Anti-CD7 allogeneic WU-CART-007 in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma: a phase 1/2 trial.

Relapsed/refractory T-cell acute lymphoblastic leukemia (ALL)/lymphoma (LBL) represent a significant unmet medical need. WU-CART-007 is a CD7-targeting, allogeneic, fratricide-resistant chimeric antigen receptor T cell product generated from healthy donor T cells. WU-CART-007 was evaluated in a phase 1/2 study with a 3 + 3 dose-escalation design followed by cohort expansion in relapsed/refractory T-ALL/LBL. Patients received one infusion of WU-CART-007 after standard or enhanced lymphodepleting chemotherapy. The primary objectives, to characterize safety and assess the composite complete remission rate, were met. Of 26 patients enrolled, 13 received the recommended phase 2 dose (RP2D) of 900 million cells of WU-CART-007 with enhanced lymphodepletion. The most common treatment-related adverse event was cytokine release syndrome (88.5%; 19.2% grade 3-4). Biochemical abnormalities consistent with grade 2 hemophagocytic lymphohistiocytosis were seen in one patient (3.8%). Grade 1 immune effector cell-associated neurotoxicity syndrome events (7.7%) and one grade 2 acute graft-vs-host disease event occurred. Grade 5 events (11.5%) were due to fungal infection and multi-organ failure. The composite complete remission rate was 81.8% among 11/13 patients evaluable for response at the RP2D. WU-CART-007 at the RP2D demonstrated a high response rate in patients with relapsed/refractory T-ALL/LBL and has the potential to provide a new treatment option. ClinicalTrials.gov registration: NCT04984356.

Environmentally Responsive Materials for Building Envelopes: A Review on Manufacturing and Biomimicry-Based Approaches.

Buildings must adapt and respond dynamically to their environment to reduce their energy loads and mitigate environmental impacts. Several approaches have addressed responsive behavior in buildings, such as adaptive and biomimetic envelopes. However, biomimetic approaches lack sustainability consideration, as conducted in biomimicry approaches. This study provides a comprehensive review of biomimicry approaches to develop responsive envelopes, aiming to understand the connection between material selection and manufacturing. This review of the last five years of building construction and architecture-related studies consisted of a two-phase search query, including keywords that answered three research questions relating to the biomimicry and biomimetic-based building envelopes and their materials and manufacturing and excluding other non-related industrial sectors. The first phase focused on understanding biomimicry approaches implemented in building envelopes by reviewing the mechanisms, species, functions, strategies, materials, and morphology. The second concerned the case studies relating to biomimicry approaches and envelopes. Results highlighted that most of the existing responsive envelope characteristics are achievable with complex materials requiring manufacturing processes with no environmentally friendly techniques. Additive and controlled subtractive manufacturing processes may improve sustainability, but there is still some challenge to developing materials that fully adapt to large-scale and sustainability needs, leaving a significant gap in this field.

Lateral flow devices for samples collected by straw sampling method for postmortem canine rabies diagnosis.

The direct fluorescent antibody test (dFAT) using brain sample after opening the skull is the standard rabies diagnostic test in animal rabies. However, it is not feasible in many resource-limited settings. Lateral flow devices (LFD) combined with a simple sampling methodology is quicker, simpler, and less hazardous than the standard test and can be a useful tool. We conducted a prospective on-site study to evaluate the diagnostic accuracy of the LFD with the straw sampling method compared with that of the dFAT with the skull opening procedure for post-mortem canine rabies diagnosis. We collected 97 rabies-suspected animals between December 1, 2020 and March 31, 2021. Among the 97 samples, 53 and 50 cases were positive tests for dFAT and LFD, respectively. The sensitivity and specificity of LFD with straw sampling method were 94.3% (95% confidence interval [CI], 84.3-98.8%) and 100% (95% CI, 92.0-100%), respectively. The performance of LFD by the straw sampling method showed relatively high sensitivity and 100% specificity compared with that of dFAT performed on samples collected after opening the skull. This methodology can be beneficial and is a strong tool to overcome limited animal surveillance in remote areas. However, because of our limited sample size, more data using fresh samples on-site and the optimizations are urgently needed for the further implementation in endemic areas.

Outbreak of hepatitis B and hepatitis C virus infections associated with a cardiology clinic, West Virginia, 2012-2014.

