Attempted replication of pharmacogenetic association of variants in PPP1R14C and CCDC148 with aromatase inhibitor-induced musculoskeletal symptoms.

Third-generation aromatase inhibitors (AI) are the standard treatment for patients with hormone receptor positive (HR+) breast cancer. While effective, AI can lead to severe adverse events, including AI-induced musculoskeletal syndrome (AIMSS). Genetic predictors of AIMSS have the potential to personalize AI treatment and improve outcomes. We attempted to replicate results from a previous genome-wide association study that found a lower risk of AIMSS in patients carrying PPP1R14C rs912571 and a higher risk in patients carrying CCDC148 rs79048288. AIMSS data were collected prospectively from patients with HR+ breast cancer prior to starting and after 3 and 6 months of adjuvant AI via the Patient-Reported Outcome Measurement Information System and Functional Assessment of Cancer Therapy-Endocrine Symptom. Germline genotypes for PPP1R14C rs912571 and CCDC148 rs79048288 were tested for a similar association with AIMSS as previously reported via $2 tests. Of the 143 patients with AIMSS and genetics data were included in the analysis. There was no association identified between PPP1R14C rs912571 and AIMSS risk ( P  > 0.05). Patients carrying CCDC148 rs79048288 variant alleles had lower AIMSS incidence in a secondary analysis ( P  = 0.04); however, this was in the opposite direction of the previous finding. The study did not replicate previously reported associations with AIMSS risk for genetic variants in PPP1R14C and CCDC148 and AIMSS risk. Further research is needed to discover and validate genetic predictors of AIMSS that can be used to personalize treatment in patients with HR+ breast cancer.

Transmission of yellow fever vaccine virus through blood transfusion and organ transplantation in the USA in 2021: report of an investigation.

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases.

Factors associated with weight gain in pre- and post-menopausal women receiving adjuvant endocrine therapy for breast cancer.

PURPOSE: Weight gain after breast cancer poses health risks. We aimed to identify factors associated with weight gain during adjuvant endocrine therapy (AET). METHODS: Women initiating AET enrolled in a prospective cohort. Participants completed FACT-ES plus PROMIS pain interference, depression, anxiety, fatigue, sleep disturbance and physical function measures at baseline, 3, 6, 12, 24, 36, 48 and 60 months. Treatment-emergent symptoms were defined as changes in scores in the direction indicative of worsening symptoms that exceeded the minimal important difference at 3 and/or 6 months compared to baseline. We used logistic regression to evaluate associations of clinicodemographic features and treatment-emergent symptoms with clinically significant weight gain over 60 months (defined as ≥ 5% compared to baseline) in pre- and post-menopausal participants. RESULTS: Of 309 participants, 99 (32%) were pre-menopausal. The 60 months cumulative incidence of clinically significant weight gain was greater in pre- than post-menopausal participants (67% vs 43%, p < 0.001). Among pre-menopausal participants, treatment-emergent pain interference (OR 2.49), aromatase inhibitor receipt (OR 2.8), mastectomy, (OR 2.06) and White race (OR 7.13) were associated with weight gain. Among post-menopausal participants, treatment-emergent endocrine symptoms (OR 2.86), higher stage (OR 2.25) and White race (OR 2.29) were associated with weight gain while treatment-emergent physical function decline (OR 0.30) was associated with lower likelihood of weight gain. CONCLUSIONS: Weight gain during AET is common, especially for pre-menopausal women. Clinicodemographic features and early treatment-emergent symptoms may identify at risk individuals. IMPLICATIONS FOR CANCER SURVIVORS: Patients at risk for weight gain can be identified early during AET. GOV IDENTIFIER: NCT01937052, registered September 3, 2013.

Increase in Colorado Tick Fever Virus Disease Cases and Effect of COVID-19 Pandemic on Behaviors and Testing Practices, Montana, 2020.

