Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial.

BACKGROUND: Glucocorticoids probably improve outcomes in patients hospitalised for community acquired pneumonia (CAP). In this a priori planned exploratory subgroup analysis of the phase 3 randomised controlled Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial, we aimed to investigate responses to hydrocortisone plus fludrocortisone between CAP and non-CAP related septic shock. METHODS: APROCCHSS was a randomised controlled trial that investigated the effects of hydrocortisone plus fludrocortisone, drotrecogin-alfa (activated), or both on mortality in septic shock in a two-by-two factorial design; after drotrecogin-alfa was withdrawn on October 2011, from the market, the trial continued on two parallel groups. It was conducted in 34 centres in France. In this subgroup study, patients with CAP were a preselected subgroup for an exploratory secondary analysis of the APROCCHSS trial of hydrocortisone plus fludrocortisone in septic shock. Adults with septic shock were randomised 1:1 to receive, in a double-blind manner, a 7-day treatment with daily administration of intravenous hydrocortisone 50 mg bolus every 6h and a tablet of 50 µg of fludrocortisone via the nasogastric tube, or their placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included all-cause mortality at intensive care unit (ICU) and hospital discharge, 28-day and 180-day mortality, the number of days alive and free of vasopressors, mechanical ventilation, or organ failure, and ICU and hospital free-days to 90-days. Analysis was done in the intention-to-treat population. The trial was registered at ClinicalTrials.gov (NCT00625209). FINDINGS: Of 1241 patients included in the APROCCHSS trial, CAP could not be ruled in or out in 31 patients, 562 had a diagnosis of CAP (279 in the placebo group and 283 in the corticosteroid group), and 648 patients did not have CAP (329 in the placebo group and 319 in the corticosteroid group). In patients with CAP, there were 109 (39%) deaths of 283 patients at day 90 with hydrocortisone plus fludrocortisone and 143 (51%) of 279 patients receiving placebo (odds ratio [OR] 0·60, 95% CI 0·43-0·83). In patients without CAP, there were 148 (46%) deaths of 319 patients at day 90 in the hydrocortisone and fludrocortisone group and 157 (48%) of 329 patients in the placebo group (OR 0·95, 95% CI 0·70-1·29). There was significant heterogeneity in corticosteroid effects on 90-day mortality across subgroups with CAP and without CAP (p=0·046 for both multiplicative and additive interaction tests; moderate credibility). Of 1241 patients included in the APROCCHSS trial, 648 (52%) had ARDS (328 in the placebo group and 320 in the corticosteroid group). There were 155 (48%) deaths of 320 patients at day 90 in the corticosteroid group and 186 (57%) of 328 patients in the placebo group. The OR for death at day 90 was 0·72 (95% CI 0·53-0·98) in patients with ARDS and 0·85 (0·61-1·20) in patients without ARDS (p=0·45 for multiplicative interaction and p=0·42 for additive interaction). The OR for observing at least one serious adverse event (corticosteroid group vs placebo) within 180 days post randomisation was 0·64 (95% CI 0·46-0·89) in the CAP subgroup and 1·02 (0·75-1·39) in the non-CAP subgroup (p=0·044 for multiplicative interaction and p=0·042 for additive interaction). INTERPRETATION: In a pre-specified subgroup analysis of the APROCCHSS trial of patients with CAP and septic shock, hydrocortisone plus fludrocortisone reduced mortality as compared with placebo. Although a large proportion of patients with CAP also met criteria for ARDS, the subgroup analysis was underpowered to fully discriminate between ARDS and CAP modifying effects on mortality reduction with corticosteroids. There was no evidence of a significant treatment effect of corticosteroids in the non-CAP subgroup. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health, by Programme d'Investissements d'Avenir, France 2030, and IAHU-ANR-0004.

COVID-19, air quality and space monitoring.

Due to the worldwide spread of the coronavirus disease 2019 (COVID-19), human mobility and economic activity have slowed down considerably since early 2020. A relatively high number of those infected develop serious pneumonia leading to progressive respiratory failure, system disease and often death. Apart from close human-to-human contact, the acceleration and global diffusion of this pandemic has been shown to be associated with changes in atmospheric chemistry and air pollution by microscopic particulate matter (PM). Breathing air with high concentrations of nitrogen dioxide and PM can result in over-expression of the angiotensin converting enzyme-2 (ACE-2) leading to stress of organs, such as heart and kidneys. Satellite monitoring can play a crucial role in spatio-temporal surveillance of the disease by producing data on pollution as proxy for industrial activity, transport and traffic circulation. Real-time monitoring of COVID-19 in air and chemical pollution of the atmospheric boundary layer available from Earth-observing satellites commuting with Health Information Systems (HIS) would be useful for decision makers involved with public health.

