Isolated left ventricular assist device implantation produces variable changes to patient body mass index.

BACKGROUND: Body mass index (BMI) is an important consideration for transplant-eligible left ventricular assist device (LVAD) recipients. LVAD therapy's impact on BMI is unclear. We evaluated BMI changes in patients who underwent LVAD implantation. The association between these patients' BMI and the transplant was studied. METHODS: This was a retrospective cohort study of patients who underwent LVAD implantation between January 1, 2012 and December 31, 2018 at our institution. Patients were stratified by preoperative BMI (kg/m2 ) into four groups: <30, 30-34.9, 34.9-39.9, and ≥40. BMI data were collected at 12 and 6 months prior to implantation, time of implantation, and 3- and 6- months postimplantation. RESULTS: A total of 107 patients underwent LVAD implantation at our institution. Data were available for 80 patients. Baseline characteristics included a mean age of 56.0 years, 69% male, and a mean implant BMI of 29.9 ± 6.8 kg/m2 . The mean BMI (kg/m2 ) for each of the BMI (kg/m2 ) groups <30, 30-34.9, 35-39.9, and ≥40 (n = 60, 25, 12, and 10, respectively) was 25.1, 32.5, 36.8, and 43.8, respectively. There was no consistent pattern with weight change across differing implant BMIs. No patient with a BMI of <30 gained sufficient weight to impact transplant candidacy. Twenty-three percent of patients with a BMI of 30-34.9 kg/m2 , 60% of patients with a BMI of 35-39.9 kg/m2 , and 87.5% of patients with a BMI of ≥40 kg/m2 had a 6-month BMI potentially affecting transplant. CONCLUSIONS: Associated weight changes during LVAD support may significantly impact transplant candidacy. Higher BMI groups may benefit from multimodal and multidisciplinary targeted weight-loss interventions.

Protocolized screening effectively identifies myocardial recovery following destination therapy left ventricular assist device implantation.

BACKGROUND: Myocardial recovery following left ventricular assist device (LVAD) implantation has been of interest in transplant candidates with non-ischemic cardiomyopathy but is rare. Evidence suggests that a combination of left ventricular unloading and pharmacologic reverse remodeling is beneficial. Recovery in non-transplant candidates (i.e., destination therapy [DT]) patients is believed to be even rarer. METHODS: All DT LVADs between January 1, 2017 and November 23, 2020 were reviewed. All patients were subjected to an institutional protocol consisting of combined pharmacologic remodeling and mechanical unloading with proactive screening for recovery. The primary outcome of interest was the cumulative incidence of myocardial recovery. Baseline characteristics and operative outcomes were compared between recovered and non-recovered DT patients using non-parametric tests to identify predictive factors. RESULTS: A total of 49 patients received DT LVADs. Nine patients were identified as myocardial recovery candidates using the protocol screening criteria. Overall, 11 patients underwent formal confirmatory testing for recovery, of which 10 were deemed recovered and underwent LVAD explant, defunctionalization, or transplantation. 37.5% of patients that had a concomitant coronary artery bypass during LVAD implantation achieved recovery. An equal proportion of ischemic and non-ischemic cardiomyopathy patients achieved recovery. The cumulative incidence of myocardial recovery was 25.1% at 36 months. No factors were identified as being predictive of recovery. CONCLUSION: Myocardial recovery in DT LVAD patients can be achieved at a higher rate than previously reported. Revascularization at the time of LVAD is safe and may be beneficial. LVAD therapy may not be the final destination in these patients.

