Metabolomic Association and Risk Prediction With Heart Failure in Older Adults.

BACKGROUND: Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults. METHODS: Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication. RESULTS: Sixty metabolites (hazard ratios range, 0.79-1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19-1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017-0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors (P<0.05). CONCLUSIONS: Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.

Does endovascular repair of post-traumatic thoracic vascular injury of the subclavian/axillary arteries followed by brachial plexus injury improve outcome?

Traumatic injuries to the axillary artery or subclavian artery along with a brachial plexus injury are infrequent. Although the traditional management has been conservative because of robust collaterals, the functional improvement of the limb depends on the degree of brachial plexus injury and on the revascularization status. We report three cases of endovascular repair post-traumatic axillo-subclavian artery injuries followed by brachial plexus injury with good functional outcomes. Endovascular repair of post-traumatic subclavian and axillary artery injuries followed by brachial plexus injury is safe and feasible, and improves limb outcomes.

De novo arteriovenous malformations in post-thrombotic limbs.

A 50-year-old woman presented with progressive, painful and disabling swelling of the left lower limb following a left ovarian cyst excision 2 years ago. She had gross oedema of the left lower limb with multiple pubic varices. Contrast-enhanced CT and digital subtraction imaging revealed diffuse arteriovenous malformation (AVM) with feeders from the left internal iliac artery and a short segment significant stenosis of the proximal left common iliac vein. She underwent angioplasty and stenting of the left iliac vein. Her symptoms dramatically improved following the procedure and her limb swelling regressed within 6 months. The occurrence of post-thrombotic AVMs has been long established in the dural and portal systems. This report deals with an analogous phenomenon following iatrogenic deep venous thrombosis of the left lower limb, its pathogenesis, natural history and a review of treatment options.

Progress and Challenges in Physiological Artifacts' Detection in Electroencephalographic Readings.

BACKGROUND: Electroencephalographic (EEG) recordings are used to trace neural activity within the cortex to study brain functioning over time. INTRODUCTION: During data acquisition, the unequivocal way to reduce artifact is to avoid artifact stimulating events. Though there are certain artifacts that make this task challenging due to their association with the internal human mechanism, in the human-computer interface, these physiological artifacts are of great assistance and act as a command signal for controlling a device or an application (communication). That is why pre-processing of electroencephalographic readings has been a progressive area of exploration, as none of the published work can be viewed as a benchmark for constructive artifact handling. METHODS: This review offers a comprehensive insight into state of the art physiological artifact removal techniques listed so far. The study commences from the single-stage traditional techniques to the multistage techniques, examining the pros and cons of each discussed technique. Also, this review paper gives a general idea of various datasets available and briefs the topical trend in EEG signal processing. RESULTS: Comparing the state of the art techniques with hybrid ones on the basis of performance and computational complexity, it has been observed that the single-channel techniques save computational time but lack in effective artifact removal especially physiological artifacts. On the other hand, hybrid techniques merge the essential characteristics resulting in increased performance, but time consumption and complexity remain an issue. CONCLUSION: Considering the high probability of the presence of multiple artifacts in EEG channels, a trade-off between performance, time and computational complexity is the only key for effective processing of artifacts in the time ahead. This paper is anticipated to facilitate upcoming researchers in enriching the contemporary artifact handling techniques to mitigate the expert's burden.

New persistent opioid use after surgery in patients with a history of remote opioid use.

