A Contemporary Population-Based Profile of Infective Endocarditis Using the Expanded Rochester Epidemiology Project

ObjectiveTo develop a contemporary profile of infective endocarditis (IE) among a population in 6 counties of Olmsted, Dodge, Mower, Steele, Waseca, and Freeborn in southern Minnesota between 2014 and 2018.Patients and MethodsAll possible and definite cases of IE (≥18 years) among residents of 6 counties in southern Minnesota, including Olmsted County, diagnosed between January 1, 2014, and December 31, 2018, were included in this retrospective, population-based investigation, using the Expanded Rochester Epidemiology Project (E-REP).ResultsOverall, 137 patients with IE developed incident IE in the 6-county region, corresponding to an age- and sex-adjusted incidence rate of 11.9 per 100,000 person-years. Men had a significantly higher incidence of IE (17.9 vs 6.8 per 100,000 person-years), and rates increased exponentially with age in both sexes. The median age of incident cases was 68.2 years, and 67.9% were male patients. The percentage of patients with histories of injection-drug use was low, at 6.7%. Bicuspid aortic valve was the most common (9.6%) native valve predisposing condition. Staphylococcus aureus was identified as the predominant pathogen in the overall group (34.8%), with viridans-group streptococci accounting for only 19.3% cases. Central nervous system and musculoskeletal complications were common. The 30-day readmission rate was 27.9%, and the 6-month mortality rate was 31.8%.ConclusionTo our knowledge, this is the first time that the population-based E-REP has been used to determine an age- and sex-adjusted IE incidence. Older male patients predominated, and S aureus was the most common pathogen. Based on these findings, it is not surprising that IE complications were frequently seen.     

A case of mediastinal abscess and infected aortic aneurysm caused by dissemination of Mycobacterium abscessus subsp. massiliense pulmonary disease

An 81-year-old man was admitted to our hospital because of fever and malaise that had persisted for 3 months. The patient had undergone two aortic valve replacements, 10 and 5 years previously, because of aortic valve regurgitation and infectious endocarditis. He also had had asymptomatic Mycobacterium abscessus complex (MABC) pulmonary disease for the two previous years. Contrast-enhanced computed tomography showed a mediastinal abscess and an ascending aortic aneurysm. Mycobacterium abscessus subsp. massiliense was cultured from his blood, suggesting the aortic aneurysm was secondary to infection of an implanted device. After enlargement over only a few days, a leakage of contrast medium to the mediastinal abscess was found on computed tomography. The patient was diagnosed with rupture of an infectious aortic aneurysm, and emergency aortic replacement and drainage of the mediastinal abscess were successful. The patient was treated with several antibiotics, including meropenem, amikacin, and clarithromycin, and his general condition improved. Cultures from both the mediastinal abscess and a pericardial patch that was placed at the time of surgery 5 years previously revealed MABC. In our case, the infected aortic aneurysm most likely resulted from MABC pulmonary disease rather than from previous intraoperative contamination. This route of infection is rare. Physicians should be aware of the possibility of dissemination and subsequent infection of implants related to MABC pulmonary disease.     

Clinical Outcomes of Adults With Bicuspid Aortic Valve: A European Perspective

ObjectiveTo describe the clinical history of patients with a wide age range diagnosed with bicuspid aortic valve (BAV) and no surgical indication and to evaluate the long-term outcome of patients with BAV referred for elective surgery.Patients and MethodsBetween 2005 and 2017, 350 consecutive patients with no surgical indication (surveillance group, mean age 53±16, 71% men) and 191 with a surgical indication (surgical group, mean age 59±13, 71% men) were prospectively included. Median follow-up was 80 (32 to 115) months.ResultsIn the surveillance group, the 5-year and 10-year survival rates were 93±1% and 89±2%, respectively, with a relative survival of patients with BAV compared with an age- and sex-matched control population of 98.7%. During follow-up, the cumulative 10-year incidence of aortic valve and aorta surgery was high; of 35±4%, the incidence of native valve infective endocarditis (IE) of 0.2% per patient-year, and no cases of aortic dissection were observed. In the surgical group, the 5-year and 10-year survival rates were 97±1% and 89±3%, respectively, with a relative survival of 99.4% compared with the general population. The incidence of IE was 0.4% per patient-year, and no cases of aortic dissection were observed.ConclusionThis regional cohort shows that the 10-year survival rates of patients with BAV and a wide age range, but mostly middle-aged adults, were similar to those of the general population with a very low rate of complications. Adherence to prophylactic surgical indications and younger age might have contributed to this lack of difference.     

