Organising football matches with spectators during the COVID-19 pandemic: What can we learn from the Amir Cup Football Final of Qatar 2020? A call for action.

The COVID-19 pandemic is a potential threat to professional sporting events when they eventually return to their usual calendar with spectators' capacity of football stadiums usually exceeding 40,000 seats for important events. Hence, a strategy for safe return to sporting events is needed in the COVID-19 pandemic to pave the way towards a new normalcy. We reviewed the guidelines and policies implemented in organising the Amir Cup Football Final of Qatar, which hosted about 20,000 fans. The authors evaluated the publicly available information on the official websites of the various organizations involved and highlight the importance and usefulness of the Covid-19 Rapid Antigen Assay-Kit as a tool for screening sports spectators as well as the importance of a rigorous spectator pathway, including their accurate traceability thanks to a specific mobile phone application. Despite the surging of COVID-19 all over the world, a big football event with around 20,000 spectators in the same stadium has been hosted under strongly controlled preventative measures. These preventative measures show that it is possible to organize a major football match held outdoors, with the presence of thousands of supporters. This article is a call for action for the organisers of such events where the supporters' health status is traceable to provide the scientific community with actual data of post-event infection rates. Therefore, it is suggested to consider using procedures like the ones described in the present article as a potential model in the process of organizing big sporting events with spectators in times of COVID-19.

Extradural Spinal Hamartoma Causing Spinal Cord Compression in an Adolescent Male: An Extremely Rare Case and Review of the Literature.

Spinal hamartoma is an extremely rare, benign spinal lesion occurring in children. It may cause spinal cord compression and subsequent neurological deficits. On reviewing the literature, of a total of 20 cases, only 2 cases are reported in an adolescent age group. It may be a pure spinal hamartoma, or sometimes it may be associated with either neurofibromatosis type I or spinal dysraphism. MRI is the investigation of choice. Surgical excision of the lesion and the decompression of the cord are the definitive treatment. Here, we pre-sent a similar case in a 16-year-old adolescent male, its diagnosis and further management.

Human ex-vivo oral tissue imaging using spectral domain polarization sensitive optical coherence tomography.

We report the use of spectral domain polarization sensitive optical coherence tomography for ex-vivo imaging of human oral mandibular tissue samples. Our results show that compared to the changes observed in the epithelium thickness and the decay constant of A-scan intensity profile, a much larger degree of change was observed in the phase retardation for tissue sites progressing from normal to the malignant state. These results suggest that monitoring of tissue retardance can help in better differentiation of normal and cancerous oral tissue sites.

Comparison of efficacy of cell block versus conventional smear study in exudative fluids.

INTRODUCTION: Cytological examination of serous effusions helps in staging, prognostication and management of patients with malignancy. The method has disadvantage of lower sensitivity in differentiating reactive atypical mesothelial cells from malignant cells. AIM: The aim of this study is to compare the cytological features of pleural and peritoneal exudative fluids by conventional smear (CS) method and cell block (CB) method and also to assess the utility of a combined approach for cytodiagnosis of these effusions. MATERIALS AND METHODS: One hundred and fifty-three pleural and peritoneal exudative fluid samples were subjected to evaluation by both CS and CB methods over a period of 2 years. Cellularity, architecture patterns, morphological features and yield for malignancy were compared, using the two methods. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for diagnosing malignancy were calculated by both methods, using histology as a gold standard. RESULTS: CB method provided higher cellularity, better architectural patterns and additional yield for malignancy as compared to CS method (P < 0.005). Sensitivity, specificity, PPV, NPV, and accuracy by CS method were 69.2%, 95%, 56.25%, 97.08% and 92.8%, while by CB method were 92.30%, 99.2%, 92.30%, 99.28% and 98.6%. CONCLUSION: The present study shows that it is advisable to routinely make CBs before discarding specimens that are suspicious for malignancy by smear examination.

Candida glabrata candidemia: An emerging threat in critically ill patients.

