Glucose-dependent insulinotropic polypeptide receptor (
) overexpression has been recently described in a proportion of
somatotropinomas and suggested to be associated with the paradoxical increase ...of GH (GH-PI) during an oral glucose load.
This study was aimed at linking the GIP/GIPR pathway to GH secretion in 25 somatotropinomas-derived primary cultures and correlating molecular with clinical features in acromegalic patients. Given the impairment of the GIP/GIPR axis in acromegaly, an additional aim was to assess the effect of GH/IGF-1 stimulation on GIP expression in the enteroendocrine cell line STC-1.
Nearly 80% of
-expressing somatotropinomas, all of them negative for
mutations, show increased GH secretion upon GIP stimulation, higher sensitivity to Forskolin but not to somatostatin analogs. Besides increased frequency of GH-PI,
overexpression does not appear to affect acromegalic patients' clinical features. In STC-1 cells transfected with GIP promoter-driven luciferase vector, IGF-1 but not GH induced dose-dependent increase in luciferase activity.
We demonstrate that
mediates the GH-PI in a significant proportion of
acromegalic patients. In these cases, the stimulatory effect of IGF-1 on GIP promoter support the hypothesis of a functional GH/IGF-1/GIP axis. Further studies based on larger cohorts and the development of a stable transgenic model with inducible GIPR overexpression targeted to pituitary somatotroph lineage will be mandatory to establish the real role of GIPR in the pathogenesis of somatotropinomas.
Osteoporotic vertebral compression fractures (VCFs) are a growing public health problem with important socio-economic effects in western countries. In the USA, 10 million people over 50 suffer from ...osteoporosis. In these patients, 1.5 million annual fractures have been registered, and 50% of these are vertebral compression.
We performed a comprehensive search of PubMed, Medline, Cochrane, CINAHL and Embase databases using various combinations of the keywords 'osteoporosis', 'vertebral compression fractures', 'brace', 'bracing', 'orthosis', 'conservative management' and 'rehabilitation' over the years 1966-2011. All articles relevant to the subject were retrieved, and their bibliographies were hand searched for further references in the context of conservative management of osteoporotic vertebral fractures.
Conservative management for patients with osteoporotic vertebral fractures includes bed rest, pain medication, physiotherapy and bracing.
A conservative management for patients with osteoporotic VCFs s has not been standardized. The utility of vertebral augmentation techniques has been questioned by recent randomized controlled trials.
Randomized controlled trials are being performed worldwide on vertebral augmentation techniques.
Although spinal orthoses are commonly used for the management of patients with osteoporotic vertebral fractures, in the literature there is only one randomized controlled trial on bracing for this condition. While the best conservative management for subjects with osteoporotic VCFs s is not defined and standardized, no conclusions on the superiority of vertebral augmentation techniques over conservative management can be drawn.
Rating scales for low back pain Longo, Umile Giuseppe; Loppini, Mattia; Denaro, Luca ...
British medical bulletin,
06/2010, Letnik:
94, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Introduction During the past decades several rating scales have been developed to assess the functional status of patients with low back pain. Methods We performed a search using the keywords ‘spine’ ...in combination with ‘scoring system’, ‘scale’, ‘scores’, ‘outcome assessment’, ‘low back pain’ and ‘clinical evaluation’. Results Twenty-eight scoring systems are currently available for the evaluation of low back pain. Each of them evaluates low back pain using specific variables. All these scoring systems are presented. Discussion Although many scoring systems have been used to evaluate the back function, we are still far from a single outcome evaluation system that is reliable, valid and sensitive to clinically relevant changes, taken into account both patients' and physicians' perspective and is short and practical to use. Conclusion Further studies are required to evaluate the reliability, validity and sensitivity of the low back pain scoring systems used in the common clinical practice.
Introduction
Vagus nerve stimulation (VNS) is a neuromodulation technique approved for Treatment-Resistant Depression (TRD). Evidence regarding its long-term efficacy and safety is still scarce.
...Objectives
To descriptively report a case series of 3 patients undergoing adjunctive VNS for TRD with an over 10-year follow-up.
Methods
We investigated outcomes of clinical interest in patients with ongoing VNS for at least 10 years after the device implantation. They had participated in a larger single-arm interventional study conducted at the University Hospital of Padua. They were diagnosed with chronic unipolar (1), recurrent unipolar (1), and bipolar (1) TRD.