OBJECTIVE: To stop transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in association with myocardial perfusion imaging (MPI) at a cardiology clinic. DESIGN: Outbreak investigation and quasispecies analysis of HCV hypervariable region 1 genome. SETTING: Outpatient cardiology clinic. PATIENTS: Patients undergoing MPI. METHODS: Case patients met definitions for HBV or HCV infection. Cases were identified through surveillance registry cross-matching against clinic records and serological screening. Observations of clinic practices were performed. RESULTS: During 2012-2014, 7 cases of HCV and 4 cases of HBV occurred in 4 distinct clusters among patients at a cardiology clinic. Among 3 case patients with HCV infection who had MPI on June 25, 2014, 2 had 98.48% genetic identity of HCV RNA. Among 4 case patients with HCV infection who had MPI on March 13, 2014, 3 had 96.96%-99.24% molecular identity of HCV RNA. Also, 2 clusters of 2 patients each with HBV infection had MPI on March 7, 2012, and December 4, 2014. Clinic staff reused saline vials for >1 patient. No infection control breaches were identified at the compounding pharmacy that supplied the clinic. Patients seen in clinic through March 27, 2015, were encouraged to seek testing for HBV, HCV, and human immunodeficiency virus. The clinic switched to all single-dose medications and single-use intravenous flushes on March 27, 2015, and no further cases were identified. CONCLUSIONS: This prolonged healthcare-associated outbreak of HBV and HCV was most likely related to breaches in injection safety. Providers should follow injection safety guidelines in all practice settings.

Varicella Outbreak Surveillance in Schools in Sentinel Jurisdictions, 2012-2015.

BACKGROUND: In 2007, a routine second dose of varicella vaccine was recommended in the United States for children aged 4 to 6 years to better control varicella-zoster virus circulation and outbreaks. Sentinel varicella outbreak surveillance was established to assess feasibility of surveillance and describe outbreaks that are occurring. METHODS: Through the Centers for Disease Control and Prevention Epidemiology Laboratory Capacity funding, health departments conducted active surveillance for varicella outbreaks in schools from 2012 to 2015. Outbreaks of varicella were defined as ≥5 cases in a school within at least 1 incubation period (21 days). School nurses, healthcare providers, or laboratories reported cases and outbreaks of varicella to health departments; demographic, vaccination, and clinical data were collected. RESULTS: Georgia, Houston, Maine, Minnesota, New York City, and Philadelphia participated in all 3 years; Puerto Rico and West Virginia participated in 2012 to 2013; and Kansas and Arkansas participated in 2014 to 2015. Twenty-nine outbreaks including 262 cases were reported. The median size of the outbreaks was 7 cases (range, 5-31 cases), and the median duration was 31 days (range, 4-100 days). Of the case-patients associated with larger outbreaks (≥8 cases), 55.4% were unvaccinated, and 15.7% and 18.1% had received 1 or 2 doses of vaccine, respectively. In small outbreaks (5-7 cases), 33.3% of case-patients were unvaccinated, and 16.7% and 38.5% had received 1 or 2 doses of vaccine, respectively. CONCLUSIONS: The majority of cases associated with outbreaks occurred in undervaccinated children (unvaccinated and 1-dose vaccine recipients). Outbreaks with a greater proportion of 2-dose vaccine recipients were smaller. Varicella outbreak surveillance is feasible, and continued monitoring of outbreaks remains important for describing the epidemiology of varicella during the 2-dose varicella vaccination program.

Hospital Impact After a Chemical Spill That Compromised the Potable Water Supply: West Virginia, January 2014.

In January 2014, a chemical spill of 4-methylcyclohexanemethanol and propylene glycol phenyl ethers contaminated the potable water supply of approximately 300,000 West Virginia residents. To understand the spill's impact on hospital operations, we surveyed representatives from 10 hospitals in the affected area during January 2014. We found that the spill-related loss of potable water affected many aspects of hospital patient care (eg, surgery, endoscopy, hemodialysis, and infection control of Clostridium difficile). Hospital emergency preparedness planning could be enhanced by specifying alternative sources of potable water sufficient for hemodialysis, C. difficile infection control, and hospital processing and cleaning needs (in addition to drinking water). (Disaster Med Public Health Preparedness. 2017;11:621-624).

Impact of the US Two-dose Varicella Vaccination Program on the Epidemiology of Varicella Outbreaks: Data from Nine States, 2005-2012.