BACKGROUND: Candidemia is an important nosocomial blood stream infection in critically ill patients. Although several studies have addressed candidemia, very few have reviewed the impact of Candida glabrata candidemia in Intensive Care Unit (ICU) patients. MATERIALS AND METHODS: The medical records of ICU patients between 2006 and 2010 were reviewed retrospectively. The epidemiology, clinical features and mortality related risk factors among our adult ICU patients were seen. RESULTS: Among 144 episodes of candidemia, C. glabrata (n = 26; 18.05%) was the third most common species isolated. The incidence of C. glabrata candidemia was 0.21/1000 ICU admissions. The most common risk factors were prior exposure to broad spectrum antibiotics (100%), central venous catheter (100%), mechanical ventilation (76.9%), diabetes mellitus (50%), age >65 years (46.15%). Urine (23%) was the most common source of C. glabrata candidemia. Overall in hospital 30 days mortality rate due to C. glabrata fungemia was 53.8%. Patients who were treated with fluconazole showed better outcome than patients treated with amphotericin B. Renal failure requiring hemodialysis was the significantly associated with mortality in our study. CONCLUSION: Candida glabrata was the 3(rd) most common Candida causing candidemia in our ICUs with a incidence of 0.21/1000 ICU admissions. The outcome of ICU acquired C. glabrata candidemia was poor with 30 days mortality rate of 53.8%. Renal failure requiring hemodialysis was the only risk factor associated with mortality. Further studies are required to identify the other risk factors associated with mortality in C. glabrata candidemia.

Leukocyte activity in patients with ST-segment elevation acute myocardial infarction treated with anakinra.

Anakinra, the recombinant form of the human interleukin (IL)-1 receptor antagonist, blunts the acute systemic inflammatory response in patients with ST-segment elevation myocardial infarction (STEMI), by determining a fall in peripheral blood leukocyte and plasma C-reactive protein levels. The aim of the present study was to determine the effects of anakinra on the activity of leukocytes measured ex vivo. Blood was collected 72 h after admission in 17 patients enrolled in the Virginia Commonwealth University-Anakirna Remodeling Trial (2) (VCU-ART2) and randomly treated with anakinra (N=7) or placebo (N=10). Whole blood was cultured at 37°C for 24 h to measure spontaneous production of IL-6 or stimulated with Escherichia coli lipopolysaccharide (LPS) for toll-like receptor (TLR)-4 or heat-killed Staphylococcus epidermidis (SE) for TLR-2 activation. The cultures of anakinra-treated patients produced significantly less IL-6 spontaneously (71 pg/mL [27-114]) compared with placebo-treated patients (290 pg/mL [211-617], p=0.005). LPS- or SE-induced IL-6 production, on the other hand, was not statistically different between anakinra-versus placebo-treated patients (344 pg/mL [94-560] versus 370 pg/mL [306-991], p=0.32 for LPS, and 484 pg/mL [77-612] versus 615 pg/mL [413-871], p=0.31 for SE, respectively). IL-1 blockade with anakinra in STEMI patients results in reduced spontaneous leukocyte activity ex vivo without impairing the responsiveness to bacterial stimuli.

Infective endocarditis in an Indian setup: Are we entering the 'modern' era?

