New nonculture-based methods for the diagnosis of invasive candidiasis.

PURPOSE OF REVIEW: Invasive candidiasis is a severe infectious complication occurring mostly in onco-hematologic and surgical patients. Its conventional diagnosis is insensitive and often late, leading to a delayed treatment and a high mortality. The purpose of this article is to review recent contributions in the nonconventional diagnostic approaches of invasive candidiasis, both for the detection of the epidose and the characterization of the etiologic agent. RECENT FINDINGS: Antigen-based tests to detect invasive candidiasis comprise a specific test, mannan, as well as a nonspecific test, beta-D-glucan. Both have a moderate sensitivity and a high specificity, and cannot be recommended alone as a negative screening tool or a positive syndrome driven diagnostic tool. Molecular-based tests still have not reached the stage of rapid, easy to use, standardized tests ideally complementing blood culture at the time of blood sampling. New tests (fluorescence in-situ hybridization or mass spectrometry) significantly reduce the delay of identification of Candida at the species level in positive blood cultures, and should have a positive impact on earlier appropriate antifungal therapy and possibly on outcome. SUMMARY: Both antigen-based and molecular tests appear as promising new tools to complement and accelerate the conventional diagnosis of invasive candidiasis with an expected significant impact on earlier and more focused treatment and on prognosis.

Hypertonie oculaire dans l'orbitopathie dysthyroidienne: considerations physiopathologiques, diagnostiques et therapeutiques. A propos de trois cas significatifs. [Intraocular high pressure in thyroid-associated orbitopathy: physiopathological mechanisms, diagnosis, and management. Three case reports]

PURPOSE: To determine the mechanisms and treatment of ocular hypertension in patients with thyroid-associated orbitopathy and to differenciate it from glaucomatous damage. DESIGN: Three case reports. METHODS: Retrospective review of clinical findings, course, and treatment of the three patients. RESULTS: Elevated intraocular pressure in thyroid-associated orbitopathy observed in the three cases may involve different physiopathological abnormalities such as disturbances of venous circulation, compression by infiltrative muscles, and long corticosteroid use. In the first two cases, defects demonstrated in the perimetry are in consistent with glaucomatous damage. In the third case, visual field abnormalities may be compatible with a glaucomatous disease, but all defects resolved after therapy. Treatement was of the greatest difficulty for the three cases, associating antiglaucomatous medication, steroids, orbital radiotherapy, orbital decompression and extraocular muscle surgery. Intraocular pressure was controlled in all cases. CONCLUSIONS: Elevated intraocular pressure in thyroid-associated orbitopathy is distinguished from glaucomatous disease by its physiopathological mechanisms, clinical course, visual field defects, and treatment. The management of this hypertension is closely related to the treatment of dysthyroid orbitopathy.

Establishment of HEV RNA reverse transcriptase PCR assays for the diagnosis of acute and chronic hepatitis E

Background and aim: H epatitis E v irus (HEV) infection has emerged as a c ause o f travel-related a nd autochthonous a cute hepatitis as well as chronic hepatitis in immunosuppressed patients. While t ravel-related cases a re c aused primarily b y infections w ith HEV of g enotype 1 ( HEV-1), autochthonous c ases a nd chronic cases a re d ue t o genotype 3 (HEV-3), which is s hared between humans and diverse animal species. The aim of this study was to establish HEV RNA detection assays f or q uantitative v iral load testing and genotyping. Methods: V iral RNA was p urified from plasma or s erum a nd converted to cDNA prior to (1) multiplex real-time PCR for HEV RNA quantification and (2) multiplex PCR coupled to DNA sequencing for HEV genotype determination. Real-time PCR was d esigned to match a ll known HEV genotypes available i n Genbank while PCR was designed using conserved primers flanking a variable region of the HEV RNA. Results: In a validation panel, the newly developed assays allowed for the reliable detection and genotyping of HEV-1 or HEV-3. Cases of t ravel-related and a utochthonous a cute h epatitis E a s well a s chronic hepatitis E i n immunosuppressed patients have b een identified using t hese a ssays a nd will be p resented in detail. Anti- HEV antibodies were n egative i n three well-characterized patients with chronic hepatitis E after organ transplantation. Conclusions: We developed and validated a quantitative HEV RNA detection assay that c an now be o ffered on a r outine basis (www.chuv.ch/imul/imu-collaborations-viral_hepatitis). Genotyping can also be offered on selected cases. HEV RNA detection is key in diagnosing chronic hepatitis E i n immunosuppressed patients with unexplained transaminase elevations, as serology can be negative in these patients.

Diagnosis and management of enophthalmos

Enophthalmos is a relatively frequent and misdiagnosed clinical sign in orbital diseases. The knowledge of the different etiologies of enophthalmos and its adequate management are important, because in some cases, it could be the first sign revealing a life-threatening disease. This article provides a comprehensive review of the pathophysiology, evaluation, and management of enophthalmos. The main etiologies, such as trauma, chronic maxillary atelectasis (silent sinus syndrome), breast cancer metastasis, and orbital varix, will be discussed. Its objective is to enable the reader to recognize, assess, and treat the spectrum of disorders causing enophthalmos.

