Remote Dielectric Sensing Before and After Discharge in Patients With ADHF: The ReDS-SAFE HF Trial.

BACKGROUND: Incomplete treatment of congestion often leads to worsening heart failure (HF). The remote dielectric sensing (ReDS) system is an electromagnetic energy-based technology that accurately quantifies changes in lung fluid concentration noninvasively. OBJECTIVES: This study sought to assess whether an ReDS-guided strategy during acutely decompensated HF hospitalization is superior to routine care for improving outcomes at 1 month postdischarge. METHODS: ReDS-SAFE HF (Use of ReDS for a SAFE discharge in patients with acute Heart Failure) was an investigator-initiated, multicenter, single-blind, randomized, proof-of-concept trial in which 100 patients were randomized to a routine care strategy, with discharge criteria based on current clinical practice, or an ReDS-guided decongestion strategy, with discharge criteria requiring an ReDS value of ≤35%. ReDS measurements were performed daily and at a 7-day follow-up visit, with patients and treating physicians in the routine care arm blinded to the results. The primary outcome was a composite of unplanned visits for HF, HF rehospitalization, or death at 1 month after discharge. RESULTS: The mean age was 67 ± 14 years, and 74% were male. On admission, left ventricular ejection fraction was 37% ± 16%, and B-type natriuretic peptide was 940 pg/L (Q1-Q3: 529-1,665 pg/L). The primary endpoint occurred in 10 (20%) patients in the routine care group and 1 (2%) in the ReDS-guided strategy group (log-rank P = 0.005). The ReDS-guided strategy group experienced a lower event rate, with an HR of 0.094 (95% CI: 0.012-0.731; P = 0.003), and a number of patients needed to treat of 6 to avoid an event (95% CI: 3-17), mainly resulting from a decrease in HF readmissions. The median length of stay was 2 days longer in the ReDS-guided group vs the routine care group (8 vs 6; P = 0.203). CONCLUSIONS: A ReDS-guided strategy to treat congestion improved 1-month prognosis postdischarge in this proof-of-concept study, mainly because of a decrease of the number of HF readmissions. (Use of ReDS for a SAFE discharge in patients with acute Heart Failure [ReDS-SAFE HF]; NCT04305717).

Consensus on the approach to hydrosaline overload in acute heart failure. SEMI/SEC/S.E.N. recommendations.

Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.).

Trends in epidemiology, surgical management, and prognosis of infective endocarditis during the XXI century in Spain: A population-based nationwide study.

BACKGROUND: Few population-based studies have evaluated the epidemiology of infective endocarditis (IE). Changes in population demographics and guidelines on IE may have affected both the incidence and outcomes of IE. Therefore, the aim of our study is to provide contemporary population-based epidemiological data of IE in Spain. METHODS: Retrospective nationwide observational study using data from the Spanish National Health System Discharge Database. We included all patients hospitalized with IE from January 2000 to December 2019. RESULTS: A total of 64,550 IE episodes were included. The incidence of IE rose from 5.25 cases/100,000 person-year in 2000 to 7.21 in 2019, with a 2% annual percentage change (95% CI 1.3-2.6). IE incidence was higher among those aged 85 or older (43.5 cases/100.000 person-years). Trends across the study period varied with sex and age. Patients with IE were progressively older (63.9 years in 2000-2004 to 70.0 in 2015-2019, p < 0.001) and had more frequent comorbidities and predispositions, including, previous valvular prosthesis (12.1% vs 20.9%, p < 0.001). After adjustment, a progressive reduction in mortality was noted including in 2015-2019 compared to 2010-2014 (adjusted odds ratio 0.93, 95% confident interval 0.88-0.99, p = 0.023)., which was associated with more frequent cardiac surgery in recent years (15.1% in 2010-2014 vs 19.9% in 2015-2019). CONCLUSIONS: In Spain, the incidence of IE has increased during the XXI century, with a more pronounced increase in elderly individuals. Adjusted-mortality decreased over the years, which could be related to a higher percentage of surgery. Our results highlight the changing epidemiology of IE.

Intrarenal Venous Flow Pattern Changes Do Relate With Renal Function Alterations in Acute Heart Failure.

