Peri-operative, oncological and functional outcomes of robotic versus transanal total mesorectal excision in patients with rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Comparative outcomes of robotic low anterior resection (rTME) and trans-anal total mesorectal excision (TaTME) in patients with low rectal cancer were evaluated. METHODS: A systematic online search was conducted using the following databases: PubMed, Scopus, Cochrane database, The Virtual Health Library, Clinical trials.gov and Science Direct. Comparative studies of rTME versus TaTME for low rectal cancer were included. Primary outcomes were postoperative complications, including anastomotic leak, surgical site infection, and Clavien-Dindo complication rate. Total operative time, conversion to open surgery, intra-operative blood loss, intensive therapy unit (ITU) and total hospital length of stay (LOS), oncological outcomes and functional outcomes were the other evaluated outcome parameters. RESULTS: A total of 12 studies with a total number of 3025 patients divided between rTME (n = 1881) and TaTME (n = 1144) groups were included. There was no significant difference between the two groups for total operative time (P = 0.39), conversion to open surgery (P = 0.29) and intra-operative blood loss (P = 0.62). Clavien-Dindo ≥ 3 complication rate (P = 0.47), anastomotic leak (P = 0.89), rates of re-operation (P = 0.62) and re-admission (P = 0.92), R0 resections (P = 0.52), ITU LOS (P = 0.63) and total hospital LOS (P = 0.30) also showed similar results between the two groups. However, the rTME group had higher rates of total harvested lymph nodes (P = 0.04) and complete total mesorectal excision (TME) resections (P = 0.05). Albeit with a limited dataset, the Wexner and low anterior resection syndrome (LARS) scores showed better functional results in the rTME group compared with the TaTME group (P = 0.0009 and P = 0.00001, respectively). CONCLUSION: Compared with TaTME, rTME seems to provide better functional outcomes, higher lymph node yield and more complete TME resections with a similar post-operative complications profile.

Clinico-epidemiological Characteristics of the Physician Affected with Covid-19.

Coronavirus disease 2019 (Covid-19) disease have been associated with significant mortality amongst doctors globally including Bangladesh. To delineate the clinico-epidemiological characteristics of the physician affected with Covid-19 was the objective of the study. This cross-sectional 'Facebook' based survey was conducted in the period of August 2020 to September 2020. Snowball sampling methods was followed. A total of 151 physicians affected with Covid-19 participated in this survey. Self-reported perceived severity scale (zero meaning not severe at all and ten denoting the most severe) was used. Collected data were analyzed by SPSS 25.0. Among the participants, the majority were male, 98(64.9%). The most prevalent affected age groups were 24-35 years 131(86.8%). Approximately 45.0% worked in COVID dedicated hospital. Entry-level physicians (Medical Officer or Assistant Surgeon) were the most affected 117(94.4%). One-third of the physicians had at least the one co-morbidity. Bronchial asthma, obesity and diabetes were the most frequent. Predominate symptoms of the infection were fever 94(62.3%), cough 94(62.3%) and myalgia 92(60.9%). Half of the participants had sore throat, anosmia, gastro-intestinal symptoms and one-third of the patients developed dyspnea. Perceived severity of the symptoms ranged between 2 and 6. The pattern of drug use to prevent the Covid-19 showed no uniformity. However, intake of Zinc, Vitamin C, Vitamin D, antihistamine and Ivermectin was found in 74.8%, 67.5%, 41.7%, 49.0% and 37.7% respectively. As the current pandemic continues to evolve, physicians must be equipped with appropriate knowledge, skills and must be cautious on the prevention measures against Covid-19.

Exploring Importance and Regulation of Autophagy in Cancer Stem Cells and Stem Cell-Based Therapies.

