Impact of Left Atrial Pressure on Outcomes After Mitral Transcatheter Edge-to-Edge Repair.

Background: Increased left atrial pressure (LAP) has been associated with adverse outcomes after mitral transcatheter edge-to-edge repair (M-TEER). We sought to evaluate outcomes based on differences in post-procedural LAP measured after final clip deployment. Methods: We included consecutive patients who underwent M-TEER at our institution between 2014-2022 with LAP monitoring. Patients were stratified into 3 groups according to tertiles of post-TEER mean LAP. Outcomes were assessed using Kaplan-Meier analysis and Cox proportional hazard models. Results: We included 273 patients (mean age 76.8±10.8 years, 42.5% women, 78.4% Caucasian). The mean post-TEER LAP was 8.7±1.7 mmHg in tertile 1 (N=85), 14.4±1.6 mmHg in tertile 2 (N=95), and 21.9±3.8 mmHg in tertile 3 (N=93). In comparison with tertile 1, both tertiles 2 and 3 were associated with increased risk of all-cause mortality or heart failure hospitalization at 2 years (adjHR 2.27, 95% CI 1.25-4.12; and adjHR 3.00, 95% CI 1.59-5.64 respectively). Among patients with primary MR, higher LAP was associated with increased risk of 2-year all-cause mortality or heart failure hospitalization [tertile 2 vs. 1: adjHR 3.00, 95% CI 1.37-6.56; and tertile 3 vs. 1: adjHR 5.52, 95% CI 2.04-14.95). However, in patients with secondary MR, neither being in tertile 2 (adjHR 1.53; 95% CI 0.55-4.24), nor tertile 3 (adjHR 2.18; 95% CI 0.82-5.77) were associated with the composite outcome compared with tertile 1. Any degree of LAP reduction following M-TEER was associated with lower mortality or heart failure hospitalization compared with no LAP reduction (adjHR 0.59; 95% CI 0.39-0.88). Conclusions: Elevated LAP after M-TEER was associated with increased 2-year risk of mortality or heart failure hospitalization. Exploration of reasons for elevated LAP after M-TEER, and ways to lower it warrant further investigation.

Pacing-Related Differences After SAPIEN-3 TAVI: Clinical and Echocardiographic Correlates.

Data regarding the impact of pacing on outcomes after transcatheter aortic valve implantation (TAVI) is evolving especially with regards to pre-existing permanent pacemaker (PPM). We examined the impact of new and previous PPM on the clinical and hemodynamic outcomes after SAPIEN-3 TAVI. We included all consecutive patients who underwent transfemoral TAVI using SAPIEN-3 valve from 2015 to 2018 at our institution. Among 1,028 patients, 10.2% required a new PPM within 30 days, whereas 14% had a pre-existing PPM. The presence of either previous or new PPM had no impact on the 3-year mortality (log-rank p = 0.6) or 1-year major adverse cardiac and cerebrovascular events (log-rank p = 0.65). New PPM was associated with lower left ventricular (LV) ejection fraction (LVEF) at both 30 days (54.4 ± 11.3% vs 58.4 ± 10.1%, p = 0.001) and 1 year (54.2 ± 12% vs 59.1 ± 9.9%, p = 0.009) than no PPM. Similarly, previous PPM was associated with worse LVEF at 30 days (53.6 ± 12.3%, p <0.001) and 1 year (55.5 ± 12.1%, p = 0.006) than no PPM. Interestingly, new PPM was associated with lower 1-year mean gradient (11.4 ± 3.8 vs 12.6 ± 5.6 mm Hg, p = 0.04) and peak gradient (21.3 ± 6.5 vs 24.1 ± 10.4 mm Hg, p = 0.01), despite no baseline differences. Previous PPM was also associated with lower 1-year mean gradient (10.3 ± 4.4 mm Hg, p = 0.001) and peak gradient (19.4 ± 8 mm Hg, p <0.001) and higher Doppler velocity index (0.51 ± 0.12 vs 0.47 ± 0.13, p = 0.039). Moreover, 1-year LV end-systolic volume index was higher with new (23.2 ± 16.1 vs 20 ± 10.8 ml/m2, p = 0.038) and previous PPM (24.5 ± 19.7, p = 0.038) than no PPM. Previous PPM was associated with higher moderate-to-severe tricuspid regurgitation (35.3% vs 17.7%, p <0.001). There were no differences regarding the rest of the studied echocardiographic outcomes at 1 year. In conclusion, new and previous PPM did not affect 3-year mortality or 1-year major adverse cardiac and cerebrovascular events; however, they were associated with worse LVEF, higher 1-year LV end-systolic volume index, and lower mean and peak gradients on follow-up than no PPM.

