Histological characterization of liver involvement in systemic mastocytosis.

BACKGROUND AND AIMS: Systemic mastocytosis (SM) is characterized by the accumulation of atypical mast cells (MCs) in organs. Liver histology of SM has been marginally described and accurate histological classification is critical, given the consequences of aggressive SM diagnosis. We aimed to describe the histological features associated with liver SM using updated tools. METHODS: Using the database of the French Reference Centre for Mastocytosis, we retrospectively identified patients with a liver biopsy (LB) and a diagnosis of SM. All LB procedures were performed according to the local physician in charge and centrally reviewed by an expert pathologist. RESULTS: A total of 28 patients were included: 6 had indolent SM, 9 had aggressive SM, and 13 had SM with an associated hematologic neoplasm. Twenty-five (89%) patients presented hepatomegaly, and 19 (68%) had portal hypertension. The LB frequently showed slight sinusoid dilatation (82%). Fibrosis was observed in 3/6 indolent SM and in almost all advanced SM cases (21/22), but none of them showed cirrhosis. A high MC burden (>50 MCs/high-power field) was correlated with elevated blood alkaline phosphatase levels (p = .030). The presence of portal hypertension was associated with a higher mean fibrosis grade (1.6 vs. 0.8 in its absence; p = .026). In advanced SM, the presence of nodular regenerative hyperplasia (NRH) was associated with decreased overall survival (9.5 vs. 46.3 months, p = .002). CONCLUSIONS: MC infiltration induced polymorphic hepatic lesions and the degree of fibrosis is associated with portal hypertension. NRH identifies a poor prognosis subgroup of patients with advanced SM. Assessing liver histology can aid in SM prognostic evaluation.

Laboratory tests for investigating anemia: From an expert system to artificial intelligence.

Objective: To compare the laboratory tests conducted in real-life settings for patients with anemia with the expected prescriptions derived from an optimal checkup. Methods: A panel of experts formulated an "optimal laboratory test assessment" specific to each anemia profile. A retrospective analysis was done of the laboratory tests conducted according to the type of anemia (microcytic, normocytic or macrocytic). Using an algorithmic system, the laboratory tests performed in real-life practice were compared with the recommendations suggested in the "optimal laboratory test assessment" and with seemingly "unnecessary" laboratory tests. Results: In the analysis of the "optimal laboratory test assessment", of the 1179 patients with microcytic anemia, 269 (22.8%) had had one of the three tests recommended by the expert system, and only 33 (2.8%) had all three tests. For normocytic anemia, 1054 of 2313 patients (45.6%) had one of the eleven recommended tests, and none had all eleven. Of the 384 patients with macrocytic anemia, 196 (51%) had one of the four recommended tests, and none had all four. In the analysis of "unnecessary laboratory tests", one lab test was unnecessarily done in 727/3876 patients (18.8%), i.e. 339 of 1179 (28.8%) microcytic, 171 of 2313 (7.4%) normocytic, and 217 of 384 (56.5 %) macrocytic anemias. Conclusion: Laboratory investigations of anemia remain imperfect as more than half of the cases did not receive the expected tests. Analyzing other diagnostic domains, the authors are currently developing an artificial intelligence system to assist physicians in enhancing the efficiency of their laboratory test prescriptions.

Pathophysiologic implications of elevated prevalence of hereditary alpha-tryptasemia in all mastocytosis subtypes.

