Hyperbaric oxygen therapy ameliorates osteonecrosis in patients by modulating inflammation and oxidative stress

Early stages of avascular necrosis of the femoral head (AVNFH) can be conservatively treated with hyperbaric oxygen therapy (HBOT). This study investigated how HBOT modulates inflammatory markers and reactive oxygen species (ROS) in patients with AVNFH. Twenty-three male patients were treated with two cycles of HBOT, 30 sessions each with a 30 days break between cycles. Each session consisted of 90 minutes of 100% inspired oxygen at 2.5 absolute atmospheres of pressure. Plasma levels of tumor necrosis factor alfa (TNF-α), interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and ROS production were measured before treatment (T0), after 15 and 30 HBOT sessions (T1 and T2), after the 30-day break (T3), and after 60 sessions (T4). Results showed a significant reduction in TNF-α and IL-6 plasma levels over time. This decrease in inflammatory markers mirrored observed reductions in bone marrow edema and reductions in patient self-reported pain

α1-adrenoceptor ligands inhibit chemokine receptor heteromerization partners of α1B/D-adrenoceptors via interference with heteromer formation

We reported previously that α1-adrenoceptor (α1-AR) ligands inhibit chemokine receptor (CR) heteromerization partners of α1B/D-AR. The underlying mechanisms are unknown and in vivo evidence for such effects is missing. Utilizing CCR2 and α1B-AR as prototypical partners, we observed in recombinant systems and THP-1 cells that α1B-AR enhanced whereas its absence inhibited Gαi signaling of CCR2. Phenylephrine and phentolamine reduced the CCR2:α1B-AR heteromerization propensity and inhibited Gαi signaling of CCR2. Phenylephrine cross-recruited β-arrestin-2 to CCR2, and reduced expression of α1B/D-AR, CR partners (CCR1/2, CXCR4) and corresponding heteromers. Phentolamine reduced CR:α1B/D-AR heteromers without affecting β-arrestin-2 recruitment or receptor expression. Phenylephrine/phentolamine prevented leukocyte infiltration mediated via CR heteromerization partners in a murine air pouch model. Our findings document that α1-AR ligands inhibit leukocyte migration mediated by CR heteromerization partners in vivo and suggest interference with α1B-AR:CR heteromerization as a mechanism by which CR partners are inhibited. These findings provide new insights into the pharmacology of GPCR heteromers and indicate that an agonist and antagonist at one GPCR can act as antagonists at heteromerization partners of their target receptors

Critical Review and Meta-Analysis of Postoperative Sedation after Adult Cardiac Surgery: Dexmedetomidine Versus Propofol

Objective: To evaluate reports from the published literature of all randomized clinical trials (RCT) comparing postoperative sedation with dexmedetomidine versus propofol in adult patients, after open cardiac surgery.Design: A computerized search on Medline, EMBASE, Web of Science, and Agency for Healthcare Research and Quality databases was completed through June 2020. Meta-analysis of all published RCT comparing dexmedetomidine versus propofol utilization in the postoperative phase, using the standard Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.Setting: Assemblage and critical discussion of 11 RCTs comparing postoperative sedation from standard published reports from 2003 to 2019.Participants: The study comprised 1,184 patients and analyzed critical discussion of time-based parameters (time to extubation, intensive care unit length of stay, and hospital length of stay) and nontime-dependent factors (delirium, bradycardia, and hypotension).Measurements and Main Results: Time to extubation was significantly reduced in the dexmedetomidine group (standardized mean difference [SMD] = -0.70, 95% confidence interval [CI] -0.98 to -0.42, p < 0.001); however, no difference in mechanical ventilation time was observed (SMD = -0.72, 95% CI -1.60 to 0.15, N.S.). Dexmedetomidine significantly reduced the intensive care unit length of stay (SMD = 0.23, 95% CI -1.06 to -0.16, p = 0.008), but this did not translate into a reduced hospital length of stay (SMD = -1.13, 95% CI -2.43 to 0.16, N.S). For nontime-dependent factors, incidence of delirium was unaffected between groups (odds ratio [OR]: 0.68, 95% CI 0.43-1.06, N.S), and higher rates of bradycardia (OR: 3.39, 95% CI: 1.20-9.55, p = 0.020) and hypotension (OR: 1.68, 95% CI 1.09-2.58, p = 0.017) were reported with propofol.Conclusions: Despite the ICU time advantages afforded by dexmedetomidine over propofol, the former did not seem to contribute to an overall reduction in hospital length of stay or improvement in postoperative outcomes of heart valve surgery and CABG patients. (C) 2020 Published by Elsevier Inc

