Transcatheter aortic valve-in-valve implantation to treat aortic para-valvular regurgitation after TAVI.

BACKGROUND: Para-valvular regurgitation (PVR) after transcatheter aortic valve (TAV) implantation is associated with increased mortality. Redo-TAVI may be applied to treat PVR, yet with unknown efficacy. We thought to assess redo-TAVI efficacy in reducing PVR using the Redo-TAVI registry (45 centers; 600 TAV-in-TAV cases). METHODS: Patients were excluded if redo-TAVI was done urgently (N = 253), for isolated TAV stenosis (N = 107) or if regurgitation location at presentation remained undetermined (N = 123). The study group of patients with PVR (N = 70) were compared against patients with intra-valvular regurgitation (IVR) (N = 41). Echocardiographic examinations of 67 (60%) patients were reassessed in a core-lab for data accuracy validation. RESULTS: Core-lab examination validated the jet location in 66 (98.5%) patients. At 30 days, the rate of residual AR ≥ moderate was 7 (10%) in the PVR cohort vs. 1 (2.4%) in the IVR cohort, p = 0.137. The rate of procedural success was 53 (75.7%) vs. 33 (80.5%), p = 0.561; procedural safety 51 (72.8%) vs. 31 (75.6%), p = 0.727; and mortality 2 (2.9%) vs. 1 (2.4%), p = 0.896 at 30 days and 7 (18.6%) vs. 2 (11.5%), p = 0.671 at 1 year, respectively. Of patients with residual PVR ≥ moderate at 30 days, 5/7 occurred after implanting balloon-expandable in self-expanding TAV and 2/7 after balloon-expandable in balloon-expandable TAV. CONCLUSIONS: This study puts in perspective redo-TAVI efficacy and limitations to treat PVR after TAVI. Patient selection for this and other therapies for PVR needs further investigation.

Incidence, Causes, and Outcomes Associated With Urgent Implantation of a Supplementary Valve During Transcatheter Aortic Valve Replacement.

Importance: Transcatheter aortic valve replacement (TAVR) failure is often managed by an urgent implantation of a supplementary valve during the procedure (2-valve TAVR [2V-TAVR]). Little is known about the factors associated with or sequelae of 2V-TAVR. Objective: To examine the incidence, causes, and outcomes of 2V-TAVR. Design, Setting, and Participants: A retrospective cohort study was performed using data from an international registry of 21 298 TAVR procedures performed from January 1, 2014, through February 28, 2019. Among the 21 298 patients undergoing TAVR, 223 patients (1.0%) undergoing 2V-TAVR were identified. Patient-level data were available for all the patients undergoing 2V-TAVR and for 12 052 patients (56.6%) undergoing 1V-TAVR. After excluding patients with missing 30-day follow-up or data inconsistencies, 213 2V-TAVR and 10 010 1V-TAVR patients were studied. The 2V-TAVR patients were compared against control TAVR patients undergoing a 1-valve TAVR (1V-TAVR) using 1:4 17 propensity score matching. Final analysis included 1065 (213:852) patients. Exposures: Urgent implantation of a supplementary valve during TAVR. Main Outcomes and Measures: Mortality at 30 days and 1 year. Results: The 213 patients undergoing 2V-TAVR had similar age (mean [SD], 81.3 [0.5] years) and sex (110 [51.6%] female) as the 10 010 patients undergoing 1V-TAVR (mean [SD] age, 81.2 [0.5] years; 110 [51.6%] female). The 2V-TAVR incidence decreased from 2.9% in 2014 to 1.0% in 2018 and was similar between repositionable and nonrepositionable valves. Bicuspid aortic valve (odds ratio [OR], 2.20; 95% CI, 1.17-4.15; P = .02), aortic regurgitation of moderate or greater severity (OR, 2.02; 95% CI, 1.49-2.73; P < .001), atrial fibrillation (OR, 1.43; 95% CI, 1.07-1.93; P = .02), alternative access (OR, 2.59; 95% CI, 1.72-3.89; P < .001), early-generation valve (OR, 2.32; 95% CI, 1.69-3.19; P < .001), and self-expandable valve (OR, 1.69; 95% CI, 1.17-2.43; P = .004) were associated with higher 2V-TAVR risk. In 165 patients (80%), the supplementary valve was implanted because of residual aortic regurgitation after primary valve malposition (94 [46.4%] too high and 71 [34.2%] too low). In the matched 2V-TAVR vs 1V-TAVR cohorts, the rate of device success was 147 (70.4%) vs 783 (92.2%) (P < .001), the rate of coronary obstruction was 5 (2.3%) vs 3 (0.4%) (P = .10), stroke rate was 9 (4.6%) vs 13 (1.6%) (P = .09), major bleeding rates were 25 (11.8%) vs 46 (5.5%) (P = .03) and annular rupture rate was 7 (3.3%) vs 3 (0.4%) (P = .03). The hazard ratios for mortality were 2.58 (95% CI, 1.04-6.45; P = .04) at 30 days, 1.45 (95% CI, 0.84-2.51; P = .18) at 1 year, and 1.20 (95% CI, 0.77-1.88; P = .42) at 2 years. Nontransfemoral access and certain periprocedural complications were independently associated with higher risk of death 1 year after 2V-TAVR. Conclusions and Relevance: In this cohort study, valve malposition was the most common indication for 2V-TAVR. Incidence decreased over time and was low overall, although patients with a bicuspid or regurgitant aortic valve, nontransfemoral access, and early-generation or self-expandable valve were at higher risk. These findings suggest that compared with 1V-TAVR, 2V-TAVR is associated with high burden of complications and mortality at 30 days but not at 1 year.