BACKGROUND: Mastocytosis and monoclonal mast cell (MC) activation syndrome (MMAS) are heterogeneous conditions characterized by the accumulation of atypical MCs. Despite the recurrent involvement of KIT mutations, the pathophysiologic origin of mastocytosis and MMAS is unclear. Although hereditary α-tryptasemia (HαT, related to TPSAB1 gene duplication) is abnormally frequent in these diseases, it is not known whether the association is coincidental or causal. OBJECTIVE: We evaluated the prevalence of HαT in all mastocytosis subtypes and MMAS and assessed the pathophysiologic association with HαT. METHODS: Clinical data, laboratory data, KIT mutations, TPSAB1 duplication (assessed by droplet digital PCR), and HαT prevalence were retrospectively recorded for all patients with mastocytosis and MMAS registered in the French national referral center database and compared to a control cohort. To increase the power of our analysis for advanced systemic mastocytosis (advSM), we pooled our cohort with literature cases. RESULTS: We included 583 patients (27 with MMAS and 556 with mastocytosis). The prevalence of HαT in mastocytosis was 12.6%, significantly higher than in the general population (5.7%, P = .002) and lower than in MMAS (33.3%, P = .02). HαT+ patients were more likely to have anaphylactic reactions and less likely to have cutaneous lesions than HαT- patients (43.0% vs 24.4%, P = .006; 57.7% vs 75.6%, respectively, P = .006). In the pooled analysis, the prevalence of HαT was higher in advSM (11.5%) than in control cohorts (5.2%, P = .01). CONCLUSION: Here we confirm the increase incidence of anaphylaxis in HαT+ mastocytosis patients. The increased prevalence of HαT in all subtypes of systemic mastocytosis (including advSM) is suggestive of pathophysiologic involvement.

Consequences of sarcolemma fatigue on maximal muscle strength production in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

BACKGROUND: Myalgic encephalomyelitis is an invalidating chronic disease often associated with exercise-induced alterations of muscle membrane excitability (M wave). No simultaneous measurements of maximal isometric force production and sarcolemma fatigue in the same muscle group have been previously reported. We hypothesized that M wave alterations could be partly responsible for the reduced muscle force present in this invalidating disease. METHODS: This retrospective study compared two groups of patients who presented (n = 30) or not (n = 28) alterations of M waves evoked by direct muscle stimulation during and after a cycling exercise bout. The maximal handgrip strength was measured before and after exercise, concomitantly with electromyogram recordings from flexor digitorum longus muscle. The patients also answered a questionnaire to identify eventual exacerbation of their clinical symptoms following the exercise test. FINDINGS: The M wave amplitude significantly decreased in muscles and the M wave duration significantly increased in the group of patients with M wave alterations after exercise. Resting values of handgrip were significantly lower in patients with exercise-induced M-wave alterations than in patients without M-wave abnormalities. In patients with exercise-induced M-wave alterations, handgrip significantly decreased after exercise and the changes in handgrip and M wave were positively correlated. The frequency of post-exertion malaise, increased fatigue, myalgia, headache and cognitive dysfunction was significantly higher in patients with M-wave alterations and variations in handgrip after exercise. INTERPRETATION: These data suggest that post-exercise sarcolemma fatigue often measured in patients with myalgic encephalomyelitis could be the cause of muscle failure.

Anti-spike protein to determine SARS-CoV-2 antibody levels: Is there a specific threshold conferring protection in immunocompromised patients?

BACKGROUND: Identifying a specific threshold level of SARS-CoV-2 antibodies that confers protection in immunocompromised patients has been very challenging. The aim was to assess the threshold of 264 binding antibody units (BAU)/ml using four different SARS-CoV-2 antibody assays (Abbott, Beckman, Roche, and Siemens) and to establish a new optimal threshold of protection for each of the four antibody assays. METHODS: This study was performed on data retrieved from 69 individuals, who received at least one dose of the Pfizer/BioNTech BNT162b2 or Moderna COVID-19 vaccine (Spikevax) at the Alphabio Laboratory in Marseille, France (European Hospital, Alphabio-Biogroup). The results were compared to the percent inhibition calculated using a functional surrogate of a standardized virus neutralization test (Genscript). RESULTS: Samples from 69 patients were analyzed. For a reference cutoff of 264 BAU/ml, assays showed moderate to good overall concordance with Genscript: 87% concordance for Abbott, 78% for Beckman, 75% for Roche, and 88% for Siemens. Overall concordance increased consistently after applying new thresholds, i.e., 148 BAU/ml (Abbott), 48 (Beckman), 559 (Roche), and 270 (Siemens). CONCLUSION: We suggest specific adjusted thresholds (BAU/ml) for the four commercial antibody assays that are used to assess pre-exposure prophylaxis in immunocompromised patients.

