Functional Consequences In Patients Research Articles

A genome wide association study to identify germline copy number variants associated with cancer cachexia: a preliminary analysis

AbstractBackgroundCancer cachexia is characterized by severe loss of muscle and fat involving a complex interplay of host–tumour interactions. While much emphasis has been placed on understanding the molecular mechanisms associated with cachexia, understanding the heritable component of cachexia remains less explored. The current study aims to identify copy number variants (CNV) as genetic susceptibility determinants for weight loss in patients with cancer cachexia using genome wide association study (GWAS) approach.MethodsA total of 174 age‐matched patients with oesophagogastric or lung cancer were classified as weight losing (>10% weight loss) or weight stable participants (<2% weight loss). DNA was genotyped using Affymetrix SNP 6.0 arrays to profile CNVs. We tested CNVs with >5% frequency in the population for association with weight loss. Pathway analysis was performed using the genes embedded within CNVs. To understand if the CNVs in the present study are also expressed in skeletal muscle of patients with cachexia, we utilized two publicly available human gene expression datasets to infer the relevance of identified genes in the context of cachexia.ResultsAmong the associated CNVs, 5414 CNVs had embedded protein coding genes. Of these, 1583 CNVs were present at >5% frequency. We combined multiple contiguous CNVs within the same genomic region and called them Copy Number Variable Region (CNVR). This led to identifying 896 non‐redundant CNV/CNVRs, which encompassed 803 protein coding genes. Genes embedded within CNVs were enriched for several pathways implicated in cachexia and muscle wasting including JAK–STAT signalling, Oncostatin M signalling, Wnt signalling and PI3K‐Akt signalling. This is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. Further, we show that a subset of CNV/CNVR embedded genes identified in the current study are common with the previously published skeletal muscle gene expression datasets, indicating that expression of CNV/CNVR genes in muscle may have functional consequences in patients with cachexia. These genes include CPT1B, SPON1, LOXL1, NFAT5, RBFOX1, and PCSK6 to name a few.ConclusionsThis is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. The data generated will aid in future replication studies in larger cohorts to account for genetic susceptibility to weight loss in patients with cancer cachexia.

Airway luminal area in long COVID patients compared to acute COVID-19 patients

Background: Patients with respiratory manifestations of acute COVID-19 infection have enlarged luminal areas of central conducting airways demonstrated on computed tomography imaging and abnormal pulmonary function. In some cases, COVID-19 symptoms may persist for more than 4 weeks, referred to as long COVID, and the effect on airway luminal area remains unknown. Herein, we report airway luminal cross-sections areas among a long COVID group, compared to individuals with an acute COVID-19. We aim to investigate if large conducting airways sizes are different between acute COVID-19 and long COVID patients. Methods: A cohort of 181 people with long COVID were screened, of which 20 people (9 men, 11 women; 55.9 ± 14.1 years) were included in analyses. Twenty age, height, and sex matched patients with an acute (< 4 weeks of persistent symptoms from diagnosis) COVID-19 infection (55.7 ± 15.2 years) served as a comparison group. We used a three-dimensional reconstruction of computed tomography imaging to measure luminal areas of the trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi at proximal, middle, and distal cross-sectional points in both groups. Airway luminal area was taken as the average of the three points. We compared average lumen area of long COVID patients with acute COVID-19 individuals, using an independent samples t-test. Results: We found no significant difference comparing measurements of the following airway luminal cross-sectional areas: trachea (277.7 ± 100.4 vs. 268.0 ± 70.5 mm 2 p=0.73), right main bronchus (191.0 ± 66.1 vs. 190.1 ± 49.0 mm 2 , p=0.96), bronchus intermediate (112.3 ± 33.4 vs. 109.3 ± 27.9 mm 2 , p=0.76), right upper lobe bronchus (74.4 ± 21.0 vs. 73.7 ± 25.5 mm 2 , p=0.92), left main bronchus (129.1 ± 50.1 vs. 136.9 ± 38.0 mm 2 , p=0.58), left lower lobe bronchus (57.8 ± 18.2 vs. 59.0 ± 13.4 mm 2 , p=0.82), and left upper lobe bronchus (80.1 ± 19.5 vs. 77.9 ± 22.9 mm 2 , p=0.75) in the long COVID and acute COVID-19 groups respectively. Conclusion: In patients with long COVID, compared to those with an acute COVID-19 infection, we did not see differences in central airway luminal areas. Further analysis of a larger cohort is needed to determine whether enlarged airway luminal areas, associated with acute COVID-19, persist in long COVID. This research will expand knowledge on functional consequences for patients with long COVID. Funding: F32HL154320 to JWS; 5R35HL139854 to MJJ. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