Bacteremia caused by Slackia exigua: A report of two cases and literature review

Slackia exigua is an obligate anaerobic coccobacillus associated with dental infection, but rarely causes extraoral infection. We report two cases of monomicrobial bacteremia caused by S. exigua isolated from two institutions. The first case involved community-acquired bacteremia associated with pleural empyema in a 69-year-old man. The second case involved hospital-acquired bacteremia secondary to postoperative intra-abdominal abscess in a 73-year-old man with primary intestinal diffuse large B-cell lymphoma. S. exigua was finally identified by 16S ribosomal RNA gene sequencing analyses in both cases. In the first case, our attempts to identify the organism using commercial identification kits for anaerobes resulted in inaccurate identification as Gemella morbillorum. However, S. exigua was promptly identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry in the second case. The epidemiology and clinical characteristics of S. exigua extraoral infection remain unclear because of the limitations in accurate identification and because only 19 cases of extraoral S. exigua infection have been reported previously, including four cases of bacteremia. Physicians should focus on this species, which can cause community-acquired infections and spread via various routes even in patients with no comorbidities. Further studies are needed to clarify the clinical characteristics of extraoral S. exigua infections.     

Pre-admission and In-Hospital Statin Use is Associated With Reduced Short-Term Mortality in Infective Endocarditis

ObjectiveTo investigate for potential protective effects of statin use among patients with infective endocarditis (IE) with consideration for underlying diseases and bacterial culture — variables which have prognostic implications and show considerable geographic variation yet are unappreciated in previous pharmacoepidemiological studies.Patients and MethodsPatients diagnosed with IE between January 1, 1996, and December 31, 2019, were identified. We estimated the effect on mortality of pre-admission statin use (≥90 cumulative days of use before index date) and in-hospital use (use beginning within 2 days of admission), compared with nonusers and discontinued users, respectively, through propensity score analytics.ResultsOf 6700 IE patients (mean age, 58.0 years; 63.3% male [n=4251]), 776 patients had pre-admission statin use, with 626 continuing statin use following admission (in-hospital users). Pre-admission statin users had a 31% lower risk of 1-year mortality (HR, 0.69; 95% CI, 0.58 to 0.82) compared with nonusers. In-hospital users had a 48% lower risk of 1-year mortality (HR, 0.52; 95% CI, 0.34 to 0.78) compared with discontinued users. Subgroup analyses showed significant protective effects of statin use for patients with varying causative agents, underlying diseases, and with or without prosthetic valves. Results were consistent across different statins, and were dose-dependent.ConclusionIn patients with IE, pre-admission and in-hospital use of statin, when compared with statin nonusers and discontinued users, respectively, were associated with a lower risk of 1-year mortality.     

Sex Differences in Children and Young Adults With Bicuspid Aortic Valve Disease in First Two Decades of Life

