ABSTRACT
Objective:To compare the efficacy of endoscopic sinus surgery and conservative treatment for orbital apex syndrome caused by sinus lesions. Methods:The clinical data of 56 patients with orbital apex syndrome caused by sinus lesions who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to August 2023 were retrospectively analyzed and divided into a surgical group of 21 cases and a conservative group of 35 cases. The clinical features and prognosis of the two groups were compared. Results:Among the sinus lesions in the surgical group, 61.9% were fungal sinusitis, 28.6% were bacterial sinusitis, and 9.5% were sphenoid sinus tumors. In the conservative group, non-fungal sinusitis accounted for 65.7% and fungal sinusitis accounted for 34.3%. In addition to sinus lesions, patients had underlying diseases. In the surgical group, 71.4% had hypertension and 80.9% had diabetes; in the conservative group, 28.6% had hypertension and 42.9% had diabetes. After a follow-up of 1 month to 5 years, the symptom improvement rate in the surgical group was 85.7%, with 1 case of recurrence. No recurrence was found after reoperation, while the symptom improvement rate in the conservative group was 22.9%, and 6 cases recurred after symptom improvement, and were transferred to rhinology department. No recurrence was seen after surgery. Conclusion:Most of the sinus lesions in this study were fungal sinusitis. In addition, patients with underlying diseases such as diabetes, hypertension, nephrotic syndrome, etc. have reduced nasal immunity, which significantly increases the risk of disease. Since early nasal symptoms are not obvious, multidisciplinary cooperation in diagnosis and treatment is very necessary. Once imaging examination suggests orbital apex syndrome caused by sinus lesions, endoscopic sinus opening should be performed as soon as possible.
Subject(s)
Endoscopy , Humans , Retrospective Studies , Male , Female , Middle Aged , Treatment Outcome , Adult , Sinusitis/complications , Orbital Diseases/etiology , Syndrome , Conservative Treatment/methods , Paranasal Sinus Diseases/complications , Paranasal Sinus Diseases/surgery , PrognosisABSTRACT
PURPOSE: To assess the utility of a marginal full thickness blepharotomy (MFTB) for the treatment of orbital compartment syndrome. METHODS: An experimental study design employing a cadaver model for orbital compartment syndrome was used to assess the efficacy of an MFTB. Elevated orbital compartment pressures were created in 12 orbits of 6 fresh cadaver heads. Intraocular pressure, as an analog of orbital pressure, was measured before and after inferior and superior MFTBs were performed. Statistical analysis was performed on the collected data to assess the efficacy of the procedure. RESULTS: Both procedures were found to significantly lower the orbital compartment pressure. MFTB of the inferior lateral eyelid decreased orbital compartment pressure by an average of 62.2 mm Hg (95% CI, 56.9-67.5). MFTB of the superior lateral eyelid following MFTB of the inferior lateral eyelid decreased the orbital compartment pressure by an additional average of 10.3 mm Hg (total average reduction of 72.5 mm Hg; 95% CI, 68.1-76.9). CONCLUSIONS: Orbital compartment syndrome is a time-sensitive vision-threatening emergency that requires prompt diagnosis and intervention to prevent irreversible vision loss. The authors describe the MTFB, a simple one-step procedure that when performed correctly results in a significant decrease in orbital compartment pressure, making it a viable option when canthotomy and cantholysis fails or is unable to be performed.
