[Short antibiotic therapy in hospitalized pneumonia: A cohort study]. / Antibiothérapie courte au cours de la pneumonie : PNEUMOSHORT.

INTRODUCTION: Pneumonia is one of the most common indications for antibiotic. Shortening the duration of antibiotic therapy should help reduce bacterial resistance. To date, three randomized control trials have shown non-inferiority of short courses of antibiotic therapy (3 days) compared with 7 days in non-severe pneumonia. The aim of this study was to assess this strategy in real life. METHOD: This retrospective observational cohort study included all patients with pneumonia hospitalized in an internal medical ward from 11/01/2022 to 05/31/2023. We implemented the strategy based on early discontinuation of antibiotic therapy in patients with pneumonia who were clinically stable after 3 days of ß-lactam treatment. RESULTS: Among 49 patients included, median age was 72, median antibiotic duration was 4 days (IQR 3-6), and cure rate at D30 was 88 %. At day 30, we observed one death (2 %), four new antibiotic therapy (9 %), and two new hospitalisation (5 %), among five immunosuppressed patients. Among immunosuppressed patients (n=17; 35 %), failure rate was three times higher in case of short antibiotic courses (3/8; 38 %) than long antibiotic courses (1/7; 14 %). CONCLUSION: Strategy based on early discontinuation of antibiotic therapy in immunocompetent patients with pneumonia who were clinically stable after 3 days of ß-lactam treatment is safe, and easy to implement in a medical ward.

Preexisting autoantibodies as predictor of immune related adverse events (irAEs) for advanced solid tumors treated with immune checkpoint inhibitors (ICIs).

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are now standard of care in many cancers. They can generate immune-related adverse events (irAEs), but no biomarkers are available to identify patients who are more likely to develop irAEs. We assess the association between pre-existing autoantibodies and occurrence of irAEs. PATIENTS AND METHODS: We prospectively collected data from consecutive patients receiving ICIs for advanced cancers, in a single center between May 2015 and July 2021. Autoantibodies testing was performed before ICIs initiation including AntiNeutrophil Cytoplasmic Antibodies, Antinuclear Antibodies, Rheumatoid Factor anti-Thyroid Peroxidase and anti-Thyroglobulin. We analyzed the associations of pre-existing autoantibodies with onset, severity, time to irAEs and with survival outcomes. RESULTS: Of the 221 patients included, most had renal cell carcinoma (n = 99; 45%) or lung carcinoma (n = 90; 41%). Grade ≥2 irAEs were more frequent among patients with pre-existing autoantibodies: 64 (50%) vs. 20 (22%) patients (Odds-Ratio= 3.5 [95% CI=1.8-6.8]; p < 0.001) in the positive vs negative group, respectively. irAEs occurred earlier in the positive group with a median time interval between ICI initiation and irAE of 13 weeks (IQR = 8.8-21.6) vs. 28.5 weeks (IQR=10.6-55.1) in the negative group (p = 0.01). Twelve patients (9.4%) experienced multiple (≥2) irAEs in the positive group vs. 2 (2%) in the negative group (OR = 4.5 [95% CI: 0.98-36], p = 0.04). After a median follow-up of 25 months, median PFS and OS were significantly longer among patients experiencing irAE (p = 0.00034 and p = 0.016, respectively). CONCLUSION: The presence of pre-existing autoantibodies is significantly associated with the occurrence of grade ≥2 irAEs, with earlier and multiple irAEs in patients treated with ICIs.

[Splenic dysfunction in sickle cell disease: An update]. / Dysfonction splénique au cours de la drépanocytose : mise au point.

