Tapentadol prolonged release and the long-term management of chronic musculoskeletal pain in the elderly - focus on anxiety, depression, cognitive status and life quality: the TaPE study.

OBJECTIVE: The use of long-term opioids for the management of chronic musculoskeletal pain is a hot topic in the scientific community, especially when it concerns the elderly. This paper aimed at assessing the efficacy and tolerability of tapentadol prolonged release (PR), a molecule with a unique mechanism of action combining µ-opioid-receptor (MOR) agonism and noradrenaline reuptake inhibition (NRI), administered to patients aged ≥80 years with chronic persistent pain. The effect of this molecule on anxiety, depression, cognitive status, and overall quality of life were investigated. PATIENTS AND METHODS: This was a spontaneous, observational, open-label, prospective study, in 80 older patients aged ≥80 years, naïve to strong opioids, presenting moderate-to-severe chronic pain from different etiologies. Tapentadol PR was initially prescribed at the dose of 25-50 mg/day and increased gradually in case of insufficient analgesia. Pain intensity was assessed by a 10-point Numeric Rating Scale (NRS). Other endpoints were as follows: DN4 questionnaire for the evaluation of the neuropathic component of pain, SF12, HADS, and MMSE questionnaires to evaluate the quality of life, anxiety, and cognitive impairment, respectively. Safety evaluations were also performed through the assessment of the frequency and severity of adverse events. RESULTS: At T45, NRS score reduction was achieved in 86.0% of patients. On average, pain decreased by 55% from a mean of 8.2 to a mean of 3.6. At T90, tapentadol PR did not affect the psychophysical and cognitive abilities of older patients. CONCLUSIONS: The benefits with tapentadol PR in controlling pain have improved the quality of life of our patients, also showing a favorable effect on their cognitive performance.

What impact can hospitalization environment produce on the ANS functioning in patients with Unresponsive Wakefulness Syndrome? - 24-hour monitoring.

Objectives: Studies showed that the recovery of patients with Unresponsive Wakefulness Syndrome (UWS) is also correlated to the recovery of circadian rhythms. In this study, we observed the correlations between patients with UWS biometrical and ambient parameters. Methods: A dedicated monitoring system was realized to record and correlate the level of noise and luminosity with biometric Heart Rate (HR), Heart Rate Variability (HRV) and Breath Rate (BR) parameters. Eleven patients with UWS were recruited and monitored for 13 ± 7 days. Correlation of ambient and biometric parameters was analyzed by Spearman's test. Wilcoxon's test was used to compare the biometric parameters in two different moments of daily activity in the rehabilitation unit (night and day). Patients showed a moderate negative or positive correlation between biometric and ambient parameters. Results: Significant differences between night and morning (0.0001 < p ≤ 0.001) were found for HR, HRV and BR in seven, five and four patients, respectively, at Wilcoxon's test. HR and BR were higher during the night while HRV was lower. Conclusion: In patients with UWS, lower HRV and higher HR and BR during the night might be indicative of interference in sleep/wake cycles. The modifications of the environment surrounding the patient due to the unit procedures of the staff and/or some interaction modalities of the relatives may have an effect on residual endogenous mechanisms of self-regulation. However, differences between night and day in the biometrical parameters are not necessarily linked to the changes in the environment care unit.

The novel HBx mutation F30V correlates with hepatocellular carcinoma in vivo, reduces hepatitis B virus replicative efficiency and enhances anti-apoptotic activity of HBx N terminus in vitro.

