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Immunocompromised patients with B-cell deficiencies are at risk for prolonged symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We describe 4 patients treated for B-cell malignancies with B-cell-depleting therapies who developed persistent SARS-CoV-2 infection and had resolution of symptoms following an extended course of nirmatrelvir/ritonavir.

The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates.Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees.Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation.Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

In this paper a low temperature metallization i.e. standardization of electroless Ni plating on alumina ceramic is summarized. It includes three main steps (i) pre-treatment, (ii) activation and (iii) Ni plating. Pre-treatment includes degreasing with non-silicate soap solution followed by ultrasonic cleaning in acetone and etching the alumina surface to generate roughness for making it suitable for adhesion. Etching has been obtained by immersion in 10% NaOH at 50℃ for 10 minutes and 50% HF for 15 minutes at room temperature. Activation of the surface is the most important step before electroless plating on alumina ceramic. Activation has been achieved with Ginplate 442 (commercial chemical) by immersing the alumina specimen for 5 minutes at room temperature. Activated alumina samples have been used for electroless Ni plating in Ginplate 418 bath at 88°C.Uniform, densely compact coating has been achieved as revealed by SEM image. XRD plot confirms the presence of metallic nickel together with phases of Ni2P, NiP, Ni3P confirming the nickel phosphite based plating. Subsequently, tube to tube joining of these metallized alumina ceramic tubes has been conducted through vacuum brazing process with copper silver eutectic alloy (28Cu-72Ag) whose cross section showed good joint with excellent wettability of Cu-Ag with Ni plating.

The genital epithelial barrier is a crucial first line of defence against HIV, and epithelial disruption may enhance HIV susceptibility. Assessment of genital epithelial integrity require biopsies, but their collection is not practical in many research settings. A validated biomarker of genital epithelial barrier integrity would therefore be useful. E-cadherin, an adhesion component of the cell-cell junction in epithelial tissues, may be released as soluble E-cadherin (sE-cad) upon epithelial trauma, and so we evaluated sE-cad as a marker of genital epithelial disruption. First, using an in vitro monolayer of immortalised endocervical epithelial cells, we demonstrate that sE-cad, IL-1β, and IL-1α levels are immediately increased after physical disruption, followed by a delayed increase in IL-6 levels compared to undisrupted controls. In vivo studies confirmed that sE-cad levels in cervicovaginal secretions were significantly elevated 6 hours after endocervical cytobrush sampling. Furthermore, the level of sE-cad in coronal sulcus swabs from Ugandan men was inversely correlated with the amount of membrane-bound E-cadherin within the overlying foreskin tissues. Our results validate the use of soluble E-cadherin as a marker of epithelial disruption and demonstrate that the processes of physical disruption and inflammation in the genital tract are strongly intertwined.

Thin films of in-bulk unstable multiferroic hexagonal LuFeO3 were synthesized on coherent (111) and for the first time on incoherent (100) YSZ and Pt/YSZ surfaces by the metal–organic chemical vapo...

The temperature–frequency spectra of the complex dielectric permittivity of the LuFe2O4 multiferroics have been studied in the temperature range 100–400 K at frequencies 20 Hz–120 MHz. It is found that the temperature coefficient of the dielectric permittivity changes its sign and the ac conductivity has maxima and minima in the temperature range ~150–350 K and in the frequency range ~30–120 MHz. These specific features are due to independent resonance mechanisms: the coincidence of frequency of the measuring ac voltage with the frequency of electron jumps as the hopping conductivity takes place; the proximity of the measurement signal period to the time of formation of a barrier layer at the boundary of contact with the sample; and the approximation of the frequency of an ac external field to the frequency of the sample structural elements.

