Broad Diagnostic Workup Research Articles

Cancer screening with multicancer detection tests: A translational science review.

Multicancer detection (MCD) tests use a single, easily obtainable biospecimen, such as blood, to screen for more than one cancer concurrently. MCD tests can potentially be used to improve early cancer detection, including cancers that currently lack effective screening methods. However, these tests have unknown and unquantified benefits and harms. MCD tests differ from conventional cancer screening tests in that the organ responsible for a positive test is unknown, and a broad diagnostic workup may be necessary to confirm the location and type of underlying cancer. Among two prospective studies involving greater than 16,000 individuals, MCD tests identified those who had some cancers without currently recommended screening tests, including pancreas, ovary, liver, uterus, small intestine, oropharyngeal, bone, thyroid, and hematologic malignancies, at early stages. Reported MCD test sensitivities range from 27% to 95% but differ by organ and are lower for early stage cancers, for which treatment toxicity would be lowest and the potential for cure might be highest. False reassurance from a negative MCD result may reduce screening adherence, risking a loss in proven public health benefits from standard-of-care screening. Prospective clinical trials are needed to address uncertainties about MCD accuracy to detect different cancers in asymptomatic individuals, whether these tests can detect cancer sufficiently early for effective treatment and mortality reduction, the degree to which these tests may contribute to cancer overdiagnosis and overtreatment, whether MCD tests work equally well across all populations, and the appropriate diagnostic evaluation and follow-up for patients with a positive test.

Neonatal Intestinal Obstruction Caused by a Perforated Duodenal Web

Aim: To report the clinical courses of two patients with intestinal obstruction caused by duodenal web, who were diagnosed with this rare congenital anomaly at Clinical Hospital Center Rijeka in a span of 5 months. Case report: One of the patients was prenatally suspected to have duodenal obstruction due to ultrasonographic findings, while the other showed signs of obstruction by not tolerating oral intake from the second day of life (DOL). Ceasing enteral feeding, placing a nasogastric tube and introducing intravenous hydration and parenteral nutrition was performed as initial management. Abdominal ultrasonography, abdominal radiography, upper gastrointestinal contrast study and contrast enema were performed but showed no signs of obstruction. Both patients showed improvement in tolerating oral intake over the next few days. However, the first patient did not tolerate meals exceeding 15 mL of infant formula, and the second patient again did not tolerate any oral intake from the 15th day of life. A broad diagnostic workup was repeated but did not show conclusive evidence of obstruction regarding the first patient. Esophagogastroduodenoscopy found duodenal obstruction of unknown origin regarding the second patient. Laparotomy was performed on the 19th and 25th DOL, respectively. Duodenal web was visualized and excised in both patients following duodenotomy. Postoperative recovery was orderly with minor nonsurgical complications. The patients were discharged from hospital on the 21st and 36th postoperative day, respectively. Conclusions: Diagnosing a perforated duodenal web is often challenging because of possible intermittent nature of its symptoms. Exploratory laparotomy is sometimes required to reach diagnosis.

Cardiovascular predictors of mortality and exacerbations in patients with COPD

In chronic obstructive pulmonary disease (COPD), comorbidities and worse functional status predict worse outcomes, but how these predictors compare with regard to different outcomes is not well studied. We thus compared the role of cardiovascular comorbidities for mortality and exacerbations. Data from baseline and up to four follow-up visits of the COSYCONET cohort were used. Cox or Poisson regression was employed to determine the relationship of predictors to mortality or mean annual exacerbation rate, respectively. Predictors comprised major comorbidities (including cardiovascular disease), lung function (forced expiratory volume in 1 s [FEV1], diffusion capacity for carbon monoxide [TLCO]) and their changes over time, baseline symptoms, exacerbations, physical activity, and cardiovascular medication. Overall, 1817 patients were included. Chronic coronary artery disease (p = 0.005), hypertension (p = 0.044) and the annual decline in TLCO (p = 0.001), but not FEV1 decline, were predictors of mortality. In contrast, the annual decline of FEV1 (p = 0.019) but not that of TLCO or cardiovascular comorbidities were linked to annual exacerbation rate. In conclusion, the presence of chronic coronary artery disease and hypertension were predictors of increased mortality in COPD, but not of increased exacerbation risk. This emphasizes the need for broad diagnostic workup in COPD, including the assessment of cardiovascular comorbidity.Clinical Trials: NCT01245933.

