Extensive Workup Research Articles

Spectrophotometric and fluorimetric high-throughput assays for phenolic acid decarboxylase.

Biocatalytic decarboxylation of hydroxycinnamic acids yields phenolic styrenes, which are important precursors for antioxidants, epoxy coatings, adhesives and other polymeric materials. Bacillus subtilis decarboxylase (BsPAD) is a cofactor-independent enzyme that catalyzes the cleavage of carbon dioxide from p-coumaric-, caffeic-, and ferulic acid with high catalytic efficiency. Real-time spectroscopic assays for decarboxylase reactions remove the necessity of extensive sample workup, which is required for HPLC, mass spectrometry, gas chromatography, or NMR methods. This work presents two robust and sensitive assays based on photometry and fluorimetry that allow following decarboxylation reactions with high sensitivity while avoiding product extraction and long analysis times. Optimized assay procedures were used to measure BsPAD activity in cell lysates and to determine the kinetic constants (KM and Vmax) of the purified enzyme for p-coumaric-, caffeic- and ferulic acid. Substrate inhibition was shown for caffeic acid.

Secondary Central Nervous System Demyelinating Disorders in the Elderly: A Narrative Review.

Secondary demyelinating diseases comprise a wide spectrum group of pathological conditions and may either be attributed to a disorder primarily affecting the neurons or axons, followed by demyelination, or to an underlying condition leading to secondary damage of the myelin sheath. In the elderly, primary demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis, are relatively uncommon. However, secondary causes of CNS demyelination may often occur and in this case, extensive diagnostic workup is usually needed. Infectious, postinfectious, or postvaccinal demyelination may be observed, attributed to age-related alterations of the immune system in this population. Osmotic disturbances and nutritional deficiencies, more commonly observed in the elderly, may lead to conditions such as pontine/extrapontine myelinolysis, Wernicke encephalopathy, and demyelination of the posterior columns of the spinal cord. The prevalence of malignancies is higher in the elderly, sometimes leading to radiation-induced, immunotherapy-related, or paraneoplastic CNS demyelination. This review intends to aid clinical neurologists in broadening their diagnostic approach to secondary CNS demyelinating diseases in the elderly. Common clinical conditions leading to secondary demyelination and their clinical manifestations are summarized here, while the current knowledge of the underlying pathophysiological mechanisms is additionally presented.

Plasmablastic transformation of chronic lymphocytic leukemia: a review of literature and report on 2 cases.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common leukemia in adults in Western countries. Transformation of CLL/SLL to plasmablastic lymphoma (PBL) is exceedingly rare and often has an extremely poor response to treatment. A thorough molecular workup may help in determining clonality-relatedness and prognosis. We describe two cases of CLL/SLL that transformed into PBL, with an extensive molecular workup in one case, and a review of the literature.

Paroxysmal sympathetic hyperactivity in a child with stroke: a case report

BackgroundParoxysmal sympathetic hyperactivity (PSH) is the result of dysregulated autonomic function with sympathetic symptoms characterised by increased heart rate, respiratory rate, blood pressure and temperature with abnormal posture, which predominately occur periodically but can be persistent in severe cases. Common causes that present in similar fashion such as infectious process (bacteremia, meningitis, etc.); non-PSH neurological deterioration (increased intracranial pressure, intracranial haemorrhage, intracranial oedema, seizures, encephalitis); pulmonary embolism; thyrotoxicosis, alcohol or drug withdrawal; neuroleptic malignant syndrome; serotonin syndrome; and malignant hyperthermia need to be excluded before diagnosing PSH. The earlier the diagnosis made, the better the prognosis.Case presentationWe report a case of a 3-year-old male child who was a diagnosed case of Tetralogy of Fallot presented with left focal seizure with secondary generalisation. Child also had respiratory complaints prior to convulsion. He had developed signs of raised intracranial pressure. Blood culture sent to rule out infective endocarditis was negative. CT brain showed bilateral diffuse cortical infarct. Child developed signs and symptoms of PSH such as fever, tachycardia, tachypnoea, hypertension, diaphoresis, dystonia and bilateral completely dilated pupils. Other common causes such as infective endocarditis, increased intracranial pressure, intracranial oedema, intracranial haemorrhage, seizure, encephalitis and infectious processes (bacteremia, meningitis and infective endocarditis) were ruled out. The diagnosis of PSH was made and started on propranolol along with clonidine. Child responded well to the treatment.ConclusionThe complex pathophysiology of PSH warrants extensive work-up to rule out other common causes. The outcome of our patient shows the importance of early diagnosis and multidisciplinary treatment for better outcome.

