Corpse or not? Two peculiar cases of misidentification.

Irrespective of whether they are intended for collectors or for the fetish market, dolls are being produced to look more and more realistic with such a degree of life-like detail that they can be mistaken for a real person. This paper reports two cases of misidentification due to this increasing similarity: In the first case, a sex doll was mistaken for a corpse; in the second case, a corpse was mistaken for a doll. While in the latter case, only medical laypersons were at the discovery site, in the first case, an emergency doctor had issued a medical certificate of death for the purported corpse. The medicolegal examiner who was subsequently called to the scene could still rectify the misconception on-site. Mistakes of this nature are likely rare phenomena. It, however, remains to be seen if the increasingly life-like appearance of dolls on the one hand, and the increasingly doll-like appearance of some people, e.g., through cosmetic surgery, will lead to a rise in such cases. To avoid misidentification as in the first reported case, it is essential to prepare medical students well for the task of performing a primary external postmortem examination; it is equally important that fully-trained doctors regularly refresh their expertise in this respect.

Time Trends in Causes of Death in People With HIV: Insights From the Swiss HIV Cohort Study.

BACKGROUND: Advancements in access to antiretroviral therapy (ART) and human immunodeficiency virus (HIV) care have led to a decline in AIDS-related deaths among people with HIV (PWH) in Switzerland. However, data on the ongoing changes in causes of death among PWH over the past 15 years are scarce. METHODS: We investigated all reported deaths in the Swiss HIV Cohort Study between 2005 and 2022. Causes of death were categorized using the Coding Causes of Death in HIV protocol. The statistical analysis included demographic stratification to identify time trends and logistic regression models to determine associated factors for the underlying cause of death. RESULTS: In total, 1630 deaths were reported, with 23.7% of individuals assigned female sex at birth. These deaths included 147 (9.0%) HIV/AIDS-related deaths, 373 (22.9%) due to non-AIDS, non-hepatic cancers, 166 (10.2%) liver-related deaths, and 158 (9.7%) cardiovascular-related deaths. The median age at death (interquartile range) increased from 45.0 (40.0-53.0) years in 2005-2007 to 61.0 (56.0-69.5) years in 2020-2022. HIV/AIDS- and liver-related deaths decreased, whereas deaths from non-AIDS, non-hepatic cancers increased and cardiovascular-related deaths remained relatively stable. CONCLUSIONS: The proportionally decreasing HIV/AIDS and liver-related deaths showcase the effectiveness of ART, comprehensive HIV patient care, and interventions targeting hepatitis C virus coinfection. Future research should focus on managing cancer and cardiovascular-related conditions as the new leading causes of death among PWH. Comprehensive healthcare strategies focusing on non-AIDS-related comorbid conditions, cancer management, and sustaining liver and cardiovascular health are needed to bridge the ongoing health disparities between PWH and the general population.

MRI identification of pseudolesions in the distal tibia articular surface: Frequency and diagnostic criteria.

