Unraveling the Myth of Radiation Resistance in Soft Tissue Sarcomas.

There is a misconception that sarcomas are resistant to radiotherapy. This manuscript summarizes available (pre-) clinical data on the radiosensitivity of soft tissue sarcomas. Currently, clinical practice guidelines suggest irradiating sarcomas in 1.8-2 Gy once daily fractions. Careful observation of myxoid liposarcomas patients during preoperative radiotherapy led to the discovery of this subtype's remarkable radiosensitivity. It resulted subsequently in an international prospective clinical trial demonstrating the safety of a reduced total dose, yet still delivered with conventional 1.8-2 Gy fractions. In several areas of oncology, especially for tumors of epithelial origin where radiotherapy plays a curative role, the concurrent application of systemic compounds aiming for radiosensitization has been incorporated into routine clinical practice. This approach has also been investigated in sarcomas and is summarized in this manuscript. Observing relatively low α/ß ratios after preclinical cellular investigations, investigators have explored hypofractionation with daily doses ranging from 2.85-8.0 Gy per day in prospective clinical studies, and the data are presented. Finally, we summarize work with mouse models and genomic investigations to predict observed responses to radiotherapy in sarcoma patients. Taken together, these data indicate that sarcomas are not resistant to radiation therapy.

Assessment of Serum Homocysteine Level to Predict Early Prognosis of Ischaemic Stroke.

Cerebrovascular disease is the third most familiar cause of mortality worldwide and in Bangladesh. The reported prevalence of stroke in Bangladesh is 0.3%. Age, high serum glucose, elevated admission blood pressure, fever, large infarction size, and hyperhomocysteinemia has been reported to be risk factor for early post-stroke neurological deterioration. Early serum homocysteine level estimation can predict the early prognosis of ischemic stroke. In a developing country like Bangladesh, an earlier stroke outcome prediction for guiding therapeutic approach is essential. This study aimed to specify the role of estimating serum homocysteine during the early phase of acute ischemic stroke to assume an early prognosis that would guide- a management plan, the need to stay in the hospital and the need for intervention. This cross-sectional descriptive study was performed at the Department of Medicine, Mymensingh Medical College Hospital, Bangladesh from October 2021 to April 2022. Radiologically confirmed all ischemic stroke patients admitted at the Department of Medicine, Mymensingh Medical College Hospital, during the study period fulfilling the inclusion and exclusion criteria were included in this study. Non-probability purposive sampling technique was used. Data was collected using a pre-designed case record form. Quantitative data were represented as mean and standard deviation and qualitative data as frequency and percentage. The comparison was made by Chi-square test and independent samples t-test using SPSS (version 26.0). During the study period, among 716 stroke patients, 59 ischemic stroke patients were included in this study. The mean age of the patients was 64.0±11.72 years. After 72 hours of supportive treatment, early neurological outcomes were observed using NIHSS scoring. Out of 59 patients, the condition of 45(76.0%) patients improved or remained stable (END-) and the state of 14(24.0%) patients worsened (END+). Elderly age-raised temperature and elevated blood glucose level are known to increase infarction size, but only elevated temperature (p value 0.009) has statistical significance in this study. The mean homocysteine level ±SD was 20.22±6.95µmol/L, which is above the normal (<15µmol/L). The level was above average for both outcome groups. Serum homocysteine level was significantly higher in END(+) group (31.59±2.98µmol/L) than END(-) group (16.69±2.66µmol/L) and p value was <0.001.

A Case Report of an Unusual Cause of Dysphagia from Enlarged Subcarinal Lymph Node.

Cough, hemoptysis, chest pain, and weight loss are classic symptoms of bronchial carcinoma. Small cell lung cancer presents late with obviously abnormal chest radiographs and with bulky, usually mediastinal lymph node involvement. Dysphagia rarely occurs in patients with bronchial carcinoma. There are many causes of dysphagia in bronchial carcinoma such as mediastinal lymphadenopathy, direct tumor invasion of the mediastinum, radiotherapy, secondary achalasia. This report presents a case of progressive dysphagia to solid foods and weight loss of a 28-year-old male, non-smoker due to subcarinal lymph node enlargement from metastatic bronchial adenocarcinoma.

OX40 and 4-1BB delineate distinct immune profiles in sarcoma.

