Atlantoaxial intra-articular cage fusion by posterior intermuscular approach for treating reducible atlantoaxial dislocation: a technique note with case series.

PURPOSE: To evaluate the clinical feasibility of atlantoaxial intra-articular cage (AIC) fusion via intermuscular approach for treating reducible atlantoaxial dislocation (AAD). METHODS: An analysis was conducted on the data of 10 patients who underwent C1-C2 segmental fixation and AIC fusion for AAD by unilateral intermuscular approach and contralateral open approach. Outcome assessments included Japanese Orthopaedic Association score (JOA) and Visual Analog Scale Score for Neck Pain (VASSNP). The duration of surgical exposure, screw insertion and cage insertion, and postoperative drainage volume were also compared between two approaches. Bone fusion was evaluated through computed tomography (CT) reconstruction. Postoperative paravertebral tissue edema was evaluated by paravertebral tissue cross-sectional area (CSA) and signal intensity on T2 weighted sequence of magnetic resonance imaging (MRI) at 3 days postoperatively. RESULTS: The intermuscular approach exhibited a longer exposure time but lower drainage postoperatively compared to the open approach (P < 0.05). After operation, JOA scores significant improved (P < 0.05), while VASSNP scores significantly decreased (P < 0.05). There was no significant difference in preoperative CSA between two approaches (P > 0.05). However, compared to the open approach, the intermuscular approach exhibited less CSA (P < 0.05) and lower T2 signal intensity on MRI postoperatively, indicating less invasive to the paravertebral tissues. CONCLUSIONS: AIC fusion by intermuscular approach is an effective and safe technique in the treatment of reducible AAD. Intermuscular approach could reduce the postoperative drainage volume and the extent of paravertebral tissue edema compared to open approach.

Hypothesis: Drainage of the peripheral tissue edema by the hyperbaric oxygen therapy because of hyperoxygenation that constricts arterioles and alters the downstream capillary fluid traffic in affected tissues.

Hyperbaric oxygen (HBO) therapy still lacks proper interpretations of its many actions. This hypothesis is based on reports of temporarily elevated peripheral vascular resistance (PVR) during HBO sessions. Besides that, during HBO sessions, hyperoxygenated tissues can reduce their perfusion so much that CO2 can accumulate in them. Tissue perfusion depends on vascular innervation and on the balance between systemic constrictors and local dilators. During an HBO session, increased tissue oxygen levels suppress dilatory mechanisms. Tissue hyperoxygenation increases PVR, suggesting that the HBO action on an edematous tissue may be caused by an oxygen-induced disbalance among Starling capillary forces. The presented hypothesis is that oxygen-caused arteriolar constriction reduces the hydrostatic pressure in downstream capillaries. Thus, more tissue fluid is absorbed in vascular capillaries, under the condition that the plasma colloid osmotic pressure remains unaltered during the HBO session. Among several known mechanisms behind the HBO actions, the vasoconstriction has been listed as a therapeutic modality for the reduction of the tissue edema, for a crush injury, for burns (in an acute phase), and for the compartment syndrome. The Bell's palsy is among often listed indications for the HBO treatment, although evidence is poor and reports of randomized trials are scarce.

How can assessing hemodynamics help to assess volume status?

In critically ill patients, fluid infusion is aimed at increasing cardiac output and tissue perfusion. However, it may contribute to fluid overload which may be harmful. Thus, volume status, risks and potential efficacy of fluid administration and/or removal should be carefully evaluated, and monitoring techniques help for this purpose. Central venous pressure is a marker of right ventricular preload. Very low values indicate hypovolemia, while extremely high values suggest fluid harmfulness. The pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile and is particularly useful for indicating the risk of pulmonary oedema through the pulmonary artery occlusion pressure. Besides cardiac output and preload, transpulmonary thermodilution measures extravascular lung water, which reflects the extent of lung flooding and assesses the risk of fluid infusion. Echocardiography estimates the volume status through intravascular volumes and pressures. Finally, lung ultrasound estimates lung edema. Guided by these variables, the decision to infuse fluid should first consider specific triggers, such as signs of tissue hypoperfusion. Second, benefits and risks of fluid infusion should be weighted. Thereafter, fluid responsiveness should be assessed. Monitoring techniques help for this purpose, especially by providing real time and precise measurements of cardiac output. When decided, fluid resuscitation should be performed through fluid challenges, the effects of which should be assessed through critical endpoints including cardiac output. This comprehensive evaluation of the risk, benefits and efficacy of fluid infusion helps to individualize fluid management, which should be preferred over a fixed restrictive or liberal strategy.