Autophagy is a globally conserved cellular activity that plays a critical role in maintaining cellular homeostasis through the breakdown and recycling of cellular constituents. In recent years, there has been much emphasis given to its complex role in cancer stem cells (CSCs) and stem cell treatment. This study examines the molecular processes that support autophagy and how it is regulated in the context of CSCs and stem cell treatment. Although autophagy plays a dual role in the management of CSCs, affecting their removal as well as their maintenance, the intricate interaction between the several signaling channels that control cellular survival and death as part of the molecular mechanism of autophagy has not been well elucidated. Given that CSCs have a role in the development, progression, and resistance to treatment of tumors, it is imperative to comprehend their biological activities. CSCs are important for cancer biology because they also show a tissue regeneration model that helps with organoid regeneration. In other words, the manipulation of autophagy is a viable therapeutic approach in the treatment of cancer and stem cell therapy. Both synthetic and natural substances that target autophagy pathways have demonstrated promise in improving stem cell-based therapies and eliminating CSCs. Nevertheless, there are difficulties associated with the limitations of autophagy in CSC regulation, including resistance mechanisms and off-target effects. Thus, the regulation of autophagy offers a versatile strategy for focusing on CSCs and enhancing the results of stem cell therapy. Therefore, understanding the complex interactions between autophagy and CSC biology would be essential for creating therapeutic treatments that work in both regenerative medicine and cancer treatment.

Interplay of interleukins (IL6, IL10) and 25 hydroxycholecalciferol in asthmatic subjects with chronic post-COVID condition (PCC).

The study aimed to compare and correlate serum levels of IL-6, 10, and 25-hydroxycholecalciferol in individuals with asthma with and without post-COVID condition (PCC). The study was designed to investigate the inflammatory response and serum 25-hydroxycholecalciferol status in asthmatics with and without PCC. A cross-sectional study of 252 subjects (128 asthmatics and 124 non-asthmatic subjects) was carried out. Interleukins and 25-hydroxycholecalciferol levels were estimated on ELISA. The principle findings were that IL-6 and 25-hydroxycholecalciferol levels were significantly increased (p<0.001), while IL-10 levels were non-significant in asthmatics with PCC compared to those without PCC. However, 25-hydroxycholecalciferol levels were significantly increased, but no significant change was observed in IL-6, and IL-10 levels in non-asthmatics with and without chronic PCC. A significant positive correlation (r = 0.258) was found between 25-hydroxycholecalciferol and IL-6 but a significant negative correlation (r = -0.227) with IL-10 in asthmatics with PCC. Similarly, a significant negative correlation (r = -0.285) was found between 25-hydroxycholecalciferol and IL-10 but was non-significant with IL-6 in asthmatics without PCC. The correlation of 25-hydroxycholecalciferol with IL-10 was significant (0.683), but IL-6 was non-significant in non-asthmatics with PCC. Multiple regression analysis showed that age, IL-6, gender, and PCC were significantly related in adjusted values to 25-hydroxycholecalciferol. This study sheds light on the complex liaison between 25-hydroxycholecalciferol levels and inflammatory responses in asthmatics, especially those with PCC. The findings suggest that although asthmatics with PCC maintain sufficient levels of 25-hydroxycholecalciferol, they show a substantial increase in the proinflammatory response. This suggests that PCC exacerbates the pro-inflammatory response in asthma. Moreover, the study reveals that asthmatics, whether with or without PCC, display a negative correlation between 25-hydroxycholecalciferol and the anti-inflammatory response. This emphasizes the main influence of asthma on the overall inflammatory response. These findings reveal a complex interplay between vitamin D levels and inflammatory mediators in asthmatic individuals with and without PCC.

Nasopharyngeal malignant melanoma masquerading in the gallbladder: the importance of histological assessment.

Metastatic melanoma of the gallbladder is a rare entity that is often diagnosed late, leading to a poor prognosis. The disease may present insidiously as acute cholecystitis or remain asymptomatic. Optimal management remains unclear but surgical resection is considered the mainstay of treatment for this condition. We report the case of a 47-year-old man who suffered a protracted course of generalised abdominal symptoms eventually culminating in a diagnosis of acute cholecystitis. Following an emergency laparoscopic cholecystectomy, the histology revealed a melanoma with an unknown primary. Subsequently this was traced to the nasopharynx. Because of the presence of concurrent liver metastasis, systemic immunotherapy with palliative intent was commenced following a multidisciplinary team discussion. This case highlights the importance of sending clinical specimens for histological analysis. We argue against selectively choosing which specimens to send for histology because radiological and/or intraoperative macroscopic inspection of resected tissue alone can result in a missed diagnosis.

Should routine surgical wound drainage after ventral hernia repair be avoided? A systematic review and meta-analysis.