Extracorporeal membrane oxygenation for COVID-19: An evolving experience through multiple waves.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has shown variable results in COVID-19 pneumonia however, some evidence supports benefit. Here we compare our institution's ECMO outcomes across multiple waves of the COVID-19 pandemic. METHODS: All patients who received ECMO for COVID-19 between March 1, 2020, and March 1, 2021, were reviewed. Patients received venovenous (VV) or right ventricular assist device (RVAD/ECMO) ECMO. Early (March 1-July 6, 2020, Era 1) and late (July 7, 2020-March 1, 2021, Era 2) pandemic RVAD/ECMO patients were compared. RESULTS: Fifty-four patients received ECMO of which 16 (29.6%) patients received VV ECMO and 38 (70.4%) RVAD/ECMO. Median age was 53.0 years, body mass index 36.1 kg/m2 , 41.2% female, and 49% Caucasian. The most common pre-cannulation treatments included steroids (79.6%) and convalescent plasma (70.4%). Median time from admission to cannulation was 7.0 days. Median support time was 30.5 days (VV ECMO 35.0 days, RVAD/ECMO 26.0 days). In- hospital mortality was 42.6% (39.5% RVAD/ECMO, 50.0% VV ECMO). Significant morbidities included infection (80.8%), bleeding events (74.5%), and renal replacement therapy (30.8%). Cumulative mortality 120-days post-cannulation was 45.7% (VV ECMO 60.8%, RVAD/ECMO 40.0%). RVAD/ECMO Era 1 demonstrated a significantly lower cumulative mortality (16.2%) compared to Era 2 (60.4%). Competing risk analysis found age (HR 0.95, [95% CI 0.92, 0.98] p = 0.005) to be a protective factor for survival. CONCLUSION: ECMO support for COVID-19 is beneficial but carries significant morbidity. RVAD/ECMO support demonstrated consistent advantages in survival to VV-ECMO, but with declining efficacy across time during the COVID-19 pandemic.

Extracorporeal Membrane Oxygenation with Right Ventricular Assist Device for COVID-19 ARDS.

BACKGROUND: Right ventricular failure is an underrecognized consequence of COVID-19 pneumonia. Those with severe disease are treated with extracorporeal membrane oxygenation (ECMO) but with poor outcomes. Concomitant right ventricular assist device (RVAD) may be beneficial. METHODS: A retrospective analysis of intensive care unit patients admitted with COVID-19 ARDS (Acute Respiratory Distress Syndrome) was performed. Nonintubated patients, those with acute kidney injury, and age > 75 were excluded. Patients who underwent RVAD/ECMO support were compared with those managed via invasive mechanical ventilation (IMV) alone. The primary outcome was in-hospital mortality. Secondary outcomes included 30-d mortality, acute kidney injury, length of ICU stay, and duration of mechanical ventilation. RESULTS: A total of 145 patients were admitted to the ICU with COVID-19. Thirty-nine patients met inclusion criteria. Of these, 21 received IMV, and 18 received RVAD/ECMO. In-hospital (52.4 versus 11.1%, P = 0.008) and 30-d mortality (42.9 versus 5.6%, P= 0.011) were significantly lower in patients treated with RVAD/ECMO. Acute kidney injury occurred in 15 (71.4%) patients in the IMV group and zero RVAD/ECMO patients (P< 0.001). ICU (11.5 versus 21 d, P= 0.067) and hospital (14 versus 25.5 d, P = 0.054) length of stay were not significantly different. There were no RVAD/ECMO device complications. The duration of mechanical ventilation was not significantly different (10 versus 5 d, P = 0.44). CONCLUSIONS: RVAD support at the time of ECMO initiation resulted in the no secondary end-organ damage and higher in-hospital and 30-d survival versus IMV in specially selected patients with severe COVID-19 ARDS. Management of severe COVID-19 ARDS should prioritize right ventricular support.

Solid organ donor-recipient race-matching: analysis of the United Network for Organ Sharing database.

Donor ethnicity is a prognosticator in organ transplant. However, the impact of donor/recipient race-matching is unclear. We hypothesized that there would be increased survival in donor-recipient race-matched organ recipients because of genetic and physiologic similarities. The UNOS database from 1999 to 2018 was queried for all solid organ transplantations including heart, lung, liver, kidney, and pancreas transplants. Data were sorted by donor and recipient race into matched and unmatched categories for Caucasian, African American, and Hispanic transplant recipients. After controlling for potential confounders via inverse propensity of treatment weighting, post-transplant patient and graft survival were compared between race-matched and -unmatched donor groups for each organ. Race-matched Caucasian recipients experienced 1-3% improvement in mortality across most time points in lung, liver, and pancreas transplants, while Hispanics did not benefit. Matched African American recipients experienced 4-6% improvement in patient and graft survival in liver transplant but had 7-9% worse survival rates at 5 years in lung and pancreas transplants. Race-matching does not influence patient outcomes enough to factor into organ transplant offers. African American liver transplant recipients benefited the most. Matching was detrimental to African American lung and pancreas transplant recipients indicating there may be other factors influencing the outcomes of these transplants.

Seasonal trends in donor heart availability: an analysis of the UNOS database.