Systemic relapse after radiotherapy and surgery is the major cause of disease-related mortality in sarcoma patients. Combining radiotherapy and immunotherapy is under investigation as a means to improve response rates. However, the immune contexture of sarcoma is understudied. Here, we use a retrospective cohort of sarcoma patients, treated with neoadjuvant radiotherapy, and TCGA data. We explore therapeutic targets of relevance to sarcoma, using genomics and multispectral immunohistochemistry to provide insights into the tumor immune microenvironment across sarcoma subtypes. Differential gene expression between radioresponsive myxoid liposarcoma (MLPS) and more radioresistant undifferentiated pleomorphic sarcoma (UPS) indicated UPS contained higher transcript levels of a number of immunotherapy targets (CD73/NT5E, CD39/ENTPD1, CD25/IL2RA, and 4-1BB/TNFRSF9). We focused on 4-1BB/TNFRSF9 and other costimulatory molecules. In TCGA data, 4-1BB correlated to an inflamed and exhausted phenotype. OX40/TNFRSF4 and 4-1BB/TNFRSF9 were highly expressed in sarcoma subtypes versus other cancers. Despite OX40 and 4-1BB being described as Treg markers, we identified that they delineate distinct tumor immune profiles. This was true for sarcoma and other cancers. While only a limited number of samples could be analyzed, spatial analysis of OX40 expression identified two diverse phenotypes of OX40+ Tregs, one associated with and one independent of tertiary lymphoid structures (TLSs). Patient stratification is of intense interest for immunotherapies. We provide data supporting the viewpoint that a cohort of sarcoma patients, appropriately selected, are promising candidates for immunotherapies. Spatial profiling of OX40+ Tregs, in relation to TLSs, could be an additional metric to improve future patient stratification.

Physician's Perception about the Use of PPE, COVID-19 Prevention and Management in Bangladesh.

This study aims to explore physician's perceptions about the use of Personal Protective Equipment (PPE), COVID prevention, and management during the COVID pandemic since knowledge on these might explain the reason behind infection and death of physicians in Bangladesh at an unexpected rate. This cross-sectional study was conducted based on an online questionnaire on 346 physicians (n=346) by the Department of Gastroenterology of Mymensingh Medical College Hospital, Bangladesh from 15th July 2020 to 14th September 2020. Physicians of different health care facilities across Bangladesh were invited to take part. Knowledge on specific points of the questionnaire was evaluated, scored, and compared between different groups by Independent sample t-test. Mean knowledge score between the respondents working up to 8 hours and beyond 8 hours per day was 17.28±1.28, 16.90±1.40 respectively (p=0.03). Mean knowledge score observed between graduate and post-graduate physicians and work experience of 5 years and beyond 5 years were 17.26±1.36 vs. 17.16±1.27; (p=0.40), 16.87±1.75 vs. 17.27±1.21; (p=0.11) respectively. Physician's safety should be first concern that is highlighted through proper use of PPE and prevention of COVID. Patient management skills would be better if physicians are trained well on infection prevention and control which in turn will reduce infection and death of physicians.

Hybrid Piezo/Magnetic Electromechanical Transformer.

This paper presents a hybrid electromechanical transformer that passively transfers electrical power between galvanically isolated ports by coupling electrodynamic and piezoelectric transducers. The use of these two complementary electromechanical transduction methods along with a high-Q mechanical resonance affords very large transformations of voltage, current, or impedance at particular electrical frequencies. A chip-size prototype is designed, simulated, fabricated, and experimentally characterized. The 7.6 mm × 7.6 mm × 1.65 mm device achieves an open-circuit voltage gain of 31.4 and 48.7 when operating as a step-up transformer at 729.5 Hz and 1015 Hz resonance frequencies, respectively. When operating as a step-down transformer, the resonance frequencies and the corresponding voltage gains are 728 Hz, 1002 Hz, and 0.0097, 0.0128, respectively. In one operational mode, the system shows a minimum power dissipation of only 0.9 µW corresponding to a power conversion efficiency of 11.8%.

Priorities and preferences of advanced soft tissue sarcoma patients starting palliative chemotherapy: baseline results from the HOLISTIC study.

