Objectives
To determine whether preoperative anemia, perioperative blood transfusion, and predischarge anemia affect function and health‐related quality of life (HRQoL) after hip fracture surgery.
...Design
Retrospective single‐center cohort study
Participants
Individuals undergoing traumatic hip fracture surgery from 2012 to 2016 (N=973).
Measurements
Demographic data, Charlson Comorbidity Index, preoperative hemoglobin level, perioperative blood transfusion, predischarge hemoglobin level, type of surgery (replacement or fixation). Anemia was divided into quintiles at 10.0, 11.0, 12.0, and 13.0 g/dL. Baseline, 6‐week, and 6‐month Harris Hip Scale (HHS), Parker Mobility Scale (PMS), and Medical Outcomes Study 36‐item Short‐Form Health Survey (SF‐36) scores were obtained. PMS; HHS and SF‐36 role physical (RP), physical function (PF), and social functioning (SF) domains had more than 20% change from baseline to 6 weeks and from 6 weeks to 6 months. Univariate and multivariate analyses were conducted to examine the association between preoperative anemia, transfusion and predischarge anemia on 6‐month scores.
Results
On univariate analysis, preoperative hemoglobin less than 10.0 g/dL was associated with lower baseline prefall PMS, PF, RP, and SF scores. Predischarge anemia did not affect 6‐month scores. On multivariate analysis, preoperative anemia (hemoglobin <10.0 g/dL) was associated with lower 6‐month HHS, PMS, PF, and RP scores, whereas transfusion was not significant.
Conclusion
Preoperative anemia (hemoglobin <10.0 g/dL) is associated with poorer physical function and HRQoL after hip fracture surgery. Perioperative blood transfusion and predischarge anemia had no effect.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In the mid-nineteenth century the Irish question-the governance of the island of Ireland-demanded attention on both sides of the Atlantic. InA Union Forever, David Sim examines how Irish nationalists ...and their American sympathizers attempted to convince legislators and statesmen to use the burgeoning global influence of the United States to achieve Irish independence. Simultaneously, he tracks how American politicians used the Irish question as means of furthering their own diplomatic and political ends.
Combining an innovative transnational methodology with attention to the complexities of American statecraft, Sim rewrites the diplomatic history of this neglected topic. He considers the impact that nonstate actors had on formal affairs between the United States and Britain, finding that not only did Irish nationalists fail to involve the United States in their cause but actually fostered an Anglo-American rapprochement in the final third of the nineteenth century. Their failures led them to seek out new means of promoting Irish self-determination, including an altogether more radical, revolutionary strategy that would alter the course of Irish and British history over the next century.
Globalization has resulted in epidemiologic transition in developing countries from infectious disease and nutritional deficiencies to non-communicable diseases. Epidemiologic data on heart failure ...(HF), particularly advanced HF therapy, in Asia are increasingly becoming available, although they remain sparse. Heart transplantation for advanced stage HF remains very low in Asia-approximately 0.075 heart transplants per 1 million population. North America, which comprises 7.5% of the world population, accounted for 55.8% of transplants recorded in the 2012 International Society for Heart and Lung Transplantation (ISHLT) Registry, whereas Asia, with 62.5% of the world population, accounted for 5.7% of transplants. There is also lack of reporting from heart transplant centers in Asia to the ISHLT Registry. Most transplant programs in Asia are in economically stable South East Asian countries, whereas in other parts of developing countries, the cost and health care infrastructures remain prohibitive for the development of these programs. Multi-cultural and racial factors, religious beliefs, and diverse traditions of many centuries have resulted in reluctance to organ donation. Mechanical circulatory support (MCS) is emerging as a viable alternative to transplantation, but despite technical capabilities, limitations in embracing MCS in Asia exist. Discrepant practices in the reimbursement of costly MCS therapy have led to differences in the availability of these devices to patients in the region. The HeartMate II (St. Jude Medical, Inc, St. Paul, MN) left ventricular assist device is currently the most widely used durable device in Asia, whereas the HeartWare HVAD (HeartWare, Inc, Framingham, MA) is used most often in Australia. By September 9, 2015, 341 HeartMate implants (293 as bridge to transplant and 48 as destination therapy) had been performed, of which 180 implants were in Japan. The overall 4-year survival is 88%. The longest duration of support is 6.5 years. By the end of 2015, 243 HeartWare HVADs had been implanted in Asia Pacific. There is a need for focused efforts at improving the reporting of data and intensifying health policy within the region to advocate organ transplantation. Individual governments need to take national responsibility to fulfill organ donation and transplantation needs of their populations. International collaboratives, coordinated by societies such as the ISHLT, will be essential in moving this field forward in Asia Pacific.
Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential.
The goal of this study was to test the hypothesis that vasopressin-driven ...urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment.
DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance.
Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor–naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51–4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d 95% CI: 1.98–3.51; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L 95% CI: 0.45-10.5; P < 0.05) and late (7.8 pmol/L 95% CI: 2.77–12.81; P < 0.01), leading to proportional reductions in free water clearance (early: −9.1 mL/kg/d 95% CI: −14 to −4.12; P < 0.001; late: −11.0 mL/kg/d 95% CI: −15.94 to −6.07; P < 0.0001) and elevated urine concentrations (late: 134 mmol/L 95% CI: 39.28–229.12; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d 95% CI: −1.97 to 7.48; P = 0.25; mean difference late: 0.9 mL/kg/d 95% CI: −3.83 to 5.62; P = 0.70).
Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment DAPA-Shuttle1; NCT04080518).
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BACKGROUND:Dilated cardiomyopathy (DCM) is genetically heterogeneous, with >100 purported disease genes tested in clinical laboratories. However, many genes were originally identified based on ...candidate-gene studies that did not adequately account for background population variation. Here we define the frequency of rare variation in 2538 patients with DCM across protein-coding regions of 56 commonly tested genes and compare this to both 912 confirmed healthy controls and a reference population of 60 706 individuals to identify clinically interpretable genes robustly associated with dominant monogenic DCM.
METHODS:We used the TruSight Cardio sequencing panel to evaluate the burden of rare variants in 56 putative DCM genes in 1040 patients with DCM and 912 healthy volunteers processed with identical sequencing and bioinformatics pipelines. We further aggregated data from 1498 patients with DCM sequenced in diagnostic laboratories and the Exome Aggregation Consortium database for replication and meta-analysis.
RESULTS:Truncating variants in TTN and DSP were associated with DCM in all comparisons. Variants in MYH7, LMNA, BAG3, TNNT2, TNNC1, PLN, ACTC1, NEXN, TPM1, and VCL were significantly enriched in specific patient subsets, with the last 2 genes potentially contributing primarily to early-onset forms of DCM. Overall, rare variants in these 12 genes potentially explained 17% of cases in the outpatient clinic cohort representing a broad range of adult patients with DCM and 26% of cases in the diagnostic referral cohort enriched in familial and early-onset DCM. Although the absence of a significant excess in other genes cannot preclude a limited role in disease, such genes have limited diagnostic value because novel variants will be uninterpretable and their diagnostic yield is minimal.
CONCLUSIONS:In the largest sequenced DCM cohort yet described, we observe robust disease association with 12 genes, highlighting their importance in DCM and translating into high interpretability in diagnostic testing. The other genes analyzed here will need to be rigorously evaluated in ongoing curation efforts to determine their validity as Mendelian DCM genes but have limited value in diagnostic testing in DCM at present. This data will contribute to community gene curation efforts and will reduce erroneous and inconclusive findings in diagnostic testing.
Background
Gastrointestinal bleeding (GIB) is a complication reported in patients post left ventricular assist device (LVAD) implantation that is associated with high mortality rates. Thalidomide is ...an anti-angiogenic compound that may offer a potential option for management of refractory LVAD-related GIB.
Methods
A single-center, retrospective review was conducted from January 2009 to October 2016 at a tertiary cardiology center. It included LVAD patients initiated on thalidomide for refractory GIB.
Results
All patients (n = 11) were started on thalidomide 50 mg nocte and there was resolution of GIB in all patients except one (90.9%) during initial thalidomide treatment.