BACKGROUND: There is scarce evidence supporting the clinical utility of congestive intrarenal venous flow (IRVF) patterns in patients with acute heart failure. OBJECTIVES: This study aims to: 1) investigate the association between IRVF patterns and the odds of worsening renal function (WRF); 2) track the longitudinal changes of serum creatinine (sCr) across IRVF at predetermined points and its association with decongestion; and 3) explore the relationship between IRVF/WRF categories and patient outcomes. METHODS: IRVF was assessed at baseline (pre-decongestive therapy), 72 hours, and 30 and 90 days postdischarge. Changes in sCr trajectories across dynamic IRVF variations and parameters of decongestion were assessed using linear mixed effect models. The association between IRVF/WRF categories and outcomes was evaluated using univariable/multivariable models. RESULTS: In this prospective, multicenter study with 188 participants, discontinuous IRVF patterns indicated higher odds of WRF (OR: 3.90 [95% CI: 1.24-12.20]; P = 0.020 at 72 hours; and OR: 5.76 [95% CI: 1.67-19.86]; P = 0.006 at 30 days) and an increase in sCr (Δ-72 hours 0.14 mg/dL [95% CI: 0.06-0.22]; P = 0.001; Δ-discharge 0.13 mg/dL [95% CI: 0.03-0.23]; P = 0.007). However, the diuretic response and decongestion significantly influenced the magnitude of these changes. Patients exhibiting both WRF and discontinuous IRVF at 30 days experienced an increased hazard of adverse events (HR: 5.96 [95% CI: 2.63-13.52]; P < 0.001). CONCLUSIONS: Discontinuous IRVF identifies patients with higher odds of WRF during admission and postdischarge periods. Nonetheless, adequate diuretic response and decongestion could modify this association. Patients showing both WRF and discontinuous IRVF at 30 days had increased rates of adverse events.

Multidisciplinary approach to patients with heart failure and kidney disease: preliminary experience of an integrated cardiorenal unit.

Background: Cardiorenal programs have emerged to improve the management of cardiorenal disease (CRD). Evidence about the benefits of these programs is still scarce. This work aims to evaluate the performance of a novel cardiorenal program and describe the clinical profile and outcomes of patients with CRD. Methods: We conducted a retrospective observational study of patients with CRD attended in a cardiorenal unit (CRU) from February 2021 to February 2022. Demographics and laboratory tests were collected and events (all-cause death and cardiovascular hospitalizations) were evaluated. Optimization of comorbidities and protective therapies was also assessed. Results: Eighty-two patients were included, with a mean age of 76.8 years [standard deviation (SD) 8.5] and 72% were men. A total of 58.5% (n = 47) had left ventricular ejection fraction <50%. The mean follow-up was 11 months (SD 4.0). Almost 54% of the patients (n = 44) required hospitalization, 30.5% for heart failure (HF) decompensation. Total hospitalizations significantly decreased after CRU inclusion: 0.70 versus 0.45 admissions/year (P < .02). Global mortality was 17.1% (n = 14). The percentage of patients with HF with reduced ejection fraction on quadruple therapy increased by 20%, and up to 60% of the patients were on three drugs. A total of 39% of the patients with HF and preserved ejection fraction started treatment with sodium-glucose co-transporter inhibitors. Hyperkalaemia required the use of potassium binders in 12.2% of the patients and treatment of secondary hyperparathyroidism was started in 42.7% and renal anaemia in 23.2%. Renal replacement therapy was initiated in 10% of the patients (n = 8). Conclusion: CRD confers a considerable risk of adverse outcomes. Cardiorenal programs may improve cardiorenal syndrome management by optimizing therapies, treating comorbidities and reducing hospitalizations.

Kidney function changes in acute heart failure: a practical approach to interpretation and management.

Worsening kidney function (WKF) is common in patients with acute heart failure (AHF) syndromes. Although WKF has traditionally been associated with worse outcomes on a population level, serum creatinine concentrations vary greatly during episodes of worsening heart failure, with substantial individual heterogeneity in terms of their clinical meaning. Consequently, interpreting such changes within the appropriate clinical context is essential to unravel the pathophysiology of kidney function changes and appropriately interpret their clinical meaning. This article aims to provide a critical overview of WKF in AHF, aiming to provide physicians with some tips and tricks to appropriately interpret kidney function changes in the context of AHF.