BACKGROUND: Postoperative pain management is particularly challenging in patients using opioids preoperatively, but previous studies have not stratified patients not using opioids at the time of surgery according to history of opioid use. This study was designed to test the hypothesis that history of opioid use among patients not reporting opioid use at the time of surgery was independently associated with new persistent opioid use after surgery. METHODS: Using prospective perioperative data from the Analgesic Outcomes Study, we assessed outcomes of patients 18 years of age or older who underwent elective surgery between December 2015 and January 2019 and were not using opioids at the time of surgery. Patient self-reported outcome measures were collected on the day of surgery and at 2 weeks, 1 month, and 3 months postoperatively. The primary outcome was new persistent opioid use, defined as continued opioid use 3 months after surgery. The primary explanatory variable was history of opioid use, which was categorized as no history of opioid use, history of non-continuous opioid use, or history of continuous opioid use (defined as daily or almost every day for 3 months or longer). Other covariates included demographics, validated measures (pain, mood), surgery type and approach, comorbidities, and use of tobacco, alcohol, cannabis, and benzodiazepines. Backward stepwise logistic regression models were used to determine patient factors associated with new persistent opioid use and refill after surgery. RESULTS: A total of 1,249 patients not taking opioids preoperatively were included in the study cohort for new persistent opioid use. A total of 54 (4.3%) patients had continued use 3 months after surgery. New persistent opioid use after surgery was independently associated with non-continuous opioid use history (adjusted odds ratio 2.9, [95% confidence interval, 1.21 to 6.94]), continuous opioid use history (adjusted odds ratio 5.0, [95% confidence interval, 1.48 to 16.76]), and moderate to high alcohol use (adjusted odds ratio 2.5, [95% confidence interval, 1.24 to 4.93]). Similarly, opioid prescription refill at 1 month after surgery was independently associated with history of non-continuous opioid use (adjusted odds ratio 1.6, [95% confidence interval, 1.12 to 2.24]), history of continuous opioid use (adjusted odds ratio 2.2, [95% confidence interval, 1.15 to 4.06]), and moderate to high alcohol use (adjusted odds ratio 1.7, [95% confidence interval, 1.18 to 2.48]). CONCLUSION: Among patients not using opioids preoperatively, a history of opioid use was independently associated with new persistent opioid use after surgery, especially those with a history of continuous opioid use.

Transcutaneous Partial Pressure of Oxygen Measurement in Advanced Chronic Venous Insufficiency as a Marker of Tissue Oxygenation.

PURPOSE: Determination of oxygen concentration in tissues affected by chronic venous insufficiency (CVI) has shown inconsistent results over the years and has confounded the pathophysiology of venous diseases. This study measured transcutaneous partial oxygen pressure (TcPO2) levels in patients with CVI to assess oxygenation and variation in oxygenation according to CVI stage. Materials and. METHODS: A prospective study was performed on consecutive patients with unilateral CVI. TcPO2 of diseased and unaffected limbs was measured in the supine and dependent positions. A single TcPO2 value was measured at the site of greatest skin change or at the edge of the ulcer. The TcPO2 values were analyzed and compared according to stage. RESULTS: A total of 96 patients were included in the study with C4 (24.0%), C5 (19.8%), and C6 (56.3%) disease. The mean age was 44.7 years, and 85 (88.5%) were male. There was a statistically significant (P<0.01) difference in mean TcPO2 levels between the unaffected limb (supine, 32.1 mmHg; dependent, 50.7 mmHg), C5 diseased limb (supine, 16.6 mmHg; dependent, 35.5 mmHg), and C6 diseased limb (supine, 24.2 mmHg; dependent, 40.4 mmHg). In the supine and dependent positions, the mean TcPO2 in the affected limb was significantly lower (P<0.01) than that in the unaffected limb. CONCLUSION: TcPO2 in advanced CVI can be used as a marker of oxygenation status. This is the first study in an Indian population looking at the relevance of TcPO2 in the prognostication of advanced CVI.

Systematic Review of Erythropoietin (EPO) for Neuroprotection in Human Studies.

Erythropoietin (EPO) is an exciting neurotherapeutic option. Despite its potential, concerns exist regarding the potential for thrombosis and adverse events with EPO administration in normonemic adults. Systematic review of literature using PRISMA guidelines to examine the application and risks of EPO as a treatment option for neuroprotection in normonemic adults. Independent, systematic searches were performed in July 2019. PubMed (1960-2019) and the Cochrane Controlled Trials Register (1960-2019) were screened. Search terms included erythropoietin, neuroprotection, and humans. The PubMed search resulted in the following search strategy: ("erythropoietin" [MeSH Terms] OR "erythropoietin" [All Fields] OR "epoetin alfa" [MeSH Terms] OR ("epoetin" [All Fields] AND "alfa" [All Fields]) OR "epoetin alfa" [All Fields]) AND ("neuroprotection" [MeSH Terms] OR "neuroprotection" [All Fields]) AND "humans" [MeSH Terms]. PubMed, Cochrane Controlled Trials Register, and articles based on prior searches yielded 388 citations. 50 studies were included, comprising of 4351 patients. There were 13 studies that noted adverse effects from EPO. Three attributed serious adverse effects to EPO and complications were statistically significant. Two of these studies related the adverse events to the co-administration of EPO with tPA. Minor adverse effects associated with the EPO group included nausea, pyrexia, headache, generalized weakness and superficial phlebitis. Most published studies focus on spinal cord injury, peri-surgical outcomes and central effects of EPO. We found no studies to date evaluating the role of EPO in post-operative pain. Future trials could evaluate this application in persistent post-surgical pain and in the peri-operative period.