STRUCTURAL AND FUNCTIONAL CONDITION OF THE KNEE JOINT IN PATIENTS WITH MONOGONARTHROSIS IN THE STAGE OF EXACERBATION

The goal is to study the structural changes of the elements of the knee joint and their functional consequences in patients with monogonarthrosis of the 1st-2nd grade in the stage of exacerbation according to the data of a complex clinical and arthroscopic study.
 Materials and Methods. Materials - protocols of clinical, radiological and arthroscopic examination of 125 patients (54 (43.2%) men; 71 (57.8%) women), aged 18 - 79 years, with a previous diagnosis: Monoarthrosis of the knee joint in the stage of exacerbation. Research methods: questionnaire, orthopedic examination, X-ray diagnostics, arthroscopy, laboratory diagnostics of blood (determination of C-reactive protein (CRP) as a serological marker of inflammation), synovial fluid (analyses of physical properties, biochemical, cytological, bacteriological), statistical.
 Results and Discussion. According to the results of the comprehensive examination, the presence of primary monoarthrosis was confirmed in 118 (94.4%) patients (group A). Based on the definition of CRP, subgroups were distinguished: A1 (n=71; 56.8%) with a normal level and A2 (n=47; 37.6%) with elevated CRP. In 7 (5.6%) patients diagnosed seropositive unspecified rheumatoid monoarthritis with hypertrophic synovitis (group B). A significant predominance of women compared to men insubgroup A2 was revealed (p<0.05). It was investigated that the features of complaints, nature of pain sensations and indicators of orthopedic status in patients from subgroups A1 and A2 did not reliably differ in groups of patients with different levels of CRP. A significant predominance of normal contours of the affected knee joint was found in subgroups A1 (p<0.001) and A2 (p<0.01). Structural changes in knee joint elements according to X-ray and arthroscopic examination have no significant differences in subgroups of patients A1 and A2.
 Conclusions. The structural and functional state of the knee joints in patients with monogonarthrosis of the 1st-2nd grade according to the Kellgren-Lawrence classification is characterized by degenerative changes in almost all elements of the knee joint with moderate pain syndrome and functional disorders.

Impact of Conservative and Operative Treatment on Functional Consequences in Patients with the Fracture of Metacarpals Bones: A Longitudinal Study

Aim: The aim of this study was to compare the healing and functional outcomes of metacarpal bone fractures treated conservatively versus surgically. Study design: A longitudinal study Place and Duration: This study was conducted at Ghulam Mohammed Mahar Medical College Sukkur Pakistan. from June 2020 to June 2021 Methodology: The study comprised a total of 80 people with varied forms of metacarpal fractures. The fractures were treated conservatively or surgically in the orthopedic department. The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire score, which was used to assess the ability to execute various tasks, inspired the creation of the questionnaire. The least level of disability was assigned a score of 0, and the most degree of disability was assigned a score of 100. Results: In the DASH questionnaire, a scale score ranging from Zero to 100 was calculated. The greater the score, the worse the scenario. The majority of the subject obtained a score of 21 to 25, suggesting that they were generally pleased with their therapy. The Michigan questionnaire was used to assess patient satisfaction as the next questionnaire. Patients' primary expectation is restoring maximum hand function, and the functional outcome is critical. Conclusion: Most metacarpal fractures have a satisfactory outcome with nonoperative therapy because there is a lot of tolerance for angulation and shortening. Physical therapy and mobilization are critical components of treating these fractures and are an important part of the rehabilitation process. More study is required to help develop a definite treatment regimen while maintaining our patients' quality of care and overall wellness. Keywords: Fracture, Metacarpals, Conservative Treatment,

Light emitting diode-red light for reduction of post-surgical scarring: Results from a dose-ranging, split-face, randomized controlled trial.

