A case report of high-output heart failure due to arteriovenous shunt without bowel: how to address?

Background: High-output heart failure (HF) is a form of HF where patients present with a high-output state with low systemic vascular resistance. This report presents the case of high-output HF in a patient with an arteriovenous shunt and no options for oral-administered drugs. Case summary: A 70-year-old male with a terminal jejunostomy fully depending on parenteral feeding through a vena saphena magna shunt presented with symptoms of shortness of breath. Echocardiography revealed eccentric hypertrophy with reduced left ventricular ejection fraction (LVEF) and atrial fibrillation with a heart rate of 70-100 b.p.m. Cardiac magnetic resonance imaging, endomyocardial biopsy, and cardiomyopathy lab revealed no cause of HF. High-output HF based on right heart catheterization due to the arteriovenous shunt or related to irregularity due to atrial fibrillation were potential causes. As a result of his malfunctioning gastrointestinal system, the pharmacological options were limited. He was treated with captopril sublingual, initially 6.25 mg three times daily (TID) and later 12.5 mg TID, which reduced blood pressure. Electrical cardioversion to sinus rhythm was successful but did not improve LVEF. Therefore, the patient was opted for surgically reducing the blood flow through the shunt, resulting in normalization of LVEF. Discussion: High-output HF is an uncommon form of HF with an uncertain prevalence. The most common aetiologies reported in the literature are obesity, cirrhosis, and arteriovenous shunts. Sublingual administration of captopril can be an effective treatment option for HF patients unable to absorb oral-administered drugs.

Comorbidity and long-term clinical outcome of laryngotracheal clefts types III and IV: Systematic analysis of new cases.

BACKGROUND: Long segment laryngotracheoesophageal clefts (LTECs) are very rare large-airway malformations. Over the last 40 years mortality rates declined substantially due to improved intensive care and surgical procedures. Nevertheless, long-term morbidity, comorbidity, and clinical outcomes have rarely been assessed systematically. METHODS: In this retrospective case series, the clinical presentation, comorbidities, treatment, and clinical outcomes of all children with long-segment LTEC that were seen at our department in the last 15 years were collected and analyzed systematically. RESULTS: Nine children were diagnosed with long segment LTEC (four children with LTEC type III and five patients with LTEC type IV). All children had additional tracheobronchial, gastrointestinal, or cardiac malformations. Tracheostomy for long-time ventilation and jejunostomy for adequate nutrition was necessary in all cases. During follow-up one child died from multiorgan failure due to sepsis at the age of 43 days. The clinical course of the other eight children (median follow-up time 5.2 years) was stable. Relapses of the cleft, recurrent aspirations, and respiratory tract infections led to repeated hospital admissions. CONCLUSIONS: Long-segment LTECs are consistently associated with additional malformations, which substantially influence long-term morbidity. For optimal management, a multidisciplinary approach is essential.

Differences in the Response to DNA Double-Strand Breaks between Rod Photoreceptors of Rodents, Pigs, and Humans.

Genome editing (GE) represents a powerful approach to fight inherited blinding diseases in which the underlying mutations cause the degeneration of the light sensing photoreceptor cells of the retina. Successful GE requires the efficient repair of DNA double-stranded breaks (DSBs) generated during the treatment. Rod photoreceptors of adult mice have a highly specialized chromatin organization, do not efficiently express a variety of DSB response genes and repair DSBs very inefficiently. The DSB repair efficiency in rods of other species including humans is unknown. Here, we used ionizing radiation to analyze the DSB response in rods of various nocturnal and diurnal species, including genetically modified mice, pigs, and humans. We show that the inefficient repair of DSBs in adult mouse rods does not result from their specialized chromatin organization. Instead, the DSB repair efficiency in rods correlates with the level of Kruppel-associated protein-1 (KAP1) expression and its ataxia-telangiectasia mutated (ATM)-dependent phosphorylation. Strikingly, we detected robust KAP1 expression and phosphorylation only in human rods but not in rods of other diurnal species including pigs. Hence, our study provides important information about the uniqueness of the DSB response in human rods which needs to be considered when choosing model systems for the development of GE strategies.

Redox Regulation of the Actin Cytoskeleton in Cell Migration and Adhesion: On the Way to a Spatiotemporal View.

The actin cytoskeleton of eukaryotic cells is a dynamic, fibrous network that is regulated by the concerted action of actin-binding proteins (ABPs). In particular, rapid polarization of cells in response to internal and external stimuli is fundamental to cell migration and invasion. Various isoforms of ABPs in different tissues equip cells with variable degrees of migratory and adhesive capacities. In addition, regulation of ABPs by posttranslational modifications (PTM) is pivotal to the rapid responsiveness of cells. In this context, phosphorylation of ABPs and its functional consequences have been studied extensively. However, the study of reduction/oxidation (redox) modifications of oxidation-sensitive cysteine and methionine residues of actin, ABPs, adhesion molecules, and signaling proteins regulating actin cytoskeletal dynamics has only recently emerged as a field. The relevance of such protein oxidations to cellular physiology and pathophysiology has remained largely elusive. Importantly, studying protein oxidation spatiotemporally can provide novel insights into localized redox regulation of cellular functions. In this review, we focus on the redox regulation of the actin cytoskeleton, its challenges, and recently developed tools to study its physiological and pathophysiological consequences.

