What can we learn from long-term studies on chronic low back pain?:A scoping review

PURPOSE: A scoping review was conducted with the objective to identify and map the available evidence from long-term studies on chronic non-specific low back pain (LBP), to examine how these studies are conducted, and to address potential knowledge gaps. METHOD: We searched MEDLINE and EMBASE up to march 2021, not restricted by date or language. Experimental and observational study types were included. Inclusion criteria were: participants between 18 and 65 years old with non-specific sub-acute or chronic LBP, minimum average follow-up of > 2 years, and studies had to report at least one of the following outcome measures: disability, quality of life, work participation, or health care utilization. Methodological quality was assessed using the Effective Public Health Practice Project quality assessment. Data were extracted, tabulated, and reported thematically. RESULTS: Ninety studies met the inclusion criteria. Studies examined invasive treatments (72%), conservative (21%), or a comparison of both (7%). No natural cohorts were included. Methodological quality was weak (16% of studies), moderate (63%), or strong (21%) and generally improved after 2010. Disability (92%) and pain (86%) outcomes were most commonly reported, followed by work (25%), quality of life (15%), and health care utilization (4%). Most studies reported significant improvement at long-term follow-up (median 51 months, range 26 months-18 years). Only 10 (11%) studies took more than one measurement > 2 year after baseline. CONCLUSION: Patients with persistent non-specific LBP seem to experience improvement in pain, disability and quality of life years after seeking treatment. However, it remains unclear what factors might have influenced these improvements, and whether they are treatment-related. Studies varied greatly in design, patient population, and methods of data collection. There is still little insight into the long-term natural course of LBP. Additionally, few studies perform repeated measurements during long-term follow-up or report on patient-centered outcomes other than pain or disability

Mesenchymal stem cell-derived HGF attenuates radiation-induced senescence in salivary glands via compensatory proliferation

BACKGROUND &amp; AIM: Irradiation of the salivary glands during head and neck cancer treatment induces cellular senescence in response to DNA damage and contributes to radiation-induced hyposalivation by affecting the salivary gland stem/progenitor cell (SGSC) niche. Cellular senescence, such as that induced by radiation, is a state of cell-cycle arrest, accompanied by an altered pro-inflammatory secretome known as the senescence-associated secretory phenotype (SASP) with potential detrimental effects on the surrounding microenvironment. We hypothesized that the pro-regenerative properties of mesenchymal stem cells (MSCs) may attenuate cellular senescence post-irradiation. Therefore, here we evaluated the effects of adipose-derived MSCs (ADSCs) on the radiation-induced response of salivary gland organoids (SGOs).METHODS: Proteomic analyses to identify soluble mediators released by ADSCs co-cultured with SGOS revealed secretion of hepatocyte growth factor (HGF) in ADSCs, suggesting a possible role in the stem cell crosstalk. Next, the effect of recombinant HGF in the culture media of ex vivo grown salivary gland cells was tested in 2D monolayers and 3D organoid models.RESULTS: Treatment with HGF robustly increased salivary gland cell proliferation. Importantly, HGF supplementation post-irradiation enhanced proliferation at lower doses of radiation (0, 3, 7 Gy), but not at higher doses (10, 14 Gy) where most cells stained positive for senescence-associated beta-galactosidase. Furthermore, HGF had no effect on the senescence-associated secretory phenotype (SASP) of irradiated SGOs, suggesting there may be compensatory proliferation by cell-division competent cells instead of a reversal of cellular senescence after irradiation.CONCLUSION: ADSCs may positively influence radiation recovery through HGF secretion and can promote the ex vivo expansion of salivary gland stem/progenitor cells to enhance the effects of co-transplanted SGSC.</p

Mesenchymal stem cell-derived HGF attenuates radiation-induced senescence in salivary glands via compensatory proliferation

BACKGROUND &amp; AIM: Irradiation of the salivary glands during head and neck cancer treatment induces cellular senescence in response to DNA damage and contributes to radiation-induced hyposalivation by affecting the salivary gland stem/progenitor cell (SGSC) niche. Cellular senescence, such as that induced by radiation, is a state of cell-cycle arrest, accompanied by an altered pro-inflammatory secretome known as the senescence-associated secretory phenotype (SASP) with potential detrimental effects on the surrounding microenvironment. We hypothesized that the pro-regenerative properties of mesenchymal stem cells (MSCs) may attenuate cellular senescence post-irradiation. Therefore, here we evaluated the effects of adipose-derived MSCs (ADSCs) on the radiation-induced response of salivary gland organoids (SGOs).METHODS: Proteomic analyses to identify soluble mediators released by ADSCs co-cultured with SGOS revealed secretion of hepatocyte growth factor (HGF) in ADSCs, suggesting a possible role in the stem cell crosstalk. Next, the effect of recombinant HGF in the culture media of ex vivo grown salivary gland cells was tested in 2D monolayers and 3D organoid models.RESULTS: Treatment with HGF robustly increased salivary gland cell proliferation. Importantly, HGF supplementation post-irradiation enhanced proliferation at lower doses of radiation (0, 3, 7 Gy), but not at higher doses (10, 14 Gy) where most cells stained positive for senescence-associated beta-galactosidase. Furthermore, HGF had no effect on the senescence-associated secretory phenotype (SASP) of irradiated SGOs, suggesting there may be compensatory proliferation by cell-division competent cells instead of a reversal of cellular senescence after irradiation.CONCLUSION: ADSCs may positively influence radiation recovery through HGF secretion and can promote the ex vivo expansion of salivary gland stem/progenitor cells to enhance the effects of co-transplanted SGSC.</p