The Green Surgical Block 4.0: Automation of the operating theatre's climate conditions through a real-time patient-flow solution.

The energy consumed by surgery units constitutes a staggering part of the overall healthcare carbon footprint. Partly due to the demanding climate conditions necessitated by operating theatres (OTs), energy is also wasted because of poorly managed heating, ventilation and air-conditioning systems (HVACs) that consume up to 57% of the total energy used in a hospital. With their goal of optimising OTs' performance and reducing patient waiting lists, heads of surgery units worldwide do not dare to risk cancelling scheduled surgery because of problems with the OT environment conditions (ie temperature, humidity, pressure). Current solutions are monolithic, complex and completely disconnected from healthcare logic, failing to take into account the idiosyncrasy of hospitals. This article presents an innovation that uses real-time patient flow data to automate and optimise the OT's climate conditions.

Thiazides in chronic kidney disease: "back to the future".

The thiazide class diuretics are first-line agents for managing hypertension either as monotherapy or as a fixed-dose combination with other antihypertensive drugs. However, despite the extensive experience with these drugs for >60 years, there is general reluctance to use these agents in patients with advanced chronic kidney disease (CKD) because of concerns about their efficacy and safety as kidney function declines. In this issue of Clinical Kidney Journal, Minutolo et al. performed an updated review of the pharmacological properties, efficacy and side effects and randomized controlled trials that tested these drugs in patients with CKD.

Assessment of filling pressures and fluid overload in heart failure: an updated perspective.

Congestion plays a major role in the pathogenesis, presentation, and prognosis of heart failure and is an important therapeutic target. However, its severity and organ and compartment distribution vary widely among patients, illustrating the complexity of this phenomenon. Although clinical symptoms and signs are useful to assess congestion and manage volume status in individual patients, they have limited sensitivity and do not allow identification of congestion phenotype. This leads to diagnostic uncertainty and hampers therapeutic decision-making. The present article provides an updated overview of circulating biomarkers, imaging modalities (ie, cardiac and extracardiac ultrasound), and invasive techniques that might help clinicians to identify different congestion profiles and guide the management strategy in this diverse population of high-risk patients with heart failure.

Sex differences in the impact of frailty in elderly outpatients with heart failure.

Introduction: Frailty is common among patients with heart failure (HF). Our aim was to address the role of frailty in the management and prognosis of elderly men and women with HF. Methods and results: Prospective multicenter registry that included 499 HF outpatients ≥75 years old. Mean age was 81.4 ± 4.3 years, and 193 (38%) were women. Compared with men, women were older (81.9 ± 4.3 vs. 81.0 ± 4.2 years, p = 0.03) and had higher left ventricular ejection fraction (46 vs. 40%, p < 0.001) and less ischemic heart disease (30 vs. 57%, p < 0.001). Women had a higher prevalence of frailty (22 vs. 10% with Clinical Frailty Scale, 34 vs. 15% with FRAIL, and 67% vs. 46% with the mobility visual scale, all p-values < 0.001) and other geriatric conditions (Barthel index ≤90: 14.9 vs. 6.2%, p = 0.003; malnutrition according to Mini Nutritional Assessment Short Formulary ≤11: 55% vs. 42%, p = 0.007; Pfeiffer cognitive test's errors: 1.6 ± 1.7 vs. 1.0 ± 1.6, p < 0.001; depression according to Yesavage test; p < 0.001) and lower comorbidity (Charlson index ≥4: 14.1% vs. 22.1%, p = 0.038). Women also showed worse self-reported quality of life (6.5 ± 2.1 vs. 6.9 ± 1.9, on a scale from 0 to 10, p = 0.012). In the univariate analysis, frailty was an independent predictor of mortality in men [Hazard ratio (HR) 3.18, 95% confidence interval (CI) 1.29-7.83, p = 0.012; HR 4.53, 95% CI 2.08-9.89, p < 0.001; and HR 2.61, 95% CI 1.23-5.43, p = 0.010, according to FRAIL, Clinical Frailty Scale, and visual mobility scale, respectively], but not in women. In the multivariable analysis, frailty identified by the visual mobility scale was an independent predictor of mortality (HR 1.95, 95% CI 1.04-3.67, p = 0.03) and mortality/readmission (HR 2.06, 95% CI 1.05-4.04, p = 0.03) in men. Conclusions: In elderly outpatients with HF frailty is more common in women than in men. However, frailty is only associated with mortality in men.