The median duration of thalidomide therapy was 98 days (interquartile range: 34–215). The dose of thalidomide was reduced for 2 patients due to adverse effects. Thalidomide therapy was discontinued in 6 patients due to cessation of GIB (n = 4) and adverse effects (n = 2). Reported adverse effects included LVAD thrombosis (n = 2), somnolence (n = 1), neuropathy (n = 1), constipation (n = 1), and transaminitis (n = 1).
Recurrent GIB occurred in 4 patients (45.4%) post-discontinuation of thalidomide therapy, which led to the re-initiation of therapy.
Conclusions
Thalidomide appears to be a safe and effective option for management of refractory LVAD-related GIB. Monitoring for recurrent GIB should be performed closely following cessation of thalidomide therapy.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Introduction: The impact of sex and diabetes mellitus (DM) on patients with heart failure with mildly reduced ejection fraction (HFmrEF) is not well elucidated. This study aims to evaluate sex ...differences in the clinical profile and outcomes in Asian HFmrEF patients with and without DM.
Methods: Patients admitted nationally for HFmrEF (ejection fraction 40–49%) between 2008 and 2014 were included and followed up until December 2016. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular (CV) death and/or heart failure (HF) rehospitalisations.
Results: A total of 2,272 HFmrEF patients (56% male) were included. More women had DM than men (60% versus 55%, P=0.013). Regardless of DM status, HFmrEF females were older, less likely to smoke, had less coronary artery disease, narrower QRS and lower haemoglobin compared to men. The odds of having DM decreases in smokers who are women as opposed to men (Pinteraction =0.017). In multivariate analysis, DM reached statistical analysis for all-cause mortality and combined CV mortality or HF rehospitalisation in both men and women. However, the results suggest that there may be sex differences in terms of outcomes. DM (vs non-DM) was less strongly associated with increased all-cause mortality (adjusted hazards ratio adj HR 1.234 vs adj HR 1.290, Pinteraction <0.001 but more strongly associated with the combined CV death/HF rehospitalisation (adj HR 1.429 vs adj HR 1.317, Pinteraction =0.027) in women (vs men).
Conclusion: Asian women with HFmrEF had a higher prevalence of DM, with differences in clinical characteristics, compared to men. While diabetes conferred poor outcomes regardless of sex, there were distinct sex differences. These highlight the need for sex-specific management strategies.
Keywords: Asian, diabetes mellitus, heart failure with mildly reduced ejection fraction, sex
Reports of SARS-CoV-2 coronavirus (COVID-19) vaccine-related myocarditis, particularly after mRNA vaccines, have raised concerns amongst the general public. This review examined the literature ...regarding myocarditis post COVID-19 vaccination, drawing from vaccine safety surveillance databases and case reports.
Combinations of search terms were used in PubMed and COVID-19-specific repositories – LitCovid and the Cochrane COVID-19 Study Register – between 1 October 2020 and 31 October 2021. Manual searches of GoogleScholar and screening of article bibliographies were also performed.
Information was obtained from five vaccine safety surveillance databases. Fifty-two (52) case reports totalling 200 cases of possible COVID-19 vaccine-related myocarditis were summarised. Vaccine surveillance databases differed in reporting formats and vaccination rates; however, gross estimates suggested low overall incidence rates of 2–5 per million mRNA vaccines. The incidence appeared to be higher in younger male populations, with onset of symptoms within a few days, usually after the second dose. Some with prior COVID-19 infections had onset after the first dose. Cases with prior unrelated myocarditis were also noted. Almost all presented with chest pain (98.0%). Troponin elevation was universally described and cardiac magnetic resonance imaging was commonly reported based on the updated Lake Louise criteria. Clinical course was mild in the majority, with response to anti-inflammatory treatment.
COVID-19 vaccine-related myocarditis is an important but rare adverse event. More research is needed into its pathogenesis and reasons for its predominance in young males, while gaps in data exist in those aged <16 years, as well as those with prior COVID-19 infections and prior myocarditis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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