Site-level variability in the processes of care and outcomes over time among patients with COVID-19 and myocardial injury: Insights from the American Heart Association's COVID-19 Cardiovascular Disease Registry.

Background: Elevated cardiac troponin (cTn) levels in patients with COVID-19 has been associated with worse outcomes. Guidelines on best practices of those patients remain uncertain. Methods: We included patients with COVID-19 and cTn above the assay-specific upper limit of normal (ULN) enrolled in the American Heart Association's COVID-19 registry between March 2020-January 2021. Site-level variability in invasive coronary angiography, LVEF assessment, ICU utilization, and inpatient mortality were determined by calculating adjusted median odds ratio (MOR) using hierarchical logistic regression models. Temporal trends were assessed with Cochran-Armitage trend test. Results: Among 32,636 patients, we included 6234 (19.4 %) with cTn above ULN (age 68.7 ± 16.0 years, 56.5 % male, 51.5 % Caucasian), of whom 1365 (21.6 %) had ≥5-fold elevations. Across 55 sites, the median rate of invasive coronary angiography was 0.1 % with adjusted MOR 1.5(1.0,2.3), median LVEF assessment was 25.5 %, MOR 3.0(2.2,3.9), ICU utilization was 41.7 %, MOR 2.2(1.8,2.6), and mortality was 20.9 %, MOR 1.7(1.5,2.0). Over time, we noted a significant increase in invasive coronary angiography (p-trend = 0.001), and LVEF assessment (p-trend<0.001), and reduction in mortality (p-trend<0.001), without significant change in ICU admissions (p-trend = 0.08). Similar variability and temporal trends were seen among patients with ≥5-fold cTn elevation. Conclusions: The use of invasive coronary angiography among patients with COVID-19 and myocardial injury was very low during the early pandemic. We found moderate institutional variability in processes of care with an uptrend in invasive catheterization and LVEF assessment, and downtrend in mortality. Comparative effectiveness studies are needed to examine whether variability in care is associated with differences in outcomes.

Clinical and echocardiographic outcomes with new-onset left bundle branch block after SAPIEN-3 transcatheter aortic valve replacement.

BACKGROUND: New-onset left bundle branch block (LBBB) can develop after transcatheter aortic valve replacement (TAVR) resulting in worse outcomes. AIMS: Describe clinical and echocardiographic outcomes with new-onset LBBB after TAVR. METHODS: We included consecutive patients who underwent transfemoral-TAVR with SAPIEN-3 (S3) valve between April 2015 and December 2018. Exclusion criteria included pre-existing LBBB, right BBB, left anterior hemiblock, left posterior hemiblock, wide QRS ≥ 120ms, prior permanent pacemaker (PPM), and nontransfemoral access. RESULTS: Among 612 patients, 11.4% developed new-onset LBBB upon discharge. The length of stay was longer with new-onset LBBB compared with no LBBB [3 (2-5) days versus 2 (1-3) days; p < 0.001]. New-onset LBBB was associated with higher rates of 30-day PPM requirement (18.6% vs. 5.4%; p < 0.001) and 1-year heart failure hospitalizations (10.7% vs. 4.4%; p = 0.033). There was no difference in 3-year mortality between both groups (30.9% vs. 30.6%; p = 0.829). Further, new-onset LBBB was associated with lower left ventricular ejection fraction (LVEF) at both 30 days (55.9 ± 11.4% vs. 59.3 ± 9%; p = 0.026) and 1 year (55 ± 12% vs. 60.1 ± 8.9%; p = 0.002). These changes were still present when we stratified patients according to baseline LVEF (≥50% or <50%). New-onset LBBBs were associated with a higher 1-year LV end-diastolic volume index (51.4 ± 18.6 vs. 46.4 ± 15.1 ml/m2 ; p = 0.036), and LV end-systolic volume index (23.2 ± 14.1 vs. 18.9 ± 9.7 ml/m2 ; p = 0.009). Compared with resolved new-onset LBBB, persistent new-onset LBBB was associated with worse LVEF and higher PPM at 1 year. CONCLUSIONS: New-onset LBBB after S3 TAVR was associated with higher PPM requirement, worse LVEF, higher LV volumes, and increased heart failure hospitalizations, with no difference in mortality.