ObjectiveTo elucidate sex differences in valve morphology, disease phenotype, progression, and outcomes among children and young adults with bicuspid aortic valve (BAV).Patients and MethodsThis is a retrospective cohort study examining all children and young adults (aged ≤22 years) with isolated BAV diagnosed, by excluding patients with concomitant congenital heart defects or genetic syndromes, from January 1, 1990, through December 1, 2016, at Mayo Clinic in Rochester, Minnesota.ResultsOf 1010 patients with BAV, 558 had isolated BAV. Distributions of morphology were right-left in 65.8% (n=367), right-noncoronary in 34% (n=190), and left-noncoronary cusp fusion in 0.2% (n=1) of patients; with no sex differences. Male to female ratio was 3:1. At the first echocardiographic evaluation in the study, there were no sex differences in terms of frequency of aortic valve stenosis or regurgitation. However, males had significantly higher grades of aortic valve regurgitation at 17 years of age onward (P<.0001). Males had significantly larger mid-ascending aorta (P=.01) and sinus of Valsalva dimensions (z score; P=.0001) as compared with females, with a novel finding of peak aortic dimensions around 8 years of age. Males also had more than 2-fold higher risk for sinus of Valsalva dilation (z score >2) as compared with females (odds ratio, 2.3; 95% CI, 1.2 to 4.2; P=.01). There were no significant sex differences in the primary cardiac outcomes of interventions on aortic valve and/or aorta, aortic dissection, or death.ConclusionIn children and young adults with BAV, males have a higher grade of aortic regurgitation in late adolescence, significantly larger aortic dimensions, different patterns of aortic growth, and more frequent sinus of Valsalva dilation as compared with females. Overall, the rate of primary cardiac events is lower in young patients, with no significant sex differences.     

Prevalence and Natural History of Mitral Annulus Calcification and Related Valve Dysfunction

ObjectiveTo evaluate the prevalence and natural history of mitral annulus calcification (MAC) and associated mitral valve dysfunction (MVD) in patients undergoing clinically indicated echocardiography.MethodsA retrospective review was conducted of all adults who underwent echocardiography in 2015. Mitral valve dysfunction was defined as mitral regurgitation or mitral stenosis (MS) of moderate or greater severity. All-cause mortality during 3.0 (0.4 to 4.2) years of follow-up was compared between groups stratified according to the presence of MAC or MVD.ResultsOf 24,414 evaluated patients, 5502 (23%) had MAC. Patients with MAC were older (75±10 years vs 60±16 years; P<.001) and more frequently had MVD (MS: 6.6% vs 0.5% [P<.001]; mitral regurgitation without MS: 9.5% vs 6.1% [P<.001]). Associated with MS in patients with MAC were aortic valve dysfunction, female sex, chest irradiation, renal dysfunction, and coronary artery disease. Kaplan-Meier 1-year survival was 76% in MAC+/MVD+, 87% in MAC+/MVD?, 86% in MAC?/MVD+, and 92% in MAC?/MVD?. Adjusted for age, diabetes, renal dysfunction, cancer, chest irradiation, ejection fraction below 50%, aortic stenosis, tricuspid regurgitation, and pulmonary hypertension, MAC was associated with higher mortality during follow-up (adjusted hazard ratio, 1.40; 95% CI, 1.31 to 1.49; P<.001); MVD was associated with even higher mortality in patients with MAC (adjusted hazard ratio, 1.79; 95% CI, 1.58 to 2.01; P<.001). There was no significant interaction between MAC and MVD for mortality (P=.10).ConclusionIn a large cohort of adults undergoing echocardiography, the prevalence of MAC was 23%. Mitral valve dysfunction was more than twice as prevalent in patients with MAC. Adjusted mortality was increased in patients with MAC and worse with both MAC and MVD.     

Age-Related 2-Year Mortality After Transcatheter Aortic Valve Replacement: the YOUNG TAVR Registry

