Pain Relief after Stereotactic Radiotherapy of Pancreatic Adenocarcinoma: An Updated Systematic Review

Severe pain is frequent in patients with locally advanced pancreatic ductal adenocarcinoma (PDCA). Stereotactic body radiotherapy (SBRT) provides high local control rates in these patients. The aim of this review was to systematically analyze the available evidence on pain relief in patients with PDCA. We updated our previous systematic review through a search on PubMed of papers published from 1 January 2018 to 30 June 2021. Studies with full available text, published in English, and reporting pain relief after SBRT on PDCA were included in this analysis. Statistical analysis was carried out using the MEDCALC statistical software. All tests were two-sided. The I² statistic was used to quantify statistical heterogeneity (high heterogeneity level: >50%). Nineteen papers were included in this updated literature review. None of them specifically aimed at assessing pain and/or quality of life. The rate of analgesics reduction or suspension ranged between 40.0 and 100.0% (median: 60.3%) in six studies. The pooled rate was 71.5% (95% CI, 61.6–80.0%), with high heterogeneity between studies (Q² test: p < 0.0001; I² = 83.8%). The rate of complete response of pain after SBRT ranged between 30.0 and 81.3% (median: 48.4%) in three studies. The pooled rate was 51.9% (95% CI, 39.3–64.3%), with high heterogeneity (Q² test: p < 0.008; I² = 79.1%). The rate of partial plus complete pain response ranged between 44.4 and 100% (median: 78.6%) in nine studies. The pooled rate was 78.3% (95% CI, 71.0–84.5%), with high heterogeneity (Q² test: p < 0.0001; I² = 79.4%). A linear regression with sensitivity analysis showed significantly improved overall pain response as the EQD2α/β:10 increases (p: 0.005). Eight papers did not report any side effect during and after SBRT. In three studies only transient acute effects were recorded. The results of the included studies showed high heterogeneity. However, SBRT of PDCA resulted reasonably effective in producing pain relief in these patients. Further studies are needed to assess the impact of SBRT in this setting based on Patient-Reported Outcomes.     

Overinflation of pneumatic antishock garments in the elderly

The hemodynamic effects of pneumatic antishock garment application in high-risk elderly patients were examined in 10 preoperative patients (mean age 66.5 +/- 6.4 years) with the pneumatic antishock garments uninflated, after 15 minutes of inflation to 50 mm Hg, and after 15 minutes of inflation to 75 mm Hg. After inflation, significant increases in right atrial pressure (89 percent), pulmonary capillary wedge pressure (34 percent), and mean pulmonary artery pressure (21 percent) were noted. Mean peripheral arterial pressure increased 11.2 percent. Depression of the cardiac index (18 percent), left ventricular stroke work (20 percent), and right ventricular stroke work (16.4 percent) with associated increases in total peripheral resistance (26 percent) and pulmonary vascular resistance (18 percent) occurred in 5 of 10 patients. Left ventricular function curves revealed a progressive decrease in ventricular function at 50 mm Hg and 75 mm Hg. We have concluded that the effect of the pneumatic antishock garment on myocardial function is variable and unpredictably dangerous in the elderly patient with diminished myocardial reserve. As no significant benefit was derived from inflation pressures greater than 50 mm Hg in these patients, the lowest combination of pressures producing the most efficacious results should be used.     

Thymic extracellular matrix in myasthenia gravis. II. Immunohistochemical evidence for increased type I collagen degradation

By immunohistochemistry, we studied the breakdown of type I collagen in frozen sections of normal and hyperplastic (myasthenia gravis-associated) human thymuses. This analysis was carried out using a specific polyclonal antibody directed against the alpha 2-CB(3,5) peptide, a degradation product of type I collagen. In the normal thymus, virtually no labeling was observed within thymic septae or intralobular regions. In contrast, bright fluorescent staining was consistently detected in myasthenia gravis-associated hyperplastic thymuses. Such immunoreactivity was found not only in septal regions but also in the intralobular connective tissue meshwork that exists in these thymuses. Our results represent further evidence for a defect in extracellular matrix metabolism in hyperplastic thymuses, which may be related to the abnormal intrathymic penetration of B cells, known to occur in this disease.     

Molecular identification of coliform bacteria from colicky breastfed infants

Objective:  To determine the presence of intestinal coliform bacteria in colicky vs healthy infants.
Study design:  We isolated coliform strains from faeces and performed quantitative bacterial cultures in 41 colicky and 39 healthy breastfed infants, identified using PCR with species-specific primers, strain-specific Automated Ribotyping and the API-50E kit for Enterobacteriaceae to identify the most frequent strains.
Results:  Coliform strains were more abundant in colicky infants (median 6.04 log₁₀ CFU/g faeces, range 2.00–8.76) vs controls (median 4.47 log₁₀ CFU/g faeces, range 1.00–8.08) (p = 0.026). Escherichia coli , Klebsiella pneumoniae , K. oxytoca , Enterobacter cloacae , E. aerogenes and Enterococcus faecalis were the predominant species in colicky and healthy infants. The counts of each bacterial species differed between the two groups, and the difference was significant (p = 0.002) for E. coli : median 6.30 log₁₀ CFU/g faeces (range 3.00–8.74) in colicky infants, and median 4.70 log₁₀ CFU/g faeces (range 2.00–5.85) in controls.
Conclusions:  This is the first study to evaluate the colonization patterns of gas-forming coliforms in colicky infants and healthy controls identified by molecular methods. Coliform bacteria, particularly Escherichia coli, were found to be more abundant in colicky infants. Our data could help to shed light on the cause of infantile colic.     