Longitudinal associations of blood pressure with aortic stiffness and pulsatility: the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To characterize the longitudinal relationships between blood pressure measured over 24 years and arterial stiffness in late life measured as pulse wave velocity (PWV). METHODS: Carotid--femoral (cf) and femoral--ankle (fa) PWV were measured in 4166 adults at the visit 5 Atherosclerosis Risk in Communities study cohort examination (2011-2013). Participants were categorized into tertiles of PWV measurements. Blood pressure measurements were made at baseline (1987-1989), three subsequent triennial examinations, and visit 5. RESULTS: Partial correlation coefficients between visit 5 cfPWV and SBP ranged from 0.13 for visit 1 SBP to 0.32 for visit 5 SBP. For visit 5 faPWV, correlations were ∼0 for visits 1 to 4 SBP, but was 0.20 for visit 5 SBP. Over 24 years of follow-up, those with higher average SBP were more likely to fall in the middle and upper tertiles of visit 5 cfPWV. Average pulse pressure and mean arterial pressure over 24 years had similar but weaker associations with cfPWV tertiles. DBP had no clear association with cfPWV. Blood pressure measurements were positively associated with faPWV tertiles only cross-sectionally at visit 5. CONCLUSION: Adult life-course measures of SBP, more so than mean arterial and pulse pressure, were associated with later life central arterial stiffness. By contrast, only contemporaneous measures of blood pressure were associated with peripheral arterial stiffness. Although arterial stiffness was only measured at later life, these results are consistent with the notion that elevated blood pressure over time is involved in the pathogenesis of arterial stiffening.

Salmonella typhi as cause of neonatal sepsis: case report and literature review.

Salmonella typhi is a rare cause of neonatal sepsis and can present with life threating complications, thus leading to increase in neonatal mortality and morbidity. The clinical features of neonatal Salmonella typhi infection are not different to neonatal sepsis caused by other gram-negative organism in this age group. The mode of transmission of neonatal Salmonella typhi is still not known and has been postulated to be both vertical and horizontal. The diagnosis of Salmonella typhi is made by growth of the organism in blood culture as Serum Widal test is not helpful in diagnosis. The management includes supportive care and intravenous antibiotics. We report two neonates who were admitted in our neonatal intensive care unit for neonatal sepsis and were diagnosed of having Salmonella typhi sepsis.

To compare nasal mask with binasal prongs in delivering continuous positive airway pressure for reducing need of invasive ventilation: randomized controlled trial.

AIMS: To compare nasal mask with binasal prongs in delivering bubble continuous positive airway pressure (CPAP) for reducing need of invasive ventilation in VLBW infants: randomized controlled trial. METHODS: In this randomized control trial 178 infants were enrolled, 90 were randomized to nasal mask group and 88 to nasal prong group for delivering bubble CPAP. Preterm neonates between 26 and 32 weeks of gestational age requiring CPAP for respiratory distress within 6 h of life were assessed for eligibility and were included if neonates had spontaneous respiratory efforts with respiratory distress in the form of tachypnea (respiratory rate >60/min), intercostal/subcostal retractions, grunting (audible with/without stethoscope), Silverman Anderson score ≥3, increased respiratory efforts or cyanosis. Infants received either nasal mask or binasal prongs for delivery of bubble CPAP. The primary outcome was the need for mechanical ventilation in first 72 h of life. RESULTS: Baseline characteristics were comparable between the two groups. There was significant reduction in incidence of CPAP failure [15 (16.6%) versus 26 (29.5%); RR 0.47 (95% CI 0.23-0.97), p = .04]; nasal trauma (any grade) [14 (15.9%) versus 38 (43.2%); RR 0.26 (95% CI 0.12-0.52), p = .0002]; nasal trauma grade I [12 (13.3%) versus 23 (26.1%); RR 0.43 (95% CI 0.20-0.94), p = .03]; nasal trauma grade II [1 (1.1%) versus 10 (11.3%); RR 0.08 (95% CI 0.01-0.70), p = .02]; nasal trauma severe grade (II and III) [2 (2.2%) versus 15 (17.0%);RR 0.11 (95% CI 0.02-0.49), p = .004] and bronchopulmonary dysplasia [4 (4.4%) versus 12 (13.6%); RR 0.30 (95% CI 0.10-0.95), p = .04] in nasal mask group when compared to nasal prong group. CONCLUSION: Nasal mask leads to significant reduction in need for mechanical ventilation in initial 72 h.