Scarring has significant esthetic and functional consequences for patients. A need exists for anti-scarring therapeutics. Light emitting diode-red light (LED-RL) has been shown to modulate skin fibrosis. The aim of this study is to evaluate the safety and efficacy of LED-RL to reduce post-operative scarring. Cutaneous Understanding of Red-light Efficacy on Scarring was a randomized, mock-controlled, single-blind, dose-ranging, split-face phase II clinical trial. Starting 1 week post-surgery, patients received LED-RL irradiation and temperature-controlled mock therapy to incision sites at fluences of 160, 320 or 480 J/cm2 , triweekly for 3 weeks. Efficacy was assessed at 1, 3 and 6-12 months. The primary endpoint was difference in scar pliability between LED-RL-treated and control sites. Secondary outcomes included Patient and Observer Scar Assessment Scale, collagen and water concentration, and adverse events. There were no significant differences in scar pliability between treated and control scars. At certain fluences, treated scars showed greater improvements in observer rating and scar pliability, reflected by greater reductions in induration, from baseline to 6months compared to control scars. Treatment-site adverse events included blistering (n=2) and swelling (n=1), which were mild and resolved without sequelae. LED-RL phototherapy is safe in the early postoperative period and may reduce scarring.

Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients.

Context: Primary hypercholesterolemia (PH) is a lipid disorder characterized by elevated levels of cholesterol and low-density lipoprotein (LDL). Low-grade systemic inflammation is associated with PH, which might explain the higher incidence of cardiovascular diseases in this setting. Objective: To evaluate the effect of an oral unsaturated fat load (OUFL) on different immune parameters and functional consequences in patients with PH in postprandial state. Design: A commercial liquid preparation of long-chain triglycerides (Supracal®; ω6/ω3 ratio >20/1, OUFL) was administered to 20 patients and 10 age-matched controls. Whole blood was collected before (fasting state) and 4 h after administration (postprandial state). Flow cytometry was employed to determine platelet and leukocyte activation, and the levels of circulating platelet-leukocyte aggregates. Soluble markers were determined by ELISA, and the parallel-plate flow chamber was employed to study leukocyte adhesion to the dysfunctional arterial endothelium. Results: The PH group had a lower percentage of activated platelets and circulating type 1 monocytes, and blunted neutrophil activation after the OUFL, accompanied by a significant increase in the percentage of regulatory T lymphocytes. In this group, the OUFL led to a significant impairment of leukocyte adhesion to the dysfunctional [tumor necrosis factor α (TNFα)-stimulated] endothelium and reduced the plasma levels of soluble P-selectin, platelet factor-4 (PF-4)/CXCL4, CXCL8, CCL2, CCL5, and TNFα. Conclusion: The OUFL has a beneficial impact on the pro-thrombotic and pro-inflammatory state of PH patients and might be a promising macronutrient approach to dampen the systemic inflammation associated with PH and the development of further cardiovascular events.

Limited expression of TLR9 on T cells and its functional consequences in patients with nonalcoholic fatty liver disease.

Background/AimsToll-like receptors (TLRs) modulate T cell responses in diverse diseases. Co-stimulation of T cell activation via TLR9 induces production of interferon gamma (IFN-γ), priming of which is critical for differentiation of pro-inflammatory macrophages. These macrophages have a crucial role in nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the expression of TLR9 protein on T cells and the consequences of TLR9-mediated triggering of these cells in patients with NAFLD. MethodsOur study included 34 patients with simple steatosis, 34 patients with nonalcoholic steatohepatitis, eight patients with NAFLD who met general diagnostic criteria but lacked histological diagnosis, and 51 control subjects. We used a synthetic TLR9 ligand to co-stimulate T cells. We measured TLR9 expression in liver and peripheral T cells and CD69 and IFN-γ as phenotypic markers of T cell activation and differentiation by flow cytometry. ResultsTLR9 expression on liver and peripheral T cells was lowest in patients with simple steatosis and was positively associated with anthropometric, biochemical, and histopathological features of NAFLD. In vitro co-stimulation of T cells from patients with simple steatosis induced a limited number of IFN-γ-producing CD8+ T cells. At baseline, these patients showed a low frequency of circulating type 1 CD8+ cells. ConclusionsThe positive associations between TLR9 and anthropometric, clinical, and histological features and the crucial role of IFN-γ-in NAFLD suggest that limited TLR9 expression and production of IFN-γ play a protective role in patients with simple steatosis.