Personal and Societal Impact of Low Back Pain:The Groningen Spine Cohort

Study Design. Cross-sectional study. Objective. The aim of this study was to study the personal and societal impact of low back pain (LBP) in patients admitted to a multidisciplinary spine center. Summary of Background Data. The socioeconomic burden of 113P is very high. A minority of patients visit secondary or tertiary care because of severe and long-lasting complaints. This subgroup may account for a major part of disability and costs, yet could potentially gain most from treatment. Currently, little is known about the personal and societal burden in patients with chronic complex LBP visiting secondary/tertiary care. Methods. Baseline data were acquired through patient-reported questionnaires and health insurance claims. Primary outcomes were LBP impact (Impact Stratification, range 8-50), functioning (Pain Disability Index, PDI; 0-70), quality of life (EuroQol-5D, EQ5D; -0.33 to 1.00), work ability (Work Ability Score, WAS; 0 10), work participation, productivity costs (Productivity Cost Questionnaire), and healthcare costs 1 year before baseline. Healthcare costs were compared with matched primary and secondary care LBP samples. Descriptive and inferential statistics were applied. Results. In total, 1502 patients (age 46.3 +/- 12.8 years, 57% female) were included. Impact Stratification was 35.2 +/- 7.5 with severe impact (>= 35) for 58% of patients. PDI was 38.2 +/- 14.1, EQ5D 0.39 (interquartile range, IQR: 0.17-0.72); WAS 4.0 (IQR: 1.0-6.0) and 17% were permanently work-disabled. Mean total health care costs ((sic)4875, 95% confidence interval [CI]: 4309-5498) were higher compared to the matched primary care sample (n =4995) ((sic)2365, 95% CI: 2219-2526, P <0.001), and similar to the matched secondary care sample (n -4993) ((sic)4379, 95% CI: 4180-4590). Productivity loss was estimated at (sic)4315 per patient (95% CI: 3898 4688) during 6 months. Conclusion. In patients seeking multidisciplinary spine care, the personal and societal impact of LBP is very high. Specifically, quality of life and work ability are poor and health care costs are twice as high compared to patients seeking primary LBP care

Early to late sparing of radiation damage to the parotid gland by adrenergic and muscarinic receptor agonists

Damage to salivary glands after radiotherapeutic treatment of head and neck tumours can severely impair the quality of life of the patients. In the current study we have investigated the early-to-late pathogenesis of the parotid gland after radiation. Also the ability to ameliorate the damage using pretreatment with adrenergic or muscarinic receptor agonists is studied. Rats were locally irradiated with or without i.p. pretreatment with phenylephrine (α-adrenoceptor agonist, 5 mg kg−1), isoproterenol (β-adrenoceptor agonist, 5 mg kg−1), pilocarpine (4 mg kg−1), methacholine (3.75 mg kg−1) (muscarinic receptor agonists) or methacholine plus phenylephrine. Parotid salivary flow rate, amylase secretion, the number of cells and gland histology were monitored sequentially up to 240 days postirradiation. The effects were described in 4 distinct phases. The first phase (0–10 days) was characterised by a rapid decline in flow rate without changes in amylase secretion or acinar cell number. The second phase (10–60 days) consists of a decrease in amylase secretion and is paralleled by acinar cell loss. Flow rate, amylase secretion and acinar cell numbers do not change in the third phase (60–120 days). The fourth phase (120–240 days) is determined by a further deterioration of gland function but an increase in acinar cell number, albeit with poor tissue morphology. All drug pretreatments used could reduce radiation effects in phase I and II. The protective effects were lost during phase IV, with the exception of methacholine plus phenylephrine pretreatment. The latter combination of drugs ameliorated radiation-damage throughout the entire follow-up time. The data show that combined pre-irradiation stimulation of muscarinic acetylcholine receptors with methacholine plus α-adrenoceptors with phenylephrine can reduce both early and late damage, possibly involving the PLC/PIP2 second messenger pathways. This opens perspectives for the development of clinical applicable methods for long-term sparing of parotid glands subjected to radiotherapy of head and neck cancer patients. © 2001 Cancer Research Campaignhttp://www.bjcancer.co