The spleen filters blood cells and contributes to the immune defense. The red pulp clears the blood from altered red blood cells via its unique microcirculatory network ; while the white pulp is a secondary lymphoid organ, directly connected to the bloodstream, whose specificity is the defense against encapsulated bacteria through the production of "natural" IgM in the marginal zone. Various health conditions can cause acquired impairment of the splenic function (or hyposplenism) directly and/or through therapeutic splenectomy. Hypo/asplenia is complicated by an increased susceptibility to encapsulated germ infections, but an increased risk of thrombosis and pulmonary hypertension has also been reported after surgical splenectomy. Homozygous sickle cell disease is the most common disease associated with functional asplenia. The latter appears early in childhood likely through repeated ischemic alterations caused by the sickling of red blood cells. In addition, specific complications such as hypersplenism and acute splenic sequestration can occur and may be life-threatening. We provide here an update on the role and physiology of the spleen, which will allow a better understanding of the pathophysiology of spleen damage and its consequences in sickle cell disease.

[Contribution and limits of "OSCE", "long-case" and "global end-of-placement marking" as end-of-rotation assessment methods. Experience from two internal medicine wards]. / Apport et limites des « ECOS ¼, « examen clinique au lit du malade ¼ et « appréciation globale de stage ¼ comme modalité d'évaluation de fin de stage. Expérience de deux services de médecine interne.

INTRODUCTION: During placements, there is an opportunity to learn clinical skills and to assess their application. However, it represents two different goals. The validity of an end-of-placement assessment is questionable, as the medical competency is contextual. We decided to evaluate the contribution and limits of different assessment modalities as an end-of-placement assessment. MATERIAL AND METHODS: Internal medicine clerks were assessed using the Mini-Cex grid by a structured objective clinical examination (OSCE), a long-case clinical examination (LCE) and a global end-of-placement marking (GEPM). Following these evaluations, students and teachers fulfilled an open questionnaire. RESULTS: In 2021, 41 students and 16 teachers participated in the study. Physical examination was evaluated in 0%, 97% et 76% of cases during OSCE, LCE and GEPM, respectively; teaching skills were assessed for 100, 42 et 49% of students in OSCE, LCE and GEPM, respectively. As compared to OSCE, there was a perceived superiority of LCE regarding its formative value (P=0.07 and P=0.03) and its summative value (P=0.0007 and P=0.02), for students and teachers, respectively. Qualitative analysis highlights the breadth of clinical skills that could be assessed during OSCE stations. Integration into a team was an additional skill that could specifically be assessed during GEPM. GEPM could also take into account the progress made during placement. CONCLUSION: Despite its subjectivity, LCE seemed to be the preferred modality for an end-of-rotation assessment.

[Acute chest syndrome in adult sickle cell patients]. / Syndrome thoracique aigu chez les patients drépanocytaires adultes.

Sickle cell disease is a frequent genetic condition, due to a mutation of the ß-globin gene, leading to the production of an abnormal S hemoglobin and characterized by multiple vaso-occlusive events. The acute chest syndrome is a severe complication associated with a significant disability and mortality. It is defined by the association of one or more clinical respiratory manifestations and a new infiltrate on lung imaging. Its pathophysiology is complex and implies vaso-occlusive phenomena (pulmonary vascular thrombosis, fat embolism), infection, and alveolar hypoventilation. S/S or S/ß0-thalassemia genotype, a history of vaso-occlusive crisis or acute chest syndrome, a low F hemoglobin level (<5%), a high steady-state hemoglobin level (> 10 g/dL), or a high steady-state leukocytosis (>10 G/L) are the main risk factors. Febrile chest pain, dyspnea, sometimes cough with expectorations are its main clinical manifestations, and bi-basal crackles are found at auscultation. Inferior alveolar opacities with or without pleural effusions are identified on chest X-ray or CT-scan. Management of the acute chest syndrome should be prompt and implies, besides the recognition of severity signs, a multimodal analgesia, oxygen supplementation, sometimes a parenteral antibiotic treatment and the frequent use of blood transfusions especially in the most severe cases. Prevention is important and includes a regular monitoring of hospitalized patients and the use of incentive spirometry.

