Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study

CONTEXT The polyuria-polydipsia syndrome comprises primary polydipsia (PP) and central and nephrogenic diabetes insipidus (DI). Correctly discriminating these entities is mandatory, given that inadequate treatment causes serious complications. The diagnostic "gold standard" is the water deprivation test with assessment of arginine vasopressin (AVP) activity. However, test interpretation and AVP measurement are challenging. OBJECTIVE The objective was to evaluate the accuracy of copeptin, a stable peptide stoichiometrically cosecreted with AVP, in the differential diagnosis of polyuria-polydipsia syndrome. DESIGN, SETTING, AND PATIENTS This was a prospective multicenter observational cohort study from four Swiss or German tertiary referral centers of adults >18 years old with the history of polyuria and polydipsia. MEASUREMENTS A standardized combined water deprivation/3% saline infusion test was performed and terminated when serum sodium exceeded 147 mmol/L. Circulating copeptin and AVP levels were measured regularly throughout the test. Final diagnosis was based on the water deprivation/saline infusion test results, clinical information, and the treatment response. RESULTS Fifty-five patients were enrolled (11 with complete central DI, 16 with partial central DI, 18 with PP, and 10 with nephrogenic DI). Without prior thirsting, a single baseline copeptin level >21.4 pmol/L differentiated nephrogenic DI from other etiologies with a 100% sensitivity and specificity, rendering a water deprivation testing unnecessary in such cases. A stimulated copeptin >4.9 pmol/L (at sodium levels >147 mmol/L) differentiated between patients with PP and patients with partial central DI with a 94.0% specificity and a 94.4% sensitivity. A stimulated AVP >1.8 pg/mL differentiated between the same categories with a 93.0% specificity and a 83.0% sensitivity. LIMITATION This study was limited by incorporation bias from including AVP levels as a diagnostic criterion. CONCLUSION Copeptin is a promising new tool in the differential diagnosis of the polyuria-polydipsia syndrome, and a valid surrogate marker for AVP. Primary Funding Sources: Swiss National Science Foundation, University of Basel.

Differential diagnosis of the honey bee trypanosomatids Crithidia mellificae and Lotmaria passim

Trypanosomatids infecting honey bees have been poorly studied with molecular methods until recently. After the description of Crithidia mellificae (Langridge and McGhee, 1967) it took about forty years until molecular data for honey bee trypanosomatids became available and were used to identify and describe a new trypanosomatid species from honey bees, Lotmaria passim (Evans and Schwarz, 2014). However, an easy method to distinguish them without sequencing is not yet available. Research on the related bumble bee parasites Crithidia bombi and Crithidia expoeki revealed a fragment length polymorphism in the internal transcribed spacer 1 (ITS1), which enabled species discrimination. In search of fragment length polymorphisms for differential diagnostics in honey bee trypanosomatids, we studied honey bee trypanosomatid cell cultures of C. mellificae and L. passim. This research resulted in the identification of fragment length polymorphisms in ITS1 and ITS1-2 markers, which enabled us to develop a diagnostic method to differentiate both honey bee trypanosomatid species without the need for sequencing. However, the amplification success of the ITS1 marker depends probably on the trypanosomatid infection level. Further investigation confirmed that L. passim is the dominant species in Belgium, Japan and Switzerland. We found C. mellificae only rarely in Belgian honey bee samples, but not in honey bee samples from other countries. C. mellificae was also detected in mason bees (Osmia bicornis and Osmia cornuta) besides in honey bees. Further, the characterization and comparison of additional markers from L. passim strain SF (published as C. mellificae strain SF) and a Belgian honey bee sample revealed very low divergence in the 18S rRNA, ITS1-2, 28S rRNA and cytochrome b sequences. Nevertheless, a variable stretch was observed in the gp63 virulence factor.