BACKGROUND: The clinical profile of infective endocarditis (IE) has been continuously evolving over last 3-4 decades as highlighted by many studies from developed world. OBJECTIVES: To evaluate the recent changes in the spectrum and clinical profile, and outcome of IE in an Indian setup. MATERIALS AND METHODS: This was a descriptive, cross-sectional study. Demographic, clinical, characteristics, treatment, and outcome were examined in 'definite' cases of IE admitted at our institute between July 2005 and December 2010. RESULTS: 61 'definite' cases were identified. Mean patient age was 49.3 ± 13.7 years. Male to female ratio was 3.3:1. Rheumatic heart disease was the underlying heart disease in 23 (37.7%) patients. 33 (54.1%) patients had already received antibiotic therapy before presentation to us. Blood cultures were positive in 41 (67.2%) patients. Streptococci and staphylococci were the commonest microbial isolates, 9 (21.4%) patients each. Transesophageal echocardiography (TEE) was done for all the patients. Vegetations were detected in 54 (88%) patients. Surgery was done in 30 (49.2%) patients. In-hospital mortality happened in 4 (6.5%) patients. CONCLUSIONS: WE RECORDED SEVERAL NEW TRENDS, LIKE: 1) an increasing age, 2) an increasing proportion of patients with no previously known heart disease, 3) improving culture positivity rates, 4) rise in staphylococcal infections, 5) increased usage of TEE, 6) high elective surgical rate, and 7) apparent improved survival rates. These changes point to the fact that 'modern era' changes in the profile of IE have started to appear in a selected population in India.

Endometrial Histopathology in Abnormal Uterine Bleeding and Its Relation With Thyroid Profile and Endometrial Thickness.

INTRODUCTION: Abnormal uterine bleeding (AUB) is a common complaint in postmenopausal and perimenopausal women, caused by a range of disorders, including structural and systemic diseases. The evaluation of endometrial thickness (ET) via radiological methods, followed by a histopathological examination of the endometrium, is useful for proper diagnosis. Among systemic diseases, thyroid dysfunction, specifically hypothyroidism and hyperthyroidism, contribute significantly to AUB cases. MATERIALS AND METHODS: This descriptive cross-sectional study was conducted at Sri Aurobindo Medical College, Indore, Madhya Pradesh, India, over a period of 16 months, from May 2021 to September 2022. Patients presenting with abnormal uterine bleeding and undergoing thyroid function tests (TFTs), ultrasonography, and endometrial biopsy/hysterectomy at the gynecological outpatient department were included. Hospital records were used to obtain clinical details and investigation results. Endometrial thickness and thyroid status were recorded, and descriptive statistics were used to analyze the collected data. RESULTS: This study included 150 patients with abnormal uterine bleeding, with a mean age of 44 years and 80.6% of patients in the premenopausal age group. A total of 48% of patients had a deranged thyroid profile, with hypothyroidism being more common (91.6%). Structural causes of AUB were identified in 81.3% of cases, with adenomyosis (33.65%), concomitant adenomyosis and leiomyoma (31.5%), and leiomyoma (14.8%) being the most common. Endometrial polyps (4.6%) and endometrial carcinoma (0.6%) were also observed and were consistent with the final histopathology. The remaining 18 patients had no structural causes and were categorized as cases of dysfunctional uterine bleeding (DUB). Increased ET was more commonly observed in postmenopausal patients (4.3%) compared to premenopausal patients (0.7%) among those with AUB, while the reverse was true for patients with DUB. Increased ET was commonly associated with hypothyroidism in both groups. Histopathological examination of endometrial biopsies/hysterectomy specimens revealed additional findings in some patients, including hyperplasia of the endometrium with (0.7%) and without atypia (4%), leading to a more accurate diagnosis. CONCLUSION: AUB is a prevalent condition affecting women in both pre-menopausal and postmenopausal stages, frequently caused by structural anomalies. However, thyroid dysfunction, especially hypothyroidism, is also a significant contributing factor. As such, thyroid function tests (TFTs) are an effective and economical means of identifying potential underlying causes of AUB. Hypothyroidism is frequently associated with increased endometrial thickness, and histopathological examination remains the gold standard for determining the precise cause of AUB.

Management of diabetic dyslipidemia in Indians: Expert consensus statement from the Lipid Association of India.

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians.

Point of care serum lactate levels as a prognostic marker of outcome in complex pediatric cardiac surgery patients: Can we utilize it?