Sino-orbital aspergillosis with obstructive cervical lymphadenopathy in a cat caused by Aspergillus viridinutans complex

Case summary This report describes an indoor-only cat with a rare form of sino-orbital aspergillosis (SOA) with cervical lymphadenopathy causing local obstruction. Extensive work-up on initial presentation failed to identify the underlying etiology and the diagnosis was not determined until the disease progressed during a prolonged course of glucocorticoid therapy. Relevance and novel information SOA caused by Aspergillus viridinutans complex is increasingly recognized as a significant cause of mortality in cats in recent years, with most cases reported in Australia, Europe and Asia. Feline SOA carries a poor prognosis owing to its invasive nature and resistance to antifungal therapy. This case demonstrates the importance of clinical awareness of SOA as a differential for cats with chronic nasal signs and exophthalmos in the USA. Moreover, it demonstrates a rare form of presentation and potential difficulty in achieving a correct diagnosis.

Hyperammonemia Secondary to 5-Fluorouracil.

5-fluorouracil (5-FU) is one of the most common adjuvant antineoplastic agents used in the treatment of localized and metastatic colon cancer. Frequent side effects of 5-FU include myelosuppression, mucositis, nausea, vomiting, and diarrhea. However, hyperammonemic encephalopathy is a rare neurologic toxicity that can occur after 5-FU chemotherapy administration. Patients with 5-FU-induced hyperammonemic encephalopathy often exhibit symptoms of altered mental status with no radiologic abnormalities or laboratory abnormalities except for significantly elevated ammonia levels with occasional lactic acidosis and respiratory alkalosis. We report a case of a patient with stage IV colon adenocarcinoma who experienced altered state of consciousness due to hyperammonemia during the administration of palliative chemotherapy with 5-FU, bevacizumab, and leucovorin. On cycle 1 day 2 of chemotherapy, the patient became drowsy and confused at home, prompting a visit to the emergency department and ultimately hospital admission. Laboratory tests revealed an elevated blood ammonia level (838 μg/dL). After an extensive negative workup, his altered state of consciousness was thought to be secondary to 5-FU-induced hyperammonemia. Upon admission, 5-FU was immediately discontinued and the patient was treated with lactulose enemas, intravenous fluids, rifaximin, and continuous renal replacement therapy with gradual recovery to baseline mental status. It is crucial for advanced practitioners to be aware of this rare side effect to ensure prompt diagnosis and maximize treatment effectiveness.

Primary Endobronchial Conventional Chondrosarcoma Right Lung Upper Lobe: A Case Report and Literature Review

Primary endobronchial chondrosarcoma is extremely rare and hardly reported while reported chondrosarcomas of primary lung origin are rare with most literature coming from a series of case reports and small case series. These tumours can present as centrally located masses and therefore, require extensive workup to exclude alternative aetiology and to confirm diagnosis. Literature review revealed only four reports of primary endobronchial and 29 primary pulmonary chondrosarcoma cases, excluding the current report. We present a rare case of biopsy-proven non-metastatic primary endobronchial conventional chondrosarcoma of the right upper lobar bronchus extending into the right main bronchus managed with technically challenging sleeve bilobectomy of right upper and middle lobes and a viable anastomosis of lower lobe bronchus with the right main bronchus stump and thus, prevented a pneumonectomy. Final histopathology confirmed the diagnosis. Thus, these tumours are difficult to diagnose and challenging to manage and need more data in future to establish protocols.

Emergency Presentations for Dizziness-Radiological Findings, Final Diagnoses, and Mortality.

