Inhibition of CaMKII Attenuates Progressing Disruption of Ca2+ Homeostasis Upon Left Ventricular Assist Device Implantation in Human Heart Failure

In heart failure, left ventricular assist device (LVAD) implantation is performed to ensure sufficient cardiac output. Whereas some patients are subsequently weaned from LVAD support, other patients still need heart transplantation. To elucidate underlying mechanisms, we assessed the arrhythmogenic SR‐Ca²⁺ leak at the time of LVAD implantation (HF‐Im) and heart transplantation (HF‐Tx) and evaluated the effects of CaMKII‐inhibition. Human left‐ventricular cardiomyocytes were isolated, paced at 1 Hz for 10 beats to ensure SR‐Ca²⁺ loading and scanned for diastolic Ca²⁺ sparks (confocal microscopy). In HF‐Im, the high diastolic spark frequency (CaSpF) of 0.76 ± 0.12 × 100 μm^?1 × s^?1 could be reduced to 0.48 ± 0.10 × 100 μm^?1 × s^?1 by CaMKII inhibition (AIP, 1 μM). The amplitude of Ca²⁺ sparks, width, and length was not significantly altered. In sum, CaMKII inhibition yielded a clear tendency toward a reduction of the SR‐Ca²⁺ leak (n cells/patients = 76/6 vs. 108/6, P = 0.08). In HF‐Tx, we detected an even higher CaSpF of 1.00 ± 0.10 100 μm^?1 × s^?1 and a higher SR‐Ca²⁺ leak compared with HF‐Im (increase by 81 ± 33%, n cells/patients = 156/7 vs. 130/7, P < 0.05), which fits to the further decreased LV function. Here, CaMKII inhibition likewise reduced CaSpF (0.35 ± 0.09 100 μm^?1 × s^?1, P = 0.06) and significantly reduced spark duration (n sparks/patients = 58/3 vs. 159/3, P < 0.05). Conclusively, the SR‐Ca²⁺ leak was reduced by 69 ± 12% in HF‐Tx upon CaMKII inhibition (n cells/patients = 53/3 vs. 91/3, P < 0.05). These data show that the SR‐Ca²⁺ leak correlates with the development of LV function after LVAD implantation and may represent an important pathomechanism. The fact that CaMKII inhibition reduces the SR‐Ca²⁺ leak in HF‐Tx suggests that CaMKII inhibition may be a promising option to beneficially influence clinical course after LVAD implantation.     

Impaired longitudinal deformation measured by speckle-tracking echocardiography in children with end-stage renal disease

Background

Left ventricular dysfunction is an important co-morbidity of end-stage renal disease (ESRD) and is associated with a poor prognosis in the adult population. In pediatric ESRD, left ventricular function is generally well preserved, but limited information is available on early changes in myocardial function. The aim of this study was to investigate myocardial mechanics in pediatric patients with ESRD using speckle-tracking echocardiography (STE).

Methods

Echocardiographic studies, including M-mode, tissue Doppler imaging (TDI) and STE, were performed in 19 children on dialysis, 17 transplant patients and 33 age-matched controls. Strain measurements were performed from the apical four-chamber and the short axis view, respectively.

Results

The interventricular and left ventricular posterior wall thickness was significantly increased in dialysis and transplant patients compared to healthy controls. No significant differences were found in shortening fraction, ejection fraction and systolic tissue Doppler velocities. Dialysis and transplant patients had a decreased mean longitudinal strain compared to healthy controls, with a mean difference of 3.1 [95 % confidence interval (CI) 2.0–4.4] and 2.7 (95 % CI 1.2–4.2), respectively. No differences were found for radial and circumferential strain.

Conclusions

Speckle-tracking echocardiography may reveal early myocardial dysfunction in the absence of systolic dysfunction measured by conventional ultrasound or TDI in children with ESRD.

     

Determining clinical practice of expert physiotherapy for patients undergoing lumbar spinal fusion: a cross-sectional survey study

Purpose

To determine the content of current Dutch expert hospital physiotherapy practice for patients undergoing lumbar spinal fusion (LSF), to gain insight into expert-based clinical practice.

