The European Academy for Cognitive Behavioural Therapy for Insomnia: An initiative of the European Insomnia Network to promote implementation and dissemination of treatment.

Insomnia, the most prevalent sleep disorder worldwide, confers marked risks for both physical and mental health. Furthermore, insomnia is associated with considerable direct and indirect healthcare costs. Recent guidelines in the US and Europe unequivocally conclude that cognitive behavioural therapy for insomnia (CBT-I) should be the first-line treatment for the disorder. Current treatment approaches are in stark contrast to these clear recommendations, not least across Europe, where, if any treatment at all is delivered, hypnotic medication still is the dominant therapeutic modality. To address this situation, a Task Force of the European Sleep Research Society and the European Insomnia Network met in May 2018. The Task Force proposed establishing a European CBT-I Academy that would enable a Europe-wide system of standardized CBT-I training and training centre accreditation. This article summarizes the deliberations of the Task Force concerning definition and ingredients of CBT-I, preconditions for health professionals to teach CBT-I, the way in which CBT-I should be taught, who should be taught CBT-I and to whom CBT-I should be administered. Furthermore, diverse aspects of CBT-I care and delivery were discussed and incorporated into a stepped-care model for insomnia.

Quantitative analysis of hepatic macro- and microvascular alterations during cirrhogenesis in the rat.

Cirrhosis represents the end-stage of any persistent chronically active liver disease. It is characterized by the complete replacement of normal liver tissue by fibrosis, regenerative nodules, and complete fibrotic vascularized septa. The resulting angioarchitectural distortion contributes to an increasing intrahepatic vascular resistance, impeding liver perfusion and leading to portal hypertension. To date, knowledge on the dynamically evolving pathological changes of the hepatic vasculature during cirrhogenesis remains limited. More specifically, detailed anatomical data on the vascular adaptations during disease development is lacking. To address this need, we studied the 3D architecture of the hepatic vasculature during induction of cirrhogenesis in a rat model. Cirrhosis was chemically induced with thioacetamide (TAA). At predefined time points, the hepatic vasculature was fixed and visualized using a combination of vascular corrosion casting and deep tissue microscopy. Three-dimensional reconstruction and data-fitting enabled cirrhogenic features to extracted at multiple scales, portraying the impact of cirrhosis on the hepatic vasculature. At the macrolevel, we noticed that regenerative nodules severely compressed pliant venous vessels from 12 weeks of TAA intoxication onwards. Especially hepatic veins were highly affected by this compression, with collapsed vessel segments severely reducing perfusion capabilities. At the microlevel, we discovered zone-specific sinusoidal degeneration, with sinusoids located near the surface being more affected than those in the middle of a liver lobe. Our data shed light on and quantify the evolving angioarchitecture during cirrhogenesis. These findings may prove helpful for future targeted invasive interventions.

A multilevel framework to reconstruct anatomical 3D models of the hepatic vasculature in rat livers.

The intricate (micro)vascular architecture of the liver has not yet been fully unravelled. Although current models are often idealized simplifications of the complex anatomical reality, correct morphological information is instrumental for scientific and clinical purposes. Previously, both vascular corrosion casting (VCC) and immunohistochemistry (IHC) have been separately used to study the hepatic vasculature. Nevertheless, these techniques still face a number of challenges such as dual casting in VCC and limited imaging depths for IHC. We have optimized both techniques and combined their complementary strengths to develop a framework for multilevel reconstruction of the hepatic circulation in the rat. The VCC and micro-CT scanning protocol was improved by enabling dual casting, optimizing the contrast agent concentration, and adjusting the viscosity of the resin (PU4ii). IHC was improved with an optimized clearing technique (CUBIC) that extended the imaging depth for confocal microscopy more than five-fold. Using in-house developed software (DeLiver), the vascular network - in both VCC and IHC datasets - was automatically segmented and/or morphologically analysed. Our methodological framework allows 3D reconstruction and quantification of the hepatic circulation, ranging from the major blood vessels down to the intertwined and interconnected sinusoids. We believe that the presented framework will have value beyond studies of the liver, and will facilitate a better understanding of various parenchymal organs in general, in physiological and pathological circumstances.

A multilevel modeling framework to study hepatic perfusion characteristics in case of liver cirrhosis.