Small Intestinal Bacterial Overgrowths and Intestinal Methanogen Overgrowths Breath Testing in a Real-Life French Cohort.

INTRODUCTION: Breath testing has become a widely used tool to diagnose small intestinal bacterial overgrowths (SIBOs) and intestinal methanogen overgrowths (IMOs) in clinical settings. Owing to the heterogeneity in clinical manifestations and lack of standardization among centers performing breath testing, SIBO and IMO can be easily overlooked by the clinician. We studied the prevalence and symptoms of SIBO/IMO in French patients referred for breath testing after seeking medical advice. METHODS: Breath test data and symptoms of 331 patients were assessed for SIBO/IMO using the H 2 /CH 4 lactulose breath test (LBT). Wilcoxon test or χ 2 test were used to compare patients with SIBO/IMO with patients without SIBO/IMO. LBT positive patients (H 2 +, CH 4 +, and CH 4 +/H 2 +) were compared using Kruskal-Wallis test for continuous data or χ 2 test for categorical data. RESULTS: Among the 186 (68.1%) patients tested positive for an overgrowth with 40.3%, 47.3%, and 12.4% for H 2 +, CH 4 + and CH 4 +/H 2 +, respectively, the presence of diarrhea was significantly increased in hydrogen type overgrowths ( P < 0.001). No significant difference according to age, gender, and symptoms was associated with a positive test except for joint pain that was less prevalent among LBT positive patients ( P = 0.038). In 86.5% of IMOs, positivity with CH 4 values ≥10 ppm could be identified at baseline. DISCUSSION: There are little discriminating symptoms that can help the clinician to identify patients likely to have a SIBO/IMO. However, SIBO/IMOs remain a common disorder widely underdiagnosed that need further studies to better apprehend functional bowel disorders.

Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study.

BACKGROUND: Patients with long-COVID often complain of continuous fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise. No data are available on EMG recording of evoked myopotentials (M-waves) or exercise-induced alterations in long-COVID patients, providing evidence of muscle membrane fatigue. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops in more than half of patients after an infectious disease, particularly viral diseases. A large proportion (around 70%) of these patients have neuromuscular disorders with M-wave alterations during and after exercise. Our hypothesis was that M-wave alterations would be also found in long-COVID patients, in association with neuromuscular symptoms, similar to ME/CFS. METHODS: This retrospective observational ColGEM (Covid LonG Encéphalomyelite Myalgique) study compared 59 patients with long-COVID and 55 ME/CFS patients with a history of severe infection who presented before the COVID pandemic. All of these patients underwent the same protocol consisting of a questionnaire focusing on neural and neuromuscular disorders and M-wave recording in the rectus femoris muscle before, during, and 10 min after a progressive cycling exercise. Maximal handgrip strength (MHGS) and maximal exercise power were also measured. The frequency of symptoms and magnitude of M-wave changes in the two groups were compared using non-parametric and parametric tests. RESULTS: The frequency of fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise as well as the magnitude of exercise-induced M-wave alterations were the same in the two groups. By contrast, digestive problems were less present in long-COVID. M-wave alterations were greater in ME/CFS patients as in those with long-COVID when the highest muscle strength and highest exercise performance were measured. CONCLUSIONS: These high clinical and biological similarities between long-COVID and ME/CFS support the hypothesis that SARS-Cov-2 infection can cause ME/CFS symptoms. Trial registration Registered retrospectively.

A cohort analysis of sexually transmitted infections among different groups of men who have sex with men in the early era of HIV pre-exposure prophylaxis in France.