Primäre ZNS-Vaskulitis

Primary CNS Vasculitis - An Overview Abstract. Cerebral vasculitis, especially the primary vasculitis of the central nervous systems (primary CNS vasculitis), are rare inflammatory diseases of the small- and medium-sized vessels of the CNS. The pathogenesis of primary CNS vasculitis is unclear. Infectious triggers are hypothesized to induce an activation of the immune system with resulting inflammation of the blood vessels within the CNS. Clinically, primary CNS vasculitis presents heterogeneously with leading symptoms such as headache, memory impairment and other neurological deficits. A broad diagnostic work-up prior to treatment initiation is crucial. Treatment consists of immunotherapy (pulse and maintenance therapy) and requires long-term neurological treatment and follow-up due to the increased risk of recurrence of the disease.

Study on "Atypical" Migraine Auras in the Pediatric Age: The Role of Cortical Spreading Depression and the Physiopathogenetic Hypothesis Arising from Our Clinical Cases.

Migraine is a complex neurologic disorder by which several systems of the central nervous system (autonomous system, affective, cognitive, sensory and motor system) may be affected on different levels. About a fourth of migraine patients have migraine auras. The most common aura is the visual aura followed by the sensorial aura but motor deficits, as well as deficits of higher cortical centers (disorders of thinking, orientation, coherence, or concentration), may occur as well. In analogy with a headache diary, an aura diary can deliver important help in the diagnostic process of rare migraine manifestations and prevent the under-diagnosis of unusual migraine manifestations. Complex migraine manifestations are a diagnosis of exclusion, and a broad diagnostic work-up is necessary in order to exclude dangerous neurologic pathologies. In addition, here, we discuss the atypical clinical presentation and possible physio-pathogenetic related aspects of these atypical migraine aura features in the developmental age. In addition, we wanted to stress and analyze the clinical aspects of our children/adolescents with atypical auras, which seem to be more difficult to frame with the mechanisms originally proposed to explain the physio-pathogenetic relationship between CSD and aura. Finally, we discuss in detail the complex aspects of this topic on the basis of available data and propose new terminology: “Multiple, Synchronous and Asynchronous, Cortical and Subcortical Spreading Depression”.

Ticagrelor induced systemic inflammatory response syndrome

BackgroundTicagrelor is a reversible and direct-acting oral antagonist of the adenosine diphosphate receptor P2Y12. Possible adenosine-mediated effects of ticagrelor on inflammation are complex and incompletely understood. To our knowledge, ticagrelor-induced systemic inflammatory response syndrome (SIRS) has not yet been described.Case presentationWe report the case of an 84 years old patient presenting with SIRS subsequent to initiation of ticagrelor after implantation of two drug eluting stents. A broad diagnostic work-up for alternative causes and therapeutic measures were unrevealing. Discontinuation of the agent was followed by rapid improvement in clinical and laboratory signs of SIRS.ConclusionsAfter exclusion of other causes, ticagrelor needs to be considered as a possible causative agent for SIRS. Due to the widespread use of ticagrelor, clinicians should be aware of this possible adverse drug reaction.

Unusual Migraine Manifestations

Migraine is a complex neurologic disorder by which several systems of the central nervous system (autonomous system, affective, cognitive, sensoric and motoric system) may be affected on different levels. Around a fourth of the patients have migraine aura. The most common aura is the visual aura, followed by sensoric aura. But motoric deficits as well as deficits of higher cortical centers (disorders of thinking, orientation, coherence or concentration) may occur as well. In analogy with a headache calendar, an aura calendar can deliver important help in the diagnostic process of rare migraine manifestations and prevent underdiagnosis of unusual migraine manifestations. Complex migraine manifestations are diagnoses of exlusion, and a broad diagnostic work-up is warranted in order to exclude dangerous neurologic pathologies. There are no specific therapeutic recommendations, as there is a lack of randomized controlled studies.

