. We now report a case of acute profound thrombocytopenia following re-administration of abciximab successfully treated with a combination of platelet transfusion and intravenous corticosteroid.

Combination of abciximab with primary stenting in patients with acute myocardial infarction: a community hospital experience.

Abciximab administration during primary coronary angioplasty in patients with acute myocardial infarction (AMI) reduces death, reinfarction, and the need for urgent target vessel revascularization (TVR). Stenting in AMI reduces the rate of repeat in-hospital TVR. There is limited information on the effectiveness and one-year clinical event rate of combined abciximab and primary stenting in patients with AMI at community hospitals. We evaluated the outcome of 40 consecutive patients treated with both abciximab and primary stenting at our institution. All patients underwent primary stenting of the infarct-related artery. All patients received abciximab, aspirin, ticlopidine, and heparin. TIMI grade 3 flow was established in all 40 patients. No patient required urgent TVR. There was no in-hospital reinfarction or cardiac-related death. All patients were followed for at least one year, and no patient died after hospital discharge. Thallium exercise stress test revealed no evidence of ischemia at 12 months follow-up. We conclude that combined abciximab and primary stenting in this series of patients with AMI was associated with excellent results.

Characterization of the inhibition of DNA synthesis in proliferating mink lung epithelial cells by insulin-like growth factor binding protein-3.

Insulin-like growth factor binding protein-3 (IGFBP-3) can inhibit cell growth by directly interacting with cells, as well as by forming complexes with IGF-I and IGF-II that prevent their growth-promoting activity. The present study examines the mechanism of inhibition of DNA synthesis by IGFBP-3 in CCL64 mink lung epithelial cells. DNA synthesis was measured by the incorporation of 5-bromo-2'-deoxyuridine, using an immunocolorimetric assay. Recombinant human IGFBP-3 (rh[N109D,N172D]IGFBP-3) inhibited DNA synthesis in proliferating and quiescent CCL64 cells. Inhibition was abolished by co-incubation of IGFBP-3 with a 20% molar excess of Leu(60)-IGF-I, a biologically inactive IGF-I analogue that binds to IGFBP-3 but not to IGF-I receptors. DNA synthesis was not inhibited by incubation with a preformed 1:1 molar complex of Leu(60)-IGF-I and IGFBP-3, indicating that only free IGFBP-3 inhibits CCL64 DNA synthesis. Inhibition by IGFBP-3 is not due to the formation of biologically inactive complexes with free IGF, since endogenous IGFs could not be detected in CCL64 conditioned media; any IGFs that might have been present could only have existed in inactive complexes, since endogenous IGFBPs were present in excess; and biologically active IGFs were not displaced from endogenous IGFBP complexes by Leu(60)-IGF-I. After incubation with CCL64 cells, (125)I-IGFBP-3 was covalently cross-linked to a major thick similar400-kDa complex. This complex co-migrated with a complex formed after incubation with (125)I-labeled transforming growth factor-beta (TGF-beta) that has been designated the type V TGF-beta receptor. (125)I-IGFBP-3 binding to the thick similar400-kDa receptor was inhibited by co-incubation with unlabeled IGF-I or Leu(60)-IGF-I. The ability of Leu(60)-IGF-I to decrease both the inhibition of DNA synthesis by IGFBP-3 and IGFBP-3 binding to the thick similar400-kDa receptor is consistent with the hypothesis that the thick similar400-kDa IGFBP-3 receptor mediates the inhibition of CCL64 DNA synthesis by IGFBP-3.

Abciximab readministration: A single-operator community-hospital experience.

Abciximab, a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor, reduces ischemic complications of coronary interventions after first administration. In this study, We sought to determine whether readministration of abciximab is associated with equal efficacy and safety. We retrospectively reviewed the charts of 35 patients who received two doses of abciximab at separate intervals. We monitored patients clinically for recurrent ischemia, bleeding complications, and thrombocytopenia. We measured hemoglobin and platelet counts before and after readministration of abciximab. There was no cardiac-related death, myocardial infarction, or recurrent ischemia. No obvious bleeding occurred in any of the 35 patients, although 1 patient had a drop of hemoglobin >3 gm/dl. We observed one episode of severe thrombocytopenia without any complication, and this patient improved without requiring platelet transfusion. There was no profound thrombocytopenia. We conclude that readministration of abciximab was well tolerated without any evidence of altered efficacy or safety. Cathet. Cardiovasc. Intervent. 47:294-296, 1999.

Normal electrocardiogram with total occlusion of the left anterior descending coronary artery.

Total occlusion of the left anterior descending coronary artery is usually characterized by ST-segment elevation in the anterior leads of the surface electrocardiogram. We report a case of a patient who had a persistently normal electrocardiogram throughout his hospitalization despite the angiographic findings of total occlusion of the left anterior descending coronary artery and no collateral vessels. Percutaneous transluminal coronary angioplasty with stent placement was performed successfully.

Acute profound thrombocytopenia without bleeding complications after abciximab administration.

Abciximab (c7E3) is the Fab fragment of the chimeric monoclonal antibody directed against glycoprotein IIb/IIIa found on the surface of platelets. It is the first FDA-approved platelet receptor glycoprotein inhibitor. Severe thrombocytopenia (defined as platelet count < 50 x 109/L) on first administration is a rare complication, occurring in only 1.6% of patients in the EPIC (Evaluation of 7E3 for the Prevention of Ischemic Complications) study. Bleeding complications were the rule in these thrombocytopenic patients as reported by EPIC investigators, Kereiakes et al. and Berkowitz et al. Platelet transfusions are required to reverse the bleeding diathesis. Intravenous IgG has not reportedly been helpful in reversing thrombocytopenia, and experience with corticosteroids is not reported in the literature. We report a case of acute profound thrombocytopenia following abciximab administration treated with platelet transfusion augmented by intravenous corticosteroids, in whom there was no bleeding complication.

Negotiating the maze of biotech "tool patents".

Circumventing existing patents may be a shortcut to getting your recombinant protein to market.

High-level expression of eukaryotic polypeptides from bacterial chromosomes.

Attractive economics and short development timelines have often been cited as reasons for using bacteria to express eukaryotic proteins on a commercial scale. Nevertheless, routine techniques for bacterial expression of heterologous proteins are beset by a variety of technical and legal difficulties. In particular, the use of plasmids to express foreign proteins, popular promoter systems, protein fusion partners, and histidine tags and the recovery of proteins from inclusion bodies are affected by a host of issued patents. Chromosomally encoded leaderless fusions (CELF) offer a variety of technical and legal advantages over existing bacterial expression systems. In this study, we show that CELF can be used to produce a wide assortment of eukaryotic proteins at 10-liter fermentation scale.