Living kidney donation is widely practiced throughout the world. During the past 2 decades, various groups have provided guidance about the evaluation and care of living donors. However, during this time, our knowledge in the field has advanced substantially and many agreed on the need for a comprehensive, unifying document. KDIGO (Kidney Disease: Improving Global Outcomes) addressed this issue at an international level with the publication of its clinical practice guideline on the evaluation and care of living kidney donors. The KDIGO work group extensively reviewed the available literature and wrote a series of guideline recommendations using various degrees of evidence when available. As has become recent practice, NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) convened a work group to provide a commentary on the KDIGO guideline, with a focus on how these recommendations apply in the context of the United States. In the United States, the United Network for Organ Sharing (UNOS) guides and regulates the practice of living kidney donation. While the KDIGO guideline for the care of living kidney donors and UNOS policy are similar in most aspects of the care of living kidney donors, several important areas are not consistent or do not align with common practice by US transplantation programs in areas in which UNOS has not set specific policy. For the time being, and recognizing the value of the KDIGO guidelines, US transplantation programs should continue to follow UNOS policy.

Funding Acknowledgements Type of funding sources: None. Background The 2020 ESC guidelines for managing NSTE-ACS recommend against routine pre-treatment with a P2Y12 receptor inhibitor if coronary anatomy is not known and an early (24h) invasive management, pre-treatment may be considered in selected cases. Purpose Evaluate antiplatelet pre-treatment practices for NSTE-ACS in a tertiary cardiology centre in Australia. Methods Retrospective analysis of NSTE-ACS cases from January to August 2021 were obtained from the cardiac laboratory database. Patients on a P2Y12 inhibitor prior to presentation were excluded. Clinical, demographic, angiographic and medication data were obtained from the electronic database. Results 85 cases were included. Mean age was 62 ± 11.5 and 81% were male. The prevalence of hypertension, hypercholesterolaemia, type 2 diabetes and active smoking was 54.8%, 51.2%, 38.1% and 34.5% respectively. Mean time to angiography was 1.7 ± 1.4 days and the median peak pre-procedural troponin T was 191.5 (80 to 852). Access was predominantly radial (84.5%) with the remainder femoral (15.5%). Angiographic findings included, obstructive disease amenable to percutaneous coronary intervention (50.0%), obstructive disease for surgical revascularisation (22.6%), and non-obstructive disease (27.4%). The mean time from angiography to surgical revascularisation was 6.4 ± 4.4 days. Three patients (3.6%) had bleeding [managed conservatively], specifically upper limb haematoma, groin haematoma, and haemoptysis. The majority of patients (79.8%) received P2Y12 inhibitors (40.5% clopidogrel and 39.3% ticagrelor) prior to angiography. Of these, 49.3% had percutaneous angioplasty, 17.9% had surgical revascularisation and 32.8% had non-obstructive disease (managed with single antithrombotic agent). Of those who did not receive P2Y12 inhibitors [n = 17, 20.2%]. Of these, 53% had percutaneous angioplasty, 40% had surgical revascularisation, and 5% had non-obstructive disease. Conclusions Overall, pre-treatment with a P2Y12 inhibitor was still very common, risking delays to bypass surgery and increasing bleeding. Practice did not generally align with contemporary ESC 2020 guidelines. Understanding the reasons for guideline non-compliance would be important for optimising treatments. Education for emergency and cardiology staff as well as creation of local practice policies may help increase compliance with evidence-based guidelines.

