Molecular Epidemiology of Blastomyces gilchristii Clusters, Minnesota, USA.

We characterized 2 clusters of blastomycosis cases in Minnesota, USA, using whole-genome sequencing and single-nucleotide polymorphism analyses. Blastomyces gilchristii was confirmed as the cause of infection. Genomic analyses corresponded with epidemiologic findings for cases of B. gilchristii infections, demonstrating the utility of genomic methods for future blastomycosis outbreak investigations.

Treatment Practices for Adults With Candidemia at 9 Active Surveillance Sites-United States, 2017-2018.

BACKGROUND: Candidemia is a common opportunistic infection causing substantial morbidity and mortality. Because of an increasing proportion of non-albicans Candida species and rising antifungal drug resistance, the Infectious Diseases Society of America (IDSA) changed treatment guidelines in 2016 to recommend echinocandins over fluconazole as first-line treatment for adults with candidemia. We describe candidemia treatment practices and adherence to the updated guidelines. METHODS: During 2017-2018, the Emerging Infections Program conducted active population-based candidemia surveillance at 9 US sites using a standardized case definition. We assessed factors associated with initial antifungal treatment for the first candidemia case among adults using multivariable logistic regression models. To identify instances of potentially inappropriate treatment, we compared the first antifungal drug received with species and antifungal susceptibility testing (AFST) results from initial blood cultures. RESULTS: Among 1835 patients who received antifungal treatment, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment. Cirrhosis (adjusted odds ratio = 2.06; 95% confidence interval, 1.29-3.29) was the only underlying medical condition significantly associated with initial receipt of an echinocandin (versus fluconazole). More than one-half (n = 304, 56.0%) of patients initially treated with fluconazole grew a non-albicans species. Among 265 patients initially treated with fluconazole and with fluconazole AFST results, 28 (10.6%) had a fluconazole-resistant isolate. CONCLUSIONS: A substantial proportion of patients with candidemia were initially treated with fluconazole, resulting in potentially inappropriate treatment for those involving non-albicans or fluconazole-resistant species. Reasons for nonadherence to IDSA guidelines should be evaluated, and clinician education is needed.

Live births following Karyomapping of human blastocysts: experience from clinical application of the method.

The clinical application of a new, widely applicable method known as Karyomapping to carry out a total of 55 clinical cases of preimplantation genetic diagnosis (PGD) for single gene disorders is reported. Conventional polymerase chain reaction (PCR) testing was carried out in parallel to the new method for all cases. Clinical application of Karyomapping in this study resulted in three live births and nine clinical pregnancies out of 20 cases with a transfer. All in all, results presented in this study indicate that Karyomapping is a highly efficient, accurate and robust method for PGD of single gene disorders. Karyomapping can offer a more comprehensive assessment of the region of interest than conventional PCR analysis, allowing for more embryos to receive diagnosis (99.6% versus 96.8%), whereas its wide applicability reduces substantially the time that patients have to wait before starting their in vitro fertilization (IVF) cycle. Nonetheless, inclusion of elements of conventional PCR methodology, such as direct mutation detection, may be required in cases in which the gene of interest is in a region with reduced single nucleotide polymorphism (SNP) coverage (e.g. telomeric regions), when offering PGD for consanguineous couples, or in cases where no samples from additional family members are available.

Validation of array comparative genome hybridization for diagnosis of translocations in preimplantation human embryos.

Fluorescent in-situ hybridization (FISH) for preimplantation genetic diagnosis (PGD) of structural chromosome abnormalities has limitations, including carrier testing, inconclusive results and limited aneuploidy screening. Array comparative genome hybridization (CGH) was used in PGD cases for translocations. Unbalances could be identified if three fragments were detectable. Smallest detectable fragments were ∼6 Mbp and ∼5 Mbp for blastomeres and trophectoderm, respectively. Cases in which three or more fragments were detectable by array CGH underwent PGD by FISH and concordance was obtained in 53/54 (98.1%). The error rate for array CGH was 1.9% (1/54). Of 402 embryos analysed, 81 were normal or balanced, 92 unbalanced but euploid, 123 unbalanced and aneuploid and 106 balanced but aneuploid. FISH with additional probes to detect other aneuploidies would have missed 28 abnormal embryos in the reciprocal group and 10 in the Robertsonian group. PGD cases (926) were retrospectively reviewed for reciprocal translocations performed by FISH to identify which could have been analysed by array CGH. This study validates array CGH in PGD for translocations and shows that it can identify all embryos with unbalanced reciprocal and Robertsonian translocations. Array CGH is a better approach than FISH since it allows simultaneous screening of all chromosomes for aneuploidy.