Combined use of minimal access craniotomy, intraoperative magnetic resonance imaging, and awake functional mapping for the resection of gliomas in 61 patients.

Current management of gliomas involves a multidisciplinary approach, including a combination of maximal safe resection, radiotherapy, and chemotherapy. The use of intraoperative MRI (iMRI) helps to maximize extent of resection (EOR), and use of awake functional mapping supports preservation of eloquent areas of the brain. This study reports on the combined use of these surgical adjuncts. The authors performed a retrospective review of patients with gliomas who underwent minimal access craniotomy in their iMRI suite (IMRIS) with awake functional mapping between 2010 and 2017. Patient demographics, tumor characteristics, intraoperative and postoperative adverse events, and treatment details were obtained. Volumetric analysis of preoperative tumor volume as well as intraoperative and postoperative residual volumes was performed. A total of 61 patients requiring 62 tumor resections met the inclusion criteria. Of the tumors resected, 45.9% were WHO grade I or II and 54.1% were WHO grade III or IV. Intraoperative neurophysiological monitoring modalities included speech alone in 23 cases (37.1%), motor alone in 24 (38.7%), and both speech and motor in 15 (24.2%). Intraoperative MRI demonstrated residual tumor in 48 cases (77.4%), 41 (85.4%) of whom underwent further resection. Median EOR on iMRI and postoperative MRI was 86.0% and 98.5%, respectively, with a mean difference of 10% and a median difference of 10.5% (p < 0.001). Seventeen of 62 cases achieved an increased EOR > 15% related to use of iMRI. Seventeen (60.7%) of 28 low-grade gliomas and 10 (30.3%) of 33 high-grade gliomas achieved complete resection. Significant intraoperative events included at least temporary new or worsened speech alteration in 7 of 38 cases who underwent speech mapping (18.4%), new or worsened weakness in 7 of 39 cases who underwent motor mapping (18.0%), numbness in 2 cases (3.2%), agitation in 2 (3.2%), and seizures in 2 (3.2%). Among the patients with new intraoperative deficits, 2 had residual speech difficulty, and 2 had weakness postoperatively, which improved to baseline strength by 6 months. In this retrospective case series, the combined use of iMRI and awake functional mapping was demonstrated to be safe and feasible. This combined approach allows one to achieve the dual goals of maximal tumor removal and minimal functional consequences in patients undergoing glioma resection.

Use of a combination strategy to improve neuroprotection and neuroregeneration in a rat model of acute spinal cord injury.

Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied in clinical practice. In this study, we analyzed the combination of different strategies as a potential therapy for spinal cord injury. Immunization with neural derived peptides (INDP), inhibition of glial scar formation (dipyridyl: DPY), as well as the use of biocompatible matrix (fibrin glue: FG) impregnated with bone marrow mesenchymal stem cells (MSCs) were combined and then its beneficial effects were evaluated in the induction of neuroprotection and neuroregeneration after acute SCI. Sprague-Dawley female rats were subjected to a moderate spinal cord injury and then randomly allocated into five groups: 1) phosphate buffered saline; 2) DPY; 3) INDP + DPY; 4) DPY+ FG; 5) INDP + DPY + FG + MSCs. In all rats, intervention was performed 72 hours after spinal cord injury. Locomotor and sensibility recovery was assessed in all rats. At 60 days after treatment, histological examinations of the spinal cord (hematoxylin-eosin and Bielschowsky staining) were performed. Our results showed that the combination therapy (DPY+ INDP + FG + MSCs) was the best strategy to promote motor and sensibility recovery. In addition, significant increases in tissue preservation and axonal density were observed in the combination therapy group. Findings from this study suggest that the combination theapy (DPY+ INDP + FG + MSCs) exhibits potential effects on the protection and regeneration of neural tissue after acute spinal cord injury. All procedures were approved by the Animal Bioethics and Welfare Committee (approval No. 178544; CSNBTBIBAJ 090812960) on August 15, 2016.