BACKGROUND: Post-operative course after complex pediatric cardiac surgery is unpredictable. Although, change in arterial lactate levels has been used as a surrogate marker for many years, scientific evidence correlating the early perioperative lactate levels with outcome is still lacking. OBJECTIVE: To evaluate the trends in lactate levels from intraoperative period to an extended post-operative period in pediatric intensive care unit (PICU) and to assess its usefulness as a prognostic marker. DESIGN: Prospective observational study. SETTING: Tertiary pediatric cardiac surgical unit. PATIENTS: Thirty-five non-consecutive children aged 1-140 months who underwent surgery for congenital heart diseases (CHD) on cardiopulmonary bypass (CPB). INTERVENTION: None. MATERIALS AND METHODS: ARTERIAL BLOOD LACTATE LEVELS WERE OBTAINED AT THE FOLLOWING TIME POINTS: After induction of anesthesia, 15 and 45 min after institution of CPB, at the start of rewarming, after sternotomy closure, then at 1, 6, 24, and 48 h in PICU. Other hemodynamic and clinical variables, CPB variables, blood gas values, and laboratory variables were also recorded. RESULTS: Four patients died out of 35 patients (11.4%). Non-survivors showed significant persistent elevation in lactates (>4.0 mmol/l). Peak lactates correlate significantly with longer aortic cross clamp time, CPB duration, ventilation hours and PICU stay. CONCLUSION: Early point of care lactate can be a useful prognostic marker in post-cardiac surgery patients in adjunct with other parameters measured in PICU. This reiterates the importance of measuring lactates and timely recognition of at-risk patients, which on early intervention can help in reducing post-operative morbidity and mortality.

Design-computer-aided manufacturing guided implant-supported prosthesis in a fibular graft reconstructed mandible: A 7-year follow-up of a case.

Reconstruction of functional occlusion in case of a large surgical defect of the mandible involving partial mandibulectomy remains a significant challenge to the maxillofacial surgeon and prosthodontist. Removable appliances and the conventional implant-supported prosthesis are precluded in this case due to the absence of normal anatomical contours of the bone. In recent years, due to the advancement of technology, bone graft reconstruction with computer-guided rehabilitation of the functional occlusion has been advocated to reverse the debilitating effects of the hemimandibulectomy defect. This clinical report describes the prosthodontic management of fibular graft reconstructed mandible by computer-aided design-computer-aided manufacturing guided implant-supported prosthesis.

Age and clinical signs as predictors of COVID-19 symptoms and cycle threshold value.

Many COVID-19 infected people remain asymptomatic, and hence the diagnosis at first presentation remains a challenge. Assessment at a presentation in primary care settings is usually done by visual triaging and basic clinical examination. This retrospective study involved investigating the medical e-records of COVID-19 positive patients who presented to a COVID-19 centre in Qatar for July 2020. The presence (symptomatic group) or the absence (asymptomatic group) of symptoms along with objective vital examination (ie; heart-rate (HR), temperature, haemoglobin saturation (SpO2)) were analysed and linked to the viral load (ie; cycle threshold (Ct)) of COVID-19 positive patients. Four hundred eighty-one symptomatic (230 males) and 216 asymptomatic (101 males) patients were included. Compared to the asymptomatic male group, the symptomatic male group was older, had lower Ct value and SpO2, and higher temperature and HR. Compared to the females asymptomatic group, the symptomatic females group had lower Ct value, and higher temperature. Compared to the asymptomatic group, the symptomatic group had lower Ct value and SpO2, and higher temperature and HR. Compared to the asymptomatic group, the symptomatic group had lower Ct values (age groups [21-30], [31-40], [41-50] and [51-60]), higher temperature (age groups [21-30] and [31-40], Ct ranges [20.01-25.00] and [25.01-30.00]), higher HR (age groups [21-30] and [31-40], Ct range [15.01-20.00]); and lower SpO2 (age groups [41-50] and [51-60], Ct ranges [15.01-20.00] and [35.01-40.00]). Compared with asymptomatic patients, symptomatic patients with COVID-19 are most likely to be febrile, tachycardic, hypoxic and having higher viral load. Higher viral load was associated with higher HR, higher temperature, lower SpO2, but there was no relation between viral load and age.