AIMS: To evaluate outcomes of drain use vs. no-drain use during ventral hernia repair. METHODS: A PRISMA-compliant systematic review was conducted using the following databases: PubMed, Scopus, Cochrane database, The Virtual Health Library, Clinical trials.gov and Science Direct. Studies comparing use of drains with no-drain during ventral hernia repair (primary or incisional) were included. Wound-related complications, operative time, need for mesh removal and early recurrence were the evaluated outcome parameters. RESULTS: Eight studies reporting a total number of two thousand four hundred and sixty-eight patients (drain group = 1214; no-drain group = 1254) were included. The drain group had a significantly higher rate of surgical site infections (SSI) and longer operative time compared with the no-drain group [odds ratio (OR): 1.63, P = 0.01] and [mean difference (MD): 57.30, P = 0.007], respectively. Overall wound-related complications [OR: 0.95, P = 0.88], seroma formation [OR: 0.66, P = 0.24], haematoma occurrence [OR: 0.78, P = 0.61], mesh removal [OR: 1.32, P = 0.74] and early hernia recurrence [OR: 1.10, P = 0.94] did not differ significantly between the two groups. CONCLUSION: The available evidence does not seem to support the routine use of surgical drains during primary or incisional ventral hernia repairs. They are associated with increased rates of SSIs and longer total operative time with no significant advantage in terms of wound-related complications.

Knowledge, attitude and practices regarding dengue and its vector among medical practitioners in Malakand region, Pakistan

Abstract Dengue fever (DF) is increasingly recognized as one of the worlds major mosquito borne diseases and causes significant morbidity and mortality in tropical and subtropical countries. Dengue fever is endemic in most part of Pakistan and continues to be a public health concern. Knowledge, attitude and practices can play an important role in management of the disease. Current study was aimed to determine the level of knowledge, attitude and practices regarding dengue fever among health practitioners, to study the level of knowledge and attitude with preventive practices for dengue fever. A cross sectional study was carried out in medical practitioners of the four districts of Malakand region during October to November 2019. A pre-structured questionnaire was used to collect data from medical practitioners. Data was analyzed using Graph Pad version 5. Significant value was considered when less than 0.05 (at 95% confidence of interval). The results revealed that most of participants have seen dengue vector (62%), the media being the most quoted source of information. Nearly 81.2% participants were aware from transmission of dengue fever is by mosquito bite. Practices based upon preventive measures were found to be predominantly focused towards prevention of mosquito bites rather than elimination of breeding places. Although the knowledge regarding DF and mosquito control measure was quite high among the medical practitioners but this knowledge was not put into practice. Further studies are required to aware the people about dengue and its vector in order to get prevention and control.

Resumo A dengue (DF) é cada vez mais reconhecida como uma das principais doenças transmitidas por mosquitos do mundo e causa significativa morbidade e mortalidade em países tropicais e subtropicais. A dengue é endêmica na maior parte do Paquistão e continua a ser um problema de saúde pública. Conhecimento, atitude e práticas podem desempenhar papel importante no manejo da doença. O presente estudo teve como objetivo determinar o nível de conhecimento, atitude e práticas em relação à dengue entre os profissionais de saúde, para estudar o nível de conhecimento e atitude com as práticas preventivas da dengue. Um estudo transversal foi realizado com médicos dos quatro distritos da região de Malakand de outubro a novembro de 2019. Um questionário pré-estruturado foi usado para coletar dados de médicos. Os dados foram analisados no Graph Pad versão 5. Valor significativo foi considerado quando menor que 0,05 (com intervalo de confiança de 95%). Os resultados revelaram que a maioria dos participantes já viu o vetor da dengue (62%), sendo a mídia a fonte de informação mais citada. Quase 81,2% dos participantes sabiam que a transmissão da dengue é por picada de mosquito. Constatou-se que as práticas baseadas em medidas preventivas se concentravam predominantemente na prevenção de picadas de mosquitos, e não na eliminação de criadouros. Embora o conhecimento sobre DF e medidas de controle de mosquitos fosse bastante elevado entre os médicos, esse conhecimento não foi colocado em prática. Mais estudos são necessários para conscientizar a população sobre a dengue e seu vetor, a fim de se obter prevenção e controle.

Association of Diastolic Dysfunction with Angiographic Severity of Coronary Artery Disease in patients with Non-ST Elevation Myocardial Infarction.