BACKGROUND: MSM are at particular risk of STIs due to sexual behavior and substance use. HIV PrEP use may increase this risk. DESIGN: Our aim was to comparatively assess incident STIs among different at-risk groups-PLWHIV, HIV-negative PrEP and no-PrEP users-seen at our center early after PrEP implementation. METHODS: Clinical data were retrospectively collected on 636 MSM seen at the Infectious Diseases Department between September 2016 and October 2018. STI incidence rate was assessed among groups for the whole period, as well as separately for each year of the study. RESULTS: Overall STI incidence rate ratio was higher in HIV-neg when compared to PLWHIV. In multivariate analysis, STI risk was significantly higher among HIV-neg no-PrEP users compared to PLWHIV, while not different between PLWHIV and PrEP users.STI incidence globally increased during the first 2 years after PrEP approval among PLWHIV and no-PrEP users, stated by odds ratio (OR = 1.77 [1.23-2.55], p = 0.0020 and OR = 2.29 [0.91-5.73], p = 0.0774 respectively) while it remained rather stable for HIV-neg PrEP users (OR = 1.19 [0.60-2.38], p = 0.6181). The HIV-neg no-PrEP group remained at higher risk of STI than PLWHIV and PrEP users during the two periods. CONCLUSION: These results suggest that a proactive approach of an efficient follow-up of MSM participants since PrEP approval may have prevented an increase of the incidence of STIs among PrEP users.

Human Stool Preservation Impacts Taxonomic Profiles in 16S Metagenomics Studies.

Microbiotas play critical roles in human health, yet in most cases scientists lack standardized and reproducible methods from collection and preservation of samples, as well as the choice of omic analysis, up to the data processing. To date, stool sample preservation remains a source of technological bias in metagenomic sequencing, despite newly developed storage solutions. Here, we conducted a comparative study of 10 storage methods for human stool over a 14-day period of storage at fluctuating temperatures. We first compared the performance of each stabilizer with observed bacterial composition variation within the same specimen. Then, we identified the nature of the observed variations to determine which bacterial populations were more impacted by the stabilizer. We found that DNA stabilizers display various stabilizing efficacies and affect the recovered bacterial profiles thus highlighting that some solutions are more performant in preserving the true gut microbial community. Furthermore, our results showed that the bias associated with the stabilizers can be linked to the phenotypical traits of the bacterial populations present in the studied samples. Although newly developed storage solutions have improved our capacity to stabilize stool microbial content over time, they are nevertheless not devoid of biases hence requiring the implantation of standard operating procedures. Acknowledging the biases and limitations of the implemented method is key to better interpret and support true associated microbiome patterns that will then lead us towards personalized medicine, in which the microbiota profile could constitute a reliable tool for clinical practice.

An optimized stepwise algorithm combining rapid antigen and RT-qPCR for screening of COVID-19 patients.

BACKGROUND & AIM: We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19. METHODS: From August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates. RESULTS: The overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT-qPCR were 72% (95%CI 62%-81%), 99% (95% CI95%-100%), 99% (95%CI 93%-100%), and 78% (95%CI 70%-85%), 0.28 (95%CI 0.21-0.39), and 72 (95%CI 10-208) respectively. Sensitivity was higher for patients with Ct ≤ 25 regardless of TSO: TSO ≤ 4 days 92% (95%CI 75%-99%), TSO > 4 days 100% (95%CI 54%-100%), and asymptomatic 100% (95%CI 78-100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed. CONCLUSIONS: This study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.

Hypnotherapy in Treatment of Mastocytosis: A Prospective Study.

Mastocytosis is an orphan disease associated with many systemic symptoms, chronic handicap, and potentially marked social consequences despite improved therapies. In this study, the authors aimed to measure the effect of 2 hypnosis sessions on mastocytosis symptoms in a clinical setting. Questionnaires (pain, flushes, energy, digestive symptoms, quality of life, perceived symptom severity, and global impression of change) were completed pre- and posthypnosis intervention. Data from 20 patients were analyzed (mean age: 53.3 years, 75% female). Compared to baseline assessment, patients exhibited a significant improvement immediately after the first and second hypnosis sessions with regard to the number of days with abdominal pain, abdominal pain intensity and fatigue (p = .03 and p = .005; p = .05 and p = .02; p = .034, and p = .039, respectively). Perceived severity of symptoms was significantly improved throughout the study (p = .0075). Long-term improvement in global impression of change was observed in half the responders (8/16). Patients with mastocytosis had an improvement in disabling symptoms with the impact of hypnotic intervention persisting at 1 month. Several patients experienced long-term improvement.