Dementia with lewy bodies--diagnosis and treatment

Dementia with Lewy bodies (DLB) accounts for 15-20% of all autopsy confirmed dementias in old age. Characteristic histopathological changes are intracellular Lewy bodies and Lewy neurites, with abundant senile plaques but sparse neurofibrillary tangles. Core clinical features are fluctuating cognitive impairment, persistent visual hallucinations and extrapyramidal motor symptoms (parkinsonism). One of these core features has to be present for a diagnosis of possible DLB, and two for probable DLB. Supportive features are repeated falls, syncope, transient loss of consciousness, neuroleptic sensitivity, delusions and hallucinations in other modalities. DLB is clinically under-diagnosed and frequently misclassified as systemic delirium or dementia due to Alzheimer's disease or cerebrovascular disease. Therapeutic approaches to DLB can pose difficult dilemmas in pharmacological management. Neuroleptic medication is relatively contraindicated because some patients show severe neuroleptic sensitivity, which is associated with increased morbidity and mortality. Antiparkinsonian medication has the potential to exacerbate psychotic symptoms and may be relatively ineffective at relieving extrapyramidal motor symptoms. Recently there is converging evidence that treatment with cholinesterase inhibitors can offer a safe alternative for the symptomatic treatment of cognitive and neuropsychiatric features in DLB. This review will focus on the clinical characteristics of DLB, its differential diagnosis and on possible management strategies.

Diagnosis and management of filler adverse effects: an algorithm.

Fillers are frequently used in beautifying procedures. Despite major advancements of the chemical and biological features of injected materials, filler-related adverse events may occur, and can substantially impact the clinical outcome. Filler granulomas become manifest as visible grains, nodules, or papules around the site of the primary injection. Early recognition and proper treatment of filler-related complications is important because effective treatment options are available. In this report, we provide a comprehensive overview of the differential diagnosis and diagnostics and develop an algorithm of successful therapy regimens.

Diagnosis of diabetes insipidus observed in Swiss Duroc boars

Background Diabetes insipidus (DI) is a rare disease in humans and animals, which is caused by the lack of production, malfunction or dysfunction of the distal nephron to the antidiuretic effect of the antidiuretic hormone (ADH). Diagnosis requires a thorough medical history, clinical examination and further laboratory confirmation. This case report describes the appearance of DI in five Duroc boars in Switzerland. Case presentation Two purebred intact Duroc boars at the age of 8 months and 1.5 years, respectively, with a history of polyuric and polydipsic symptoms had been referred to the Swine Clinic in Berne. Based on the case history, the results of clinical examination and the analysis of blood and urine, a tentative diagnosis of DI was concluded. Finally, the diagnosis was confirmed by findings from a modified water deprivation test, macroscopic examinations and histopathology. Following the diagnosis, three genes known to be involved in inherited DI in humans were analyzed in order to explore a possible genetic background of the affected boars. Conclusion The etiology of DI in pigs is supposed to be the same as in humans, although this disease has never been described in pigs before. Thus, although occurring only on rare occasions, DI should be considered as a differential diagnosis in pigs with polyuria and polydipsia. It seems that a modified water deprivation test may be a helpful tool for confirming a diagnosis in pigs. Since hereditary forms of DI have been described in humans, the occurrence of DI in pigs should be considered in breeding programs although we were not able to identify a disease associated mutation.

Serological diagnosis of echinococcosis: the diagnostic potential of native antigens