OBJECTIVE: Pseudolesions of joints are known as focal irregularities of chondral or subchondral bone in typical joint areas and occur frequent but without clinical relevance. This study aims to report the prevalence and describe MRI findings of a previously unreported chondral, mostly posterior located pseudolesion of the distal tibia, and to define criteria to distinguish it from pathologic osteochondral lesions, as well as from another known pseudolesion of this area - the so called "Notch of Harty". MATERIAL AND METHODS: A tri-centric retrospective case-control study included a total of 2,428 patients with ankle MRI examinations performed over a period of 6 years. MRI scans were evaluated by three radiologists in consensus for any cartilage irregularity of the distal tibial articular surface. For this purpose, the tibial articular surface was divided into 9 topographic regions. Proton-density weighted, fat-suppressed sequences in sagittal and coronal acquisition were used to assess the postero-medial articular surface of the tibia. Imaging features such as size and localization of cartilage irregularity and/or a cortical mould as well as presence of associated edema and/or subchondral cysts were reported. Demographic data (sex, age, and weight) was also recorded. Clinical data comprised presence of pain, movement impairment, and concomitant pathologies. RESULTS: A total of 68 patients (34 male, 34 female) with a lesion of the distal tibia were identified that had a new pseudolesion (prevalence of 3%). These lesions occurred most frequently (50 out of 68, 74%) in the postero-medial distal tibia plafond and were more commonly detected in the age group of 9-30 years (47%). In 13 of these 68 cases, the cartilage irregularity was the sole lesion without subchondral abnormalities. By defining these cases as definite pseudolesions, the prevalence was 1% and their age distribution was similar to that of the 55 other lesions with subchondral changes. Here with 11 of the 13 cases the majority (85%) were seen in the posterior part, especially in the postero-medial part (55%) of the distal tibia. The size of the cartilage defect ranged from 1 to 7 mm, and the majority (69%) sized from 2 to 3 mm. In 36 of 68 patients, we have seen subchondral alterations such as edema and/or cysts in addition to cartilage irregularity. 66% (n = 45) of these changes were edema and 37% (n = 25) were cysts. None of these 68 new pseudolesions with or without subchondral changes needed surgical or arthroscopic intervention. In the radiological and orthopaedic reports, clinical symptoms such as pain or instability were never associated with our observed lesions and there was no significant correlation between the presence of motion-related pain and imaging findings of cartilage irregularity, subchondral edema, and subchondral cysts. Thirteen patients had MRI follow-up examinations. Here the lesions did not show any MR morphological changes or clinical deterioration. Besides the new pseudolesion, which occured mainly in the posterior part of the tibia surface, we observed the "Notch of Harty" with a higher prevalence (25%) in our patient cohort. The typical localization was in the antero-medial tibial articular surface, without any edema or cysts. There were no coincidences of patients with both a new pseudolesion and the "Notch of Harty" CONCLUSION: A new pseudolesion is typically seen in the postero-central and postero-medial tibial articular surface with a prevalence of 3% and may be associated with only a small cartilage irregularity. In many cases, however, additional findings such as bone edema and/or an adjacent bone cysts were found, which impairs differentiation of these lesions from pathologic osteochondral lesions. The latter are obviously often associated with a larger cartilage defect and clinical symptoms. Due to the balanced age distribution between those pseudolesions with and without subchondral changes and the lack of clinical symptoms, we conclude that the here reported pseudolesions are not a predilection for a clinically manifest osteochondral lesion (OCL). At the very least, the apparent lack of clinical relevance increases the likelihood that we are dealing with a new true pseudolesion.

PET/CT-identified atrial hypermetabolism is an index of atrial inflammation in patients with atrial fibrillation.

BACKGROUND: Although atrial inflammation has been implicated in the pathophysiology of atrial fibrillation (AF), the identification of atrial inflammation remains challenging. We aimed to establish a positron emission tomography/computed tomography (PET/CT) protocol with 18Fluor-labeled fluorodeoxyglucose (18F-FDG) for the detection of atrial hypermetabolism as surrogate for inflammation in AF. METHODS: We included n = 75 AF and n = 75 non-AF patients undergoing three common PET/CT protocols (n = 25 per group) optimized for the detection of (a) inflammation and (b) malignancy in predefined fasting protocols, and (c) cardiac viability allowing for maximized glucose uptake. 18F-FDG-uptake was analyzed in predefined loci. RESULTS: Differences of visual atrial uptake in AF vs non-AF patients were observed in fasting (inflammation [13/25 vs 0/25] and malignancy [10/25 vs 0/25]) protocols while viability protocols showed non-specific uptake in both the groups. In the inflammation protocol, AF patients showed higher uptake in the right atrium [(SUVmax: 2.5 ± .7 vs 2.0 ± .7, P = .01), atrial appendage (SUVmax: 2.4 ± .7 vs 2.0 ± .6, P = .03), and epicardial adipose tissue (SUVmax: 1.4 ± .5 vs 1.1 ± .4, P = .04)]. Malignancy and viability protocols failed to differentiate between AF and non-AF. CONCLUSION: Glucose uptake suppression protocols appear suitable in detecting differential atrial 18F-FDG uptake between AF and non-AF patients. Imaging-based assessment of inflammation might help to stratify AF patients offering individualized therapeutic approaches.