Subject(s)
Cadaver , Compartment Syndromes , Eyelids , Intraocular Pressure , Orbital Diseases , Humans , Compartment Syndromes/surgery , Compartment Syndromes/diagnosis , Compartment Syndromes/physiopathology , Compartment Syndromes/etiology , Eyelids/surgery , Intraocular Pressure/physiology , Orbital Diseases/surgery , Orbital Diseases/diagnosis , Orbit/surgery , Ophthalmologic Surgical Procedures/methodsABSTRACT
PURPOSE: Within the large umbrella of histiocytosis are a few similar yet heterogenous entities involving the orbit and periocular tissues with or without systemic infiltration, termed adult onset xanthogranuloma or orbital xanthogranuloma. Due to rarity of these conditions, different classifications in use, diverse clinical presentations and still unknown etiology, the aim of this paper was to provide an up-to-date literature review of the actual understanding of histiocytosis and its subgroups involving the orbit and periocular area, diagnostic strategies and therapeutic modalities. METHODS: We present a review of literature and small case series comprising four patients diagnosed and treated in the period from 2001 until 2023 in our hospital. Clinical files of 4 patients with adult-onset xanthogranulomatous disease of the orbit and ocular adnexa (AOXGD) were reviewed retrospectively. Clinical, laboratory, radiological, histopathological, and immunohistochemical findings were reexamined. RESULTS: Reviewing medical records of our patients with AOXGD, we found significant overlap between histiocytosis and different immune disorders. A broad workup should be considered in these patients as they can harbour severe immune disfunctions and hematologic disorders. Preferred treatment modality depends on a histopathologic type of AOXGD, clinical presentation and systemic involvement and should be conducted multidisciplinary. CONCLUSION: The diagnosis is often delayed because of its rarity and diverse clinical findings. Development of molecular genetic tests, detection of BRAF V600E mutation and different types of kinase mutations, mutations in transcriptional regulatory genes as well as tyrosine kinase receptors have shed a new light on the etiopathogenesis and potential targeted treatment of histiocytosis.
Subject(s)
Orbital Diseases , Adult , Female , Humans , Male , Middle Aged , Granuloma/diagnosis , Histiocytosis/diagnosis , Orbital Diseases/diagnosis , Retrospective Studies , Tomography, X-Ray Computed , Xanthomatosis/diagnosis , AgedSubject(s)
Abscess , Orbital Diseases , Schizophyllum , Humans , Abscess/microbiology , Abscess/drug therapy , Abscess/diagnostic imaging , Orbital Diseases/microbiology , Orbital Diseases/diagnosis , Orbital Diseases/drug therapy , Schizophyllum/isolation & purification , Male , Mycoses/diagnosis , Mycoses/drug therapy , Mycoses/microbiology , Antifungal Agents/therapeutic use , Tomography, X-Ray Computed , FemaleABSTRACT
This case report discusses a diagnosis of rhino-orbital-cerebral mucormycosis in a man aged 61 years who presented with vision loss, ophthalmoplegia, and ptosis.
Subject(s)
Eye Infections, Fungal , Mucormycosis , Orbital Diseases , Humans , Mucormycosis/diagnosis , Mucormycosis/microbiology , Mucormycosis/drug therapy , Orbital Diseases/microbiology , Orbital Diseases/diagnosis , Orbital Diseases/drug therapy , Eye Infections, Fungal/microbiology , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/drug therapy , Male , Antifungal Agents/therapeutic use , Magnetic Resonance Imaging , Paranasal Sinus Diseases/microbiology , Paranasal Sinus Diseases/diagnosis , Paranasal Sinus Diseases/drug therapy , Tomography, X-Ray Computed , Nose Diseases/microbiology , Nose Diseases/diagnosis , Nose Diseases/drug therapy , Female , Middle Aged , Amphotericin B/therapeutic useABSTRACT
Rhino-orbital-cerebral mucormycosis (ROCM) is a rare, invasive, and fatal fungal disease that is often easily misdiagnosed in the early stages due to the lack of specific clinical manifestations and adequate auxiliary examinations. Early diagnosis and timely therapy are essential for successful treatment. In this report, we presented a 46-year-old man with diabetes who experienced gradual vision loss, right ptosis, swelling, and headaches that progressively worsened to death within 4 days after admission. It was finally confirmed as a fungal Rhizopus arrhizus infection by metagenomics next-generation sequencing (mNGS). Our report has proved that mNGS testing should be strongly recommended in highly suspected patients.