INTRODUCTION: Palliative chemotherapy is the principal treatment of patients with advanced soft tissue sarcomas (STS); however prognosis is limited (median overall survival 12-19 months). In this setting, patient values and priorities are central to personalised treatment decisions. PATIENTS AND METHODS: The prospective HOLISTIC study was conducted in the UK and the Netherlands assessing health-related quality of life in STS patients receiving palliative chemotherapy. Participants completed a questionnaire before starting chemotherapy, including attitudes towards quality of life (QoL) versus length of life (LoL), decisional control preferences, and decisional conflict. Chi-square and Fisher's exact tests were used to evaluate associations between patient characteristics and preferences. RESULTS: One hundred and thirty-seven patients with advanced STS participated (UK: n = 72, the Netherlands: n = 65). Median age was 62 (27-79) years. Preference for extended LoL (n = 66, 48%) was slightly more common than preference for QoL (n = 56, 41%); 12 patients (9%) valued LoL and QoL equally (missing: n = 3). Younger patients (age <40 years) prioritised LoL, whereas two-thirds of older patients (aged ≥65 years) felt that QoL was equally or more important than LoL (P = 0.020). Decisional conflict was most common in patients who prioritised QoL (P = 0.024). Most patients preferred an active (n = 45, 33%) or collaborative (n = 59, 44%) role in treatment decisions. Gender, performance status, and country were significantly associated with preferred role. Concordance between preferred and actual role in chemotherapy decision was high (n = 104, 76%). CONCLUSIONS: Heterogeneous priorities and preferences among advanced STS patients support personalised decisions about palliative treatment. Considering individual differences during treatment discussions may enhance communication and optimise patient-centred care.

Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts.

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.

Prolonged Jaundice in a Patient with Coexisting Hepatitis A Virus Infection and Wilson's Disease.

Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis in the world. Infection with hepatitis A virus can cause severe or even fatal illness in patients with chronic liver disease. Here we present a case which seems to be an isolated acute viral hepatitis A infection at the beginning but later found to be coexisted with Wilson's disease. A 14-year-old girl presented in the Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh on 11th April 2019 with progressive jaundice with prodrome, dark urine, itching, hepatomegaly and thyromegaly. She was found positive for serum IgM HAV antibody. Her jaundice was increasing along with prolonged prothrombin time and low albumin. She had coexisting Wilson's disease evidenced by increased 24 hours urinary copper (138µgm/day). She was treated with D-Penicillamine and Zinc acetate. Hepatitis A can be considered as a factor for acute decompensation in undiagnosed patients with Wilson's disease. So it is very crucial to investigate Wilson's disease in appropriate clinical setting of prolonged jaundice and liver dysfunction.

Embryonal and Alveolar Rhabdomyosarcoma in Adults: Real-Life Data From a Tertiary Sarcoma Centre.

AIMS: Embryonal and alveolar rhabdomyosarcoma (ERMS, ARMS) are subtypes of RMS that mainly occur in children, with relatively good outcomes. The incidence in adults is extremely low and survival is significantly worse compared with children. Data are scarce and literature generally combines all RMS subtypes, including pleomorphic RMS, which primarily occurs in adults and behaves more like undifferentiated pleomorphic sarcoma. The aim of this study was to evaluate patient and tumour characteristics, outcome and prognostic factors in adult patients with ERMS and ARMS. MATERIALS AND METHODS: All adult (18 years or older) ERMS and ARMS patients (presenting 1990-2016) were identified from a prospectively maintained database and were included in this analysis. RESULTS: Overall, 66 patients were included (42 men, 24 women). The median age at presentation was 28 years (range 18-71). The median overall survival for all ARMS (n = 42) and ERMS (n = 24) patients was 18 months, with a 5-year overall survival rate of 27%. Patients presenting with localised disease (n = 38, 58%) and metastatic disease (n = 25, 42%), had a 5-year overall survival rate of 36% and 11%, respectively. In univariate analysis we found alveolar subtype, fusion gene positivity, infiltrative tumour and metastatic presentation to be negative prognostic factors. CONCLUSION: Survival in adult ERMS and ARMS patients is poor and the current data may be useful in the design of trials with novel agents. Ideally, paediatric and adult oncologists should set up trials together to get a better understanding of biological, genetic and clinically relevant factors in this disease.

Evaluation of Duodenal Eosinophil Count in Adult Patients with Functional Dyspepsia.

Several mechanisms have been proposed to explain the symptoms of functional dyspepsia but actual pathogenesis is still poorly understood. Recent studies support duodenal abnormality to be the most important causal link to explain symptoms and to understand abnormal pathophysiology of functional dyspepsia. The aim of this prospective observational study is to compare eosinophil count in duodenal mucosa between patients with functional dyspepsia and control subjects without dyspepsia and was done at the department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from December 2015 to December 2016. Total 42 patients of functional dyspepsia based on Bangla validated version of ROME III criteria and 42 controls who were referred for upper gastrointestinal endoscopy for reasons other than dyspepsia were included. Biopsy specimens were collected from the second part (D2) of the duodenum of all participants. Eosinophil count was quantitatively evaluated by hematoxylin and eosin staining and expressed in numbers per 5 HPF. Significantly increased duodenal eosinophil count was found in functional dyspepsia group than non dyspeptic patients (22.78±08.78 vs. 14.90±10.70, p=0.001). Higher duodenal eosinophil count was found in patients with postprandial distress syndrome. Increased duodenal eosinophil count was found in patient of functional dyspepsia. It requires further large scale multicenter studies to establish duodenal eosinophilia as a biomarker of functional dyspepsia.