PURPOSE: Human alveolar (AE) and cystic echinococcosis (CE) caused by the metacestode stages of Echinococcus multilocularis and E. granulosus, respectively, lack pathognomonic clinical signs. Diagnosis therefore relies on the results of imaging and serological studies. The primary goal of this study was to evaluate the efficacy of several easy-to-produce crude or partially purified E. granulosus and E. multilocularis metacestode-derived antigens as tools for the serological diagnosis and differential diagnosis of patients suspicious for AE or CE. METHODS: The sera of 51 treatment-naïve AE and 32 CE patients, 98 Swiss blood donors and 38 patients who were initially suspicious for echinococcosis but suffering from various other liver diseases (e.g., liver neoplasia, etc.) were analysed. RESULTS: According to the results of enzyme-linked immunosorbent assays (ELISA), metacestode-derived antigens of E. granulosus had sensitivities varying from 81 to 97% and >99.9% for the diagnosis of CE and AE, respectively. Antigens derived from E. multilocularis metacestodes had sensitivities ranging from 84 to 91% and >99.9% for the diagnosis of CE and AE, respectively. Specificities ranged from 92 to >99.9%. Post-test probabilities for the differential diagnosis of AE from liver neoplasias, CE from cystic liver lesions, and screening for AE in Switzerland were around 95, 86 and 2.2%, respectively. Cross-reactions with antibodies in sera of patients with other parasitic affections (fasciolosis, schistosomosis, amebosis, cysticercosis, and filarioses) did occur at variable frequencies, but could be eliminated through the use of confirmatory testing. CONCLUSIONS: Different metacestode-derived antigens of E. granulosus and E. multilocularis are valuable, widely accessible, and cost-efficient tools for the serological diagnosis of echinococcosis. However, confirmatory testing is necessary, due to the lack of species specificity and the occurrence of cross-reactions to other helminthic diseases.

Ventricular enlargement due to acute hypernatremia in a patient with a ventriculoperitoneal shunt

Patients requiring CSF shunts frequently have comorbidities that can influence water and electrolyte balances. The authors report on a case involving a ventriculoperitoneal shunt in a patient who underwent intravenous hyperhydration and withdrawal of vasopressin substitution prior to scheduled high-dose chemotherapy regimen for a metastatic suprasellar germinoma. After acute neurological deterioration, the patient underwent CT scanning that demonstrated ventriculomegaly. A shunt tap revealed no flow and negative opening pressure. Due to suspicion of proximal shunt malfunction, the comatose patient underwent immediate surgical exploration of the ventricle catheter, which was found to be patent. However, acute severe hypernatremia was diagnosed during the procedure. After correction of the electrolyte disturbances, the patient regained consciousness and made a good recovery. Although rare, the effects of acute severe hypernatremia on brain volume and ventricular size should be considered in the differential diagnosis of ventriculoperitoneal shunt failure.

Oncocytic ependymoma: a new morphological variant of high-grade ependymal neoplasm composed of mitochondrion-rich epithelioid cells

Oncocytomas are defined as tumors containing in excess of 50% large mitochondrion-rich cells, irrespective of histogenesis and dignity. Along the central neuraxis, oncocytomas are distinctly uncommon but relevant to the differential diagnosis of neoplasia marked by prominent cytoplasmic granularity. We describe an anaplastic ependymoma (WHO grade III) with a prevailing oncocytic component that was surgically resected from the right fronto-insular region of a 43-year-old female. Preoperative imaging showed a fairly circumscribed, partly cystic, contrast-enhancing mass of 2 cm × 2 cm × 1.7 cm. Histology revealed a biphasic neoplasm wherein conventional ependymal features coexisted with plump epithelioid cells replete with brightly eosinophilic granules. Whereas both components displayed an overtly ependymal immunophenotype, including positivity for S100 protein and GFAP, as well as "dot-like" staining for EMA, the oncocytic population also tended to intensely react with the antimitochondrial antibody 113-1. Conversely, failure to bind CD68 indicated absence of significant lysosomal storage. Negative reactions for both pan-cytokeratin (MNF 116) and low molecular weight cytokeratin (CAM 5.2), as well as synaptophysin and thyroglobulin, further assisted in ruling out metastatic carcinoma. In addition to confirming the presence of "zipper-like" intercellular junctions and microvillus-bearing cytoplasmic microlumina, electron microscopy allowed for the pervasive accumulation of mitochondria in tumor cells to be directly visualized. A previously not documented variant, oncocytic ependymoma, is felt to add a reasonably relevant novel item to the differential diagnosis of granule-bearing central nervous system neoplasia, in particular oncocytic meningioma, granular cell astrocytoma, as well as metastatic deposits by oncocytic malignancies from extracranial sites.