BACKGROUND: A routine 2-dose varicella vaccination program was adopted in 2007 in the US to help further decrease varicella disease and prevent varicella outbreaks. We describe trends and characteristics of varicella outbreaks reported to the Centers for Disease Control and Prevention (CDC) during 2005-2012 from 9 states. METHODS: Data on varicella outbreaks collected by 9 state health departments were submitted to CDC using the CDC outbreak reporting worksheet. Information was collected on dates of the outbreak, outbreak setting and number of cases by outbreak; aggregate data were provided on the numbers of outbreak-related cases by age group, vaccination status and laboratory confirmation. RESULTS: Nine hundred and twenty-nine outbreaks were reported from the 6 states, which provided data for each year during 2005-2012. Based on data from these 6 states, the number of outbreaks declined by 78%, decreasing from 147 in 2005 to 33 outbreaks in 2012 (P = 0.0001). There were a total of 1015 varicella outbreaks involving 13,595 cases reported by the 9 states from 2005 to 2012. The size and duration of outbreaks declined significantly over time (P < 0.001). The median size of outbreaks was 12, 9 and 7 cases and median duration of outbreaks was 38, 35 and 26 days during 2005-2006, 2007-2009 and 2010-2012, respectively. Majority of outbreaks (95%) were reported from schools, declining from 97% in 2005-2006 to 89% in 2010-2012. Sixty-five percent of outbreak-related cases occurred among 5-year to 9-year olds, with the proportion declining from 76% in 2005-2006 to 45% during 2010-2012. CONCLUSIONS: The routine 2-dose varicella vaccination program appears to have significantly reduced the number, size and duration of varicella outbreaks in the US.

Two-dose varicella vaccine effectiveness and rash severity in outbreaks of varicella among public school students.

BACKGROUND: Universal 2-dose varicella vaccination was recommended in 2006 to further reduce varicella disease burden. This study examined 2-dose varicella vaccine effectiveness (VE) and rash severity in the setting of school-associated varicella outbreaks. METHODS: A case control study was conducted from January 2010 to May 2011 in all West Virginia public schools. Clinically diagnosed cases from varicella outbreaks were matched with classmate controls. Vaccination information was collected from school, health department and healthcare provider immunization information systems. RESULTS: Among the 133 cases and 365 controls enrolled, VE against all varicella was 83.2% [95% confidence interval (CI): 69.2%-90.8%] for 1-dose of varicella vaccine and 93.9% (95% CI: 86.9%-97.1%) for 2-dose; the incremental VE (2-dose vs. 1-dose) was 63.6% (95% CI: 32.6%-80.3%). In preventing moderate/severe varicella, 1-dose varicella vaccine was 88.2% (95% CI: 72.7%- 94.9%) effective, and 2-dose vaccination was 97.5% (95% CI: 91.6%-99.2%) effective, with the incremental VE of 78.6% (95% CI: 40.9%-92.3%). One-dose VE declined along with time since vaccination (VE = 93.0%, 88.0% and 81.8% in <5, 5-9 and ≥ 10 years after vaccination, P = 0.001 for trend). Both 1- and 2-dose breakthrough cases had milder rash than unvaccinated cases (<50 lesion: 24.6%, 49.1% and 70.0% in unvaccinated, 1-dose and 2-dose cases, P < 0.001), and no severe disease was found in 2-dose cases. CONCLUSIONS: Two-dose varicella vaccination is highly effective and confers higher protection than a 1-dose regimen. High 2-dose varicella vaccination coverage should maximize the benefits of the varicella vaccination program and further reduce varicella disease burden in the United States.

Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man.

Environmental manganese (Mn) toxicity causes an extrapyramidal, parkinsonian-type movement disorder with characteristic magnetic resonance images of Mn accumulation in the basal ganglia. We have recently reported a suspected autosomal recessively inherited syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia in cases without environmental Mn exposure. Whole-genome mapping of two consanguineous families identified SLC30A10 as the affected gene in this inherited type of hypermanganesemia. This gene was subsequently sequenced in eight families, and homozygous sequence changes were identified in all affected individuals. The function of the wild-type protein and the effect of sequence changes were studied in the manganese-sensitive yeast strain Δpmr1. Expressing human wild-type SLC30A10 in the Δpmr1 yeast strain rescued growth in high Mn conditions, confirming its role in Mn transport. The presence of missense (c.266T>C [p.Leu89Pro]) and nonsense (c.585del [p.Thr196Profs(∗)17]) mutations in SLC30A10 failed to restore Mn resistance. Previously, SLC30A10 had been presumed to be a zinc transporter. However, this work has confirmed that SLC30A10 functions as a Mn transporter in humans that, when defective, causes Mn accumulation in liver and brain. This is an important step toward understanding Mn transport and its role in neurodegenerative processes.