In 2020, Montana, USA, reported a large increase in Colorado tick fever (CTF) cases. To investigate potential causes of the increase, we conducted a case-control study of Montana residents who tested positive or negative for CTF during 2020, assessed healthcare providers' CTF awareness and testing practices, and reviewed CTF testing methods. Case-patients reported more time recreating outdoors on weekends, and all reported finding a tick on themselves before illness. No consistent changes were identified in provider practices. Previously, only CTF serologic testing was used in Montana. In 2020, because of SARS-CoV-2 testing needs, the state laboratory sent specimens for CTF testing to the Centers for Disease Control and Prevention, where more sensitive molecular methods are used. This change in testing probably increased the number of CTF cases detected. Molecular testing is optimal for CTF diagnosis during acute illness. Tick bite prevention measures should continue to be advised for persons doing outdoor activities.

Transfusion-Transmitted Cache Valley Virus Infection in a Kidney Transplant Recipient With Meningoencephalitis.

BACKGROUND: Cache Valley virus (CVV) is a mosquito-borne virus that is a rare cause of disease in humans. In the fall of 2020, a patient developed encephalitis 6 weeks following kidney transplantation and receipt of multiple blood transfusions. METHODS: After ruling out more common etiologies, metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) was performed. We reviewed the medical histories of the index kidney recipient, organ donor, and recipients of other organs from the same donor and conducted a blood traceback investigation to evaluate blood transfusion as a possible source of infection in the kidney recipient. We tested patient specimens using reverse-transcription polymerase chain reaction (RT-PCR), the plaque reduction neutralization test, cell culture, and whole-genome sequencing. RESULTS: CVV was detected in CSF from the index patient by mNGS, and this result was confirmed by RT-PCR, viral culture, and additional whole-genome sequencing. The organ donor and other organ recipients had no evidence of infection with CVV by molecular or serologic testing. Neutralizing antibodies against CVV were detected in serum from a donor of red blood cells received by the index patient immediately prior to transplant. CVV neutralizing antibodies were also detected in serum from a patient who received the co-component plasma from the same blood donation. CONCLUSIONS: Our investigation demonstrates probable CVV transmission through blood transfusion. Clinicians should consider arboviral infections in unexplained meningoencephalitis after blood transfusion or organ transplantation. The use of mNGS might facilitate detection of rare, unexpected infections, particularly in immunocompromised patients.

Tick bite risk factors and prevention measures in an area with emerging Powassan virus disease.

Background: In the United States (U.S.), Powassan virus is primarily transmitted to humans by the black-legged tick (Ixodes scapularis). Rarely, infections can present as severe neuroinvasive disease. In 2019, four neuroinvasive disease cases were reported in Sussex County, New Jersey, U.S. We administered a survey to county residents to better understand tick bite risk factors and the performance of personal prevention measures. Methods: A survey was administered in October 2019 to adult residents of randomly selected households. Questions focused on tick bite prevention and risk factors. Crude and adjusted odds ratios (ORs) and 95% confidence intervals were calculated for various outcomes. Results: Of 274 participants, 25% were previously diagnosed with a tick-borne disease, and 42% reported finding an attached tick in 2019. Yardwork and gardening (OR = 7.38) and spending >50 hours outdoors per week (OR = 8.15) were associated with finding an attached tick. Finding an attached tick was inversely associated with the number of prevention measures used, indicating that a layered approach could reduce the risk of tick bites. Those who performed post-outdoor activity prevention measures (e.g., tick checks) were less likely to have a tick attached compared to finding a crawling tick. Conclusion: Compliance with prevention recommendations was low, despite a high prevalence of reported tick bites and significant outdoor exposures. Older adults and persons who spend significant time outdoors or engage in yardwork or gardening were at the highest risk of tick bites. Additional research is needed to further understand the barriers to tick bite prevention.

Factors associated with worsening sexual function during adjuvant endocrine therapy in a prospective clinic-based cohort of women with early-stage breast cancer.