Characteristics and Outcome of SARS-CoV-2 Infection in Cancer Patients.

BACKGROUND: Concerns have emerged about the higher risk of fatal coronavirus disease 2019 (COVID-19) in cancer patients. In this article, we review the experience of a comprehensive cancer center. METHODS: A prospective registry was set up at Institut Curie at the beginning of the COVID-19 pandemic. All cancer patients with suspected or proven COVID-19 were entered and actively followed for 28 days. RESULTS: Among 9842 patients treated at Institut Curie between March 13 and May 1, 2020, 141 (1.4%) were diagnosed with COVID-19, based on reverse transcription polymerase chain reaction testing and/or computerized tomography scan. In line with our case mix, breast cancer (40.4%) was the most common tumor type, followed by hematological and lung malignancies. Patients with active cancer therapy or/and advanced cancer accounted for 87.9% and 68.9% of patients, respectively. At diagnosis, 78.7% of patients had COVID-19-related symptoms, with an extent of lung parenchyma involvement inferior to 50% in 95.8% of patients. Blood count variations and C-reactive protein elevation were the most common laboratory abnormalities. Antibiotics and antiviral agents were administered in 48.2% and 6.4% of patients, respectively. At the time of analysis, 26 patients (18.4%) have died from COVID-19, and 100 (70.9%) were cured. Independent prognostic factors at the time of COVID-19 diagnosis associated with death or intensive care unit admission were extent of COVID-19 pneumonia and decreased O2 saturation. CONCLUSIONS: COVID-19 incidence and presentation in cancer patients appear to be very similar to those in the general population. The outcome of COVID-19 is primarily driven by the initial severity of infection rather than patient or cancer characteristics.

A Radiation Therapy Contouring Atlas for Cardiac Conduction Node Delineation.

PURPOSE: The heart is a complex organ at risk. Currently, radiation therapy cardiac delineation atlases do not include conduction system substructures, which exposure may clinically translate into arrhythmia and conduction disorders. We present a method to reproducibly delineate conduction nodes on noncontrast simulation computed tomography scans. METHODS AND MATERIALS: Localization and dimensioning of the sinoatrial and atrioventricular nodes volumes on noncontrast simulation computed tomography scans were proposed based on radio-anatomic and histologic considerations and agreed upon by a multidisciplinary staff. RESULTS: The proposed atlas enables the dosimetric evaluation of the sinoatrial and atrioventricular nodes exposure, and both contours correspond to 2-cm diameter spheres. CONCLUSIONS: This delineation atlas should facilitate the delineation of cardiac conduction nodes in clinical research and daily practice.

Assessment of Bacterial Colonization of Intracranial Pressure Transducers: A Prospective Study.

OBJECTIVES: Cerebral infections related to the presence of an intraparenchymal intracranial pressure transducer (ICPT) are rare. We assessed the incidence of ICPT-related infections and colonization using culture, molecular biology, and electron microscopy. METHODS: All consecutive patients in a neurosurgical intensive care unit who had an ICPT inserted between March 2017 and February 2018 were prospectively included. Presence of colonization on the ICPTs was assessed after removal using culture, scanning electron microscopy (SEM), and next-generation sequencing (NGS). RESULTS: Fifty-three ICPTs (53 patients), indwelling for a median of 4 (range 3-7) days, were studied. Median patient follow-up was 3 months. SEM, microbial culture, and NGS were performed for 91%, 79%, and 72% of ICPTs, respectively; 28 ICPTs (53%) were assessed using all three techniques. No patient developed ICPT-related infection. Microbial cultures were positive for two of the ICPTs (5%); colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was observed on 35/48 (73%) of ICPTs. A median of 10 (8-12) operational taxonomic units were identified for each ICPT, most being of environmental origin. There was no association between biofilm maturity and antimicrobial treatment or duration of ICPT insertion. Antimicrobial treatment was associated with decreased alpha and beta-diversity (p = 0.01). CONCLUSIONS: We observed no ICPT-related cerebral infections although colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was the main bacterial lifestyle on the ICPTs.