Subject(s)
High-Throughput Nucleotide Sequencing , Metagenomics , Mucormycosis , Rhizopus , Humans , Mucormycosis/diagnosis , Mucormycosis/microbiology , Male , Rhizopus/genetics , Rhizopus/isolation & purification , Middle Aged , Metagenomics/methods , Fatal Outcome , Orbital Diseases/diagnosis , Orbital Diseases/microbiology , Antifungal Agents/therapeutic useABSTRACT
Orbital disorders in children consist of varied pathologies affecting the orbits, orbital contents, visual pathway, and innervation of the extraocular or intraocular muscles. The underlying etiology of these disorders may be traumatic or nontraumatic. Presumed location of the lesion along with the additional findings, such as eye pain, swelling, exophthalmos/enophthalmos, erythema, conjunctival vascular dilatation, intraocular pressure, etc, help in determining if imaging is needed, modality of choice, and extent of coverage (orbits and/or head). Occasionally, clinical signs and symptoms may be nonspecific, and, in these cases, diagnostic imaging studies play a key role in depicting the nature and extent of the injury or disease. In this document, various clinical scenarios are discussed by which a child may present with an orbital or vision abnormality. Imaging studies that might be most appropriate (based on the best available evidence or expert consensus) in these clinical scenarios are also discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
Subject(s)
Orbital Diseases , Humans , Child , United States , Orbital Diseases/diagnostic imaging , Evidence-Based Medicine , Societies, Medical , Diagnostic Imaging/methods , Blindness/diagnostic imagingABSTRACT
Orbital disorders in children consist of varied pathologies affecting the orbits, orbital contents, visual pathway, and innervation of the extraocular or intraocular muscles. The underlying etiology of these disorders may be traumatic or nontraumatic. Presumed location of the lesion along with the additional findings, such as eye pain, swelling, exophthalmos/enophthalmos, erythema, conjunctival vascular dilatation, intraocular pressure, etc, help in determining if imaging is needed, modality of choice, and extent of coverage (orbits and/or head). Occasionally, clinical signs and symptoms may be nonspecific, and, in these cases, diagnostic imaging studies play a key role in depicting the nature and extent of the injury or disease. In this document, various clinical scenarios are discussed by which a child may present with an orbital or vision abnormality. Imaging studies that might be most appropriate (based on the best available evidence or expert consensus) in these clinical scenarios are also discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
Subject(s)
Humans , Child , Orbital Diseases/diagnostic imaging , Oculomotor Muscles/injuriesABSTRACT
PURPOSE: Topical prostaglandin analogues are commonly used to treat patients with glaucoma, but may cause periocular and periorbital complications known as prostaglandin-associated periorbitopathy syndrome (PAPS). METHODS: A literature review was conducted on PAPS. Given the lack of consensus on grading PAPS, glaucoma specialists from Asia convened to evaluate current PAPS grading systems and propose additional considerations in grading PAPS. RESULTS: Existing grading systems are limited by the lack of specificity in defining grades and consideration for patients' subjective perception of symptoms. Patient-reported symptoms (e.g., via a self-assessment tool) and additional clinical assessments (e.g., exophthalmometry, lid laxity, differences between tonometry results, baseline measurements, and external ocular photographs) would be beneficial for grading PAPS systematically. CONCLUSIONS: Effective management of PAPS could be facilitated by a common clinical grading system to consistently and accurately diagnose and characterise symptoms. Further research is required to validate specific recommendations and approaches to stage and monitor PAPS.
Subject(s)
Glaucoma , Humans , Glaucoma/drug therapy , Intraocular Pressure/physiology , Intraocular Pressure/drug effects , Orbital Diseases/chemically induced , Orbital Diseases/diagnosis , Asia/epidemiology , Syndrome , Prostaglandins, Synthetic/adverse effects , Antihypertensive Agents/adverse effectsABSTRACT
Facial fractures and their historical link to potential blindness have been well-documented, often attributed to optic canal injuries or retinal vascular occlusion. This dire consequence can result from both direct and indirect ocular trauma, including retrobulbar hemorrhage. Traumatic orbital compression can manifest in various forms, such as hematomas, fractured bone fragments, and emphysema, all posing a significant threat to vision, necessitating immediate intervention. In this study, 9 clinical cases of traumatic orbital compression are presented, each characterized by distinct etiologies. The study delves into traumatic orbital compressive syndromes, underscoring the critical imperative of early recognition and treatment to prevent vision loss. Orbital compression, whether from edema, hematoma, or emphysema, collectively culminates in elevated intraorbital pressure and the potential for optic nerve ischemia. Through the presentation of these 9 clinical cases, the article emphasizes the pressing need for timely intervention in addressing orbital compressive syndromes to avert vision loss. Various surgical techniques are elucidated, highlighting the pivotal role of expeditious medical intervention. This article offers invaluable insights into the diagnosis, management, and outcomes of traumatic orbital compressive syndromes.