Association of pepper intake with all-cause and specific cause mortality - A systematic review and meta-analysis.

OBJECTIVE: To conduct a comprehensive systematic review and meta-analysis to compare mortality and other clinical outcomes associated with chili pepper (CP) consumption versus no/rare consumption of CP. METHODS: A comprehensive search was performed using Ovid, Cochrane, Medline, EMBASE, and Scopus from inception till January 16, 2020. Observational studies and randomized controlled trials were included, while pediatric/animal studies, letters/case reports, reviews, abstracts, and book chapters were excluded. All-cause mortality was studied as the primary outcome. Cardiovascular mortality, cancer-related deaths and cerebrovascular accidents were studied as secondary outcomes. RESULTS: From 4729 studies, four studies met the inclusion criteria. Random effects pooled analysis showed that all-cause mortality among CP consumers was lower, compared to rare/non-consumers, with a hazard ratio (HR) of 0.87 [95% CI: 0.85-0.90; p<0.0001; I 2=1%]. HR for cardiovascular mortality was 0.83 [95% CI: 0.74-0.95; p = 0.005, I 2=66%] and for cancer-related mortality as 0.92 [95% CI: 0.87-0.97; p = 0.001; I 2=0%]. However, the HR for CVA was 0.78 [95% CI: 0.56-1.09; p = 0.26; I2 =60%]. The mode and amount of CP consumption varied across the studies, and data were insufficient to design an optimal strategy guiding its intake. CONCLUSION: Regular CP consumption was associated with significantly lower all-cause, cardiovascular, and cancer-related mortalities. However, based on current literature, it is difficult to derive a standardized approach to guide the optimal mode and amount of CP consumption. This warrants well-designed prospective studies to further investigate the potential health benefits of CP consumption.

Characteristics and Outcomes of Patients With Acute Coronary Syndrome Who Received Percutaneous Coronary Intervention During Snowy Days.

BACKGROUND: Acute coronary syndrome (ACS) is affected by several weather conditions. Studies from different geographical locations have yielded mixed results regarding the outcomes of patients presenting with ACS during snowy days, and we aim to report the Cleveland Clinic experience. METHODS: Patients who presented with an ACS and underwent percutaneous coronary intervention (PCI) from July 1, 2009 to September 30, 2017 were divided into ST-segment elevation myocardial infarction (STEMI), and non-ST segment elevation ACS (NSTE-ACS). According to snowy day arrival, we compared in-hospital mortality, culprit lesion anatomy, and door-to-balloon (DTB) time (in STEMI patients). Findings were confirmed in propensity-score matched cohorts. RESULTS: A total of 6878 patients were included: 1608 patients with STEMI (139 snowy-day vs 1469 non-snowy day PCIs) and 5270 NSTE-ACS (419 snowy-day vs 4851 non-snowy day PCIs). Right coronary artery territories accounted for most of the stented culprit lesions in all STEMI and NSTE-ACS snowy-day PCIs. While left anterior descending artery lesions were predominant in NSTE-ACS non-snowy day PCIs. There was no difference in in-hospital mortality between the snowy-day vs non-snowy day groups (4.3% vs 4.5% in the STEMI group [P=.92] and 1.2% vs 1.7% in the NSTE-ACS group [P=41]). In STEMI patients, mean DTB times were similar (43 ± 55.1 minutes vs 46.7 ± 59.6 minutes; P=.61), which remained true after hours, during weekends and holidays. Outcomes were similar in propensity-score matched cohorts. CONCLUSION: At our institution, snowy days do not seem to affect in-patient mortality. In STEMI patients, DTB times were similar in those who underwent PCI regardless of the snowfall.