PURPOSE: Sexual function problems are common but under-reported among women receiving adjuvant endocrine therapy for breast cancer. Worsening scores on patient-reported outcomes (PROs) may identify those at risk for sexual function problems during treatment. We performed a secondary analysis of prospectively collected PROs in women receiving adjuvant endocrine therapy to identify factors associated with worsening sexual function. METHODS: Women with stage 0-III breast cancer initiating adjuvant endocrine therapy participating in a prospective cohort completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60 months. Sexual function was evaluated by the MOS-SP measure. Other measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance and the Endocrine Symptom Subscale of the FACT-ES. We evaluated associations between score worsening of at least the minimal important difference (MID) in PROMIS T-scores (4 points) and FACT-ES scores (5 points) with score worsening of at least the MID in MOS-SP scores (8 points) using logistic regression. RESULTS: Among 300 participants, 45.7% experienced ≥ 8-point worsening of MOS-SP score at any time point compared to baseline. Worsening endocrine symptoms (OR 1.34, 95% CI 1.22-1.49, p < 0.001), worsening physical function (OR 1.09, 95% CI 1.00-1.18, p = 0.06), and prior mastectomy (OR 1.45, 95% CI 0.94-2.23, p = 0.09) were associated with MOS-SP score worsening by at least the MID. CONCLUSION: Worsening endocrine symptoms and physical function identified on PROs are associated with worsening sexual function during adjuvant endocrine therapy. Routine assessment of these domains with PROs may identify women at risk for sexual function problems. TRIAL REGISTRATION NUMBER: NCT01937052; Date of Registration: 09/09/2013.

Development of an automated liquid biopsy assay for methylated markers in advanced breast cancer.

Current molecular liquid biopsy assays to detect recurrence or monitor response to treatment require sophisticated technology, highly trained personnel, and a turnaround time of weeks. We describe the development and technical validation of an automated Liquid Biopsy for Breast Cancer Methylation (LBx-BCM) prototype, a DNA methylation detection cartridge assay that is simple to perform and quantitatively detects nine methylated markers within 4.5 h. LBx-BCM demonstrated high interassay reproducibility when analyzing exogenous methylated DNA (75-300 DNA copies) spiked into plasma (Coefficient of Variation, CV = 7.1 - 10.9%) and serum (CV = 19.1 - 36.1%). It also demonstrated high interuser reproducibility (Spearman r = 0.887, P < 0.0001) when samples of metastatic breast cancer (MBC, N = 11) and normal control (N = 4) were evaluated independently by two users. Analyses of interplatform reproducibility indicated very high concordance between LBx-BCM and the reference assay, cMethDNA, among 66 paired plasma samples (MBC N = 40, controls N = 26; Spearman r = 0.891; 95% CI = 0.825 - 0.933, P< 0.0001). LBx-BCM achieved a ROC AUC = 0.909 (95% CI = 0.836 - 0.982), 83% sensitivity and 92% specificity; cMethDNA achieved a ROC AUC = 0.896 (95% CI = 0.817 - 0.974), 83% sensitivity and 92% specificity in test set samples. The automated LBx-BCM cartridge prototype is fast, with performance levels equivalent to the highly sensitive, manual cMethDNA method. Future prospective clinical studies will evaluate LBx-BCM detection sensitivity and its ability to monitor therapeutic response during treatment for advanced breast cancer.

SARS-CoV-2 infection risk among vaccinated and unvaccinated household members during the Alpha variant surge - Denver, Colorado, and San Diego, California, January-April 2021.

