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Background: Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the "Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)" study aims to monitor these processes to gain new insight into this perplexing disease.Methods: The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time.Discussion: Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory.Trial Registration: This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994. [ABSTRACT FROM AUTHOR]

Objective: Limited data exist regarding safety and efficacy of antihyperglycemic drugs in older patients with type 2 diabetes. The Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) was a randomized, double-blind, placebo-controlled trial assessing the impact of sitagliptin on a primary composite outcome of cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, or unstable angina hospitalizations in patients with type 2 diabetes (HbA1c ≥6.5% [48 mmol/mol] and ≤8.0% [64 mmol/mol]) and cardiovascular disease. We analyzed baseline characteristics and clinical outcomes for TECOS participants aged ≥75 years.Research Design and Methods: Clinical and safety event summaries are presented for older versus younger participants and for the treatment groups within the older cohort.Results: Of 14,351 participants with age recorded, 2,004 (14%) were ≥75 years old (mean age 78.3 years [SD 3.1]), with 68% men and type 2 diabetes duration median 12.0 years (IQR 7, 21). During 2.9 years median follow-up, older participants had higher rates of the primary outcome (6.46 vs. 3.67 events per 100 person-years; hazard ratio 1.72 [95% CI 1.52-1.94]), death (2.52 [2.20-2.89]), severe hypoglycemia (1.53 [1.15-2.03]), and fractures (1.84 [1.44-2.35]). In the older cohort, sitagliptin did not significantly impact the primary composite (1.10 [0.89-1.36]), death (1.05 [0.83-1.32]), heart failure hospitalization (0.99 [0.65-1.49]), severe hypoglycemia (1.03 [0.62-1.71]), rates of acute pancreatitis and pancreatic cancer, or serious adverse events.Conclusions: Among older patients with well-controlled type 2 diabetes and cardiovascular disease, sitagliptin had neutral effects on cardiovascular risk and raised no significant safety concerns. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare the short-term effectiveness of three different types of immediate, non-pharmacological intervention for alleviation of the painful symptoms of temporomandibular disorders (TMD).Material and Methods: Thirty-six patients (mean age 41.6 ± 16.7 years, 25 females) diagnosed with non-dysfunctional painful TMD received counselling and subsequently were randomly allocated to three treatment groups: patients in Group A received prefabricated oral splints with water-filled elastic pads (Aqualizer(®)), those in Group B were provided with vacuum-formed co-polyester oral splints and those in Group C were given appointments to receive Michigan-type hard splints. Clinical examination was conducted, at baseline and after 2 weeks, by use of the RDC/TMD. Current pain intensity was determined by evaluation of graded chronic pain status (GCPS) on a numerical rating scale (NRS). Active maximum mouth opening without pain (AMMOP) was also measured. Paired sample t-tests and one-way analysis of variance with a significance level of p ≤ 0.05 were conducted.Results: After 2 weeks, overall mean current pain was reduced by 41.95% (p < 0.001). Current pain reduction was significant for Group B (66.6%, p < 0.001) but not for Groups A (37.88%, p = 0.56) and C (22.29%, p = 0.26). After 2 weeks, current pain level for Group B was significantly lower than that for Group C (p = 0.041). Overall, there was a statistically significant increase of AMMOP (p = 0.01).Conclusion: All therapeutic options were pain-reducing. The results from this study suggest that cost-effective and time-effective intervention of counselling combined with use of a vacuum-formed splint is a favourable option for initial, short-term treatment of painful TMD. [ABSTRACT FROM AUTHOR]