I thought I was being blessed.

This is a clinical case presentation of a Catholic hospital chaplain, who, like thousands of deeply wounded children from around the world, was sexually abused by his parish priest. Believing he had received 'a special blessing' contributed to his denial, rationalization and ultimate identification with his abuser. For 58 years, having repressed his earlier experience, this man lived as a Catholic cleric, abusing others. Entering analysis provided him with an opportunity to work with his dreams and memories. Analysis enabled him to consciously come to terms with and benefit from a future that fostered his individuation and allowed him to become a spokesman for the rehabilitation of others suffering a similar fate.

Ceci est la présentation d'un cas clinique, celui d'un aumônier catholique des hôpitaux qui, comme des milliers d'enfants profondément blessés dans le monde entier, fut abusé sexuellement par le prêtre de sa paroisse. Sa croyance - qu'il avait reçu « une bénédiction spéciale ¼ - contribua à son déni, à sa rationalisation et finalement à son identification avec son agresseur. Pendant 58 années, ayant réprimé ses expériences précoces, cet homme a vécu comme un membre du clergé catholique, abusant d'autres personnes. Entrer en analyse lui a fourni l'opportunité de travailler avec ses rêves et ses souvenirs. L'analyse l'a rendu capable de faire face consciemment à un avenir qui soutiendrait son individuation et lui permettrait de devenir un porte-parole pour la réhabilitation d'autres personnes victimes d'un même destin.

Esta es la presentación de un caso clínico de un capellán católico de un hospital, quien, como miles de niños profundamente heridos de alrededor del mundo, fue abusado sexualmente por el sacerdote de su parroquia. La creencia de que había recibido 'una bendición especial' contribuyó a su negación, racionalización, y a la identificación con su abusador. Habiendo reprimido esta experiencia temprana, este hombre vivió como un clérigo católico, abusando de otros, durante 58 años. El inicio de análisis le dio la oportunidad de trabajar con sus sueños y memorias. El análisis le permitió una confrontación consciente y también la posibilidad de beneficiarse de un futuro que favorezca su individuación, permitiéndole devenir en portavoz para la rehabilitación de otros que sufren destinos similares.

Esta é uma apresentação de caso clínico de um capelão do hospital católico, que, como milhares de crianças profundamente feridas de todo o mundo, foi abusada sexualmente por seu pároco. Acreditar que ele havia recebido "uma bênção especial" contribuiu para sua negação, racionalização e identificação final com seu agressor. Por 58 anos, tendo reprimido sua experiência anterior, esse homem viveu como clérigo católico, abusando dos outros. Entrar na análise proporcionou a ele a oportunidade de trabalhar com seus sonhos e memórias. A análise permitiu que ele concordasse conscientemente e se beneficiasse de um futuro que promoveu sua individuação e lhe permitiu se tornar um porta-voz da reabilitação de outros que sofrem um destino semelhante.

Candida auris Direct Detection from Surveillance Swabs, Blood, and Urine Using a Laboratory-Developed PCR Method.

Candida auris is an emerging fungal pathogen with cases reported in countries around the world and in 19 states within the United States as of August 2020. The CDC has recommended that hospitals perform active surveillance upon admission for patients with the appropriate risk factors. Currently, active surveillance requires that local hospitals send surveillance swabs to a public health laboratory for analysis. In this work, a real-time PCR assay was developed for the specific detection of C. auris from surveillance swabs, blood, and urine to enable rapid detection of this pathogen. The assay uses commercially available primers and reporter probes and it was verified on the LightCycler 480 PCR platform. Contrived specimens and prospectively collected composite groin/axilla surveillance swabs were used to validate the assay. The performance of the PCR assay on surveillance swabs was also compared to a second PCR assay targeting C. auris that was performed at the Minnesota Department of Health-Public Health Laboratory (MDH-PHL). Our PCR assay is able to detect and differentiate C. auris from closely related Candida species such as C. duobushaemulonii, C. haemulonii, and C. pseudohaemulonii on the basis of melting curve temperature differences.

Preimplantation genetic diagnosis (PGD) improves pregnancy outcome for translocation carriers with a history of recurrent losses.