BACKGROUND: COVID-19 vaccination reduces SARS-CoV-2 infection and transmission. However, evidence is emerging on the degree of protection across variants and in high-transmission settings. To better understand the protection afforded by vaccination specifically in a high-transmission setting, we examined household transmission of SARS-CoV-2 during a period of high community incidence with predominant SARS-CoV-2 B.1.1.7 (Alpha) variant, among vaccinated and unvaccinated contacts. METHODS: We conducted a household transmission investigation in San Diego County, California, and Denver, Colorado, during January-April 2021. Households were enrolled if they had at least one person with documented SARS-CoV-2 infection. We collected nasopharyngeal swabs, blood, demographic information, and vaccination history from all consenting household members. We compared infection risks (IRs), RT-PCR cycle threshold values, SARS-CoV-2 culture results, and antibody statuses among vaccinated and unvaccinated household contacts. RESULTS: We enrolled 493 individuals from 138 households. The SARS-CoV-2 variant was identified from 121/138 households (88%). The most common variants were Alpha (75/121, 62%) and Epsilon (19/121, 16%). There were no households with discordant lineages among household members. One fully vaccinated secondary case was symptomatic (13%); the other 5 were asymptomatic (87%). Among unvaccinated secondary cases, 105/108 (97%) were symptomatic. Among 127 households with a single primary case, the IR for household contacts was 45% (146/322; 95% Confidence Interval [CI] 40-51%). The observed IR was higher in unvaccinated (130/257, 49%, 95% CI 45-57%) than fully vaccinated contacts (6/26, 23%, 95% CI 11-42%). A lower proportion of households with a fully vaccinated primary case had secondary cases (1/5, 20%) than households with an unvaccinated primary case (66/108, 62%). CONCLUSIONS: Although SARS-CoV-2 infections in vaccinated household contacts were reported in this high transmission setting, full vaccination protected against SARS-CoV-2 infection. These findings further support the protective effect of COVID-19 vaccination and highlight the need for ongoing vaccination among eligible persons.

Association of treatment-emergent symptoms identified by patient-reported outcomes with adjuvant endocrine therapy discontinuation.

Many patients discontinue endocrine therapy for breast cancer due to intolerance. Identification of patients at risk for discontinuation is challenging. The minimal important difference (MID) is the smallest change in a score on a patient-reported outcome (PRO) that is clinically significant. We evaluated the association between treatment-emergent symptoms detected by worsening PRO scores in units equal to the MID with discontinuation. We enrolled females with stage 0-III breast cancer initiating endocrine therapy in a prospective cohort. Participants completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60 months. Measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance; Endocrine Subscale of the FACT-ES; and MOS-Sexual Problems (MOS-SP). We evaluated associations between continuous PRO scores in units corresponding to MIDs (PROMIS: 4-points; FACT-ES: 5-points; MOS-SP: 8-points) with time to endocrine therapy discontinuation using Cox proportional hazards models. Among 321 participants, 140 (43.6%) initiated tamoxifen and 181 (56.4%) initiated aromatase inhibitor (AI). The cumulative probability of discontinuation was 23% (95% CI 18-27%) at 48 months. For every 5- and 4-point worsening in endocrine symptoms and sleep disturbance respectively, participants were 13 and 14% more likely to discontinue endocrine therapy respectively (endocrine symptoms HR 1.13, 95% CI 1.02-1.25, p = 0.02; sleep disturbance HR 1.14, 95% CI 1.01-1.29, p = 0.03). AI treatment was associated with greater likelihood of discontinuation than tamoxifen. Treatment-emergent endocrine symptoms and sleep disturbance are associated with endocrine therapy discontinuation. Monitoring for worsening scores meeting or exceeding the MID on PROs may identify patients at risk for discontinuation.

Seroprevalence of Powassan Virus Infection in an Area Experiencing a Cluster of Disease Cases: Sussex County, New Jersey, 2019.

In 2019, a geographically focal cluster of 3 Powassan virus neuroinvasive disease cases occurred in New Jersey. We conducted a serosurvey of 273 adult area residents and estimated that immunoglobulin M seroprevalence was 0.31% (95% confidence interval [CI], .04%-1.00%) and 23% (95% CI, 7%-100%) of infections result in neuroinvasive disease.

Olaparib Use in Patients With Metastatic Breast Cancer Harboring Somatic BRCA1/2 Mutations or Mutations in Non-BRCA1/2, DNA Damage Repair Genes.