[Gallstone complications in sickle cell patients]. / Complications lithiasiques chez les patients drépanocytaires.

Chronic haemolysis exposes patients with sickle cell disease (SCD) to the development of black pigment gallstones, which can trigger biliary complications. In order to avoid these complications, elective cholecystectomy is recommended in France for all SCD patients with detected gallstones. However, all surgeries, and especially abdominal surgeries, entail an increased risk of vaso-occlusive complications in the peri- and post-operative periods, the most dreadful one being the acute chest syndrome. Preoperative transfusion has been shown in several studies to reduce acute postoperative complications, but exposes the patient to definitive alloimmunization, or even delayed post- transfusion haemolysis, justifying a recent trend towards transfusion sparing. The conditions for avoiding transfusion for a simple and frequent surgery such as cholecystectomy are based on a benefit- risk balance, and must be discussed on a case-by-case basis by the SCD specialist. In particular, it seems fully justified to perform prophylactic preoperative transfusion in patients with a history of recent vaso-occlusive crisis or acute chest syndrome (within 6 months preoperatively), and those operated on in an emergency setting, who are particularly at risk of postoperative events.

A data-driven pipeline to extract potential adverse drug reactions through prescription, procedures and medical diagnoses analysis: application to a cohort study of 2,010 patients taking hydroxychloroquine with an 11-year follow-up.

CONTEXT: Real-life data consist of exhaustive data which are not subject to selection bias. These data enable to study drug-safety profiles but are underused because of their temporality, necessitating complex models (i.e., safety depends on the dose, timing, and duration of treatment). We aimed to create a data-driven pipeline strategy that manages the complex temporality of real-life data to highlight the safety profile of a given drug. METHODS: We proposed to apply the weighted cumulative exposure (WCE) statistical model to all health events occurring after a drug introduction (in this paper HCQ) and performed bootstrap to select relevant diagnoses, drugs and interventions which could reflect an adverse drug reactions (ADRs). We applied this data-driven pipeline on a French national medico-administrative database to extract the safety profile of hydroxychloroquine (HCQ) from a cohort of 2,010 patients. RESULTS: The proposed method selected eight drugs (metopimazine, anethole trithione, tropicamide, alendronic acid & colecalciferol, hydrocortisone, chlormadinone, valsartan and tixocortol), twelve procedures (six ophthalmic procedures, two dental procedures, two skin lesions procedures and osteodensitometry procedure) and two medical diagnoses (systemic lupus erythematous, unspecified and discoid lupus erythematous) to be significantly associated with HCQ exposure. CONCLUSION: We provide a method extracting the broad spectrum of diagnoses, drugs and interventions associated to any given drug, potentially highlighting ADRs. Applied to hydroxychloroquine, this method extracted among others already known ADRs.

Specific Follicular Helper T Cell Signature in Takayasu Arteritis.

OBJECTIVE: Our aim was to compare transcriptome and phenotype profiles of CD4+ T cells and CD19+ B cells in patients with Takayasu arteritis (TAK), patients with giant cell arteritis (GCA), and healthy donors. METHODS: Gene expression analyses, flow cytometry immunophenotyping, T cell receptor (TCR) gene sequencing, and functional assessments of cells from peripheral blood and arterial lesions from TAK patients, GCA patients, and healthy donors were performed. RESULTS: Among the most significantly dysregulated genes in CD4+ T cells of TAK patients compared to GCA patients (n = 720 genes) and in CD4+ T cells of TAK patients compared to healthy donors (n = 1,447 genes), we identified a follicular helper T (Tfh) cell signature, which included CXCR5, CCR6, and CCL20 genes, that was transcriptionally up-regulated in TAK patients. Phenotypically, there was an increase in CD4+CXCR5+CCR6+CXCR3- Tfh17 cells in TAK patients that was associated with a significant enrichment of CD19+ B cell activation. Functionally, Tfh cells helped B cells to proliferate, differentiate into memory cells, and secrete IgG antibodies. Maturation of B cells was inhibited by JAK inhibitors. Locally, in areas of arterial inflammation, we found a higher proportion of tertiary lymphoid structures comprised CD4+, CXCR5+, programmed death 1+, and CD20+ cells in TAK patients compared to GCA patients. CD4+CXCR5+ T cells in the aortas of TAK patients had an oligoclonal α/ß TCR repertoire. CONCLUSION: We established the presence of a specific Tfh cell signature in both circulating and aorta-infiltrating CD4+ T cells from TAK patients. The cooperation of Tfh cells and B cells might be critical in the occurrence of vascular inflammation in patients with TAK.