Is there a diurnal variation of COVID-19 patients warranting presentation to the health centre? A chronobiological observational cross-sectional study.

BACKGROUND: The circadian clock regulates the function of the immune system, the replication of viruses, and the magnitude of infections. The aim of this study was to analyse whether hospital attendance in Coronavirus disease 2019 (COVID-19) patients presents a diurnal variation. METHODS: Data from the electronic medical records of 1094 COVID-19 patients who presented to a Health Centre in Qatar during the month of July 2020 was retrospectively analysed. The following demographic (i.e. time of day (TOD), sex, age), clinical (i.e. cycle threshold (CT), temperature, oxy-haemoglobin saturation and resting heart-rate), biochemical (i.e. uraemia, glycaemia and albuminia) and haematological (i.e. leukocytes, erythrocytes ad platelets) parameters were collected. RESULTS: Univariate analysis showed a significant effect of TOD on hospital admission (p < 0.001), with patients attending the health care centre more during the active behavioural phase (08h00-00h00) compared to the resting phase (00h00-08h00). COVID-19 infection blunted the circadian rhythms of core body temperature, neutrophils and leukocytes family and shifted the circadian rhythms of resting heart-rate and uraemia. Correlation analysis showed a near perfect negative correlation between the age of patients and the TOD (r=-0.97), with older patients attending the care centre earlier during the day. CONCLUSION: COVID-19 infection affected the circadian rhythms of the host through disrupting the circadian rhythms of core temperature and innate immunity mediators. Old patients attend the health care centre earlier compared to younger ones. However, CT during polymerase chain reaction-test was unaffected by the TOD, which limits the conclusion that COVID-19 viral infection exhibits diurnal variation.

Maiden visit of visceral leishmaniasis to Malwa region.

Visceral leishmaniasis (VL) is a well known public health problem in eastern parts of India. So far the cases have not been reported from Malwa plateu of Madhya Pradesh, to the best of our knowledge and available literature. We report here two cases of Visceral Leishmaniasis first time from the Malwa region. Both the cases are from the migratory population of Bihar. The diseases like Leishmaniasis which were previously restricted to endemic areas of the country are spreading to non-endemic areas along with the large migratory population, which is seen with the development of the country. The cases are reported to inform the National health authorities to take proper steps to curb the spread of the disease to non-endemic areas and to emphasize the need of vector surveys in these areas.

Impression Cytology Screening for Ocular Surface changes in various forms of Vernal Keratoconjunctivitis in Subtropical Central Zone in India.

INTRODUCTION: Vernal keratoconjunctivitis (VKC) is a chronic recurrent allergic disorder of the eye more common in warm and dry climates like central India. Chronic and recurrent nature of disease requires long duration of treatment which leads to changes in ocular surface leading to cytomorphological distortion of goblet cells, that can be evaluated by impression cytology. Clinical presentation and impact of disease on cytomorphology of ocular surface was analysed in various forms of the VKC. The objective of this study was to find correlation of clinical profile and cytomorphological changes in ocular surface in patients with various forms of vernal keratoconjunctivitis. MATERIALS AND METHODS: This cross sectional study analysed 120 eyes of 60 patients of various forms of vernal keratoconjunctivitis. Detailed history was taken along with complete ophthalmic examination. Vernal keratoconjunctivitis was graded as per Gokhale et al classification. Impression cytology for goblet cell morphology and metaplasia according to classification given by Saini et al was done. Cytological changes were noted for different age groups, duration of disease, and severity of disease. RESULTS: Vernal keratoconjunctivitis was seen more commonly in males and in the second decade of life which shows a changing trend towards higher age. Milder forms were more commonly present than moderate and severe forms. Mostly Grade 2 changes were seen on impression cytology. CONCLUSION: Increasing severity, duration of disease and age of presentation was directly proportionate to greater cytological changes on ocular surface.

Does lunar cycle affect biological parameters in young healthy men?