Laryngeal mask airway versus endotracheal tube for percutaneous dilatational tracheostomy in critically ill adult patients.

BACKGROUND: Percutaneous dilatational tracheostomy (PDT) is one of the most common bedside surgical procedures performed in critically ill adult patients on intensive care units (ICUs) who require long-term ventilation. PDT is generally associated with relevant life-threatening complications (e.g. cuff rupture leading to possible hypoxia or aspiration, puncture of the oesophagus, accidental extubation, mediastinitis, pneumothorax, emphysema). The patient's airway can be secured with an endotracheal tube (ETT) or a laryngeal mask airway (LMA). OBJECTIVES: To assess the safety and effectiveness of ETT versus LMA in critically ill adult patients undergoing PDT on the ICU.This review addresses the following research questions.1. Is an LMA more effective than an ETT in terms of procedure-related or all-cause mortality?2. Is an LMA safer than an ETT in terms of procedure-related life-threatening complications during a PDT procedure?3. Does use of an LMA influence the conditions for performing a tracheostomy (e.g. duration of procedure)? SEARCH METHODS: We searched the Cochrane Database of Systematic Reviews (CDSR); the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 6 (part ofThe Cochrane Library); MEDLINE (from 1984 to 27 June 2013) and EMBASE (from 1984 to 27 June 2013). We searched for reports of ongoing trials in the metaRegister of Controlled Trials (mRCT). We handsearched for relevant studies in conference proceedings of the International Symposium on Intensive Care and Emergency Medicine (ISICEM), the Annual Congress of the European Society of Intensive Care Medicine (ESICM), the Annual Congress of the Society of Critical Care Medicine (SCCM), the American Thoracic Society (ATS) and the Annual Meeting of the American College of Chest Physicians (ACCP). We contacted study authors and experts concerning unpublished data and ongoing trials. We searched for further relevant studies in the reference lists of all included trials and of relevant systematic reviews identified in theCDSR. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared use of endotracheal tubes versus laryngeal mask airways in critically ill adult patients undergoing PDT on the ICU. We imposed no restrictions with regard to language, timing or technique of PDT performed. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and methodological quality of each study and carried out data extraction. We resolved disagreements by discussion. Our primary outcomes were all-cause mortality, procedure-related mortality and tally of participants with one or more serious adverse events. When available, we reported on our secondary outcomes, which included duration of the procedure, failure of the procedure requiring conversion to any other procedure, time to extubation after tracheostomy, length of ICU stay after tracheostomy, length of hospital stay after tracheostomy and any other serious adverse events. When possible, we combined homogeneous studies for meta-analysis. We used the risk of bias tool of The Cochrane Collaboration to assess the internal validity of all included studies in six different domains. MAIN RESULTS: We included in this review eight RCTs involving 467 participants. The included trials exclusively assessed critically ill participants (e.g. with head injury, neurological disease, multi-trauma, sepsis, acute respiratory failure (ARF) and/or chronic obstructive pulmonary disease (COPD)). Internal validity was considerably low in studies with a high or unclear risk of bias. The main reason for this was low methodological quality or missing data, even after study authors were contacted. Study size was generally small, with a minimum of 40 and a maximum of 73 participants. Only one study (40 participants) reported on overall mortality, showing no clear evidence of a difference between treatment groups (risk ratio (RR) 1.5, 95% confidence interval (CI) 0.28 to 8.04, Fisher test P value 1.0, low-quality evidence). Four studies (231 participants) reported that no procedure-related deaths occurred with any intervention. Seven studies reported the numbers of participants with adverse events, showing no clear evidence of benefit of either LMA or ETT during PDT (RR 0.73, 95% CI 0.35 to 1.52, P value 0.41, low-quality evidence). The tally of participants in included studies with adverse events ranged from 0% to 33% in the LMA group and from 0% to 50% in the ETT group. However, the duration of the procedure was significantly shorter in the LMA group (mean difference (MD) -1.46 minutes, 95% CI -1.92 to -1.01 minutes, 324 participants, P value ≤ 0.00001, low-quality evidence). No clear evidence of a difference between ETT and LMA groups was found for all other outcomes. Only one study provided follow-up data for late complications related to the intervention, showing no clear evidence of benefit for any treatment group. AUTHORS' CONCLUSIONS: Evidence on the safety of LMA for PDT is too limited to allow conclusions to be drawn on its efficacy or safety compared with ETT. Although the LMA procedure is shorter because of optimal visual conditions, its effect on especially late complications has not been investigated sufficiently. Studies focusing on late complications and relevant patient-related outcomes are necessary for definitive conclusions on safety issues related to this procedure.