OBJECTIVE: To determine if preimplantation genetic diagnosis (PGD) for translocation carriers with three or more pregnancy losses reduces loss rates. DESIGN: Retrospective review of data. SETTING: Preimplantation genetic diagnosis laboratory servicing IVF groups. PATIENT(S): Patients (n = 192) undergoing PGD for either a reciprocal translocation or Robertsonian translocation who had three or more previous pregnancy losses. INTERVENTION(S): Preimplantation genetic diagnosis for translocations. MAIN OUTCOME MEASURE(S): Pregnancy loss rate, pregnancy success rate defined as delivery of at least one child or an ongoing pregnancy in the third trimester, and length of time to success. RESULT(S): Pregnancy loss rate was significantly reduced to 13% post-PGD compared with 88.5% in previous non-PGD pregnancies and to 35% to 64% from naturally conceived pregnancies as reported in the literature. Pregnancy success rate was 87%. Conception occurred after an average of 1.4 cycles or <4 months. CONCLUSION(S): Individuals with translocations who have experienced three or more losses benefit from PGD by realizing a significant reduction in loss rate and improvement in rate of success of pregnancy. Length of time to conceive is also dramatically reduced compared with data in the literature for similar populations not undergoing PGD.

Preimplantation genetic diagnosis of single-gene disorders: experience with more than 200 cycles conducted by a reference laboratory in the United States.

OBJECTIVE: To evaluate trends and outcomes from preimplantation genetic diagnosis (PGD) cycles. DESIGN: Retrospective data review. SETTING: A reference laboratory specializing in the provision of PGD services. PATIENT(S): One hundred sixty-two patients at risk of transmitting a serious monogenic disorder to their children. INTERVENTION(S): In vitro fertilization and PGD. MAIN OUTCOME MEASURE(S): Results of PGD cycles. RESULT(S): Two hundred twenty-four PGD cycles were referred by 59 different IVF centers. Forty-six different disorders were diagnosed, including several not previously diagnosed at the preimplantation stage. Cystic fibrosis was the most common reason for referral (73 cases). A diagnosis was obtained for 84.4% of tested embryos, with results available 6 to 36 hours from sample receipt. Only 10.7% of cycles had no transfer. The pregnancy rate per cycle with ET was 43.4%. CONCLUSION(S): Unlike previous reports of multiple PGD cycles, all of the cases in this study involved shipping of biopsied cells to a specialist reference laboratory for diagnosis. This approach, sometimes referred to as "transport PGD," accounts for the vast majority of PGD cycles in the United States. Preimplantation genetic diagnosis was shown to be an effective alternative to prenatal diagnosis for patients with an ethical or a religious objection to pregnancy termination and for infertile patients carrying a genetic disorder. Demand for this service at our center doubled in each of the last 4 years. Pregnancy rates per ET were encouraging, almost half of all patients undergoing their first PGD cycle achieving a birth or ongoing pregnancy.

Preimplantation genetic diagnosis significantly reduces pregnancy loss in infertile couples: a multicenter study.

OBJECTIVE: The inicidence of miscarriage is correlated with maternal age. The majority of miscarriages are chromosomally abnormal. The purpose of this study was to determine in a large population of infertility patients (>2000 cycles) if preimplantation genetic diagnosis (PGD) reduced the rate of spontaneous abortions. DESIGN: Multicenter retrospective controlled study. SETTING: One hundred IVF centers referring samples to a reference PGD laboratory. PATIENT(S): Infertile women. INTERVENTION(S): The spontaneous abortion rate after PGD was retrospectively compared to non-PGD cycles from the 2002 American Society for Reproductive Medicine-Society for Assisted Reproduction Technology report on IVF cycles. MAIN OUTCOME MEASURE(S): Spontaneous abortions and trisomic offspring rates. RESULT(S): The study included 2,279 cycles of PGD. The pregnancy rate per retrieval was 26.7% (average age 39.6). The mean pregnancy loss for the PGD group (0.167) was significantly lower than for the general IVF group (0.215) (P<.001). After PGD, the spontaneous abortion rate was 14.1% for ages 35-40, and 22.2% for women over 40, compared to 19.4% (P=.03) and 40.6% (P<.001), respectively, in controls. The clinical error rate of PGD (1.2%) was significantly lower than expected (4.7%) (P<.001). CONCLUSION(S): The data suggests that PGD significantly reduces the risk of spontaneous abortions in women undergoing IVF and PGD, particularly in women over 40. In addition, PGD may also reduce the risk of trisomic offspring.