Adverse Events Induced by PD-1/PD-L1 Inhibitors: A Real-World Single-Centre Experience with a Management-Based Approach.

AIM: To assess the efficacy and tolerance of programmed death-1 (PD-1) and PD-ligand 1 (PD-L1) inhibitors and the impact of a standardised management-based protocol in a real-world setting. PATIENTS AND METHODS: Data from patients who had received anti-PD-(L)1 were collected from our pharmacy database. Clinical response and toxicity were assessed using RECIST criteria and CTCAE version 5.0, respectively. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method. Potential prognostic factors were identified using Cox's model. RESULTS: A total of 196 patients and 201 lines of treatment were included (median age: 66 (range: 38-89) years). Types of cancer included non-small cell lung cancer (73%), transitional cell carcinoma (10%), renal cell carcinoma (6%), small cell lung cancer (5%), head and neck squamous cell carcinoma (4%) and classical Hodgkin's lymphoma (1%). Twenty-five (12%) patients had pre-existing autoimmune conditions. Our standardised management-based protocol included 129 (64%) patients. Objective response rate was 29%, median OS was 10 months (IQR: 7-15) and median PFS was 5 months (IQR: 1-22). Patients with an abnormal baseline complete blood count had a worse OS (HR=2.48 [95% CI: 1.24-4.96]; p=0.0103). Thirty-three (16%) patients experienced severe (grade 3 or 4) immune-related adverse event (irAE). There were three (1%) irAE-related deaths. AEs resolved faster when patients were assessed by an internist before anti-PD-(L)1 initiation (p=0.0205). CONCLUSION: PD-1 and PD-L1 inhibitors are effective and safe in a real-world setting. Implementation of a standardised management-based protocol with internal medicine specialists is an effective way to optimise irAE management.

Frailty phenotype is associated with antiretroviral exposure among older persons living with HIV.

PURPOSE OF REVIEW: This multicentre, cross-sectional study was carried out in the South of France to assess the association between frailty phenotype and antiretroviral therapy (ART) in older persons living with HIV (PLWHIV). Sociodemographic and HIV data, geriatric assessment, comorbidities, behavioral and age-related variables and the five frailty markers of Fried were recorded. Exposure to any pharmacological class of ART and all regimens were retrieved from medical records. RECENT FINDINGS: The 509 PLWHIV analysed (72.7% male) received a mean of 6.01 ART regimens and 12.5 years exposure to ART. The prevalence of at least one frailty marker [frail and prefrail phenotype (FPFP)] was 66.4%. Duration of exposure to protease inhibitors and reverse transcriptase inhibitors, number of ART regimens and comorbidities, dyslipidaemia, cancer, depression, falls, disability and pain were significantly associated with FPFP by univariate analysis. In logistic regression multivariable analysis, independent predictors for FPFP were a large number of ART regimens, presence of cancer and pain. No significant association was found with HIV-related parameters neither with ART class and duration. SUMMARY: A significant association was found between FPFP and a large number of different ART regimens among older PLWHIV. The burden of cancer and pain in these patients shows the importance of comprehensive care.

Prospective screening of liver fibrosis in a primary care cohort using systematic calculation of fib-4 in routine results.