INI1 (BAF 47) immunohistochemistry is an essential diagnostic tool for children with hepatic tumors and low alpha fetoprotein

Malignant rhabdoid tumor (MRT) of the liver is a rare malignancy with grave prognosis. This entity should be considered in the differential diagnosis of any aggressive liver tumor with low levels of alpha fetoprotein. We report 2 cases of hepatic MRT presenting in infancy. In these 2 cases, we show that loss of INI1 facilitates making the correct diagnosis of primary hepatic MRT utilizing BAF 47 (INI1 gene product) immunostains. Difficulty encountered in making this rare diagnosis, including the need for repeated biopsies, can be avoided if MRT is considered in the differential diagnosis early on and BAF 47 immunohistochemistry is ordered.

Meningocerebral angiodysplasia with metanephric induction failure: Broadening the spectrum of an emerging maldevelopmental syndrome

The uncommon simultaneous occurrence of an exuberant, angioma-like proliferation of superficial cerebral microvessels along with absence of the kidneys has been proposed to constitute a syndromic complex for which the term "meningocerebral angiodysplasia (or angiomatosis) with renal agenesis" (MCA-RA) is being descriptively used. We observed this constellation in one of a pair of dichorionic male twins following postpartal death in the 38th week of pregnancy. General autopsy revealed rudimentary metanephric anlagen made up of few residual glomeruli, cysts lined by flattened tubular epithelium, and islands of cartilage - corresponding to renal aplastic dysplasia. Largely inconspicuous with respect to its gyral pattern, as well as the configuration of the ventricular system, the brain microscopically showed extensive replacement of the cortex by a lattice of proliferating capillaries with necrosis of the intervening parenchyma. Minute foci of calcified necrosis were scattered in the deep subcortical white matter as well, while the ventricular ependyma and the subventricular germ cell layer remained remarkably intact. The cerebellum and brain stem appeared unaffected as well. Karyotyping of skin fibroblasts indicated a normal chromosome set of 46XY without gross structural anomalies. We interpret these findings as ones apt to being reasonably accommodated within the spectrum of MCA-RA. Although exceedingly rare, accurate identification of individual cases of MCA-RA is relevant both to differential diagnosis from its prognostically different look-alike "proliferative vasculopathy and hydranencephaly-hydrocephaly" (PVHH), and to refine the nosology of unconventional pediatric vascular malformations, for which the rather nonspecific label "angiodysgenetic necrotizing encephalopathy" is still commonly used.

Manifestation of a sellar hemangioblastoma due to pituitary apoplexy: a case report

Introduction Hemangioblastomas are rare, benign tumors occurring in any part of the nervous system. Most are found as sporadic tumors in the cerebellum or spinal cord. However, these neoplasms are also associated with von Hippel-Lindau disease. We report a rare case of a sporadic sellar hemangioblastoma that became symptomatic due to pituitary apoplexy. Case presentation An 80-year-old, otherwise healthy Caucasian woman presented to our facility with severe headache attacks, hypocortisolism and blurred vision. A magnetic resonance imaging scan showed an acute hemorrhage of a known, stable and asymptomatic sellar mass lesion with chiasmatic compression accounting for our patient's acute visual impairment. The tumor was resected by a transnasal, transsphenoidal approach and histological examination revealed a capillary hemangioblastoma (World Health Organization grade I). Our patient recovered well and substitutional therapy was started for panhypopituitarism. A follow-up magnetic resonance imaging scan performed 16 months postoperatively showed good chiasmatic decompression with no tumor recurrence. Conclusions A review of the literature confirmed supratentorial locations of hemangioblastomas to be very unusual, especially within the sellar region. However, intrasellar hemangioblastoma must be considered in the differential diagnosis of pituitary apoplexy.