Prévalence et facteurs de risque de la rétinopathie drépanocytaire dans un centre de suivi drépanocytaire d’Afrique subsaharienne

IntroductionRetinopathy is a chronic complication with severe functional consequences in patients with sickle cell disease. Its prevalence is not well known in sub-Saharan Africa because of the absence of screening. We report here the results of a routine screening for sickle retinopathy in a Comprehensive Sickle Cell Center in Sub-Saharan Africa. MethodsScreening of sickle retinopathy was carried out in all sickle cell patients aged 10 and over, followed between 2010 and 2012. Retinopathy was screened by dilated indirect fundoscopic examination and retinal angiography, if necessary. The gender, age and hematological parameters of patients with sickle retinopathy were compared with those of controls randomly selected from the cohort of sickle cell patients without retinopathy followed during the same period. ResultsThe overall prevalence of sickle cell retinopathy was 8.8% (142/1604): 12.4% (91/731) in SC, 5.2% (38/734) in SS, 9.4% (5/53) in Sβ°-thalassemia patients and 9.3% (8/86) in Sβ+-thalassemia patients. Proliferative retinopathy was more common in SC patients (P<0.01). High levels of hemoglobin or of hematocrit were associated with retinopathy in all patients and with proliferative retinopathy in SC patients. In SS or Sβ0thalassemia patients, high leukocyte count was associated with proliferative retinopathy. Low fetal hemoglobin level was associated with retinopathy in all groups. ConclusionThe prevalence of sickle cell retinopathy is high and negatively associated to the level of fetal hemoglobin. The efficiency of a routine screening for sickle cell retinopathy must be assessed in Africa as well as the benefit of phlebotomy and hydroxyurea therapy as a preventive treatments.

Abstract P3-14-14: Endoscopic 3D latissimus dorsi muscle harvesting for immediate breast reconstruction. Results of our 7 patients experience in Antoine Lacassagne Nice Cancer Center

Abstract Introduction : The harvest of the latissimus dorsi muscle for the realization of immediate breast reconstruction induces a large dorsal scar measuring up to 20 centimeters, while only the muscle is used. We present here the results of our experience of endoscopic harvesting of the latissimus dorsi muscle using 3D technology. Our main objective is to reduce the dorsal scar and second assess the functional consequences for patients. Methods: Between December 1st, 2015 , and June 1st, 2016, there were 7 patients who underwent latissimus dorsi endoscopic harvesting, with 3D technology, for an immediate breast reconstruction after a skin-sparing or nipple sparing mastectomy. Results: 4 patients had latissimus dorsi muscle with breast implant and 3 patients by latissimus dorsi muscle only. The age average was 55 years (range 45-70). The mean length of surgery was 250 minutes (range 150- 380). The mean length of hospitalization was 7 days (range 4-12 days). One patient treated for local recurrence had skin necrosis because of previous radiotherapy. Donor site seroma was the main post surgery drawback. Patients on average benefited from 3 evacuations (range 1-5) of 850ml (range 640-1270ml). Acceptance of the reconstructed breast was good in six cases, and poor in one case. Only one patient reported discomfort at the donor site 1 month after surgery. Conclusion: The endoscopic 3D latissimus dorsi flap harvesting allows to reduce donor site scar. There is no significant difference concerning complications or post-operative pain and functional discomfort between the endoscopic and classic harvesting procedure. Citation Format: Barranger E, Dejode M. Endoscopic 3D latissimus dorsi muscle harvesting for immediate breast reconstruction. Results of our 7 patients experience in Antoine Lacassagne Nice Cancer Center [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-14-14.