BACKGROUND: Poly-ADP ribose polymerase (PARP) inhibitors (PARPi) are active in patients with germline BRCA1/2 (gBRCA1/2)-mutated breast cancer, accounting for 5% to 10% of all breast cancers. Another 5% to 10% harbor somatic BRCA1/2 (sBRCA1/2) mutations or mutations in non-BRCA1/2, homologous recombination repair (HRR) genes but until recently, there were no data for the use of PARPi in these patients. This study examines the use of olaparib in patients with metastatic breast cancer harboring sBRCA1/2 or germline or somatic non-BRCA1/2, HRR mutations and demonstrates potential activity of PARPi in this setting. METHODS: In this retrospective, single institution study, patients who were treated with off-label, off-protocol olaparib for metastatic breast cancer harboring sBRCA1/2 or germline or somatic non-BRCA1/2, HRR mutations were identified. The primary aim was to describe these patients' demographics, tumor characteristics, mutations, safety and tolerability, response rates, progression free survival, PARPi-associated survival and subsequent treatment. RESULTS: Seven patients were treated off-label, off-trial with olaparib for sBRCA1/2-mutated cancers (n = 4) or non-BRCA1/2, HRR-mutated cancers (n = 3). All patients with sBRCA1/2-mutated cancers responded to PARP inhibition; patients with non-BRCA1/2, HRR-mutated cancers did not respond. The median progression free survival in patients with a sBRCA1/2 mutation was 6.5 months (range 5-9 months) vs. 3 months (range 2-4 months) in patients with non-BRCA1/2, HRR mutations. CONCLUSION: This single institution experience adds to recent larger reports confirming evidence for PARPi therapy in patients with metastatic breast cancer harboring sBRCA1/2 mutations. No activity was observed in patients with either germline or somatic non-BRCA1/2, HRR-mutated cancers.

Further Evidence That OPG rs2073618 Is Associated With Increased Risk of Musculoskeletal Symptoms in Patients Receiving Aromatase Inhibitors for Early Breast Cancer.

BACKGROUND: Aromatase inhibitors (AI) reduce recurrence and death in patients with early-stage hormone receptor-positive (HR +) breast cancer. Treatment-related toxicities, including AI-induced musculoskeletal symptoms (AIMSS), are common and may lead to early AI discontinuation. The objective of this study was to replicate previously reported associations for candidate germline genetic polymorphisms with AIMSS. METHODS: Women with stage 0-III HR + breast cancer initiating adjuvant AI were enrolled in a prospective clinic-based observational cohort. AIMSS were assessed by patient-reported outcomes (PRO) including the PROMIS pain interference and physical function measures plus the FACT-ES joint pain question at baseline and after 3 and 6 months. For the primary analysis, AIMSS were defined as ≥ 4-point increase in the pain interference T-score from baseline. Secondary AIMSS endpoints were defined as ≥ 4-point decrease in the physical function T-score from baseline and as ≥ 1-point increase on the FACT-ES joint pain question from baseline. The primary hypothesis was that TCL1A rs11849538 would be associated with AIMSS. Twelve other germline variants in CYP19A1, VDR, PIRC66, OPG, ESR1, CYP27B1, CYP17A1, and RANKL were also analyzed assuming a dominant genetic effect and prespecified direction of effect on AIMSS using univariate logistic regression with an unadjusted α = 0.05. Significant univariate associations in the expected direction were adjusted for age, race, body mass index (BMI), prior taxane, and the type of AI using multivariable logistic regression. RESULTS: A total of 143 participants with PRO and genetic data were included in this analysis, most of whom were treated with anastrozole (78%) or letrozole (20%). On primary analysis, participants carrying TCL1A rs11849538 were not more likely to develop AIMSS (odds ratio = 1.29, 95% confidence interval: 0.55-3.07, p = 0.56). In the statistically uncorrected secondary analysis, OPG rs2073618 was associated with AIMSS defined by worsening on the FACT-ES joint pain question (OR = 3.33, p = 0.004), and this association maintained significance after covariate adjustment (OR = 3.98, p = 0.003). CONCLUSION: Carriers of OPG rs2073618 may be at increased risk of AIMSS. If confirmed in other cohorts, OPG genotyping can be used to identify individuals with HR + early breast cancer in whom alternate endocrine therapy or interventions to enhance symptom detection and implement strategies to reduce musculoskeletal symptoms may be needed.

HSV-1 mastitis in a 30-year-old woman.

