Myocardial tuberculosis and beyond: A rare form of extra pulmonary TB in a young boy.

Myocardial tuberculosis is an exceptionally rare form of extra-pulmonary TB. Few cases were reported world-wide. Here a young snake charmer who had skin tuberculosis 5 yrs back admitted into National institute of diseases of Chest and hospital (NIDCH), Dhaka with the complaints of cough, palpitation and breathlessness for 2 months. He had right axillary firm matted lymphadenopathy, left sided large pleural effusion, left ventricular and septal hypertrophy with band and mass inside the ventricle (evident on CT scan of heart and echocardiography). His ESR was 95 mm in1st hr, Mantaux test was 15mm, Pleural fluid was exudative lymphocyte predominant with adenosin deaminase (ADA) 68.6 U/L. Fine needle aspirates from right axillary LNs showed Mycobacterium tuberculosis on GeneXpert for MTB/RIF testing and caseous granuloma on cytopathological study. Whole Body F18 FDG PET-CT revealed numerous low FDG avid size significant lymph nodes in right side of neck, mediastinum and right axilla with cardiomegaly with focal FDG avid within the left ventricular cavity likely to be prominent papillary muscle. MRI of heart or Myocardial biopsy for histology was not done due to their cost and invasiveness and also for that there was sufficient evidence of having tuberculosis in lymph node, pleura nas myocardium. This patient was treated with anti tubercular medications (3HRZE2S/5HRE) with prednisolone for six months. After treatment, myocardial lesions, pleural effusion and lymphadenopathy were found resolved. Thus a case of fatal and serious tuberculosis was explored and managed successfully.

The Administration of the Synbiotic Lactobacillus bulgaricus 6c3 Strain, Inulin and Fructooligosaccharide Decreases the Concentrations of Indoxyl Sulfate and Kidney Damage in a Rat Model.

Indoxyl sulfate (IS) is involved in the progression of chronic kidney disease (CKD) and in its cardiovascular complications. One of the approaches proposed to decrease IS is the administration of synbiotics. This work aimed to search for a probiotic strain capable to decrease serum IS levels and mix it with two prebiotics (inulin and fructooligosaccharide (FOS)) to produce a putative synbiotic and test it in a rat CKD model. Two groups of Sprague-Dawley rats were nephrectomized. One group (Lac) received the mixture for 16 weeks in drinking water and the other no (Nef). A control group (C) included sham-nephrectomized rats. Serum creatinine and IS concentrations were measured using high-performance liquid chromatography with diode array detector (HPLC-DAD). Optical microscopy and two-photon excitation microscopy was used to study kidney and heart samples. The Lac group, which received the synbiotic, reduced IS by 0.8% while the Nef group increased it by 38.8%. Histological analysis of kidneys showed that the Lac group increased fibrotic areas by 12% and the Nef group did it by 25%. The synbiotic did not reduce cardiac fibrosis. Therefore, the putative synbiotic showed that function reducing IS and the progression of CKD in a rat model, but no heart protection was observed.

Cardiac thrombus and stroke in a child with Mycoplasma pneumoniae pneumonia: A case report.

RATIONALE: Cardiac thrombus and stroke are rare complications in Mycoplasma pneumoniae infection, which is a common cause of community-acquired pneumonia in children. Early detection and prevention of thrombus in children with M pneumoniae pneumonia is relatively difficult. PATIENT CONCERNS: A 5-year-old boy with severe M pneumoniae pneumonia was referred to our center. During the treatment with sufficient antibiotics, an echocardiography surprisingly revealed a thrombus in the left atrium, with significant changes in D-dimer level and anti-phospholipid antibodies. At day 12 after admission, the patient showed impaired consciousness, aphasia, and reduced limb muscle power. Magnetic resonance angiography (MRA) showed right middle cerebral artery infarction. DIAGNOSES: Cardiac thrombus and stroke associated with M pneumoniae pneumonia. INTERVENTIONS: He was started on aggressive antibiotic therapy and urokinase thrombolytic therapy for 24 hours, continued with low molecular heparin calcium and aspirin along with rehabilitation training. OUTCOMES: On follow up, the D-dimer decreased slowly and echocardiograms showed a steadily decreasing size of thrombus with eventual disappearance at day 22 after admission. His left limb muscle power was improved after rehabilitation for 2 months. LESSONS: Early diagnosis and treatment with multiple modalities maybe useful for improving prognosis of cardiac thrombus and stroke in M pneumoniae pneumonia. Changes in D-dimer level and anti-phospholipid antibodies should be routinely monitored in severe M pneumoniae pneumonia.