Background Sepsis is a leading cause of death, particularly in immunocompromised people. The revised definition of sepsis (Sepsis-3) uses the Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) to identify patients with sepsis. The aim of this study was to evaluate the performance of SOFA, qSOFA, and systemic inflammatory response syndrome (SIRS) in immunocompromised patients. Methods Adult immunocompromised patients admitted to Michigan Medicine between 2012 and 2018 with suspected infection were included based on criteria adopted from the Sepsis-3 study. Each clinical score (SOFA ≥2, qSOFA ≥2, SIRS ≥2) was added to the baseline risk model as an ordinal variable as well as a dichotomous variable, and area under the receiver operating characteristic curve (AUROC) values were calculated. In addition, breakpoints of SOFA between 2 and 10 were assessed to identify the breakpoints with the highest sensitivity and specificity for hospital mortality. The analysis was stratified for intensive care unit (ICU) status. Results Of 2822 immunocompromised patients with a mean age of 56.8±15.6 years, 213 (7.5%) died during hospitalization. When added to the baseline risk model, SOFA score had the greatest predictive validity for hospital mortality (AUROC,0.802; 95% CI, 0.771–0.832), followed by qSOFA (AUROC,0.783; 95% CI, 0.754–0.812) and SIRS (AUROC,0.741; 95% CI, 0.708–0.774). Among the SOFA breakpoints that were evaluated, SOFA ≥6 had the greatest predictive validity and a moderate positive likelihood ratio (2.75) for hospital mortality. Conclusions The predictive validity for hospital mortality of qSOFA was similar among immunocompromised patients as that reported in the Sepsis-3 study. The sensitivity of qSOFA ≥2 for hospital mortality was low. SOFA ≥6 might be an effective tool to identify immunocompromised patients with suspected infection at high risk for clinical deterioration.

The purpose of this study was to explore how a semester-long scholar practitioner workshop influenced student affairs professionals’ quantitative research and statistics competency. Participants’ p...

—2G HTSC tapes YBCO/LZO/Ni-5W and YBCO/Y2O3/LZO/Ni-5W with the minimum number of layers are obtained. Heteroepitaxial structures (layers La2Zr2O7, Y2O3 and YBa2Cu3O7) are formed by chemical deposition from a solution and chemical vapor deposition. Their textural quality is confirmed by XRD. The influence of the layers on each other is shown. Many factors for improving the quality of the 2G HTSC tapes obtained by chemical methods are considered.

The microstructure of GdBa2Cu3O7−δ based on superconducting tapes with BaSnO3 and BaZrO3 artificial pinning centers formed by high-rate pulse laser deposition in SuperOx Japan was studied by scanning/transmission electron microscopy. The artificial pinning centers have adopted columnar morphology with average diameter of about 8 nm (BaSnO3-doped sample) and 6.5 nm (BaZrO3-doped sample) and density of 500 μm−2 for the both samples. The average length of the BaSnO3 nanocolumns is about two times higher than the BaZrO3 nanocolumns. The angular dependences of critical current in magnetic field up to 1 Tesla at 77 and 65 K have been obtained. The critical current and its anisotropy depend on artificial pinning centers presence and their type. The angular dependence of resistivity in the field up to 9 Tesla was also studied and discussed.

This study examined teacher beliefs regarding research-based practices in gifted education and how these beliefs or other barriers influenced the implementation of practices in their classroom. An online survey was sent to gifted education teachers in a large suburban district. The teacher belief statements were developed based on the National Association for Gifted Children (NAGC) Pre-K-Grade 12 Gifted Programming Standards. Although a majority of the teachers agreed with the research-based belief statements, fewer implemented the practice in their classrooms frequently. If they did implement the practice, they perceived positive student outcomes. Teachers did identify these obstacles related to implementation: limited resources, training, skill level, and the school system curriculum.

Secondary data analysis can benefit researchers of advanced academics by providing large sample sizes and a variety of data on multiple topics. However, using secondary data comes with unique challenges. This article will outline how gifted education researchers can find, access, and use secondary data. Data are available on children from birth to adulthood and are typically accessed through the Inter-university Consortium for Political and Social Research (ICPSR) or the National Center for Education Statistics (NCES). The majority of data sources have public-use files available, but some sensitive data may require special permissions. This article includes examples of advanced academic research that used popular databases along with software options for utilizing available data. We conclude with considerations researchers should take into account when considering using secondary data analysis, such as computer memory and technical skills.

