Citations

Background Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS. Methods and Results Patients with TTS were enrolled from the International Takotsubo Registry, which is a multinational network with 26 participating centers in Europe and the United States. Patients were dichotomized according to the presence or absence of AF at the time of admission. Of 1584 patients with TTS, 112 (7.1%) had AF. The mean age was higher ( P <0.001), and there were fewer women ( P =0.046) in the AF than in the non‐AF group. Left ventricular ejection fraction was significantly lower ( P =0.001), and cardiogenic shock was more often observed ( P <0.001) in the AF group. Both in‐hospital ( P <0.001) and long‐term mortality ( P <0.001) were higher in the AF group. Multivariable Cox regression analysis revealed that AF was independently associated with higher long‐term mortality (hazard ratio, 2.31; 95% CI, 1.50–3.55; P <0.001). Among patients with AF on admission, 42% had no known history of AF before the acute TTS event, and such patients had comparable in‐hospital and long‐term outcomes compared with those with a history of AF. Conclusions In patients presenting with TTS, AF on admission is significantly associated with increased in‐hospital and long‐term mortality rates. Whether antiarrhythmics and/or cardioversion are beneficial in TTS with AF should thus be tested in a future trial. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01947621.

Background: Little is known about the relationship between Type A Acute Aortic Dissection (TAAAD) and pulse pressure (PP), defined as the difference between systolic and diastolic blood pressure. This study explores the association between PP and presentation, complications and outcomes of TAAAD patients. Methods: PP at hospital presentation was used to divide 1,960 non-iatrogenic TAAAD patients into quartiles: narrowed (≤39 mmHg; n=430), normal (40-56 mmHg; n=554), mildly elevated (57-75 mmHg; n=490) and markedly elevated (≥76 mmHg; n=486). Variables relating to index presentation and in-hospital outcomes were analyzed. Results: TAAAD patients (patients) in the narrowed PP quartiles were more frequently older and Caucasian while patients with markedly elevated PPs tended to be male and have a history of hypertension. Patients who demonstrated abdominal vessel involvement more commonly demonstrated elevated PPs whereas patients with narrowed PPs were more likely to have periaortic hematoma and/or pericardial effusion. Narrowed PPs were also correlated with higher incidences of hypotension, cardiac tamponade and mortality. TAAAD patients who were managed with endovascular and hybrid procedures and those with renal failure tended to have elevated PPs. No difference in aortic regurgitation at presentation was noted between groups. Conclusions: TAAAD patients in the middle two PP quartiles had better in-hospital outcomes than patients in the outer quartiles. Patients with narrowed PPs experienced more cardiac complications, particularly cardiac tamponade, while those with elevated PPs were more likely to have abdominal aortic involvement. Presenting PP offers a clue to different manifestations of AAD that may facilitate initial triage and care.

Background: The debate for the optimal treatment of complicated Type B Acute Aortic Dissection (TBAAD) is primarily focused upon open surgical intervention versus thoracic endovascular aortic repair (TEVAR). The technique of fenestration with stenting has been proposed to resolve malperfusion. This study evaluated post-procedural outcomes of all three approaches for TBAAD. Methods: TBAAD patients enrolled in the International Registry of Acute Aortic Dissection were stratified by management type: TEVAR, fenestration and stenting, and surgery. Results: Of the 552 patients with TBAAD, 231 (41.8%) underwent TEVAR, 214 (38.8%) standard open surgery, and 107 (19.4%) fenestration and stenting. TEVAR or fenestration and stenting were more likely to be performed in classic double barrel aortic dissection when compared to open surgery (73.2%, 76.6%, 52.8% respectively; p<0.001). Patients treated with open repair were less likely to have distal extension into the abdominal aorta than those with TEVAR or fenestration and stenting (47.7%, 62.7%, 86.4%, respectively; p<0.001). In-hospital mortality was similar between groups (11.7% TEVAR, 14.0% fenestration and stenting, 15.9% surgery). At five years, Kaplan-Meier post-discharge all-cause survival estimates were highest for TEVAR, followed by endovascular fenestration and finally open surgical intervention (85.2%, 78.3%, 67.2%, respectively; p=0.039). Conclusion: Patients treated by endovascular approaches, whether with flap fenestration or thoracic endovascular aortic repair, had lower five year mortality when compared to patients who required open repair in the setting of TBAAD. Either endovascular approach may be helpful in the treatment of TBAAD. Further research is needed to determine how much of the observed difference represents patient selection versus differential effects of treatment.