78.: Leptomeningeal rheumatoid nodules: Diagnosis and failed therapeutics

A 67-year-old lady presented with recurrent transient ischemic attack (TIA)-like episodes in the setting of nodular enhancing leptomeningeal changes on MRI that were consistent with meningeal rheumatoid nodules on biopsy. The patient’s nodular disease continues to progress and regress both clinically and radiologically irrespective of her disease modifying agents and peripheral and serological rheumatoid arthritis control. We discuss this patient’s unique presentation and diagnostic work-up alongside the dilemma of therapeutic management of meningeal rheumatoid nodules. We investigated our patient’s unique presentation and radiological changes. We conducted extensive work-up for malignancy alongside other causes of leptomeningeal thickening before proceeding to biopsy that was imperative to making the diagnosis of leptomeningeal rheumatoid nodules. We then observed that the leptomeningeal nodules have regressed and progressed over time with on-going TIA like episodes and without any response to different immunological and biological therapies. Leptomeningeal rheumatoid nodules is a rare condition. The three pertinent points that our patient highlights (1) the differential diagnoses for transient neurological symptoms with MRI evidence of leptomeningeal thickening is large and varied and requires a systematic and broad diagnostic work-up, (2) biopsy and histological confirmation was crucial to making the diagnosis of leptomeningeal rheumatoid nodules and guiding future appropriate therapies, and (3) there is a lack of evidence with respect to satisfactorily treating cerebral rheumatoid nodules and there is a need for further evidence with respect to the newer biological agents.

Macrocytic Anaemia In Patients With Newly Diagnosed Anaemia: Causes and Prognosis

IntroductionMacrocytic anaemia (MCV ≥ 100 fl) is regularly encountered in general practice and in hospital settings. However, the incidence of macrocytic anaemia in newly diagnosed patients remains elusive. In addition, factors influencing laboratory diagnosis and prognosis are unclear. PAGAS (Project of Anaemia from the General practitioner to the Albert Schweitzer hospital) is a collaboration of 63 general practitioners and the Albert Schweitzer hospital (Dordrecht, the Netherlands), which aims at improving quality of care for anaemic patients. We set out to clarify the incidence of newly discovered macrocytic anaemia in the PAGAS cohort and to determine the underlying causes of macrocytic anaemia. MethodsAnaemia was defined as a haemoglobin level below 13.7 g/dL for men and below 12.1 g/dL for women. These values were used for persons older than 16 years. Patients who were included in the PAGAS study had to present to their general practitioner with a newly diagnosed anaemia i.e. no known anaemia in the preceding two years. Women were included when aged 50 years or older, in order to prevent an overabundance of iron deficiency anaemia (IDA) due to hypermenorrhea. Men were included when aged 17 or older. Patients were included between the 1st of February 2007 and the 1st of February 2013. For each patient an extensive laboratory work-up was performed, considering a broad range of causes of anaemia. Furthermore all additional hospital work-up was analyzed as well, including bone marrow examinations and a report of alcohol abuse when present.A classification system was developed that included the following causes: 1) anaemia of chronic disease (ACD 2) haemolysis 3) bone marrow disease 4) vitamin B12 deficiency 5) folic acid deficiency 6) iron deficiency 7) reported alcohol abuse 8) renal anaemia and 9) other. If no cause could be established, it was classified as unknown. The cause of each anaemia was established by 2 independent observers. In case of a discrepancy, the observers deliberated until a consensus was reached. ResultsOver the span of 6 years a total of 2738 patients were included in the PAGAS study. 190 (6,9%) of these 2738 patients presented with a macrocytic anaemia; 108 men (56,8%) and 82 (43,2%) women. Men were aged 70,7 years on average at the time of inclusion while women had an average age of 79 years when included. In 83,7% of patients (N=159), the underlying cause of the anaemia could be established. Seven patients displayed a double underlying cause. Bone marrow disease was found 18 times (9,1%), vitamin B12 deficiency 27 times (13,7%), folic acid deficiency 10 times (5,1%), haemolysis 7 times (3,6%) and alcohol abuse 27 times (13,7%). In addition, we found 39 patients (19,8%) with ACD, 4 patients (2,0%) with IDA and 29 patients (14,7%) with renal anaemia. Five cases of anaemia (2,5%) were classified as other.Overall survival was 57 months (95% CI 52,6-61,4) after entry into the study. The survival of patients with a nutrient deficiency, vitamin B12 or folic acid, was significantly shorter (41,8 months, 95% CI 33,2-50,3) when compared to the survival of the other patients in the cohort (58,3 months, 95% CI 53,7-63) (p-value = 0,024). See figure 1. [Display omitted] Significantly more alcohol abuse was found as a cause in the age group of 50-64 years (20 of 27 cases) compared to the other four age groups (17-49, 65-74, 75-84 and 85+ years) combined (p-value = 0,000). In addition, the number of cases of renal anaemia found in the combined 75-84 and 85+ age groups (27 of 29 cases) differed significantly when compared to the other three age groups combined (p-value = 0,000). Nutrient deficiency was observed more often in the two highest age groups combined (24 of 37 cases) when compared to the lower three combined but this difference was not significant (p-value = 0,165). DiscussionIn our cohort study the well known causes of macrocytic anaemia – bone marrow disease, alcohol abuse, haemolysis and vitamin B12 and folic acid deficiency – were found in 45,2% of patients. However, ACD, IDA and renal anaemia, typically reported in normocytic and microcytic anaemic patients, were leading causes of anaemia in 36,5% of patients.As shown in our population the causes of macrocytic anaemia are diverse. Therefore we consider a broad diagnostic work-up warranted to completely elucidate the underlying cause. Disclosures:No relevant conflicts of interest to declare.

