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Background. Manual therapy (MT) is a treatment recommended by clinical practice guidelines in the management of patients with neck pain. However, the mechanisms through which MT works remain unknown. The aim of the present study is to investigate if MT is mediated by mechanisms related to conditioned pain modulation (CPM), comparing the effects of painful with a pain-free MT treatment. Methods. A two-arm, parallel, randomized controlled clinical trial with concealed allocation and blinding of the outcome assessor was conducted in university students with chronic or recurrent nonspecific neck pain (NSNP). Participants received either a painful or pain-free MT session. Psychophysical variables including pressure pain thresholds, CPM, temporal summation of pain and cold pain intensity were assessed before and immediately after treatment. In addition, changes in neck pain intensity over the following 7 days and self-perceived improvement immediately and 7 days after treatment were assessed. Results: No significant differences were found between groups in any of the psychophysical variables or in patients' self-perceived improvement. Only a significantly greater decrease in neck pain intensity immediately after treatment was found in the pain-free MT group compared to the painful MT group. Conclusion: The results suggest that the immediate and short-term effects of MT on NSNP are not mediated by CPM-related mechanisms. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction, and oxidative stress in a cohort of familial Mediterranean fever (FMF) patients with Serum Amyloid A amyloidosis, in a non-randomized, 24-week open-label interventional study. Morinda citrifolia (anti-atherosclerotic-AAL), omega-3 (anti-inflammatory-AIC), and extract with Alaskan blueberry (antioxidant-AOL) were given to patients with FMF-related biopsy-proven AA amyloidosis. Patients were >18 years and had proteinuria (>3500 mg/day) but a normal estimated glomerular filtration rate (eGFR). Arterial flow-mediated dilatation (FMD), carotid intima media thickness (CIMT), and serum biomarkers asymmetric dimethylarginine (ADMA), high sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and glutathione peroxidase (GSH-Px) were studied at baseline and after 24 weeks of treatment. A total of 67 FMF-related amyloidosis patients (52 male (77.6%); median age 36 years (range 21–66)) were enrolled. At the end of a 24-week treatment period with AAL, AIC, and AOL combination therapy, ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px, and FMD levels were significantly increased. Changes in inflammatory markers PTX3, and hsCRP were negatively correlated with FMD change, and positively correlated with decreases in proteinuria, ADMA, MDA, cholesterol, and CIMT. Treatment with AAL, AIC and AOL combination for 24 weeks were significantly associated with reduction in inflammatory markers, improved endothelial functions, and oxidative state. Efficient control of these three mechanisms can have long term cardiovascular and renal benefits for patients with AA amyloidosis. [ABSTRACT FROM AUTHOR]

The central goal of regenerative medicine is to replace damaged or diseased tissue with cells that integrate and function optimally. The capacity of pluripotent stem cells to produce unlimited numbers of differentiated cells is of considerable therapeutic interest, with several clinical trials underway. However, the host immune response represents an important barrier to clinical translation. Here we describe the role of the host innate and adaptive immune responses as triggers of allogeneic graft rejection. We discuss how the immune response is determined by the cellular therapy. Additionally, we describe the range of available in vitro and in vivo experimental approaches to examine the immunogenicity of cellular therapies, and finally we review potential strategies to ameliorate immune rejection. In conclusion, we advocate establishment of platforms that bring together the multidisciplinary expertise and infrastructure necessary to comprehensively investigate the immunogenicity of cellular therapies to ensure their clinical safety and efficacy. In this Review, Petrus-Reurer et al describe the roles of both innate and adaptive immune responses in allogeneic graft rejection, in addition to discuss how such responses are determined by the cellular therapy of interest. They also describe the range of in vitro and in vivo approaches used to examine the immunogenicity of cellular therapies and consider potential confounders and strategies that can be employed to ameliorate immune rejection. [ABSTRACT FROM AUTHOR]

Focused Very-High Energy Electron (VHEE, 50–300 MeV) and Ultra-High Energy Electron (UHEE, > 300 MeV) beams can accurately target both large and deeply seated human tumors with high sparing properties, while avoiding the spatial requirements and cost of proton and heavy ion facilities. Advanced testing phases are underway at the CLEAR facilities at CERN (Switzerland), NLCTA at Stanford (USA), and SPARC at INFN (Italy), aiming to accelerate the transition to clinical application. Currently, Monte Carlo (MC) transport is the sole paradigm supporting preclinical trials and imminent clinical deployment. In this paper, we propose an alternative: the first extension of the nuclear-reactor deterministic chain Njoy-Dragon for VHEE and UHEE applications. We have extended the Boltzmann-Fokker-Planck (BFP) multigroup formalism and validated it using standard radio-oncology benchmarks, complex assemblies with a wide range of atomic numbers, and comprehensive irradiation of the entire periodic table. We report that 99 % of water voxels exhibit a BFP-MC deviation below 2 % for electron energies under 1.5 GeV . Additionally, we demonstrate that at least 97 % of voxels of bone, lung, adipose tissue, muscle, soft tissue, tumor, steel, and aluminum meet the same criterion between 50 MeV and 1.5 GeV . For water, the thorax, and the breast intra-operative benchmark, typical average BFP-MC deviations of 0.3 % and 0.4 % were observed at 300 MeV and 1 GeV , respectively. By irradiating the entire periodic table, we observed similar performance between lithium ( Z = 3 ) and cerium ( Z = 58 ). Deficiencies observed between praseodymium ( Z = 59 ) and einsteinium ( Z = 99 ) have been reported, analyzed, and quantified, offering critical insights for the ongoing development of the Evaluated Nuclear Data File mode in Njoy. [ABSTRACT FROM AUTHOR]

Immunotherapy emerged as a new treatment modality for breast cancer, and its use is approved in combination with chemotherapy for first-line therapy in metastatic triple-negative breast cancer overexpressing PD-L1. As immune checkpoint inhibitors alone have modest clinical activity in advanced breast cancer, there is a growing interest in combinatorial modalities, and particularly for their rapid development in the early disease setting. The plethora of ongoing immunotherapy trials in early breast cancer comes at a time when solid data in advanced disease are still imperfect. This review offers a perspective on the efforts to establish the efficacy and safety of immunotherapeutic agents in early breast cancer. • The investigation of immunotherapeutic agents for breast cancer has shifted from the metastatic to the early setting. • Different scenarios and designs exist for clinical trials testing immunotherapy in early breast cancer. • Combinatorial strategies may increase the activity of immunotherapy in early breast cancer across different subtypes. • Biomarkers for predicting upfront resistance, treatment response, and immune-related toxicities are needed. • Collaborative research is required for the understanding of the available data and the rational design of future trials. [ABSTRACT FROM AUTHOR]