Route and duration of antibiotic therapy in acute cellulitis: A systematic review and meta-analysis of the effectiveness and harms of antibiotic treatment.

OBJECTIVES: Compared with guideline recommendations, antibiotic overuse is common in treating cellulitis. We conducted a systematic review and meta-analyses on antibiotic route and duration of treatment for cellulitis in adults and children. METHODS: We searched MEDLINE, EMBASE and trial registries from inception to Dec 11, 2019 for interventional and observational studies of antibiotic treatment for cellulitis. Exclusions included case series/reports, pre-septal/orbital cellulitis and non-English language articles. Random-effects meta-analyses were used to produce summary relative risk (RR) estimates for our primary outcome of clinical response. PROSPERO: CRD42018100602. RESULTS: We included 47/8423 articles, incorporating data from eleven trials (1855 patients) in two meta-analyses. The overall risk of bias was moderate. Only two trials compared the same antibiotic agent in each group. We found no evidence of difference in clinical response rates for antibiotic route or duration (RR(oral:IV)=1.12, 95%CI 0.98-1.27, I2=32% and RR(shorter:longer)=0.99, 95%CI 0•96-1.03, I2 = 0%, respectively). Findings were consistent in observational studies. Follow-up data beyond 30 days were sparse. CONCLUSIONS: The evidence base for antibiotic treatment decisions in cellulitis is flawed by biased comparisons, short follow-up and lack of data around harms of antibiotic overuse. Future research should focus on developing patient-tailored antibiotic prescribing for cellulitis to reduce unnecessary antibiotic use.

Blood culture negative endocarditis in the modern era of 16S rRNA sequencing.

Blood culture negative endocarditis (BCNE) accounts for up to 20% of infective endocarditis. While the most common cause of BCNE remains the initiation of antibiotics prior to culture, intracellular organisms such as Coxiella and Bartonella spp account for a significant proportion of cases. Identifying the infecting organism remains important to ensure optimal antimicrobial treatment. However, these organisms can be difficult to diagnose. We outline a systematic approach to BCNE. Over half of patients with infective endocarditis now undergo early surgery and 16S ribosomal ribonucleic acid (rRNA) polymerase chain reaction (PCR) of excised tissue can be vitally important to secure a diagnosis. Molecular testing is likely to become a key tool in improving outcomes from BCNE and contribute to an improved understanding of the aetiology. We advocate modifying the Duke criteria to incorporate organisms identified on molecular testing, including 16S rRNA PCR, in particular from explanted tissue.

An ascending aortic mass infected with Citrobacter koseri in a young woman.

BACKGROUND: Isolated aortic infection is rare and is typically associated with an underlying aortic aneurysm or a prosthetic aortic graft. CASE SUMMARY: A 38-year-old woman was admitted with symptoms of left upper limb ischaemia and had imaging findings suggestive of thrombus extending from the ascending aorta into the subclavian and brachial arteries. She underwent evacuation of the aortic masses and replacement of the ascending aorta. Citrobacter koseri was isolated from the excised tissue and the patient received 6 weeks of appropriate antibiotic therapy. DISCUSSION: This is an unusual case of acute upper limb ischaemia due to a mass infected with Citrobacter koseri in the ascending aorta without heart valve involvement.

Bilateral adrenal haemorrhagic infarction in a patient with antiphospholipid syndrome.

A 68-year-old woman with antiphospholipid syndrome presented with a 3-day history of bilateral loin pain, vomiting, fever and confusion. On examination she was febrile, hypotensive and tachycardic. Investigations revealed raised inflammatory markers, renal impairment and hyponatraemia. Abdominal ultrasound revealed two well-defined heterogeneous areas bilaterally in the region of the adrenal glands. This prompted serum cortisol measurement and a CT of the abdomen. Cortisol was low in the context of sepsis at 48 nmol/L, and CT confirmed bilateral heterogeneous adrenal pathology. The patient was managed for septic shock and adrenal insufficiency. She was recognised to have several risk factors for haemorrhagic infarction of the adrenals: antiphospholipid syndrome, sepsis, postoperative state and anticoagulant therapy. She was discharged well on glucocorticoid and mineralocorticoid therapy and a repeat CT at 4 weeks confirmed the diagnosis of bilateral adrenal infarct and haemorrhage.