Syndrome de Cogan.

"Typical" Cogan's syndrome is defined as a non-syphilitic interstitial keratitis associated with audio-vestibular resembling Ménière's disease with a 2-year maximum delay between these 2 organ impairment. Cogan syndrome is classified as "atypical" in the absence of interstitial keratitis and the presence of other inflammatory eye manifestations, an audio-vestibular impairment different from typical Menière-like disease, or a delay longer than 2 years between eye and audio-vestibular manifestations. Constitutional signs and large-vessel vasculitis is also possible, mostly affecting the thoracic aorta. The presence of acute-phase reactants is common, but no specific laboratory tests are available. The prognosis is dominated by the audio-vestibular impairment and in particular the risk of deafness, while other complications especially vascular complications being rare. Treatment with glucocorticoids is usually necessary and the combination to other immunosuppressive therapies or biological-targeted drugs needs to be determined.

Effects of a multifaceted intervention to promote the use of intravenous iron sucrose complex instead of ferric carboxymaltose in patients admitted for more than 24 h.

PURPOSE: Although more practical for use, the impact of ferric carboxymaltose (FCM) on the hospital budget is considerable, and intravenous iron sucrose complex (ISC) represents a cost-saving alternative for the management of iron deficiency anemia in patients during hospitalization. The Drug Committee decided to reserve FCM for day hospitalizations and contraindications to ISC, especially allergy. ISC was available for prescription for all other situations. METHODS: The impact of a multifaceted intervention promoting a switch from FCM to ISC was evaluated using an interrupted time series model with segmented regression analysis. The standardized rate of the dispensing of FCM, ISC, and oral iron by the hospital pharmacy, as well as the rate of the dispensing of packed red blood cells and the number of biological iron status measurements, was analyzed before and after the intervention. RESULTS: There was an immediate decrease in FCM consumption following the intervention, with a reduction of 88% (RR: 0.12 [CI95% 0.10 to 0.15]). Conversely, there was a large increase in ISC use (RR: 5.1 [CI95% 4.4 to 5.9]). We did not observe a prescription shift to packed red blood cells or oral iron after the intervention. The time series analysis showed the frequency of iron status testing to remain stable before and after. The direct savings for intravenous iron for 8 months were 187,417.54 €. CONCLUSION: Our intervention to lower the impact of intravenous iron therapy on the hospital budget was effective.

[Sickle cell trait complications: A case series of 6 patients]. / Complications du trait drépanocytaire : à propos d'une série de 6 cas.

INTRODUCTION: Patients with sickle cell trait (SCT) are commonly considered as asymptomatic carriers. However, some clinical manifestations may occur. METHODS: Here we present a retrospective descriptive study about SCT subjects with at least one complication diagnosed in a sickle cell disease referral center, in Paris, between 2008 and 2019. We also performed a literature review on the complications of SCT subjects. RESULTS: Six patients (between 19 and 65 years old) were included. SCT was already known only for 4 of them at the time of the complication. Four patients presented with a splenic infarct after a stay in high altitude or a plane trip, one of them was associated with papillary necrosis; one patient had isolated papillary necrosis, and the last one had splenic sequestration. These complications happened for most of them after exposure to an unusual situation of hypoxia or deshydratation. Five out of 6 patients had a marked elevated C reactive protein. CONCLUSION: SCT may cause acute ischemic complications in a context of prolonged hypoxia or dehydration. The most commonly reported are the splenic infarct and the renal papillary necrosis. A study of hemoglobin should be considered in these clinical situations in patients with compatible ethnic origin.