Isoflavones are a group of (poly)phenols, also defined as phytoestrogens, with chemical structures comparable with estrogen, that exert weak estrogenic effects. These phytochemical compounds have been targeted for their proven antioxidant and protective effects. Recognizing the increasing prevalence of cardiovascular diseases (CVD), there is a growing interest in understanding the potential cardiovascular benefits associated with these phytochemical compounds. Gut microbiota may play a key role in mediating the effects of isoflavones on vascular and endothelial functions, as it is directly implicated in isoflavones metabolism. The findings from randomized clinical trials indicate that isoflavone supplementation may exert putative effects on vascular biomarkers among healthy individuals, but not among patients affected by cardiometabolic disorders. These results might be explained by the enzymatic transformation to which isoflavones are subjected by the gut microbiota, suggesting that a diverse composition of the microbiota may determine the diverse bioavailability of these compounds. Specifically, the conversion of isoflavones in equol—a microbiota-derived metabolite—seems to differ between individuals. Further studies are needed to clarify the intricate molecular mechanisms behind these contrasting results. [ABSTRACT FROM AUTHOR]

Solid organ transplantation remains the treatment of choice for end-stage organ failure. Whilst the short-term outcomes post-transplant have improved in the last decades, chronic rejection and immunosuppressant side effects remain an ongoing concern. Hematopoietic stem cell transplantation is a well-established procedure for the treatment of patients with haematological disorders. However, donor T cells are continually primed and activated to react against the host causing graft-versus-host disease (Gv HD) that leads to tissue damages and death. Regulatory T cells (Tregs) play an essential role in maintaining tolerance to self-antigens, preventing excessive immune responses and abrogating autoimmunity. Due to their suppressive properties, Tregs have been extensively studied for their use as a cellular therapy aiming to treat Gv HD and limit immune responses responsible for graft rejection. Several clinical trials have been conducted or are currently ongoing to investigate safety and feasibility of Treg-based therapy. This review summarizes the general understanding of Treg biology and presents the methods used to isolate and expand Tregs. Furthermore, we describe data from the first clinical trials using Tregs, explaining the limitations and future application of these cells. [ABSTRACT FROM AUTHOR]

Background: Annually, non-communicable diseases (NCDs) kill 38 million people worldwide, with low and middle-income countries accounting for three-quarters of these deaths. High-quality clinical practice guidelines (CPGs) are fundamental to improving NCD management. The present study evaluated the methodological rigor and transparency of Brazilian CPGs that recommend pharmacological treatment for the most prevalent NCDs. Methods: We conducted a systematic search for CPGs of the following NCDs: asthma, atrial fibrillation, benign prostatic hyperplasia, chronic obstructive pulmonary disease, congestive heart failure, coronary artery disease and/or stable angina, dementia, depression, diabetes, gastroesophageal reflux disease, hypercholesterolemia, hypertension, osteoarthritis, and osteoporosis. CPGs comprising pharmacological treatment recommendations were included. No language or year restrictions were applied. CPGs were excluded if they were merely for local use and referred to NCDs not listed above. CPG quality was independently assessed by two reviewers using the Appraisal of Guidelines Research and Evaluation instrument, version II (AGREE II). Main Findings: “Scope and purpose” and “clarity and presentation” domains received the highest scores. Sixteen of 26 CPGs were classified as low quality, and none were classified as high overall quality. No CPG was recommended without modification (77% were not recommended at all). After 2009, 2 domain scores (“rigor of development” and “clarity and presentation”) increased (61% and 73%, respectively). However, “rigor of development” was still rated < 30%. Conclusion: Brazilian healthcare professionals should be concerned with CPG quality for the treatment of selected NCDs. Features that undermined AGREE II scores included the lack of a multidisciplinary team for the development group, no consideration of patients’ preferences, insufficient information regarding literature searches, lack of selection criteria, formulating recommendations, authors’ conflict of interest disclosures, and funding body influence. [ABSTRACT FROM AUTHOR]

Thyroid malignant neoplasm develops from follicular or parafollicular thyroid cells. A higher proportion of anaplastic thyroid cancer has an adverse prognosis. New drugs are being used in clinical treatment. However, for advanced thyroid malignant neoplasm such as anaplastic thyroid carcinoma, the major impediment to successful control of the disease is the absence of effective therapies. Oncolytic virotherapy has significantly progressed as therapeutics in recent years. The advance is that oncolytic viruses can be designed with biological specificity to infect, replicate and lyse tumor cells. Significant advances in virotherapy have being achieved to improve the accessibility, safety and efficacy of the treatment. Therefore, it is necessary to summarize and bring together the main areas covered by these investigations for the virotherapy of thyroid malignant neoplasm. We provide an overview of the progress in virotherapy research and clinical trials, which employ virotherapy for thyroid malignant neoplasm as well as the future prospect for virotherapy of thyroid malignant neoplasms. [ABSTRACT FROM AUTHOR]

The purpose of this study is to assess the effect of palmitoylethanolamide (PEA) oral administration on intraocular pressure (IOP) and visual field damage progression in normal-tension glaucoma (NTG) patients. Thirty-two consecutive patients affected by NTG were enrolled and randomized in a 1:1 ratio to receive PEA treatment (group A) or no treatment (group B). Group A patients took ultramicronized 300 mg PEA tablets two times per day for six months. Best-corrected visual acuity (BCVA), IOP, and visual field test were evaluated at baseline and at the end of the six-month follow-up. No significant differences in clinical parameters between the two groups were observed at baseline. At six months, group A patients showed significant IOP reduction (from 14.4±3.2 mm Hg to 11.1±4.3 mm Hg, p<0.01). No statistically significant changes were seen in BCVA in either group. Visual field parameters significantly diminished in patients receiving PEA compared to baseline values (−7.65±6.55 dB vs. −4.55±5.31 dB, p<0.001; 5.21±4.08 dB vs. 3.81±3.02 dB, p<0.02; mean deviation [MD] and pattern standard deviation [PSD] respectively), while no significant changes were seen in group B. A generalized linear model demonstrated that the final IOP, MD, and PSD was affected only by the systemic PEA treatment ( p<0.01 each) and not affected by demographic or clinical characteristic between the groups. Hence, systemic administration of PEA reduces IOP and improves visual field indices in individuals affected by NTG. Neither ocular nor systemic side effects were recorded during the study period. [ABSTRACT FROM AUTHOR]

