Decrease in treatment intensity predicts worse outcome in patients with locally advanced head and neck squamous cell carcinoma undergoing radiochemotherapy.

PURPOSE: Radiochemotherapy (RCT) is an effective standard therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Nonetheless, toxicity is common, with patients often requiring dose modifications. METHODS: To investigate associations of RCT toxicities according to CTCAE version 5.0 and subsequent therapy modifications with short- and long-term treatment outcomes, we studied all 193 patients with HNSCC who received RCT (70 Gy + platinum agent) at an academic center between 03/2010 and 04/2018. RESULTS: During RCT, 77 (41%, 95% CI 34-49) patients developed at least one ≥ grade 3 toxicity, including seven grade 4 and 3 fatal grade 5 toxicities. The most frequent any-grade toxicities were xerostomia (n = 187), stomatitis (n = 181), dermatitis (n = 174), and leucopenia (n = 98). Eleven patients (6%) had their radiotherapy schedule modified (mean radiotherapy dose reduction = 12 Gy), and 120 patients (64%) had chemotherapy modifications (permanent discontinuation: n = 67, pause: n = 34, dose reduction: n = 7, change to other chemotherapy: n = 10). Objective response rates to RCT were 55% and 88% in patients with and without radiotherapy modifications (p = 0.003), and 84% and 88% in patients with and without chemotherapy modifications (p = 0.468), respectively. Five-year progression-free survival estimates were 20% and 50% in patients with and without radiotherapy modifications (p = < 0.001), and 53% and 40% in patients with and without chemotherapy modifications (p = 0.88), respectively. CONCLUSIONS: Reductions of radiotherapy dose were associated with impaired long-term outcomes, whereas reductions in chemotherapy intensity were not. This suggests that toxicities during RCT should be primarily managed by modifying chemotherapy rather than radiotherapy.

Point-of-care Hepatitis C virus testing and linkage to treatment in an Australian inner-city emergency department.

BACKGROUND: In Australia, Hepatitis C Virus (HCV) treatment is declining, despite broad access to direct-acting antiviral medication. People who inject drugs are proportionally over-represented in emergency department presentations. Emergency department assessment of people who have injected drugs for HCV presents an opportunity to engage this marginalised population with treatment. We describe the outcomes of risk-based screening and point-of-care anti-HCV testing for emergency department patients, and linkage to outpatient antiviral treatment. METHODS: During the three-month study period, consecutive adult patients who presented to the emergency department during the study times were screened for risk factors and offered the OraQuick oral HCV antibody test. Those with reactive results were offered venepuncture in the emergency department for confirmatory testing and direct-acting antiviral treatment in clinic. The main outcome measures were the number and proportion of viremic participants that were linked to the hepatitis clinic, commenced treatment and achieved a sustained viral response. Secondary outcome measures were the proportion (%) of presentations screened that were oral antibody reactive, and the prevalence and type of HCV risk factors. RESULTS: During the study period, 2408 of the 3931 (61%) presentations to the emergency department were eligible for screening. Of these 2408 patients, 1122 (47%) participated, 307 (13%) declined participation and 977 (41%) could not be approached during their time in the emergency department. Among the 1122 participants, 378 (34%) reported at least one risk factor. Subsequently, 368 (97%) of the 378 participants underwent OraQuick anti-HCV test, and 50 (14%) had a reactive result. A risk factor of ever having injected drugs was present in 44 (88%) of participants who were sero-positive. Of the 45 that had blood tested, 30 (67%) were HCV ribonucleic acid (RNA) positive. Three participants died. Of the 27 remaining participants, 10 (37%) commenced treatment and 7 of these 10 (70%) obtained a cure. There was a high rate of homelessness (24%) among anti-HCV positive participants. CONCLUSION: Among emergency department participants with a risk factor for HCV, positive serology was common using a rapid point-of-care test. A history of injecting drug use was identified as the risk factor with highest yield for positive HCV serology, and is suitable as a single screening question. However, linkage to care post ED presentation was low in this marginalised population. There is a need for new pathways to improve the care cascade for marginalised individuals living with HCV infection.

Self-reported cognitive function in a large international cohort of people with multiple sclerosis: associations with lifestyle and other factors.