Prophylactic clipping using the over-the-scope clip (OTSC) system after complex ESD and EMR of large colon polyps.

BACKGROUND: Delayed bleeding is the most frequent complication after endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) of large colon polyps. Today, prophylactic clipping with through-the-scope clips (TTSCs) is commonly used to reduce the risk of bleeding. However, the over-the-scope clip (OTSC) system might be superior to TTSCs in achieving hemostasis. This study aims to evaluate the efficacy and safety of prophylactic clipping using the OTSC system after ESD or EMR of large colon polyps. METHODS: This is a retrospective analysis of a prospective collected database from 2009 until 2021 of three endoscopic centers. Patients with large (≥ 20 mm) colon polyps were enrolled. All polyps were removed by either ESD or EMR. After the resection, OTSCs were prophylactically applied on parts of the mucosal defect with a high risk of delayed bleeding or/and perforation. The main outcome measurement was delayed bleeding. RESULTS: A total of 75 patients underwent ESD (67%, 50/75) or EMR (33%, 25/75) in the colorectum. The mean resected specimen diameter was 57 mm ± 24.1 (range 22-98 mm). The mean number of OTSCs placed on the mucosal defect was 2 (range 1-5). None of the mucosal defects were completely closed. Intraprocedural bleeding occurred in 5.3% (ESD 2.0% vs. EMR 12.0%; P = 0.105), and intraprocedural perforation occurred in 6.7% (ESD 8% vs. EMR 4%; P = 0.659) of the patients. Hemostasis was achieved in 100% of cases of intraprocedural bleeding, whereas two patients required surgical conversion due to intraprocedural perforation. Among the remaining 73 patients who received prosphylactic clipping, delayed bleeding occurred in 1.4% (ESD 0% vs. EMR 4.2%; P = 0.329), and delayed perforation occurred in 0%. CONCLUSIONS: The prophylactic partial closure of large post-ESD/EMR mucosal defects using OTSCs could serve as an effective strategy to reduce the risk of delayed bleeding and perforation. The prophylactic partial closure of large complex post-ESD/EMR mucosal defects using OTSCs could serve as an effective strategy to reduce the risk of delayed bleeding and perforation.

French recommendations for the management of non-infectious chronic uveitis.

This French National Diagnostic and Care Protocol (NDPC) includes both pediatric and adult patients with non-infectious chronic uveitis (NICU) or non-infectious recurrent uveitis (NIRU). NICU is defined as uveitis that persists for at least 3 months or with frequent relapses occurring less than 3 months after cessation of treatment. NIRU is repeated episodes of uveitis separated by periods of inactivity of at least 3 months in the absence of treatment. Some of these NICU and NIRU are isolated. Others are associated with diseases that may affect various organs, such as uveitis associated with certain types of juvenile idiopathic arthritis, adult spondyloarthropathies or systemic diseases in children and adults such as Behçet's disease, granulomatoses or multiple sclerosis. The differential diagnoses of pseudo-uveitis, sometimes related to neoplasia, and uveitis of infectious origin are discussed, as well as the different forms of uveitis according to their main anatomical location (anterior, intermediate, posterior or panuveitis). We also describe the symptoms, known physiopathological mechanisms, useful complementary ophthalmological and extra-ophthalmological examinations, therapeutic management, monitoring and useful information on the risks associated with the disease or treatment. Finally, this protocol presents more general information on the care pathway, the professionals involved, patient associations, adaptations in the school or professional environment and other measures that may be implemented to manage the repercussions of these chronic diseases. Because local or systemic corticosteroids are usually necessary, these treatments and the risks associated with their prolonged use are the subject of particular attention and specific recommendations. The same information is provided for systemic immunomodulatory treatments, immunosuppressive drugs, sometimes including anti-TNFα antibodies or other biotherapies. Certain particularly important recommendations for patient management are highlighted in summary tables.

Consistent Value of Two-Stage Pedicle Flaps in the Age of Microsurgical Maxillofacial Reconstruction.