Incidence and predictors of ischemic cerebrovascular stroke among patients on extracorporeal membrane oxygenation support

There are scant data on the predictors of ischemic cerebrovascular stroke occurring during extracorporeal membrane oxygenation (ECMO). We investigated the incidence and predictors of ischemic stroke in subjects receiving ECMO support. A retrospective chart review was conducted on consecutive adult subjects (>18 years of age) who received ECMO at Tampa General Hospital from 2007 to 2014 with the main outcome variable being the onset of radiologically confirmed ischemic stroke during ECMO support. We examined various risk factors for ischemic stroke including patients' demographics, clinical and laboratory variables, ECMO characteristics, type and amount of transfused blood products, and the indications necessitating ECMO support. To identify independent risk factors of ischemic stroke during ECMO and adjust for confounding variables, a multivariate logistic regression analysis was used. A total of 171 subjects received ECMO (mean age was 51 years, and 74.9% were male) for cardiac or pulmonary indications. Ten subjects (5.8%) developed ischemic stroke during ECMO. Cases with ischemic stroke had a higher mean pre-ECMO lactic acid level (10.6 ± 6.5 vs 6.3 ± 5.2 mmol/L, P= .039) and a higher frequency of pre-ECMO lactic acid level > 10 mmol/L (71.4% vs 24.8%, P = .019). Multivariate analysis identified that a pre-ECMO lactic acid greater than 10 mmol/L (odds ratio, 7.586; 95% CI, 1.396-41.223; P = .019) is an independent predictor of ischemic stroke occurring during ECMO support. Ischemic stroke is not uncommon in subjects receiving ECMO support with independent risk factor being a pre-ECMO lactic acid greater than 10 mmol/L

Femoral condylar necrosis: treatment with hyperbaric oxygen therapy

Osteonecrosis of the knee (ONK) is a form of aseptic necrosis resulting from ischemia to subchondral bone tissue. Typically, treatment is invasive. Hyperbaric oxygen therapy (HBOT) may provide a noninvasive alternative by improving oxygenation and reperfusion of ischemic areas. This study evaluates the efficacy of HBOT in a series of ONK patients

Effects of chemokine (C-C motif) receptor 2 and 3 antagonists in rat models of hemorrhagic shock.

Systemic concentrations of chemokine CCL2, an agonist at chemokine receptors CCR2/3/5, have been associated with hemodynamic instability after traumatic-hemorrhagic shock. We reported previously that the CCR2 antagonist INCB3284 prevents cardiovascular collapse and reduces fluid requirements after 30min of hemorrhagic shock (HS), whereas the CCR5 antagonist Maraviroc was ineffective. The effects of CCR3 blockade after HS are unknown and information on the therapeutic potential of INCB3284 after longer periods of HS and in HS models in the absence of fluid resuscitation (FR) is lacking. The aims of the present study were to assess the effects of CCR3 blockade with SB328437 and to further define the therapeutic efficacy of INCB3284. In series 1-3, Sprague-Dawley rats were hemorrhaged to a mean arterial blood pressure (MAP) of 30mmHg, followed by FR to MAP of 60mmHg or systolic blood pressure of 90mmHg. Series 1: 30min HS and FR until t = 90min. SB328437 at t = 30min dose-dependently reduced fluid requirements by >60%. Series 2: 60min HS and FR until t = 300min. INCB3284 and SB328437 at t = 60min reduced fluid requirements by more than 65% (p0.05 vs. vehicle), respectively, until t = 220min. Thereafter, all animals developed a steep increase in fluid requirements. Median survival time was 290min with SB328437 and >300min after vehicle and INCB3284 treatment (p<0.05). Series 3: HS/FR as in series 2. INCB3284 at t = 60min and t = 200min reduced fluid requirements by 75% until t = 300min (p<0.05 vs. vehicle). Mortality was 70% with vehicle and zero with INCB3284 treatment (p<0.05). Series 4: INCB3284 and SB328437 did not affect survival time in a lethal HS model without FR. Our findings further support the assumption that blockade of the major CCL2 receptor CCR2 is a promising approach to improve FR after HS and document that the dosing of INCB3284 can be optimized