Oral Calcium Supplements Associate With Serial Coronary Calcification: Insights From Intravascular Ultrasound.

OBJECTIVES: This study sought to evaluate and assess the extent of serial coronary artery calcification in response to oral calcium supplementation. BACKGROUND: Oral calcium supplements are frequently used despite their cardiovascular safety remaining controversial. Their effects on serial coronary calcification are not well established. METHODS: In a post hoc patient-level analysis of 9 prospective randomized trials using serial coronary intravascular ultrasound, changes in serial percentage of atheroma volume (PAV) and calcium indices (CaI) were compared in matched segments of patients coronary artery disease who were receiving concomitant calcium supplements (n = 447) and in those who did not receive supplements (n = 4,700) during an 18- to 24-month trial period. RESULTS: Patients (mean age 58 ± 9 years; 73% were men; 43% received concomitant high-intensity statins) demonstrated overall annualized changes in PAV and CaI with a mean of -0.02 ± 1.9% (p = 0.44) and a median of 0.02 (interquartile range: 0.00 to 0.06) (p < 0.001) from baseline, respectively. Following propensity-weighted mixed modeling adjusting for treatment and a range of demographic, clinical, ultrasonic, and laboratory parameters (including but not limited to sex, race, baseline, and annualized change in PAV, baseline CaI, concomitant high-intensity statins, diabetes mellitus, renal function), there were no significant between-group differences in annualized changes in PAV (least-squares mean: 0.09; 95% confidence interval [CI]: -0.20 to 0.37 vs. 0.01; 95% CI: -0.27 to 0.29; p = 0.092) according to calcium supplement intake. Per a multivariable logistic regression model accounting for the range of covariates described, calcium supplementation independently associated with an increase in annualized CaI (odds ratio: 1.15; 95% CI: 1.05 to 1.26; p = 0.004). CONCLUSIONS: Oral calcium supplementation may increase calcium deposition in the coronary vasculature independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes requires further investigation.

The utilization of single versus double Perclose devices for transfemoral aortic valve replacement access site closure: Insights from Cleveland Clinic Aortic Valve Center.

INTRODUCTION: Percutaneous femoral access is the preferred access route for transcatheter aortic valve replacement (TAVR). The majority of experienced TAVR centers use two 6F Perclose ProGlide™ devices to close the primary vascular access site, deployed prior to upsizing sheath size with closure completed at the end of the case (the "preclose" approach). A strategy of utilizing a single Perclose device to preclose may have advantages including fewer complications, complexity, and cost, but the safety of this is unknown. This study examines in the safety and efficacy of using a single Perclose versus double Perclose for perclosure of large bore access during TAVR. METHODS: Patients undergoing Transfemoral (TF) TAVR from January 2014 to December 2017 within the Cleveland Clinic Aortic Valve Center were identified. A retrospective review of medical charts was conducted. Vascular complications were defined according to the VARC-2 criteria. RESULTS: A total of 740 patients were included; 487 (65.8%) received a single Perclose device while 253 (34.2%) received double Perclose devices. Baseline characteristics were similar with no differences between the single versus double Perclose groups, respectively. The access sheath size was similar in both groups with (14, 16, and 18 F) being the most common sizes utilized. Of the total 487 patients with single Perclose, 75.6% needed additional closure device (AngioSeal). With double Perclose strategy, additional closure device (AngioSeal) was used in 40.3% patients with 470 (63.5%) patients being successfully perclosed. Vascular complication rates including hematoma, stenosis requiring stenting, pseudoaneurysm, and other major vascular complications were similar between both groups. CONCLUSION: Single 6F ProGlide use for preclosure is a safe strategy for TF TAVR using the S3 valve. Additional closure device was not needed in almost one-quarter of the patients. When necessary, residual bleeding can be controlled with the AngioSeal Device at the end of the procedure. This single device preclose strategy can help to reduce the cost of TAVR procedure without increasing risk.