Study of the Prevalence of Dyspepsia in the Adult Population in a Rural Community of Bangladesh.

Dyspepsia is a symptom complex that includes epigastric pain, post-prandial fullness, bloating, early satiety, belching, nausea, vomiting, heartburn, acid regurgitations and anorexia. The most widely applied definition of dyspepsia is the Rome working team formulation namely chronic or recurrent pain or discomfort centered in the upper abdomen. Till date the prevalence of dyspepsia in Bangladesh has not been studied much. The last study was done in 1987 in a rural community and the prevalence of dyspepsia was found to be 41.4%. However, associated risk factors were not assessed and definition of dyspepsia was much narrower as well as the dysmotility type dyspepsia was not included in that study. Hence it is now high time to carry out another study to see the prevalence of dyspepsia in Bangladesh and the risk factors associated with it. To determine the prevalence of dyspepsia and the demographic risk factors associated with dyspepsia in the adult population in the rural community of Bangladesh. This cross sectional population based study carried out in Ghior Union of Manikgonj district of Bangladesh from January 2007 to April 2008. All persons 18 years or above living in Ghior Union were considered as the study populations with using a pre-designed questionnaire. This study showed that the prevalence of dyspepsia to be 61.9%. Reflux- like dyspepsia was the commonest sub-type of dyspepsia without reflux symptoms comprising 43.9% of the total population and 70.9% of the dyspeptics. Dysmotility like dyspepsia comprised more than half of the dyspeptics. Nausea (40.7%) was the most predominant dysmotility like dyspeptic symptoms followed by early satiety (38.4%); 13.9% of the population had history of recurrent upper abdominal pain and 11.9% of the population had gastro-esophageal reflux disease (GERD). There was considerable overlapping (16.7%) of IBS with dyspepsia. Female sex, younger age (<40 years), low family income (<5000 Taka per month), lower educational level (up to primary level), smoking and use of NSAIDs were significantly associated with dyspepsia. The prevalence of dyspepsia in adult population of Bangladesh is 61.9% which is very high compared to other countries and also much higher than the prevalence found in our country thirty years back. A great change in the socio-economic status and lifestyle of the people along with environmental pollution and food adulteration may be responsible for this increase in prevalence. This study was conducted in only one union of this country, so it was not representative of the whole population of the country. Therefore further study with large population size including rural and urban peoples from different parts of Bangladesh is needed to estimate the accurate prevalence of dyspepsia in our country.

Evaluation of Knowledge Regarding Oral Anti-diabetic Agents among Hospitalized Diabetic Patients.

Knowledge regarding oral anti-diabetic agents help to enhance compliance among diabetic patients. Though it is an important aspect of management, data evaluating it is scarce in our country. This cross sectional observational study carried out in the Department of Medicine, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from September 2013 to February 2014 and was undertaken to determine basic knowledge about oral anti-diabetic agents among hospitalized diabetic patients taking or took oral anti-diabetic agents. In this study main outcome measures were socio-demographic characteristics, knowledge regarding oral anti-diabetic agents, frequency of previous hospital admission, regularity in taking oral anti-diabetic agents, causes of irregularity in taking medicine and knowledge related to hypoglycemia. Mean±SD age was 55±7.14 years, of the patients who were included in this study. Only 33% of patients knew side effects of oral anti-diabetic agents, 34% didn't know that drug should not be stopped before giving blood for glucose estimation, in answering to 9 basic question related to oral anti-diabetic agents 56% obtained score within 0-5, overall mean 5.2±1.47. Among them 38% used to take drug irregularly. Correlation with knowledge score and regularity in taking drug showed significant relation (p<0.01). This study has demonstrated unsatisfactory knowledge on oral anti-diabetic agents among type 2 diabetic patients and significant relation with knowledge on oral anti-diabetic agents and patients compliance. An improvement with this respect may be achieved through continuing patients education about diabetes and its treatment.

Aggressive fibromatosis response to tamoxifen: lack of correlation between MRI and symptomatic response.