Novel FGFR1 mutations in Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism: evidence for the involvement of an alternatively spliced isoform

To determine the prevalence of fibroblast growth factor receptor 1 (FGFR1) mutations and their predicted functional consequences in patients with idiopathic hypogonadotropic hypogonadism (IHH). Cross-sectional study. Multicentric. Fifty unrelated patients with IHH (21 with Kallmann syndrome and 29 with normosmic IHH). None. Patients were screened for mutations in FGFR1. The functional consequences of mutations were predicted by in silico structural and conservation analysis. Heterozygous FGFR1 mutations were identified in six (12%) kindreds. These consisted of frameshift mutations (p.Pro33-Alafs*17 and p.Tyr654*) and missense mutations in the signal peptide (p.Trp4Cys), in the D1 extracellular domain (p.Ser96Cys) and in the cytoplasmic tyrosine kinase domain (p.Met719Val). A missense mutation was identified in the alternatively spliced exon 8A (p.Ala353Thr) that exclusively affects the D3 extracellular domain of FGFR1 isoform IIIb. Structure-based and sequence-based prediction methods and the absence of these variants in 200 normal controls were all consistent with a critical role for the mutations in the activity of the receptor. Oligogenic inheritance (FGFR1/CHD7/PROKR2) was found in one patient. Two FGFR1 isoforms, IIIb and IIIc, result from alternative splicing of exons 8A and 8B, respectively. Loss-of-function of isoform IIIc is a cause of IHH, whereas isoform IIIb is thought to be redundant. Ours is the first report of normosmic IHH associated with a mutation in the alternatively spliced exon 8A and suggests that this disorder can be caused by defects in either of the two alternatively spliced FGFR1 isoforms.

The role of MAGT1 in genetic syndromes

Disturbances in magnesium homeostasis, often linked to altered expression and/or function of magnesium channels, have been implicated in a plethora of diseases. This review focuses on magnesium transporter 1 (MAGT1), as recently described changes in this gene have further extended our understanding of the role of magnesium in human health and disease. The identification of genetic changes and their functional consequences in patients with immunodeficiency revealed that magnesium and MAGT1 are key molecular players for T cell-mediated immune responses. This led to the description of XMEN (X-linked immunodeficiency with magnesium defect, Epstein Barr Virus infection, and neoplasia) syndrome, for which Mg2+ supplementation has been shown to be beneficial. Similarly, the identification of a copy-number variation (CNV) leading to dysfunctional MAGT1 in a family with atypical ATRX syndrome and skin abnormalities, suggested that the MAGT1 defect could be responsible for the cutaneous problems. On the other hand, recent genetic investigations question the previously proposed role for MAGT1 in intellectual disability. Understanding the molecular basis of the involvement of magnesium and its channels in human pathogenesis will improve opportunities for Mg2+ therapies in the clinic.

Scapula fractures.

Over the past decade, there has been an increased interest in understanding the operative indications and techniques in treating scapular fractures and tracking their outcomes. Multiple studies have documented poor functional outcomes following nonoperative management of displaced scapular fractures. There is a groundswell of recognition that severe deformity from scapular malunion is associated with functional consequences for patients. This has led to a growing recognition that scapular fractures should be held to the same standards as other bodily fractures with regard to fracture fixation principles, including anatomic articular reduction, proper alignment, and stable internal fixation. Through research, there has been an improved understanding of scapular fracture patterns and the relevant surgical approaches and exposures used for fracture fixation. As with many bones, however, there still remains the absence of a compelling study that defines thresholds for surgical indication based on degrees of deformity and amounts of displacement.

Oligodontia with taurodontism in monozygous twins

Oligodontia with taurodontism in monozygous twins

Transdermal Buprenorphine for the Treatment of Cancer Pain: Results from a Multicenter, Observational, Post-Marketing Study in Spain (RELIEF Study)