Liver cirrhosis represents the end-stage of different liver disorders, progressively affecting hepatic architecture, hemodynamics, and function. Morphologically, cirrhosis is characterized by diffuse fibrosis, the conversion of normal liver architecture into structurally abnormal regenerative nodules and the formation of an abundant vascular network. To date, the vascular remodeling and altered hemodynamics due to cirrhosis are still poorly understood, even though they seem to play a pivotal role in cirrhogenesis. This study aims to determine the perfusion characteristics of the cirrhotic circulation using a multilevel modeling approach including computational fluid dynamics (CFD) simulations. Vascular corrosion casting and multilevel micro-CT imaging of a single human cirrhotic liver generated detailed datasets of the hepatic circulation, including typical pathological characteristics of cirrhosis such as shunt vessels and dilated sinusoids. Image processing resulted in anatomically correct 3D reconstructions of the microvasculature up to a diameter of about 500 µm. Subsequently, two cubic samples (150 × 150 × 150 µm³) were virtually dissected from vascularized zones in between regenerative nodules and applied for CFD simulations to study the altered cirrhotic microperfusion and permeability. Additionally, a conceptual 3D model of the cirrhotic macrocirculation was developed to reveal the hemodynamic impact of regenerative nodules. Our results illustrate that the cirrhotic microcirculation is characterized by an anisotropic permeability showing the highest value in the direction parallel to the central vein (kd,zz = 1.68 × 10-13 m² and kd,zz = 7.79 × 10⁻¹³ m² for sample 1 and 2, respectively) and lower values in the circumferential (kd,ϑϑ = 5.78 × 10⁻¹4 m² and kd,ϑϑ = 5.65 × 10⁻¹³ m² for sample 1 and 2, respectively) and radial (kd,rr = 9.87 × 10⁻¹4 m² and kd,rr = 5.13 × 10⁻¹³ m² for sample 1 and 2, respectively) direction. Overall, the observed permeabilities are markedly higher compared to a normal liver, implying a locally decreased intrahepatic vascular resistance (IVR) probably due to local compensation mechanisms (dilated sinusoids and shunt vessels). These counteract the IVR increase caused by the presence of regenerative nodules and dynamic contraction mechanisms (e.g., stellate cells, NO-concentration, etc.). Our conceptual 3D model of the cirrhotic macrocirculation indicates that regenerative nodules severely increase the IVR beyond about 65 vol. % of regenerative nodules. Numerical modeling allows quantifying perfusion characteristics of the cirrhotic macro- and microcirculation, i.e., the effect of regenerative nodules and compensation mechanisms such as dilated sinusoids and shunt vessels. Future research will focus on the development of models to study time-dependent degenerative adaptation of the cirrhotic macro- and microcirculation.

Match and Mismatch between Lived Experiences of Daytime Sleepiness and Diagnostic Instruments: A Qualitative Study amongst Patients with Sleep Disorders.

Excessive daytime sleepiness is a common symptom of sleep disorders. Despite its prevalence, it remains difficult to define, detect, and address. The difficulties surrounding sleepiness have been linked to an ambiguous conceptualization, a large variety of scales and measures, and the overlap with other constructs, such as fatigue. The present study aims to investigate patients' descriptions of sleepiness-related daytime complaints and their phenomenology. We performed semi-directed interviews with patients diagnosed with obstructive sleep apnea (N = 15) or narcolepsy (N = 5). The interviewers took care of utilizing the participants' terminology when describing daytime complaints related to their sleep disorder. Various aspects of the daytime complaints were investigated, such as their description and temporality. The transcribed content was thematically analyzed using an eclectic coding system, yielding five themes. The participants used different interchangeable descriptors (tired, sleepy, fatigued, exhausted) to express their daytime complaints. They enriched their description with indexes of magnitude (ranging from 'not especially' to 'most gigantic, extreme'), oppositions to other states (using antipodes like energy, alertness, wakefulness, or rest), and indications of fluctuations over the day. Interestingly, the participants often used metaphors to express their experiences and their struggles. The lived experiences of the patients were found to not always align with common self-reported monitoring tools of sleepiness and to relate only in part with current conceptions. In practice, it is important to probe daytime complaints, such as daytime sleepiness, with a broader consideration, for example, by exploring antipodes, consequences, and time-of-day fluctuations.