Neuroendocrine control of thymus physiology

The thymus gland is a central lymphoid organ in which bone marrow-derived T cell precursors undergo differentiation, eventually leading to migration of positively selected thymocytes to the peripheral lymphoid organs. This differentiation occurs along with cell migration in the context of the thymic microenvironment, formed of epithelial cells, macrophages, dendritic cells, fibroblasts, and extracellular matrix components. Various interactions occurring between microenvironmental cells and differentiating thymocytes are under neuroendocrine control. In this review, we summarize data showing that thymus physiology is pleiotropically influenced by hormones and neuropeptides. These molecules modulate the expression of major histocompatibility complex gene products by microenvironmental cells and the extracellular matrix-mediated interactions, leading to enhanced thymocyte adhesion to thymic epithelial cells. Cytokine production and thymic endocrine function (herein exemplified by thymulin production) are also hormonally controlled, and, interestingly in this latter case, a bidirectional circuitry seems to exist since thymic-derived peptides also modulate hormonal production. In addition to their role in thymic cell proliferation and apoptosis, hormones and neuropeptides also modulate intrathymic T cell differentiation, influencing the generation of the T cell repertoire. Finally, neuroendocrine control of the thymus appears extremely complex, with possible influence of biological circuitry involving the intrathymic production of a variety of hormones and neuropeptides and the expression of their respective receptors by thymic cells.     

Acute demyelinating optic neuritis

Acute demyelinating optic neuritis associated with multiple sclerosis (MS) is the most common cause of inflammation of the optic nerve. The Optic Neuritis Treatment Trial (ONTT) has provided important clinical data on the use of corticosteroids, and demonstrated that patients with characteristic inflammatory lesions within the brain on magnetic resonance imaging had a greater chance of developing clinically definite MS (CDMS). The current approach to patients with optic neuritis has been modified by the results of the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS). Patients with an initial clinical episode of demyelination (optic neuritis, incomplete transverse myelitis, or brain-stem/cerebellar syndrome) and at least two characteristic demyelinating lesions within the brain were randomized to receive interferon beta-1a or placebo after initial treatment with intravenous corticosteroids. At the 3-year point patients treated with interferon beta-1a showed a 50% less risk of CDMS. The results of this study have set the standard for patients with a first bout of demyelinating optic neuritis.     

Effects of IL-6 variants in multiple myeloma: growth inhibition and induction of apoptosis in primary cells

Interleukin-6 (IL-6) plays a pathogenetic role in B-cell malignancies and is a growth factor for multiple myeloma (MM) cells. Elevated serum IL-6 levels and a higher proliferative activity of bone marrow plasma cells are poor prognostic factors in MM patients. In addition to clinical trials with anti-IL-6 monoclonal antibodies, an alternative therapeutic approach based on the use of IL-6 receptor (R) super-antagonists (Sants) has been proposed. Sants are variants of the native cytokine characterized by a wild type affinity for the ligand-specific receptor chain IL-6R alpha and by a reduced ability to bind and/or dimerize the signaling chain gp-130. We report the in vitro effects of four different Sants on cell kinetic modulation and induction of apoptosis of primary cells from MM patients. Ten MM samples were cultured in the presence of four different Sants and heterogeneous effects in terms of reduction of proliferation and induction of apoptosis could be observed. A decrease of the S phase cells (> or = 25%) coupled with the induction of apoptosis was obtained in 4/10 samples: three of these samples had a diploid DNA stem line and an inferior initial percentage of S phase cells. Serum IL-6 concentrations did not correlate with the anti-proliferative activities of the Sants. Cell growth inhibition was observed especially in samples with soluble IL-6R serum concentrations > 200 ng/ml. We conclude that Sants can exert antiproliferative effects on selected MM samples. Such effects may depend on the availability of large amounts of soluble IL-6R. Further studies should aim at defining the conditions necessary for optimal antiproliferative activity.     

Effect of repeated administration of prolactin releasing peptide on feeding behavior in rats

Prolactin releasing peptide (PrRP) has been reported to reduce food intake in rats. We tested the effect of i.c.v. administration of PrRP-31 on food intake in both food deprived and free-feeding rats. We did not find any effect of PrRP-31 on food intake after single injections of up to an 8-nmol dose, but observed a marked decrease in food intake and body weight in rats that received a repeated twice daily administration of 8 nmol of PrRP-31. This effect was associated with an adverse behavioral pattern, indicating that the repeated high doses of the peptide caused non-specific effects inducing anorexia. We also tested several other behavioral parameters like locomotion and exploratory time, grooming and resting time, using lower doses of PrRP that did not cause the adverse behavior. Moreover, we carried out locomotor and sensory motor activity tests at the doses that exerted the most pronounced effect on the food intake. None of these tests suggested any specific behavioral effect of PrRP. We conclude that the behavioral pattern induced by PrRP is likely to be different from those induced by many other neuropeptides affecting food intake in rats.