Risk Of Systemic Complications Research Articles

Ex Vivo Machine Thrombolysis Reduces Rethrombosis Rates in Salvaged Thrombosed Myocutaneous Flaps in Swine.

There is a risk for thrombotic complications (2 to 5 percent) associated with microsurgical reconstruction. Current thrombolytic therapy has a salvage rate between 60 and 70 percent, but it is afflicted by bleeding complications (2 to 6 percent). The use of machine perfusion for delivering thrombolytic agents is a new method that could potentially reduce these complications. In this article, the authors compared flap salvage outcomes comparing machine thrombolysis versus a manual flush with tissue plasminogen activator. Sixteen bilateral flaps (12 × 9 cm) were dissected from eight female Dutch Landrace pigs (70 kg). Thrombosis was induced in free rectus abdominis flaps by clamping the pedicle's veins for 2 hours. Flaps were either thrombolysed with 2 mg tissue plasminogen activator (1 mg/ml) during 2 hours of machine perfusion (perfusion group; n = 8) or injected intraarterially (manual group; n = 8) before replantation. Near-infrared fluorescence angiography was used to confirm thrombus formation and to assess tissue perfusion; muscle biopsy specimens were analyzed for ischemia/reperfusion injury directly after thrombolysis and 15 hours after replantation. A higher incidence of secondary thrombosis was seen in the manual group compared to the perfusion group ( n = 6 versus n = 0, respectively; p < 0.001), resulting in two complete flap failures. Fifteen hours after replantation, mean fluorescence intensities were 13.0 (95 percent CI, 10.1 to 15.8) and 24.6 (95 percent CI, 22.0 to 27.2) in the perfusion and manual group, respectively ( p < 0.001), and mean muscle injury scores were comparable, measuring 7.5 ± 1.5. Two hours of machine thrombolysis of compromised flaps in a porcine model showed higher salvage rates compared to a manual injection with tissue plasminogen activator and reduced the incidence of secondary thrombosis. Using machine perfusion systems for ex vivo thrombolysis provides the benefits of local treatment of a composite tissue without the risk of systemic complications and may improve salvage rates and reduce the incidence of secondary thrombosis.

Oral Hygiene and Periodontal Treatment Needs in Adult Patients with Cystic Fibrosis (CF).

Cystic Fibrosis (CF) is an autosomal multisystem recessive genetic disease. Patients with Cystic Fibrosis, oral bacteria related to dental and periodontal diseases that can also inhabit the lungs, increases the risk for systemic complications. Our study aimed at assessing oral hygiene status of cystic fibrosis adult patients. The study was conducted on 40 patients diagnosed with CF and 40 healthy participants. The following indices were included: Simplified Oral Hygiene (OHI-S), Approximal Plaque Index (API), Community Periodontal Index of Treatment Needs (CPITN), and a questionnaire. Obtained results proved that the API was 44.63% in the study group, indicating sufficient hygiene, and 37% in the control group, indicating quite good hygiene. Significantly higher OHI-S was found in the study group. It was found based on the analysis of treatment needs that home care and professional instructions on proper oral hygiene were more often needed in the control group compared to CF patients. In conclusion, the obtained API and OHI-S values in adult CF patients were indicative of satisfactory oral hygiene. Periodontal treatment needs assessed based on the CPITN index in patients with CF indicated the need for professional preventive treatments. An interdisciplinary dental care to support oral health could be recommendable in individuals with chronic respiratory diseases such as Cystic Fibrosis.

