Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer.

Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR] = 0.3 in the targeted sequencing and OR = 0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR = 6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, non-responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.

Next generation pan-cancer blood proteome profiling using proximity extension assay.

A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.

End-of-life care for people with advanced dementia and pain: a qualitative study in Swedish nursing homes.

BACKGROUND: Of the Swedish people with advanced dementia, the majority die in nursing homes. Unresolved pain can occur in people with a terminal illness such as dementia. However, pain management in people with advanced dementia is often suboptimal and inadequate, with fewer palliative care interventions than offered to cancer patients. Although they are largely responsible for the care of these people, few studies have addressed the experiences of registered nurses in this respect. Therefore, the aim of this study was to describe the experiences of nurses in caring for people with advanced dementia and pain at the end of life. METHODS: The study had a descriptive explorative design. Individual qualitative, semi-structured interviews were carried out with 13 nurses from 12 nursing homes in Sweden. The results were analysed using thematic content analysis. RESULTS: The nurses described communicative, relational and organisational challenges. One major issue involved difficulties communicating with the person with advanced dementia, resulting in uncertain pain assessment. Other difficulties involved the differentiation of pain from anxiety, the balance of benefits and risks with morphine administration, and the creation of good relationships with healthcare personnel and the persons' relatives. Relatives can greatly affect the assessment and management of pain, both because of their ability to interpret pain behaviour and by questioning the care given. Good pain management was facilitated by good communication and relationships with healthcare staff and relatives, extensive professional nursing experience, and already knowing the person with advanced dementia. CONCLUSIONS: This study highlights the need for nursing homes to employ specialist nurses who have been trained in the appropriate knowledge and skills to deal with the challenges of end-of-life care for people with advanced dementia and pain. Additionally, there should be resources and strategies available for providing information to family members and for involving them in the decision-making process, as they are often unfamiliar with the multitude of considerations involved in decisions such as whether to administer morphine or not.

Microbial neoformation of volatiles: implications for the estimation of post-mortem interval in decomposed human remains in an indoor setting.

The objective of this study was to determine if a relationship between microbial neoformation of volatiles and the post-mortem interval (PMI) exists, and if the volatiles could be used as a tool to improve the precision of PMI estimation in decomposed human remains found in an indoor setting. Chromatograms from alcohol analysis (femoral vein blood) of 412 cases were retrospectively assessed for the presence of ethanol, N-propanol, 1-butanol, and acetaldehyde. The most common finding was acetaldehyde (83% of the cases), followed by ethanol (37%), N-propanol (21%), and 1-butanol (4%). A direct link between the volatiles and the PMI or the degree of decomposition was not observed. However, the decomposition had progressed faster in cases with microbial neoformation than in cases without signs of neoformation. Microbial neoformation may therefore act as an indicator of the decomposition rate within the early decomposition to bloating stages. This may be used in PMI estimation based on the total body score (TBS) and accumulated degree days (ADD) model, to potentially improve the model's precision.

Major depression subtypes are differentially associated with migraine subtype, prevalence and severity.

OBJECTIVE: Migraine and major depressive disorder show a high rate of comorbidity, but little is known about the associations between the subtypes of major depressive disorder and migraine. In this cross-sectional study we aimed at investigating a) the lifetime associations between the atypical, melancholic, combined and unspecified subtype of major depressive disorder and migraine with and without aura and b) the associations between major depressive disorder and its subtypes and the severity of migraine. METHODS: A total of 446 subjects with migraine (migraine without aura: n = 294; migraine with aura: n = 152) and 2511 controls from the population-based CoLaus/PsyCoLaus study, Switzerland, were included. Associations between major depressive disorder subtypes and migraine characteristics were tested using binary logistic or linear regression. RESULTS: Melancholic, combined and unspecified major depressive disorder were associated with increased frequency of migraine with aura, whereas only melancholic major depressive disorder was associated with increased frequency of migraine without aura. Lifetime and unspecified major depressive disorder were associated with severe migraine intensity among subjects with migraine with aura but not migraine without aura, while combined major depressive disorder was associated with higher migraine frequency independently from migraine subtype. CONCLUSION: This study suggests that melancholic but not atypical major depressive disorder is associated with migraine and migraine subtypes. Future studies exploring pathophysiological mechanisms shared between melancholic depression and migraine are warranted.

Surveillance of mosquito vectors in Southern Sweden for Flaviviruses and Sindbis virus.

There are three human pathogenic bird-viruses transmitted by Culex mosquitoes in Europe: the alphavirus Sindbis and the flaviviruses West Nile virus and Usutu virus. Cases of Sindbis fever occur in the north while the flaviviruses are reported from southern Europe. In this study, 7933 Culex pipiens/torrentium mosquitoes from southern Sweden were screened by RTqPCR for these viruses. None of the mosquitoes were positive for viral RNA. The importance of mosquito species composition is discussed as a potential explanation to the lack of detection of mosquito-borne viruses in southern Sweden. However, continued surveillance of mosquitoes for Flaviviruses would be valuable as an early warning for public health awareness.

Detecting individual extracellular vesicles using a multicolor in situ proximity ligation assay with flow cytometric readout.

Flow cytometry is a powerful method for quantitative and qualitative analysis of individual cells. However, flow cytometric analysis of extracellular vesicles (EVs), and the proteins present on their surfaces has been hampered by the small size of the EVs - in particular for the smallest EVs, which can be as little as 40 nm in diameter, the limited number of antigens present, and their low refractive index. We addressed these limitations for detection and characterization of EV by flow cytometry through the use of multiplex and multicolor in situ proximity ligation assays (in situ PLA), allowing each detected EV to be easily recorded over background noise using a conventional flow cytometer. By targeting sets of proteins on the surface that are specific for distinct classes of EVs, the method allows for selective recognition of populations of EVs in samples containing more than one type of EVs. The method presented herein opens up for analyses of EVs using flow cytometry for their characterization and quantification.