In recent years, diastolic dysfunction is an evolving context. Presence of left ventricular diastolic dysfunction (LVDD) indicates a poor prognosis in patients with an ACS and chronic coronary artery diseases. This study evaluated the association of LVDD and angiographic severity of CAD in patients with non-ST elevation myocardial infarction (NSTEMI). This cross-sectional analytical study was carried out in National Institute of Cardiovascular Diseases, Dhaka, Bangladesh, during the period of April 2017 to March 2018. A total of 120 NSTEMI patients undergoing coronary angiogram (CAG) during index hospitalization were included in the study. All patients underwent transthoracic echocardiography before they underwent CAG on different days. Presence (Group I, n=65) and absence of LVDD (Group II, n=55) was established by echocardiography. Severity of CAD was assessed by Vessel score and Leaman score. Association of traditional risk factors (smoking habit, hypertension, diabetes mellitus, dyslipidemia and family history of CAD) with severity of CAD was investigated. Vessel score showed coronary artery obstruction (CAO) was present in 62(95.4%) patients in Group I and 35(63.6%) patients in Group II, single vessel was involved in 17(27.4%) patients while multi vessel in 45(72.6%) patients was found in Group I. On the contrary 27(77.1%) single vessel patients and 8(22.9%) multi vessel patients were found in Group II. Positive Leaman score was significantly higher in Group I, 62(95.4%) than that of Group II, 35(63.6%) which is statistically significant (p<0.001). This study showed a positive correlation between LVDD and CAD severity in terms of vessel score and Leamanscore. This study also demonstrates that the severity of vessel score and Leaman score was higher in the higher grade of diastolic dysfunction. The present study concludes that LVDD is associated with angiographically severe CAD in patients with NSTEMI.

The scope for radiology to contribute to the NHS net zero target: findings from a survey of radiology staff in the UK.

AIM: To assess attitudes towards the climate emergency among radiology staff and to identify current practices that may contribute towards the National Health Service (NHS) net zero target. MATERIALS AND METHODS: An online survey of radiology staff was conducted assessing current attitudes to the climate emergency. Further questions focused on staff travel, home working, virtual conferences, and recycling. RESULTS: Two hundred and forty-two responses were received from all staff groups within radiology. There were high levels of concern about the climate emergency among radiology staff. Active travel accounts for a relatively small proportion of commuting related to provision of radiology services. Some energy-saving measures are implemented commonly in radiology departments but these are likely to account for only a small proportion of energy use within a department. CONCLUSION: There is significant scope for reducing the carbon footprint of radiology services by reducing travel, both for work and for radiology education. We discuss the potential for large savings related to energy-saving measures.

Antidiabetic and hepato-renal protective effects of medicinal plants in STZ induced diabetic rats.

The antidiabetic and hepato-renal protective effects of Citrullus colocynthis and Momordica charantia ethanol extracts were investigated in streptozotocin (STZ) induced diabetic male albino rats. Diabetic rats were treated with C. colocynthis, M. charantia or C. colocynthis + M. charantia mixed extract at a dose of 250 mg /kg body weight per oral per day for 21 days. The mean body weight of all the diabetic rat groups on day 1 of treatment (day 10 of diabetes) was significantly lower than the normal control rat group (P<0.05). The blood glucose level of all the diabetic rat groups on day 1 of treatment (day 10 of diabetes) was significantly (P<0.05) higher (> 200 mg/dl) than the normal control rat group (95.5 ± 2.7). At the end of treatment (day 21), the diabetic rats treated with plant extracts showed significant increase (P<0.05) in body weight and significant (P<0.05) reduction in blood glucose level when compared to diabetic control animals. Significant increase (< 0.05) was observed in the serum bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea and creatinine levels of diabetic control rat group. The serum levels of these liver and kidney-related parameters of diabetic rats treated with plant extract were significantly lower when compared to diabetic control rat group (p < 0.05). Photomicrographs of liver and kidney microsections from diabetic rats treated with these plant extracts showed amelioration in the hepato-renal histoarchitectures. It was concluded that the C. colocynthis and M. charantia methanol extracts are antidiabetic and hepato-renal protective in STZ induced diabetic male rats. Treatment of the diabetic rats with C. colocynthis + M. charantia mixed extract is more effective in the amelioration of diabetes and hepato-renal injuries in STZ induced diabetic male rats.

Factors predictive of Ponseti casting for treating clubfoot: analysis of Bayesian Poisson regression model.