Volume-reduced platelet concentrates: optimization of production and storage conditions.

BACKGROUND: Plasma can be removed from platelet (PLT) concentrates (PCs) when volume reduction for PLT transfusion is indicated. Volume-reduced PCs are currently produced from pooled buffy coat (BC) PCs or apheresis PCs by pretransfusion volume reduction, followed by transfer to a syringe for immediate transfusion. We evaluated the maximal storage time of the volume-reduced PCs in gas-permeable containers. STUDY DESIGN AND METHODS: Volume-reduced PCs were produced from BC-derived and apheresis PCs by hard-spin centrifugation. Supernatant was removed and the PLTs were resuspended in 20 mL of retained original PC and had PLT concentrations ranging from 10.8 × 10(9) to 13.8 × 10(9) PLTs/mL. Volume-reduced PCs were stored either in syringes or in containers made from diethylhexyl phthalate (DEHP)-polyvinylchloride (PVC) or butyryl trihexyl citrate (BTHC)-PVC plastic. Units were sampled at t = 0, 1, 3, and 6 hours for in vitro measurements. RESULTS: When prepared from 2-day-old PCs (n = 4), volume-reduced PCs from BCs in a syringe had a pH(37°C) of 5.76 ± 0.04 at t = 6 hours after volume reduction. In the DEHP-PVC container, pH was 5.85 ± 0.15 (not significant), and in the BTHC-PVC, 6.34 ± 0.16 (p < 0.001), at t = 6 hours. When made from 7-day-old PCs, pH was lower for all storage conditions: 5.68 ± 0.06 in the syringe, 5.70 ± 0.09 in the DEHP-PVC container (not significant), and 6.07 ± 0.24 in the BTHC-PVC container (p < 0.01) at t = 6 hours. Volume-reduced 2-day-old apheresis PCs had a pH of 6.47 ± 0.20 at t = 6 hours. CONCLUSIONS: Adult-dose PCs derived from BC or apheresis can be volume-reduced to approximately 20 mL in a closed gas-permeable system. Volume-reduced PCs in BTHC-PVC containers retain a mean pH of more than 6.0 up to 6 hours after production. Syringes allow only 3 hours of storage.

Long-term results of laparoscopic sleeve gastrectomy for obesity.

OBJECTIVE: To determine the mid- and long-term efficacy and possible side effects of laparoscopic sleeve gastrectomy as treatment for morbid obesity. SUMMARY BACKGROUND DATA: Laparoscopic sleeve gastrectomy is still controversial as single and final treatment for morbid obesity. Some favorable short-term results have been published, however long-term results are still lacking. METHODS: In the period between November 2001 and October 2002, 53 consecutive morbidly obese patients who, according to our personal algorithm, were qualified for restrictive surgery were selected for laparoscopic sleeve gastrectomy. Of the 53 patients, 11 received an additional malabsorptive procedure at a later stage because of weight regain. The percentage of excess weight loss (EWL) was assessed at 3 and 6 years postoperatively. A retrospective review of a prospectively collected database was performed for evaluation after 3 years. Recently, after the sixth postoperative year, patients were again contacted and invited to fill out a questionnaire. RESULTS: Full cooperation was obtained in 41 patients, a response rate of 78%. Although after 3 years a mean EWL of 72.8% was documented, after 6 years EWL had dropped to 57.3%, which according to the Reinhold criteria is still satisfactory. These results included 11 patients who had benefited from an additional malabsorptive procedure (duodenal switch) and 2 patients who underwent a "resleeve" between the third and sixth postoperative year. Analyzing the results of the subgroup of 30 patients receiving only sleeve gastrectomy, we found a 3-year %EWL of 77.5% and 6+ year %EWL of 53.3%. The differences between the third and sixth postoperative year were statistically significant in both groups. Concerning long-term quality of life patient acceptance stayed good after 6 + years despite the fact that late, new gastro-esophageal reflux complaints appeared in 21% of patients. CONCLUSIONS: In this long-term report of laparoscopic sleeve gastrectomy, it appears that after 6+ years the mean excess weight loss exceeds 50%. However, weight regain and de novo gastroesophageal reflux symptoms appear between the third and the sixth postoperative year. This unfavorable evolution might have been prevented in some patients by continued follow-up office visits beyond the third year. Patient acceptance remains good after 6+ years.