SUMMARY This study evaluated health outcomes in patients with cancer pain during treatment with transdermal buprenorphine, including quality of life, effectiveness, tolerability, and functional consequences for patients and their carers. In this 3-month, noncomparative, multicenter, observational study performed in a normal clinical practice setting in Spain, patients received transdermal buprenorphine 37, 52.5 or 70 µg/h, with patches changed every 96 h. The effect of transdermal buprenorphine on quality of life (primary study focus) was assessed using the Visual Analog Scale (VAS) component of the EuroQol 5 Dimensions™ (EQ-5D). In addition, pain (assessed using the Brief Pain Inventory - Short Form [BPI-SF] and VAS-pain), the impact of pain on patients and carers (assessed using the Beck Depression Inventory, sleep quality analysis, VAS-patient limitation, VAS-carer limitation and the Palliative Care Scale), patient's use of health resources, patient satisfaction, and tolerability, were evaluated. Of 116 patients entering the study, 42 completed the 3-month study period. Five patients withdrew due to adverse events. The two main reasons for study discontinuation were nontreatment-related death (27.1%) and lost to follow-up (18.8%). The mean age was 62.9 years and the mean baseline duration of pain was 7.78 weeks. In the month prior to starting transdermal buprenorphine, 80% of patients had received at least one nonopioid analgesic medication; 21% had received an opioid analgesic (most commonly tramadol). The most common dose of transdermal buprenorphine used was 35 µg/h. The mean improvement from baseline in the EQ-5D VAS score among 65 patients with data was 15.20 ± 24.96 (p < 0.0001). EQ-5D descriptive parameters also improved during the study (not statistically significant). Mean improvements in BPI scores for worst pain (3.76) and average pain (3.03) were significant (p < 0.0001). The other measures of pain relief also supported transdermal buprenorphine as an effective analgesic. Sleep quality improved during the study. VAS scores (100 mm scale) for patient limitation and caregiver burden due to pain improved, with a significant mean change in VAS-carer limitation score (30.34; p < 0.0001). Adverse events were reported by ten (8.6%) patients, most commonly affecting the gastrointestinal system (vomiting [4.3% of patients], nausea [2.6%] and constipation [0.9%]). The majority of patients reported satisfaction with their analgesic treatment. In this observational study in normal clinical practice, transdermal buprenorphine provided effective pain relief and was generally well tolerated by patients with cancer pain. It also improved quality of life for patients and reduced caregiver burden. Considering the high number of study discontinuations (mainly due to nontreatment-related death and lost to follow-up), the results of this study need to be evaluated with caution.

RDH12andRPE65, Visual Cycle Genes Causing Leber Congenital Amaurosis, Differ in Disease Expression

Human blindness caused by mutation of visual cycle genes has been discussed as potentially treatable by retinoid replacement either through gene transfer or pharmacological bypass. Mutations in the RDH12 gene disrupt the visual cycle in vitro, but little is known of the in vivo effects of mutant RDH12, other than the association with severe early-onset autosomal recessive retinal disease. The relationship of retinal organization and visual function in patients with RDH12 mutations was determined and comparisons made with the disease from mutations in another visual cycle gene, RPE65. Young patients with RDH12 mutations were studied with optical coherence tomography (OCT) and colocalized measures of vision with dark-adapted absolute thresholds. Results were compared to those in patients with RPE65 mutations. Retinal architecture of patients with RDH12 mutations was appreciably distorted, precluding identification of the normal laminae. Some RDH12-mutant retinas were remarkably thick and others were thin, but all had the same dysplastic pattern. A comparison with the structural and functional consequences in patients with mutations in RPE65 indicated that the pathogenesis of retinal degeneration in RDH12 mutations was distinctly different. The results demand critical consideration of the human disease mechanism and the therapeutic approach in patients with mutations in the putative visual cycle gene RDH12.

Les symptômes psychologiques et comportementaux de la démence : description et prise en charge

Behavioral and Psychological Symptoms in Dementia (BPSD) are, beside cognitive disorders, major features of Alzheimer's disease and related disorders. Diagnosis is important to enhance our knowledge of the pathophysiology of dementia and of their functional consequences for patients and caregivers. Pharmacological and non-pharmacological management of dementia depends to a large extent on the presence of BPSD. A committee of geriatricians, neurologists and psychiatrists specialized in dementia (THEMA 2) has promoted an epidemiological, diagnostic and therapeutic update in this field. This work was based on the BPSD Consensus Conference Report edited in 2000 by the International Psychogeriatric Association. This report was updated with the most recent literature reports, and was adapted to the French environment. This paper is a synthesis of this meeting, validated and corrected by the entire Thema 2 group.