Subject(s)
Orbital Diseases , Humans , Male , Adult , Female , Middle Aged , Orbital Diseases/etiology , Orbital Diseases/therapy , Orbital Diseases/surgery , Retrobulbar Hemorrhage/etiology , Orbital Fractures/surgery , Orbital Fractures/complications , Hematoma/etiology , Treatment Outcome , Emphysema/etiology , Emphysema/therapy , Edema/etiology , Syndrome , Aged , Tomography, X-Ray Computed , Blindness/etiology , Decompression, Surgical/methodsABSTRACT
Adult orbital xanthogranulomatous disease (AOXGD) is a spectrum of histiocytoses with four subtypes. Mitogen-activated protein kinase (MAPK) pathway mutations have been detected in various histiocytic neoplasms, little is known about this in AOXGD. Targeted regions of cancer- and histiocytosis-related genes were analyzed and immunohistochemical staining of phosphorylated ERK (pERK), cyclin D1 and PU.1 was performed in 28 AOXGD and 10 control xanthelasma biopsies to assess MAPK pathway activation. Mutations were detected in 7/28 (25%) patients. Positive staining for pERK and/or cyclin D1 was found across all subtypes in 17/27 (63%) patients of whom 12/17 (71%) did not harbour a mutation. Xanthelasma tissue stained negative for pERK and cyclin D1. Relapse occurred in 5/7 (71%) patients with a MAPK pathway mutation compared to 8/21 (38%) patients in whom no mutation could be detected. Molecular analysis and evaluation for systemic disease is warranted to identify patients at risk of recurrent xanthomatous disease.
Subject(s)
MAP Kinase Signaling System , Mutation , Xanthomatosis , Humans , Female , Male , Middle Aged , Adult , MAP Kinase Signaling System/genetics , Aged , Xanthomatosis/genetics , Orbital Diseases/genetics , Cyclin D1/genetics , Cyclin D1/metabolism , Young Adult , Granuloma/geneticsABSTRACT
INTRODUCTION: Subperiosteal orbital abscesses (SPOA) are the most common suppurative complications of acute bacterial sinusitis. Medial SPOAs arise from infection of the ipsilateral ethmoid sinus and favor initial conservative management reserving surgical drainage for patients who do not demonstrate clinical improvement. No standard algorithm defining medical versus surgical treatment of medial SPOAs exist in the pediatric population. OBJECTIVES: To identify a size cutoff for medial SPOAs to predict the likelihood for surgical drainage. METHODS: This is a retrospective review of patients with medial SPOAs at a tertiary care center from 2003 to 2017. Diagnosis of SPOA was based on radiographic findings. Variables included are patient demographics, antibiotic therapy, surgical intervention, and length of stay. RESULTS: 82 patients with a medial SPOA were included with an average age at presentation of 6.27 (range 0-15) years were included in this study. 62 patients were male (75.6 %), and 20 were female (24.4 %). The average abscess length was 16.1 mm, range 4.5-30.7 mm. The average abscess width was 4.17 mm, range 1.5-14.6 mm. The odds ratio for surgical treatment with every 1 mm increase in abscess width was 1.89 (95CI:1.33-2.69, p < 0.001). Abscesses over 3.6 mm width were 6.65 times more likely to undergo surgical drainage than those less than 3.6 mm (OR:6.65, 95CI:2.52-17.54, p < 0.001). The average(SD) length of stay was 5.4(3.0) days for patients who underwent surgery and 4.0(0.9) days for patients treated with conservative measures, p < 0.001. CONCLUSION: Medial SPOAs greater than 3.6 mm were more likely to undergo surgical drainage; however there was no difference in the likelihood of drainage between anteriorly and posteriorly based medial abscesses. These findings help further characterize the landscape of pediatric subperiosteal abscesses that are managed with surgical drainage.