Mechanism of Multi-Organ Injury in Experimental COVID-19 and Its Inhibition by a Small Molecule Peptide.

Severe disease from SARS-CoV-2 infection often progresses to multi-organ failure and results in an increased mortality rate amongst these patients. However, underlying mechanisms of SARS- CoV-2-induced multi-organ failure and subsequent death are still largely unknown. Cytokine storm, increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs contribute to the pathogenesis of COVID-19. One potential consequence of immune/inflammatory events is the acute progression of generalized edema, which may lead to death. We, therefore, examined the involvement of water channels in the development of edema in multiple organs and their contribution to organ dysfunction in a Murine Hepatitis Virus-1 (MHV-1) mouse model of COVID-19. Using this model, we recently reported multi-organ pathological abnormalities and animal death similar to that reported in humans with SARS-CoV-2 infection. We now identified an alteration in protein levels of AQPs 1, 4, 5, and 8 and associated oxidative stress, along with various degrees of tissue edema in multiple organs, which correlate well with animal survival post-MHV-1 infection. Furthermore, our newly created drug (a 15 amino acid synthetic peptide, known as SPIKENET) that was designed to prevent the binding of spike glycoproteins with their receptor(s), angiotensin- converting enzyme 2 (ACE2), and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) (SARS-CoV-2 and MHV-1, respectively), ameliorated animal death and reversed altered levels of AQPs and oxidative stress post-MHV-1 infection. Collectively, our findings suggest the possible involvement of altered aquaporins and the subsequent edema, likely mediated by the virus-induced inflammatory and oxidative stress response, in the pathogenesis of COVID- 19 and the potential of SPIKENET as a therapeutic option.

The role of MLC901 in reducing VEGF as a vascular permeability marker in rats with spinal cord injury.

Background: Damaged neural tissue caused by SCI could induce vascular endothelial growth factor (VEGF) that can worsen the condition in the late phase by increasing vascular permeability, thus inducing tissue oedema, which can worsen the infarction. MLC 901 has been widely used in Asia for stroke patients because its mechanism is known to down-regulate VEGF levels in ischemic tissue. Methods: Ten Sprague-Dawley rats were used in this experiment. To create a severe spinal cord injury in animal models. The animals were then randomly divided into two groups. MLC 901 was given to the first group, which was the intervention group, and placebo to the second group, which was the control group. Results: This study showed a decrease in the mean VEGF mRNA expression in the group given MLC 901 compared to the control group, which had a very high mean VEGF mRNA expression starting after 1 h of administration of MLC 901 until day 14 after spinal cord injury. In addition, there was a decrease in VEGF levels in the MLC 901 group compared to the control group from 3 h after spinal cord injury (1 h after MLC 901 administration) to 14 days after spinal cord injury. Conclusion: It can be concluded that administration of MLC 901 can reduce vascular permeability, one of the mechanisms that is thought to occur is to reduce VEGF levels. MLC 901 also maintains the neuroprotective effect provided by VEGF by maintaining this level above the basal level until day 14.

Hyaluronidase to reduce a prolapsed incontinent ischemic ileovesicostomy.

Stomal prolapse is a known late complication of urinary diversions commonly used in urology. While rare, it can lead to ischemia, necrosis, and obstruction of the stoma, requiring urgent reduction before formal revision can be undertaken. Several measures can be attempted to reduce the prolapse including manual pressure and topical osmotic agents. One method that has not been reported in the urologic literature is the use of hyaluronidase. Herein, we report the first case in the literature of hyaluronidase usage to assist in reduction of an ischemic and obstructed prolapsed incontinent ileovesicostomy after manual compression failed.