Primary De novo ductal adenocarcinoma of the lacrimal gland.

BACKGROUND: Primary ductal adenocarcinoma of the lacrimal gland is a rare and aggressive malignant epithelial lacrimal gland neoplasm, morphologically and phenotypically resembles salivary duct carcinoma, and both strongly resemble infiltrating ductal carcinoma of breast. METHOD: Retrospective Chart review of cases of malignant lacrimal gland tumors from 2013 July to 2020 July. Authors describe the clinico radiological, morphological and immunohistochemical features of primary ductal adenocarcinoma (PDA) of lacrimal gland. Extensive review of literature of PDA of lacrimal gland and salivary gland ductal carcinoma has been performed. RESULTS: Retrospective chart review of the last 7 years yielded 22 malignant lacrimal gland neoplasms of which 4 cases demonstrated features of primary ductal adenocarcinoma of lacrimal gland, 2/4 cases showed an evidence of a pre existing pleomorphic adenoma and 2 were found to be de novo ductal adenocarcinomas. PDA of lacrimal gland showed expression of CK7, CK19, AR, HER2, cyclin D1 and were negative for CK5/14, CK 20, ER, PR, PSA, TTF-1, S-100 and SMA. Expression of GCDFP-15 was noted in one case. The presence of multiple events of loco-regional recurrences and/or distant metastasis necessitated a multidisciplinary approach. CONCLUSIONS: Authors have expressed the need of clinical correlation; thorough tissue sampling and extensive immunohistochemical work up in identification of de novo PDA's and their molecular subtypes. A multi-institutional study might help in formulating the diagnostic criteria, identification of actionable targets, and thus study the role of targeted therapy in this rare and aggressive tumor which may result in better patient outcomes.

Patterns of arterial involvement and feasibility of revascularization in thromboangiitis obliterans: a tertiary care centre experience.

BACKGROUND: Arterial revascularization is seldom considered as a treatment option in thromboangiitis obliterans (TAO) due to diffuse segmental involvement of medium- and small-sized extremity vessels. Although typical angiographic features include bilaterally symmetrical involvement of infrapopliteal vessels, larger vessels too can be affected. Similarly, there could be distal target vessels feasible for revascularization. This study was conducted to describe the patterns of arterial involvement in TAO and assess the feasibility of revascularization. METHODS: The study was approved by the Institutional Review Board and research ethics committee of Christian Medical College, Vellore (IRB no: 12034). A retrospective study was conducted in the Department of Vascular Surgery, Christian Medical College, Vellore, India, between January 2009 and December 2018. There were 329 patients who fulfilled the clinical criteria for TAO of whom 83 had an angiogram done. These 83 patients formed the study cohort. RESULTS: Large vessel involvement was seen in 56.6% of patients and 79.5% of patients had at least one or more distal target artery feasible for revascularization. The anterior tibial artery and peroneal artery were the most common target vessels that were patent for revascularization. Of the 22 patients who underwent revascularization (16 bypasses and six angioplasties), the patency rate was 64.8% and the limb salvage rate was 80.9% at the end of 6 months. CONCLUSION: The study shows that one-third of our patients with TAO have a distal target artery feasible for revascularization. As most of the affected patients are in the economically productive age group, every attempt should be made to salvage the limb with revascularization for which the use of angiography should be more liberal.

Predictors of Mortality by Sex and Race in Heart Failure With Preserved Ejection Fraction: ARIC Community Surveillance Study.