Recurrent Upper Motor Neuron Facial Weakness of Possible Epileptic Etiology: A Case Report

We report on an otherwise healthy infant who presented with clusters of alternating central facial nerve paresis. At 11 months of age, the patient showed intermittent facial asymmetry compatible with right-sided upper motor neuron facial paresis and accompanying incomplete upper motor neuron hypoglossal paresis. Laboratory work-up and imaging studies did not reveal signs of infection, infarction or structural lesions, and after one week, symptoms spontaneously resolved. Similar episodes affecting alternate sides were noted at ages of 17, 27 and 49 months lasting for 4-14 days. At 49 months, EEG showed right temporo-occipital benign sharp waves with activation during drowsiness and sleep. A diagnosis of benign focal epilepsy with negative motor phenomena was made. She is now 60 months old and no further episodes have occurred without antiepileptic treatment. Ictal orofacial phenomena are the clinical hallmark of benign focal epilepsy with centro-temporal sharp waves (BECTS). As in our patient, negative epileptic motor phenomena frequently lead to a broad diagnostic work-up. In infants presenting with episodic central facial nerve paresis, the possibility of negative epileptic motor phenomena should be considered.

Seronegative Lyme Neuroborreliosis in a Patient on Treatment for Chronic Lymphatic Leukemia

We report on a patient who developed seronegative Lyme neuroborreliosis complicating chemotherapy for chronic lymphatic leukemia. After the fifth cycle of chemotherapy (FCR: fludarabine, cyclophosphamide, rituximab and prednisone) the 63-year-old patient developed night sweat, arthralgia in elbows, wrists, proximal interphalangeal joints (PIPs) and strong neuropathic pain in both legs, followed by paresthesia and hypesthesia in the feet, arms and face. Laboratory analysis revealed an elevated C-reactive protein (CRP), a slight elevation of liver enzymes and decreased IgG levels. Cerebrospinal fluid (CSF) analysis showed a lymphomononuclear pleocytosis and an elevation of protein. A broad diagnostic work-up was negative including a negative Borrelia IgG and IgM ELISA. The patient did not remember recent tick bites, but after specific questioning he recollected a transient erythema on his leg developing just before the start of the last cycle of chemotherapy. As the combination of neuropathic pain and arthralgia, the transient erythema and the lymphomononuclear pleocytosis raised the suspicion of Lyme neuroborreliosis, the patient was treated for 3 weeks with ceftriaxone. On therapy all symptoms resolved and CRP normalized. Retrospective PCR analysis of a CSF sample confirmed the clinical diagnosis by detecting Borrelia garinii DNA. This case demonstrates that in immunosuppressed patients borrelial serology may be negative and that additional diagnostic approaches (including tests for direct Borrelia detection) may be needed to demonstrate borrelial infection.