Imaging assessment of fibrodysplasia ossificans progressiva: Qualitative, quantitative and questionable.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare autosomal dominant genetic disorder of heterotopic ossification (HO) characterized by skeletal anomalies and episodic soft tissue swelling (flare-ups) that can transform into heterotopic bone. The progressive development of heterotopic bone and progressive arthropathy leads to significant limitation of mobility. This paper will review various imaging modalities used in evaluating episodic soft tissue swelling (flare-ups), heterotopic bone and skeletal anomalies. Different imaging modalities are required at different stages of the disease. Ultrasound and MRI can be useful for evaluating edema in early stages of a flare-up; MRI being superior to ultrasonography. Plain radiographs and computed tomography (CT) can evaluate heterotopic bone in later stages of HO, but CT scan is better at evaluating presence and the volume of heterotopic bone. Functional imaging demonstrates increased activity at sites of flare-ups, their utility in determining disease progression need to be further evaluated. Cost, radiation exposure, availability of various imaging modalities and the ability of FOP patients to fit in the scanner are all considerations when requesting radiographic tests in a patient with FOP. Future studies are required to determine if early radiographic findings can determine disease progression and response to treatment in this disorder.

The role of steroid administration in the management of dysphagia in anterior cervical procedures.

Dysphagia is a common postoperative symptom for patients undergoing anterior cervical spine procedures. The purpose of this study is to present the current literature regarding the effect of steroid administration in dysphagia after anterior cervical spine procedures. We performed a literature search in the PubMed database, using the following terms: "dysphagia," "ACDF," "cervical," "surgery," "anterior," "spine," "steroids," "treatment," and "complications." We included in our review any study correlating postoperative dysphagia and steroid administration in anterior cervical spine surgery. Studies, which did not evaluate, pre- and postoperatively, dysphagia with a specific clinical or laboratory methodology were excluded from our literature review. Five studies were included in our results. All were randomized, prospective studies, with one being double blinded. Steroid administration protocol was different in every study. In two studies, dexamethasone was used. Methylprednisolone was administrated in three studies. In four studies, steroids were applied intravenously, while in one study, locally in the retropharyngeal space. Short-term dysphagia and prevertebral soft tissue edema were diminished by steroid administration, according to the results of two studies. In one study, prevertebral soft tissue edema was not affected by the steroid usage. Furthermore, short-term osseous fusion rate was impaired by the steroid administration, according to the findings of one study. The usage of steroids in patients undergoing anterior cervical spine procedures remains controversial. Multicenter, large-scale, randomized, prospective studies applying the same protocol of steroid administration and universal outcome criteria should be performed for extracting statistically powerful and clinically meaningful results.

Potential of Plant-sourced Phenols for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an uncontrolled chronic inflammatory intestinal disorder, which requires medications for long-term therapy. Facing the challenges of severe side effects and drug resistance of conventional medications, to develop the strategies meet the stringent safety and effectiveness in the long-term treatment are urgent in the clinics. In this regard, a growing body of evidence confirms plant-sourced phenols, such as flavonoids, catechins, stilbenes, coumarins, quinones, lignans, phenylethanoids, cannabinoid phenols, tannins, phenolic acids and hydroxyphenols, exert potent protective benefits with fewer undesirable effects in conditions of acute or chronic intestinal inflammation through improvement of colonic oxidative and pro-inflammatory status, preservation of the epithelial barrier function and modulation of gut microbiota. In this review, the great potential of plant-sourced phenols and their action mechanisms for the treatment or prevention of IBD in recent research are summarized, which may help further development of new preventive/adjuvant regimens for IBD.

Tissue Edema, Fluid Balance, and Patient Outcomes in Severe Sepsis: An Organ Systems Review.

Severe sepsis and septic shock remain among the deadliest diseases managed in the intensive care unit. Fluid resuscitation has been a mainstay of early treatment, but the deleterious effects of excessive fluid administration leading to tissue edema are becoming clearer. A positive fluid balance at 72 hours is associated with significantly increased mortality, yet ongoing fluid administration beyond a durable increase in cardiac output is common. We review the pathophysiologic and clinical data showing the negative effects of edema on pulmonary, renal, central nervous, hepatic, and cardiovascular systems. We discuss data showing increased morbidity and mortality following nonjudicious fluid administration and challenge the assumption that patients who are fluid responsive are also likely to benefit from that fluid. The distinctions between fluid requirement, responsiveness, and tolerance are central to newer concepts of resuscitation. We summarize data in each organ system showing a predictable increase in morbidity and mortality with nonbeneficial fluid administration, providing a better framework for precision in volume management of the patient with severe sepsis.