Results
Our 3 cases had an average 14-year history of psychiatric disease before surgery. Afterward, all subjects achieved clinical remission within two years. 2 patients experienced relapses within the first 4 years of treatment (respectively, 1 and 2 episodes). The other case showed a recurrent trend of brief relapses every two years. Only 1 individual needed to be admitted to the psychiatric unit once. None of them committed suicidal attempts. Prescription of antidepressants remained almost unchanged after the first two years. 2 individuals improved and 1 maintained their working position. Common adverse events were voice alteration (3/3), neck pain (2/3), and cough (2/3).
Conclusions
Very few cases of 10-year VNS for TRD have been reported so far. For our subjects, VNS was most likely to have a major impact on the clinical course of the disease. This treatment can be a safe and effective adjunctive intervention in a subgroup of patients with TRD.
Relative radiometric normalization (RRN) minimizes radiometric differences among images caused by inconsistencies of acquisition condition. In this study, a cross-sensor RRN method is proposed for ...optical satellite images from Landsat 8 OLI (L8) and Landsat 7 ETM+ (L7) sensors. The data from these two sensors have different pixel depths. Therefore, a rescaling on the radiometry resolution is performed in the preprocessing. Then, multivariate alteration detection (MAD) based on kernel canonical correlation analysis (KCCA) is adopted, which is called KCCA-based MAD, to select pseudo-invariant features (PIFs). The process of RRN is performed by using polynomial regression with Gaussian weighted regression. In experiments, qualitative and quantitative analyses on images from different sensors are conducted. The experimental result demonstrates the superiority of the proposed nonlinear transformation, in terms of regression quality and radiometric consistency, compared with RRN using linear regression.
Tractography of the facial nerve based on single-shell diffusion MR imaging is thought to be helpful before surgery for resection of vestibular schwannoma. However, this paradigm can be vitiated by ...the isotropic diffusion of the CSF, the convoluted path of the facial nerve, and its crossing with other bundles. Here we propose a multishell diffusion MR imaging acquisition scheme combined with probabilistic tractography that has the potential to provide a presurgical facial nerve reconstruction uncontaminated by such effects.
Five patients scheduled for vestibular schwannoma resection underwent multishell diffusion MR imaging (b-values = 0, 300, 1000, 2000 s/mm
). Facial nerve tractography was performed with a probabilistic algorithm and anatomic seeds located in the brain stem, cerebellopontine cistern, and internal auditory canal. A single-shell diffusion MR imaging (b-value = 0, 1000 s/mm
) subset was extrapolated from the multishell diffusion MR imaging data. The quality of the facial nerve reconstruction based on both multishell diffusion MR imaging and single-shell diffusion MR imaging sequences was assessed against intraoperative videos recorded during the operation.
Single-shell diffusion MR imaging-based tractography was characterized by failures in facial nerve tracking (2/5 cases) and inaccurate facial nerve reconstructions displaying false-positives and partial volume effects. In contrast, multishell diffusion MR imaging-based tractography provided accurate facial nerve reconstructions (4/5 cases), even in the presence of ostensibly complex patterns.
In comparison with single-shell diffusion MR imaging, the combination of multishell diffusion MR imaging-based tractography and probabilistic algorithms is a more valuable aid for surgeons before vestibular schwannoma resection, providing more accurate facial nerve reconstructions, which may ultimately improve the postsurgical patient's outcome.
The current treatment options for acoustic neuromas (AN) - observation, microsurgery and radiotherapy - should assure no additional morbidity on cranial nerves VII and VIII. Outcomes in terms of ...disease control and facial function are similar, while the main difference lies in hearing. From 2012 to 2016, 91 of 169 patients (54%) met inclusion criteria for the present study, being diagnosed with unilateral, sporadic, intrameatal or extrameatal AN up to 1 cm in the cerebello-pontine angle; the remaining 78 patients (46%) had larger AN and were all addressed to surgery. The treatment protocol for small AN included observation, translabyrinthine surgery, hearing preservation surgery (HPS) and radiotherapy. Hearing function was assessed according to the Tokyo classification and the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) classification. Sixty-one patients (71%) underwent observation, 19 (22%) HPS and 6 (7%) translabyrinthine surgery; 5 patients were lost to follow-up. Median follow-up was 25 months. In the observation group, 24.6% of patients abandoned the wait-and-see policy for an active treatment; the risk of switching from observation to active treatment was significant for tumour growth (p = 0.0035) at multivariate analysis. Hearing deteriorated in 28% of cases without correlation with tumour growth; the rate of hearing preservation for classes C-D was higher than for classes A-B (p = 0.032). Patients submitted to HPS maintained an overall preoperative hearing class of Tokyo and AAO-HNS in 63% and 68% of cases, respectively. Hearing preservation rate was significantly higher for patients presenting with preoperative favourable conditions (in-protocol) (p = 0.046). A multi-option management for small AN appeared to be an effective strategy in terms of hearing outcomes.
Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor ...antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long‐term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4‐Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft‐mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3‐dioxigenase were observed only in CTLA4‐Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long‐term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation.
The intragraft expression of CTLA4‐Ig, a costimulation blocker, and the duration of the peripheral immunosuppressive treatment can improve cell survival and delay local xenogeneic T cell activation following intracerebral transplantation of transgenic CTLA4‐Ig+/+ pig xenografts in parkinsonian nonhuman primates.
Cushing’s disease (CD) is associated with increased morbidity and mortality. Until now, no medical treatment has been shown to be totally satisfactory when administrated alone. This study aimed to ...assess the effectiveness of cabergoline with added ketoconazole and of the same combination in reverse, using urinary free cortisol (UFC) and late night salivary cortisol (LNSC) levels as biochemical markers of the treatments’ efficacy in CD patients. A prospective analysis conducted on 14 patients (f/m = 12/2; median age 52, range 33–70 years) divided into two groups: 6 patients initially treated with cabergoline for 4–6 months (rising from 0.5–1 mg/week up to 3.0 mg/week), after which ketoconazole was added (group A); and 8 patients first took ketoconazole alone for 4–6 months (rising from 200 mg/day to 600 mg/day), then cabergoline was added (group B). Patients were compared with 14 age-matched patients in prolonged remission after effective neurosurgery for CD. The combination therapy led to UFC normalization in 79 % of patients with no differences between the groups; only one patient failed to respond at all. Neither drug succeeded in controlling the disease when taken alone. LNSC dropped when compared to baseline levels, but not to a significant degree (
p
= 0.06), and it remained significantly higher than in controls (
p
= 0.0006). Associating cabergoline with ketoconazole may represent an effective second-line treatment, achieving a satisfactory reduction in UFC levels and clinical improvement. Although the combined treatment lowered patients’ LNSC levels, they remained higher than normal, indicating a persistent subclinical hypercortisolism; the implications of this condition need to be considered. No differences emerged between the two treatment schedules.
Glioblastoma (GBM) is the most common primary malignant brain tumour in adults and frequently relapses. The aim of this study was to assess the efficacy and safety of metronomic temozolomide (TMZ) in ...the recurrent GBM population.
All patients treated at our centre between September 2013 and March 2021 were retrospectively reviewed. The main inclusion criteria were first-line therapy with the Stupp protocol, relapse after the first or subsequent line of therapy, treatment with a metronomic TMZ schedule (50 mg/m2 continuously) and histological diagnosis of isocitrate dehydrogenase wild-type GBM according to World Health Organization 2016 classification.
In total, 120 patients were enrolled. The median follow-up was 15.6 months, the median age was 59 years, Eastern Cooperative Oncology Group performance status (ECOG-PS) was 0–2 in 107 patients (89%). O6-methylguanine-DNA-methyltransferase (MGMT) was methylated in 66 of 105 (62%) evaluable patients. The median number of prior lines of treatment was 2 (range 1–7). Three (2%) patients showed a partial response; 48 (40%) had stable disease; 69 (57%) had progressive disease. The median overall survival from the start of metronomic TMZ was 5.4 months (95% confidence interval 4.3–6.4), whereas the median progression-free survival (PFS) was 2.6 months (95% confidence interval 2.3–2.8). At univariate analysis, MGMT methylated and unmethylated patients had a median PFS of 2.9 and 2.1 months (P = 0.001) and a median overall survival of 5.6 and 4.4 months (P = 0.03), respectively. At multivariate analysis, the absence of MGMT methylation (hazard ratio = 2.3, 95% confidence interval 1.3–3.9, P = 0.004) and ECOG-PS ≤ 2 (hazard ratio = 0.5, 95% confidence interval 0.3–0.9, P = 0.017) remained significantly associated with PFS, whereas ECOG-PS ≤ 2 (hazard ratio = 0.4, 95% confidence interval 0.3–07, P = 0.001) was the only factor associated with overall survival. The most common grade 3–4 toxicities were haematological (lymphopenia 10%, thrombocytopenia 3%).
Rechallenge with metronomic TMZ is a well-tolerated option for recurrent GBM, even in pretreated patients. Patients with methylated MGMT disease and good ECOG-PS seem to benefit the most from this treatment.
•Glioblastoma is the most common primary brain tumour in adults.•There is no general consensus about the best therapy at relapse.•Temozolomide at 50 mg/m2 continuously can be a viable therapeutic option for recurrent glioblastoma patients.•Heavily pretreated patients could benefit from metronomic temozolomide with a satisfying safety profile.
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