P78. EFFICACY OF TUNABLE DYE LASER THERAPY FOR THE TREATMENT OF INFANTILE HEMANGIOMAS

PURPOSE: Infantile Hemangiomas (IH) are the most common tumor of childhood. Current treatment guidelines recommend oral propranolol, as the first line therapy for large IH. Tunable dye laser therapy (TDL) may offer an efficacious alternative without the risk of systemic complications. We aim to show the efficacy of laser treatment leading to the resolution without major complications. METHODS: A retrospective cohort analysis of 100 patients with 138 IHs from 2016-2021 was performed. Patients were identified and divided into two groups: oral propranolol with TDL therapy (dual therapy) or TDL therapy only. Patient characteristics included: patients’ age of onset and diagnoses, sex, associated syndromes, and history of prematurity. Clinical characteristics and treatment efficacy included size and number of hemangiomas, type of hemangioma, location, duration and number of treatments, and associated complications. RESULTS: 100 patients met the inclusion criteria: 74 underwent TDL therapy and 26 underwent dual therapy. Cohorts were similar in age of onset and diagnoses, number of hemangiomas per patient, hemangioma size, type, location, sex, associated syndromes, and history of prematurity. Both treatment cohorts had similar involution rates, however patients in the dual therapy cohort experienced systemic side effects (n = 4 [15.4 percent] versus n = 0 [0 percent], p = .004). 80.8% of patients were successfully weaned off propranolol in the dual therapy group. CONCLUSION: Both treatment cohorts had similar rates of involution in the treatment of large IH, however, dual therapy was associated with systemic side effects. TDL monotherapy serves as a safe and efficacious alternative.

Advances in treatments for Sjögren's syndrome: the glass is half full.

Sjögren's syndrome is a disabling systemic autoimmune disease characterised by pain, fatigue, and mucosal dryness, with risk of systemic complications (joints, lungs, skin, and peripheral nerves being the most frequently involved) in 30–50% of patients.1 So far, there is no effective immunomodulatory treatment for disease-related systemic complications because most randomised controlled trials (RCTs) on Sjögren's syndrome done in the past two decades have been negative.2 Of note, the primary outcome criteria of most previous RCTs were based on patient-reported outcomes, such as pain, fatigue, or dryness visual analogue scales, and most trials included only a small proportion of patients with systemic complications.

P137 LOCAL CRAC CHANNEL BLOCKADE TREATS COLITIS IN MICE

The Ca2+ release activated Ca2+ (CRAC) channel is an exciting new pharmacological target for the treatment of Inflammatory Bowel Disease (IBD) because it is upstream in the inflammatory cascade and absolutely necessary for immune responses. Calcium-selective CRAC channels become activated when T cells recognize antigen and allow calcium influx to the cytoplasm leading to increased NF-κB and NFAT-mediated gene expression driving inflammation. We have developed VV2003 which is a small molecule that blocks the CRAC channel and can be delivered orally. It has limited epithelial permeability allowing VV2003 to function locally at the site of inflammation with little risk for systemic complications. Following oral administration in healthy and colitic mice, VV2003 demonstrates low systemic absorption while maintaining therapeutic levels in the colon tissue for greater than 12 hours. In rat pharmacokinetic studies, VV2003 demonstrates low percent bioavailability and rapid clearance. The drug candidate diffuses into the intestinal mucosa and submucosa where it ameliorates inflammation without systemic activity. We have tested VV2003 in the DSS and Adoptive Transfer mouse models for colitis and have seen improvements in multiple endpoints including: disease activity index, fecal calprotectin and histologic scores. Notably, it is non-inferior to several systemically-active treatments which are currently the standard of care. We find that the CRAC channel is upregulated in biopsy samples from patients with IBD, and VV2003 suppresses inflammatory cytokines from PBMCs in-vitro. Importantly, there have been no signs of toxicity in any of our experiments. Overall, these data demonstrate that VV2003 has potential to become a novel next-generation oral therapy for colitis because it effectively limits leukocyte function in-vitro and in-vivo and is expected to have local delivery to the sites of pathology with minimal off target effects. In the near future, we plan to begin clinical trials to determine if VV2003 will be effective in treating patients with IBD. This project is supported by: VA CDA 5IK2BX003518, NIH NCATS TR001415; NIH NIAID R43AI134205.

Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice.

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of “whitening” of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.