Postoperative Visceral Tissue Edema Assessed by Computed Tomography Is a Predictor for Severe Complications After Pancreaticoduodenectomy.

BACKGROUND/AIMS: In pancreatoduodenectomy (PD), the adverse impact of tissue edema owing to intraoperative fluid overload remains unclear. This study aims to evaluate how visceral tissue edema due to fluid overload affects severe postoperative complications after PD. It aims to clarify the usefulness of assessment by computed tomography (CT) of postoperative tissue edema. METHODS: We classified 200 patients who underwent PD as either liberal fluid management (LFM) group (n = 100) or goal-directed fluid therapy (GDFT) group (n = 100), based on intraoperative fluid management. We assessed postoperative tissue edema by cross section of the body trunk area using pre- and postoperative CT. RESULTS: Severe complication (Clavien-Dindo more than grade III) rate was significantly higher in LFM group than GDFT group (37 vs. 17%, P = 0.001). Independent risk factors of severe complications after PD included diameter of main pancreatic duct ≤ 3 mm at the cut surface (P = 0.041; OR 2.274; 95% CI 1.034-5.001), LFM (P = 0.005; OR 2.720; 95% CI 1.355-5.462), and increased rate of body trunk area ≥ 20% (P < 0.001; OR 3.448; 95% CI 1.723-5.462). In subgroup analysis of patients with no transfusion, LFM and increased rate of body trunk area ≥ 20% were independent risk factors of severe postoperative complications. CONCLUSIONS: Visceral tissue edema evaluation is a valuable method to predict severe complications after PD.

Demyelinating diseases as a result of cerebral edema?

Due to the elastic properties of the human organs, tissue edema causes an increased tissue pressure. This phenomenon leads to a reduction of blood circulation or ischemia, and thus leads to the hypothesis that tissue edema can be the cause of demyelinating lesions. Even though brain edema occurs in the whole brain, the authors assume that the characteristically focal appearance of demyelinated lesions, for instance of multiple sclerosis plaques, are attributable to anatomical and structural characteristics of the brain. In an experimental section, a balloon inserted into the brain and other organs removed during autopsies produces an increased tissue pressure. This model shows tissue pressure in the vicinity of the balloon up to 80mmHg. The height of the produced pressure varies in different organs and special regions of the brain. The verified pressures in the pons cerebri show that stretched myelinated fiber bundles in outer regions can induce strong pressures in enclosed edematous tissue, as seen in central pontine myelinolysis. The presented experimental results support the hypothesis that demyelinated lesions, as seen in multiple sclerosis, may be caused by increased tissue pressure, or respectively, brain edema.

Noninfectious prevertebral soft-tissue inflammation and hematoma eliciting swelling after anterior cervical discectomy and fusion.

OBJECTIVE Anterior cervical discectomy and fusion (ACDF) procedures are performed to treat patients with cervical myelopathy or radiculopathy. Dysphagia is a post-ACDF complication. When it coincides with prevertebral space enlargement and inflammation, surgical site infection and pharyngoesophageal perforation must be considered. The association between dysphagia and prevertebral inflammation has not been reported. The authors investigated factors eliciting severe dysphagia and its relationship with prevertebral inflammation in patients who had undergone ACDF. MATERIALS The clinical data of 299 patients who underwent 307 ACDF procedures for cervical radiculopathy or myelopathy at Kushiro Kojinkai Memorial Hospital and Kushiro Neurosurgical Hospital between December 2007 and August 2014 were reviewed. RESULTS After 7 ACDF procedures (2.3%), 7 patients suffered severe prolonged and/or delayed dysphagia and odynophagia that prevented ingestion. In all 7 patients the prevertebral space was enlarged. In 5 (1.6%) the symptom was thought to be associated with prevertebral soft-tissue edema; in all 5 an inflammatory response, hyperthermia, and an increase in the white blood cell count and in C-reactive protein level was observed. After 2 procedures (0.7%), we noted prevertebral hematoma without an inflammatory response. None of the patients who had undergone 307 ACDF procedures manifested pharyngoesophageal perforation or surgical site infection. CONCLUSIONS Severe dysphagia and odynophagia are post-ACDF complications. In most instances they are attributable to prevertebral soft-tissue edema accompanied by inflammatory responses such as fever and an increase in the white blood cell count and in C-reactive protein. In other cases these anomalies are elicited by hematoma not associated with inflammation.