Negligible interchromosomal effect in embryos of Robertsonian translocation carriers.

It has been suggested that translocations, and perhaps other chromosome rearrangements, disturb meiotic disjunction of chromosome pairs not involved in the translocation, resulting in non-disjunction in those chromosomes (interchromosomal effect) and predisposition to trisomy offspring. Other reports have suggested an increased risk of mosaicism and chaotic embryos in translocation carriers. This study was designed to determine if such interchromosomal effects are producing significantly more chromosome abnormalities than those expected from unbalanced gametes. For that purpose, two groups of PGD patients were compared, Robertsonian translocation carriers (RBT) and carriers of X-linked diseases (XLI), of similar age. Both groups were analysed by FISH with similar DNA probes. The results indicate that overall, the higher rate of chromosome abnormalities in the RBT group was solely due to unbalanced gametes and not to an interchromosomal effect or higher incidence of mosaicism. If unbalanced and normal were combined, this proportion was 53% in XLI and 59% in RBT. However, when specific RBT translocations were studied, only a slight increase in embryos with aneuploidy for chromosome 22 was found for the t(13;14) translocation carriers, while a higher rate of post-zygotic abnormalities was observed in the more rare RBT. In conclusion, the overall rate of non-translocation related abnormalities was not increased in the RBT group compared with the control group, but a slight interchromosomal effect may exist, as some Robertsonian translocations may be more prone to produce mosaic and chaotic embryos.

Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years and older with a history of recurrent miscarriages.

OBJECTIVE: To determine whether preimplantation genetic diagnosis (PGD) and transfer of euploid embryos would decrease spontaneous abortion rates in recurrent miscarriage (RM) patients. DESIGN: Controlled clinical study. SETTING: In vitro fertilization centers and PGD reference laboratory. PATIENT(S): Recurrent-miscarriage patients with three or more prior lost pregnancies with no known etiology. INTERVENTION(S): Biopsy of a single blastomere from each day 3 embryo, followed by fluorescence in situ hybridization analysis. MAIN OUTCOME MEASURE(S): The rate of spontaneous abortions in RM subjects undergoing PGD were compared with [1] their own a priori expectations and [2] a comparison group of women undergoing PGD for advanced maternal age (> or =35 years). RESULT(S): Before PGD, RM patients had lost 87% (262/301) of their pregnancies, with an expected loss rate of 36.5%. After, they only lost 16.7% pregnancies. This difference was mostly due to reduction in pregnancy loss in the > or =35-years age subgroup, to 12% from an expected 44.5%. CONCLUSION(S): Preimplantation genetic diagnosis aneuploidy screening has a beneficial effect on pregnancy outcome in RM couples, especially those in which the woman is aged > or =35 years. Our data indicate that PGD reduces the risk of miscarriage in RM patients to baseline levels.

Minimal neuropsychological assessment of MS patients: a consensus approach.

Cognitive impairment is common in multiple sclerosis (MS), yet patients seen in MS clinics and neurologic practices are not routinely assessed neuropsychologically. In part, poor utilization of NP services may be attributed to a lack of consensus among neuropsychologists regarding the optimal approach for evaluating MS patients. An expert panel composed of neuropsychologists and psychologists from the United States, Canada, United Kingdom, and Australia was convened by the Consortium of MS Centers (CMSC) in April, 2001. Our objectives were to: (a) propose a minimal neuropsychological (NP) examination for clinical monitoring of MS patients and research, and (b) identify strategies for improving NP assessment of MS patients in the future. The panel reviewed pertinent literature on MS-related cognitive dysfunction, considered psychometric factors relevant to NP assessment, defined the purpose and optimal characteristics of a minimal NP examination in MS, and rated the psychometric and practical properties of 36 candidate NP measures based on available literature. A 90-minute NP battery, the Minimal Assessment of Cognitive Function in MS (MACFIMS), emerged from this discussion. The MACFIMS is composed of seven neuropsychological tests, covering five cognitive domains commonly impaired in MS (processing speed/working memory, learning and memory, executive function, visual-spatial processing, and word retrieval). It is supplemented by a measure of estimated premorbid cognitive ability. Recommendations for assessing other factors that may potentially confound interpretation of NP data (e.g., visual/sensory/motor impairment, fatigue, and depression) are offered, as well as strategies for improving NP assessment of MS patients in the future.