Obstructive sleep apnoea and nocturnal gastroesophageal reflux are common in lung transplant patients

Background and objective: Gastroesophageal reflux (GOR) has been implicated in the pathogenesis of bronchiolitis obliterans syndrome (BOS), possibly due to pulmonary aspiration of refluxed acid. Risk of aspiration of gastric contents is increased during sleep due to decreased oesophageal clearance mechanisms and may be further increased by the presence of OSA. This study investigated the relationship between nocturnal GOR, OSA and BOS in a group of lung transplant patients. Methods: Fourteen lung transplant patients underwent overnight polysomnography with simultaneous dual oesophageal pH monitoring. Results: Patients had an FEV₁ of 84 ± 15% of their best post-transplant FEV₁. Six of the 14 patients were in various stages of BOS. The average proportion of time spent overnight with a pH of <4 was 1.7 ± 3.1%. Increased GOR was evident in 8/14 patients during the postprandial period and/or overnight in the distal and/or proximal oesophagus. All patients had OSA (AHI >5 events per hour). There were no relationships between severity of OSA or GOR and severity of BOS. Conclusion: Both nocturnal GOR and OSA were common in this group of patients but their occurrences were not related. Neither was there any relationship between the presence of nocturnal GOR or OSA and severity of BOS.     

Plowing the atrium and growing thrombi: two cases of large atrial thrombi following ablative and surgical procedure for atrial fibrillation.

AIM: We present two patients with a large left atrial (LA) thrombus following invasive treatment for atrial fibrillation and inadequate anticoagulation. METHODS AND RESULTS: Case 1: A 30-year-old woman, with a one-year history of symptomatic paroxysmal atrial fibrillation resistant to medical therapy, underwent catheter ablation for atrial fibrillation. Three days after the procedure the patient presented with dizziness, fatigue, rapid atrial fibrillation with a sub-therapeutic INR. Transesophageal echocardiography (TEE) revealed a large LA thrombus. Case 2: A 59-year-old male, with severe mitral regurgitation and chronic atrial fibrillation, underwent mitral valve repair and Cox-Maze procedure. Three months later, while asymptomatic, a follow-up transthoracic echocardiography a large posterior LA thrombus was imaged. His INR was also sub-therapeutic. Both patients were treated by enhancing anticoagulation and close echocardiographic follow-up. So far both patients have remained asymptomatic two months following discharge. CONCLUSION: Large LA thrombi detected by transthoracic echocardiography are a rare complication of the Cox-Maze procedure and radio-frequency ablation for atrial fibrillation, which may occur even in patients with restored normal sinus rhythm receiving inadequate anticoagulation therapy.     

Skin involvement in juvenile dermatomyositis is associated with loss of end row nailfold capillary loops

OBJECTIVE: To determine associations of dermatological findings in children with juvenile dermatomyositis (JDM) with specific nailfold capillary (NFC) structural abnormalities. METHODS: Sixty newly diagnosed, previously untreated children who met the Bohan-Peter criteria for definite JDM were seen between 1993 and 2002. They were classified by duration of untreated disease and by a disease activity score (DAS) composed of separate subscores for dermatological (DAS skin) and musculoskeletal (DAS muscle) findings. Routine NFC measurements yielded the number of end row loops, arboreal (bushy), and dilated capillary loops. Laboratory testing included muscle enzymes, von Willebrand Factor Antigen, and neopterin. RESULTS: DAS skin, but not DAS muscle, was associated with NFC end row capillary loss (rs = -0.394, p = 0.008). End row capillary loss (reflecting avascularity), arboreal (bushy), and dilated capillary loops (reflecting change in vascular morphology) were each associated with longer untreated symptom duration (rs = -0.401, rs = 0.534, rs = 0.371). CONCLUSION: End row capillary loss measured by NFC was associated with the dermatological, but not musculoskeletal manifestations of JDM, suggesting that damage to skin and muscle may each have distinct disease pathophysiology. In JDM, skin involvement indicates a vasculopathy that progresses with increasing duration of untreated disease and is not revealed by standard serological laboratory tests. We propose that the cutaneous manifestations of JDM are associated with vascular disease and warrant aggressive therapy.     

Conceptual and perceptual similarity between encoding and retrieval contexts and recognition memory context effects in older and younger adults

We examined the hypothesis that older adults' deficits in contextual memory result from difficulties in contending with partial encoding-to-retrieval changes in the context. We measured effects of contextual change and constancy on recognition memory for words, in older and younger adults. We assessed the ability to adjust to partial contextual changes by manipulating encoding-retrieval context similarity: identical, new and unrelated, conceptually similar, or perceptually similar. For both older and younger adults, identical and conceptually similar contexts benefited recognition of target words, whereas perceptually similar contexts did not. Older adults did not make more false alarms. In contrast, older adults' direct recognition of contextual stimuli was at chance. These results indicate that retrieval processes, rather than encoding or rigidity in the use of contextual cues, are implicated in older adults' difficulties in memory for contextual information.     