Sleep disordered breathing, fatigue, and sleepiness in HIV-infected and -uninfected men.

STUDY OBJECTIVES: We investigated the association of HIV infection and highly active antiretroviral therapy (HAART) with sleep disordered breathing (SDB), fatigue, and sleepiness. METHODS: HIV-uninfected men (HIV-; n = 60), HIV-infected men using HAART (HIV+/HAART+; n = 58), and HIV-infected men not using HAART (HIV+/HAART-; n = 41) recruited from two sites of the Multicenter AIDS cohort study (MACS) underwent a nocturnal sleep study, anthropometric assessment, and questionnaires for fatigue and the Epworth Sleepiness Scale. The prevalence of SDB in HIV- men was compared to that in men matched from the Sleep Heart Health Study (SHHS). RESULTS: The prevalence of SDB was unexpectedly high in all groups: 86.7% for HIV-, 70.7% for HIV+/HAART+, and 73.2% for HIV+/HAART-, despite lower body-mass indices (BMI) in HIV+ groups. The higher prevalence in the HIV- men was significant in univariate analyses but not after adjustment for BMI and other variables. SDB was significantly more common in HIV- men in this study than those in SHHS, and was common in participants with BMIs <25 kg/m2. HIV+ men reported fatigue more frequently than HIV- men (25.5% vs. 6.7%; p = 0.003), but self-reported sleepiness did not differ among the three groups. Sleepiness, but not fatigue, was significantly associated with SDB. CONCLUSIONS: SDB was highly prevalent in HIV- and HIV+ men, despite a normal or slightly elevated BMI. The high rate of SDB in men who have sex with men deserves further investigation. Sleepiness, but not fatigue, was related to the presence of SDB. Clinicians caring for HIV-infected patients should distinguish between fatigue and sleepiness when considering those at risk for SDB, especially in non-obese men.

Association between systemic inflammation and obstructive sleep apnea in men with or at risk for HIV infection.

BACKGROUND: We sought to determine whether markers of systemic inflammation are associated with the presence of moderate/severe obstructive sleep apnea (OSA) and whether this association differs based on HIV and HIV treatment status. METHODS: HIV-uninfected men (HIV-; n=60), HIV-infected men receiving HAART (HIV+/HAART; n=58) and HIV-infected men not receiving HAART (HIV+/no HAART; n=41) underwent polysomnograpy and measurement of plasma levels of tumour necrosis factor (TNF)-α, soluble TNF-α receptors I and II (sTNFRI and sTNFRII) and interleukin (IL)-6. The relationship between moderate/severe OSA (respiratory disturbance index ≥15 apnea/hypopnea events/h) and inflammatory markers was assessed with multivariable regression models. RESULTS: Compared with the HIV- men, HIV+/HAART men and HIV+/no HAART men had higher levels of TNF-α, sTNFRI and sTNFRII, independent of age, race, smoking status, obstructive lung disease (OLD) and body mass index (BMI). Moderate/severe OSA was present in 48% of the sample (HIV- 57%; HIV+/HAART 41%; HIV+/no HAART 44%). Among the HIV+/no HAART men, but not in the other groups, TNF-α, sTNFRII and IL-6 levels were higher in those with moderate/severe OSA compared to men with no/mild OSA after adjustment for age, race, smoking status, OLD and BMI. Within this group, the association of high TNF-α concentrations with moderate/severe OSA was also independent of CD4(+) T-cell count and plasma HIV RNA concentration. CONCLUSIONS: Compared with HIV+/HAART men and HIV- men, markers of systemic inflammation were higher in HIV+/no HAART men. In these men, TNF-α was significantly related to OSA, independent of HIV-related covariates.

Influence of gender on receipt of guideline-based antiretroviral therapy in the era of HAART.