OBJECTIVE: We aimed to investigate HBx genetic elements correlated with hepatitis B virus (HBV) -related hepatocellular carcinoma (HCC) and their impact on (a) HBV replicative efficiency, (b) HBx binding to circular covalently closed DNA (cccDNA), (c) apoptosis and cell-cycle progression, and (d) HBx structural stability. METHODS: This study included 123 individuals chronically infected with HBV: 27 with HCC (77.9% (21/27) genotype D; 22.1% (6/27) genotype A) and 96 without HCC (75% (72/96) genotype D; 25.0% (24/96) genotype A). HepG2 cells were transfected by wild-type or mutated linear HBV genome to assess pre-genomic RNA (pgRNA) and core-associated HBV-DNA levels, HBx-binding onto cccDNA by chromatin immunoprecipitation-based quantitative assay, and rate of apoptosis and cell-cycle progression by cytofluorimetry. RESULTS: F30V was the only HBx mutation correlated with HCC (18.5% (5/27) in HCC patients versus 1.0% (1/96) in non-HCC patients, p 0.002); a result confirmed by multivariate analysis. In vitro, F30V determined a 40% and 60% reduction in pgRNA and core-associated HBV-DNA compared with wild-type (p <0.05), in parallel with a significant decrease of HBx binding to cccDNA and decreased HBx stability. F30V also decreased the percentage of apoptotic cells compared with wild-type (14.8 ± 6.8% versus 19.1 ± 10.1%, p <0.01, without affecting cell-cycle progression) and increased the probability of HBx-Ser-31 being phosphorylated by PI3K-Akt kinase (known to promote anti-apoptotic activity). CONCLUSIONS: F30V was closely correlated with HBV-induced HCC in vivo, reduced HBV replicative efficiency by affecting HBx-binding to cccDNA and increased anti-apoptotic HBx activity in vitro. This suggests that F30V (although hampering HBV's replicative capacity) may promote hepatocyte survival, so potentially allowing persistent production of viral progeny and initiating HBV-driven hepatocarcinogenesis. Investigation of viral genetic markers associated with HCC is crucial to identify those patients at higher risk of HCC, who hence deserve intensive liver monitoring and/or early anti-HBV therapy.

An ecologically-controlled exoskeleton can improve balance recovery after slippage.

The evolution to bipedalism forced humans to develop suitable strategies for dynamically controlling their balance, ensuring stability, and preventing falling. The natural aging process and traumatic events such as lower-limb loss can alter the human ability to control stability significantly increasing the risk of fall and reducing the overall autonomy. Accordingly, there is an urgent need, from both end-users and society, for novel solutions that can counteract the lack of balance, thus preventing falls among older and fragile citizens. In this study, we show a novel ecological approach relying on a wearable robotic device (the Active Pelvis Orthosis, APO) aimed at facilitating balance recovery after unexpected slippages. Specifically, if the APO detects signs of balance loss, then it supplies counteracting torques at the hips to assist balance recovery. Experimental tests conducted on eight elderly persons and two transfemoral amputees revealed that stability against falls improved due to the "assisting when needed" behavior of the APO. Interestingly, our approach required a very limited personalization for each subject, and this makes it promising for real-life applications. Our findings demonstrate the potential of closed-loop controlled wearable robots to assist elderly and disabled subjects and to improve their quality of life.

Hybrid EEG/EOG-based brain/neural hand exoskeleton restores fully independent daily living activities after quadriplegia.

Direct brain control of advanced robotic systems promises substantial improvements in health care, for example, to restore intuitive control of hand movements required for activities of daily living in quadriplegics, like holding a cup and drinking, eating with cutlery, or manipulating different objects. However, such integrated, brain- or neural-controlled robotic systems have yet to enter broader clinical use or daily life environments. We demonstrate full restoration of independent daily living activities, such as eating and drinking, in an everyday life scenario across six paraplegic individuals (five males, 30 ± 14 years) who used a noninvasive, hybrid brain/neural hand exoskeleton (B/NHE) to open and close their paralyzed hand. The results broadly suggest that brain/neural-assistive technology can restore autonomy and independence in quadriplegic individuals' everyday life.

Coma recovery scale-r: variability in the disorder of consciousness.

BACKGROUND: Despite evidence from neuroimaging research, diagnosis and early prognosis in the vegetative (VS/UWS) and minimally conscious (MCS) states still depend on the observation of clinical signs of responsiveness. Multiple testing has documented a systematic variability during the day in the incidence of established signs of responsiveness. Spontaneous fluctuations of the Coma Recovery Scale-revised (CRS-r) scores are conceivable. METHODS: We retrospectively analyzed the CRS-r repeatedly administered to 7 VS/UWS and 12 MCS subjects undergoing systematic observation during a conventional 13 weeks. rehabilitation plan. RESULTS: The CRS-r global, visual and auditory scores were found higher in the morning than at the afternoon administration in both VS/UWS and MCS subgroups over the entire period of observation. The probability for a VS/UWS subject of being classified as MCS at the morning testing at least once during the 13 weeks. observation was as high as 30%, i.e., compatible with the reported misdiagnosis rate between the two clinical conditions. CONCLUSIONS: Multiple CRS-r testing is advisable to minimize the risk of misclassification; estimates of spontaneous variability could be used to characterize with greater accuracy patients with disorder of consciousness and possibly help optimize the rehabilitation plan.