Unilateral Access Is Safe and Facilitates Peripheral Bailout During Transfemoral-Approach Transcatheter Aortic Valve Replacement.

OBJECTIVES: The aim of this study was to compare the rate and trend of vascular complications when placing a second arterial sheath in the contralateral femoral artery during transcatheter aortic valve replacement (TAVR) unilaterally versus bilaterally. BACKGROUND: Vascular complications occur in approximately 5% to 8% of TAVR procedures. Many operators place a second arterial sheath in the contralateral femoral artery to perform aortic root angiography. The authors surmised that placing the second sheath ipsilateral and distal to the delivery sheath would be an easier option with similar safety. METHODS: The Cleveland Clinic Aortic Valve Center TAVR database was accessed, and data for patients undergoing transfemoral TAVR (TF-TAVR) from January 2014 to December 2017 were analyzed retrospectively. The primary outcome was the rate of peripheral vascular complications. RESULTS: A total of 1,208 patients who underwent TF-TAVR were included in this study. One thousand seven patients (83.36%) underwent bilateral femoral access, and 201 patients (16.64%) underwent TF-TAVR using a unilateral femoral approach. Over the study duration, use of the unilateral access approach trended upward significantly, reaching 43.7% of total cases in 2017. A gradual decline in access site-related vascular complications was observed, from 13.7% in 2014 to 7.4% in 2017. After propensity-score matching, peripheral vascular complications were similar between bilateral access and unilateral access (10.8% vs. 8.6%) (p = 0.543). CONCLUSIONS: There was a significant decline in vascular complications from 2014 to 2017. Unilateral-access TF-TAVR provided similar safety compared with bilateral-access TF-TAVR and is a more accessible approach for managing access site-related complications and possibly achieving better patient satisfaction.

Outcomes of patients with severe tricuspid regurgitation and congestive heart failure.

OBJECTIVES: A substantial number of patients with severe tricuspid regurgitation (TR) and congestive heart failure (CHF) are medically managed without undergoing corrective surgery. We sought to assess the characteristics and outcomes of CHF patients who underwent tricuspid valve surgery (TVS), compared with those who did not. METHODS: Retrospective observational study involving 2556 consecutive patients with severe TR from the Cleveland Clinic Echocardiographic Database. Cardiac transplant patients or those without CHF were excluded. Survival difference between patients who were medically managed versus those who underwent TVS was compared using Kaplan-Meier survival curves. Multivariate analysis was performed to identify variables associated with poor outcomes. RESULTS: Among a total of 534 patients with severe TR and CHF, only 55 (10.3%) patients underwent TVS. Among the non-surgical patients (n=479), 30% (n=143) had an identifiable indication for TVS. At 38 months, patients who underwent TVS had better survival than those who were medically managed (62% vs 35%; p<0.001). On multivariate analysis, advancing age (HR: 1.23; 95% CI 1.12 to 1.35 per 10-year increase in age), moderate (HR: 1.39; 95% CI 1.01 to 1.90) and severe (HR: 2; 95% CI 1.40 to 2.80) right ventricular dysfunction were associated with higher mortality. TVS was associated with lower mortality (HR: 0.44; 95% CI 0.27 to 0.71). CONCLUSION: Although corrective TVS is associated with better outcomes in patients with severe TR and CHF, a substantial number of them continue to be medically managed. However, since the reasons for patients not being referred to surgery could not be ascertained, further randomised studies are needed to validate our findings before clinicians can consider surgical referral for these patients.