A young woman presented with worsening bilateral periareolar mastitis associated with skin necrosis and delayed vesical formation after oral nipple manipulation by her sexual partner. After multiple failed antibiotic regimens, she was diagnosed with herpes simplex virus 1 (HSV-1) infection. This case demonstrates an uncommon etiology of breast mastitis. We highlight the importance of a timely diagnosis and early administration of antiviral therapy.

Travel-Associated and Locally Acquired Dengue Cases - United States, 2010-2017.

Dengue is a potentially fatal acute febrile illness caused by any of four mosquito-transmitted dengue viruses (DENV-1 to DENV-4) belonging to the family Flaviviridae and endemic throughout the tropics. Competent mosquito vectors of DENV are present in approximately one half of all U.S. counties. To describe epidemiologic trends in travel-associated and locally acquired dengue cases in the United States, CDC analyzed cases reported from the 50 states and District of Columbia to the national arboviral surveillance system (ArboNET). Cases are confirmed by detection of 1) virus RNA by reverse transcription-polymerase chain reaction (RT-PCR) in any body fluid or tissue, 2) DENV antigen in tissue by a validated assay, 3) DENV nonstructural protein 1 (NS1) antigen, or 4) immunoglobulin M (IgM) anti-DENV antibody if the patient did not report travel to an area with other circulating flaviviruses. When travel to an area with other flaviviruses was reported, IgM-positive cases were defined as probable. During 2010-2017, totals of 5,009 (93%) travel-associated and 378 (7%) locally acquired confirmed or probable dengue cases were reported to ArboNET. Cases were equally distributed between males and females, and median age was 41 years. Eighteen (three per 1,000) fatal cases were reported, all among travelers. Travelers should review country-specific recommendations (https://wwwnc.cdc.gov/travel/notices/watch/dengue-asia) for reducing their risk for DENV infection, including using insect repellent and staying in residences with air conditioning or screens on windows and doors.

West Nile Virus and Other Domestic Nationally Notifiable Arboviral Diseases - United States, 2018.

Arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1). Other arboviruses, including eastern equine encephalitis, Jamestown Canyon, La Crosse, Powassan, and St. Louis encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC for 2018 on nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses because they are primarily nondomestic viruses typically acquired through travel. In 2018, 48 states and the District of Columbia (DC) reported 2,813 cases of domestic arboviral disease, including 2,647 (94%) WNV disease cases. Of the WNV disease cases, 1,658 (63%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, and acute flaccid paralysis), for a national incidence of 0.51 cases of WNV neuroinvasive disease per 100,000 population. Because arboviral diseases continue to cause serious illness and have no definitive treatment, maintaining surveillance is important to direct and promote prevention activities. Health care providers should consider arboviral infections in patients with aseptic meningitis or encephalitis, perform appropriate diagnostic testing, and report cases to public health authorities.

Epidemiology of Dengue, Chikungunya, and Zika Virus Disease in U.S. States and Territories, 2017.

Dengue, chikungunya, and Zika viruses, primarily transmitted by Aedes species mosquitoes, have caused large outbreaks in the Americas, leading to travel-associated cases and local mosquito-borne transmission in the United States. We describe the epidemiology of dengue, chikungunya, and noncongenital Zika virus disease cases reported from U.S. states and territories in 2017, including 971 dengue cases, 195 chikungunya cases, and 1,118 Zika virus disease cases. Cases of all three diseases reported from the territories were reported as resulting from local mosquito-borne transmission. Cases reported from the states were primarily among travelers, with only seven locally acquired mosquito-transmitted Zika virus disease cases reported from Texas (n = 5) and Florida (n = 2). In the territories, most dengue cases (n = 508, 98%) were reported from American Samoa, whereas the majority of chikungunya (n = 39, 100%) and Zika virus disease (n = 620, 93%) cases were reported from Puerto Rico. Temporally, the highest number of Zika virus disease cases occurred at the beginning of the year, followed by a sharp decline, mirroring decreasing case numbers across the Americas following large outbreaks in 2015 and 2016. Dengue and chikungunya cases followed a more seasonal pattern, with higher case numbers from July through September. Travelers to the United States and residents of areas with active virus transmission should be informed of both the ongoing risk from dengue, chikungunya, and Zika virus disease and personal protective measures to lower their risk of mosquito bites and to help prevent the spread of these diseases.