Gut microbiota (GM) modulation can be investigated as possible solution to enhance recovery after COVID-19. An open-label, single-center, single-arm, pilot, interventional study was performed by enrolling twenty patients recently recovered from COVID-19 to investigate the role of a mixed probiotic, containing Lactobacilli, Bifidobacteria and Streptococcus thermophilus, on gastrointestinal symptoms, local and systemic inflammation, intestinal barrier integrity and GM profile. Gastrointestinal Symptom Rating Scale, cytokines, inflammatory, gut permeability, and integrity markers were evaluated before (T0) and after 8 weeks (T1) of probiotic supplementation. GM profiling was based on 16S-rRNA targeted-metagenomics and QIIME 2.0, LEfSe and PICRUSt computational algorithms. Multiple machine learning (ML) models were trained to classify GM at T0 and T1. A statistically significant reduction of IL-6 (p < 0.001), TNF-α (p < 0.001) and IL-12RA (p < 0.02), citrulline (p value < 0.001) was reported at T1. GM global distribution and microbial biomarkers strictly reflected probiotic composition, with a general increase in Bifidobacteria at T1. Twelve unique KEGG orthologs were associated only to T0, including tetracycline resistance cassettes. ML classified the GM at T1 with 100% score at phylum level. Bifidobacteriaceae and Bifidobacterium spp. inversely correlated to reduction of citrulline and inflammatory cytokines. Probiotic supplementation during post-COVID-19 may trigger anti-inflammatory effects though Bifidobacteria and related-metabolism enhancement. [ABSTRACT FROM AUTHOR]

Background Heart failure is a prevalent health problem associated with costly hospital readmissions. Transitional care programs have been shown to reduce readmissions but are costly to implement. Evidence regarding the effectiveness of telemonitoring in managing the care of this chronic condition is mixed. The objective of this randomized controlled comparative effectiveness study is to evaluate the effectiveness of a care transition intervention that includes pre-discharge education about heart failure and post-discharge telephone nurse coaching combined with home telemonitoring of weight, blood pressure, heart rate, and symptoms in reducing all-cause 180-day hospital readmissions for older adults hospitalized with heart failure. Methods/Design A multi-center, randomized controlled trial is being conducted at six academic health systems in California. A total of 1,500 patients aged 50 years and older will be enrolled during a hospitalization for treatment of heart failure. Patients in the intervention group will receive intensive patient education using the 'teach-back' method and receive instruction in using the telemonitoring equipment. Following hospital discharge, they will receive a series of nine scheduled health coaching telephone calls over 6 months from nurses located in a centralized call center. The nurses also will call patients and patients' physicians in response to alerts generated by the telemonitoring system, based on predetermined parameters. The primary outcome is readmission for any cause within 180 days. Secondary outcomes include 30-day readmission, mortality, hospital days, emergency department (ED) visits, hospital cost, and health-related quality of life. Discussion BEAT-HF is one of the largest randomized controlled trials of telemonitoring in patients with heart failure, and the first explicitly to adapt the care transition approach and combine it with remote telemonitoring. The study population also includes patients with a wide range of demographic and socioeconomic characteristics. Once completed, the study will be a rich resource of information on how best to use remote technology in the care management of patients with chronic heart failure. [ABSTRACT FROM AUTHOR]

Background: homeopathy is held in organic agriculture as a means to control disease and plagues. However, different from doctors, who have works on materia medica and repertories available to choose the most suitable homeopathic medicine for each patient, agronomists do not yet have an equivalent Homeopathic Materia Medica of Plants (HMMP) describing symptoms observed in plants. Aim: the aim of this study was to carry out a homeopathic pathogenetic trial (HPT) in plants comparing the effects elicited by boric acid in ponderable dose and dilution 6cH in two different plant species, namely bean and tomato cultivars. Methods: 4 tests were carried out, 2 on tomato and 2 on bean plants, which received 1 to 6 applications of treatments. Results: there were differences between both species regarding their sensitiveness to boric acid. None of the tomato plants that received Boron 6cH showed symptoms, differently from bean plants. On the other hand, in tests of ponderable doses of boric acid, tomato plants exhibited 3 symptoms more than bean plants. A higher number of bean plants exhibited symptoms with boric acid in ponderable dose than in dilution 6cH). Nos ensaios com feijoeiro, um maior número de plantas apresentou sintomas após o tratamento com ácido bórico na dose ponderal do que com ácido bórico 6cH. Conclusions: these results suggest that the elaboration of a HMMP must take into account the species in which symptoms were obtained. Moreover, HPTs in plants must be carried out with both ponderable doses and high dilutions in order for differences in sensitiveness among species be better identified. [ABSTRACT FROM AUTHOR]

Hepatitis C virus infects an estimated 180 million people world-wide, prompting enormous efforts to develop inhibitors targeting the essential NS3/4A protease. Resistance against the most promising protease inhibitors, telaprevir, boceprevir, and ITMN-191, has emerged in clinical trials. In this study, crystal structures of the NS3/4A protease domain reveal that viral substrates bind to the protease active site in a conserved manner defining a consensus volume, or substrate envelope. Mutations that confer the most severe resistance in the clinic occur where the inhibitors protrude from the substrate envelope, as these changes selectively weaken inhibitor binding without compromising the binding of substrates. These findings suggest a general model for predicting the susceptibility of protease inhibitors to resistance: drugs designed to fit within the substrate envelope will be less susceptible to resistance, as mutations affecting inhibitor binding would simultaneously interfere with the recognition of viral substrates. [ABSTRACT FROM AUTHOR]

The authors comment on advancement in treatment and prevention of acute ischaemic stroke from the last decade which has reduced the mortality rate. Topics discussed include intravenous recombinant tissue plasminogen activator (rtPA), antithrombotic agents use and endovascular devices in treatment. They mention the comparison of new endovascular trials and earlier studies in recanalization and tissue perfusion, and guidelines from American Heart Association (AHA).

Multiple myeloma is a chronic hematologic malignancy that obstinately tends to relapse. Basic research has made giant strides in better characterizing the molecular mechanisms of the disease. The results have led to the manufacturing of new, revolutionary drugs which have been widely tested in clinical trials. These drugs have been approved and are now part of the therapeutic armamentarium. As a consequence, it is essential to combine what we know from clinical trials with real-world data in order to improve therapeutic strategies. Starting with this premise, our review aims to describe the currently employed regimens in multiple myeloma and compare clinical trials with real-life experiences. We also intend to put a spotlight on promising therapies such as T-cell engagers and chimeric antigen receptor T-cells (CAR-T) which are proving to be effective in changing the course of advanced-stage disease. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the long-term effectiveness of quantic molecular resonance (QMR) in the treatment of inferior turbinate hypertrophy (ITH) in allergic and nonallergic rhinitis refractory to medical therapy. Methods: This study enrolled 281 patients, 160 males (56.9%) and 121 females (43.1%), mean age 37.8 ± 4.1 years, range 18 to 71. Fifty-four patients have been lost to follow up and have been therefore excluded from the final analysis. Based on skin prick test results, 69 patients were considered allergic (group A) and 158 nonallergic (group B). All subjects underwent before surgery (T0) and 3 (T1), 12 (T2), 24 (T3), and 36 months (T4) after QMR treatment to: 4-phase rhinomanometric examination, nasal endoscopy evaluation, and visual analogue scale to quantify the subjective feelings about nasal obstruction. Results: Subjective and objective parameters showed statistically significant improvement in both groups. Group B parameters not changed during follow-up, while group A showed significant worsening between T1 and subsequent assessments. T4 outcome indicates a better result in nonallergic patients. Conclusions: In accordance with the literature, our preliminary data validate QMR treatment as a successful therapeutic option for nasal obstruction due to ITH. Nonallergic patients had a very good T4 outcome. Allergic patients showed a worsening trend after 1 year probably due to other causes. [ABSTRACT FROM AUTHOR]

Presents updates related to medical ethics as of August 2002. Changes in research ethics on drug trials; Stance of the government in Africa over the use of antiretrovirals as prophyaxis for AIDS; Report by the government of Great Britain on the use of personal genetic information.