Impact of Tricuspid Regurgitation in Patients With Heart Failure and Mitral Valve Disease from a Nationwide Cohort Study.

Concomitant heart failure (HF) and mitral valve disease (MVD) portend significant morbidity and mortality. Although associated Tricuspid regurgitation (TR) is a common occurrence in this scenario, it is not well known whether there are additional prognostic implications. We sought to assess whether coexistent TR is associated with higher readmission rates or increased mortality in patients with HF and MVD. We identified 1,520,871 encounters with a primary diagnosis of HF in the 2013 to 2014 Nationwide Readmission Database. We excluded patients without MVD, patients <18 years old, those with rheumatic heart disease and infective endocarditis. We also excluded patients who were discharged in December, hospital transfers, and cases where follow-up or outcomes were missing. Logistic regression was used to evaluate the association between baseline characteristics (including the presence of tricuspid valve disease), mortality as well as 30-day readmission rates. A total of 221,127 admissions with HF and MVD were identified. Median age was 79 years (IQR, 67 to 87), 55% were female, 2.7% died during hospitalization, and the 30-day readmission rate was 20.3%. Nearly 1/3 had concomitant TR (n = 78,356, 35%). The presence of TR was neither associated with elevated risk of mortality (hazard ratio 0.98, 95% confidence interval 0.93 to 1.04) nor 30-day readmission rate (odds ratio 1.01, 95% confidence interval 0.98 to 1.03). HF accounted for 33% of 30-day readmissions, while combined cardiac causes accounted for 54%. In conclusion concomitant TR in patients with HF and MVD was not associated with worse short-term outcomes in terms of inpatient hospital mortality and 30-day readmission rates.

Time-Integrated Aortic Regurgitation Index Helps Guide Balloon Postdilation During Transcatheter Aortic Valve Replacement and Predicts Survival.

Background Balloon postdilation ( BPD ) has emerged as an effective strategy to reduce paravalvular regurgitation ( PVR ) during transcatheter aortic valve replacement ( TAVR ). We investigated the utility of a time-integrated aortic regurgitation index ( TIARI ) to guide balloon postdilation ( BPD ) after valve deployment. Methods and Results All consecutive patients who had echocardiography, aortography, and hemodynamic tracings recorded immediately after valve deployment during TAVR were included in the study. Catheter-derived invasive hemodynamic parameters were calculated offline. Among 157 patients who underwent TAVR , 49 (32%) patients required BPD to reduce significant PVR after valve deployment. Two experienced operators decided whether the patients required BPD for significant PVR . Median TIARI measured immediately after valve deployment was significantly lower in patients who required BPD when compared with patients who did not require BPD ( P<0.001). In a multivariable analysis, lower TIARI (odds ratio: 0.81; P=0.003) and higher PVR grade on aortography and echocardiography ( P<0.001 for both) were associated with BPD . Adding TIARI to echocardiography and aortographic PVR assessment resulted in a significant increase in global χ2 ( P<0.001), an integrated discrimination index of 9% ( P=0.002), and combined C-statistics of 0.99 for predicting BPD . Higher TIARI after valve deployment was associated with better survival (hazard ratio: 0.94, P=0.014), while other hemodynamic and imaging parameters did not predict mortality after TAVR . Conclusions Among patients undergoing TAVR , a TIARI measured immediately after valve deployment adds incremental value to guide BPD over aortography and echocardiography. Higher residual TIARI is associated with better survival after TAVR .

Non-uremic calciphylaxis associated with alcoholic hepatitis: A case report.