United States HIV guidelines delineate preferred antiretroviral treatment (ART) and discourage use of sub-potent, toxic, or adversely interacting combinations. It is unclear how often patients receive guideline concordant ART and what factors are correlated with receiving guideline-inconsistent ART. The objective of this study was to assess ART reported by participants of the Women's Interagency HIV Study (WIHS) and the Multicenter AIDS Cohort Study (MACS) to determine whether gender is associated with receipt of guideline-inconsistent ART. ART reported by WIHS and MACS participants from 1 January 2001, to 31 December 2007, was assessed for concordance with HIV guidelines. Logistic regression with generalized estimating equations estimated the crude and adjusted odds ratios and 95% confidence intervals associated with guideline-inconsistent regimens. Of 2937 participants, 463 subjects (WIHS n = 263; MACS n = 200) reported guideline-inconsistent ART during the study period. Age > 50 years (aOR = 2.22, 95% CI 1.14, 4.33) and HIV-1 RNA (aOR = 1.17, 95% CI 1.08, 1.25) but not participant gender (aOR = 1.21, 95% CI 0.88, 1.65) were associated with guideline-inconsistent ART. The prevalence of guideline-inconsistent ART peaked in 2004; however, there was not a statistically significant increase or decrease over time. Guideline-inconsistent ART was not related to gender, but was often used by older patients and patients with higher viral loads. Monitoring ART quality based on concordance with expert guidelines could improve treatment outcomes in a substantial number of patients.

Anthropometry in the prediction of sleep disordered breathing in HIV-positive and HIV-negative men.

BACKGROUND: Body mass index (BMI), waist circumference (WC) and neck circumference (NC) are important screening tools for sleep disordered breathing (SDB); however, the utility of anthropometry for this purpose has not been evaluated among HIV-positive patients. METHODS: HIV-negative men (n=60), HIV-positive men receiving highly active antiretroviral therapy (HIV-positive/HAART; n=58) and HIV-positive men not receiving HAART (HIV-positive/no HAART; n=41) from the Multicenter AIDS Cohort Study underwent a nocturnal sleep study and anthropomorphic assessment. Moderate-severe SDB was defined as an apnea/hypopnea event rate > or =15 episodes/h. Receiver operating characteristic (ROC) curves were used to compare the ability of different anthropometric measurements to predict SDB within each group. RESULTS: Moderate-severe SDB was found in 48% of men (HIV-negative [57%], HIV-positive/HAART [41%] and HIV-positive/no HAART [44%]). The performance of BMI, WC and NC to predict SDB was excellent among the HIV-negative men (ROC areas under the curve [AUCs] 0.83, 0.88 and 0.88, respectively) and fair among the HIV-positive/HAART group (AUC 0.71, 0.77 and 0.77, respectively). By contrast, these measurements had no predictive value in the HIV-positive/no HAART group (AUC 0.43, 0.41 and 0.45, respectively). Moreover, in the HIV-positive/no HAART group, moderate-severe SDB was independently associated with serum C-reactive protein > or =3.0 mg/l (odds ratio 6.9; P=0.04) and HIV RNA>10,000 copies/ml (odds ratio 7.1; P=0.05). CONCLUSIONS: BMI, WC and NC had a better predictive value for moderate-severe SDB in HIV-positive men compared with HIV-positive [corrected] men, and had no value among HIV-positive/no HAART men. Among this latter group, systemic inflammation might contribute to the pathogenesis of SDB.

Social skills assessment of children with autism in free-play situations.

Poor social functioning and limited play are characteristic of children with autism. Increasingly, education for children with autism is provided within mainstream settings, but given their particular difficulties, the adequate provision of educational services in such settings is challenging. This study presents observational data of the play behaviour and social interaction patterns of 10 children with autism in mainstream kindergartens and primary school playgrounds. The target children differed significantly in terms of their play and social interactions from typically developing children in the same settings. The adequacy of the provision of services for children with autism in mainstream provision is discussed.

Changes in adherence to highly active antiretroviral therapy medications in the Multicenter AIDS Cohort Study.

OBJECTIVES: To characterize the determinants of changes in adherence to antiretroviral therapy and examine whether there are persistent lower adherers. DESIGN: A cohort study with repeated measurements. METHODS: Self-reported 100% adherence was defined as taking all doses and numbers of pills over a 4-day period as prescribed for current HIV medications. Independent predictors of changing adherence (< 100% to 100% and 100% to < 100%) were determined by logistic regression, correcting for correlated repeated measures for 597 HIV-positive men reporting the use of highly active antiretroviral therapy (HAART) between October 1998 and October 2000. RESULTS: Of the 942 visit-pairs with initial 100% adherence, 106 (11.3%) reduced adherence to less than 100%, and 836 (88.7%) remained 100% adherent at the next 6-month visit. No recent outpatient visits, younger age, depression, less than college educated, and later in calendar time predicted decreasing adherence. Among 186 visit-pairs starting with less than 100% adherence, 133 (71.5%) improved adherence to 100% and 53 (28.5%) remained less than 100% adherent at the next visit. The determinants of improving adherence included not being African-American, not using recreational drugs, and having had more than three HAART regimens. Lower adherence was not a random event; it was significantly correlated across visits within the individual. CONCLUSION: Characteristics associated with improving and lowering adherence differed and should be considered in developing interventions to enhance adherence and optimize effective therapies.