Exposure History, Post-Exposure Prophylaxis Use, and Clinical Characteristics of Human Rabies Cases: A Twelve-Year Retrospective Review at a Tertiary Facility in Ghana.

BACKGROUND: Robust monitoring and reporting systems for rabies are lacking thus increasing the risk of underreporting. Highlighting the rabies cases brings to bear the needed urgent attention for more efforts at preventing and controlling the disease. OBJECTIVE: To describe the epidemiological characteristics of patients managed for clinical rabies at the largest referral facility in Ghana. METHODS: A retrospective single-center hospital-based chart review and data extraction were conducted for persons managed for clinical rabies infection at the Korle-Bu Teaching Hospital from January 2008 to December 2019. Data analysis was done using STATA. Descriptive statistics were used to summarize the epidemiological and clinical characteristics. Fisher's exact test, the Kruskal-Wallis test, and Spearman's correlation coefficient were used to explore significant associations. RESULTS: A total of 28 cases were recorded over the period of review. All of them died and most (68%) of them were males. Twenty-one percent of them were less than 15 years old. Their median age interquartile range (IQR) was 31 years (25.5 years) and the median incubation period for rabies (IQR) was 60 days (60 days). The source of rabies for cases was mainly dog bites. The vaccination status of all the animals could not be ascertained. Majority (80%) of the patients took neither anti-rabies vaccine nor immunoglobulin as post-exposure prophylaxis after the dog bite. The median time of admission before death (interquartile range) was 2 days (2 days). Majority (82%) of the cases were furious rabies. CONCLUSION: Attention should be directed at mass vaccination of dogs as dog bites are common. Ensuring availability and access to post-exposure prophylaxis (PEP) is also critical in averting rabies-related deaths.

CONTEXTE: Des systèmes de surveillance et de déclaration robustes pour la rage font défaut, augmentant ainsi le risque de sousdéclaration. Mettre en lumière les cas de rage suscite l'attention urgente nécessaire pour redoubler d'efforts dans la prévention et le contrôle de la maladie. OBJECTIF: Décrire les caractéristiques épidémiologiques des patients traités pour une rage clinique dans le plus grand établissement de référence au Ghana. MÉTHODES: Une revue rétrospective des dossiers médicaux et une extraction de données basées à l'hôpital ont été réalisées pour les personnes traitées pour une infection à la rage clinique à l'Hôpital d'Enseignement Korle-Bu de janvier 2008 à décembre 2019. L'analyse des données a été effectuée à l'aide de STATA. Des statistiques descriptives ont été utilisées pour résumer les caractéristiques épidémiologiques et cliniques. Le test exact de Fisher, le test de Kruskal-Wallis et le coefficient de corrélation de Spearman ont été utilisés pour explorer les associations significatives. RÉSULTATS: Un total de 28 cas ont été enregistrés sur la période examinée. Tous sont décédés et la plupart d'entre eux (68%) étaient des hommes. Vingt et un pour cent d'entre eux avaient moins de 15 ans. Leur âge médian (plage interquartile) était de 31 ans (25,5 ans) et la période d'incubation médiane de la rage (plage interquartile) était de 60 jours (60 jours). La principale source de rage pour les cas était principalement les morsures de chiens. Le statut vaccinal de tous les animaux n'a pas pu être déterminé. La majorité (80%) des patients n'ont pris ni vaccin antirabique ni immunoglobuline en prophylaxie post-exposition après la morsure de chien. Le délai médian d'admission avant le décès (plage interquartile) était de 2 jours (2 jours). La majorité (82%) des cas étaient atteints de rage furieuse. CONCLUSION: L'attention devrait être dirigée vers la vaccination de masse des chiens car les morsures de chien sont courantes. Assurer la disponibilité et l'accès à la prophylaxie post-exposition (PPE) est également crucial pour éviter les décès liés à la rage. MOTS-CLÉS: Rage, morsure de chien, post-exposition, prophylaxie, vaccination de masse.

Treatment Efficacy Score-continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials.