OBJECTIVE: Clubfoot is a growing public health concern in Bangladesh, with the incidence of approximately 0.64 to 6.8 in every 1000 live births. For over a decade, Ponseti method has been considered a gold standard for treating the clubfoot. Despite few studies have been estimating the number of casts required to correct the clubfoot deformities by Ponseti method, the subject of interest has always remained. Therefore, this current study aimed to investigate the significant predictive factors for the number of casts required to correct congenital clubfoot. PATIENTS AND METHODS: In this retrospective cohort study, we used Bayesian Poisson Regression Model to investigate the influencing factors that could predict how many casts are needed to correct the clubfoot. We included 69 patients with 99 affected feet, who completed their corrective phase of treatment in the Ponseti method. For this cohort study, we integrated only pre-tenotomy casting data with no age restrictions. We used Bayesian Poisson regression analysis technique to estimate the predictive factors. RESULTS: In Bayesian Poisson model, age was the most influencing predictive factor (24.3%) for increasing the number of castings to correct the clubfoot deformity. The clubfoot offspring of the ≤1-year-old was positive, and the incidence rate increased significantly with the casting number. The number of Ponseti casts in male clubfoot children was 28% higher than in female, and this was marginally statistically significant. There was no marked change estimated in the pattern of clubfoot, foot involvement and Pirani score of the severity. CONCLUSIONS: We concluded that the age factor may influence the number of casts required for the correction of clubfoot and specifically ≤ 1-year-old children are highly impacted. Treating clubfoot at an early age is suggested in this study to increase the success of clubfoot treatment and decrease the risk of relapse.

Development of Assessment Tool to Measure Children's Knowledge on Dengue Prevention Activities in Malaysia.

Dengue is one of the public health concerns in developing and developed countries. Since the main control measure for dengue is health prevention and control activities, especially among children, it is essential to assess children's knowledge on dengue prevention activities in preventing the disease. This study aimed to develop an assessment tool (CAB-IHBR-Dengue-C-01) attempting to measure children's knowledge of dengue prevention activities in Malaysia. Twelve (12) pictorials with descriptions were developed to capture children's understanding of the correct method of dengue prevention activities. Cronbach' alpha test was used to assess the internal consistency of the items, and the test and retest reliability method was used to measure the consistency of the questionnaire. For test-retest reliability analysis, tests were conducted twice, with an interval of two (2) weeks from the first test. In total, 58 respondents comprising of Malay, Chinese, and Indian aged between 7 and 12 years old were included in this study. The results showed the intraclass correlation coefficient (ICC) score was 0.640; with moderate reliability; meanwhile, Cronbach's alpha score was 0.606. In conclusion, CAB-IHBR-Dengue-C-01 (Cognitive Affective Behaviour-Institute for Health Behavioural Research-Dengue-Children-Version 01) is reliable to be used.

Knowledge, attitude and practices regarding dengue and its vector among medical practitioners in Malakand region, Pakistan.

Dengue fever (DF) is increasingly recognized as one of the world's major mosquito borne diseases and causes significant morbidity and mortality in tropical and subtropical countries. Dengue fever is endemic in most part of Pakistan and continues to be a public health concern. Knowledge, attitude and practices can play an important role in management of the disease. Current study was aimed to determine the level of knowledge, attitude and practices regarding dengue fever among health practitioners, to study the level of knowledge and attitude with preventive practices for dengue fever. A cross sectional study was carried out in medical practitioners of the four districts of Malakand region during October to November 2019. A pre-structured questionnaire was used to collect data from medical practitioners. Data was analyzed using Graph Pad version 5. Significant value was considered when less than 0.05 (at 95% confidence of interval). The results revealed that most of participants have seen dengue vector (62%), the media being the most quoted source of information. Nearly 81.2% participants were aware from transmission of dengue fever is by mosquito bite. Practices based upon preventive measures were found to be predominantly focused towards prevention of mosquito bites rather than elimination of breeding places. Although the knowledge regarding DF and mosquito control measure was quite high among the medical practitioners but this knowledge was not put into practice. Further studies are required to aware the people about dengue and its vector in order to get prevention and control.

Intradisciplinary team meeting for teledermatology: an aid to improving clinician confidence.