Hypoalbuminemia-Related Prolonged Sedation After General Anesthesia: A Case Report.

A 69-year-old man underwent total laryngopharyngectomy with radial forearm free flap reconstruction. He had lost 15 kg over a period of 6 months and did not receive any preoperative nutritional workup or management. The patient had a general total intravenous anesthetic with ketamine, lidocaine, and propofol, which was uneventful for an 8-hour surgery. The patient remained deeply sedated for 4 hours after discontinuation of all sedative medications. Diagnostic workup only revealed hypoalbuminemia and hypoproteinemia. We hypothesized relative overdosage of sedative anesthetic drugs due to preoperative malnutrition accentuated by intraoperative fluid administration.

Durability of antimicrobial activity of antibiotic-impregnated external ventricular drains: a prospective study.

BACKGROUND: Antibiotic-impregnated external ventricular drains (AI-EVDs) have a debated efficacy in clinical studies. OBJECTIVES: Our aim was to assess the durability of antimicrobial activity of AI-EVDs used in clinical settings. METHODS: From April 2017 to January 2018, all consecutive AI-EVDs (Bactiseal™) inserted in adult patients were prospectively included. After removal, each AI-EVD was cultured and assessed for antimicrobial activity on both internal and external sides of AI-EVDs. Catheters were each challenged with a single Staphylococcus strain [MSSA, MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE)]. MS was used to measure residual concentrations of rifampicin and clindamycin. RESULTS: Sixty-five AI-EVDs were included (56 patients). Among these, 21 were challenged with MSSA, 23 with MRSA and 21 with MRSE. Five ventriculostomy-related colonizations (9%) and two ventriculostomy-related infections (4%) occurred. Staphylococcus was the main bacterium responsible for colonization (4/5). AI-EVD inhibition decreased significantly against MRSA and MRSE according to duration of catheterization (for external and internal sides, P < 0.02) and overall volume of CSF drained (P < 0.005 for both sides against MRSE, P < 0.005 for external side against MRSA), but not against MSSA. Clindamycin concentration was not correlated with duration of catheterization or CSF volume drained, but <20% of initial concentration was recovered even after 5 days of AI-EVD dwelling. Conversely, rifampicin concentration showed a rapid and significant decline correlated to duration and CSF volume (P < 0.001 and P = 0.03, respectively). CONCLUSIONS: Antimicrobial activity of AI-EVDs dropped quickly in vivo. Antimicrobial impregnation did not prevent AI-EVD colonization by susceptible strains in 9% of the cases.

Natural history of ventriculostomy-related infection under appropriate treatment and risk factors of poor outcome: a retrospective study.

OBJECTIVEThe authors aimed to describe the natural history of ventriculostomy-related infections (VRIs) under appropriate treatment and to assess risk factors for poor outcome.METHODSAll patients older than 18 years in whom an external ventricular drain (EVD) had been implanted and who had developed a VRI requiring treatment were included in this retrospective study. D0 was defined as the first day of antibiotic administration. Clinical and biological parameters were compared each day beginning with D1 and ending with D10 to those of D0. The authors defined D0 in a control group as the day a CSF culture came back positive, without any sign of infection. The authors then searched for poor prognostic factors in the VRI group.RESULTSAmong 567 patients requiring an EVD between January 2007 and October 2017, 39 developed a VRI. Most were monomicrobial infections, and 47 microbes were responsible (45% were gram-positive cocci). Clinical parameters differed significantly from the control group during the first 2 days and then returned to baseline. The CSF parameters differed significantly from the control group for a longer period, returning to baseline after 5 days. CSF sterilization occurred in a median time of 2 days. An intrathecal route or EVD exchange was not associated with a poor outcome. No clinical or biological parameter between D3 and D5 was linked to outcome.CONCLUSIONSClinical status improved faster than CSF parameters (before and after D5, respectively). Some CSF parameters remained abnormal until D10. Body temperature and microbiological cultures normalized faster than other parameters.

Targeted Temperature Management With Total Liquid Ventilation After Ischemic Spinal Cord Injury.