In the era of morphologic diagnostics, any epithelial tumor on or involving the ovaries was presumed to come from and be strictly of ovarian origin, apart from the rare but clearly metastatic tumors. Thus, many women who might have had small fallopian tube primary cancers that rapidly extended on to or into the ovary were deemed to have ovarian cancer. Now, as we begin to better understand that there are different types of cancers of nonuterine Muellerian origin, we expand upon the morphologic to add the molecular characteristics. Morphomolecular characteristics are being applied to drive clinical advances including development and optimization of predictive and prognostic biomarkers, redefinition of historical controls, and consideration of novel clinical trial designs. Ovarian cancer, not a common cancer to start with, is now subdivided into types, making ever smaller clinical cohorts. The first studies evaluating tubo-ovarian Muellerian cancers of morphomolecular types have begun. Deleterious mutations in BRCA1 or 2 have been validated as the first new predictive and prognostic biomarker of the high-grade serous ovarian cancer type and polyADPribose polymerase inhibitors, the first targeted agents for this morphomolecular entity. Similar progress is developing in other tubo-ovarian cancer types. This new knowledge is driving the building of a structure–function-type relationship that is generating novel clinically applicable hypotheses for testing. [ABSTRACT FROM PUBLISHER]

The management of patients with metastatic colorectal cancer (mCRC) has the continuum of care as the treatment paradigm. To date, trifluridine/tipiracil, a biochemically modulated fluoropyrimidine, and regorafenib, a multi-kinase inhibitor, remain the main options for the majority of patients who progressed to standard doublet- or triplet-based chemotherapies, although a tailored approach could be indicated in certain circumstances. Being highly selective for vascular endothelial growth factor receptor (VEGFR)-1, -2 and -3, fruquintinib demonstrated a strong anti-tumor activity in preclinical models and received approval from China's National Medical Products Administration (NMPA) in 2018 for the treatment of patients with chemo-refractory mCRC. The approval was based on the results of the phase III FRESCO trial. Then, in order to overcome geographic differences in clinical practice, the FRESCO-2 trial was conducted in the US, Europe, Japan, and Australia. In a heavily pretreated patient population, the study met its primary endpoint, demonstrating an advantage of fruquintinib over a placebo in overall survival (OS). Here, we review the clinical development of fruquintinib and its perspectives in gastrointestinal cancers. Then, we discuss the introduction of fruquintinib in the continuum of care of CRC paying special attention to unmet needs, including the identification of cross-resistant and potentially susceptible populations, evaluation of radiological response, and identification of novel biomarkers of clinical benefit. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the short-term efficacy and safety of autologous platelet-rich plasma (a-PRP) as an adjuvant to revisional vitrectomy for refractory full-thickness macular holes (rFTMHs). We conducted a prospective, non-randomized interventional study including patients with rFTMH after a pars plana vitrectomy (PPV) with internal limiting membrane peeling and gas tamponade. We included 28 eyes from 27 patients with rFTMHs: 12 rFTMHs in highly myopic eyes (axial length greater than 26.5 mm or a refractive error greater than -6D or both); 12 large rFTMHs (minimum hole width > 400 μm); and 4 rFTMHs secondary to the optic disc pit. All patients underwent 25-G PPV with a-PRP, a median time of 3.5 ± 1.8 months after the primary repair. At the six-month follow-up, the overall rFTMH closure rate was 92.9%, distributed as follows: 11 out of 12 eyes (91.7%) in the highly myopic group, 11 out of 12 eyes (91.7%) in the large rFTMH group, and 4 out of 4 eyes (100%) in the optic disc pit group. Median best-corrected visual acuity significantly improved in all groups, in particular from 1.00 (interquartile range: 0.85 to 1.30) to 0.70 (0.40 to 0.85) LogMAR in the highly myopic group (p = 0.016), from 0.90 (0.70 to 1.49) to 0.40 (0.35 to 0.70) LogMAR in the large rFTMH group (p = 0.005), and from 0.90 (0.75 to 1.00) to 0.50 (0.28 to 0.65) LogMAR in the optic disc pit group. No intraoperative or postoperative complications were reported. In conclusion, a-PRP can be an effective adjuvant to PPV in the management of rFTMHs. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of a food supplement containing -lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L-carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG), post-prandial-glucose (PPG), glycated hemoglobin (HbA1c), fasting plasma insulin (FPI), HOMA-index (HOMA-IR), lipid profile, high sensitivity C-reactive protein (Hs-CRP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA). There was a reduction of FPG, PPG, and HbA1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L-carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers. [ABSTRACT FROM AUTHOR]

We present a theoretical basis for testing related endpoints. Typically, it is known how to construct tests of the individual hypotheses, but not how to combine them into a multiple test procedure that controls the familywise error rate. Using the closure method, we emphasize the role of consonant procedures, from an interpretive as well as a theoretical viewpoint. Surprisingly, even if each intersection test has an optimality property, the overall procedure obtained by applying closure to these tests may be inadmissible. We introduce a new procedure, which is consonant and has a maximin property under the normal model. The results are then applied to PROactive, a clinical trial designed to investigate the effectiveness of a glucose-lowering drug on macrovascular outcomes among patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Examines the breast cancer screening for women. Removal of the complement inhibitors; Application of the antiangiogenic drugs; Indication of chemotherapy.

A low-nickel (Ni) diet, a key treatment for Systemic Nickel Allergy Syndrome (SNAS), is difficult in the long term and strongly impacts quality of life (QoL). Hydroponic agriculture could be an alternative to allow the reintroduction of tomato, an essential food in the global diet. In a first interventional, randomized, double-blind, single-center crossover study, we compared the possible effects of eating tomato puree deriving from hydroponic agriculture versus tomato puree from conventional cultivation, collecting data on subjective control of SNAS symptoms, adherence to treatment, and impact on QoL. Thirty subjects were randomly assigned to one of the following treatment groups: (1) a 12-week low-Ni diet plus 100% Italian Datterino tomato puree deriving from hydroponic technology; (2) a 12-week low-Ni diet plus 100% Italian Datterino tomato puree deriving from conventional cultivation. Then, after a 2-week washout period on the low-Ni diet, each patient crossed over to the other treatment. Patients reported lower symptom scores after eating Datterino tomato puree deriving from hydroponic technology; specifically, bloating (p = 0.0111, p = 0.0060), flatulence (p = 0.0090), abdominal cramps (p = 0.0207), constipation (p = 0.0395), and diarrhea (p = 0.0105). Overall, the adherence rate was high for both treatment arms. At baseline, QoL was poor, but significant improvement was observed after two treatments. In our study, precision medicine and precision agriculture merge in a holistic approach to the challenges of food allergies. [ABSTRACT FROM AUTHOR]