ObjectiveTo comparatively assess the natural history of patients of different ages undergoing transcatheter aortic valve replacement (TAVR).Patients and MethodsFor this study, we used the YOUNG TAVR, an international, multicenter registry investigating mortality trends up to 2 years in patients with aortic valve stenosis treated by TAVR, classified according to 3 prespecified age groups: 75 years or younger (n=179), 76 to 86 years (n=602), and older than 86 years (n=221). A total of 1002 patients undergoing TAVR were included. Demographic, clinical, and outcome data in the youngest group were compared with those of patients 76 to 86 years and older than 86 years. Patients were followed up for up to 2 years.ResultsCompared with patients 75 years or younger (reference group), patients aged 76 to 86 years and older than 86 years had nonsignificantly different 30-day mortality (odds ratio, 0.76; 95% CI, 0.41-1.38; P=.37 and odds ratio, 1.27; 95% CI, 0.62-2.60; P=.51, respectively) and 1-year mortality (hazard ratio (HR), 0.72; 95% CI, 0.48-1.09; P=.12 and HR, 1.11; 95% CI, 0.88-1.40; P=.34, respectively). Mortality at 2 years was significantly lower among patients aged 76 to 86 years (HR, 0.62; 95% CI, 0.42-0.90; P=.01) but not among the older group (HR, 1.06; 95% CI, 0.68-1.67; P=.79). The Society of Thoracic Surgeons 30-day mortality score was lower in younger patients who, however, had a significantly higher prevalence of chronic obstructive pulmonary disease (P=.005 vs the intermediate group and P=.02 vs the older group) and bicuspid aortic valves (P=.02 vs both older groups), larger left ventricles, and lower ejection fractions.ConclusionIn the present registry, mortality at 2 years after TAVR among patients 75 years or younger was higher compared with that of patients aged 75 to 86 years and was not markedly different from that of patients older than 86 years. The findings are attributable at least in part to a greater burden of comorbidities in the younger age group that are not entirely captured by current risk assessment tools.     

Filifactor alocis brain abscess identified by 16S ribosomal RNA gene sequencing: A case report

We report a clinical case of Filifactor alocis brain abscess in an 85-year-old man who had decayed teeth 1 week prior. In this case, the abscess was surgically drained after empirical antibiotics had been initiated. Although the causative organism could not be identified by culture, F. alocis was detected via 16S ribosomal RNA (16S rRNA) gene sequencing of the pus isolated from the abscess. The patient recovered without serious sequelae after surgical drainage and prolonged antibiotic treatment, including metronidazole, ceftriaxone and meropenem for 8 weeks. The findings in this case emphasize that 16S rRNA gene sequencing allows bacterial diagnosis of brain abscess when phenotypic identification fails, such as in cases where patients are undergoing antimicrobial treatment at the time of sampling or where patients are infected with fastidious organisms.     

Challenges in the diagnosis and management of central line-associated blood stream infection due to Exophiala dermatitidis in an adult cancer patient

BackgroundExophiala (Wangiella) dermatitidis is a clinically relevant black yeast. Although E. dermatitidis rarely causes human infection, it can cause superficial and deep-seated infections, and cutaneous and subcutaneous diseases. Cases of fungemia and central line-associated bloodstream infections due to E. dermatitidis are extremely uncommon, and their clinical manifestations and prognosis are still not well-known. Herein, we report a case of central line-associated bloodstream infections in a patient with cancer. These infections were caused by melanized yeast that was finally identified as E. dermatitidis via internal transcribed spacer sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.Case presentationA 75-year-old man with thoracic esophageal cancer and early gastric cancer presented with a 1-day history of fever during his hospitalization at our hospital. A central venous port was placed in the patient for total parenteral nutrition. Two E. dermatitidis isolates were recovered from two blood samples drawn at different times from a peripheral vein and this central venous port. The isolate was identified as E. dermatitidis by internal transcribed spacer sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The central venous port was removed, and the patient was administered micafungin and voriconazole. Although the minimum inhibitory concentrations of E. dermatitidis for voriconazole and minimum effective concentrations for micafungin were 2 μg/mL and 4 μg/m, respectively, the bacteremia was successfully treated.ConclusionsAlthough no clear treatment guidelines have been proposed for E. dermatitidis infections, immediate removal of central venous catheters is the key to improving central line-associated bloodstream infections.     