Discrimination of geographical origin of lentils (Lens culinaris Medik.) using isotope ratio mass spectrometry combined with chemometrics.

The aim of this study was to predict the geographic origin of lentils by using isotope ratio mass spectrometry (IRMS) in combination with chemometrics. Lentil samples from two origins, i.e. Italy and Canada, were analysed obtaining the stable isotope ratios of δ(13)C, δ(15)N, δ(2)H, δ(18)O, and δ(34)S. A comparison between median values (U-test) highlighted statistically significant differences (p<0.05) for all isotopic parameters between the lentils produced in these two different geographic areas, except for δ(15)N. Applying principal component analysis, grouping of samples was observed on the basis of origin but with overlapping zones; consequently, two supervised discriminant techniques, i.e. partial least squares discriminant analysis and k-nearest neighbours algorithm were used. Both models showed good performances with external prediction abilities of about 93% demonstrating the suitability of the methods developed. Subsequently, isotopic determinations were also performed on the protein and starch fractions and the relevant results are reported.

Qualitative characterization of a transesterification product of coconut oil by FIA-APCI-MS.

OBJECTIVES: The purpose of this work was the qualitative characterization of a recently transesterification product obtained from the coconut oil in the presence of polyglycerol-6 to produce a new PEG-free secondary surfactant. The purpose of a secondary surfactant is to reduce the harshness of a skin cleanser. METHODS: The transesterification product was qualitatively characterized in our laboratory by flow injection analysis-atmospheric pressure chemical ionization-mass spectrometry (FIA-APCI-MS). The mass spectrum of the transesterification product was compared to those of the starting materials (polyglycerol and coconut oil). RESULTS: The analyses highlighted the disappearance of the starting oil peaks and the appearance of new peaks assignable to the reaction products, mainly corresponding to diesters of polyglycerol. Additionally, peaks of unreacted polyglycerol are present as well as peaks of cyclization products derived from the polyglycerol starting material. CONCLUSIONS: The development of this fast and easy analytical method, requesting only few minutes to be performed, represents a very useful tool for the characterization of transesterification products during the quality control of batches under production.

A study of the reliability of the Nociception Coma Scale.

OBJECTIVE: In this study, we investigated the reliability of the Nociception Coma Scale which has recently been developed to assess nociception in non-communicative, severely brain-injured patients. DESIGN: Prospective cross-sequential study. SETTING: Semi-intensive care unit and long-term brain injury care. SUBJECTS: Forty-four patients diagnosed as being in a vegetative state (n=26) or in a minimally conscious state (n=18). INTERVENTIONS: Patients were assessed by two experts (rater A and rater B) on two consecutive weeks to measure inter-rater agreement and test-retest reliability. MAIN MEASURES: Total scores and subscores of the Nociception Coma Scale. RESULTS: We performed a total of 176 assessments. The inter-rater agreement was moderate for the total scores (k = 0.57) and fair to substantial for the subscores (0.33 ≤ k ≤ 0.62) on week 2. The test-retest reliability was substantial for the total scores (k = 0.66) and moderate to almost perfect for the subscores (0.53 ≤ k ≤ 0.96) for rater A. The inter-rater agreement was weaker on week 1, whereas the test-retest reliability was lower for the least experienced rater (rater B). CONCLUSIONS: This study provides further evidence of the psychometric qualities of the Nociception Coma Scale. Future studies should assess the impact of practical experience and background on administration and scoring of the scale.

NeuroAIDS: virological aspects of HIV infection.