Review on hyperbaric oxygen treatment in femoral head necrosis

Femoral head necrosis (FHN) is a common invalidating disease with an unclear etiology and pathophysiology that affects middle-aged people. FHN may lead to joint collapse and require invasive treatments. Because of its clinical and socioeconomic significance, an early diagnosis, staging and appropriate treatment are required. Unfortunately, to date a unique algorithm for the treatment of FHN has not been defined

Human Botfly: A Case Report and Overview of Differential Diagnosis

Dermatobia hominis , commonly known as the human botfly, is native to Tropical America. As such, cutaneous infestation by its developing larvae, or myiasis, is quite common in this region. The distinct dermatological presentation of D hominis myiasis allows for its early recognition and noninvasive treatment by locals. However, it can prove quite perplexing for those unfamiliar with the lesion’s unique appearance. Common erroneous diagnoses include the following: folliculitis, benign dermatocyst, and embedded foreign body with localized infection. We present a patient who acquired D hominis while she was in Belize. In this report, we discuss the presentation, differential diagnosis, diagnostic tests, and therapeutic approaches of human botfly lesion to raise the awareness about human botfly

A Collaborative Initiative for Reducing Operating Room Waste of Unused Refrigerated Medication.

BACKGROUND: Inappropriate management of anesthetic medications requiring refrigeration creates waste and increases costs of intraoperative care. At Tampa General Hospital, pharmacy personnel refill medications in cardiovascular operating rooms (CVOR) nightly and noticed large amounts of unattended medications at room temperature for unknown periods of time. Per protocol, these medications were disposed. OBJECTIVE: To effectively decrease pharmaceutical waste in the CVOR. METHODS: A pharmacy-led anesthesia committee identified the most used intraoperative medications requiring refrigeration and implemented changes to decrease waste. As a result, norepinephrine intravenous piggyback (IVPB), norepinephrine vials, nitroglycerin vials, and epinephrine IVPB were physically relocated into preexisting mini-refrigerators inside each CVOR. Vasopressin vials and phenylephrine syringes/vials were relocated into automated anesthesia cabinets. Amounts and cost of wasted medication were analyzed before and after protocol implementation. RESULTS: Average weekly cost of wasted medication was significantly reduced (preintervention: US$1188.59 vs postintervention: US$322.96; CONCLUSION: Recorded weekly savings of US$865.63 (∼annual savings of \u3eUS$45 000) reflect only the explicit cost of waste. True savings are higher when including opportunity costs such as salary of pharmacy personnel and supplies needed to replace wasted medications. We demonstrate the benefits of a collaborative approach to improving inefficiencies in health care

Single dose SB328437 treatment reduces fluid resuscitation requirements after 30 min of hemorrhagic shock.

All data are mean ± SE. Arrows represent the time point of drug/vehicle injection. Open circles: animals treated with vehicle (n = 5). Open triangles: animals treated with 0.25 μmol/kg SB328437 (n = 3). Grey triangles: animals treated with 1.1 μmol/kg SB328437 (n = 3). *: p < 0.05 vs. animals treated with vehicle. (A) Hemorrhage volumes for maintain mean arterial blood pressure (MAP of 30 mmHg). %TBV: percent of total blood volume. (B) MAP (mmHg) (C) Fluid resuscitation in mL/kg required to maintain MAP of 60 mmHg or systolic blood pressure (SBP) of 90 mmHg.</p