Despite the widespread belief that donor organ availability varies around holidays and seasons, there is little empirical data supporting this long-held belief. Variations in donor heart availability may be of interest to patients and clinicians. The UNOS/OPTN registry was queried for all heart donations from October 1987 through March 2017. Daily heart donation rates were modeled nationally using Poisson regression including splines for year and day of the year. Seasonality was assessed using a likelihood ratio test for the spine terms for day of the year. The holiday effect was assessed using conditional logistic regression. Seasonal plots suggest a significant, although modest, increase in organ availability during the summer months, except for region 1. The regions with the highest amplitude were region 7 (peak: June 21, amplitude: 16.63%) and region 6 (peak: July 5, amplitude: 11.29%). There was no significant difference in the odds of heart donation when comparing holidays vs. non-holidays using national data (odds ratio [95% CI]: 1.01 [0.98, 1.03], P = 0.560) or any regional subsets. There was no observable correlation between donor heart availability and holidays. However, a significant seasonality effect was observed with higher donation rates occurring during warmer months.

Temporary mechanical circulatory support prevents the occurrence of a low-output state in high-risk coronary artery bypass grafting: A case series.

BACKGROUND: Coronary artery bypass grafting (CABG) is a durable treatment for coronary artery disease. Left ventricular dysfunction (LVD) (a division of cardiothoracic surgery) (ejection fraction < 35%) significantly elevates perioperative risk for patients pursuing surgical revascularization. Periprocedural support with temporary mechanical circulatory support (tMCS) has shown benefit in this patient population. METHODS: Four patients with ischemic cardiomyopathy and LVD underwent CABG at our institution between 2017 and 2018. Each patient received perioperative ventricular support using a microaxial tMCS device (Impella 5.0®). The occurrence of a postoperative low-output state (LOS) was assessed for as well as postoperative morbidity and mortality, device-specific complications, and tMCS support duration. RESULTS: All patients survived to device explant without device-related complications. Two patients required reoperation for nondevice-related bleeding. All patients were without an LOS at 24 h postoperatively with cardiac indices of 2.9-3.6 L/min/m2 , normalized serum lactate, and vasoactive-inotrope scores of 0-12.0. There was a notably high incidence of acute renal failure (50%), which was observed in patients with preoperative cardiogenic shock. One patient died 10 days after the device explant. Of the three patients that survived to discharge, two were alive at the most recent follow-up. Postoperative device support varied widely (0-500 h). CONCLUSION: Perioperative tMCS may be a viable strategy for preventing postoperative LOS in high-risk CABG patients with a low complication rate and acceptable morbidity. The application of microaxial tMCS devices in CABG is an area that warrants further investigation to delineate its impact on perioperative outcomes and potentially expand the indications for such devices.

Minimally invasive single-vessel left internal mammary to left anterior descending artery bypass grafting improves outcomes over conventional sternotomy: A single-institution retrospective cohort study.

BACKGROUND: Coronary artery bypass grafting (CABG) can be performed through a variety of approaches. Minimally-invasive CABG (MICABG) may reduce perioperative morbidity. Previous results demonstrate improved perioperative outcomes; however, adoption has been limited. METHODS: The Society of Thoracic Surgeons (STS) database and electronic medical record at a single institution were reviewed for isolated left internal mammary to left anterior descending artery (LIMA-LAD) bypass procedures performed between 2011 and 2018. Patients were grouped on the basis of operative approach, comparing sternotomy to non-sternotomy (minimally-invasive). Patient characteristics, perioperative variables, and short- and long-term outcomes were compared. Primary outcomes included mortality and major adverse cardiac events (MACE). Secondary outcomes were morbidity. RESULTS: A total of 42 MICABG and 54 conventional LIMA-LAD procedures were performed with 95.2% of MICABG procedures performed by two surgeons. MICABG were more often elective (83.3 vs 38.9%, P < .001). STS risk scores predicted equitable mortality and morbidity for MICABG dependent on operative indication. MICABG was associated with fewer pulmonary complications (0.0 vs 11.1%, P = .033), in-hospital events (11.9 vs 37.0%, P = .005), and shorter intensive care unit (34.1 vs 66.0 hours, P = .022) and total length of stay (3.7 vs 6.5 days, P = .002). There were no observed strokes, myocardial infarctions, or reoperations. MICABG patients demonstrated reduced thirty-day mortality (0.0 vs 10.9%, P = .036) and improved Kaplan-Meier 5-year (95.2 vs 77.9%, P = .016) and MACE-free survival (89.2 vs 63.9%, P = .010). CONCLUSIONS: Minimally-invasive LIMA-LAD CABG demonstrates improved early postoperative morbidity and a long-term mortality benefit. In select patients, minimally-invasive approaches to single-vessel grafting may be beneficial when performed by experienced surgeons in the elective setting.