Melatonin Alleviates Cardiac Dysfunction Via Increasing Sirt1-Mediated Beclin-1 Deacetylation and Autophagy During Sepsis.

Cardiac dysfunction is a major cause leading to multiple organ failure in sepsis. Beclin-1-dependent autophagy has been evidenced to exert protective effects on hearts in sepsis. However, the mechanisms on how Beclin-1 and autophagy are regulated remains enigmatic. To explore the detailed mechanisms controlling Beclin-1-dependent autophagy in septic heart and whether melatonin could protect against sepsis via regulating cardiac autophagy, adult Sprague-Dawley (SD) rats were subjected to cecal ligation and puncture (CLP) to induce sepsis. Rats were intraperitoneally administrated with 30 mg/kg melatonin within 5-min post-CLP surgery. Our data showed that sepsis induced Becline-1 acetylation and inhibited autophagy in hearts, resulting in impaired cardiac function. However, melatonin treatment facilitated Beclin-1 deacetylation and increased autophagy in septic hearts, thus improved cardiac function. Moreover, melatonin increased the expression and activity of Sirtuin 1 (Sirt1), and inhibition of Sirt1 abolished the protective effects of melatonin on Beclin-1 deacetylation and cardiac function. In conclusion, increased Beclin-1 acetylation was involved in impaired autophagy in septic hearts, while melatonin contributed to Beclin-1 deacetylation via Sirt1, leading to improved autophagy and cardiac function in sepsis. Our study sheds light on the important role of Beclin-1 acetylation in regulating autophagy in sepsis and suggests that melatonin is a potential candidate drug for the treatment of sepsis.

Cardiac Microlesions Form During Severe Bacteremic Enterococcus faecalis Infection.

Enterococcus  faecalis is a significant cause of hospital-acquired bacteremia. Herein, the discovery is reported that cardiac microlesions form during severe bacteremic E. faecalis infection in mice. The cardiac microlesions were identical in appearance to those formed by Streptococcus pneumoniae during invasive pneumococcal disease. However, E. faecalis does not encode the virulence determinants implicated in pneumococcal microlesion formation. Rather, disulfide bond forming protein A (DsbA) was found to be required for E. faecalis virulence in a Caenorhabditis elegans model and was necessary for efficient cardiac microlesion formation. Furthermore, E. faecalis promoted cardiomyocyte apoptotic and necroptotic cell death at sites of microlesion formation. Additionally, loss of DsbA caused an increase in proinflammatory cytokines, unlike the wild-type strain, which suppressed the immune response. In conclusion, we establish that E. faecalis is capable of forming cardiac microlesions and identify features of both the bacterium and the host response that are mechanistically involved.

Multi-walled carbon nanotubes exacerbate doxorubicin-induced cardiotoxicity by altering gut microbiota and pulmonary and colonic macrophage phenotype in mice.

Epidemiologic studies show that the levels of air pollutants and particulate matter are positively associated with the morbidity and mortality of cardiovascular diseases. Here we demonstrate that the intratracheal instillation of multi-walled carbon nanotubes (MWCNTs), a standard fine particle, exacerbate doxorubicin (DOX)-induced cardiotoxicity in mice through altering gut microbiota and pulmonary and colonic macrophage phenotype. MWCNTs (25 µg/kg per day, 5 days a week for 3 weeks) promoted cardiotoxicity and apoptosis in the DOX (2 mg/kg, twice a week for 5 weeks)-treated C57BL/6 mice. MWCNTs exaggerated DOX-induced gut microbiota dysbiosis characterized by the increased abundances of Helicobacteraceae and Coriobacteriaceae. In addition, MWCNTs promoted DOX-induced M1-like polarization of colonic macrophages with an increase in TNF-α, IL-1ß and CC chemokine ligand 2 in peripheral blood. Importantly, treatment with the antibiotics attenuated MWCNTs plus DOX-induced apoptosis of cardiomyocytes and M1-like polarization of colonic macrophages. The fecal microbiota transplantation demonstrated that MWCNTs exaggerated DOX-induced cardiotoxicity with M1-like polarization of colonic macrophages. The conditioned medium from MWCNTs-treated pulmonary macrophages promoted DOX-induced gut microbiota dysbiosis and colonic macrophage polarization. Furthermore, the co-culture of macrophages and fecal bacteria promoted M1-like macrophage polarization and their production of TNF-α and IL-1ß, and thereby exacerbated the effects of MWCNTs. Moreover, IL-1ß and TNF-α blockade, either alone or in combination attenuated MWCNTs-exacerbated cardiotoxicity. In summary, MWCNTs exacerbate DOX-induced cardiotoxicity in mice through gut microbiota and pulmonary and colonic macrophage interaction. Our findings identify a novel mechanism of action of inhaled particle-driven cardiotoxicity.