Dizziness is a frequent presentation in patients presenting to emergency departments (EDs), often triggering extensive work-up, including neuroimaging. Therefore, gathering knowledge on final diagnoses and outcomes is important. We aimed to describe the incidence of dizziness as primary or secondary complaint, to list final diagnoses, and to determine the use and yield of neuroimaging and outcomes in these patients. Secondary analysis of two observational cohort studies, including all patients presenting to the ED of the University Hospital of Basel from 30th January 2017-19th February 2017 and from 18th March 2019-20th May 2019. Baseline demographics, Emergency Severity Index (ESI), hospitalization, admission to Intensive Care Units (ICUs), and mortality were extracted from the electronic health record database. At presentation, patients underwent a structured interview about their symptoms, defining their primary and secondary complaints. Neuroimaging results were obtained from the picture archiving and communication system (PACS). Patients were categorized into three non-overlapping groups: dizziness as primary complaint, dizziness as secondary complaint, and absence of dizziness. Of 10076 presentations, 232 (2.3%) indicated dizziness as their primary and 984 (9.8%) as their secondary complaint. In dizziness as primary complaint, the three (out of 73 main conditions defined) main diagnoses were nonspecific dizziness (47, 20.3%), dysfunction of the peripheral vestibular system (37, 15.9%), as well as somatization, depression, and anxiety (20, 8.6%). 104 of 232 patients (44.8%) underwent neuroimaging, with relevant findings in 5 (4.8%). In dizziness as primary complaint 30-day mortality was 0%. Work-up for dizziness in emergency presentations has to consider a broad differential diagnosis, but due to the low yield, it should include neuroimaging only in few and selected cases, particularly with additional neurological abnormalities. Presentation with primary dizziness carries a generally favorable prognosis lacking short-term mortality. .

Are Patients with HHV-8 Associated Castleman Disease Successfully Treated with Rituximab at Risk of Subsequently Developing HHV-8 Negative (Idiopathic) Castleman Disease?

Multicentric Castleman disease (MCD) is a lymphoproliferative disorder characterized by lymph node histopathology and systemic symptoms. To our knowledge, there are no descriptions in the literature of long-term outcomes of human herpesvirus-8 (HHV-8)-associated MCD. We report a case of a 70-year-old male living with human immunodeficiency virus and a history of human herpesvirus-8 (HHV-8)-associated MCD. The patient reported having had low-grade fever for two weeks. Extensive workup revealed systemic lymphadenopathy without evidence of autoimmune disease or malignancy. Lymph node biopsy was consistent with HHV-8-negative idiopathic MCD (iMCD). The patient was subsequently scheduled for anti-interleukin-6 therapy. The present case is the first report of probable development of iMCD after long-term follow-up for HHV-8-associated MCD. The case illustrates the possible long-term consequences of MCD, suggesting the necessity of further research on the pathogenesis of CD. Given the uncertainty in the long-term outcomes of HHV-8-associated MCD, periodic surveillance of patients with a history of HHV-8-associated MCD is warranted. Prospective nationwide cohort studies comparing characteristics of HHV-8-associated MCD and iMCD would bring further insights. This is the first case describing the probable development of HHV-8-negative idiopathic MCD after HHV-8-associated MCD.Little is known of long-term outcomes of HHV-8-associated MCD and idiopathic MCD, necessitating periodic surveillance.HHV-8-negative idiopathic MCD patients are treated with siltuximab, an interleukin-6 inhibitor, unlike patients with HHV-8-associated MCD, who benefit most from rituximab.

Systemic Capillary Leak Syndrome With Cerebral Involvement in a C9orf72 Expansion Carrier: Case Report and Review of the Literature.

Systemic capillary leak syndrome (SCLS) is a rare condition associated with episodes of hypotension, hemoconcentration, hypoalbuminemia, and rhabdomyolysis. We describe a middle-aged man presenting with several distinct SCLS-like episodes, the last being fatal. In addition, in the year before the final event, he developed rapid cognitive decline with contrast-enhancing lesions on MRI and highly elevated neurofilament light protein levels in CSF. Data and imaging were obtained from patient medical records. At the time, the SCLS-like episodes were interpreted as myositis secondary to viral infection. A thorough workup for other causes, including genetic testing, was negative. As for the rapid cognitive decline, despite an extensive workup for infectious and inflammatory causes, no definitive diagnosis was made. Whole genome sequencing however identified a C9orf72 hexanucleotide expansion. The C9orf72 expansion is associated with frontotemporal dementia and amyotrophic lateral sclerosis but has also been shown to increase susceptibility to neuroinflammation. Recent findings also suggest C9orf72 to exert functions in the immune system, in particular regulation of type I interferon responses, in turn shown to be associated with SCLS. This case suggests a possible link between SCLS, cerebral inflammation, dysregulated type I interferon signaling, and expansions in C9orf72.

Chronic neutropenia in adults.

Neutrophils are an important component of the innate immune system, and they prevent bacterial and fungal infections by phagocytosis and killing of pathogens. Neutropenia is defined as an abnormally low number of circulating neutrophils, and the term chronic neutropenia is used when it lasts more than three months. The objective of this clinical review is to raise awareness among doctors in Norway of chronic neutropenia and possible causes. A patient with severe neutropenia and fever requires immediate admission to hospital and initiation of empiric sepsis treatment before the cause of neutropenia has been determined, but patients with chronic neutropenia do not always require rapid and extensive workup.