Surgical outcomes in recurrent glioma

The object of this study was to assess outcomes after surgery for recurrent intracranial glioma. The authors retrospectively reviewed cases involving adult patients with intracranial glioma patients undergoing initial surgery (biopsy or resection) and one or more additional surgeries at their institution. A total of 323 operations were performed in 131 patients. The median survival was 76 months after first surgery, 36 months after second, 24 months after third, and 26.5 months after 4 or more surgeries. The overall complication rate was 12.8% after first surgery, 27.0% after second (OR 2.52, p = 0.0068), 22.0% after third (OR 1.92, not statistically significant [NS]), and 22.2% after 4 or more (OR 1.95, NS). Neurological complications occurred in 4.8% of patients at first surgery, 12.1% at second (OR 2.7, p = 0.0437), 8.2% at third (OR 1.75, NS), and 11.1% at 4 or more surgeries (OR 2.4583, NS). Regional complications occurred in 6.2% after first surgery, 9.9% after second surgery (OR 2.30, p = 0.095), 13.7% after third surgery (OR 3.31, p = 0.015), and 22.2% after 4 or more surgeries (OR 5.95, p = 0.056). Systemic complications occurred in 3.2% after first surgery, in 7.3% after second surgery (OR 2.3, p = 0.NS), in 4.1% after third surgery (OR 1.3, NS), and 0% after 4 or more surgeries. Reduction in Karnofsky Performance Status score occurred in 0% after first surgery, 8.1% after second surgery (OR 3.13, p = 0.0018), 10.2% after third surgery (OR 5.52, p < 0.0001), and 11.1% after 4 or more surgeries (OR 1.037, NS). Postoperative survival is relatively prolonged but complication risk increases in patients with glioma who undergo multiple cranial surgeries. The largest increase in neurological risk occurs between the first and second surgery. In contrast, regional complication risk increases consistently with each surgery. The risk of systemic complications is not significantly altered with increasing surgeries. However, these complications only result in a modestly increased risk of functional decline after 2 or more surgeries. These findings may help counsel patients considering multiple glioma surgeries.

Comparison of Simultaneous Bilateral and Staged Bilateral Total Knee Arthroplasty in Terms of Perioperative Complications

We compared bilateral total knee arthroplasty (TKA) performed at a single session vs those performed at 2 separate sessions with respect to complications, amount of blood loss, and length of hospital stay. Study participants included 119 consecutive patients undergoing simultaneous bilateral TKA and an additional 119 patients undergoing staged bilateral TKA. Systemic complication in the simultaneous bilateral TKA was significantly higher statistically than that in the staged bilateral TKA. Therefore, performing simultaneous bilateral TKA in elderly or high-risk patients results in a significantly higher rate of systemic complications. Simultaneous bilateral TKA is a relatively safe and beneficial procedure with a minimal increase in the risk of systemic complications. However, this procedure should be conducted carefully, particularly in elderly and high-risk patients.

Hydrofluoric acid burn: a case report

A case of occupational hydrofluoric acid exposure is presented, accentuating the importance of eliciting an occupational history during the initial emergency department evaluation. Patients who present with major hydrofluoric acid burns are at risk for systemic complications, including potentially fatal hypocalcemia. Information regarding the accident and workplace circumstances may well allow the physician to anticipate the exposed patient's course. These patients should be considered occupational index cases that will require follow up by government occupational health services. Identification of potential hazards, risk assessment and enforcement of recommendations for change (such as engineering controls, personal protective equipment, education) may be key to preventing similar injuries in the future.

Cataract surgery performed with continuous positive airway pressure (CPAP) ventilation

PURPOSE: To report a case in which cataract surgery was performed under local anesthesia, with continuous positive airway pressure–assisted ventilation. METHODS: A 40-year-old woman with myotonic dystrophy and severe orthopnea, who could not lie supine because of severe orthopnea, and who was a high-risk candidate for general anesthesia, underwent cataract surgery with continuos positive airway pressure ventilation by face mask. RESULTS: The patient underwent uneventful phacoemulsification and intraocular lens implantation in her left eye, while under continuous positive airway pressure ventilation. CONCLUSION: Selected patients who are unable to lie supine for ocular surgery because of severe orthopnea, and who are at risk for systemic complications under general anesthesia, may be evaluated for continuos positive airway pressure–assisted surgery.