BACKGROUND AND PURPOSE: We aimed to estimate the prevalence of perceived cognitive impairment (PCI) and explore its associations with lifestyle and disease characteristics in a large international cohort of people with multiple sclerosis (MS). METHODS: This study was a cross-sectional analysis. Participants rated their cognitive function over the preceding 4 weeks using four questions in a subscale within the Multiple Sclerosis Quality of Life questionnaire (MSQOL-54). These questions assessed perceived concentration, attention and memory by the patient and family/friends. Four definitions of PCI were derived, ranging from lowest to highest specificity. Associations with PCI were assessed by log-binomial regression. RESULTS: The prevalence of PCI in our sample ranged from 41.0% (95% confidence interval, 39.0-43.0) using the least-specific definition to 11.6% (95% confidence interval, 10.3-12.9) using the most specific definition. A number of factors were associated with PCI, increasing in magnitude as the definition specificity increased, including positive associations for smoking and body mass index, whereas physical activity, dietary quality and use of vitamin D/omega-3 supplements were inversely associated with PCI. CONCLUSIONS: Our study reports associations between healthy lifestyle behaviours and PCI in people with MS. Although reverse causality is a potential explanation for our findings, previous studies have shown comparable associations with healthy lifestyle and MS onset and progression. Subject to external validation, these results suggest benefits realized from a healthy lifestyle in people with MS.

C-reactive protein is an independent prognostic marker in patients with tongue carcinoma - A retrospective study.

OBJECTIVES: Reliable prognostic markers are lacking for tongue carcinoma. C-reactive protein (CRP) and a ratio from neutrophils/lymphocytes (NLR) are biomarkers, associated with prognosis in solid cancers. Aim of this work was to investigate the role of CRP and NLR in prognosis of patients with tongue carcinoma. DESIGN: Retrospective cohort study. SETTING: We retrospectively analysed data of patients treated for tongue carcinoma at our institution. Levels of CRP, Neutrophils and Lymphocytes were measured pretherapeutic. PARTICIPANTS: 197 patients treated for squamous cell carcinoma of the tongue between 2002 and 2015. MAIN OUTCOME MEASURES: Overall survival, disease-free survival. RESULTS: Elevated CRP was significantly associated with shorter overall survival in our cohort in uni- and multivariate analysis. NLR was not associated with prognosis. CONCLUSION: In the present study we could confirm the role of CRP as an independent prognostic marker in patients with tongue carcinoma. Incorporating this marker in prognostication could represent a valuable and moreover inexpensive tool for improved decisions making concerning therapy in the future.

Skills, expertise and role of Australian emergency clinicians in caring for people with advanced cancer.

OBJECTIVES: To explore the views of Australian emergency department (ED) clinicians about their skills, role and expertise in caring for people with advanced cancer. METHODS: A cross-sectional electronic survey of doctors and nurses working in Australian EDs was undertaken. Comparisons were made by demographics and whether respondents had received palliative care education. RESULTS: The sample comprised 444 doctors (response rate 13.5%), the majority Fellows (emergency medicine specialists) of the Australasian College for Emergency Medicine, and 237 nurses, from all states, territories and regions (metropolitan and regional). A minority (n=123, 20.6%) felt that the ED was not an appropriate place for patients with advanced cancer to present for acute care, while almost two-thirds (n=397, 64.8%) found caring for such patients rewarding, particularly nurses and those who had received palliative care education; very few (n=40, 6.5%) reported feeling uncomfortable talking to the families of dying patients. A minority (n=129, 21.0%) felt that it was not appropriate for junior medical staff to assess these patients, nurses much more than doctors (42.9% vs 8.5%, p<0.001). Over half (n=338, 55.1%) felt sufficiently skilled in managing pain for people with advanced cancer, with Fellows, more experienced doctors, and those who had received palliative care education more likely to feel skilled. CONCLUSIONS: ED clinicians in Australia, particularly those who have received palliative care education, feel comfortable and adequately skilled in managing people with advanced cancer presenting to EDs, and most find it rewarding. The importance of palliative care education to emergency clinicians' training should be recognised.

Care of the dying cancer patient in the emergency department: findings from a National survey of Australian emergency department clinicians.