Management of a patient with common variable immunodeficiency and hepatopathy

BackgroundCommon variable Immunodeficiency (CVID) is a primary immunodeficiency disorder and the most common form of severe antibody deficiency. Both children and adults are affected and clinical manifestations vary widely. Often, CVID manifests with infections, autoimmune phenomena or chronic lung disease, but it also frequently affects the liver. The differential diagnoses of hepatopathies in CVID patients are diverse and the characteristics of CVID patients often make it difficult to determine the correct diagnosis.Case presentationWe present the case of a 39-year-old patient with CVID and elevated liver enzymes, nausea and unintended weight loss, who was referred to our clinic with the suspected diagnose of autoimmune hepatitis or immunoglobulin-induced hepatopathy. Prior, the patient had undergone an extensive diagnostic work-up including liver biopsy but viral hepatitides had only been investigated serologically – with negative antibody results. We searched for viral nucleic acid by polymerase chain reaction and detected hepatitis E virus-RNA. Antiviral therapy was started and the patient recovered quickly.ConclusionHepatopathies in CVID patients are common with a broad spectrum of possible causes. While treating CVID patients, the distinct diagnostic and therapeutic requirements of the CVID patients should be closely considered and diagnosed by the appropriate measures.

Laryngeal NK/T Cell Lymphoma, Nasal Type: Case Report and Literature Review

Extranodal Natural Killer T-cell lymphoma, nasal type represent a rare and aggressive entity of the non-Hodgkin's lymphomas. Laryngeal localization is rare and has a poor prognosis. We report the case of a 66-year-old patient who consulted for dyspnea, dysphonia and dysphagia. Endoscopic examination revealed an endo-laryngeal lesion. Anatomopathological study with immunohistochemistry concluded to a peripheral T NK/T-cell lymphoma nasal type. The extension workup was without abnormalities. Induction chemotherapy without anthracyclines was administered followed by conformal radiotherapy with intensity modulation in arctotherapy. Significant advances have been made over the past decade including better clarification of clinical heterogeneity, more accurate classification using imaging modalities, establishment of new prognostic models, and sequential use of anthracycline-free radiotherapy and chemotherapy in early stages and risk-adapted first-line treatment strategies in advanced stages.

Tacrolimus-Induced Esophageal and Colon Ulcers

ABSTRACT We report a case of a 44-year-old woman with a history of orthotopic heart transplant on tacrolimus (TC) for immunosuppression who developed large-volume hematochezia. She was found to have a large mid-esophageal ulcer and several large colon ulcers. Biopsies showed granulation tissue and inflammatory debris without an identifiable culprit. Extensive workup was performed, including for infectious causes, which was unrevealing. TC was ultimately considered to be a possible culprit, and after stopping it, all her symptoms improved. We suggest considering TC as the possible cause of gastrointestinal ulcers if no other culprit can be identified.

Delayed diagnosis of duodenal duplication cyst in a child with recurrent pancreatitis operated by Whipple procedure: a case report.

The authors present the case of a 12-year-old Arab male who was admitted to our hospital with worsening, severe epigastric pain, stabbing in nature, and radiating to the back, suggestive of acute pancreatitis. Serum lipase levels were significantly elevated. The patient received appropriate care. His medical history is notable for multiple bouts of pancreatitis in the last 18 months. Previous investigations at other hospitals were mostly unrevealing. A more extensive workup was performed, revealing a duodenal cystic structure. This led to the diagnosis of a duodenal duplication cyst. The Whipple procedure was decided upon due to his recurrent pancreatitis, which caused fibrotic adhesions and anatomic region distortion. The patient underwent surgery and recovered uneventfully. Acute pancreatitis in children is frequent and can be caused by unrecognized duodenal duplication cysts. When symptomatic, the majority present with vague abdominal pain. Despite using ultrasound as an adjunctive for diagnosis, the cyst might not become apparent until the condition has progressed to an advanced stage. A delayed diagnosis may result in complications necessitating risky surgeries. Children with recurrent pancreatitis should be evaluated for a duodenal duplication cyst. Early use of computed tomography scans may be necessary to identify the cause and spare the patient from risky procedures like Whipple surgery.