Super Mario brothers and sisters: Associations between coplaying video games and sibling conflict and affection.

Video games can be played in many different contexts. This study examined associations between coplaying video games between siblings and levels of affection and conflict in the relationship. Participants were 508 adolescents (M age = 16.31 years of age, SD = 1.08) who completed questionnaires on video game use and sibling relationships. Participants were recruited from a large Northwestern city and a moderate city in the Mountain West of the United States. Video games played between siblings were coded by an independent sample to assess levels of physical aggression and prosocial behavior in each game. Playing video games with a sibling was associated with higher levels of sibling affection for both boys and girls, but higher levels of conflict for boys only. Playing a violent video game with a brother was associated with lower levels of conflict in the sibling relationship, whereas playing a prosocial video game was not related to any sibling outcome. The value of video games in sibling relationships will be discussed, with a focus on the type of game and the sex of the adolescent.

Functional profiling of neurons through cellular neuropharmacology.

We describe a functional profiling strategy to identify and characterize subtypes of neurons present in a peripheral ganglion, which should be extendable to neurons in the CNS. In this study, dissociated dorsal-root ganglion neurons from mice were exposed to various pharmacological agents (challenge compounds), while at the same time the individual responses of >100 neurons were simultaneously monitored by calcium imaging. Each challenge compound elicited responses in only a subset of dorsal-root ganglion neurons. Two general types of challenge compounds were used: agonists of receptors (ionotropic and metabotropic) that alter cytoplasmic calcium concentration (receptor-agonist challenges) and compounds that affect voltage-gated ion channels (membrane-potential challenges). Notably, among the latter are K-channel antagonists, which elicited unexpectedly diverse types of calcium responses in different cells (i.e., phenotypes). We used various challenge compounds to identify several putative neuronal subtypes on the basis of their shared and/or divergent functional, phenotypic profiles. Our results indicate that multiple receptor-agonist and membrane-potential challenges may be applied to a neuronal population to identify, characterize, and discriminate among neuronal subtypes. This experimental approach can uncover constellations of plasma membrane macromolecules that are functionally coupled to confer a specific phenotypic profile on each neuronal subtype. This experimental platform has the potential to bridge a gap between systems and molecular neuroscience with a cellular-focused neuropharmacology, ultimately leading to the identification and functional characterization of all neuronal subtypes at a given locus in the nervous system.

Peripherally inserted concomitant surgical right and left ventricular support, the Propella, is associated with low rates of limb ischemia, with mortality comparable with peripheral venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Mechanical circulatory support effectively treats adult cardiogenic shock. Whereas cardiogenic shock confers high mortality, acute limb ischemia is a known complication of mechanical circulatory support that confers significant morbidity. We compared our novel approach to peripheral mechanical circulatory support with a conventional femoral approach, with a focus on the incidence of acute limb ischemia. METHODS: This was a retrospective cohort study of patients treated with mechanical circulatory support between January 1, 2015 and December 5, 2021 at our institution. Patients receiving any femoral peripheral venoarterial extracorporeal membrane oxygenation were compared with those receiving minimally invasive, peripherally inserted, concomitant right and left ventricular assist devices. These included the Impella 5.0 (Abiomed, Danvers, MA) left ventricular assist device and the ProtekDuo (LivaNova, London, UK) right ventricular assist device used concomitantly (Propella) approach. The primary outcome was incidence of acute limb ischemia. The baseline patient characteristics, hemodynamic data, and post-mechanical circulatory support outcomes were collected. Fisher exact test and Wilcoxon rank sum test was used for the categorical and continuous variables, respectively. Kaplan-Meier curves and log-rank test were used to estimate overall survival probabilities and survival experience, respectively. RESULTS: Fifty patients were treated with mechanical circulatory support at our institution for cardiogenic shock, with 13 patients supported with the novel Propella strategy and 37 with peripheral venoarterial extracorporeal membrane oxygenation. The baseline characteristics, including patient organ function and medical comorbidities, were similar among the groups. Nine patients suffered mortality in ≤48 hours of mechanical circulatory support initiation and were excluded. Twenty patients (69%) suffered acute limb ischemia in the peripheral venoarterial extracorporeal membrane oxygenation group; 0 patients receiving Propella suffered acute limb ischemia (P < .001). The percentages of patients surviving to discharge in peripheral venoarterial extracorporeal membrane oxygenation and Propella groups were 24% and 69%, respectively (P = .007). CONCLUSION: Patients treated with the Propella experienced a lower incidence of acute limb ischemia compared with patients treated with peripheral venoarterial extracorporeal membrane oxygenation.