BACKGROUND: Ischemic spinal cord injury is a devastating condition after aortic surgery. We determined whether ultrafast and short whole-body hypothermia provided by total liquid ventilation (TLV) attenuated lower limb paralysis after aortic cross-clamping with a targeted temperature management at 33°C versus 36°C. METHODS: Anesthetized rabbits were submitted to infrarenal aortic cross-clamping during 15 min. A control group (n = 7) was maintained at normothermia (38°C to 38.5°C) with conventional mechanical ventilation. In TLV groups, TLV was started after reperfusion and maintained during 30 min with a target temperature at either 33°C or 36°C (TLV-33°C and TLV-36°C, respectively; n = 7 in each condition). After TLV, animals were resumed to conventional ventilation. Hypothermia was maintained during 120 min, before rewarming and awakening. Hind limb motor function was assessed with modified Tarlov score at day 2 and infarct size in the spinal cord was determined using triphenyltetrazolium chloride staining. RESULTS: Target temperature was achieved within 20 minutes in the two TLV groups. At day 2, the modified Tarlov score was significantly lower in the control group, as compared with TLV-33°C and TLV-36°C groups (0.0 ± 0.0 versus 3.1 ± 0.7 and 2.6 ± 0.6, respectively). The infarct size of the spinal cord was also significantly higher in the control group compared with TLV-33°C and TLV-36°C groups (75% ± 10% versus 32% ± 7% and 28% ± 10%, respectively). Neither motor function nor infarct size differed significantly between TLV-33°C and TLV-36°C groups. CONCLUSIONS: Ultrafast hypothermic TLV attenuates spinal cord injury when applied after ischemic insult. Neurological outcome was similar with targeted temperature management at either 33°C or 36°C.

Development and validation of a pre-hospital "Red Flag" alert for activation of intra-hospital haemorrhage control response in blunt trauma.

BACKGROUND: Haemorrhagic shock is the leading cause of early preventable death in severe trauma. Delayed treatment is a recognized prognostic factor that can be prevented by efficient organization of care. This study aimed to develop and validate Red Flag, a binary alert identifying blunt trauma patients with high risk of severe haemorrhage (SH), to be used by the pre-hospital trauma team in order to trigger an adequate intra-hospital standardized haemorrhage control response: massive transfusion protocol and/or immediate haemostatic procedures. METHODS: A multicentre retrospective study of prospectively collected data from a trauma registry (Traumabase®) was performed. SH was defined as: packed red blood cell (RBC) transfusion in the trauma room, or transfusion ≥ 4 RBC in the first 6 h, or lactate ≥ 5 mmol/L, or immediate haemostatic surgery, or interventional radiology and/or death of haemorrhagic shock. Pre-hospital characteristics were selected using a multiple logistic regression model in a derivation cohort to develop a Red Flag binary alert whose performances were confirmed in a validation cohort. RESULTS: Among the 3675 patients of the derivation cohort, 672 (18%) had SH. The final prediction model included five pre-hospital variables: Shock Index ≥ 1, mean arterial blood pressure ≤ 70 mmHg, point of care haemoglobin ≤ 13 g/dl, unstable pelvis and pre-hospital intubation. The Red Flag alert was triggered by the presence of any combination of at least two criteria. Its predictive performances were sensitivity 75% (72-79%), specificity 79% (77-80%) and area under the receiver operating characteristic curve 0.83 (0.81-0.84) in the derivation cohort, and were not significantly different in the independent validation cohort of 2999 patients. CONCLUSION: The Red Flag alert developed and validated in this study has high performance to accurately predict or exclude SH.

Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.

BACKGROUND: Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock. METHODS: In this multicenter, double-blind, randomized trial with a 2-by-2 factorial design, we evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at intensive care unit (ICU) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors, mechanical ventilation, or organ failure. After drotrecogin alfa (activated) was withdrawn from the market, the trial continued with a two-group parallel design. The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not (placebo group). RESULTS: Among the 1241 patients included in the trial, the 90-day mortality was 43.0% (264 of 614 patients) in the hydrocortisone-plus-fludrocortisone group and 49.1% (308 of 627 patients) in the placebo group (P=0.03). The relative risk of death in the hydrocortisone-plus-fludrocortisone group was 0.88 (95% confidence interval, 0.78 to 0.99). Mortality was significantly lower in the hydrocortisone-plus-fludrocortisone group than in the placebo group at ICU discharge (35.4% vs. 41.0%, P=0.04), hospital discharge (39.0% vs. 45.3%, P=0.02), and day 180 (46.6% vs. 52.5%, P=0.04) but not at day 28 (33.7% and 38.9%, respectively; P=0.06). The number of vasopressor-free days to day 28 was significantly higher in the hydrocortisone-plus-fludrocortisone group than in the placebo group (17 vs. 15 days, P<0.001), as was the number of organ-failure-free days (14 vs. 12 days, P=0.003). The number of ventilator-free days was similar in the two groups (11 days in the hydrocortisone-plus-fludrocortisone group and 10 in the placebo group, P=0.07). The rate of serious adverse events did not differ significantly between the two groups, but hyperglycemia was more common in hydrocortisone-plus-fludrocortisone group. CONCLUSIONS: In this trial involving patients with septic shock, 90-day all-cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo. (Funded by Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of Social Affairs and Health; APROCCHSS ClinicalTrials.gov number, NCT00625209 .).