BACKGROUND: Difference in pathologic complete response (pCR) rate after neoadjuvant chemotherapy does not capture the impact of treatment on downstaging of residual cancer in the experimental arm. We developed a method to compare the entire distribution of residual cancer burden (RCB) values between clinical trial arms to better quantify the differences in cytotoxic efficacy of treatments. PATIENTS AND METHODS: The Treatment Efficacy Score (TES) reflects the area between the weighted cumulative distribution functions of RCB values from two trial arms. TES is based on a modified Kolmogorov-Smirnov test with added weight function to capture the importance of high RCB values and uses the area under the difference between two distribution functions as a statistical metric. The higher the TES the greater the shift to lower RCB values in the experimental arm. We developed TES from the durvalumab + olaparib arm (n = 72) and corresponding controls (n = 282) of the I-SPY2 trial. The 11 other experimental arms and control cohorts (n = 947) were used as validation sets to assess the performance of TES. We compared TES to Kolmogorov-Smirnov, Mann-Whitney, and Fisher's exact tests to identify trial arms with higher cytotoxic efficacy and assessed associations with trial arm level survival differences. Significance was assessed with a permutation test. RESULTS: In the validation set, TES identified arms with a higher pCR rate but was more accurate to identify regimens as less effective if treatment did not reduce the frequency of high RCB values, even if the pCR rate improved. The correlation between TES and survival was higher than the correlation between the pCR rate difference and survival. CONCLUSIONS: TES quantifies the difference between the entire distribution of pathologic responses observed in trial arms and could serve as a better early surrogate to predict trial arm level survival differences than pCR rate difference alone.

Sodium thiosulfate for postoperative cisplatin induced nephrotoxicity following hyperthermic intraperitoneal chemotherapy: A case report.

•Cisplatin induced nephrotoxicity can occur days after administration.•Hyperthermic intraperitoneal chemotherapy with cisplatin for ovarian cancer is increasing in utilization.•Sodium thiosulfate can be used following cisplatin induced nephrotoxicity for treatment.

B Cell Receptor Genes Associated With Tolerance Identify a Cohort of Immunosuppressed Patients With Improved Renal Allograft Graft Function.

We previously reported that two B cell receptor genes, IGKV1D-13 and IGKV4-1, were associated with tolerance following kidney transplantation. To assess the potential utility of this "signature," we conducted a prospective, multicenter study to determine the frequency of patients predicted tolerant within a cohort of patients deemed to be candidates for immunosuppressive minimization. At any single time point, 25-30% of patients were predicted to be tolerant, while 13.7% consistently displayed the tolerance "signature" over the 2-year study. We also examined the relationship of the presence of the tolerance "signature" on drug use and graft function. Contrary to expectations, the frequency of predicted tolerance was increased in patients receiving tacrolimus and reduced in those receiving corticosteroids, mycophenolate mofetil, or Thymoglobulin as induction. Surprisingly, patients consistently predicted to be tolerant displayed a statistically and clinically significant improvement in estimated glomerular filtration rate that increased over time following transplantation. These findings indicate that the frequency of patients consistently predicted to be tolerant is sufficiently high to be clinically relevant and confirm recent findings by others that immunosuppressive agents impact putative biomarkers of tolerance. The association of a B cell-based "signature" with graft function suggests that B cells may contribute to the function/survival of transplanted kidneys.

Longitudinal studies of a B cell-derived signature of tolerance in renal transplant recipients.

Biomarkers of transplant tolerance would enhance the safety and feasibility of clinical tolerance trials and potentially facilitate management of patients receiving immunosuppression. To this end, we examined blood from spontaneously tolerant renal transplant recipients and patients enrolled in two interventional tolerance trials using flow cytometry and gene expression profiling. Using a previously reported tolerant cohort as well as newly identified tolerant patients, we confirmed our previous finding that tolerance was associated with increased expression of B cell-associated genes relative to immunosuppressed patients. This was not accounted for merely by an increase in total B cell numbers, but was associated with the increased frequencies of transitional and naïve B cells. Moreover, serial measurements of gene expression demonstrated that this pattern persisted over several years, although patients receiving immunosuppression also displayed an increase in the two most dominant tolerance-related B cell genes, IGKV1D-13 and IGLL-1, over time. Importantly, patients rendered tolerant via induction of transient mixed chimerism, and those weaned to minimal immunosuppression, showed similar increases in IGKV1D-13 as did spontaneously tolerant individuals. Collectively, these findings support the notion that alterations in B cells may be a common theme for tolerant kidney transplant recipients, and that it is a useful monitoring tool in prospective trials.

Effector cell signature in peripheral blood following nasal allergen challenge in grass pollen allergic individuals.