[Pituitary apoplexy following coronary bypass surgery: A case report and literature review]. / Apoplexie hypophysaire après pontage aorto-coronarien : à propos d'une observation et revue de la littérature.

INTRODUCTION: Pituitary apoplexy is a >rare entity that presents with a sudden onset of headache associated with visual and endocrinological disturbances due to pituitary hemorrhage or infarction. It usually occurs in patients with an unknown pituitary adenoma. Cardiac surgery, and especially coronary artery bypass grafting, can be a precipitating factor in these patients. CASE REPORT: We report an 82-year-old male patient who presented with sudden headache and delirium, a right sixth cranial nerve palsy, a right temporal hemianopsia, and a severe loss of left eye visual acuity in the immediate post-operative course of a coronary artery bypass surgery. Pituitary apoplexy was demonstrated on both MRI and CT-scan. Trans-sphenoidal surgical decompression was performed 13 days after coronary artery bypass grafting, with immediate beneficial effect on the delirium and a partial recovery of visual disturbances. CONCLUSION: Pituitary apoplexy is a rare and life-threatening complication that may occur after cardiac surgery (coronary artery bypass, cardiac valve surgery), often precipitated by the use of cardiopulmonary bypass. It can occur after other surgical procedures (orthopedic, digestive, thoracic). The diagnosis must be considered during the early postoperative period in the presence of unusual and severe headache associated with visual disturbances.

[Botulism: A case report and literature review]. / Botulisme : à propos d'un cas et revue de la littérature.

INTRODUCTION: Botulism is a rare syndrome resulting from the action of a neurotoxin produced by Clostridium botulinum, that it is potentially life threatening if diagnosis is delayed. CASE REPORT: We report a 26-year-old woman who presented an acute onset of bilateral cranial neuropathies associated with an anticholinergic syndrome in the absence fever leading to consider and confirm the diagnosis of botulism. At the end of follow-up, 7 weeks later, the outcome was favorable with an almost complete neurologic recovery. CONCLUSION: Although botulism is uncommon, better awareness of its manifestations and high clinical suspicion should shorten diagnostic delay that makes the use of specific antitoxin ineffective. An acute onset of a bilateral oculomotor palsy, a fixed pupillary dilation and descending weakness in the absence of fever is typical of botulism. Outcome is usually favorable with a slow but full neurological recovery.

[Improvement of antibiotic therapy adequacy with local guidelines and their reassessment through a multidisciplinary action: Prospective study in an Internal Medicine department]. / Amélioration de l'adéquation des antibiothérapies aux recommandations et de leur réévaluation par une action pluridisciplinaire : étude prospective dans un service de médecine interne.

INTRODUCTION: The implementation of antimicrobial stewardship actions is important in the fight against antimicrobial resistance. The objective of our study was to evaluate the impact of a multidisciplinary program on the adequacy of antibiotic prescriptions with local guidelines in terms of indication, molecule, dosage and treatment duration during the 48-72h reassessment in an internal medicine department. METHOD: This was a before/after monocentric, prospective study. All patients hospitalized in the internal medicine department who were treated with antibiotics for at least 48h were included. The intervention had two components: training of residents about antibiotic treatment and development of a multidisciplinary 48-72h reassessment team. Our primary endpoint was the adequacy of prescriptions with local guidelines, assessed by an independent blinded committee. We also measured antibiotic consumptions. RESULTS: One hundred and twelve patients were included. Adequacy with local recommendations increased from 57.1% to 97.8% (P<0.01), including for the duration of treatment. Traceability of reassessment in medical records increased from 65.3 % to 97.8 % (P<0.01). Finally, the part of consumption of antibiotics with high risk of resistance selection decreased during the period "after" (-10.2 %, P<0.01). CONCLUSION: The set-up of a multimodal (association of pedagogic and incentive actions) and multidisciplinary (internist, clinical pharmacist and antimicrobial stewards) action improved the adequacy of antibiotic prescriptions with local guidelines.