INTRODUCTION: Significant variability between colonoscopy operators contributes to postcolonoscopy colorectal cancers (CRCs). We aimed to estimate postcolonoscopy colorectal neoplasia (CRN) detection by multi-target stool DNA (mt-sDNA), which has not previously been studied for this purpose. METHODS: In a retrospective cohort of patients with +mt-sDNA and completed follow-up colonoscopy, positive predictive value (PPV) for endpoints of any CRN, advanced adenoma, right-sided neoplasia, sessile serrated polyps (SSP), and CRC were stratified by the time since previous colonoscopy (0–9, 10, and ≥11 years). mt-sDNA PPV at ≤9 years from previous average-risk screening colonoscopy was used to estimate CRN missed at previous screening colonoscopy. RESULTS: Among the 850 studied patients with +mt-sDNA after a previous negative screening colonoscopy, any CRN was found in 535 (PPV 63%). Among 107 average-risk patients having +mt-sDNA ≤9 years after last negative colonoscopy, any CRN was found in 67 (PPV 63%), advanced neoplasia in 16 (PPV 15%), right-sided CRN in 48 (PPV 46%), and SSP in 20 (PPV 19%). These rates were similar to those in 47 additional average risk persons with previous incomplete colonoscopy and in an additional 68 persons at increased CRC risk. One CRC (stage I) was found in an average risk patient who was mt-sDNA positive 6 years after negative screening colonoscopy. DISCUSSION: The high PPV of mt-sDNA 0–9 years after a negative screening colonoscopy suggests that lesions were likely missed on previous examination or may have arisen de novo . mt-sDNA as an interval test after negative screening colonoscopy warrants further study.

Abstract Background Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the impact of PTS on outcomes of mCRC patients. Methods PTS data of 9277 mCRC patients from 12 first-line randomized trials in the ARCAD database were pooled. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status, prior radiation/chemotherapy, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (cetuximab plus chemotherapy vs chemotherapy alone). All statistical tests were 2-sided. Results Compared with right-sided metastatic colorectal cancer patients (n = 2421, 26.1%), left-sided metastatic colorectal cancer patients (n = 6856, 73.9%) had better OS (median = 21.6 vs 15.9 months; adjusted hazard ratio [HRadj] = 0.71, 95% confidence interval [CI] = 0.67 to 0.76; P &lt; .001) and PFS (median = 8.6 vs 7.5 months; HRadj = 0.80, 95% CI = 0.75 to 0.84; P &lt; .001). Interaction between PTS and KRAS mutation was statistically significant (Pinteraction &lt; .001); left-sidedness was associated with better prognosis among KRAS wild-type (WT) (OS HRadj = 0.59, 95% CI = 0.53 to 0.66; PFS HRadj =0.68, 95% CI = 0.61 to 0.75) but not among KRAS mutated tumors. Among KRAS-WT tumors, survival benefit from anti-EGFR was confirmed for left-sidedness (OS HRadj = 0.85, 95% CI = 0.75 to 0.97; P = .01; PFS HRadj = 0.77, 95% CI = 0.67 to 0.88; P &lt; .001) but not for right-sidedness. Conclusions The prognostic value of PTS is restricted to the KRAS-WT population. PTS is predictive of anti-EGFR efficacy, with a statistically significant improvement of survival for left-sidedness mCRC patients. These results suggest treatment choice in mCRC should be based on both PTS and KRAS status.

Donation after circulatory death (DCD) grafts are commonly used in liver transplantation. Attributable to the additional ischemic event during the donor warm ischemia time (DWIT), DCD grafts carry an increased risk for severe ischemia/reperfusion injury and postoperative complications, such as ischemic cholangiopathy. The actual ischemia during DWIT depends on the course of vital parameters after withdrawal of life support and varies widely between donors. The ischemic period (functional DWIT) starts when either Sp o 2 or blood pressure drop below a certain point and lasts until the start of cold perfusion during organ retrieval. Over the years, multiple definitions and thresholds of functional DWIT duration have been used. The International Liver Transplantation Society organized a Consensus Conference on DCD, Liver Preservation, and Machine Perfusion on January 31, 2020 in Venice, Italy. The aim of this conference was to reach consensus about various aspects of DCD liver transplantation in context of currently available evidence. Here we present the recommendations with regards to the definitions used for DWIT and functional DWIT, the importance of vital parameters after withdrawal of life support, and acceptable thresholds of duration of functional DWIT to proceed with liver transplantation.

Abstract The aim of this book is to provide the clinician with a comprehensive and clinical relevant survey of emerging concepts on the organization and function of the nervous system and neurologic disease mechanisms, at the molecular, cellular, and system levels. The content of is based on the review of information obtained from recent advances in genetic, molecular, and cell biology techniques; electrophysiological recordings; brain mapping; and mouse models, emphasizing the clinical and possible therapeutic implications. Many chapters of this book contain information that will be relevant not only to clinical neurologists but also to psychiatrists and physical therapists. The scope includes the mechanisms and abnormalities of DNA/RNA metabolism, proteostasis, vesicular biogenesis, and axonal transport and mechanisms of neurodegeneration; the role of the mitochondria in cell function and death mechanisms; ion channels, neurotransmission and mechanisms of channelopathies and synaptopathies; the functions of astrocytes, oligodendrocytes, and microglia and their involvement in disease; the local circuits and synaptic interactions at the level of the cerebral cortex, thalamus, basal ganglia, cerebellum, brainstem, and spinal cord transmission regulating sensory processing, behavioral state, and motor functions; the peripheral and central mechanisms of pain and homeostasis; and networks involved in emotion, memory, language, and executive function.