Oral kanglaite injection (KLTI) attenuates the lung cancer-promoting effect of high-fat diet (HFD)-induced obesity.

Obesity is a risk factor for cancer and cancer-related mortality, however, its role in lung cancer progression remains controversial. This study aimed to assess whether high-fat diet (HFD)-induced obesity promotes lung cancer progression and whether the promotion can be decreased by Kanglaite injection (KLTI). In vivo, HFD-induced overweight or obesity increases the lung carcinoma incidence and multiplicity in a urethane-induced lung carcinogenic model and cancer-related mortality in a LLC allograft model by increasing oxidative stress and cellular signaling molecules including JAK, STAT3, Akt, mTOR, NF-κB and cyclin D1. These changes resulted in increases in vascular disruption and the lung water content, thereby promoting lung epithelial proliferation and the epithelial-mesenchymal transition (EMT) during carcinogenesis. Chronic KLTI treatment substantially prevented the weight gain resulting from HFD consumption, thereby reversing the metabolic dysfunction-related physiological changes and reducing susceptibility to lung carcinogenesis. In vitro, KLTI significantly suppressed the proliferation and induced apoptosis and differentiation in 3T3-L1 preadipocyte cells and attenuated endothelial cell permeability in HUVECs. Our study indicates that there is a potential relationship between obesity and lung cancer. This is the first study to show that obesity can directly accelerate carcinogen-induced lung cancer progression and that KLTI can decrease the lung cancer-promoting effect of HFD-induced obesity.

New continuous-flow total artificial heart and vascular permeability.

BACKGROUND: We tested the short-term effects of completely nonpulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability. METHODS: Ten calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10-25 mm Hg) at a rate of 40 pulses per minute (PP). The remaining five calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (PODs) 1, 7, and 14. Skeletal muscle-tissue water content was measured, and morphologic alterations of skeletal muscle were assessed. VE-cadherin, phospho-VE-cadherin, and CD31 were analyzed by immunohistochemistry. RESULTS: There were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, PODs 1, 7, and 14, respectively. There were no significant alterations in the expression and/or distribution of VE-cadherin, phospho-VE-cadherin, and CD31 in skeletal muscle vasculature at baseline, PODs 1, 7, and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histologic damage scores at PODs 7 and 14, it failed to reach statistical significance. CONCLUSIONS: There was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability.

MRI findings of the shoulder and hip joint in patients with polymyalgia rheumatica.

OBJECTIVES: The purpose of this study is to evaluate magnetic resonance imaging (MRI) findings of the shoulder and hip joint in patients with polymyalgia rheumatica (PMR). METHODS: MR images of a total of 25 PMR patients (23 shoulders and 6 hips), 43 rheumatoid arthritis (RA) patients (22 shoulders and 22 hips), and 50 control patients (25 shoulders and 25 hips) were examined. The following MRI findings were evaluated: In the shoulder, thickness and abnormalities of the supraspinatus tendon, effusion around the glenohumeral joint, subacromial-subdeltoid bursa, and the biceps tendon; In the hip, effusion around the acetabulofemoral joint, iliopsoas bursa, and trochanteric bursa. Periarticular soft-tissue edema and bone findings were also analyzed. RESULTS: The supraspinatus tendon was significantly thicker in PMR patients than in RA patients and control patients (p < 0.05). Severe rotator cuff tendinopathy was frequently observed in PMR patients (p = 0.002). The scores for the amount of effusions (joint, bursa, and tendon sheath in the shoulder and bursa in the hip) were much higher in PMR patients (p < 0.05). Periarticular soft tissue edema was detected more frequently in PMR patients than in RA patients and control patients (p < 0.05). CONCLUSIONS: Thick supraspinatus tendon, severe rotator cuff tendinopathy, effusion around the joints, and periarticular soft tissue edema can be good indicators for the diagnosis of PMR.