Sarcoidosis

Sarcoidosis is the most common granulomatous disease in northern Europe. Adistinction is made between acute forms of sarcoidosis and chronic sarcoidosis. Chronic sarcoidosis can affect practically all organs but the lungs are affected in 90-95% of patients. The clinical appearance varies between asymptomatic and oligosymptomatic courses, which are diagnosed more by chance, to courses with acute organ failure. An extensive organ work-up is necessary at the time of the initial diagnosis in order to record the extent of organ involvement and to make appropriate treatment decisions. Asymptomatic courses with purely pulmonary sarcoidosis do not require treatment and can be observed over the course of the disease, whereas courses with extensive organ involvement or organ dysfunction require treatment. The treatment consists primarily of the administration of glucocorticoids. If the effect of the glucocorticoids is insufficient or if there are side effects, various immunosuppressive agents, including biologics can be added.

ID: 219777 Neuromodulation in a 10-Year-Old With Chronic Abdominal Pain: A Case Report

Chronic abdominal pain in the pediatric population is complex, and identifiable causes may be difficult to elucidate. Median arcuate ligament syndrome is a rare disease in which diagnosis has been controversial in the medical community. Patients typically present with chronic postprandial abdominal pain accompanied with nausea, vomiting and weight loss. It is a diagnosis of exclusion with unclear pathophysiology typically thought to have both a structural component via compression of the celiac artery by the median arcuate ligament, as well as a neuropathic component mediated by the celiac ganglia. Optimal treatment is also debated but generally involves surgical intervention to decompress the celiac artery with or without neurolysis of the celiac plexus. We present the case of a 10-year-old female with chronic abdominal pain refractory to aggressive medical and surgical treatments, who found relief with spinal cord stimulator implantation. Before evaluation in the pain clinic, the patient received extensive gastroenterological workup and treatments including arcuate ligament release with neurolysis of the celiac ganglion that provided relief for nearly two months. She had increasing abdominal pain since five years of age and required a feeding tube for adequate nutritional intake.

A 48-year-old Caucasian man with unilateral "smudge" in inferior visual field.

To report an increasingly prevalent fundoscopic manifestation of syphilitic uveitis. Case report of a patient with acute retinal necrosis secondary to syphilis. A 48-year-old man presented with decreased vision, anterior segment inflammation, and a wedge-shaped retinal lesion in the superior periphery, with a diaphanous leading edge extending down towards the superior arcade. The patient was HIV+ and poorly compliant with therapy. The top three differential diagnoses were herpetic necrotizing retinitis, syphilis, and lymphoma. An extensive lab workup was positive for syphilis. The patient was treated with IV penicillin G and demonstrated improvement in visual acuity and exam. There have been an increasing number of reports of syphilis patients, especially in the population of men who have sex with men, who present with fundus findings similar to acute retinal necrosis. These findings include a characteristic ground glass, translucent appearance of unifocal or multifocal lesions, primarily affecting the inner retina and sometimes associated with co-localizing occlusive vasculitis. Treatment with IV penicillin G is warranted and has demonstrated good visual recovery.

Angiosarcoma of the scalp A zosteriform presentation

Cutaneous angiosarcoma is a rare and agressive tumor with poor outcome, and early diagnosis is paramount, but its often delayed because of the long delay in the appearance of lesions and the variable clinical presentation of this neoplasia. This article reports the case of an 84-year-old patient who presented with persistant ulcerated placard of the scalp and face evolving since one year and treated as herpes zoster ophthalmicus. Incisional biopsy revealed a morphological aspect of high grade angiosarcoma with CD 31 + / CD 34 -. An extension workup made of thoraco-abdominal and pelvic CT scans showed hepatic, adrenal and bone metastasis. Given his advanced age, and his general condition and visceral metastasis at the moment of diagnosis, the decision of the multidisciplinary concertation meeting was to put him under palliative care, he passed away 8 months after the diagnosis of angiosarcoma was made, 18 months after the occurrence of the first symptoms. Cutaneous angiosarcoma (CA) is a rare aggressive malignant tumor, that occurs in elderly white man. Because of the variability of its presentation and its insidious evolution, the appearance of lesions may not concern patients or practitioners for some time,Therefore correct diagnosis may be delayed, often dramatically limiting the tools of treatment options and altering the outcome of the patients.

Adult-onset Still’s disease with secondary macrophage activation syndrome: a case report

We describe a case of adult-onset Still’s disease (AOSD) with secondary macrophage activation syndrome. AOSD is a rare disease with unknown origin. Rarely it’s complicated by secondary macrophage activation syndrome, which is a life-threatening disorder. Because the diagnosis of AOSD is essential for exclusion and complications are life-threatening, it is mandatory for a prompt and extensive diagnostic workup and treatment.