NeuroAIDS is one of the main complications of chronic HIV-infection. The Central Nervous System is an immunologic sanctuary for HIV and allows the persistence of the virus despite an efficient antiretroviral therapy. HIV-1 could promote the neurodegeneration through the induction of inflammation by the release of neurotoxins from infected cells. In addition, several viral proteins can directly contribute to the neuronal damages, activate cell-signaling involved in the control of cellular survival and apoptosis, favoring functional alterations in the target cells. Macrophages play a key role in the pathogenesis of NeuroAIDS, they are the main reservoirs of the infection in brain, promoting the inflammatory escalation, astrogliosis and degeneration process. This review aims to highlight the virological aspects associated with NeuroAIDS including pathogenesis, and treatment of HIV-1 in the CNS sanctuaries.

HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells.

HPV-16 is the major causes of cervical cancer. Persistence of infection is a necessary event for progression of the infection to cancer. Among other factors, virus persistence is due the viral proteins fighting the immune response. HPV-16 E5 down-regulates MHC/HLA class I, which is much reduced on the cell surface and accumulates in the Golgi apparatus in cells expressing E5. This effect is observed also in W12 cells, which mimic early cervical intraepithelial progression to cervical cancer. The functional effect of MHC I down-regulation on human CD8 T cells is not known, because of the need for HLA-matched, HPV-specific T cells that recognise E5 expressing-cells. Here we employ a heterologous cell/MHC I system which uses mouse cells expressing both E5 and HLA-A2, and A2-restricted CTLs; we show that the E5-induced reduction of HLA-A2 has a functional impact by reducing recognition of E5 expressing cells by HPV specific CD8+ T cells.

Effectiveness of primary inguinal orchiopexy as treatment of non-palpable testes in the first two years of age.

AIM: The best treatment of non-palpable testes is currently argument of debate. The aim of present study was to describe authors' experience in surgical treatment with inguinal standard orchidopexy of non-palpable testes. METHODS: In the last 17 years we have treated 2002 cryptorchid testes, among these 327 (16.33%) were non palpable. Age and distribution of cryptorchid testes was: 0-1 y (165 NPT), 1-2 y (84 NPT), 2-5 y (43 NPT), 5-10 y (16 NPT) and >10 y (19 NPT). RESULTS: Non-palpable testes were diagnosed and treated earlier (76.14% in the first two years). At surgical examination 204 (62.38%) were intrabdominal, 80 (24.46%) were atrophic and 43 (13.14%) vanishing. Among atrophic testes 54 (67.5%) were intracanicular, 21 (26.5%) were at the external inguinal ring, 4 (5%) were intrabdominal and 1 (1.25%) ectopic; among vanishing testes 22 (51.16%) were intrabdominal, 14 (32.55%) intracanicular and 7 (16.27%) at the external ring of inguinal canal. CONCLUSION: Atrophic and vanishing testes were in intrabdominal location in 26 cases: only in these cases (7.95% of all non palpable testes) laparoscopy should have avoided inguinal surgery. Inguinal standard orchiopexy performed as day-surgery with general anaesthesia associated to caudal analgesia should be considered effective and less invasive than laparoscopic approach.

The value of lung scintigraphy in the management of airways foreign bodies in children.

AIM: A retrospective analysis was made to evaluate our experience in the management of tracheobronchial foreign bodies (TFB) in children (age

Sperm count of young men surgically treated for cryptorchidism in the first and second year of life: fertility is better in children treated at a younger age.

INTRODUCTION: Recent data has indicated the usefulness of performing orchiopexy in the first years of life. In this study, we evaluated testicular function in young men operated on for cryptorchidism in the first year of life. To our knowledge, this is the first report on the effects of such an early treatment. MATERIALS AND METHODS: Testicular function was assessed in a group of young men operated for cryptorchidism during the first year of life (Group A, n=13) and during the second year of life (Group B, n=16). RESULTS: Total sperm counts were clearly higher in Group A (52.3+/-14.3 million/ml vs. 30.4+/-23.5 million/ml, p=0.005) as was sperm motility (36.2+/-8.7 vs. 23.1+/-15.7%, p=0.009). A clear inverse relationship was found between age at orchiopexy and total sperm count (r=-0.394, p=0.034) and sperm motility (r=-0.382, p=0.041). The relationship between volume of testes, position at surgery, uni/bilaterality of cryptorchidism, evidence of Ad spermatogonia at biopsy performed during surgery and treatment with LHRH and hCG performed before surgery and fertility was not significant. The latter findings may be partially explained by the low number of patients participating in the study and need further investigation. CONCLUSIONS: We obtained, for the first time, results showing the benefit of treating cryptorchidism during the first year of life rather than in the second year or even later.