Background Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure hospitalizations, with limited data on predictors of mortality by sex and race. We evaluated for differences in predictors of all-cause mortality by sex and race among hospitalized patients with HFpEF in the ARIC (Atherosclerosis Risk in Communities) Community Surveillance Study. Methods and Results Adjudicated HFpEF hospitalization events from 2005 to 2013 were analyzed from the ARIC Community Surveillance Study, comprising 4 US communities. Comparisons between clinical characteristics and mortality at 1 year were made by sex and race. Of 4335 adjudicated acute decompensated heart failure cases, 1892 cases (weighted n=8987) were categorized as HFpEF. Men had an increased risk of 1-year mortality compared with women in adjusted analysis (hazard ratio [HR], 1.27; 95% CI, 1.06-1.52 [P=0.01]). Black participants had lower mortality compared with White participants in unadjusted and adjusted analyses (HR, 0.79; 95% CI, 0.64-0.97 [P=0.02]). Age, heart rate, worsening renal function, and low hemoglobin were associated with increased mortality in all subgroups. Higher body mass index was associated with improved survival in men, with borderline interaction by sex. Higher blood pressure was associated with improved survival among all groups, with significant interaction by race. Conclusions In a diverse HFpEF population, men had worse survival compared with women, and Black participants had improved survival compared with White participants. Age, heart rate, and worsening renal function were associated with increased mortality across all subgroups; high blood pressure was associated with decreased mortality with interaction by race. These insights into sex- and race-based differences in predictors of mortality may help strategize targeted management of HFpEF.

Post-traumatic preauricular pulsatile swelling in a patient on oral anticoagulation therapy.

The differential diagnoses for preauricular swellings include dermoid cyst, lymph nodes, lipoma, nerve sheath tumours, parotid swelling, mastoiditis, vascular malformations and arterio-venous fistulas aneurysms/pseudoaneurysms. Superficial temporal artery pseudoaneurysm(s) (STAPA) are rare (1% of all aneurysms) vascular complications, which occur following a blunt injury of the head or iatrogenic causes. The use of anticoagulation therapy increases the risk of pseudoaneurysm formation. We present a case of traumatic STAPA while on oral anticoagulation. He was treated with surgical exploration, STAPA excision with ligation of the vessel. He had an uneventful recovery with a good functional and cosmetic outcome at 1 year.

Mycotic abdominal aortic aneurysm complicated by infective spondylitis due to P seudomonas aeruginosa.

A 67-year-old man with diabetes and hypertension presented with complaints of abdominal pain and lower back ache for 7 months, with intermittent episodes of fever. On examination, there was an expansile mass in the upper abdomen with bruit on auscultation. He also had tenderness in the L1-L2 vertebral space with paraspinal fullness, causing painful restriction of lower limb motor functions but without affecting sensation. On evaluation, he was found to have an abdominal aortic aneurysm with infective lumbar spondylodiscitis. The aspirate from the paravertebral infected tissue and cultures from blood grew Pseudomonas aeruginosa, a rare causative agent of mycotic aortic aneurysm. Whether the infective spondylitis spread to the abdominal aorta causing the mycotic aneurysm or vice versa is a dilemma in such a case. However, the mainstay of treatment remains adequate source control and repair of the aneurysm with appropriate antibiotic therapy. Our patient received intravenous antibiotics for P . aeruginosa based on sensitivity, following which he underwent debridement of the infective spondylodiscitis with aneurysmorrhaphy. He had an uneventful recovery and was well at 3-month follow-up.

Acid and heat fastness in microsporidia: How acid fast are acid fast microsporidium?

Microsporidia are obligate spore-forming microorganisms with strong resemblance to fungi and can affect almost every organ system in immunocompetent or immunocompromised individuals. Mixed infections are also reported in immunocompromised hosts. Microsporidial spores show marked morphological variations and the small and slender forms can resemble bacilli. Modified Zeihl Neelsen (ZN) stain, cold method demonstrates them as bright red in color, leaving several spores blue or incompletely stained; thus, they are reported as weakly or variably acid fast. Variability in staining results with ZN stain and considering the fact that Mycobacterium tuberculosis, the commoner bug in developing countries is identified by its resistance to stronger acids on ZN staining, authors wished to demonstrate acid and heat fastness in microsporidium using corneal tissue specimens. Microsporidial spores stained bright red in color with conventional ZN stain, demonstrated strong acid fastness, and interestingly the staining results improved on heating. Thus, the authors conclude that they are strongly acid and heat fast and care must be warranted so that they are not misdiagnosed as Mycobacterium or other acid-fast organisms. Careful observation of morphology, battery of special stains, and molecular diagnostics should be advocated for diagnostic confirmation. To the best of the authors' knowledge, this is the first explicit report on acid and heat fastness on microsporidial spores.