Effects of Long-term Anesthesia, Blood Sampling, Transportation, and Infection Status on Hearts and Brains in Pigs Inoculated with Staphylococcus aureus and Used for Imaging Studies.

Laboratory animals are widely used in imaging studies, including infection, heart, and brain research. Compared with rodents, pigs are especially useful because of their large organ sizes, ability to tolerate long-term anesthesia, and substantial blood volume, which allows repeated blood sampling. These factors are particularly important in positron emission tomography studies of potential new radioactive tracers, because the scans often are prolonged; in addition, kinetic studies involving repeated blood sampling may be performed to establish the optimal scan time. However, protracted studies may affect the cardiovascular system, brain, and other organs. This raises the question of how to monitor and counteract the effects of longterm anesthesia in pigs in a typical experimental setting yet prevent introducing bias into the experiment. To address this question, we investigated the effects of long-term anesthesia (maximum, 18 h), repeated blood sampling (maximum of 20 mL blood per kilogram body weight), and road transportation (as long as 1.5 h between 2 imaging centers) on key variables of lung, heart, and brain function in the context of a well-established pig model of Staphylococcus aureus infection. Pulse rate, oxygen saturation, body temperature, arterial pressure of CO2, and urine production were stable during anesthesia for at least 16 h, whereas blood glucose slowly decreased. Hct and leukocyte count decreased due to repeated blood sampling. During road transportation, blood lactate levels increased 5 fold and arterial pressure of O2 decreased by 50%. Repeated CT scans, necropsy results, and histopathology findings documented progressive lung changes and acute cardiac necrosis. No lesions indicative of hypoxia were found in brain. The study data show that the typical monitoring parameters do not fully depict the cardiovascular state of pigs during prolonged anesthesia. We recommend streamlining experimental protocols for imaging studies in pigs to avoid organ pathology.

Case Report: Concurrent Rheumatic Fever and Acute Post-Streptococcal Glomerulonephritis in a High-Burden Setting.

We report a case of acute rheumatic fever with severe pancarditis occurring simultaneously with probable acute post-streptococcal glomerulonephritis in a previously well, Australian Aboriginal, 29-year-old male. These autoimmune streptococcal sequelae are usually considered pathogenetically distinct, and concurrence has not previously been reported from this high-burden setting. We hypothesize that a single type of infecting group A Streptococcus (Strep A) triggered both autoimmune sequelae. Salient features included mitral and aortic regurgitation that worsened during the acute illness, painful pericarditis, and high troponin; severe acute kidney injury with oliguria, hematuria, and macroalbuminuria; reduced complement (C3); and elevated streptococcal serology. The case highlights important diagnostic and management challenges. It also illustrates the serious morbidity impact of the complications of Strep A.

Dexmedetomidine prevents septic myocardial dysfunction in rats via activation of α7nAChR and PI3K/Akt- mediated autophagy.

BACKGROUND AND PURPOSE: Dexmedetomidine (Dex) has been shown to elicit cardio-protective effects in sepsis. The aim of this study was to investigate the role of autophagy in the protective effects of Dex and its possible mechanism in vivo and vitro. EXPERIMENTAL APPROACH: 6-8-week-old male Wistar rats were performed cecal ligation puncture (CLP) and administered 0.9% saline (CLP group), 50 µg/kg Dex (Dex group), Dex plus chloroquine (20 mg/kg; Dex + CQ group), or 40 µg/kg methyllycaconitin (Dex + MLA group), or 25 µM LY294002 (Dex + LY294002 group). After study, cardiac histology, cardiac function, level of autophagy, cardiomyocytes apoptosis and inflammatory mediators including protein IL-1ß, IL-6, and TNF-α were measured. The LPS induced-H9C2 cardiomyocytes were treated with Dex, Dex + CQ and detected for cell apoptosis, autophagy level and cell cycle. KEY RESULTS: CLP-induced sepsis resulted in cardiac dysfunction, apoptosis, and inflammatory response. Dex exhibited protective effects on the myocardium by the induction of myocardial autophagy and ameliorated the LPS-induced blockade of autophagic flux in H9C2 cells. CQ was found to significantly inhibit Dex-mediated protection of myocardial apoptosis and inflammation. CLP rats treated with Dex in combination with MLA, an antagonist of α7 nicotinic acetylcholine receptor (α7nAChR), exhibited decreased autophagy and increased inflammation and cell death, identifying α7nAchR was involved in the Dex-mediated pathway. In addition, we found that the PI3K/Akt pathway is involved in Dex-mediated autophagy and convergent with α7nAChR-mediated stimulation of autophagy response. CONCLUSIONS AND IMPLICATIONS: For the first time, these data indicate that autophagy is central in Dex-mediated cardio-protection in sepsis. These observations provide the foundation for further study, and may serve as the basis for innovative therapeutic strategies against septic myocardial dysfunction.