[A rare case of esophageal atresia type I]. / Eccezionale caso di atresia esofagea di tipo I.

An extremely rare case of type A esophageal atresia is reported. The baby girl patient born spontaneously after a 38-week pregnancy, was diagnosed prenatally with suspected type A esophageal atresia. Diagnosis was confirmed at birth by chest and abdominal X-ray. As per protocol, a naso-esophageal tube was positioned in aspiration and a Stamm gastrostomy made for nutritional purposes. Evaluation of the distance between blind pouches at one month of life showed they were overlapping. At intervention the pouches were found to be united by a fibrous bridge about 1.5 cm long. Anastomosis was carried out with ease. The postoperative course was trouble-free. On the X day the baby girl was being fed completely per os. Histolo-gical examination of the fibrous residue excluded the presence of a mucosa-lined lumen. X-ray examination of the esophageal-gastric passage, one month after the operation, showed the smooth transit of the contrast medium and an adequate anastomotic lumen. At follow-up, at the age of 9 months, the baby was growing normally and being fed per os with a diet appropriate for her age; no oesophageal dilatation was necessary. Type A oesophageal atresias are long-gap forms: they are treated with direct anastomosis after the blind pouches come together spontaneously in the first four months of life. Stress is laid on the rarity of the case. According to Kluth's classification of 1976, this form was described by Mason in 1855 and Jlott in 1905 on the basis of autopsy findings. A review of the literature did not show any similar clinical cases.

Isolation compliance among university students during a mumps outbreak, Kansas 2006.

A large mumps outbreak occurred among students at a Kansas university in 2006. To reduce transmission, students with mumps were asked to isolate themselves. We describe isolation measures and student compliance with these measures. Questionnaires were administered to students suspected of having mumps. Of the 132 students instructed to stay isolated, 75% stayed isolated for the number of days recommended and were considered compliant. Case-students told to stay isolated for 1-4 days were more likely to be compliant [86% vs. 66%; adjusted odds ratio (aOR) 3.6, 95% CI 1.4-9.0] than those told to stay isolated for 5-9 days. Those who rated avoiding contact with others during isolation as very important were also more likely to be compliant (83% vs. 60%; aOR 3.6, 95% CI 1.5-8.4) than those who rated the importance lower. In a college setting, it may be difficult to achieve high compliance with guidelines recommending that persons stay isolated for much longer than 4 days.

Immunohistochemical findings in rectal duplication mimicking rectal prolapse.

Alimentary tract duplications represent rare anomalies, with only 5 % occurring in the rectum. The variety in clinical presentation may lead to a delay in diagnosis or to incorrect and multiple surgical procedures. We report the clinical, histological and immunohistochemical characteristics of a rectal duplication occurring in a 3-month-old male with an unusual clinical presentation. Using routine histology and immunohistochemistry, the rectal duplication showed the diffuse presence of gastric mucosa with a characteristic immunophenotype (i.e., diffuse cytokeratin 7 positivity and scattered chromogranin immunoreactivity). As far as we know, this is the first report showing an immunohistochemical differentiation pattern of gastric lining in a rectal duplication. Our results, showing the presence of gastric mucosa, are suggestive of a possible origin from the embryonic foregut.

[Conservative treatment of children constipation with Macrogol 4,000]. / Il trattamento conservativo della stipsi del bambino con macrogol 4000.