This study aimed to assess the effects of the lunar cycle on diurnal variation of biological, i.e, hormonal, biochemical, and hematological, profiles of diurnally active healthy men. Blood samples of 20 males were collected on four occasions [full moon (FM) and new moon (NM), in the morning (06:00-07:00 h) and evening (19:00-20:00 h)]. The results showed that melatonin and testosterone levels and neutrophils count were lower during the FM as compared to the NM in the morning (p < .001; d = 4.13, p < .001; d = 3.84, p < .01; d = 0.77, respectively) and evening (p < .001; d = 6.36, p < .001; d = 4.03, p < .05; d = 1.07, respectively) samples. However, cortisol level was higher during the FM compared to the NM, in the morning (p < .001; d = 0.74) and evening (p < .001; d = 3.54). Hemoglobinemia was higher only in the evening during the FM compared to the evening of the NM (p < .01; d = 1.22). In summary, this study confirmed that lunar cycle can affect human biological parameters independently of time of day.

Covid-19 and diabetes in primary care - How do hematological parameters present in this cohort?

Objectives: Changes in hematological parameters are becoming evident as important early markers of COVID-19. Type 2 Diabetes Mellitus (T2DM) has been shown to be associated with increased severity of COVID-19. In this study, we aim to explore the various hematological variables in COVID-19 positive patients with T2DM, so as to act early and improve patient outcomes.Methods: Medical e-records of seventy adult patients with T2DM who were COVID-19 positive have been analyzed in this retrospective cohort study. Demographic, clinical and laboratory parameters for these patients were examined.Results: Of the seventy patients with T2DM, 48.88% had poorly controlled diabetes. 70.69% were pyrexial, 56.25% were tachycardic and 38.58% were asymptomatic on presentation. Amongst the hematological parameters, anemia was seen in 10% of males and 15.38% of females. 20% had a high red-blood-cell-distribution-width (RDW). 7.27% had thrombocytosis and 3.64% had thrombocytopenia. 73.3% had a high platelet-distribution-width (PDW) and 44.44% had an increased mean-platelet-volume (MPV). 16.36% were neutropenic and 16.67% had lymphocytopenia.Conclusion: Diabetic COVID-19 positive patients have been shown to have prominent manifestations of the hemopoietic-system with varied hematological profiles. Recognizing the implications of these variables early in primary-care, can help clinicians aid management decisions and dictate early referral to secondary-care services, to help improve prognosis.

Phosphodiesterase-5 inhibitor, tadalafil, protects against myocardial ischemia/reperfusion through protein-kinase g-dependent generation of hydrogen sulfide.

BACKGROUND: Tadalafil is a novel long-acting inhibitor of phosphodiesterase-5. Because cGMP-dependent protein kinase (PKG) signaling plays a key role in cardioprotection, we hypothesized that PKG activation with tadalafil would limit myocardial ischemia/reperfusion (I/R) injury and dysfunction. Additionally, we contemplated that cardioprotection with tadalafil is mediated by hydrogen sulfide (H(2)S) signaling in a PKG-dependent fashion. METHODS AND RESULTS: After baseline transthoracic echocardiography (TTE), adult ICR mice were injected i.p. with vehicle (10% DMSO) or tadalafil (1 mg/kg) with or without KT5823 (KT, PKG blocker, 1 mg/kg) or dl-propargylglycine (PAG, Cystathionine-gamma-lyase [CSE, H(2)S-producing enzyme] blocker; 50 mg/kg) 1 hour before coronary artery ligation for 30 minutes and reperfusion for 24 hours, whereas C57BL wild-type and CSE-knockout mice were treated with either vehicle or tadalafil. After reperfusion, TTE was performed and hearts were collected for infarct size (IS) measurement using TTC staining. Survival was increased with tadalafil (95%) compared with control (65%, P<0.05). Infarct size was reduced with tadalafil (13.2+/-1.7%) compared to vehicle (40.6+/-2.5%; P<0.05). KT and PAG abolished tadalafil-induced protection (IS: 39.2+/-1% and 51.2+/-2.4%, respectively) similar to genetic deletion of CSE (47.2+/-5.1%). Moreover, tadalafil preserved fractional shortening (FS: 31+/-1.5%) compared to control (FS: 22+/-4.8%, P<0.05). Baseline FS was 44+/-1.7%. KT and PAG abrogated the preservation of LV function with tadalafil by decline in FS to 17+/-1% and 23+/-3%, respectively. Compared to vehicle, myocardial H(2)S production was significantly increased with tadalafil and was abolished with KT. CONCLUSIONS: PKG activation with tadalafil limits myocardial infarction and preserves LV function through H(2)S signaling.