Surgical block 4.0: a digital intervention based on a real-time location patient-flow solution to support the automation of surgical pathways.

As internet of things (IoT) technologies are increasingly adopted by healthcare and hospitals, new opportunities are emerging to transform patient pathways and achieve efficient delivery of care. This implemented project follows the drivers and requirements of industry 4.0, based on surgical process analysis and optimisation using IoT technology, with the goal of creating '4.0 hospitals'. Our study presents the implementation of a novel IoT application, aiming to give support to multidisciplinary surgical teams through the optimisation of patient pathways to facilitate the surgical process. The implemented solution is based on real-time location systems (RTLS) technology, a subgroup within IoT, and it originated through the hospital needing to address the sudden surge of surgical elective care demand. The solution also enhances patient safety, facilitates quality of care by increasing communication and reduces costs. This IoT tool has facilitated the increase of theatre utilisation from 70.02% to 82.5% in 2 years, which has translated into an increase of surgical activity capacity, with an impact on reducing the waiting list.

Frailty and prognosis of older patients with chronic heart failure.

INTRODUCTION AND OBJECTIVES: Heart failure (HF) is prevalent in advanced ages. Our objective was to assess the impact of frailty on 1-year mortality in older patients with ambulatory HF. METHODS: Our data come from the FRAGIC study (Spanish acronym for "Study of the impact of frailty and other geriatric syndromes on the clinical management and prognosis of elderly outpatients with heart failure"), a multicenter prospective registry conducted in 16 Spanish hospitals including outpatients ≥ 75 years with HF followed up by cardiology services in Spain. RESULTS: We included 499 patients with a mean age of 81.4±4.3 years, of whom 193 (38%) were women. A total of 268 (54%) had left ventricular ejection fraction <40%, and 84.6% was in NYHA II functional class. The FRAIL scale identified 244 (49%) pre-frail and 111 (22%) frail patients. Frail patients were significantly older, were more frequently female (both, P <.001), and had higher comorbidity according to the Charlson index (P=.017) and a higher prevalence of geriatric syndromes (P <.001). During a median follow-up of 371 [361-387] days, 58 patients (11.6%) died. On multivariate analysis (Cox regression model), frailty detected with the FRAIL scale was marginally associated with mortality (HR=2.35; 95%CI, 0.96-5.71; P=.059), while frailty identified by the visual mobility scale was an independent predictor of mortality (HR=2.26; 95%CI, 1.16-4.38; P=.015); this association was maintained after adjustment for confounding variables (HR=2.13; 95%CI, 1.08-4.20; P=.02). CONCLUSIONS: In elderly outpatients with HF, frailty is independently associated with mortality at 1 year of follow-up. It is essential to identify frailty as part of the comprehensive approach to elderly patients with HF.

The unmet need of evidence-based therapy for patients with advanced chronic kidney disease and heart failure: Position paper from the Cardiorenal Working Groups of the Spanish Society of Nephrology and the Spanish Society of Cardiology.

Despite the high prevalence of chronic kidney disease (CKD) and its high cardiovascular risk, patients with CKD, especially those with advanced CKD (stages 4-5 and patients on kidney replacement therapy), are excluded from most cardiovascular clinical trials. It is particularly relevant in patients with advanced CKD and heart failure (HF) who have been underrepresented in many pivotal randomized trials that have modified the management of HF. For this reason, there is little or no direct evidence for HF therapies in patients with advanced CKD and treatment is extrapolated from patients without CKD or patients with earlier CKD stages. The major consequence of the lack of direct evidence is the under-prescription of HF drugs to this patient population. As patients with advanced CKD and HF represent probably the highest cardiovascular risk population, the exclusion of these patients from HF trials is a serious deontological fault that must be solved. There is an urgent need to generate evidence on how to treat HF in patients with advanced CKD. This article briefly reviews the management challenges posed by HF in patients with CKD and proposes a road map to address them.

Introduction to the cognitive hospital.