BACKGROUND: Calciphylaxis is a form of vascular calcification more commonly associated with renal disease. While the exact mechanism of calciphylaxis is poorly understood, most cases are due to end stage kidney disease. However, it can also be found in patients without kidney disease and in such cases is termed non-uremic calciphylaxis for which have multiple proposed etiologies. CASE SUMMARY: We describe a case of a thirty-year-old morbidly obese Caucasian female who had a positive history of alcoholic hepatitis and presented with painful calciphylaxis wounds of the abdomen, hips, and thighs. The hypercoagulability panel showed low levels of Protein C and normal Protein S, low Antithrombin III and positive lupus anticoagulant and negative anticardiolipin. Wound biopsy confirmed the diagnosis of non-uremic calciphylaxis in the setting of alcoholic liver disease. The calciphylaxis wounds did not improve when Sodium Thiosulfate was used alone. The patient underwent a series of bedside and surgical debridement. Broad spectrum antibiotics were also used for secondary wound bacterial infections. The patient passed away shortly after due to sepsis and multiorgan failure. CONCLUSION: Non-uremic Calciphylaxis can occur in the setting of alcoholic liver disease. The treatment of choice is still unknown.

Hyperbaric oxygen and aerobic exercise in the long-term treatment of fibromyalgia: A narrative review.

Chronic pain is one of the most common clinical presentations in the primary care settings. In the US, Fibromyalgia (FM) affects about 1-3% of adults and commonly occurs in adults between the ages of 40-50 years. FM causes widespread muscular pain and tenderness with hyperalgesia and allodynia and may be associated with other somatic complaints. Hyperbaric oxygen therapy (HBOT) has been utilized and has recently shown promising effects in the management of FM and other chronic pain disorders. In HBOT, the intermittent breathing of 100% oxygen in a pressurized chamber where the pressure is higher than 1 atmosphere absolute (ATA) has been utilized. HBOT exhibits a significant anti-inflammatory effect through reducing production of glial cells and inflammatory mediators which results in pain alleviation in different chronic pain conditions. HBOT can also influence neuroplasticity and affects the mitochondrial mechanisms resulting in functional brain changes. In addition to that, HBOT stimulates nitric oxide (NO) synthesis which helps in alleviating hyperalgesia and NO-dependent release of endogenous opioids which seemed to be the primary HBOT mechanism of antinociception. Moreover, aerobic exercise and meditative movement therapies (MMT) have gained attention for their role in pain alleviation through different anti-inflammatory and antioxidant mechanisms. In this review, we aim to elucidate the different mechanisms of HBOT and aerobic exercise in attenuating pain as adjuvant therapy in the multidisciplinary treatment strategy of chronic pain, and more particularly fibromyalgia.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Secondary to Furosemide: Case Report and Review of Literature.

BACKGROUND DRESS is a rare, life threatening syndrome that occurs following exposure to certain medications, most commonly antibiotics and antiepileptics. While sulfonamide antibiotics are frequently implicated as causative agents for DRESS syndrome, furosemide, a nonantibiotic sulfonamide, has not been routinely reported as the causative agent despite its widespread use. CASE REPORT A 63 year old male who started furosemide for lower extremity edema 10 weeks prior presented with diarrhea, fever of 39.4°C, dry cough and maculopapular rash involving >50% of his body. He self-discontinued furosemide due to concern for dehydration. The diarrhea spontaneously resolved, but he developed hypoxia requiring hospitalization. CT scan demonstrated mediastinal lymphadenopathy and interstitial infiltrates. Laboratory evaluation revealed leukocytosis, eosinophilia and thrombocytopenia. He was treated empirically for atypical pneumonia, and after resuming furosemide for fluid excess, he developed AKI, worsening rash, fever and eosinophilia of 2,394 cell/µL. Extensive infectious and inflammatory work up was negative. Skin biopsy was consistent with a severe drug reaction. Latency from introduction and clinical worsening following re-exposure indicated furosemide was the likely inciter of DRESS. The RegiSCAR scoring system categorized this case as "definite" with a score of 8. CONCLUSIONS We report a case of severe DRESS syndrome secondary to furosemide, only the second case report in medical literature implicating furosemide. Given its widespread use, the potentially life-threatening nature of DRESS syndrome and the commonly delayed time course in establishing the diagnosis, it is important to remember that, albeit rare, furosemide can be a cause of DRESS syndrome.