Interleukin-1 trap attenuates cardiac remodeling after experimental acute myocardial infarction in mice.

BACKGROUND: Interleukin-1 (IL-1) is an inflammatory cytokine that responds as an acute phase reactant during acute myocardial infarction. Conflicting data describe the role of anti-IL-1 interventions to reduce cardiac remodeling after AMI. IL-1 Trap is a modified recombinant fusion protein that binds circulating IL-1. Our study evaluated the effects of murine IL-1 Trap on cardiac remodeling after AMI resulting from permanent surgical coronary artery ligation. METHODS: Mice received treatment with intraperitoneal injection of murine IL-1 Trap (1 mg/kg [n = 5], 5 mg/kg [n = 5], or 30 mg/kg [n = 5]) or NaCl 0.9% (saline; n = 10) every 48 hours after surgery. Transthoracic echocardiography was performed at baseline and 7 days after surgery. Inhibition of IL-1 signaling was determined by measurement of IL-6 plasma levels (enzyme-linked immunosorbent assay) after IL-1b injection. Apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) was measured in murine heart samples and in a primary culture of murine cardiomyocytes. RESULTS: Mice treated with 5 mg/kg or 30 mg/kg IL-1 Trap had more favorable cardiac remodeling and echocardiographic assessment of infarct size at 7 days compared with saline (P < 0.05 for each comparison). Treatment with IL-1 Trap also reduced apoptosis and IL-6 levels compared with saline treatment. CONCLUSIONS: IL-1 Trap ameliorates cardiac remodeling and reduces cardiomyocyte apoptosis after experimental acute myocardial infarction in the mouse.

Pharmacologic inhibition of myeloid differentiation factor 88 (MyD88) prevents left ventricular dilation and hypertrophy after experimental acute myocardial infarction in the mouse.

BACKGROUND: Myeloid differentiation factor 88 (MyD88) is an endogenous adaptor protein that coordinates the inflammatory response to agonists of the Toll-like receptor and interleukin-1 receptor families. This particular response is activated following myocardial ischemia and infarction and may represent a viable target for pharmacologic inhibition. The current study tested MyD88 inhibitors in a murine model of nonreperfused acute myocardial infarction (AMI). METHODS: AMI was induced by permanent ligation of the left coronary artery. Adult, male, Imprinting Control Region mice were randomized to daily injections with 1 of 2 MyD88 pharmacologic inhibitors (ST2825 25 mg/kg or IMG2005 1 mg/kg), saline, or pretreatment with MyD88-targeted silencing small interfering RNA (siRNA) or scrambled nontargeted siRNA (n = 6 for each group). Echocardiography was performed at baseline and 7 days after surgery to evaluate pathologic cardiac enlargement. RESULTS: Pharmacologic inhibition of MyD88 with ST2825 or IMG2005) and MyD88-targeted siRNA protected against left ventricular (LV) dilatation (reduced LV end-systolic and LV end-diastolic diameter) and hypertrophy. This protection occurred despite no measurable reduction in infarct size. CONCLUSIONS: Pharmacologic MyD88 inhibition protects against pathologic LV remodeling without altering infarct scar formation. MyD88 may be a viable target for pharmacologic inhibition in AMI.