A weekly teledermatology intradisciplinary team (IDT) meeting, attended by consultant dermatologists and dermatology trainees, was established at our centre in July 2020 to help with the diagnosis and management of challenging 2-week-wait skin cancer teledermatology cases. To assess the usefulness of the meeting, an electronic survey of attendees (consultants n = 7; trainees n = 4) was performed 6 months after introduction. The results showed that 71.4% of consultants and 100% of trainees felt the IDT meeting improved their confidence in assessing dermoscopic photographs and in managing patients via teledermatology; 100% of attendees considered the meeting would improve patient safety; and 85.7% of consultants and 100% of trainees found the meeting contributed to their professional development, demonstrating its educational value. A retrospective analysis of patient outcomes before and after implementation of the IDT meeting demonstrated an increase in the direct discharge rate from 44.7% to 56.3% and a reduction in biopsy rate from 39.6% to 30.2% (n = 400; P = 0.02). The teledermatology IDT meeting is a model that could be introduced at other centres to support clinician confidence in teledermatology, and to help with clinical decision-making and teledermatology training.

Haemorrhagic shock from solid tumours of the adrenal gland: a case of bleeding primary adrenal lymphoma.

Suprarenal or adrenal gland haemorrhage is an uncommon but potentially lethal condition if unrecognised. Adrenal masses rarely present with haemorrhage, but they remain an important differential aetiology for adrenal bleeding. We present a novel case of primary adrenal lymphoma with adrenal haemorrhage in a middle-aged woman who presented with right-sided abdominal pain and class 1 haemorrhagic shock. She was found to have spontaneous unilateral adrenal gland haemorrhage in the absence of any underlying previous pathology. Presenting features, diagnosis and subsequent oncological management are reported.

Aggressive angiomyxoma of the ischioanal fossa in a post-menopausal woman.

Aggressive angiomyxoma is a rare mesenchymal tumour, primarily arising in the soft tissue of the pelvis and perineum in women of reproductive age. There is a paucity of evidence on optimal management because of the rarity of these tumours, but the consensus has been for surgical excision. We present the case of a 65-year-old woman who was admitted with left-sided buttock pain and initially diagnosed with a perianal abscess. She underwent examination under anaesthesia rectum with surgical excision of the lesion, subsequent histopathological and immunochemical analysis was suggestive of aggressive angiomyxoma. To complement our case report, we also present a literature review focusing on aggressive angiomyxoma in the ischioanal fossa (also known as the ischiorectal fossa) with only eight cases of primary aggressive angiomyxoma involving the ischioanal fossa documented to date. The primary aims of this case report and literature review are to familiarise clinicians with the clinical, histopathological and immunochemical features of these tumours, and to increase appreciation that despite the rarity of aggressive angiomyxoma, it might be considered in the differential diagnosis of ischioanal lesions.

Study protocol for a prospective, double-blinded, observational study investigating the diagnostic accuracy of an app-based diagnostic health care application in an emergency room setting: the eRadaR trial.

INTRODUCTION: Occurrence of inaccurate or delayed diagnoses is a significant concern in patient care, particularly in emergency medicine, where decision making is often constrained by high throughput and inaccurate admission diagnoses. Artificial intelligence-based diagnostic decision support system have been developed to enhance clinical performance by suggesting differential diagnoses to a given case, based on an integrated medical knowledge base and machine learning techniques. The purpose of the study is to evaluate the diagnostic accuracy of Ada, an app-based diagnostic tool and the impact on patient outcome. METHODS AND ANALYSIS: The eRadaR trial is a prospective, double-blinded study with patients presenting to the emergency room (ER) with abdominal pain. At initial contact in the ER, a structured interview will be performed using the Ada-App and both, patients and attending physicians, will be blinded to the proposed diagnosis lists until trial completion. Throughout the study, clinical data relating to diagnostic findings and types of therapy will be obtained and the follow-up until day 90 will comprise occurrence of complications and overall survival of patients. The primary efficacy of the trial is defined by the percentage of correct diagnoses suggested by Ada compared with the final discharge diagnosis. Further, accuracy and timing of diagnosis will be compared with decision making of classical doctor-patient interaction. Secondary objectives are complications, length of hospital stay and overall survival. ETHICS AND DISSEMINATION: Ethical approval was received by the independent ethics committee (IEC) of the Goethe-University Frankfurt on 9 April 2020 including the patient information material and informed consent form. All protocol amendments must be reported to and adapted by the IEC. The results from this study will be submitted to peer-reviewed journals and reported at suitable national and international meetings. TRIAL REGISTRATION NUMBER: DRKS00019098.

Integrating Biomarker Outcomes into Clinical Trials for Alzheimer's Disease in Down Syndrome.