BACKGROUND: Several studies have demonstrated the time course of inflammatory mediators in nasal fluids following nasal allergen challenge (NAC), whereas the effects of NAC on cells in the periphery are unknown. We examined the time course of effector cell markers (for basophils, dendritic cells and T cells) in peripheral blood after nasal grass pollen allergen challenge. METHODS: Twelve participants with seasonal allergic rhinitis underwent a control (diluent) challenge followed by NAC after an interval of 14 days. Nasal symptoms and peak nasal inspiratory flow (PNIF) were recorded along with peripheral basophil, T-cell and dendritic cell responses (flow cytometry), T-cell proliferative responses (thymidine incorporation), and cytokine expression (FluoroSpot assay). RESULTS: Robust increases in nasal symptoms and decreases in PNIF were observed during the early (0-1 h) response and modest significant changes during the late (1-24 h) response. Sequential peaks in peripheral blood basophil activation markers were observed (CD107a at 3 h, CD63 at 6 h, and CD203c(bright) at 24 h). T effector/memory cells (CD4(+) CD25(lo) ) were increased at 6 h and accompanied by increases in CD80(+) and CD86(+) plasmacytoid dendritic cells (pDCs). Ex vivo grass antigen-driven T-cell proliferative responses and the frequency of IL-4(+) CD4(+) T cells were significantly increased at 6 h after NAC when compared to the control day. CONCLUSION: Basophil, T-cell, and dendritic cell activation increased the frequency of allergen-driven IL-4(+) CD4(+) T cells, and T-cell proliferative responses are detectable in the periphery after NAC. These data confirm systemic cellular activation following a local nasal provocation.

An information system for improving clinical laboratory outcomes.

Laboratories performing clinical molecular diagnostic and cytogenetic testing require improved information systems to address their specialized data processing needs. We developed an application that automates result reporting, documents quality assurance information, and tracks specimens. While similar functionality was implemented in both the molecular diagnostic and cytogenetic modules, we present an outcome assessment of the cytogenetic laboratory's use of the system since it maintained a relatively constant number of personnel, test procedures, and samples over a three-year period. Upon implementation, significant reductions occurred in the time taken from receipt of sample to the release of the final report by 44% (P < 0.001) and 48% (P < 0.001) for peripheral blood and bone marrow samples, respectively. The number of cases processed per technologist increased by 26% (P = 0.017). We attribute these gains in quality improvement to the automation of clerical tasks and decision support provided by the information system.

CpG island arrays: an application toward deciphering epigenetic signatures of breast cancer.

CpG island hypermethylation is a frequent epigenetic event in cancer. We have recently developed an array-based method, called differential methylation hybridization (DMH), allowing for a genome-wide screening of CpG island hypermethylation in breast cancer cell lines (T. H-M. Huang et al., Hum. Mol. Genet., 8: 459-470, 1999). In the present study, DMH was applied to screen 28 paired primary breast tumor and normal samples and to determine whether patterns of specific epigenetic alterations correlate with pathological parameters in the patients analyzed. Amplicons, representing a pool of methylated CpG DNA derived from these samples, were used as hybridization probes in an array panel containing 1104 CpG island tags. Close to 9% of these tags exhibited extensive hypermethylation in the majority of breast tumors relative to their normal controls, whereas others had little or no detectable changes. Pattern analysis in a subset of CpG island tags revealed that CpG island hypermethylation is associated with histological grades of breast tumors. Poorly differentiated tumors appeared to exhibit more hypermethylated CpG islands than their moderately or well-differentiated counterparts (P = 0.041). This early finding lays the groundwork for a population-based DMH study and demonstrates the need to develop a database for examining large-scale methylation data and for associating specific epigenetic signatures with clinical parameters in breast cancer.

Integrating molecular diagnostic and flow cytometric reporting for improved longitudinal monitoring of HIV patients.

Studies have shown that monitoring HIV-infected patients undergoing antiretroviral therapy is best represented by combined measurement of plasma HIV-1 RNA and CD4+ T-lymphocytes [1]. This pilot study at the University of Missouri-Columbia integrates molecular diagnostic and flow cytometric data reporting to provide current and historical HIV-1 RNA levels and CD4+ T-cell counts. The development of a single database for storage and retrieval of these values facilitates composite report generation that includes longitudinal HIV-1 RNA levels and CD4+ T-cell counts for all patients. Results are displayed in tables and plotted graphically within a web browser. This method of data presentation converts individual data points to more useful medical information and could provide clinicians with decision support for improved monitoring of HIV patients undergoing antiretroviral therapy.