Subject(s)
Abscess , Drainage , Orbital Diseases , Humans , Female , Male , Child , Retrospective Studies , Abscess/therapy , Abscess/surgery , Adolescent , Child, Preschool , Drainage/methods , Infant , Orbital Diseases/therapy , Orbital Diseases/surgery , Sinusitis/therapy , Sinusitis/surgery , Sinusitis/microbiology , Anti-Bacterial Agents/therapeutic use , Infant, Newborn , Treatment Outcome , Tomography, X-Ray Computed , Length of Stay/statistics & numerical dataABSTRACT
BACKGROUND: Echinococcosis, commonly known as hydatid disease, is a zoonotic infection resulting from the tapeworm Echinococcus granulosus. The occurrence of hydatid cysts in the orbital region is uncommon, representing less than 1% of all reported hydatid cases. This report details a unique case of an intramuscular hydatid cyst in the orbital region that led to compressive optic neuropathy. CASE PRESENTATION: A 22-year-old male from Kabul, Afghanistan presented with a five-month history of progressive proptosis in his left eye, associated with a gradual decrease in vision over the past three weeks. The left eye exhibited upward globe dystopia, ocular motility limitation, mild conjunctival injection, and chemosis. Diagnosis was achieved through imaging and histopathological examination. Treatment involves surgical removal of the cyst and prolonged albendazole therapy. The postoperative course showed significant improvement in the patient's condition and restoration of his vision. CONCLUSIONS: Despite its rarity, this case underscores the importance of awareness and knowledge of hydatid disease among physicians, especially those working in endemic areas. It emphasizes the importance of including hydatid disease in the differential diagnosis of orbital masses, particularly in endemic regions.
Subject(s)
Echinococcosis , Eye Infections, Parasitic , Optic Nerve Diseases , Orbital Diseases , Humans , Male , Echinococcosis/diagnosis , Echinococcosis/complications , Young Adult , Optic Nerve Diseases/diagnosis , Optic Nerve Diseases/parasitology , Optic Nerve Diseases/surgery , Eye Infections, Parasitic/diagnosis , Eye Infections, Parasitic/parasitology , Eye Infections, Parasitic/surgery , Orbital Diseases/parasitology , Orbital Diseases/diagnosis , Magnetic Resonance Imaging , Albendazole/therapeutic use , Tomography, X-Ray ComputedABSTRACT
PURPOSE: Histiocytosis is one of the most challenging diseases in medical practice. Because of the broad spectrum of clinical manifestations, systemic involvements, unknown etiology, and complex management, different types of histiocytosis are still a big question mark for us. Orbital histiocytosis is characterized by the abnormal proliferation of histiocytes in orbital tissues. It could affect the orbit, eyelid, conjunctiva, and uveal tract. Orbital histiocytosis can cause limited eye movement, proptosis, decreased visual acuity, and epiphora. In this study, we review the novel findings regarding the pathophysiology, diagnosis, and treatment of different types of histiocytosis, focusing on their orbital manifestations. METHOD: This review was performed based on a search of the PubMed, Scopus, and Embase databases or relevant published papers regarding orbital histiocytosis on October 9th, 2023. No time restriction was proposed, and articles were excluded if they were not referenced in English. RESULTS: 391 articles were screened, most of them being case reports. The pathophysiology of histiocytosis is still unclear. However, different mutations are found to be prevalent in most of the patients. The diagnostic path can be different based on various factors such as age, lesion site, type of histiocytosis, and the stage of the disease. Some modalities, such as corticosteroids and surgery, are used widely for treatment. On the other hand, based on some specific etiological factors for each type, alternative treatments have been proposed. CONCLUSION: Significant progress has been made in the detection of somatic molecular changes. Many case studies describe various disease patterns influencing the biological perspectives on different types of histiocytosis. It is necessary to continue investigating and clustering data from a broad range of patients with histiocytosis in children and adults to define the best ways to diagnose and treat these patients.