To determine the frequency, imaging characteristics, neuroanatomical distribution and dynamics of magnetic resonance imaging findings in HIV-associated cryptococcal meningitis in immunocompromised patients we compared patients without antiretroviral therapy with patients undergoing immune reconstitution. Neuroimaging and clinical data of 21 consecutive patients presenting to a German HIV centre in a 10-year period between 2005 and 2014 were reviewed. We identified eight patients with magnetic resonance imaging findings related to cryptococcal disease: five patients without antiretroviral therapy and three patients receiving effective antiretroviral therapy resulting in immune reconstitution. The pattern of magnetic resonance imaging manifestations was different in the two groups. In patients not on antiretroviral therapy, pseudocysts (n = 3) and lacunar ischaemic lesions (n = 2) were detected. Contrast-enhancing focal leptomeningeal and/or parenchymal lesions were found in all patients under immune reconstitution (n = 3). Magnetic resonance imaging lesions suggestive of leptomeningitis or meningoencephalitis were detected in all patients with a recurrence of cryptococcal meningitis under immune reconstitution, which differs from the classical magnetic resonance imaging findings in patients without antiretroviral therapy. In antiretroviral therapy-treated patients with past medical history of cryptococcal meningitis, detection of contrast-enhancing focal meningeal and/or parenchymal lesions should prompt further investigations for a recurrence of cryptococcal meningitis under immune reconstitution. [ABSTRACT FROM AUTHOR]

The forward bending test according to Adams and rib hump quantification by scoliometer are common clinical examination techniques in idiopathic scoliosis, although precise data about the change of axial surface rotation in forward bending posture are not available. In a pilot study the influence of leg length inequalities on the back shape of five normal subjects was clarified. Then 91 patients with idiopathic scoliosis with Cobb-angles between 20° and 82° were examined by rasterstereography, a 3D back surface analysis system. The axial back surface rotation in standing posture was compared with that in forward bending posture and additionally with a scoliometer measurement in forward bending posture. The changes of back shape in forward bending posture were correlated with the Cobb-angle, the level of the apex of the scoliotic primary curve and the age of the patient. Averaged over all patients, the back surface rotation amplitude increased from 23.1° in standing to 26.3° in forward bending posture. The standard deviation of this difference was high (6.1°). The correlation of back surface rotation amplitude in standing with that in forward bending posture was poor ( R 2=0.41) as was the correlation of back surface rotation in standing posture with the scoliometer in forward bending posture measured rotation ( R 2=0.35). No significant correlation could be found between the change of back shape in forward bending and the degree of deformity ( R 2=0.07), likewise no correlation with the height of the apex of the scoliosis ( R 2=0.005) and the age of the patient ( R 2=0.001). Before forward bending test leg length inequalities have to be compensated accurately. Compared to the standing posture, forward bending changes back surface rotation. However, this change varies greatly between patients, and is independent of the type and degree of scoliosis. Furthermore remarkable differences were found between scoliometer measurement of the rib hump and rasterstereographic measurement of the vertebral rotation. Therefore the forward bending test and the identification of idiopathic scoliosis rotation by scoliometer can be markedly different compared to rasterstereographic surface measurement in the standing posture. [ABSTRACT FROM AUTHOR]

Distal embolization after angioplasty in degenerated saphenous vein grafts (SVGs) results in high rates of periprocedural myonecrosis and mortality. Temporary protection of the distal microcirculation with aspiration of dislodged debris may improve the safety of SVG intervention. To evaluate the feasibility, safety, and efficacy of distal protection using the PercuSurge GuardWire Occlusion and Aspiration System, 103 consecutive patients undergoing planned stenting of 105 SVG lesions were prospectively enrolled in a multinational, multicenter study. Before angioplasty, protection of the distal circulation was achieved with the PercuSurge GuardWire distal balloon occlusion system, followed by stenting and debris aspiration. Quality assurance measures in the study included independent on-site data monitoring, clinical event adjudication, data analysis, and use of multiple core laboratories. Mean graft age was 8.9 ± 4.0 years. The duration of distal balloon inflation was 5.4 ± 3.7 minutes; premature balloon deflation for ischemia was not required in any patient. Macroscopically visible red and/or yellow debris was extracted in 91% of patients. By core lab analysis, postprocedural Thrombolysis In Myocardial Infarction-III flow was present in 98.9% of grafts (vs 83.5% before intervention). No patient developed angiographic evidence of no reflow or distal embolization. Postprocedural creatine phosphokinase MB isozyme levels were elevated to >3 × normal in only 5 patients (5%), and 97 patients (94%) were free of major adverse events at 30 days. We conclude that the GuardWire distal balloon occlusion and aspiration system is an effective and safe method for protecting distal microcirculation from the adverse consequences of embolization during mechanical intervention of degenerated SVGs. [Copyright &y& Elsevier]