AA amyloidosis secondary to adult onset Still's disease: About 19 cases.

OBJECTIVE: Adult onset Still's disease (AOSD) is an inflammatory disorder characterized by high spiking fever, evanescent rash, polyarthritis, and many other systemic manifestations. Recurrent or persistent disease can lead to AA amyloidosis (AAA). Our objectives were to present 3 French cases and perform a systematic review of the literature, in order to determine the prevalence, characteristics, predisposing factors, and therapeutic response of AOSD-related AAA. METHODS: A systematic literature review was performed by searching MEDLINE from 1971 to 2018. Two independent investigators selected reports of AAA complicating AOSD. New French cases were identified with the help of the Reference Center for rare Auto-Inflammatory Diseases and Amyloidosis (CEREMAIA). Patients with juvenile idiopathic arthritis were excluded. RESULTS: The prevalence of AAA in AOSD was 0.88% (95%CI [0.49-1.28]) based on 45 articles. In addition to 3 new cases from the CEREMAIA, 16 patients were assessed for clinical presentation, risk factors, and therapeutic response of AOSD-related AAA. Mean age at AOSD onset was 29.6 ±â€¯12.6 years, with a mean delay before AAA diagnosis of 16.75±5.8 years. Renal involvement was the most common manifestation of AAA. The majority of patients presented active AOSD at AAA diagnosis. Various treatments of AOSD-related AAA were attempted including corticosteroids and biotherapies. CONCLUSION: AAA is a rare and severe complication that may occur during the course of uncontrolled active AOSD. It could be prevented by early diagnosis and better control of AOSD, with more frequent use of biotherapies.

[Legionella spp: An update]. / Actualités sur les infections à Legionella.

Legionella-related disease is caused by an intracellular bacteria mainly living in water. Contamination results from inhalation of Legionella sp containing aerosolized water. Main risk factors are tobacco, immunodeficiency, and advanced age. Antigenuria is the cornerstone of the diagnosis. Immunocompromised patients, more commonly infected with non pneumophilaLegionella, present negative antigenuria, and culture and PCR are essential for the diagnosis. Legionnaires' disease may be severe, especially in elderly and/or immunocompromised patients. Mortality rate varies from 10 % in the general population to 50 % in intensive care. Treatment is based on macrolides or fluoroquinolones. Antibiotic resistance is very rare.

[Opioid-induced adrenal insufficiency: Case report and synthesis of the literature]. / Insuffisance surrénale secondaire aux opioïdes : rapport de cas et synthèse de la littérature.

INTRODUCTION: Opioid therapy for pain relief is associated with several adverse effects. Herein, we report the potential consequences of opioid use on the adrenal function. OBSERVATION: A 49-year-old woman with sickle cell anemia (Hemoglobin SS) was admitted for the treatment of a vaso-occlusive crisis. Morphine was used for pain management, provided by intravenous intermittent dosing (patient-controlled analgesia). She developed during the hospitalization low blood pressure, due to secondary adrenal insufficiency (cortisol 74 nmol/L; ACTH 2.9pmol/L). Pituitary gland was normal on brain magnetic resonance imaging and adrenal function recovered after morphine discontinuation. CONCLUSION: Opioids suppress cortisol secretion, primarily mediated by direct negative effect on hypothalamus and pituitary gland. Further studies are needed to define the incidence and the clinical significance of opioid-induced adrenal insufficiency, as well as the need for hormone replacement.