Subject(s)
Histiocytosis , Orbital Diseases , Humans , Histiocytosis/diagnosis , Orbital Diseases/diagnosis , Orbital Diseases/etiology , Histiocytes/pathologyABSTRACT
BACKGROUND: Invasive fungal sinusitis, particularly mucormycosis, presents a significant clinical challenge, especially in pediatric populations. This retrospective epidemiologic study aimed to investigate the clinical characteristics, risk factors and outcomes associated with this rare but severe condition, with a focus on orbital morbidity. METHODS: Clinical data of 12 pediatric patients diagnosed with invasive fungal sinusitis between 2021 and 2023 were retrospectively analyzed. Diagnosis involved microbiological and histopathologic examinations, alongside radiologic imaging. Treatment comprised surgical intervention and antifungal therapy, with a detailed evaluation of orbital involvement. Statistical analysis included descriptive statistics and logistic regression. RESULTS: Predominantly affecting males, the median age of the patients was 8 years. Common symptoms included orbital swelling and impaired vision. Imaging revealed characteristic features of invasive fungal sinusitis, including fat stranding and bone erosions. Orbital involvement was extensive, with poor visual outcomes observed in several cases. Surgical debridement and antifungal therapy, including transcutaneous retrobulbar Amphotericin B, were administered. Risk factors associated with poor orbital outcomes included duration of diabetes and glycated hemoglobin levels. Mortality rate stood at 22.2%. CONCLUSIONS: Early diagnosis, aggressive surgical intervention and combined antifungal therapy are essential for improving outcomes. Timely intervention showed stabilization of the orbital disease and better outcomes in pediatric patients. Further research with larger sample sizes is warranted to better understand and address this serious condition.
Subject(s)
Algorithms , Antifungal Agents , Sinusitis , Humans , Male , Child , Female , Retrospective Studies , Sinusitis/microbiology , Sinusitis/epidemiology , Sinusitis/surgery , Sinusitis/drug therapy , Antifungal Agents/therapeutic use , Child, Preschool , Risk Factors , Adolescent , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/epidemiology , Invasive Fungal Infections/mortality , Invasive Fungal Infections/microbiology , Invasive Fungal Infections/diagnosis , Debridement , Treatment Outcome , Mucormycosis/epidemiology , Mucormycosis/drug therapy , Mucormycosis/mortality , Mucormycosis/diagnosis , Orbital Diseases/microbiology , Orbital Diseases/epidemiology , Orbital Diseases/therapy , InfantABSTRACT
INTRODUCTION: We describe the first case of ALHE in the orbit with extension to the maxillary sinus and the importance of a multidisciplinary approach to achieve removal of the lesion. CASE STUDY: A 72-year-old man presented with epiphora of the left eye and several episodes of recurrent acute dacryocystitis. Magnetic resonance imaging revealed a solid homogeneous mass located in the inferomedial region of the left orbit. In addition, it was associated with destruction of the adjacent ethmoidal wall and upper wall of the left maxillary sinus. Incisional biopsy of the orbital mass was compatible with ALHE. RESULTS: It was decided to perform surgery using an orbital floor approach, left medial wall via subconjunctival and caruncular approach together with an endoscopic nasal approach (ESS), achieving complete removal of the orbital mass and cleaning of the maxillary sinus. After one year of treatment, no tumor recurrence was evident through endoscopy and imaging tests and the patient is asymptomatic. CONCLUSIONS: ALHE is a very rare benign vascular tumor that presents subcutaneous nodules in the head and neck region. We do not know of any case of ALHE in the paranasal sinuses described in the literature, either in isolation or together with orbital or cutaneous ALHE. In conclusion, ALHE disease should be considered as a diagnosis when faced with an orbital mass with extension to the paranasal sinuses, and a complete excision through a combined endonasal and orbital approach prevents recurrence in most cases.