Predictive Model for Heart Failure Readmission Using Nationwide Readmissions Database.

Objective: To generate a heart failure (HF) readmission prediction model using the Nationwide Readmissions Database to guide management and reduce HF readmissions. Patients and Methods: A retrospective analysis was performed for patients listed for HF admissions in the Nationwide Readmissions Database from January 1, 2010, to December 31, 2014. A Cox proportional hazards model for sample survey data for the prediction of readmission for all patients with HF was implemented using a derivation cohort (2010-2012). We generated receiver operating characteristic (ROC) curves and estimated area under the ROC curve at each time point (30, 60, 90, and 180 days) to assess the accuracy of our predictive model using the derivation cohort (2010-2012) and compared it with the validation cohort (2013-2014). A risk score was computed for the validation cohort. On the basis of the total risk score, we calculated the probability of readmission at 30, 60, 90, and 180 days. Results: Approximately 1,420,564 patients were admitted for HF, contributing to 1,817,735 total HF admissions. Of these, 665,867 patients had at least 1 readmission for HF. The 10 most common comorbidities for readmitted patients included hypertension, diabetes mellitus, renal failure, chronic pulmonary disease, deficiency anemia, fluid and electrolyte disorders, obesity, hypothyroidism, peripheral vascular disorders, and depression. The area under the ROC curve for the prediction model was 0.58 in the derivation cohort and 0.59 in the validation cohort. Conclusion: The prediction model will find clinical utility at point of care in optimizing the management of patients with HF and reducing HF readmissions.

ALS-associated KIF5A mutations abolish autoinhibition resulting in a toxic gain of function.

Understanding the pathogenic mechanisms of disease mutations is critical to advancing treatments. ALS-associated mutations in the gene encoding the microtubule motor KIF5A result in skipping of exon 27 (KIF5AΔExon27) and the encoding of a protein with a novel 39 amino acid residue C-terminal sequence. Here, we report that expression of ALS-linked mutant KIF5A results in dysregulated motor activity, cellular mislocalization, altered axonal transport, and decreased neuronal survival. Single-molecule analysis revealed that the altered C terminus of mutant KIF5A results in a constitutively active state. Furthermore, mutant KIF5A possesses altered protein and RNA interactions and its expression results in altered gene expression/splicing. Taken together, our data support the hypothesis that causative ALS mutations result in a toxic gain of function in the intracellular motor KIF5A that disrupts intracellular trafficking and neuronal homeostasis.

Acute cardiopulmonary failure in a young woman with high-risk gestational trophoblastic neoplasia: A case of induction chemotherapy during extracorporeal membrane oxygenation.

•Early use of extracorporeal membrane oxygenation (ECMO) is valuable when pulmonary tumor burden from GTN is high.•Induction chemotherapy of cisplatin and etoposide was administered during ECMO successfully.•The induction chemotherapy regimen led to exponential decline in beta-HCG after 1 cycle.•Collaboration of subspecialists is necessary to treat coexisting malignancy and cardiopulmonary failure associated with GTN.

Acquired tracheomalacia due to aortic aneurysm managed with venopulmonary extracorporeal membrane oxygenation for perioperative support.

Extracorporeal membrane oxygenation (ECMO) has diverse applications. In the present report, we have described a case of tracheomalacia from a thoracic aortic aneurysm causing respiratory failure. Total arch replacement with reverse frozen elephant trunk grafting was performed. Perioperative ECMO support was accomplished with venopulmonary artery ECMO. This strategy allowed for preoperative oxygenation support, venous drainage during cardiopulmonary bypass, and postoperative support without cannula exchanges. Our patient required ECMO support for 12 days postoperatively. We have illustrated a unique case of acquired tracheomalacia but also an ECMO cannulation strategy allowing for preoperative oxygenation, seamless transition to cardiopulmonary bypass, and postoperative support.