Dramatic Increase of Amoxicillin-Induced Crystal Nephropathy Found in a Cohort Study of French Pharmacovigilance Centers.

An increase in amoxicillin-induced crystal nephropathy (AICN) incidence has been recently suggested. The aims of this study were to investigate the trend of AICN incidence through Paris' regional centers of pharmacovigilance (Paris RCPVs) and better describe this rare adverse drug reaction. Forty-five AICN cases were identified between 1985 and 2016. All cases, except one, were reported since 2010. Amoxicillin (AMX) was administered intravenously (65 [interquartile range {IQR}, 43 to 110] mg/kg of body weight/day) in all patients, either for treating infection (n = 15) or as surgical prophylaxis (n = 30). Delay between AMX administration and AICN onset was 1 (IQR, 1 to 3) day; 30, 4, and 11 patients developed KDIGO stage 1, 2, and 3 acute kidney injury, respectively. Delay between AICN onset and kidney function recovery was 4 (IQR, 2 to 6) days. Precipitating factors were identified in only one-third of cases. Twelve patients required intensive care unit admission, and 8 needed renal replacement therapy. Neither chronic kidney disease nor death was observed. We confirmed the recent and dramatic increase of AICN in the Paris RCPVs since 2010. The absence of precipitating factors in the majority of cases and the onset of AICN in apparent routine indications, such as surgical prophylaxis, are alarming and justify a high vigilance from all AMX prescribers.

The multistep road to ventilator-associated lung abscess: A retrospective study of S.aureus ventilator-associated pneumonia.

OBJECT: We observed some cases of lung abscess (LA) in ICU patients suffering S.aureus ventilator-associated pneumonia (S.aureus-VAP). We aimed to assess which of the host and/or bacteria-related features are associated with LA. METHODS: We conducted a retrospective study from January 2009 to July 2013 in a trauma surgical ICU within a teaching hospital. All adult patients presenting with S.aureus-VAP were included. We compared two groups of patients according to the formation or not of LA concomitantly to S.aureus-VAP. RESULTS: Seventy-nine S.aureus-VAP patients, predominantly males (85%) of rather young age (mean [SD]: 35yr [21-64]) with severe trauma (initial Simplified Acute Score II = 42 [32-52]) related-ICU admission, were included. Among them, 10 (14%) developed LA. Patient's characteristics significantly associated with LA development were: a younger age (p = 0.003), road traffic accidents admission (p = 0.017), head injury (p = 0.002), lower Glasgow Coma Scale (p = 0.009), blunt chest trauma (p = 0.01) pneumothorax (p = 0.01) and lung contusions (p = 0.002). No microbiological factors were significantly associated with LA formation. Abscesses were mostly bilateral, ≥5 cm of diameter and with a posterior location. CONCLUSIONS: Our results do not favor a specific virulence of S.aureus, but rather highlight the role of multiple insults to the lung, promoting LA formation. Despite a similar severity score, patients with LA had more serious trauma, combining severe both chest and head insults.

Causes and Characteristics of Death in Intensive Care Units: A Prospective Multicenter Study.