Socioeconomic gradients in mortality in the oldest old: a review.

This review aims at identifying gaps in knowledge on socioeconomic gradients in mortality in the oldest old. The authors review literature on oldest old population with a focus on unanswered questions: do socioeconomic status (SES) gradients in mortality persist after 80; does the magnitude of the gradient change as compared with younger populations; which socioeconomic/socio-demographic determinants should be used in this population with specific characteristics (e.g., with respect to sex ratio and household type)? Results are often inconsistent while conclusions drawn by selected studies are generally limited by the difficulty of disentangling the effects of age and cohort, and of generalizing results observed in preponderantly small, selected samples (which typically exclude institutionalized persons). Future research should explore the effects of socio-demographic indicators other than education and social class (e.g., marital status, loss of the partner) and adequately differentiate the social position of oldest old women. The authors recommend that research applies a life-course perspective combined with an interdisciplinary perspective to improve our understanding of the SES gradients in later life. Research is needed to elucidate which causal pathways depending on SES in younger age impact on mortality in higher ages up to oldest old.

RT-PCR diagnosis of patients with acute nonlymphocytic leukemia and inv(16)(p13q22) and identification of new alternative splicing in CBFB-MYH11 transcripts.

As acute nonlymphocytic leukemia (ANLL) with inv(16) (p13q22) or t(16;16)(p13;q22) has been shown to result from the fusion of transcription factor subunit core binding factor (CBFB) to a myosin heavy chain (MYH11), we sought to design methods to detect this rearrangement using reverse transcriptase-polymerase chain reaction (RT-PCR). In all of 27 inv(16)(p13q22) and four t(16;16)(p13;q22) cases tested, a chimeric CBFB-MYH11 transcript coding for an in-frame fusion protein was detected. In a more extensive RT-PCR analysis with different primer pairs, we detected a second new chimeric CBFB-MYH11 transcript in 10 of 11 patients tested. The CBFB-MYH11 reading frame of the second transcript was maintained in one patient but not in the others. We show that the different CBFB-MYH11 transcripts in one patient arise from alternative splicing. Translation of the transcript in which the CBFB-MYH11 reading frame is not maintained leads to a slightly truncated CBFB protein.

Congenital hydrocephalus--prevalence, prenatal diagnosis and outcome of pregnancy in four European regions.

OBJECTIVE: To describe prevalence, prenatal diagnosis and outcome for fetuses and infants with congenital hydrocephalus. METHODS: Data were taken from four European registries of congenital malformations (EUROCAT). The registries included are based on multiple sources of information and include information about livebirths, fetal deaths with GA > or = 20 weeks and terminations of pregnancy for fetal anomaly (TOPFA). All cases from the four registries diagnosed with congenital hydrocephalus and born in the period 1996-2003 were included in the study. Cases with hydrocephalus associated with neural tube defects were not included in the study. RESULTS: Eighty-seven cases with congenital hydrocephalus were identified during the study period giving an overall prevalence of 4.65 per 10,000 births. There were 41 livebirths (47%), four fetal deaths (5%) and 42 TOPFA (48%). Nine percent of all cases were from a multiple pregnancy. Additional non-cerebral major malformations were diagnosed in 38 cases (44%) and karyotype anomalies in eight cases (9%). Median GA at TOPFA was 21 weeks. Among livebirths 61% were diagnosed prenatally at a median GA of 31 weeks (range 17-40 weeks) and median GA at birth was 37 weeks. Fourteen liveborn infants (34%) died within the first year of life with the majority of deaths during the first week after birth. CONCLUSION: Congenital hydrocephalus is a severe congenital malformation often associated with other congenital anomalies. CH is often diagnosed prenatally, although sometimes late in pregnancy. A high proportion of affected pregnancies result in termination for severe fetal anomaly and there is a high mortality in livebirths.

Diagnostic value of soluble CD14 subtype (sCD14-ST) presepsin for the postmortem diagnosis of sepsis-related fatalities.

The first aim of this study was to assess the diagnostic performance of presepsin (sCD14-ST) in postmortem serum from femoral blood compared to procalcitonin (PCT) to detect sepsis-related fatalities. The second aim was to compare sCD14-ST levels found in postmortem serum to the values in pericardial fluid to investigate the usefulness of the latter as an alternative biological fluid. Two study groups were formed, a sepsis-related fatalities group and a control group. Radiology (unenhanced CT scans and postmortem angiographies), autopsies, histology, neuropathology, and toxicology as well as other postmortem biochemistry investigations were performed in all cases. Microbiological investigations on right cardiac blood were carried out exclusively in septic cases. The results of this study indicated that postmortem serum PCT and sCD14-ST levels, individually considered, allowed septic cases to be identified. Even though increases in both PCT and sCD14-ST concentrations were observed in the control cases, coherent PCT and sCD14-ST results in cases with suspected sepsis allowed the diagnosis to be confirmed. Conversely, no relevant correlation was identified between postmortem serum and pericardial fluid sCD14-ST levels in either the septic or control groups.