BACKGROUND: Patients with cancer are presenting to emergency departments (ED) for end-of-life care with increasing frequency. Little is known about this experience for patients and ED clinicians in Australia. AIMS: To assess the barriers and enablers regarding end-of-life care for cancer patients as perceived by Australian ED clinicians. METHODS: There were 4501 Australian ED clinicians invited through their professional colleges to complete an online survey, using multiple-choice and free-text responses. RESULTS: A total of 681 ED clinicians responded, most (84.2%) felt comfortable providing care to the dying and found it to be rewarding (70.9%). Although 83.8% found caring for the dying a reasonable demand on their role as clinician, 83.8% also agreed that the ED is not the right place to die. Respondents demonstrated a wide range of views regarding caring for this patient group in ED through free-text responses. In addition, 64.5% reported that futile treatment is frequently provided in the ED; the main reasons reported were that limitations of care were not clearly documented, or discussed with the patient or their family. Almost all (94.6%) agreed that advance care plans assist in caring for dying patients in the ED. CONCLUSIONS: Our findings provide important new insights into a growing area of care for ED. Barriers and enablers to optimal care of the dying patient in ED were identified, and especially the reported high occurrence of futile care, likely a result of these barriers, is detrimental to both optimal patient care and allocation of valuable healthcare resources.

Ideal care and the realities of practice: interdisciplinary relationships in the management of advanced cancer patients in Australian emergency departments.

PURPOSE: Over the course of their illness, a person with cancer is likely to see a number of different healthcare professionals, including those in the emergency department (ED). There is limited research examining the interaction and communication between the involved healthcare professionals when such a patient presents to the ED. This study aimed to explore the views and experiences of interdisciplinary interactions of healthcare professionals caring for patients with advanced cancer who present to the ED. METHODS: Focus groups and semistructured interviews were conducted with clinical staff working in ED, oncology and community and hospital-based palliative care services. Interviews and focus groups were recorded and transcribed verbatim. Thematic analysis was undertaken by three researchers independently. These themes were then discussed by the wider team and consensus reached on themes and subthemes. RESULTS: Eighty-three healthcare professionals participated in focus groups, and 11 were interviewed. The over-arching theme to emerge was one of a conflict between ideal care and the realities of practice, particularly arising where clinicians from different services were required to work together to provide care. This idea was further understood through a series of subthemes including communication, decision-making and understanding of other services. CONCLUSIONS: Participants articulated agreed upon ideals of optimal care for advanced cancer patients across all three services, however there was frequently discord between these ideals and the actual care provided. Service demands and the day-to-day stressors of practice appeared to influence people's actions and engender conflict.

An armed oncolytic measles vaccine virus eliminates human hepatoma cells independently of apoptosis.

Due to late diagnosis and a pronounced chemoresistance, most patients with hepatocellular carcinoma (HCC) have an overall poor prognosis. Measles vaccine viruses (MeV) have been shown to possess anti-tumor properties and their efficacy has been enhanced by arming with suicide genes. To test armed MeV for the treatment of HCC, we equipped it with the suicide gene Super-cytosine deaminase (SCD) and tested the efficacy in cell culture and in a mouse xenograft model of human HCC. Prodrug conversion was investigated in cell culture and quantified by high-performance liquid chromatography. We observed a strong oncolytic activity of MeV-SCD against human HCC in vitro and in vivo. The prodrug was efficiently converted in infected cells leading to a significant enhancement of the cytotoxic effect. Treatment of HCC xenografts with MeV caused long-term virus replication in tumor tissue. We show that the suicide gene therapy induces an apoptosis-like cell death but is not dependent on intact apoptosis pathways. These results demonstrate that MeV-based suicide gene therapy is a promising novel therapy regimen for HCC overcoming resistance towards conventional therapy. The independence from apoptosis raises hopes for the treatment of patients whose tumor cells exert defects in this cell death mechanism.

Hospitalisation of high-care residents of aged care facilities: are goals of care discussed?

BACKGROUND: Residents of residential aged care facilities (RACF) are commonly hospitalised towards the end of life. Determining the hospitalisation experiences, including the discussion of goals of treatment, is essential to best plan care including planning for end-of-life care for this population. AIM: To document hospital presentation characteristics, course, outcomes and care planning for high-care residents of RACF. METHODS: A retrospective review of medical records was conducted for all high-care residents aged >64 years presenting to a metropolitan hospital over a 6-month period. RESULTS: One hundred and eighty-six high-care residents of RACF presented to hospital 228 times. Transfer paperwork documented resuscitation status for 49 (21%) presentations, and a medical enduring power of attorney or advanced care plan for 85 (37%). Patients had high rates of comorbidities (average Charlson comorbidity index score = 3), polypharmacy (93%), impaired mobility (89%), impaired cognition (81%) and incontinence (76%). Resuscitation status was documented in 50 (55%) and family discussion in 38 (42%) of 91 admissions exceeding 48 h. Documented family discussion was significantly associated with complications or new events occurring during admission (odds ratio 1.56, 95% confidence interval 1.07-2.26). CONCLUSION: There were low rates of documentation of resuscitation status or family discussion for this highly vulnerable population. Neither hospitals nor community providers appear to take responsibility for future care planning. Acute hospitals could play a greater role in care planning because discussion around course of illness and goals of treatment may enhance patient management, satisfaction and reduce hospitalisations.