BACKGROUND: Different modes of death are described in selected populations, but few data report the characteristics of death in a general intensive care unit population. This study analyzed the causes and characteristics of death of critically ill patients and compared anticipated death patients to unexpected death counterparts. METHODS: An observational multicenter cohort study was performed in 96 intensive care units. During 1 yr, each intensive care unit was randomized to participate during a 1-month period. Demographic data, characteristics of organ failures (Sequential Organ Failure Assessment subscore greater than or equal to 3), and organ supports were collected on all patients who died in the intensive care unit. Modes of death were defined as anticipated (after withdrawal or withholding of treatment or brain death) or unexpected (despite engagement of full-level care or sudden refractory cardiac arrest). RESULTS: A total of 698 patients were included during the study period. At the time of death, 84% had one or more organ failures (mainly hemodynamic) and 89% required at least one organ support (mainly mechanical ventilation). Deaths were considered unexpected and anticipated in 225 and 473 cases, respectively. Compared to its anticipated counterpart, unexpected death occurred earlier (1 day vs. 5 days; P< 0.001) and had fewer organ failures (1 [1 to 2] vs. 1 [1 to 3]; P< 0.01) and more organ supports (2 [2 to 3] vs. 1 [1 to 2]; P< 0.01). Withdrawal or withholding of treatments accounted for half of the deaths. CONCLUSIONS: In a general intensive care unit population, the majority of patients present with at least one organ failure at the time of death. Anticipated and unexpected deaths represent two different modes of dying and exhibit profiles reflecting the different pathophysiologic underlying mechanisms.

Targeted temperature management after intraoperative cardiac arrest: a multicenter retrospective study.

PURPOSE: Few outcome data are available about temperature management after intraoperative cardiac arrest (IOCA). We describe targeted temperature management (TTM) (32-34 °C) modalities, adverse events, and association with 1-year functional outcome in patients with IOCA. METHODS: Patients admitted to 11 ICUs after IOCA in 2008-2013 were studied retrospectively. The main outcome measure was 1-year functional outcome. RESULTS: Of the 101 patients [35 women and 66 men; median age, 62 years (interquartile range, 42-72)], 68 (67.3%) were ASA PS I to III and 57 (56.4%) had emergent surgery. First recorded rhythms were asystole in 44 (43.6%) patients, pulseless electrical activity in 36 (35.6%), and ventricular fibrillation/tachycardia in 20 (19.8%). Median times from collapse to cardiopulmonary resuscitation and return of spontaneous circulation (ROSC) were 0 min (0-0) and 10 min (4-20), respectively. The 30 (29.7%) patients who received TTM had an increased risk of infection (P = 0.005) but not of arrhythmia, bleeding, or metabolic/electrolyte disorders. By multivariate analysis, one or more defibrillation before ROSC was positively associated with a favorable functional outcome at 1-year (OR 3.06, 95% CI 1.05-8.95, P = 0.04) and emergency surgery was negatively associated with 1-year favorable functional outcome (OR 0.36; 95% CI 0.14-0.95, P = 0.038). TTM use was not independently associated with 1-year favorable outcome (OR 0.82; 95% CI 0.27-2.46, P = 0.72). CONCLUSIONS: TTM was used in less than one-third of patients after IOCA. TTM was associated with infection but not with bleeding or coronary events in this setting. TTM did not independently predict 1-year favorable functional outcome after IOCA in this study.

Case Studies in Physiology: Maximal oxygen consumption and performance in a centenarian cyclist.

The purpose of this study was to examine the physiological characteristics of an elite centenarian cyclist who, at 101 yr old, established the 1-h cycling record for individuals ≥100 yr old (24.25 km) and to determine the physiological factors associated with his performance improvement 2 yr later at 103 yr old (26.92 km; +11%). Before each record, he performed an incremental test on a cycling ergometer. For 2 yr, he trained 5,000 km/yr with a polarized training that involved cycling 80% of mileage at "light" rate of perceived exertion (RPE) ≤12 and 20% at "hard" RPE ≥15 at a cadence between 50 and 70 rpm. His body weight and lean body mass did not change, while his maximal oxygen consumption (V̇o2max) increased (31-35 ml·kg-1·min-1; +13%). Peak power output increased from 90 to 125 W (+39%), mainly because of increasing the maximal pedaling frequency (69-90 rpm; +30%). Maximal heart rate did not change (134-137 beats/min) in contrast to the maximal ventilation (57-70 l/min, +23%), increasing with both the respiratory frequency (38-41 cycles/min; +8%) and the tidal volume (1.5-1.7 liters; +13%). Respiratory exchange ratio increased (1.03-1.14) to the same extent as tolerance to V̇co2 In conclusion, it is possible to increase performance and V̇o2max with polarized training focusing on a high pedaling cadence even after turning 100 yr old.NEW & NOTEWORTHY This study shows, for the first time, that maximal oxygen consumption (+13%) and performance (+11%) can still be increased between 101 and 103 yr old with 2 yr of training and that a centenarian is able, at 103 yr old, to cover 26.9 km/h in 1 h.