Adults With Tetralogy of Fallot: Early Postoperative Outcomes and Risk Factors for Complications

ObjectiveTo report the early postoperative outcomes in adults with tetralogy of Fallot (TOF) undergoing cardiac surgery and to identify patient factors associated with complications.Patients and MethodsWe performed a single-institution retrospective review of adults with TOF who underwent cardiac surgery from January 8, 2008, through June 21, 2018. Patients’ characteristics, preoperative imaging, surgical interventions, outcomes, and complications were analyzed.ResultsThere were 219 adults with TOF (mean age, 40 years; range, 18-83 years; 88 [40%] female) in the study. Surgical interventions included repair or replacement of the pulmonary valve (n=199 [91%]), tricuspid valve (n=70 [32%]), mitral valve (n=13 [5.9%]), and aortic valve (n=8 [3.7%]). Three patients (1.4%) underwent first-time TOF repair. The 30-day mortality rate was 1.4% (n=3). Early postoperative complications occurred in 66 (30%) and included arrhythmias requiring treatment, dialysis requirement, liver dysfunction, respiratory failure, infection, reoperation, cardiac arrest, mechanical circulatory support, and death. Multivariate analysis found older age at current surgery (odds ratio [OR], 1.04 per year; 95% CI, 1.01 to 1.06; P<.001), longer cardiopulmonary bypass time (OR, 1.01 per minute; 95% CI, 1.01 to 1.02; P<.001), right ventricular systolic dysfunction (OR, 1.31; 95%, CI 1.02 to 1.69; P=.03), diabetes mellitus (OR, 3.50; 95% CI, 1.20 to 10.2; P=.02), and history of initial palliative surgery (OR, 1.99; 95% CI, 1.01 to 3.91; P=.05) as independent predictors of complications.ConclusionSurgical interventions for adult patients with TOF can be performed with low early morbidity and mortality. Clinical characteristics and preoperative testing parameters can predict risk for complications in the postoperative period.     

Sex Differences in Outcomes of Patients With Chronic Aortic Regurgitation: Closing the Mortality Gap

ObjectiveTo examine contemporary clinical differences between men and women with hemodynamically significant chronic aortic regurgitation (AR).Patients and MethodsWe retrospectively identified 1072 consecutive patients with moderate to severe or severe AR diagnosed between February 21, 2004, and April 29, 2019. Echocardiographic data, aortic valve surgical intervention (AVS), and all-cause death were analyzed.ResultsAt baseline, the 189 women in the study group were older than the 883 men (mean ± SD age, 64±18 years vs 58±17 years), had more advanced symptoms, and had larger left ventricular end-systolic dimension index (LVESDi) (all P<.001) despite similar AR severity. An LVESDi of greater than 20 mm/m² was noted in 60 of 92 asymptomatic women (65%) vs 225 of 559 asymptomatic men (40%) (P<.001). Median follow-up was 5.6 years (interquartile range, 2.5 to 10.0 years). Female sex was associated with less AVS (P=.009), and overall 10-year survival was better in men (76%±2%) than in women (64%±5%) (P=.004). However, 10-year post-AVS survival was similar between the sexes (P=.86), and women had better left ventricular reverse remodeling than men regarding end-diastolic dimension (P=.02). Multivariable independent predictors of death were age, advanced symptoms, LVESDi, ejection fraction, and AVS (all P≤.03) but not female sex. When compared with the age-matched US population, women exhibited a 1.3-fold increased relative risk of death (P=.0383) while men had similar survival (P=.11).ConclusionIn contemporary practice, women with AR continue to exhibit an overall survival penalty not related to female sex but to late referral markers, including more advanced symptoms, larger LVESDi, and less AVS. Nonetheless, women in our study exhibited outstanding post-AVS left ventricular remodeling and had good post-AVS survival, a step forward toward closing the sex-related mortality gap. The high percentage of LVESDi of 20 mm/m² or greater in asymptomatic women represents a window of opportunity for advanced-symptom prevention and timely AR surgical correction that may close the mortality gap.     