AIM: Macrogol 4,000 is one of the new generation's osmotic laxatives. It is constituted by a heavy molecular weight polymer without additional salts. In most of patients Macrogol 4,000 shows its efficacy in 48 hours from the beginning of treatment. Daily evacuations has been reported after first week therapy with an improvement in quality of life. The aim of this observational study was to demonstrate the efficacy of Macrogol 4,000 in the treatment of constipation in children. METHODS: The effect of Macrogol 4,000 was assessed in 120 children affected by constipation treated with therapeutic doses of Macrogol 4,000. The study period ranged from September 2006 to March 2007. The data analysis was collected with the evaluations concerning clinical examination and the consultation of daily diaries assembled by parents, tracking stooling pattern; in case of loosing contacts with the patient, a telephonic survey has been carried out. The child with symptoms improvement, i.e. reduction of the pain during defecation, daily spontaneous evacuations and better stool consistence, were considered ''normal''. RESULTS: Of the 120 patients, 89 returned to the clinical follow-up, while the remaining 31, who missed the follow-up, has been contacted by telephone. To the final analysis, 103 patients (85.8%) have had a normalization of the clinical symptoms, 9 patients (7.5%) have refused Macrogol 4,000 for the unpleasant flavour, 8 patients (6.7%) did not have any improvement from the treatment. CONCLUSION: The results of this observational study suggest that Macrogol 4,000 could be very useful to treat pediatric patients with constipation, also those affected by neuronal intestinal displasia (NID) type B.

[Fertility after surgery for rAFS stage III and IV endometriosis]. / Fertilità dopo chirurgia per endometriosi stadio III e IV rAFS.

AIM: The aim of this paper was to assess the impact on fertility of surgery to eradicate endometriosis. METHODS: One-hundred and twenty-six patients aged between 20 and 40 were observed. All wished to have offspring after the operation and were subjected to conservative surgery for stage III and IV endometriosis (rAFS score > 16) in the period 1992-2002. The type of surgical approach was chosen in consideration of the patient's clinical condition and on the basis of the experience of the surgeon, with the aim of radically removing the disease and, where necessary, restoring fertility. RESULTS: Fifty-six of 126 patients (44.4%) conceived after the operation; 55 spontaneously and 1 with assisted fecundation. Of the patients observed who became pregnant, about 1/3 (32%) conceived within 6 months of the operation and 1/3 (31%) after 12 months. Forty-four (78.5%) pregnancies reached term with a positive outcome, 7 (12.5%) were in progress at the moment of follow-up, 4 (7.1%) suffered a miscarriage and 1 (1.7%) was extrauterine; 48.2% (27/56 patients) of the pregnancies were stage III, 40% (28/70 patients) were stage IV. CONCLUSIONS: It emerges clearly from the data extrapolated from our series that surgery to eradicate endometriosis increases the fertility of the patients affected, without being resolutive: more than half the patients in fact remained sterile in spite of the operation.

Drug adverse events and drop-out risk: a clinical case.

We report a brief discussion on a clinical case of a female patient, 85 years old, affected by severe cognitive impairment and chronic obstructive pulmonary disease (COPD). The patient was not taking drugs at home (apart from promazine: 10 drops when necessary to control her behavioral diseases). A previous neuropsychological evaluation had shown a severe cognitive impairment MMSE=16/30; ADL=3/6; IADL=0/8) due to multiple brain ischemic areas (confirmed in 2003 by MRI neuroimaging). When the patient was admitted to our center she was able to perform some basic activities of daily living such as eating and walking and was not too confused. She was included in cognitive rehabilitation groups. Since she showed signs of Parkinsonism, a therapy based on omeprazol 20mg, acetylsalicylic acid, donepezil 10mg, pramipexol 0.18 mg, nimodipine 10 drops, levodopa+carbidopa 100/25mg was started. A few days later she became sleepy during daytime and, once, she lost her balance and fell. She was not self-sufficient any more. At first this was attributed to a lung infection that the patient had, but her state continue after the infection was completely cured with appropriate antibiotics therapy. At that point an adverse drug reaction was suspected and therapy with pramipexol 0.18 mg was interrupted. In a few days the patient regained her previous level of consciousness and self-sufficiency. We consider this a typical case of complex management in a patient with dementia and comorbidity in which adverse drug reactions can play an important role in lowering the level of cognitive functions. In this case the relationship with the family of the patient was made difficult by the attitude of the patient's daughter who decided, after the onset of the adverse drug reaction, to interrupt her mother's stay in our center even at risk of the worst consequences.