The third industrial revolution has radically impacted the transformation of hospitals. Through the adoption of key digital technologies, hospitals have become more accessible, flexible, organised, responsive and able to deliver more personalised care. The digitalisation of patient health records, one of the most remarkable achievements to date in healthcare management, has enabled new opportunities, including the idea of hospitals evolving to become artificially intelligent. In parallel, the adoption of electronic and mobile internet technologies in hospitals has introduced new structural concepts, seeing a variety of terms blossom such as 'smart', 'intelligent', 'green' and 'liquid'. Now in the early fourth industrial revolution, driven by AI and internet-of-things technologies, this article unveils a new concept adapted to the upcoming era.

Optimizing the Procedure to Manufacture Clinical-Grade NK Cells for Adoptive Immunotherapy.

Natural killer (NK) cells represent promising tools for cancer immunotherapy. We report the optimization of an NK cell activation-expansion process and its validation on clinical-scale. METHODS: RPMI-1640, stem cell growth medium (SCGM), NK MACS and TexMACS were used as culture mediums. Activated and expanded NK cells (NKAE) were obtained by coculturing total peripheral blood mononuclear cells (PBMC) or CD45RA+ cells with irradiated K562mbIL15-41BBL or K562mbIL21-41BBL. Fold increase, NK cell purity, activation status, cytotoxicity and transcriptome profile were analyzed. Clinical-grade NKAE cells were manufactured in CliniMACS Prodigy. RESULTS: NK MACS and TexMACs achieved the highest NK cell purity and lowest T cell contamination. Obtaining NKAE cells from CD45RA+ cells was feasible although PBMC yielded higher total cell numbers and NK cell purity than CD45RA+ cells. The highest fold expansion and NK purity were achieved by using PBMC and K562mbIL21-41BBL cells. However, no differences in activation and cytotoxicity were found when using either NK cell source or activating cell line. Transcriptome profile showed to be different between basal NK cells and NKAE cells expanded with K562mbIL21-41BBL or K562mbIL15-41BBL. Clinical-grade manufactured NKAE cells complied with the specifications from the Spanish Regulatory Agency. CONCLUSIONS: GMP-grade NK cells for clinical use can be obtained by using different starting cells and aAPC.

Study design of Heart failure Events reduction with Remote Monitoring and eHealth Support (HERMeS).

AIMS: The role of non-invasive telemedicine (TM) combining telemonitoring and teleintervention by videoconference (VC) in patients recently admitted due to heart failure (HF) ('vulnerable phase' HF patients) is not well established. The aim of the Heart failure Events reduction with Remote Monitoring and eHealth Support (HERMeS) trial is to assess the impact on clinical outcomes of implementing a TM service based on mobile health (mHealth), which includes remote daily monitoring of biometric data and symptom reporting (telemonitoring) combined with VC structured, nurse-based follow-up (teleintervention). The results will be compared with those of the comprehensive HF usual care (UC) strategy based on face-to-face on-site visits at the vulnerable post-discharge phase. METHODS AND RESULTS: We designed a 24 week nationwide, multicentre, randomized, controlled, open-label, blinded endpoint adjudication trial to assess the effect on cardiovascular (CV) mortality and non-fatal HF events of a TM-based comprehensive management programme, based on mHealth, for patients with chronic HF. Approximately 508 patients with a recent hospital admission due to HF decompensation will be randomized (1:1) to either structured follow-up based on face-to-face appointments (UC group) or the delivery of health care using TM. The primary outcome will be a composite of death from CV causes or non-fatal HF events (first and recurrent) at the end of a 6 month follow-up period. Key secondary endpoints will include components of the primary event analysis, recurrent event analysis, and patient-reported outcomes. CONCLUSIONS: The HERMeS trial will assess the efficacy of a TM-based follow-up strategy for real-world 'vulnerable phase' HF patients combining telemonitoring and teleintervention.

Hospital-acquired infective endocarditis during Covid-19 pandemic.