BACKGROUND: One of the commonly used systemic agents for the treatment of aggressive fibromatosis is the anti-oestrogen drug tamoxifen. However, data on efficacy and optimum methods of response assessment are limited, consisting mainly of small case series and reports. METHODS: A retrospective database was used to identify consecutive patients diagnosed with aggressive fibromatosis (AF) and treated with tamoxifen plus/minus non-steroidal anti-inflammatory drugs at our tertiary referral centre between 2007 and 2014. MRI and symptom changes were recorded. RESULTS: Thirty-two patients (13 male 19 female, median age 41 years) were included. Median duration of treatment with tamoxifen was 316 days. Of 9 patients with progressive disease by RECIST 1.1 (28%): 4 patients experienced worsening symptoms; 3 patients had improved symptoms and 2 had no change in symptoms. Of 22 patients with stable disease (69%): 11 had no change in symptoms; 6 had improved symptoms and 5 patients had worsening symptoms. One patient achieved a partial response with improved symptoms. CONCLUSIONS: No relationship was identified between symptomatic benefit and response by RECIST 1.1 on MRI. Prospective studies in AF should incorporate endpoints focusing on patient symptoms.

Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study.

Since the publication of this paper, the authors noticed an error in Fig. 1. The X-axis on all the figure panels should read 'Time (years)', not 'Time (months)'. The corrected Fig. 1 is shown below.

Intensity modulated radiotherapy in locally advanced thyroid cancer: Outcomes of a sequential phase I dose-escalation study.

BACKGROUND AND PURPOSE: To determine the safety and tolerability of dose-escalation using modestly accelerated IMRT in high-risk locally advanced thyroid cancer requiring post-operative radiotherapy, and to report preliminary data on efficacy. MATERIALS AND METHODS: A sequential Phase I dose-escalation design was used. Dose level one (DL1) received 58.8 Gy/28F to the post-operative bed and 50 Gy/28F to elective nodes. DL2 received 66.6 Gy/30F to the thyroid bed, 60 Gy/30F to post-operative nodal levels and 54 Gy/30F to elective nodal levels. Acute (NCICTCv.2.0) and late toxicities (RTOG and modified LENTSOM) were recorded. The primary endpoint was the number of patients with ≥Grade 3 (G3) toxicity at 12 months post-treatment. RESULTS: Fifteen patients were recruited to DL1 and twenty-nine to DL2. At 12 months ≥G3 toxicities were 8.3% in both DL1 and DL2. At 60 months, ≥G3 toxicity was reported in 3 (33%) patients in DL1 and 1 (7%) in DL2. One patient in DL2 died at 24 months from radiation-induced toxicity. Time to relapse and overall survival rates were higher in DL2, but this was not statistically significant. Dose-escalation using this accelerated regimen can be safely performed with a toxicity profile similar to reported series using conventional doses.

A new look at the supposed risks of early institutional rearing.

The main focus is on the assessment of the effects of early institutional care and compares three longitudinal studies from Romania, Greece and Hong Kong/China. The findings have been strikingly contrasting. The review asks if the risks are dependent on whether or not the institutional rearing is accompanied by gross pervasive deprivation (as it was in Romania) and investigates the methodological issues to explore the causal influence of the outcomes. Evidence is considered on changing institutional practices and the benefits of doing so. Comparison is made between institutions with major deprivation and those without global deprivation. A small number of studies are discussed that look at direct comparisons between institutional and community care. The empirical and conceptual implications of the findings are discussed.

Radiation induced angiosarcoma of the breast: outcomes from a retrospective case series.

BACKGROUND: Radiation induced angiosarcoma (RIAS) of the breast is a rare and aggressive complication of radiotherapy. Due to the rarity of this disease, much of the evidence for its management is based on case reports or small retrospective series. We sought to describe the management and outcomes of RIAS in a large single-institution series. METHODS: All patients diagnosed with RIAS between January 2000 and January 2014 were identified from an institutional database. RESULTS: A total of 49 patients were identified. Median age at diagnosis was 72 years (range 51-93). Median time from completion of radiotherapy to diagnosis of RIAS was 7.5 years. Median tumour size at presentation was 5.0 cm (1.5-19.0). The majority of patients presented with localised disease (47, 95.9%). Of these, 35 (74.5%) were suitable for surgery and underwent surgery with curative intent. Twelve patients presented with localised irresectable disease. Of these, 7 received systemic chemotherapy, with a sufficient response to facilitate surgery in 3 patients. Following potentially curative surgery, 2-year local recurrence-free was 55.2%. Survival was significantly prolonged in patients presenting with resectable disease (2-year overall survival 71.1% vs 33.3%, p < 0.001). Tumour size >5 cm was prognostic of distant metastases-free survival and overall survival. CONCLUSION: RIAS are rare, aggressive soft-tissue lesions with limited treatment options and high-rates of both local and systemic relapse.