Cardiac Involvement in Travelers with Enteric Fever.

Data regarding cardiac involvement in enteric fever among travelers are scarce. In this retrospective study, 59 patients were hospitalized with enteric fever during 2004-2017 and 28 had cardiac workups. Among those, four had evidence of cardiac involvement, including clinical myocarditis, electrocardiogram changes, or troponin elevation. Cardiac involvement was higher among patients infected with Salmonella Typhi than with Salmonella Paratyphi A (P = 0.08), with a significant relative risk of 6 (95% CI: 1.15-31.22, P = 0.03). Time from symptoms onset to effective treatment was longer for patients with cardiac involvement (13 versus 7.15 days, P < 0.05). It seems that cardiac involvement in enteric fever is not uncommon in travelers. Such involvement seems to be more common in patients with delay of effective treatment to the second week of illness. Although fatal or complicated cases are rare in travelers, the cardiac complication may be an important contributor to morbidity and mortality in this group.

Nontuberculous Mycobacteria: Epidemiology and the Impact on Pulmonary and Cardiac Disease.

This article reviews the current epidemiology of nontuberculous mycobacterial pulmonary disease and the impact on thoracic disease. The prevalence of nontuberculous pulmonary disease in the United States is much higher than that of Mycobacterium tuberculosis. Estimates support an annual increase in incidence of 8% per year. Nontuberculous mycobacteria are distinguished by 2 group designations, slowly growing mycobacteria, such as Mycobacterium avium complex, and rapidly growing mycobacteria, which includes Mycobacterium abscessus. Most pulmonary infections in humans are caused by species belonging to M avium complex. This article also reviews risk factors for disease acquisition, including host and environmental risk factors.

[Multiresistant Pathogens in Oncological and Cardiological Rehabilitation - Results of a Surveillance Study in Brandenburg]. / Multiresistente Erreger in der onkologischen und kardiologischen Rehabilitation ­ Ergebnisse einer Surveillancestudie in Brandenburg.

We investigated the prevalence of multidrug resistant pathogens in patients of oncologic and cardiologic rehabilitation units with 155 oncologic and 157 cardiologic patients undergoing microbiologic screening. It was found that 4.5% of oncologic as well as cardiologic patients were colonized with multidrug resistant pathogens. 2-MRGN and ESBL were the most encountered species (2.9%). 3-MRGN were found twice as frequent in oncologic patients (2.6 and 1.3%). Overall oncologic and cardiologic patients exhibit comparatively low prevalence rates for multidrug resistant pathogens.

Histoplasma Endocarditis Diagnosed by Thrombus Aspiration.

Negative cultures in endocarditis often lead to delays in targeted life-saving therapies. We present the case of a 68-year-old man who presented with culture-negative endocarditis, which was complicated by coronary embolization resulting in anterior ST-elevation myocardial infarction (STEMI). Aspiration thrombectomy led to the diagnosis of fungal endocarditis, one of the most serious causes of culture-negative presentation.

Necrotizing infection of the heart.

A case of necrotizing infection of the heart is presented. A 70-year-old woman presented with vague chest and abdominal pain. CT of the abdomen and pelvis was initially obtained, which demonstrated gas in the myocardium of the left ventricle. Subsequent chest CT, endoscopy, and abdominal surgical exploration did not reveal perforated viscus or diaphragm compromise. At median sternotomy, the inferior wall of the heart was found to be necrotic. Culture of the excised tissue grew E. coli. The patient expired shortly after surgical exploration.