We describe the clinical manifestations and the lesion patterns of five patients with somatoparaphrenia, the denial of ownership for a paralyzed limb, who showed the rare dissociation from anosognosia for hemiplegia. Similar cases have been only occasionally cited in the literature with scanty descriptions of their symptoms and no detailed anatomical assessment. All patients had extrapersonal and at least mild personal neglect. The lesions pattern was mainly subcortical, with a significant involvement of the right thalamus, the basal ganglia and the internal capsule. A formal comparison between the anatomical pattern previously associated with anosognosia in a study performed in 2005 by Berti and colleagues, and the lesion distribution of each patient clearly shows that our pure somatoparaphrenic patients had a sparing of most of the regions associated with anosognosia for hemiplegia. The behavioral dissociation between SP and anosognosia for hemiplegia, together with this new anatomical evidence, suggests that motor awareness is not sufficient to build up a sense of ownership and therefore these two cognitive abilities are at least in part functionally independent and qualitatively different. [ABSTRACT FROM AUTHOR]

The International Society for CNS Clinical Trials and Methodology (ISCTM) held its 4th Annual Autumn Conference in Toronto, Ontario, October 6-7, 2008. The purpose of the present report is to provide an overview of one of the sessions at the conference which focused on the designs andmethodologies to be applied in clinical trials of new treatments for Alzheimer's disease (AD) with purported "disease-modifying" effects. The session began with a discussion of how neuroimaging has been applied in multiple sclerosis clinical trials (another condition for which disease modification claims have been achieved). The next two lectures provided a pharmaceutical industry perspective on some of the specific challenges and possible solutions for designing trials to measure disease progression and/or modification. The final lecture provided an academic viewpoint and the closing discussion included additional academic and regulatory perspectives on trial designs, methodologies, and statistical issues relevant to the disease modification concept. [ABSTRACT FROM AUTHOR]

Simple Summary: Neck and back pain are common ailments in animals. While there are medical and surgical treatment options available for select patients, conservative care is the most common form of management of pain, stiffness and muscle spasms. Physical therapists, osteopaths and chiropractors use mobilization and manipulation techniques to evaluate and treat muscle and joint problems in both humans and animals, but there seems to be little scientific evidence available to support their use in veterinary medicine. This study reviews the scientific literature with the goal of identifying the clinical indications, dosages, outcome parameters, and efficacy of mobilization and manipulation techniques in dogs and horses. Fourteen articles were included in this review of which 13 were equine and one was a canine study. There was a large variability in the quality of evidence that supports the use of joint mobilization or manipulation in treating pain, stiffness and muscle hypertonicity in horses. Therefore, it was difficult to draw firm conclusions despite all studies reporting positive effects. Future studies need to establish standardized methods to evaluate the optimal dosages of mobilization and manipulation for use in animals. Mobilization and manipulation techniques are often used in small animal and equine practice; however, questions remain concerning indications, dosing and efficacy. A bibliographic search was performed to identify peer-reviewed publications from 1980 to 2020 that evaluated the clinical effects of musculoskeletal mobilization and manipulation techniques in dogs, cats and horses. The search strategy identified 883 papers for review. Inclusion and exclusion criteria were applied. The clinical indications, dosages, outcome parameters, and reported efficacy within each publication were recorded and categorized for comparison with scientific quality assessed according to a standardized grading system. Fourteen articles were included in this systematic review of which 13 were equine and one was a canine study. Seven of these were cohort studies and seven were randomized controlled clinical trials. The canine study involved carpal immobilization-remobilization and all equine studies focused on the effects of passive mobilization (n = 5) or manipulation (n = 8) of the axial skeleton. Study quality was low (n = 4), moderate (n = 7), and high (n = 3) and included a wide array of outcome parameters with varying levels of efficacy and duration of therapeutic effects, which prevented further meta-analysis. Therefore, it was difficult to draw firm conclusions despite all studies reporting positive effects. Optimal technique indications and dosages need to be determined to improve the standardization of these treatment options. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. Methods: DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. Discussion: This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration: ClinicalTrials.govNCT04429854. Registered on 12 June 2020 - Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Optimal strategies to improve national congenital heart surgery outcomes and reduce variability across hospitals remain unclear. Many policy and quality improvement efforts have focused primarily on higher-risk patients and mortality alone. Improving our understanding of both morbidity and mortality and current variation across the spectrum of complexity would better inform future efforts.Methods: Hospitals participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database (2014-2017) were included. Case mix-adjusted operative mortality, major complications, and postoperative length of stay were evaluated using Bayesian models. Hospital variation was quantified by the interdecile ratio (IDR, upper versus lower 10%) and 95% credible intervals (CrIs). Stratified analyses were performed by risk group (Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery [STAT] category) and simulations evaluated the potential impact of reductions in variation.Results: A total of 102 hospitals (n=84 407) were included, representing ≈85% of US congenital heart programs. STAT category 1 to 3 (lower risk) operations comprised 74% of cases. All outcomes varied significantly across hospitals: adjusted mortality by 3-fold (upper versus lower decile 5.0% versus 1.6%, IDR 3.1 [95% CrI 2.5-3.7]), mean length of stay by 1.8-fold (19.2 versus 10.5 days, IDR 1.8 [95% CrI 1.8-1.9]), and major complications by >3-fold (23.5% versus 7.0%, IDR 3.4 [95% CrI 3.0-3.8]). The degree of variation was similar or greater for low- versus high-risk cases across outcomes, eg, ≈3-fold mortality variation across hospitals for STAT 1 to 3 (IDR 3.0 [95% CrI 2.1-4.2]) and STAT 4 or 5 (IDR 3.1 [95% CrI 2.4-3.9]) cases. High-volume hospitals had less variability across outcomes and risk categories. Simulations suggested potential reductions in deaths (n=282), major complications (n=1539), and length of stay (101 183 days) over the 4-year study period if all hospitals were to perform at the current median or better, with 37% to 60% of the improvement related to the STAT 1 to 3 (lower risk) group across outcomes.Conclusions: We demonstrate significant hospital variation in morbidity and mortality after congenital heart surgery. Contrary to traditional thinking, a substantial portion of potential improvements that could be realized on a national scale were related to variability among lower-risk cases. These findings suggest modifications to our current approaches to optimize care and outcomes in this population are needed. [ABSTRACT FROM AUTHOR]