Epidemiology and outcomes of primary pediatric lung malignancies: Updates from the SEER database.

BACKGROUND: Primary pediatric lung malignancies are rare tumors. We provide an updated analysis of the epidemiology and prognosis of these tumors since the last SEER series published in 2009. METHODS: The SEER 18 database from 1975 to 2016 was analyzed for patients ages 0-19 years with primary lung and/or bronchus neoplasms. RESULTS: 348 patients met inclusion criteria. The majority were white and ≥12 years of age. The most common histologies were neuroendocrine (41.4%) and blastoma (16.4%). 75.4% of patients had local-regional disease and 81.4% underwent surgery. Significant differences between histologies were seen for age, year at diagnosis, tumor laterality and location, stage, and treatment type. Median survival was 36.6 years (95% CI 33.3-37.4). Blastoma (HR 3.47) and squamous cell (HR 6.26) carried a significantly higher risk of death than neuroendocrine cancer diagnosis. CONCLUSION: Primary pediatric lung malignancies are rare, long-term survival is favorable but histology-dependent. Surgery continues to be an important treatment modality.

Attenuation of the Induction of TLRs 2 and 4 Mitigates Inflammation and Promotes Neurological Recovery After Focal Cerebral Ischemia.

The intense inflammatory response triggered in the brain after focal cerebral ischemia is detrimental. Recently, we showed that the suppression of toll-like receptors (TLRs) 2 and 4 attenuates infarct size and reduces the expression of pro-inflammatory cytokines in the ischemic brain. In this study, we further examined the effect of unsuppressed induction of TLRs 2 and 4 on the expression of its downstream signaling molecules and pro-inflammatory cytokines 1 week after reperfusion. The primary purpose of this study was to investigate the effect of simultaneous knockdown of TLRs 2 and 4 on M1/M2 microglial polarization dynamics and post-stroke neurological deficits and the recovery. Transient focal cerebral ischemia was induced in young adult male Sprague-Dawley rats by the middle cerebral artery occlusion (MCAO) procedure using a monofilament suture. Appropriate cohorts of rats were treated with a nanoparticle formulation of TLR2shRNA and TLR4shRNA (T2sh+T4sh) expressing plasmids (1 mg/kg each of T2sh and T4sh) or scrambled sequence inserted vector (vehicle control) expressing plasmids (2 mg/kg) intravenously via tail vein immediately after reperfusion. Animals from various cohorts were euthanized during reperfusion, and the ischemic brain tissue was isolated and utilized for PCR followed by agarose gel electrophoresis, real-time PCR, immunoblot, and immunofluorescence analysis. Appropriate groups were subjected to a battery of standard neurological tests at regular intervals until 14 days after reperfusion. The increased expression of both TLRs 2 and 4 and their downstream signaling molecules including the pro-inflammatory cytokines was observed even at 1-week after reperfusion. T2sh+T4sh treatment immediately after reperfusion attenuated the post-ischemic inflammation, preserved the motor function, and promoted recovery of the sensory and motor functions. We conclude that the post-ischemic induction of TLRs 2 and 4 persists for at least 7 days after reperfusion, contributes to the severity of acute inflammation, and impedes neurological recovery. Unlike previous studies in TLRs 2 or 4 knockout models, results of this study in a pharmacologically relevant preclinical rodent stroke model have translational significance.

Prevention of the Severity of Post-ischemic Inflammation and Brain Damage by Simultaneous Knockdown of Toll-like Receptors 2 and 4.

Toll-like receptor 2 (TLR2) and TLR4 belong to a family of highly conserved pattern recognition receptors and are well-known upstream sensors of signaling pathways of innate immunity. TLR2 and TLR4 upregulation is thought to be associated with poor outcome in stroke patients. We currently show that transient focal ischemia in adult rats induces TLR2 and TLR4 expression within hours and shRNA-mediated knockdown of TLR2 and TLR4 alone and in combination decreases the infarct size and swelling. We further show that TLR2 and TLR4 knockdown also prevented the induction of their downstream signaling molecules MyD88, IRAK1, and NFκB p65 as well as the pro-inflammatory cytokines IL-1ß, IL-6, and TNFα. This study thus shows that attenuation of the severity of TLR2- and TLR4-mediated post-stroke inflammation ameliorates ischemic brain damage.