Prevalence of Colorectal Neoplasms Among Patients With Enterococcus faecalis Endocarditis in the GAMES Cohort (2008–2017)

ObjectiveTo investigate the rate of colorectal neoplasms (CRNs) in patients who have Enterococcus faecalis infective endocarditis (EFIE) with available colonoscopies and to assess whether this is associated with the identification of a focus the infection.Patients and MethodsRetrospective analysis of data from a prospective multicenter study involving 35 centers who are members of the Grupo de Apoyo para el Manejo de la Endocarditis en España [Support Group for the Management of Infective Endocarditis in Spain] cohort. A specific set of queries regarding information on colonoscopy and histopathology of colorectal diseases was sent to each participating center. Four-hundred sixty-seven patients with EFIE were included from January 1, 2008, to December 31, 2017, from whom data on colonoscopy performance and results were available in 411 patients.ResultsOne hundred forty-two (34.5%) patients had a colonoscopy close to the EFIE episode. The overall rate of colorectal diseases was 70.4% (100 of 142), whereas the prevalence of CRN (advanced adenomas and colorectal carcinoma) was 14.8% (21 of 142), with no significant differences between the group of EFIE of unknown focus and that with an identified focus.ConclusionOur study adds to prior evidence suggesting a much higher rate of CRN among patients with EFIE than in the general population of the same age and sex. In addition, our findings suggest that this phenomenon might take place both in EFIE with an unknown and an identified source of infection.     

Outcomes and Echocardiographic Follow-up After Surgical Management of Tricuspid Regurgitation in Patients With Transvenous Right Ventricular Leads

ObjectiveTo evaluate outcomes of elective surgical management of tricuspid regurgitation (TR) in patients with transvenous right ventricular leads, and compare results between non–lead-induced and lead-induced TR patients.Patients and MethodsWe studied patients with right ventricular leads who underwent tricuspid valve surgery from January 1, 1993, through December 31, 2015, and categorized them as non–lead-induced and lead-induced TR. Propensity score (PS) for the tendency to have lead-induced TR was estimated from logistic regression and was used to adjust for group differences.ResultsFrom the initial cohort of 470 patients, 444 were included in PS-adjustment analyses (174 non–lead-induced TRs [123 repairs, 51 replacements], 270 lead-induced TRs [129 repairs, 141 replacements]). In PS-adjusted multivariable analysis, lead-induced TR was not associated with mortality (P=.73), but tricuspid valve replacement was (hazard ratio, 1.59; 95% CI, 1.13 to 2.25; P=.008). Five-year freedom from tricuspid valve re-intervention was 100% for non–lead-induced TR and 92.3% for lead-induced TR; rates adjusted for PS differed between groups (P=.005). There was significant improvement in TR postoperatively in each group (P<.001). In patients having tricuspid valve repair, TR grades tended to worsen over time, but the difference in trends was not significantly different between groups.ConclusionLead-induced TR did not affect long-term survival after elective tricuspid valve surgery. In patients with lead-induced TR, tricuspid valve re-intervention was more common. Improvement in TR was achieved in both groups after surgery; however, severity of TR tended to increase over follow-up after tricuspid valve repair.     

Prediction of presence of fastidious bacteria by the Fully Automated Urine Particle Analyzer UF-1000i in the case of ineffective antimicrobial therapy for urinary tract infection

IntroductionRecent studies have reported associations between fastidious bacteria that are difficult to grow and isolate in conventional urine culture conditions and urinary tract infections (UTIs). Because the Fully Automated Urine Particle Analyzer UF-1000i (hereinafter referred to as “UF-1000i”) detects fastidious bacteria without being affected by culture conditions, owing to its flow cytometry-based principle, we evaluated the robustness of UF-1000i detection using clinical urine samples from patients with UTIs following ineffective antimicrobial therapy.MethodsA total of 150 patients diagnosed with UTIs were enrolled, and their laboratory findings were analyzed, focusing on the discrepancy in bacterial numbers between UF-1000i and conventional culture at each antimicrobial therapy effectiveness classification. In addition, gene identification was conducted by molecular analysis using 16S ribosomal RNA gene sequencing and next-generation sequencing (NGS) to elucidate the reason for the presence of fastidious bacteria in these samples.ResultsThe ineffective therapy cases showed more than 100-fold discrepancy in bacterial counts, with a higher proportion (30.8%) than effective therapy cases without secondary administration (5.7%) between the bacterial counts in UF-1000i and conventional culture methods. The presence rates of fastidious bacteria were 100% and 66.7% in discrepant cases of ineffective and effective without secondary administrations, respectively.ConclusionThis study suggests that discrepancies in bacterial numbers between the conventional culture method and UF-1000i measurement at the primary visit can predict the presence of fastidious bacteria, especially in cases of ineffective antimicrobial therapy.     