PURPOSE The purpose of this study was to compare the safety and efficacy of two valganciclovir (VGCV) institutional dosing protocols for cytomegalovirus (CMV) prophylaxis in liver transplant (LT) recipients with CMV serotype donor +/recipient- (D+/R-). METHODS This was a single-center review of CMV D+/R- adult LT recipients who received VGCV 450 mg/day for 90 days (low-dose) or VGCV 900 mg/day for 180 days (standard-dose). The primary outcome was incidence of CMV disease at 1 year. Secondary outcomes included rates of CMV syndrome, end-organ disease, breakthrough infection, and resistance. Neutropenia, early discontinuation of VGCV, growth colony stimulating factors use (G-CSF), biopsy-proven rejection (BPAR), graft loss, and death at 1 year were analyzed. RESULTS Ninety-six CMV D+/R- LT recipients were included. Although no difference in CMV disease was observed (low-dose 26% vs. standard-dose 23%, p = 0.71), 75% of CMV infections in the low-dose group presented with end-organ disease. Ganciclovir (GCV) resistance was observed only in the low-dose group (n = 2). Significantly more patients in the standard-dose group developed neutropenia (low-dose 10% vs 60% standard-dose, p

The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger persons. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly observed in women and persons with a history of previous drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups. Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.

Few options are available for cytomegalovirus (CMV) treatment in transplant recipients resistant, refractory, or intolerant to approved agents. Letermovir (LET) is approved for prophylaxis in hematopoietic cell transplant (HCT) recipients, but little is known about efficacy in CMV infection. We conducted an observational study to determine the patterns of use and outcome of LET treatment of CMV infection in transplant recipients.Patients who received LET for treatment of CMV infection were identified at 13 transplant centers. Demographic and outcome data were collected.Twenty-seven solid organ and 21 HCT recipients (one dual) from 13 medical centers were included. Forty-five of 47 (94%) were treated with other agents prior to LET, and 57% had a history of prior CMV disease. Seventy-seven percent were intolerant to other antivirals; 32% were started on LET because of resistance concerns. Among 37 patients with viral load 1000 international units (IU)/ml at LET initiation, two experienced 1 log rise in viral load by week 12, and no deaths were attributed to CMV. Ten patients had viral load 1000 IU/ml at LET initiation, and six of 10 (60%) had a CMV viral load 1000 IU/ml at completion of therapy or last known value. LET was discontinued in two patients for an adverse event.Patients treated with LET with viral load 1000 IU/ml had good virologic outcomes. Outcomes were mixed when LET was initiated at higher viral loads. Further studies on combination therapy or alternative LET dosing are needed.

Despite emerging data suggesting reduced antibody responses among solid organ transplant recipients following SARS‐CoV‐2 vaccine, critical unanswered questions remain. The clinical implications of the reduced humoral response need to be assessed through prospective studies. Studies are likewise needed to inform which vaccine dosing strategies result in improved immunity and if such approaches maximize protection against severe infection in the vulnerable transplant population.

We describe a case of proven transmission of SARS-CoV-2 from lung donor to recipient. The donor had no clinical history or findings suggestive of infection with SARS-CoV-2 and tested negative by reverse transcriptase polymerase chain reaction (RT-PCR) on a nasopharyngeal (NP) swab obtained within 48 h of procurement. Lower respiratory tract testing was not performed. The recipient developed fever, hypotension, and pulmonary infiltrates on posttransplant day (PTD) 3, and RT-PCR testing for SARS-CoV-2 on an NP swab specimen was non-reactive, but positive on bronchoalveolar lavage (BAL) fluid. One thoracic surgeon present during the transplantation procedure developed COVID-19. Sequence analysis of isolates from donor BAL fluid (obtained at procurement), the recipient, and the infected thoracic surgeon proved donor origin of recipient and health-care worker (HCW) infection. No other organs were procured from this donor. Transplant centers and organ procurement organizations should perform SARS-CoV-2 testing of lower respiratory tract specimens from potential lung donors, and consider enhanced personal protective equipment for HCWs involved in lung procurement and transplantation.