Thyroid cancer comprises different clinical and histological entities. Whereas differentiated (DTCs) malignancies are sensitive to radioiodine therapy, anaplastic (ATCs) and medullary (MTCs) tumors do not uptake radioactive iodine and display aggressive features associated with a poor prognosis. Moreover, in a majority of DTCs, disease evolution leads to the progressive loss of iodine sensitivity. Hence, iodine-refractory DTCs, along with ATCs and MTCs, require alternative treatments reflective of their different tumor biology. In the last decade, the molecular mechanisms promoting thyroid cancer development and progression have been extensively studied. This has led to a better understanding of the genomic landscape, displayed by thyroid malignancies, and to the identification of novel therapeutic targets. Indeed, several pharmacological compounds have been developed for iodine-refractory tumors, with four multi-target tyrosine kinase inhibitors already available for DTCs (sorafenib and lenvatinib) and MTCs (cabozantib and vandetanib), and a plethora of drugs currently being evaluated in clinical trials. In this review, we will describe the genomic alterations and biological processes intertwined with thyroid cancer development, also providing a thorough overview of targeted drugs already tested or under investigation for these tumors. Furthermore, given the existing preclinical evidence, we will briefly discuss the potential role of immunotherapy as an additional therapeutic strategy for the treatment of thyroid cancer. [ABSTRACT FROM AUTHOR]

Highlights • Physiotherapeutic scoliosis-specific exercises (PSSE) have been found effective in avoiding bracing in adolescents with idiopathic scoliosis (AIS). • One hundred and forty-five patients performed the SEAS (Scientific Exercise Approach to Scoliosis) PSSE program, based on active self-correction and stabilization. • The control groups included 53 patients who were not prescribed exercises (observation) or who did not regularly exercise, and 95 who performed usual physiotherapy. • SEAS reduced the bracing rate in AIS and was more effective than usual physiotherapy or control treatment. Abstract Background In an ideal experimental setting, 2 randomized controlled trials recently showed the efficacy of physiotherapeutic scoliosis-specific exercises (PSSEs) for adolescents with idiopathic scoliosis (AIS). Now large observational studies are needed to check the generalizability of these results to everyday clinical life. Objective To explore the effectiveness of PSSEs for avoiding bracing or progression of AIS in everyday clinics. Methods This was a longitudinal comparative observational multicenter study, nested in a prospective database of outpatient tertiary referral clinics, including 327 consecutive patients. Inclusion criteria were AIS, age ≥ 10 years old at first evaluation, Risser sign 0–2, and 11–20°Cobb angle. Exclusion criteria were consultations only and brace prescription at baseline. Groups performed PSSE according to the SEAS (Scientific Exercise Approach to Scoliosis) School, usual physiotherapy (UP) and no therapy (controls [CON]). End of treatment was medical discharge, Risser sign 3, or failure (defined by the need for bracing before the end of growth or Cobb angle > 29°). The probability of failure was estimated by the risk ratio (RR) and 95% confidence interval (CI). The number needed to treat was estimated. Statistical analysis included intent-to-treat analysis, considering all participants (dropouts as failures), and efficacy analysis, considering only end-of-treatment participants. Propensity scores were used to reduce the potential effects of confounders related to the observational design. Results We included 293 eligible subjects after propensity score matching (SEAS, n = 145; UP, n = 95; controls, n = 53). The risk of success was increased 1.7-fold (P = 0.007) and 1.5-fold (P = 0.006) with SEAS versus controls in the efficacy and intent-to-treat analyses, respectively, and the number needed to treat for testing SEAS versus controls was 3.5 (95% CI 3.2–3.7) and 1.8 (95% CI 1.5–2.0), respectively. The success rate was higher with SEAS than UP in the efficacy analysis. Conclusions SEAS reduced the bracing rate in AIS and was more effective than UP. PSSEs are additional tools that can be included in the therapeutic toolbox for AIS treatment. [ABSTRACT FROM AUTHOR]

Objectives: To compare US Food and Drug Administration (FDA) and European Medicines Agency (EMA) labeling for evidence based on patient-reported outcomes (PROs) of new oncology treatments approved by both agencies.Methods: Oncology drugs and indications approved between 2012 and 2016 by both the FDA and the EMA were identified. PRO-related language and analysis reported in US product labels and drug approval packages and EMA summaries of product characteristics were compared for each indication.Results: In total, 49 oncology drugs were approved for a total of 64 indications. Of the 64 indications, 45 (70.3%) included PRO data in either regulatory submission. No FDA PRO labeling was identified. PRO language was included in the summary of product characteristics for 21 (46.7%) of 45 indications. European Organisation for Research and Treatment of Cancer and Functional Assessment of Cancer Therapy measures were used frequently in submissions. FDA's comments suggest that aspects of study design (eg, open labels) or the validity of PRO measures was the primary reason for the lack of labeling based on PRO endpoints. Both agencies identified missing PRO data as problematic for interpretation.Conclusions: During this time period, the FDA and the EMA used different evidentiary standards to assess PRO data from oncology studies, with the EMA more likely to accept data from open-label studies and broad concepts such as health-related quality of life. An understanding of the key differences between the agencies may guide sponsor PRO strategy when pursuing labeling. Patient-focused proximal concepts are more likely than distal concepts to receive positive reviews. [ABSTRACT FROM AUTHOR]

Background and purpose: The therapeutic scenario of X‐linked adrenoleukodystrophy (X‐ALD) is rapidly changing. Whereas the disease is well characterized in men, the condition remains to be fully clarified in women carrying ATP binding cassette subfamily D member 1 (ABCD1) variants. Specifically, data on clinical progression are needed, in order to recommend any appropriate management. The objective of this study was to outline the natural history of a cohort of untreated ABCD1 heterozygous female carriers. Methods: Longitudinal data from a single‐center population of 60 carriers were retrospectively reviewed. Demographics, anthropometrics, serum very long chain fatty acid (VLCFA) levels, clinical parameters and the Adult ALD Clinical Score (AACS) were collected from every recorded visit in a 7‐year period and analyzed to define the phenotype modifications, to determine factors associated with clinical features, and to estimate the annual progression rate and the subsequent sample size for interventional trials. Results: Thirty‐two patients were eligible for the study, and 59.4% were symptomatic at baseline. Clinical severity worsens with age which increases risk of symptom onset, the cut‐off of 41 years being crucial for phenoconversion. VLCFA levels were not predictive and did not change over time. Symptomatic carriers were followed up for 3.45 ± 2.1 years. The AACS increased at an annual rate of 0.24 points. The estimated sample size for 30% reduction in annual progression at 80% power was 272. Conclusions: This study provides data on the natural disease progression of untreated ABCD1 heterozygous female carriers, demonstrating the relevance of aging. The estimated annual increase of the AACS will be useful for future interventional studies. [ABSTRACT FROM AUTHOR]