Digital PCR detection of EGFR somatic mutations in non-small-cell lung cancer formalin fixed paraffin embedded samples

BackgroundDigital PCR (dPCR) is proposed to replace real time PCR and Sanger sequencing for detection and quantification of rare mutations, frequently unnoticed in the mass of tumoral cells. Screening of endothelial growth factor receptor (EGFR) mutations is mandatory before treatment with EGFR-targeted therapy with small-molecule tyrosine kinase inhibitors, which has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC).ObjectiveIn order to establish a cost-effective method for detection of mutations, we optimized dPCR identification of EGFR mutations in exons 18–21, and determined dPCR sensitivity, limits of detection (LoD) and quantification (LoQ).MethodsFor clinical validation, we compared the performance of dPCR and castPCR in 57 NSCL formalin fixed paraffin embedded samples and 10 lung cancer-free formalin fixed paraffin embedded samples.ResultsEGFR mutations DEL19, p.L858R, p.G719X, p.L861Q and p.T790 M were detected by dPCR in 27 samples versus 11 detected by castPCR (p = 0.014). LoD was determined as 100 molecules of DNA/uL and LoQ as 1%. Most of the samples (87%) identified by competitive Allele-Specific TaqMan (castPCR) as wild-type and by dPCR as mutated, presented less than 10% mutated DNA molecules (mean 4.57%). Accuracy of dPCR was 94.44%, as measured with the assay recommended by the College of American Pathologists.ConclusionThese results indicated higher sensibility and specificity of dPCR for screening EGFR mutations in NSCLC biopsies, compared to castPCR.     

The effect of pulsed-xenon ultraviolet disinfection on surfaces contaminated with vancomycin-resistant Enterococci in a Japanese hospital

IntroductionRecently, a worldwide outbreak of vancomycin-resistant Enterococci (VRE) was reported. However, due to the low incidence of VRE infection and colonization, VRE contamination of hospital environments has not been fully investigated in Japan.MethodsSurfaces were swabbed, before and after manual cleaning and after pulsed xenon ultraviolet (PX-UV) disinfection, in five patient rooms that had been occupied by patients colonized with VRE. Difference in the number of VRE-positive samples and VRE colony forming units (CFUs), before and after disinfection, for each cleaning method was estimated.ResultsWe detected VRE contamination in 22/60 (37%) and 14/60 (23%) samples collected before and after manual cleaning, respectively. In contrast, VRE contamination was not detected in the samples collected after PX-UV disinfection. In addition, 3/5 (60%) spray nozzles of electric warm-water bidet toilet seats were found to be contaminated with VRE before terminal cleaning. Manual cleaning caused a significant decrease in the number of VRE CFUs compared with that before cleaning (P = 0.031). PX-UV disinfection also caused a significant decrease in the number of VRE CFUs compared to that of manual cleaning (P < 0.001).ConclusionWe identified hot spots of severe contamination, such as private bathrooms in patient rooms and areas around the bed of patients using diapers and required assistance. VRE contamination persisted even after terminal disinfection; PX-UV disinfection in addition to terminal disinfection was effective at eliminating VRE contamination. These results can be useful in controlling the spread of VRE infections in Japanese hospitals.     

Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).MethodsPubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.ResultsThirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, ?0.54 [95% CI, ?0.88 to ?0.21]; P=.002; I²=96%), IL-6 (WMD, ?0.84 [95% CI, ?1.03 to ?0.64]; P<.001; I²=0%), and TNF-α (WMD, ?12.75 [95% CI, ?17.20 to ?8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, ?1.34 [95% CI, ?2.65 to ?0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, ?1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, ?0.75 [95% CI, ?1.17 to ?0.33]; P<.001; I²=96%).ConclusionBased on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.     

A mixed infection involving Bacteroides denticanum,Lactobacillus salivarius,and Streptococcus anginosus as causative agents of abscess around a pharyngo-esophageal anastomosis and acute vertebral osteomyelitis: Identification by ribosomal RNA sequencing of bacterial isolates

“Bacteroides denticanum” is an anaerobic, non-spore-forming, gram-negative bacterium with a rod morphology typical of canine, ovine, and macropod oral flora. There is only one report of bloodstream infection caused by “B. denticanum” from a dog bite in human. Here, we report a case with no history of animal contact who developed an abscess caused by “B. denticanum” around a pharyngo-esophageal anastomosis after undergoing balloon dilatation procedure for stenosis following laryngectomy. The patient was a 73-year-old man with laryngeal cancer, esophageal cancer, hyperuricemia, dyslipidemia, and hypertension with a 4-week history of cervical pain, sore throat, and fever. Computed tomography showed fluid collection on the posterior pharyngeal wall. Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) identified Bacteroides pyogenes, Lactobacillus salivarius, and Streptococcus anginosus from abscess aspiration. 16S ribosomal RNA sequencing re-identified the Bacteroides species as “B. denticanum”. T2-weighted magnetic resonance images showed a high signal intensity adjacent to the anterior vertebral body of C3–C7. The diagnosis was peripharyngeal esophageal anastomotic abscess and acute vertebral osteomyelitis caused by “B. denticanum”, L. salivarius, and S. anginosus. The patient was treated with sulbactam ampicillin intravenously for 14 days and then switched to oral amoxicillin with clavulanic acid for 6 weeks. To our knowledge, this is the first report of a human infection caused by “B. denticanum” without a history of animal contact. Despite remarkable advancements facilitated by MALDI-TOF MS in microbiological diagnosis, the accurate identification of novel, emerging, or uncommon microorganisms and comprehending their pathogenicity, suitable therapy, and follow up necessitate sophisticated molecular approaches.     

Paroxysmal Severe Mitral Regurgitation

ObjectiveTo investigate the clinical presentation, pathophysiology, and treatment for "paroxysmal severe mitral regurgitation" (MR), which is an underappreciated cause of heart failure with preserved left ventricular ejection fraction.MethodsWe retrospectively reviewed cases of transient severe MR that were evaluated at Mayo Clinic in Rochester, Minnesota, between January 1, 2006, and December 31, 2019. Paroxysmal severe MR was defined as the appearance of transient severe MR in patients with mild MR at rest, normal left ventricle (LV) size, left ventricular ejection fraction greater than 40%, and absence of obstructive coronary artery disease.ResultsWe identified 6 patients (5 women) with a median age of 68 years. There were 3 distinct mechanisms of paroxysmal severe MR, which we labeled types 1, 2, and 3. Type 1 MR was caused by LV dyssynchrony from a rate-dependent left bundle branch block, which led to apical leaflet tenting and incomplete coaptation. Type 2 MR occurred from mitral annular dilatation during maneuvers that increased left-sided volume. Type 3 MR was caused by coronary artery vasospasm with apical leaflet tenting. Treatments varied depending on the underlying cause and included cardiac resynchronization therapy for type 1, surgical valve replacement for type 2, and medical therapy for type 3.ConclusionParoxysmal severe MR is a rare cause of heart failure in patients with preserved LV function. We have identified 3 distinct mechanisms that can lead to this dynamic process, with treatments varying based on the underlying cause.