The Timing of Chemoprophylaxis in Autologous Microsurgical Breast Reconstruction.

BACKGROUND: Patients undergoing autologous breast reconstruction are at high risk of perioperative venous thromboembolic events. The efficacy of chemoprophylaxis in decreasing venous thromboembolic events is well established, but the timing of chemoprophylaxis remains controversial. The authors compare the incidence of bleeding following preoperative versus postoperative initiation of chemoprophylaxis in microvascular breast reconstruction. METHODS: A retrospective chart review was performed from August of 2010 to July of 2016. Initiation of chemoprophylaxis changed from postoperative to preoperative in 2013, dividing subjects into two groups. Patient demographics, comorbidities, and complications were reviewed. RESULTS: A total of 196 patients (311 flaps) were included in the study. A total of 105 patients (166 flaps) received preoperative enoxaparin (40 mg) and 91 patients (145 flaps) received postoperative chemoprophylaxis. A total of five patients required hematoma evacuation (2.6 percent). Of these, one hematoma (1 percent) occurred in the preoperative chemoprophylaxis group. Seven patients received blood transfusions: three in the preoperative group and four in the postoperative group (2.9 percent versus 4.4 percent; p = 0.419). There was a total of one flap failure, and there were no documented venous thromboembolic events in any of the groups. CONCLUSIONS: This study demonstrates that preoperative chemoprophylaxis can be used safely in patients undergoing microvascular breast reconstruction. The higher rate of bleeding in the postoperative group may be related to the onset of action of enoxaparin of 4 to 6 hours, which allows for intraoperative hemostasis in the preoperative group and possibly potentiating postoperative oozing when administered postoperatively. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2017.

Arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes or ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1). Other arboviruses, including Jamestown Canyon, La Crosse, Powassan, St. Louis encephalitis, and eastern equine encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC from U.S. states in 2017 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses because, in the continental United States, these viruses are acquired primarily through travel. In 2017, 48 states and the District of Columbia (DC) reported 2,291 cases of domestic arboviral disease, including 2,097 (92%) WNV disease cases. Among the WNV disease cases, 1,425 (68%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis), for a national rate of 0.44 cases per 100,000 population. More Jamestown Canyon and Powassan virus disease cases were reported in 2017 than in any previous year. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct and promote prevention activities.

Modified Approach to Stroke Rehabilitation (MAStR): feasibility study of a method to apply procedural memory concepts to transfer training.

OBJECTIVE: Training and implementation for a multidisciplinary stroke rehabilitation method emphasizing procedural memory. BACKGROUND: Current practice in stroke rehabilitation relies on explicit memory, often compromised by stroke, failing to capitalize on better-preserved procedural memory skills. Recruitment of procedural memory requires consistency and practice, characteristics difficulty to promote on inpatient rehabilitation units. We designed a method Modified Approach to Stroke Rehabilitation (MAStR) to maximize consistency and practice for transfer training with stroke patients. DESIGN: Phase I, single-group study. MAStR has two innovations: (1) simplification of instructions to only three words, other direction provided non-verbally; (2) having all rehabilitation staff apply the same approach for transfers. Staff training in MAStR included review of written material describing the rationale for MAStR and demonstration of a transfer using MAStR. Enrolled patients completed each transfer with MAStR in addition to standard rehabilitation therapy. RESULTS: The MAStR method was taught to a large, multidisciplinary rehabilitation staff (n = 31). Training and certification required 15 min per staff member. Five stroke patients were enrolled. No transfers with MAStR resulted in injury, no negative feedback was received from staff or patients. Staff reported satisfaction with the brief MAStR training and reported transfers were easier to complete with the MAStR method. CONCLUSIONS: Feasibility was demonstrated for an innovative application of procedural memory concepts to stroke rehabilitation. All rehabilitation disciplines were successfully trained. MAStR was well-tolerated and liked by rehabilitation staff and patients. These results support pursuit of a Phase II pilot study.