[Sarcomas and mixed mesodermal tumors of the uterus]

Malignant mesodermal tumors of the uterus are an inhomogenous group of uterine malignancies with different pathogenesis, clinical presentation and prognosis. These rare tumors represent approximately 1 % of all uterine malignancies. The aggressive carcinosarcomas or mixed muellerian tumors are defined by mixed malignant epithelial and malignant mesodermal histopathology and are of the same precursor cell origin like endometrial cancer. Thus, carcinosarcomas were reclassified by the FIGO as an aggressive type of endometrial cancer and treated like type II endometrial cancer. Adenosarcomas are also mixed tumors with benign epithelial proliferation and malignant mesodermal cell growth, have a good prognosis and represent less than 5 % of all mesodermal uterine malignancies. Besides carcinosarcomas, the pure mesodermal leiomyosarcomas are the most common mesodermal malignancies. Patients with leiomyosarcamos are usually perimenopausal, and although more than half of the patients present with symptoms, diagnosis occurs incidentally in most cases in final histopathologic workup of an excised putative myoma or uterus. Adequate anamnesis, gynecologic examination and careful imaging by transvaginal ultrasound in the preoperative setting might hint to correct differential diagnosis in many cases. Overall the prognosis of uterine leiomyomas is poor. Malignancies of the endometrial stroma are very rare and divided in two subgroups, the mostly estrogen receptor positive endometrial stromal sarcoma, which occur preferably in premenopausal women and show a favorable prognosis, and the very aggressive undifferentiated endometrial sarcomas. The more rare undifferentiated endometrial sarcomas occur in postmenopausal women and most patients die in the first two years after diagnosis. Risk stratification of preoperative differential diagnosis requires improvements and the correct histopathologic workup of mesodermal uterine malignancies is still a challenge for pathologists.

[Abdominal pain in the general doctor's practice]

Abdominal pain is a frequent symptom and in the majority of cases the underlying disease is not life threatening. The general practitioner's first task is to differentiate between inflammatory and other diseases. The patient's history, the clinical examination and laboratory tests form the basis for the differential diagnosis. A sonography is the first additional examination in the vast majority of the cases. Accidentally found gallstones usually do not require surgical intervention. Surgery in asymptomatic patients should be limited to gallbladder polyps and patients with calcifications in their gallbladder wall.

Giant Cardiac Fibroma: An Unusual Cause of Failure to Thrive

Cardiac fibromas are extremely rare in the general pediatric population and may present with a wide spectrum of clinical signs, including life-threatening arrhythmias and sudden death. We report a 14-month-old boy who presented with failure to thrive as the only symptom. Echocardiography showed a large cardiac fibroma in the right ventricle. Cardiac magnetic resonance imaging confirmed the diagnosis. After complete surgical tumor resection, the boy showed normal catch-up growth. This case underlines the diversity of clinical features of cardiac tumors, which implies that they should be considered early in the differential diagnosis of infants with failure to thrive.

Development of PCR/dot blot assay for specific detection and differentiation of taeniid cestode eggs in canids

We report the development of a colourimetric PCR/dot blot assay targeting the mitochondrial gene NADH dehydrogenase subunit 1 (nad1) for differential diagnosis of taeniid eggs. Partial sequences of the cestode nad1 gene were aligned and new primers were designed based on conserved regions. Species-specific oligonucleotide probes (S-SONP) for canine taeniid cestodes were then designed manually based on the variable region between the conserved primers. Specifically, S-SONP were designed for the Taenia crassiceps, T. hydatigena, T. multiceps, T. ovis, T. taeniaeformis, Echinococcus granulosus (genotype 1), E. multilocularis and E. vogeli. Each probe showed high specificity as no cross-hybridisation with any amplified nad1 fragment was observed. We evaluated the assay using 49 taeniid egg-positive samples collected from dogs in Zambia. DNA from 5 to 10 eggs was extracted in each sample. Using the PCR/dot blot assay, the probes successfully detected PCR products from T. hydatigena in 42 samples, T. multiceps in 3 samples, and both species (mixed infection) in the remaining 4 samples. The results indicate that the PCR/dot blot assay is a reliable alternative for differential diagnosis of taeniid eggs in faecal samples.