Introduction: Up to the second half of the twentieth century, pedicled flaps marked the gold standard in reconstructive surgery. Followed by the introduction of microsurgical techniques, these flaps were increasingly abandoned. We conducted a retrospective study to determine the value of two-stage pedicle flaps in modern maxillofacial reconstruction. Material & Methods: A chart review from October 2017 to November 2020 was performed to identify patients who were treated by a two-stage pedicle flap in our Department of Oral and Maxillofacial Surgery. Results: A total of 31 patients, 17 female and 14 males received 36 two-stage pedicle flaps. All patients were in noticeably impaired health condition with a majority of ASA-score 3. The defect location mainly contained extraoral resections (58.3%). A variety of flaps were harvested consisting of buccal flaps, Abbe flaps, forehead flaps, deltopectoral flaps, nasolabial flaps, and a tubed flap. Discussion: The study outlines two indications for the use of two-stage pedicle flaps. Firstly, as a back-up strategy in heavily pre-treated wound beds and secondly in an almost contrarily indication as a first-choice reconstructive option of the facial skin in esthetic demanding cases. Conclusion: The timesaving and straight forward surgical approach as well as their low postsurgical complications and strong long-time success rates secure the two-stage pedicle flap a justified niche role in times of microsurgical maxillofacial reconstruction. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-021-01635-9.

The OUTREACH study: oncologists of German university hospitals in rotation on a palliative care unit-evaluation of attitude and competence in palliative care and hospice.

PURPOSE: The effect of the duration of an educational rotation presented at a palliative care unit on the palliative care knowledge gain and the increase of palliative care self-efficacy expectations are unclear. METHODS: This national prospective multicenter pre-post survey conducted at twelve German University Comprehensive Cancer Centers prospectively enrolled physicians who were assigned to training rotations in specialized palliative care units for three, six, or twelve months. Palliative care knowledge [in %] and palliative care self-efficacy expectations [max. 57 points] were evaluated before and after the rotation with a validated questionnaire. RESULTS: From March 2018 to October 2020, questionnaires of 43 physicians were analyzed. Physicians participated in a 3- (n = 3), 6- (n = 21), or 12-month (n = 19) palliative care rotation after a median of 8 (0-19) professional years. The training background of rotating physicians covered a diverse spectrum of specialties; most frequently represented were medical oncology (n = 15), and anesthesiology (n = 11). After the rotation, median palliative care knowledge increased from 81.1% to 86.5% (p < .001), and median palliative care self-efficacy expectations scores increased from 38 to 50 points (p < .001). The effect of the 12-month rotation was not significantly greater than that of the 6-month rotation. CONCLUSION: An educational rotation presented in a specialized palliative care unit for at least six months significantly improves palliative care knowledge and palliative care self-efficacy expectations of physicians from various medical backgrounds.

[XEN 45® gel stent implantation in glaucoma surgery: Dual-center comparative study between steroid-induced glaucoma and primary open angle glaucoma]. / Implantation du dispositif XEN 45® dans la chirurgie du glaucome : étude bicentrique bispective s'intéressant au glaucome cortisonique par rapport au glaucome primitif à angle ouvert.

INTRODUCTION: XEN 45® gel stent is an ab interno aqueous humor drainage device indicated for moderate glaucoma refractory to medical management. Its efficacy has been demonstrated in primary open-angle glaucoma (POAG). However, there are few studies on secondary glaucoma, including steroid-induced glaucoma (CG), defined as optic neuropathy induced by using local or systemic corticosteroids without increased flare. METHODS: We conducted a dual-center comparative cohort study between April 2019 and January 2021. 66 operated eyes were included, divided into two groups: POAG (56 eyes) and GC (10 eyes). The primary endpoint was the relative reduction in intraocular pressure (IOP) at three months postoperatively in the GC group. Three outcomes were defined: total success, partial success and failure. RESULTS: The total success rate was 100% in the GC group and 42.6% in the POAG group. Preoperative IOP was 36.1±9.1mmHg and 19.0±7.3mmHg respectively. IOP reduction was 69.1±11.7% in the GC group and 21.8±30.3% in the POAG group. Patients were younger in the GC group (49.3±21.2 versus 71.1±8.4 years), and preoperative conjunctival preparation was longer in this group (12 versus 5 weeks). The needling rate was 17.9% in the POAG group and 10% in the GC group. CONCLUSION: The XEN 45® gel stent is effective in the treatment of steroid-induced glaucoma. Further studies will be required to identify predictive factors for success and to establish criteria for good candidacy.