A hybrid endo-laparoscopic therapy for common bile duct stenosis of a choledocho-duodenostomy after a Roux-en-Y gastric bypass.

The essential growth of the number of Roux-en-Y gastric bypass procedures will obviously be accompanied by an increase of cases of common bile duct lithiasis. It seems evident that a close cooperation between surgeon and endoscopist will be needed on a routine basis. A laparoscopic-assisted transgastric ERCP is a well-documented approach to investigate the pancreatico-biliary tree in patients where the duodenum has been bypassed as in Roux-en-Y gastric bypass. In this case we present the possibility of assisting the endoscopist not only by providing access to the gastric remnant but also by helping with laparoscopic instruments during duodenoscopy. A formally obese woman who had benefited from a RYGB developed recurrent jaundice despite a precedent common bile duct exploration and choledocho-duodenostomy. A laparoscopic-assisted transgastric endoscopy revealed an obstructed choledocho-duodenostomy caused by accretions around a migrated clip. The obstructing clip could be extracted by laparoscopic instruments under endoscopic control.

Management of insomnia in sleep disordered breathing.

Both obstructive sleep apnoea (OSA) and chronic insomnia disorder are highly prevalent in the general population. Whilst both disorders may occur together by mere coincidence, it appears that they share clinical features and that they may aggravate each other as a result of reciprocally adverse pathogenetic mechanisms. Comorbidity between chronic insomnia disorder and OSA is a clinically relevant condition that may confront practitioners with serious diagnostic and therapeutic challenges. Current data, while still scarce, advocate an integrated and multidisciplinary approach that seems superior over the isolated treatment of each sleep disorder alone.

Closed-Loop Lumped Parameter Modeling of Hemodynamics During Cirrhogenesis in Rats.

OBJECTIVE: Cirrhosis is the common end stage of any given chronic liver disease, developing after persistent destruction and regeneration of parenchymal liver cells. The associated architectural distortion increases the intrahepatic vascular resistance, leading to portal hypertension and systemic circulatory disorders. This study investigates the impact of the changing vascular resistances on the hepatic and global circulation hemodynamics during cirrhogenesis. METHODS: Cirrhogenesis was revisited using the thioacetamide rat model (N = 20). Rats were sacrificed at weeks 0, 6, 12, and 18. For each time-point, three-dimensional vascular geometries were created by combining hepatic vascular corrosion casting with µCT imaging. Morphological quantification of the trees branching topology provided the input for a lobe-specific lumped parameter model of the liver that was coupled to a closed-loop model of the entire circulation of the rat. Hemodynamics was simulated in physiological and pathological circumstances. RESULTS: The simulations showed the effect of the liver vascular resistances (driven by the hepatic venous resistance increase) on liver hemodynamics with portal hypertension observed after 12 weeks. The closed-loop model was further adapted to account for systemic circulatory compensation mechanisms and disorders frequently observed in cirrhosis and simulated their impact on the hepatic, systemic, and pulmonary hemodynamics. CONCLUSION: The simulations explain how vascular changes due to cirrhosis severely disrupt both hepatic and global hemodynamics. SIGNIFICANCE: This study is a priori the first to model the rat's entire blood circulation during cirrhogenesis. Since it is able to simulate cirrhosis main characteristics, the model may be translated to humans for the assessment of liver interventions.

Nanofat grafting: basic research and clinical applications.