Because of its high biocompatibility, bio-degradability, low-cost and easy availability, cellulose finds application in disparate areas of research. Here we focus our attention on the most recent and attractive potential applications of cellulose in the biomedical field. We first describe the chemical/structural composition of cellulose fibers, the cellulose sources/features and cellulose chemical modifications employed to improve its properties. We then move to the description of cellulose potential applications in biomedicine. In this field, cellulose is most considered in recent research in the form of nano-sized particle, i.e., nanofiber cellulose (NFC) or cellulose nanocrystal (CNC). NFC is obtained from cellulose via chemical and mechanical methods. CNC can be obtained from macroscopic or microscopic forms of cellulose following strong acid hydrolysis. NFC and CNC are used for several reasons including the mechanical properties, the extended surface area and the low toxicity. Here we present some potential applications of nano-sized cellulose in the fields of wound healing, bone-cartilage regeneration, dental application and different human diseases including cancer. To witness the close proximity of nano-sized cellulose to the practical biomedical use, examples of recent clinical trials are also reported. Altogether, the described examples strongly support the enormous application potential of nano-sized cellulose in the biomedical field. [ABSTRACT FROM AUTHOR]

Background: The normobaric oxygen paradox states that a short exposure to normobaric hyperoxia followed by rapid return to normoxia creates a condition of 'relative hypoxia' which stimulates erythropoietin (EPO) production. Alterations in glutathione and reactive oxygen species (ROS) may be involved in this process. We tested the effects of short-term hyperoxia on EPO levels and the microcirculation in critically ill patients. Methods: In this prospective, observational study, 20 hemodynamically stable, mechanically ventilated patients with inspired oxygen concentration (FiO2) ≤0.5 and PaO2/FiO2 ≥ 200 mmHg underwent a 2-hour exposure to hyperoxia (FiO2 1.0). A further 20 patients acted as controls. Serum EPO was measured at baseline, 24 h and 48 h. Serum glutathione (antioxidant) and ROS levels were assessed at baseline (t0), after 2 h of hyperoxia (t1) and 2 h after returning to their baseline FiO2 (t2). The microvascular response to hyperoxia was assessed using sublingual sidestream dark field videomicroscopy and thenar near-infrared spectroscopy with a vascular occlusion test. Results: EPO increased within 48 h in patients exposed to hyperoxia from 16.1 [7.4-20.2] to 22.9 [14.1-37.2] IU/L (p = 0.022). Serum ROS transiently increased at t1, and glutathione increased at t2. Early reductions in microvascular density and perfusion were seen during hyperoxia (perfused small vessel density: 85% [95% confidence interval 79-90] of baseline). The response after 2 h of hyperoxia exposure was heterogeneous. Microvascular perfusion/density normalized upon returning to baseline FiO2. Conclusions: A two-hour exposure to hyperoxia in critically ill patients was associated with a slight increase in EPO levels within 48 h. Adequately controlled studies are needed to confirm the effect of short-term hyperoxia on erythropoiesis. Trial registration: ClinicalTrials.gov (www.clinicaltrials.gov), NCT02481843, registered 15th June 2015, retrospectively registered [ABSTRACT FROM AUTHOR]

Background: The phase 3 MPACT trial in patients with metastatic pancreatic cancer demonstrated superior efficacy of nab-paclitaxel (nab-P) + gemcitabine (Gem) vs Gem monotherapy for all endpoints examined including overall survival, the primary endpoint. In the MPACT trial, patients were treated until progressive disease (PD) or unacceptable toxicity. The current exploratory analysis investigated outcomes of patients from the MPACT trial who were treated until PD, in order to understand how to maximize treatment benefit from nab-P + Gem. Methods: The trial design has been described in detail previously. Progressive disease was determined by the investigator on the basis of radiological imaging. Results: Among patients who were treated until PD, overall survival was significantly longer for those who received nab-P + Gem vs Gem (median, 9.8 vs 7.5 months; P < 0.001). Independently assessed progression-free survival and overall response rate were significantly greater among patients in the treatment-to-PD cohort who received nab-P + Gem compared with Gem (P < 0.001 for each). Although not compared statistically, patients who were treated until PD received greater treatment exposure and experienced more favourable efficacy than the intent-to-treat population of the MPACT trial. Among patients who were treated with nab-P + Gem until PD, > 50 % went on to receive a subsequent therapy. The safety profile for patients treated until PD was similar to what was reported in the overall MPACT trial. Conclusion: The nab-P + Gem regimen is an active first-line treatment option; most patients were treated until PD, and this exposure was associated with improved efficacy outcomes. Prolonged first-line treatment exposure and ability to receive subsequent therapies likely contributed to the improved survival among these patients. Our data highlight the importance of managing adverse events and indicate that patients should be treated until PD when possible. [ABSTRACT FROM AUTHOR]

Although no definitive data exist in literature, adjuvant chemotherapy is usually recommended in patients with radically resected stage III rectal cancer treated with neo-adjuvant chemo-radiotherapy. We performed a systematic review of literature with direct and indirect comparisons to assess the role of adjuvant mono- or poli-chemotherapy in radically resected rectal cancer treated with neoadjuvant chemo-radiotherapy. Neither chemotherapy (mono-or poli-chemotherapy) nor polichemotherapy with oxaliplatin-containing regimens seems to improve Overall Survival and Disease-Free Survival in patients with radically resected rectal cancer treated with neoadjuvant chemo-adiotherapy. Neither the entire population of patients radically resected after neoadjuvant chemotherapy, nor high risk patients seem to benefit from adjuvant chemotherapy. Our data seem to suggest the need of review the actual international guidelines that suggest the need of adjuvant chemotherapy at least in high risk rectal cancer treated with surgery and neoadjuvant chemo-radiotherapy. [Display omitted] • Although no definitive data exist in literature, adjuvant chemotherapy is usually recommended in patients with radically resected stage III rectal cancer treated with neo-adjuvant chemo-radiotherapy. • We performed a systematic review of literature with direct and indirect comparisons to assess the role of adjuvant mono- or poli-chemotherapy in radically resected rectal cancer treated with neoadjuvant chemo-radiotherapy. • Neither chemotherapy (mono-or poli-chemotherapy) nor polichemotherapy with oxaliplatin-containing regimens seems to improve Overall Survival and Disease-Free Survival in patients with radically resected rectal cancer treated with neoadjuvant chemo-adiotherapy. • Our data seem to suggest the need of review the actual international guidelines that suggest the need of adjuvant chemotherapy at least in high risk rectal cancer treated with surgery and neoadjuvant chemo-radiotherapy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the effectiveness of cervical lateral glide (CLG) added to median nerve neural mobilization (MNNM) in patients with neck pain (NP). Methods: A single-blinded randomized controlled clinical trial was carried out in a Pain Management Unit from a Hospital. A total sample of 72 patients with NP was recruited from a hospital. Patients were randomized to receive isolated CLG (n = 36) or CLG + MNNM (n = 36). Bilateral elbow extension range of motion (ROM) on upper limb neurodynamic test 1 (ULNT1), bilateral pressure pain thresholds (PPT) on the median nerve at elbow joint, C6 zygapophyseal joint and tibialis anterior, Visual analogue scale (VAS), body chart distribution of pain, active cervical ROM (CROM), Neck Disability Index (NDI), and Tampa Scale of Kinesiophobia (TSK-11) were measured at baseline as well as immediately, 15 days, and 1 month after treatment. Results: There were no statistically significant interactions (p > 0.05) between treatment and time for median nerve mechanosensitivity outcomes, pain intensity, symptom distribution, and PPT of the widespread pain assessment, as well as cervical function, and kinesiophobia. Conclusions: MNNM gave no additional benefit to CLG in patients with NP regarding pain intensity, symptom distribution, mechanosensitivity, functionality, and kinesiophobia. Only two treatment sessions and the short follow-up are important issues, therefore, justifying further studies to answer the research question with better methodology. [ABSTRACT FROM AUTHOR]