[Clinical radiological evaluation of teeth-part 2 : Caries, inflammatory dental changes and important differential diagnoses]. / Klinisch-radiologische Beurteilung der Zähne ­ Teil 2 : Karies, entzündliche Zahnveränderungen und wichtige Differenzialdiagnosen.

Inflammatory diseases of the teeth and periodontium are widespread and are frequent secondary diagnoses in head and neck examinations. Periapical inflammation can be the cause of sinusitis or abscess formation in the oral and maxillofacial region. Early detection is important for the patient's course of treatment. For further diagnostics, a dental presentation should be carried out. Dental radiological examinations, such as panoramic radiographs and dental films are used for specific diagnostics. This article is intended to provide an overview of the different stages of caries, the most important inflammatory dental changes and their most frequent differential diagnoses.

Postoperative recovery patterns following discectomy surgery in patients with lumbar radiculopathy.

This retrospective study of prospectively collected data aimed to identify unique pain and disability trajectories in patients following lumbar discectomy surgery. Patients of this study population presented chiefly with lumbar radiculopathy and underwent discectomy surgery from thirteen sites enrolled in the CSORN registry. Outcome variables of interest included numeric rating scales for leg/back pain and modified Oswestry disability index scores at baseline, 3, 12, and 24 months post-operatively. Latent class growth analysis was used to identify distinct courses in each outcome. Data from 524 patients revealed three unique trajectories for leg pain (excellent = 18.4%, good = 55.4%, poor = 26.3%), disability (excellent = 59.7%, fair = 35.6%, poor = 4.7%) and back pain (excellent = 13.0%, good = 56.4%, poor = 30.6%). Construct validity was supported by statistically significant differences in the proportions of patients attaining the criteria for minimal important change (MIC; 30%) or clinical success in disability (50% or Oswestry score ≤ 22) (p < 0.001). The variable proportions of patients belonging to poor outcome trajectories shows a disconnect between improved disability and persistence of pain. It will be beneficial to incorporate this information into the realm of patient expectation setting in concert with future findings of potential factors predictive of subgroup membership.

[Clinical radiological evaluation of teeth-part 1 : Anatomy and anomalies]. / Klinisch-radiologische Beurteilung der Zähne ­Teil 1 : Anatomie und Anomalien.

Radiological assessment of the teeth and periodontium is often left to the dentist. Nevertheless, it is useful to know the anatomy and possible anomalies of the teeth in order to correctly assess pathological processes in both projection radiographic and slice imaging. Dental radiological examinations, such as panoramic slice imaging (PSA) and dental film are used for targeted diagnostics. In the case of incidental findings, a dental presentation should be made for further clarification. This article first provides an overview of the anatomy and anomalies of teeth.

Performance of different osteosynthesis materials in microvascular fibula free flap reconstruction.