BACKGROUND & AIM: Liver fibrosis screening in primary care population is a major public health issue. The FIB-4 index is a simple non-invasive fibrosis test combining age, transaminases, platelets count, developed for the diagnosis of advanced fibrosis. The aim of our study was to evaluate the interest of liver fibrosis screening using systematic calculation of FIB-4 in routine blood analysis. METHODS: Between December 2018 and May 2019, we conducted a prospective screening of liver fibrosis in 134 158 patients during a medical check-up including routine blood analysis. Among these patients, 29 707 had transaminases and platelets counts available and benefited from an automatic calculation of FIB-4. Results were obtained from 21 French clinical laboratories in the Bouches du Rhône region. RESULTS: Among the 29 707 patients, 2161 (7.3%) had a high risk of advanced fibrosis (FIB-4>2.67). Individual investigation of patients with FIB-4>2.67 allowed to screen 1268 (1268/2161: 58.7%) patients who were not managed for any liver disease. CONCLUSIONS: This work demonstrates the interest of FIB-4 for the screening of liver fibrosis in primary care population. Although additional clinical validation study is required to determine the utility and applicability of Fib-4 to daily practice, our study strongly supports this easy-to-implement strategy using a simple Fib-4 measure resulting from the use of available routine test results.

Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome.

BACKGROUND: In myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), altered membrane excitability often occurs in exercising muscles demonstrating muscle dysfunction regardless of any psychiatric disorder. Increased oxidative stress is also present in many ME/CFS patients and could affect the membrane excitability of resting muscles. METHODS: Seventy-two patients were examined at rest, during an incremental cycling exercise and during a 10-min post-exercise recovery period. All patients had at least four criteria leading to a diagnosis of ME/CFS. To explore muscle membrane excitability, M-waves were recorded during exercise (rectus femoris (RF) muscle) and at rest (flexor digitorum longus (FDL) muscle). Two plasma markers of oxidative stress (thiobarbituric acid reactive substance (TBARS) and oxidation-reduction potential (ORP)) were measured. Plasma potassium (K+) concentration was also measured at rest and at the end of exercise to explore K+ outflow. RESULTS: Thirty-nine patients had marked M-wave alterations in both the RF and FDL muscles during and after exercise while the resting values of plasma TBARS and ORP were increased and exercise-induced K+ outflow was decreased. In contrast, 33 other patients with a diagnosis of ME/CFS had no M-wave alterations and had lower baseline levels of TBARS and ORP. M-wave changes were inversely proportional to TBARS and ORP levels. CONCLUSIONS: Resting muscles of ME/CFS patients have altered muscle membrane excitability. However, our data reveal heterogeneity in some major biomarkers in ME/CFS patients. Measurement of ORP may help to improve the diagnosis of ME/CFS. Trial registration Ethics Committee "Ouest II" of Angers (May 17, 2019) RCB ID: number 2019-A00611-56.

Maximal handgrip strength can predict maximal physical performance in patients with chronic fatigue.

BACKGROUND: Maximal handgrip strength is used to predict exercise performance in healthy older subjects and in patients with chronic obstructive pulmonary disease, breast cancer or cirrhosis. Our objective was to evaluate the ability of maximal handgrip strength to predict maximal exercise performance in patients with chronic fatigue. METHODS: Sixty-six patients with myalgic encephalomyelitis/chronic fatigue syndrome and 32 patients with chronic fatigue but no diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were included. The maximal physical performance was measured on a cycle ergometer to measure the peak oxygen uptake and the maximal work rate. We searched for linear regressions between maximal handgrip strength and maximal performances. FINDINGS: No significant differences in slopes and ordinates of regression lines were noted between patients with or without a diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, allowing to pool the data. Maximal handgrip strength was significantly and positively correlated with peak oxygen uptake and maximal work rate in all patients with chronic fatigue. INTERPRETATION: We conclude that handgrip strength can predict maximal exercise performance in patients with chronic fatigue.

Predicting Chemotherapy Toxicity and Death in Older Adults with Colon Cancer: Results of MOST Study.