Background: Cornelia de Lange syndrome (CdLS) is a rare autosomal-dominant disorder characterised by facial dysmorphism, growth and psychomotor developmental delay and skeletal defects. To date, causative mutations in the NIPBL (cohesin regulator) and SMC1A (cohesin structural subunit) genes account for > 50% and 6% of cases, respectively. Methods: We recruited 50 patients with a CdLS clinical diagnosis or with features that overlap with CdLS, who were negative for mutations at NIPBL and SMC1A at molecular screening. Chromosomal rearrangements accounting for the clinical diagnosis were screened for using array Comparative Genomic Hybridisation (aCGH). Results: Four patients were shown to carry imbalances considered to be candidates for having pathogenic roles in their clinical phenotypes: patient 1 had a 4.2 Mb de novo deletion at chromosome 20q11.2-q12; patient 2 had a 4.8 Mb deletion at chromosome 1p36.23-36.22; patient 3 carried an unbalanced translocation, t(7;17), with a 14 Mb duplication of chromosome 17q24.2-25.3 and a 769 Kb deletion at chromosome 7p22.3; patient 4 had an 880 Kb duplication of chromosome 19p13.3, for which his mother, who had a mild phenotype, was also shown to be a mosaic. Conclusions: Notwithstanding the variability in size and gene content of the rearrangements comprising the four different imbalances, they all map to regions containing genes encoding factors involved in cell cycle progression or genome stability. These functional similarities, also exhibited by the known CdLS genes, may explain the phenotypic overlap between the patients included in this study and CdLS. Our findings point to the complexity of the clinical diagnosis of CdLS and confirm the existence of phenocopies, caused by imbalances affecting multiple genomic regions, comprising 8% of patients included in this study, who did not have mutations at NIPBL and SMC1A. Our results suggests that analysis by aCGH should be recommended for CdLS spectrum cases with an unexplained clinical phenotype and included in the flow chart for diagnosis of cases with a clinical evaluation in the CdLS spectrum. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy.We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications. [ABSTRACT FROM AUTHOR]

Abstract: We report a new case of 8q interstitial duplication in a patient with dysmorphic features, umbilical hernia, cryptorchidism, short stature, congenital heart defect and mild mental retardation (MR). Chromosome analysis with high resolution QFQ bands showed 46,XY, 8q+, which was interpreted as a partial duplication of the distal long arm of chromosome 8 (q22 → qter). This chromosomal aberration was further characterized using fluorescence in situ hybridization (FISH) analyses with multiple DNA probes and array-CGH (Comparative Genomic Hybridization) experiment which demonstrated a de novo direct duplication (8)(q22.2-q24.3). We have compared this case with other partially trisomic 8q patients reported in literature and highlighted the common clinical features in 8q22-8q24 duplication syndrome. [Copyright &y& Elsevier]

Background. To validate feasibility, efficacy, and safeness of laparoscopic treatment of benign adnexal diseases through a single transumbilical access (LESS) in a prospective series of patients. Methods. A prospective clinical trial including 30 women has been conducted at the Division of Gynecology of Catholic University of Sacred Hearth of Rome. Patients underwent different laparoscopic procedures by LESS utilizing a multiport trocar and conventional straight laparoscopic instrumentation. Intra and perioperative outcome has been reported. Results. Ten mono/bilateral adnexectomies and 20 cystectomies have been performed by LESS approach. Laparoscopic procedures were completed through a single access in 28 cases (93.4%). No major intra- or postoperative complications were observed. Mean hospital stay was 1.3 days. Conclusions. LESS approach is feasible to treat benign adnexal disease with a very low conversion rate and no early or late complications. More clinical data are needed to confirm these advantages compared to standard laparoscopic technique. [ABSTRACT FROM AUTHOR]

The following recommendations for management of caustic and foreign body ingestion in children have been developed following a multicentre study performed by the Italian Society for Paediatric Gastroenterology, Hepatology and Nutrition (SIGENP). They are principally addressed to medical professionals involved in casualty. Because there is paucity of good quality clinical trials in children on this topic, many of the recommendations are currently extrapolated from adult experiences or based on experts opinions. The document represents a level 2 to 5 degree of evidence (according to the Oxford Centre for Evidence-basedMedicine Levels of Evidence), gathered from clinical experience, recent studies, and expert reports discussed during a consensus conference of the Endoscopic Section of the Italian Society of Paediatric Gastroenterology Hepatology and Nutrition. This working group comprises paediatricians, endoscopists, paediatric surgeons, toxicologists, and ENT surgeons, who are all actively involved in the management of these children. Recommendations are intended to serve as an aid to clinical judgement, not to replace it and therefore do not provide answers to every clinical question; nor does adherence to them ensure a successful outcome in every case. The ultimate decision on the clinical management of an individual patient will always depend on the specific clinical circumstances of the patient, and on the clinical judgement of the health care team. [ABSTRACT FROM AUTHOR]

Objective-To compare efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. Design-Randomized controlled clinical trial. Animals-253 client-owned horses with naturally occurring osteoarthritis. Procedures-Horses were treated with firocoxib (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) or phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 24 h) for 14 days. Physical examinations and lameness evaluations were performed prior to treatment and after 7 and 14 days. Clinical improvement was defined as a reduction of at least 1 lameness grade or a combined reduction of at least 3 points in scores for pain during manipulation or palpation, joint swelling, joint circumference, and range of motion. Results-Proportion of horses clinically improved on day 14 for the firocoxib group (104/1 23 [84.6%]) was not significantly different from the proportion for the phenylbutazone group (103/119 [86.6%]). Proportion of horses that were improved on day 14 was significantly greater for horses treated with firocoxib than for horses treated with phenylbutazone with regard to score for pain on manipulation or palpation (P = 0.028), joint circumference score (P = 0.026), and range of motion score (P = 0.012), but not for overall lameness score or joint swelling score. No direct treatment-related adverse effects were detected during the study. Conclusions and Clinical Relevance-Results suggested that overall clinical efficacy of a paste formulation of firocoxib in horses with naturally occurring osteoarthritis was comparable to efficacy of a paste formulation of phenylbutazone. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]