Impact of the displacement current on low-frequency electromagnetic fields computed using high-resolution anatomy models.

We present a comparison of simulated low-frequency electromagnetic fields in the human body, calculated by means of the electro-quasistatic formulation. The geometrical data in these simulations were provided by an anatomically realistic, high-resolution human body model, while the dielectric properties of the various body tissues were modelled by the parametric Cole-Cole equation. The model was examined under two different excitation sources and various spatial resolutions in a frequency range from 10 Hz to 1 MHz. An analysis of the differences in the computed fields resulting from a neglect of the permittivity was carried out. On this basis, an estimation of the impact of the displacement current on the simulated low-frequency electromagnetic fields in the human body is obtained.

[Therapy of back pain: what is evidence-based?]. / Therapie des Rückenschmerzes: Was ist durch Studien belegt?

Back pain has to be classified by localisation, duration, and existence or absence of neurological deficits. Therapy mainly depends on the severity of neurological symptoms. The time period between the onset of symptoms and efficient therapy should be short in order to prevent the development of chronic pain. Therefore a sufficient, consistent and evidence-based conservative treatment should be initiated early on, with the only exception of special emergency situations as described further down in this article. Patients should not be immobilized, a better outcome is proven in patients who immediately continued practising their daily activities. First line medication consists of non-steroidal-anti-inflammatory-drugs (NSAID). If necessary, opioids and muscle-relaxants may be applied additionally. Surgical procedures are only indicated in a small number of patients. A sufficient data base with regard to the benefit of acupuncture, orthesis, and chiropractic medicine is lacking. Local injections should only be done in very special cases. Concerning chronic back pain a multimodal, multi-disciplinary pain treatment concept with physical training and behavioural therapy should be applied in order to teach the patient to avoid a passive and maladjusted attitude. Antidepressant drugs may also be indicated in chronic back pain.

Inflammatory pseudotumor of nerve.

Two cases of inflammatory pseudotumor are described. The first patient, a 35-year-old white man, developed a progressive sensorimotor deficit in the right leg associated with a fusiform sciatic nerve mass in the posterior thigh. The lesion, compressive in nature and situated entirely within the epineurium, was totally resected. Histology revealed lymphocytic and plasmacellular inflammation as well as extensive fibrosis and collagen deposition. The patchy infiltrate consisted equally of CD2, CD3, CD5, and CD7 positive T-lymphocytes as well as CD20-and CD22-positive B-lymphocytes expressing both kappa and lambda immunoglobulin light chains. A selective biopsy of the encompassed and compressed nerve fascicles demonstrated both myelin loss and axonal injury. The second case was that of an 18-year-old woman with focal enlargement of a radial nerve by an epineurial infiltrate of multinucleate histiocytes and T as well as occasional B lymphocytes. No etiology was apparent in either case. The differential diagnosis includes non-neoplastic processes (amyloidoma and tuberculoid leprosy) as well as tumors (benign and malignant peripheral nerve sheath tumors, lymphoma). Although rare, inflammatory pseudotumors must be included in the differential diagnosis of tumor-like lesions of peripheral nerve.

Particulate silicone for use in periurethral injections: local tissue effects and search for migration.

We examined the histologic behavior and migratory tendencies of a silicone-based injectable paste (Macroplastique) with potential application in treating urinary incontinence. Thirteen female dogs were studied. Six received 2 periurethral injections of large-particle paste, with a median diameter of 110 microns, and 7 received similar injections with small-particle paste (median diameter, 73 microns). The paste was radiolabeled with cobalt-57. Histologic analysis was performed at 4 or 9 months. The pathologic appearance revealed intact large-particle injection sites. The small-particle sites had dissipated significantly. This was confirmed by nuclear imaging. Large particles produced an encapsulated fibrous sheath without local migration. There was a histiocytic reaction within the injection site but no granuloma formation. Distant migration was observed in 1 dog (short term, large particle), without an inflammatory response. Migration of silicone occurred locally and distantly in animals that received small particles. X-ray microanalysis confirmed the presence of silicone particles.