Fibular free flap (FFF) is the main reconstructive choice for large mandibular defects. Recent improvements have been made regarding planning and surgical procedure, but choice of osteosynthesis material (OSM) for segment-fixation remains controversial. A retrospective cohort study obtained clinical and radiological data from FFF-patients. Data were screened for OSM, surgical procedure and complications as OSM fractures, loosening, exposure, or insufficient osseous consolidation. Eighty patients with FFF were included. Planning was CAD/CAM (n=29), Recon Guide (n=26) or without planning (n=25). OSM was 2.0mm-miniplates in standard (n=26), preformed (n=6), CAD/CAM (n=14) or ReconGuide (n=23) variation and 2.3mm-reconstruction-plates in standard (n=5) or CAD/CAM (n=6) variation. Complications were observed in 21 cases, fractures occurred 10 times overall, but with low rates for preformed (n=1), ReconGuide (n=3) and none for CAD/CAM. Analysis detected significant correlations between used OSM and plate exposure (p = 0.000), but none regarding fracture (p = 0.275), loosening (p = 0.714) or insufficient osseous consolidation (p = 0.208). No correlations were observed between complications and OSM (p = 0.609) or diagnosis (p = 0.716). Fixation of FFF segments for reconstruction is possible with various OSM providing good clinical outcome. No significant differences were detected regarding prevention of complications by any osteosynthesis material (miniplate vs. macroplate). Although no differences were detected, miniplate usage is advocated whenever clinically reasonable, due to easier reintervention possibilities and reduced implanted foreign material. Nevertheless, decision for ideal OSM must remain patient-specific and cannot be generalised.

Protocol paper: Multi-site, cluster-randomized clinical trial for optimizing functional outcomes of older cancer survivors after chemotherapy.

BACKGROUND: Cancer survivors over the age of 65 have unique needs due to the higher prevalence of functional and cognitive impairment, comorbidities, geriatric syndromes, and greater need for social support after chemotherapy. In this study, we will evaluate whether a Geriatric Evaluation and Management-Survivorship (GEMS) intervention improves functional outcomes important to older cancer survivors following chemotherapy. METHODS: A cluster-randomized trial will be conducted in approximately 30 community oncology practices affiliated with the University of Rochester Cancer Center (URCC) National Cancer Institute Community Oncology Research Program (NCORP) Research Base. Participating sites will be randomized to the GEMS intervention, which includes Advanced Practice Practitioner (APP)-directed geriatric evaluation and management (GEM), and Survivorship Health Education (SHE) that is combined with Exercise for Cancer Patients (EXCAP©®), or usual care. Cancer survivors will be recruited from community oncology practices (of participating oncology physicians and APPs) after the enrolled clinicians have consented and completed a baseline survey. We will enroll 780 cancer survivors aged 65 years and older who have completed curative-intent chemotherapy for a solid tumor malignancy within four weeks of study enrollment. Cancer survivors will be asked to choose one caregiver to also participate for a total up to 780 caregivers. The primary aim is to compare the effectiveness of GEMS for improving patient-reported physical function at six months. The secondary aim is to compare effectiveness of GEMS for improving patient-reported cognitive function at six months. Tertiary aims include comparing the effectiveness of GEMS for improving: 1) Patient-reported physical function at twelve months; 2) objectively assessed physical function at six and twelve months; and 3) patient-reported cognitive function at twelve months and objectively assessed cognitive function at six and twelve months. Exploratory health care aims include: 1) Survivor satisfaction with care, 2) APP communication with primary care physicians (PCPs), 3) completion of referral appointments, and 4) hospitalizations at six and twelve months. Exploratory caregiver aims include: 1) Caregiver distress; 2) caregiver quality of life; 3) caregiver burden; and 4) satisfaction with patient care at six and twelve months. DISCUSSION: If successful, GEMS would be an option for a standardized APP-led survivorship care intervention. TRIAL REGISTRATION: ClinicalTrials.govNCT05006482, registered on August 9, 2021.

EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds.

Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis.

Clonal hematopoiesis results from enhanced fitness of a mutant hematopoietic stem and progenitor cell (HSPC), but how such clones expand is unclear. We developed a technique that combines mosaic mutagenesis with color labeling of HSPCs to study how acquired mutations affect clonal fitness in a native environment. Mutations in clonal hematopoiesis­associated genes such as asxl1 promoted clonal dominance. Single-cell transcriptional analysis revealed that mutations stimulated expression of proinflammatory genes in mature myeloid cells and anti-inflammatory genes in progenitor cells of the mutant clone. Biallelic loss of one such immunomodulator, nr4a1, abrogated the ability of asxl1-mutant clones to establish clonal dominance. These results support a model where clonal fitness of mutant clones is driven by enhanced resistance to inflammatory signals from their mutant mature cell progeny.