BACKGROUND: The indications for fat grafting are increasing steadily. In microfat grafting, thin injection cannulas are used. The authors describe their experience of fat injection with even thinner injection needles up to 27 gauge. The fat used for this purpose is processed into "nanofat." Clinical applications are described. Preliminary results of a study, set up to determine the cellular contents of nanofat, are presented. METHODS: Nanofat grafting was performed in 67 cases to correct superficial rhytides, scars, and dark lower eyelids. Three clinical cases are described. In the research study, three fat samples were analyzed. The first sample was a classic lipoaspirate (macrofat). The second sample was microfat, harvested with a multiport small-hole cannula. The third was microfat processed into nanofat. Processing consisted of emulsification and filtering of the lipoaspirate. Fat samples were analyzed for adipocyte viability. Cells from the stromal vascular fraction and the CD34+ subfraction were quantified. The stem cell quality was investigated by culturing the cells in standard and adipogenic media. RESULTS: No viable adipocytes were observed in the nanofat sample. Adipose-derived stem cells were still richly present in the nanofat sample. Cell cultures showed an equal proliferation and differentiation capacity of the stem cells from the three samples. Clinical applications showed remarkable improvements in skin quality 6 months postoperatively. No infections, fat cysts, granulomas, or other unwanted side effects were observed. CONCLUSIONS: Nanofat injections might become a new concept in the lipofilling area. In clinical situations, nanofat seems to be suitable for skin rejuvenation purposes.

Successful laparoscopic exploration and screw extraction for intractable pain after anterior iliosacral arthrodesis.

We report on the case of a patient suffering from L5 radicular pain after previous anterior sacroiliac arthrodesis using 2, 4-hole plates. Technical investigations indicated loosening and migration of a screw from the upper sacroiliac plate, irritating the L5 nerve root. The problem was managed by removal of the screw using an anterior transperitoneal laparoscopic approach.

pH 48 h after onset of extracorporeal membrane oxygenation is an independent predictor of survival in patients with respiratory failure.

Extracorporeal membrane oxygenation (ECMO) is a life-saving procedure in patients with severe respiratory failure, unresponsive to conventional therapy. We reviewed our series of 70 ECMO runs (April 1997 to December 2005) in patients with respiratory distress, refractory to standard ventilation. Survival at 90 days was 42.7%. Besides age, we found no statistical significant difference in patient demographics or preoperative patient data between survivors and nonsurvivors. Univariate analyses indicated that pH values at 24 and 48 h after onset of ECMO were significantly higher in survivors. In multivariate analysis, age and pH at 48 h remained independent predictors of survival. ECMO in respiratory failure saves lives. No other demographic or preoperative, patient-related parameter than age was identified as predictor of survival. Although there was no difference in pH at onset of ECMO, blood gas analysis at 48 h revealed pH as an independent predictor of survival.

Validation of the NucliSens Extractor combined with the AmpliScreen HIV version 1.5 and HCV version 2.0 test for application in NAT minipool screening.

BACKGROUND: Routine HCV NAT minipool screening (48 donations) of all blood donations was implemented in July 1999 and was combined with HIV NAT in November 2000. This report describes the validation of the NAT methods and the results of quality control testing. STUDY DESIGN AND METHODS: Nucleic acid was extracted from 2-mL plasma samples by using an automated silica-based extraction method (NucliSens Extractor, Organon Teknika). Eluates were tested with RT-PCR (AmpliScreen HIV-1 version 1.5 and AmpliScreen HCV version 2.0 test, Roche Diagnostic Systems). HIV-1 and HCV RNA reference panels and run controls (PeliCheck and PeliSpy, respectively, Sanquin-CLB) and human plasma minipools were used for NAT validation. RESULTS: The 95-percent detection limit (and 95% CI) for HIV-1 RNA genotype B, HIV-1 RNA genotype E, and HCV RNA genotype 1 was 32 (19-76), 30 (17-72), and 21 (13-44) genome equivalents (geq) per mL, respectively. During initial validation, 2332 samples for HIV-1 RNA and 2644 samples for HCV RNA were analyzed, with 13 (0.56%) and 12 (0.45%) invalid test results, respectively. Thereafter, over 19,600 samples (minipools and run controls) were analyzed during the first 11 months of routine screening. Invalid test results for HIV-1 RNA and HCV RNA were found in 1.1 and 1.07 percent of the samples tested, respectively. HIV-1 RNA minipool testing resulted in 27 (0.16%) initial false-positive results and 3 (0.02%) confirmed positive results. HCV RNA minipool testing resulted in four (0.02%) initial false-positive results and five (0.02%) confirmed positive results. CONCLUSION: Routine HIV and HCV NAT minipool screening using the NucliSens Extractor, AmpliScreen HIV-1 version 1.5, and AmpliScreen HCV version 2.0 meets the sensitivity criteria set by the regulatory bodies and provides sufficient specificity and robustness for timely release of blood donations.