The significance of atypia and histologic malignancy in pilocytic astrocytoma of the cerebellum: a clinicopathologic and flow cytometric study.

Biologically malignant pilocytic astrocytomas are rare. Precise morphologic criteria permitting their identification and clinically meaningful distinction from more ordinary pilocytic astrocytomas have not been developed. The histologic grading schemes applied to fibrillary astrocytomas--ones based on nuclear atypia, increased cellularity, mitotic activity, endothelial proliferation, and necrosis--are thought not to correlate with prognosis in pilocytic astrocytomas. Nonetheless, these features were systematically sought in 107 cerebellar pilocytic astrocytomas, four of which were histologically malignant. The clinical, morphologic, and flow cytometric features of these cases were studied. The incidence of histologic malignancy occurring spontaneously in otherwise typical pilocytic astrocytomas was 0.9%; that occurring after radiation was 1.8%. The four histologically malignant tumors occurred in two males and two females, ages 6 to 18 years. All showed increased mitotic activity (three to five mitoses per high-power microscopic field [250x]). Endothelial proliferation and necrosis were present in three and two cases each. DNA ploidy analysis showed the spontaneously occurring malignant-appearing tumors to be aneuploid, whereas both previously radiated tumors were tetraploid; 5% to 11% of cells were in S phase. The appearance of histologic malignancy in pilocytic astrocytoma is rare and less reliably correlated with prognosis than in patients with fibrillary astrocytomas. Essential features of such tumors include a high mitotic index and perhaps a high percentage of cells in S phase.

Astrocytomas of the cerebellum. A comparative clinicopathologic study of pilocytic and diffuse astrocytomas.

BACKGROUND: The majority of patients with astrocytomas of the cerebellum have an excellent prognosis; however, a small percentage of patients continue to do poorly. To clarify the clinical, pathologic, and treatment characteristics that determine prognosis and therapeutic recommendations, a large group of patients with astrocytic tumors of the cerebellum was reviewed and analyzed. METHODS: A clinicopathologic analysis was performed of all patients undergoing initial operation for astrocytomas in the cerebellum between 1960 and 1984. Of the 132 patients, 105 patients had pilocytic astrocytomas and 27 had diffuse astrocytomas. RESULTS: Multivariate analysis revealed that the division of pilocytic and diffuse histologic type was the most significant prognostic factor influencing survival. The 5-year, 10-year, and 20-year survival rates were 85%, 81%, and 79%, respectively, for patients with pilocytic astrocytomas and 7%, 7%, and 7%, respectively, for patients with diffuse astrocytomas (P < 0.001). Pilocytic astrocytomas occurred in a younger age group and were more commonly cystic and completely resected. CONCLUSIONS: Astrocytomas of the cerebellum can be divided into two principal groups, the pilocytic and the diffuse astrocytomas, each of which has distinct clinical, pathologic, and prognostic characteristics.

[Prevalence of Borrelia burgdorferi antibodies in Hamburg blood donors]. / Prävalenz von Borrelia-burgdorferi-Antikörpern bei Hamburger Blutspendern.

One thousand regular blood donors of the Department of Transfusion Medicine at the University Hospital in Hamburg were screened for antibodies against the Lyme disease spirochete, B. burgdorferi. 7.2% were initially reactive in the enzyme immunoassay, 37.5% of which were confirmed by immunoblot. The seroprevalence of anti-B. burgdorferi antibodies thus is 2.7% in Hamburg blood donors. 25 of 27 positive donors received a physical exam, which did not reveal any symptoms of acute or chronic Lyme disease. 24 of these 25 donors were tested for B. burgdorferi-specific DNA in urine by polymerase chain reaction, which came out negative in all cases. Introduction of B. burgdorferi antibody screening is not regarded an effective means to prevent transfusion-transmitted Lyme disease.

Comparison of Dacron-tipped applicator and cytobrush for detection of chlamydial infections.

Endocervical samples were obtained from 435 females for Chlamydia detection by using both a Dacron swab and a cytobrush. Positive results were obtained from 35 swabs and 34 cytobrush specimens. All specimens positive with the cytobrush were detected also with swab samples. The cytobrush and Dacron swab appear to be comparable for the detection of endocervical infections with Chlamydia trachomatis.