Severe hypoleptinaemia associated with insulin resistance in patients with common variable immunodeficiency

Objective Common variable immunodeficiency (CVI) is a primary immunodeficiency syndrome characterized by impaired production of antibodies and recurrent infections. Delay in diagnosis leads to metabolic wastage and low body weight. Leptin, a hormone produced by white adipose tissue, modulates insulin action by signal transduction cross‐talk and by direct action on pancreatic beta‐cells. We hypothesized that patients with CVI might present a defective regulation of leptin production and insulin resistance. Patients Thirteen CVI patients (39 ± 11 years) under gammaglobulin replacement were evaluated in parallel with 13 gender‐, age‐, body weight‐ and body mass index (BMI)‐matched healthy voluntaries, and with data from two large population series, the Bruneck and the Hoorn Studies. Measurements Serum leptin and insulin levels, homeostasis model assessment – insulin resistance (HOMA‐IR), body composition, haematological, biochemical and immunoglobulin measurements were obtained. Data were analysed by a one‐way analysis of variance (anova ) and by Pearson's rank analysis. The institutional ethics committee approved the study, and informed consent was obtained from patients and controls. Results No differences were found between CVI and the control group when comparing gender distribution, age, body weight, BMI, waist/hip ratio, relative body fat and fasting glucose levels. Leptin levels were lower (P < 0·05) in CVI patients than in controls and lower than fasting leptin levels detected in a large population study. CVI patients’ serum leptin levels did not correlate with BMI (r = 0·074, P = 0·8) and their high HOMA‐IR indicated insulin resistance. Conclusions CVI patients are relatively hypoleptinaemic and insulin resistant, and their serum leptin levels are not correlated to their BMI.     

Cx43 hemichannel microdomain signaling at the intercalated disc enhances cardiac excitability

Cx43, a major cardiac connexin, forms precursor hemichannels that accrue at the intercalated disc to assemble as gap junctions. While gap junctions are crucial for electrical conduction in the heart, little is known about the potential roles of hemichannels. Recent evidence suggests that inhibiting Cx43 hemichannel opening with Gap19 has antiarrhythmic effects. Here, we used multiple electrophysiology, imaging, and super-resolution techniques to understand and define the conditions underlying Cx43 hemichannel activation in ventricular cardiomyocytes, their contribution to diastolic Ca²⁺ release from the sarcoplasmic reticulum, and their impact on electrical stability. We showed that Cx43 hemichannels were activated during diastolic Ca²⁺ release in single ventricular cardiomyocytes and cardiomyocyte cell pairs from mice and pigs. This activation involved Cx43 hemichannel Ca²⁺ entry and coupling to Ca²⁺ release microdomains at the intercalated disc, resulting in enhanced Ca²⁺ dynamics. Hemichannel opening furthermore contributed to delayed afterdepolarizations and triggered action potentials. In single cardiomyocytes, cardiomyocyte cell pairs, and arterially perfused tissue wedges from failing human hearts, increased hemichannel activity contributed to electrical instability compared with nonfailing rejected donor hearts. We conclude that microdomain coupling between Cx43 hemichannels and Ca²⁺ release is a potentially novel, targetable mechanism of cardiac arrhythmogenesis in heart failure.     

Open versus Endoscopic Carpal Tunnel Release: A Meta-analysis of Randomized Controlled Trials

Background

Carpal tunnel syndrome is a common compressive neuropathy of the median nerve. The efficacy and safety of endoscopic versus open carpal tunnel release remain controversial.

Questions/purposes

The purpose of this study was to determine whether endoscopic compared with open carpal tunnel release provides better symptom relief, validated outcome scores, short- and long-term strength, and/or digital sensibility; entails a differential risk of complications such as nerve injury, scar tenderness, pillar pain, and reoperation; allows an earlier return to work; and takes less operative time.

Methods

The English-language literature was searched using MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials. Randomized controlled trials that compared endoscopic and open carpal tunnel release were included in the meta-analysis. Methodologic quality was assessed with the Consolidated Standards Of Reporting Trials (CONSORT) checklist, and a sensitivity analysis was performed. Symptom relief, Boston Carpal Tunnel Questionnaire (BCTQ) scores, strength, digital sensibility, complications, reoperation, interval to return to work, and operative time were analyzed. Twenty-one randomized controlled trials containing 1859 hands were included.

Results

Endoscopically treated patients showed similar symptom relief and BCTQ scores; better early recovery of grip strength (mean difference [MD], 3.03 kg [0.08–5.98]; p = 0.04) and pinch strength (MD, 0.77 kg [0.33–1.22]; p < 0.001) but no advantage after 6 months; lower risk of scar tenderness (risk ratio [RR], 0.53 [0.35–0.82]; p = 0.005); higher risk of nerve injury (RR, 2.84 [1.08–7.46]; p = 0.03), most of which were transient neurapraxias. Similar risk of pillar pain and reoperation; an earlier return to work (MD, −8.73 days [−12.82 to −4.65]; p < 0.001); and reduced operative time (MD, −4.81 minutes [−9.23 to −0.39]; p = 0.03).

Conclusions

High-level evidence from randomized controlled trials indicates that endoscopic release allows earlier return to work and improved strength during the early postoperative period. Results at 6 months or later are similar according to current data except that patients undergoing endoscopic release are at greater risk of nerve injury and lower risk of scar tenderness compared with open release. While endoscopic release may appeal to patients who require an early return to work and activities, surgeons should be cognizant of its elevated incidence of transient nerve injury amid its similar overall efficacy to open carpal tunnel release. Additional research is required to define the learning curve of endoscopic release and clarify the influence of surgeon volume on its safety.     

Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials

BackgroundTHEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n = 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n = 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA_1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention.ObjectivesIn these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction–defined major bleeding) and net clinical benefit varied with diabetes-related factors.MethodsOutcomes were analyzed across baseline diabetes duration, HbA_1c, and antihyperglycemic medications.ResultsIn THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and HbA_1c (6.4% for ≤6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p = 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA_1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA_1c, and antihyperglycemic medications.ConclusionTicagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population.