Severe methicillin-susceptible Staphylococcus aureus infections associated with epidural injections at an outpatient pain clinic.

BACKGROUND: Recent outbreaks in ambulatory care settings have highlighted infection control breaches as risk factors for disease transmission. In May 2009, 3 patients were hospitalized with severe methicillin-susceptible Staphylococcus aureus (MSSA) infections after receiving epidural injections at a West Virginia outpatient pain clinic. METHODS: We conducted a retrospective cohort study evaluating clinic patients who received injections during a 3-week period. A case was defined as laboratory-confirmed infection or clinical evidence of infection ≤ 14 days after a patient received an injection. Infection control procedures were assessed. MSSA isolates from patient infections and clinic staff nasal swabs were genotyped by using pulsed-field gel electrophoresis. RESULTS: Eight (7%) of 110 cohort patients met the case definition; 6 (75%) cases were laboratory confirmed. Eight (12%) of 69 patients who received epidural injections were case patients compared with none of the other 41 patients (P = .02). During procedures, staff use of face masks and preparation of patient skin were suboptimal; epidural injection syringes were reused to access shared medication vials. MSSA isolates from 2 patients and 1 staff member were indistinguishable by pulsed-field gel electrophoresis. CONCLUSION: Infection control breaches likely facilitated MSSA transmission to patients receiving epidural injections. Adhering to correct infection control practices in ambulatory care settings is critical to prevent disease transmission.

A prospective randomized trial of prophylactic platelet transfusion and bleeding incidence in hematopoietic stem cell transplant recipients: 10,000/L versus 20,000/microL trigger.

An optimal platelet-count threshold for prophylactic platelet transfusion in hematopoietic stem cell transplant (HSCT) recipients has yet to be determined. Between July 1997 and December 1999, we performed the first prospective randomized clinical trial addressing this issue in 159 HSCT recipients who received a prophylactic platelet transfusion when the morning platelet count fell below a 10,000/microL (10K) or 20,000/microL (20K) threshold. Subsequent prophylactic transfusions were administered according to a predetermined algorithm. The number of prophylactic and therapeutic transfusions and the incidence of minor and major bleeding were compared between the 2 groups. The groups were matched according to patient and transplantation characteristics. There were no significant differences in bleeding incidence or severity. Fourteen percent of patients in the 10K arm compared to 17% in the 20K arm had major bleeding events. Only 3 central nervous system bleeds occurred, 2 in the 10K group and 1 in the 20K group. No deaths were attributed to bleeding. An average of 11.4 days of bleeding occurred in both groups. An average of 10.4 platelet transfusions per patient were administered in the 10K group compared to 10.2 in the 20K group (P = .94). More transfusions were given above the assigned transfusion threshold in the 10K group than in the 20K group (4.3/patient versus 1.9/patient, respectively, P = .05). Safety measures incorporated into our study may have precluded demonstration of significant differences in platelet use between the groups. In conclusion, a platelet transfusion trigger of 10K was found to be safe; however, a decrease in platelet use was not achieved because of safety measures incorporated into our study design.

Cumplir con la legislación sanitaria ofrece calidad y seguridad: tú lo haces? / To fulfill the sanitary legislation offers quality and security, do you do it?

En la práctica, pocos son los consultorios dentales particulares que superan con éxito la supervisión de las instancias sanitarias, sin embargo, creemos que nadie desea estar fuera de la ley o pasar un mal rato, en el caso de que se presente alguna verificación sanitaria, o sea citado por alguna queja sobre la prestación de servicios odontológicos

Fractura radicular horizontal en dientes permanentes: reporte de un caso / Root horizontal fracture in permanent teeth: report of a case

Se reporta el caso de un paciente masculino de 9 años y seis meses de edad, que recibe un traumatismo alvéolodentario, presentando fractura radicular horizontal de los incisivos centrales y lateral superior derecho, con desplazamiento fuera del alvéolo del segmento inferior del incisivo lateral. Se realiza recolocación de los fragmentos y ferulización con alambre y resina por 21 días, y sin necesidad de terapia endodóntica, se mantiene en observación durante 1 año, sin registar patología pulpar o resorciones, obteniéndose la unión de los segmentos fracturados