Gastrointestinal bleeding in stroke.

Patients with ischemic or hemorrhagic stroke are at risk for systemic complications. The reasons why gastrointestinal bleeding occurs after stroke are unknown and have intuitively been attributed to stress ulcers. No study to date has addressed causes of gastrointestinal hemorrhage in stroke. Between 1976 and 1994, 17 patients identified from the Mayo Clinic medical record system as having gastrointestinal hemorrhage and ischemic stroke (n = 14) or intracerebral hemorrhage (n = 3) were reviewed for presentation, associated causes, and outcome. Results of the endoscopic procedures were compiled, and available gastric biopsies were reviewed. In 17 patients with gastrointestinal bleeding after stroke, sudden hematemesis, a decrease in hemoglobin level, or orthostatic hypotension was found as a presenting feature. One patient presented with massive hematemesis, exsanguination, and cardiac arrest. Endoscopic findings were available in 14 patients and included gastroesophageal erosions, hemorrhagic gastritis, and gastric ulcer. In one patient, an adenocarcinoma of the gastric cardia was found. Putative pathogenetic agents were found in 16 of 17 patients and included a long history of nonsteroidal anti-inflammatory drugs (n = 6), acetylsalicylic acid (n = 3), grossly prolonged anticoagulation (n = 4), Helicobacter pylori (n = 2), and corticosteroids (n = 1). Gastrointestinal bleeding after stroke is rarely severe and may not contribute significantly to mortality. Medication-induced gastrointestinal hemorrhage may be underappreciated in this setting.

Outcome and Cost Analysis of Scheduled versus Emergency Scleral Buckling Surgery

Retinal detachments are usually considered to be a surgical emergency. However, there are additional risks and costs for unnecessary emergency surgeries. The purpose of this study is to evaluate whether the conventional wisdom for treating all retinal detachments as emergencies needs to be re-examined. Forty-eight patients who had an emergency scleral buckle and 89 patients who had a scheduled procedure were randomly selected from 884 consecutive patients who had a primary scleral buckling procedure during a 4 1/2-year period. The medical records of each patient were used to obtain detailed information related to prognosis. The visual acuity measurements of each patient, taken 6 months after the procedure, were obtained from the records of the ophthalmologist following the patient. Linear regression analysis was used to compare the final visual outcome for patients who had emergency surgery with patients who had scheduled surgery after taking into account patient factors related to prognosis. Patients selected for emergency surgery had better visual prognoses than scheduled patients but had the same risk of systemic complications and the same extent of detachment if the macula was not involved. None of the 18 patients with an attached macula experienced macular involvement while awaiting scheduled surgery. There were no differences between emergency and scheduled patients in ocular or systemic complications, rate of reattachment, rate of decreased visual acuity after surgery, visual outcome adjusted for prognosis, or, since 1985, length of hospital stay. A greater cost was incurred for the patients having emergency surgery due to difference in pay scales for support personnel. Because the study is not large and the patients were not randomized to treatment, the results are not definitive. However, they suggest that emergency surgery is unnecessary for many patients with a detached retina.

Selective intra-arterial cytotostatic injections in malignant head and neck tumors.

Regional intra-arterial drug administration has been advocated in order to reduce the risks of systemic complications in conjunction with systemic tumor chemotherapy. We have been using superselective angiographic techniques to administer the antitumor drug mitomycin C directly into the feeding arteries of the tumor in 15 patients with advanced malignant head and neck tumors. No complications were observed. In five patients the tumor decreased significantly in size, in four patients, tumor cell necrosis was found. A marked decrease in pain was reported by nine of the 15 patients.