Background Reducing immunosuppression can effectively treat BK viremia (BKV) and BK nephropathy, but has been associated with increased risks for acute rejection and development of donor-specific antibodies (DSA). To date there have been no systematic evaluations of re-escalating immunosuppression in transplant patients with resolving BKV. Importantly, the safety of this approach and impact on graft survival is unclear. Methods We performed a single-center retrospective review of kidney transplant recipients between July 2011 and June 2013 who had immunosuppression reduction after developing BKV (plasma PCR ≥ 1000 copies/ml). Changes in immunosuppression and patient outcomes were tracked until occurrence of a complication event: biopsy-proven acute rejection (BPAR), detection of de novo DSA, or recurrent BKV. Patients were grouped according to whether or not net immunosuppression was eventually increased. Results Out of 88 patients with BKV, 44 (50%) had net immunosuppression increased while the other 44 did not. Duration of viremia, peak viremia, induction, and sensitization status were similar between the two groups. In a Kaplan-Meier analysis, increasing immunosuppression was associated with less BPAR (P = .001) and a trend toward less de novo DSA development (P = .06). Death-censored graft survival (P = .27) was not different between the two groups. In the net immunosuppression increase group, recurrent BKV occurred in 22.7% without any BKV-related graft losses. Conclusion These findings support potential benefits of increasing immunosuppression in patients with low-level or resolved BKV, but prospective trials are needed to better understand such an approach.

Maxillofacial injuries are usually not life-threatening and do not get priority over other associated injuries. However, some maxillofacial injuries with active oral or nasal bleeding need immediate management due to threatened airway and blood loss. In the case of major active vascular bleeding, measures such as local pressure, anterior nasal packing, posterior nasal packing, and balloon tamponade are ineffective. In these cases, angiography and transcatheter arterial embolisation (TAE) are used to treat life-threatening haemorrhage caused by maxillofacial trauma. We analysed the medical records of 39 patients with severe maxillofacial trauma and life-threatening haemorrhage that was a result of intractable oral or nasal bleeding. These patients were considered for TAE from January 2010 to December 2019. A total of 1668 patients was admitted, out of which 39 (2.3%) had severe maxillofacial injuries with life-threatening oral or nasal bleeding and underwent TAE. Out of a total of 39 patients, 38 were male and one female. Ages ranged from 16 to 65 years. Road traffic injury was the most common cause of injury (79.5%), Lefort I and II were the most common facial fractures, and traumatic brain injury was the most common associated injury. Embolisation and bleeding control were done successfully in all 39 patients with no procedure-related complications. A total of 17 deaths during the study period were due to severe traumatic brain injuries or haemorrhagic shock.

BackgroundSevere COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers. This presentation is consistent with cytokine release syndrome in chimeric antigen receptor T cell therapy, for which IL-6 blockade is approved treatment.MethodsWe assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW).Findings154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.59 (0.36, 0.95)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; pInterpretationIn this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with a decreased likelihood of death despite higher superinfection occurrence. Randomized controlled trials are urgently needed to confirm these findings.KEY POINTSQuestionCan therapy with the IL-6 receptor antagonist tocilizumab improve outcomes in patients with severe COVID-19 illness requiring mechanical ventilation?FindingsIn this observational, controlled study of 154 patients, receipt of tocilizumab was associated with a 45% reduction in the hazard of death, despite twice the frequency of superinfection (54% vs 26%), both of which were statistically significant findings.MeaningTocilizumab therapy may improve survival in patients with COVID-19 illness requiring mechanical ventilation. These results can inform clinical practice pending the results of randomized clinical trials.

Student veterans on college and university campuses are a unique, under-researched population. The current study (n = 119) investigated the criteria used when student veterans select a private, nonprofit college or university. A one-factor model of support for disability needs constructed from prior research was tested and found to have adequate fit. The factor support was used in structural equation modeling to test the relationship between demographic information, such as length of time in the military, and endorsement of disability services as a criterion for selecting the private, nonprofit college or university. Results indicate veterans who served more time in the military are more likely to select a school based on the presence of disability services.