Methods

At each hospital where LSF is performed, one expert physiotherapist received an e-mailed questionnaire, about pre- and postoperative physiotherapy and discharge after LSF. The level of uniformity in goals and interventions was graded on a scale from no uniformity (50–60 %) to very strong uniformity (91–100 %).

Results

LSF was performed at 34 of the 67 contacted hospitals. From those 34 hospitals, 28 (82 %) expert physiotherapists completed the survey. Twenty-one percent of the respondents saw patients preoperatively, generally to provide information. Stated postoperative goals and administered interventions focused mainly on performing transfers safely and keeping the patient informed. Outcome measures were scarcely used. There was no uniformity regarding advice on the activities of daily living.

Conclusion

Dutch perioperative expert physiotherapy for patients undergoing LSF is variable and lacks structural outcome assessment. Studies evaluating the effectiveness of best-practice physiotherapy are warranted.

     

Routine Postoperative Monitoring after Bariatric Surgery in Morbidly Obese Patients with Severe Obstructive Sleep Apnea: ICU Admission is not Necessary

Background and Study Aim

Obstructive sleep apnea (OSA) occurs in 70–80 % of bariatric surgery patients. Patients with severe OSA (apnea/hypopnea index (AHI) >30/h) are postoperatively admitted to an intensive care unit (ICU) for continuous monitoring, to prevent complications. The aim of this study was to assess the necessity of routine postoperative monitoring at an ICU of severe OSA patients after bariatric surgery, attempting to prevent and detect cardiorespiratory complications.

Methods

Patients undergoing bariatric surgery from November 2010 to July 2013 were entered into a database. Minimal follow-up was 1 month. Poly(somno)graphy (P(S)G) was routinely performed. Patients with severe OSA were admitted to the ICU for the first postoperative night. Oxygen saturation was continuously measured. The database was reviewed regarding patient characteristics, CPAP use, re-intubations, desaturations (saturation <90 % and severe <85 %), and complications.

Results

Severe OSA was present in 151 of the 794 patients, and all 151 were admitted to the ICU. Thirty who underwent revisional surgery were excluded. Forty-seven percent was male, median age was 51 years (27.0–68.0), and median body mass index (BMI) was 46.6 (kg/m²) (34.0–77.6). No deaths, re-intubations, or cardiopulmonary complications occurred. Eighty-two (67.8 %) patients used continuous positive airway pressure (CPAP). Twenty-one (17.4 %) patients experienced desaturations with a median of 2.0 (1–8). Six patients (5.0 %) had one episode of severe desaturation.

Conclusion

Patients with severe OSA and adequate CPAP use are at low risk of cardiopulmonary complications after (laparoscopic) bariatric surgery. Routine admission to an ICU might be superfluous. However, continuous digital oximetry remains essential.

     

An electronic nose in the discrimination of patients with asthma and controls

BACKGROUND: Exhaled breath contains thousands of volatile organic compounds (VOCs) that could serve as biomarkers of lung disease. Electronic noses can distinguish VOC mixtures by pattern recognition. OBJECTIVE: We hypothesized that an electronic nose can discriminate exhaled air of patients with asthma from healthy controls, and between patients with different disease severities. METHODS: Ten young patients with mild asthma (25.1 +/- 5.9 years; FEV(1), 99.9 +/- 7.7% predicted), 10 young controls (26.8 +/- 6.4 years; FEV(1), 101.9 +/- 10.3), 10 older patients with severe asthma (49.5 +/- 12.0 years; FEV(1), 62.3 +/- 23.6), and 10 older controls (57.3 +/- 7.1 years; FEV(1), 108.3 +/- 14.7) joined a cross-sectional study with duplicate sampling of exhaled breath with an interval of 2 to 5 minutes. Subjects inspired VOC-filtered air by tidal breathing for 5 minutes, and a single expiratory vital capacity was collected into a Tedlar bag that was sampled by electronic nose (Cyranose 320) within 10 minutes. Smellprints were analyzed by linear discriminant analysis on principal component reduction. Cross-validation values (CVVs) were calculated. RESULTS: Smellprints of patients with mild asthma were fully separated from young controls (CVV, 100%; Mahalanobis distance [M-distance], 5.32), and patients with severe asthma could be distinguished from old controls (CVV, 90%; M-distance, 2.77). Patients with mild and severe asthma could be less well discriminated (CVV, 65%; M-distance, 1.23), whereas the 2 control groups were indistinguishable (CVV, 50%; M-distance, 1.56). The duplicate samples replicated these results. CONCLUSION: An electronic nose can discriminate exhaled breath of patients with asthma from controls but is less accurate in distinguishing asthma severities. CLINICAL IMPLICATION: These findings warrant validation of electronic noses in diagnosing newly presented patients with asthma.     