PURPOSE: Older patients with colon cancer (CC) are vulnerable to chemotherapy toxicity and death. Establishing simple scores specific for patients with CC to predict severe chemotoxicity or early death is needed to select the best treatment strategy. SUBJECTS, MATERIALS, AND METHODS: This prospective multicenter study included patients aged ≥70 years with CC receiving adjuvant or first-line metastatic chemotherapy. Frailty markers (nutrition, physical activity, energy, mobility, strength), comprehensive geriatric assessment (functional status, comorbidities, falls, nutrition, cognition, and depression), and usual laboratory parameters were collected. Logistic or Cox regression was used to examine at 500 days the association between frailty markers, comprehensive geriatric assessment, laboratory parameters, and grade 3-4 toxicity or death. RESULTS: A total of 97 patients (median age, 79.0 years) received adjuvant (37.1%) or metastatic (62.9%) chemotherapy. During the first 500 days, grade 3-4 toxicity occurred in 49.5%, and 30% died. The predictive model for grade 3-4 toxicity combined (polychemotherapy × 3) + (hypoalbuminemia <32 g/L × 2) + (abnormal grip strength × 1.5) + C-reactive protein >11 mg/L + Eastern Cooperative Oncology Group performance status (ECOG-PS), cutoff score >3. The predictive model for death combined (metastasis × 5) + (age × 2) + alkaline phosphatase >100 IU/mL + sex (female) + abnormal grip strength + ECOG-PS, cutoff score >6. For chemotoxicity prediction, sensitivity was 81.6% and specificity 71.4%. For death prediction, sensitivity was 89.7% and specificity was 83.6%. CONCLUSION: These simple and efficient "ColonPrediscores" will help to better identify older patients with CC with increased risk of chemotherapy-related toxicity and/or death. IMPLICATIONS FOR PRACTICE: The two scores assessed in this study, called "ColonPrediscores", offer a major advantage in that they do not need a previous complete geriatric assessment, which makes them an easy-to-use tool in oncologic settings.

Paradoxical association between blood modular interferon signatures and quality of life in patients with systemic lupus erythematosus.

OBJECTIVES: Blood transcriptomic IFN signature is a hallmark of SLE. The impaired health-related quality of life (HRQOL) observed in SLE is poorly related to disease activity. The aim of this study was to test how IFN signatures were associated with HRQOL in SLE patients. METHODS: Among consecutive patients, blood transcriptomic profiles were analysed with a modular framework comprising 3 IFN modules: M1.2, M3.4 and M5.12. Disease activity was evaluated by the SLEDAI score, and HRQOL was assessed with the SF-36 questionnaire, which includes eight domains: physical function, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health (MH) and physical component summary and mental component summary scores. RESULTS: A total of 57 SLE patients were evaluated, among whom 27 (47%) were clinically quiescent, 30 (53%) were flaring, and 19 (33%) had active lupus nephritis. All SF-36 domains were altered in SLE patients compared with the general French population (P < 0.0001). In multivariate analysis, taking into account flares, age, ethnicity, smoking and renal severity, social functioning was independently associated with the IFN score (P = 0.027). Analyses restrained to quiescent patients (n = 27) yielded greater associations between social functioning and the three IFN modules, and between MH and M3.4. Considering all quiescent visits (n = 51), the IFN score was independently correlated with social functioning (P = 0.022) and MH (P = 0.038). CONCLUSION: This unexpected paradoxical association between IFN signature and some specific HRQOL domains argues against a pivotal role of IFNs in the persistently altered HRQOL of SLE patients.

Understanding neuromuscular disorders in chronic fatigue syndrome.

Muscle failure has been demonstrated in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Neurophysiological tools demonstrate the existence of both central and peripheral fatigue in these patients. Central fatigue is deduced from the reduced amplitude of myopotentials evoked by transcranial magnetic stimulation of the motor cortex as well as by the muscle response to interpolated twitches during sustained fatiguing efforts. An impaired muscle membrane conduction velocity assessed by the reduced amplitude and lengthened duration of myopotentials evoked by direct muscle stimulation is the defining feature of peripheral fatigue. Some patients with ME/CFS show an increased oxidative stress response to exercise. The formation of lipid hydroperoxides in the sarcolemma, which alters ionic fluxes, could explain the reduction of muscle membrane excitability and potassium outflow often measured in these patients. In patients with ME/CFS, the formation of heat shock proteins (HSPs) is also reduced. Because HSPs protect muscle cells against the deleterious effects of reactive oxygen species, the lack of their production could explain the augmented oxidative stress and the consecutive alterations of myopotentials which could open a way for future treatment of ME/CFS.