BACKGROUND: The COVID pandemic has had a major impact on healthcare in hospitals, including the diagnosis and treatment of infections. Hospital-acquired infective endocarditis (HAIE) is a severe complication of medical procedures that has shown a progressive increase in recent years. OBJECTIVES: To determine whether the incidence of HAIE during the first two months of the epidemic (March-April 2020) was higher than previously observed and to describe the clinical characteristics of these cases. The probability of the studied event (HAIE) during the study period was calculated by Poisson distribution. RESULTS: Four cases of HAIE were diagnosed in our institution during the study period. The incidence of HAIE during the study period was 2/patient-month and 0.3/patient-month during the same calender months in the previous 5 years (p=0.033). Two cases presented during admission for COVID-19 with pulmonary involvement treated with methylprednisolone and tocilizumab. The other two cases were admitted to the hospital during the epidemic. All cases underwent central venous and urinary catheterization during admission. The etiology of HAIE was Enterococcus faecalis (2 cases), Staphylococcus aureus and Candida albicans (one case each). A source of infection was identified in three cases (central venous catheter, peripheral venous catheter, sternal wound infection, respectively). One patient was operated on. Two patients died during hospital admission. CONCLUSIONS: The incidence of HAIE during COVID-19 pandemic in our institution was higher than usual. In order to reduce the risk of this serious infection, optimal catheter care and early treatment of every local infection should be prioritized during coronavirus outbreaks.

Photodynamic therapy in endodontic root canal treatment significantly increases bacterial clearance, preventing apical periodontitis.

OBJECTIVE: To analyze the antimicrobial activity of photodynamic therapy as an adjunct to conventional endodontic treatment, particularly against Enterococcus faecalis. METHOD AND MATERIALS: A total of 42 single-rooted teeth obtained from 33 patients with apical periodontitis were included. Sampling was developed in three stages: (1) immediately after accessing the root canal, (2) after chemical and mechanical instrumentation, and finally, (3) after photodynamic therapy application. The bacterial load of each sample was quantified by seeding on blood agar plates and selective M-Enterococcus agar. All growing colonies were identified using MALDI-TOF (Bruker; matrix-assisted laser desorption/ionization time-of-flight), and the entire bacterial microbiota composition was determined in the first sample by PCR-DGGE (polymerase chain reaction denaturing gradient gel electrophoresis), using 16 rDNA primers and selective nucleotide sequencing. RESULTS: The endodontic therapy obtained a mean reduction in the cultivable bacterial load of 1.12 log, whereas the photodynamic therapy combination significantly increased the bacterial clearance (P < .0001). Viable cells of E faecalis were detected in 16.6% of root canals, with a mean value of 93 CFU per tooth, which was reduced to 67 and 9 CFU/tooth after conventional endodontic and photodynamic therapy treatments, respectively. Molecular E faecalis detection demonstrated that this species was present in 23.2% of baseline samples. DGGE analysis demonstrated the existence of a more complex microbiota than those observed using classical cultures. CONCLUSION: Photodynamic therapy as an adjunct to root canal treatment produces a significant reduction in E faecalis bacterial load, and it should be considered in the prevention of apical periodontitis.

Whole-genome sequencing reveals nosocomial Clostridioides difficile transmission and a previously unsuspected epidemic scenario.

To trace the routes and frequencies of transmission of Clostridioides difficile in a tertiary-care hospital in Madrid (Spain), we sequenced the genomes from all C. difficile isolates collected over 36 months (2014-2016) that were indistinguishable from any other isolate by PCR ribotyping. From a total of 589 C. difficile infection cases, we cultivated and PCR-ribotyped 367 C. difficile isolates (62%), of which 265 were genome-sequenced. Based on close relatedness of successively collected isolates (≤2 SNPs difference in their genomes), whole-genome sequencing revealed a total of 17 independent, putative transmission clusters, caused by various C. difficile strains and each containing 2 to 18 cases, none of which had been detected previously by standard epidemiological surveillance. Proportions of linked isolates varied widely among PCR ribotypes, from 3% (1/36) for ribotype 014/020 to 60% (12/20) for ribotype 027, suggesting differential aptitudes for nosocomial spread. Remarkably, only a minority (17%) of transmission recipients had direct ward contact to their presumed donors and specific C. difficile genome types frequently went undetectable for several months before re-emerging later, suggesting reservoirs for the pathogen outside of symptomatic patients. Taken together, our analysis based on genome sequencing suggested considerable within-hospital epidemic spread of C. difficile, even though epidemiological data initially had been inconspicuous.