The NIH-funded Alzheimer's Biomarker Consortium Down Syndrome (ABC-DS) and the European Horizon 21 Consortium are collecting critical new information on the natural history of Alzheimer's Disease (AD) biomarkers in adults with Down syndrome (DS), a population genetically predisposed to developing AD. These studies are also providing key insights into which biomarkers best represent clinically meaningful outcomes that are most feasible in clinical trials. This paper considers how these data can be integrated in clinical trials for individuals with DS. The Alzheimer's Clinical Trial Consortium - Down syndrome (ACTC-DS) is a platform that brings expert researchers from both networks together to conduct clinical trials for AD in DS across international sites while building on their expertise and experience.

Reconnaissance of tumor immune microenvironment spatial heterogeneity in metastatic renal cell carcinoma and correlation with immunotherapy response.

A clearer understanding of the tumor immune microenvironment (TIME) in metastatic clear cell renal cell carcinoma (ccRCC) may help to inform precision treatment strategies. We sought to identify clinically meaningful TIME signatures in ccRCC. We studied tumors from 39 patients with metastatic ccRCC using quantitative multiplexed immunofluorescence and relevant immune marker panels. Cell densities were analyzed in three regions of interest (ROIs): tumor core, tumor-stroma interface and stroma. Patients were stratified into low- and high-marker density groups using median values as thresholds. Log-rank and Cox regression analyses while controlling for clinical variables were used to compare survival outcomes to patterns of immune cell distributions. There were significant associations with increased macrophage (CD68+ CD163+ CD206+ ) density and poor outcomes across multiple ROIs in primary and metastatic tumors. In primary tumors, T-bet+ T helper type 1 (Th1) cell density was highest at the tumor-stromal interface (P = 0·0021), and increased co-expression of CD3 and T-bet was associated with improved overall survival (P = 0·015) and survival after immunotherapy (P = 0·014). In metastatic tumor samples, decreased forkhead box protein 3 (FoxP3)+ T regulatory cell density correlated with improved survival after immunotherapy (P = 0·016). Increased macrophage markers and decreased Th1 T cell markers within the TIME correlated with poor overall survival and treatment outcomes. Immune markers such as FoxP3 showed consistent levels across the TIME, whereas others, such as T-bet, demonstrated significant variance across the distinct ROIs. These findings suggest that TIME profiling outside the tumor core may identify clinically relevant associations for patients with metastatic ccRCC.

Relationship of amyloid beta and neurofibrillary tau deposition in Neurodegeneration in Aging Down Syndrome (NiAD) study at baseline.

IMPORTANCE: Adults with Down syndrome (DS) are at high-risk of revealing Alzheimer's disease (AD) pathology, in part due to the triplication of chromosome 21 encoding the amyloid precursor protein. Adults with DS are uniformly affected by AD pathology by their 30's and have a 70% to 80% chance of clinical dementia by their 60's. Our previous studies have assessed longitudinal changes in amyloid beta (Aß) accumulation in DS. OBJECTIVE: The goal of the present study was to assess the presence of brain tau using [18F]AV-1451 positron emission tomography (PET) in DS and to assess the relationship of brain tau pathology to Aß using Pittsburgh Compound B (PiB)-PET. DESIGN: Cohort study. SETTING: Multi-center study. PARTICIPANTS: Participants consisted of a sample of individuals with DS and sibling controls recruited from the community; exclusion criteria included contraindications for magnetic resonance imaging (MRI) and/or a medical or psychiatric condition that impaired cognitive functioning. EXPOSURES: PET brain scans to assess Aß ([11C]PiB) and tau ([18F]AV-1451) burden. MAIN OUTCOMES AND MEASURES: Multiple linear regression models (adjusted for chronological age, sex and performance site) were used to examine associations between regional [18F]AV-1451 standard uptake value ratio (SUVR) (based on regions associated with Braak stages 1-6) and global [11C]PiB SUVR (as both a continuous and dichotomous variable). RESULTS: A cohort of 156 participants (mean age = 39.05, SD(8.4)) were examined. These results revealed a significant relationship between in vivo Aß and tau pathology in DS. As a dichotomous variable, [18F]AV-1451 retention was higher in each Braak region in PiB(+) participants. We also found, based on our statistical models, starting with the Braak 3 region of interest (ROI), an acceleration of [18F]AV-1451 SUVR deposition with [11C]PiB SUVR increases.