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Purpose: A new hemostatic puncture closure device (HPCD) was evaluated following femoropopliteal angioplasty. Efficacy in hemostasis and complications were compared between manual compression and the new system.Methods: One hundred patients undergoing percutaneous interventional procedures were randomly assigned to receive either manual compression or HPCD. The time to complete hemostasis (when a compression bandage was applied) was noted as well as complications such as hematoma or arterial stenosis at the puncture site. Follow-up was by clinical examination and color-coded duplex sonography (CCDS).Results: With the HPCD, immediate hemostasis was achieved in 22 patients (44%). Discrete oozing without the necessity of external compression or further consequences was observed in 11 patients. Mean manual compression time was 25 (+/- 20) min including application of the pressure bandage. Eleven patients needed additional manual compression and technical failures were observed in 6 patients (12%). The compression time in these 17 cases was 27 (+/- 12) min. Subcutaneous hematomata with a diameter of more than 5 cm developed in 15 of 48 patients in the HPCD group and in 14 of 48 patients in the manual compression group. No surgical or percutaneous intervention was necessary. The complication rate was comparably low in the experimental and control groups.Conclusion: Compared with manual compression HPCD is faster and more accurate for sealing the arterial puncture defect following angioplasty. After an initial learning curve, it is easy to handle and time-saving as well as convenient for the patient. Furthermore, immediate and full anticoagulation is possible and arterial inflow is not compromised. A drawback is the necessity of an 8 Fr sheath. Nevertheless, the complication rate is comparably low for both methods. [ABSTRACT FROM AUTHOR]

Background: A subset of patients with neuromyelitis optica spectrum disorders (NMOSD) has been shown to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).Objective: To describe the epidemiological, clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological features of a large cohort of MOG-IgG-positive patients with optic neuritis (ON) and/or myelitis (n = 50) as well as attack and long-term treatment outcomes.Methods: Retrospective multicenter study.Results: The sex ratio was 1:2.8 (m:f). Median age at onset was 31 years (range 6-70). The disease followed a multiphasic course in 80 % (median time-to-first-relapse 5 months; annualized relapse rate 0.92) and resulted in significant disability in 40 % (mean follow-up 75 ± 46.5 months), with severe visual impairment or functional blindness (36 %) and markedly impaired ambulation due to paresis or ataxia (25 %) as the most common long-term sequelae. Functional blindess in one or both eyes was noted during at least one ON attack in around 70 %. Perioptic enhancement was present in several patients. Besides acute tetra-/paraparesis, dysesthesia and pain were common in acute myelitis (70 %). Longitudinally extensive spinal cord lesions were frequent, but short lesions occurred at least once in 44 %. Fourty-one percent had a history of simultaneous ON and myelitis. Clinical or radiological involvement of the brain, brainstem, or cerebellum was present in 50 %; extra-opticospinal symptoms included intractable nausea and vomiting and respiratory insufficiency (fatal in one). CSF pleocytosis (partly neutrophilic) was present in 70 %, oligoclonal bands in only 13 %, and blood-CSF-barrier dysfunction in 32 %. Intravenous methylprednisolone (IVMP) and long-term immunosuppression were often effective; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal. Full recovery was achieved by plasma exchange in some cases, including after IVMP failure. Breakthrough attacks under azathioprine were linked to the drug-specific latency period and a lack of cotreatment with oral steroids. Methotrexate was effective in 5/6 patients. Interferon-beta was associated with ongoing or increasing disease activity. Rituximab and ofatumumab were effective in some patients. However, treatment with rituximab was followed by early relapses in several cases; end-of-dose relapses occurred 9-12 months after the first infusion. Coexisting autoimmunity was rare (9 %). Wingerchuk's 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald criteria for multiple sclerosis (MS) were met by 28 %, 32 %, 15 %, 33 %, respectively; MS had been suspected in 36 %. Disease onset or relapses were preceded by infection, vaccination, or pregnancy/delivery in several cases.Conclusion: Our findings from a predominantly Caucasian cohort strongly argue against the concept of MOG-IgG denoting a mild and usually monophasic variant of NMOSD. The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding the use of glimepiride treatment and IGF-I in adolescents with type 1 diabetes.