Family Based Association Analyses between the Serotonin Transporter Gene Polymorphism (5-HTTLPR) and Neuroticism,Anxiety and Depression

We studied the association between the short/long promotor-based length polymorphism of the serotonin transporter gene (5-HTTLPR) and neuroticism, anxiety and depression. Subjects included twins, their siblings and parents from the Netherlands Twin Register (559 parents and 1,245 offspring). Subjects had participated between one and five times in a survey study measuring neuroticism, anxiety and depression. Offspring of these families were also approached to participate in a psychiatric interview diagnosing DSM-IV major depression. Within-family and total association between 5-HTTLPR and these traits were tested. Only three of the 36 tests showed a significant effect of 5-HTTLPR (P < 0.05). These effects were in opposite directions, i.e. both negative and positive regression coefficients were found for the s allele. No additive effect of the s allele was found for DSM-IV depression. Our results strongly suggest that there is no straightforward association between 5-HTTLPR and neuroticism, anxiety and depression. Edited by Stacey Cherny     

A meta-analysis of clinical studies to estimate the 4.5-year survival rate of implants placed with the osteotome technique

PURPOSE: To estimate the survival rate of implants placed with the osteotome technique by means of a systematic review. MATERIALS AND METHODS: The literature was searched using Medline; the search was limited to the years 1953 to 2005. Inclusion criteria were: (1) clinical studies or clinical reports investigating the osteotome technique for dental implantation and (2) control or test group(s) from clinical studies or clinical reports, even if they did not fit with other criteria. By pooling the data of the included studies, overall Kaplan-Meier survival curves were constructed for the periods before and after loading. RESULTS: The initial literature search yielded 164 studies. After selection criteria were applied, 5 studies were considered suitable for inclusion. The combined data of 349 implants revealed survival probabilities of 98% (confidence interval [CI], 97.2% to 100%) until loading and 99% (CI, 94% to 100%) after 56 months of loading. At the end of the observation period 41 implants in 18 patients were still at risk. CONCLUSION: The outcome of dental implantation using the osteotome technique in terms of implant survival seems to be similar to that of implants placed by means of the conventional implantation technique.     

Oral health status and prosthodontic conditions of Chinese adults: a systematic review

PURPOSE: To assess oral health and prosthodontic conditions of Chinese adults and the changes in these conditions over time. MATERIALS AND METHODS: PubMed was searched by combining the keyword China with dental health survey, oral health, tooth loss, DMFT (decayed/missing/filled teeth), dental prosthesis, or dentures. After selection, 12 studies remained. Data were obtained from these studies on DMFT, DMFT components, and teeth present and were tested against the following independent variables using analysis of variance: age, residence, and year of data collection. RESULTS: DMFT increased with age (P = .0001). Rural subjects presented higher DMFT based on the higher "decayed" component (P = .003), which increased markedly for subjects over 45 years of age. The number of teeth present decreased with increasing age (P = .0002). The results showed that Chinese subjects who are 65 years old have an average of 20 teeth. Urban subjects had more teeth present (P= .05), although no difference was seen for the "missing" component of DMFT. In general, few prosthodontic data could be extracted from the selected studies, and these data were often unspecific or inconclusive. CONCLUSIONS: The "filled" component of DMFT remained consistently low for all ages, indicating limited care. All outcomes were independent from year of data collection, indicating unchanged care. Outcome aggregation on the number of functional teeth and prosthetic care was impossible. For future reports, it is recommended to include additional information about location and function (in terms of occluding pairs) of teeth present when describing oral health status.