Guiding Principles for Implementing Stepped Care in Mental Health: Alignment on the Bigger Picture.

Stepped care models are a mental healthcare delivery framework in which a continuum of support allows selection of a range of interventions to match a client's evolving needs and preferences. Currently in use in multiple settings worldwide, stepped care has the potential to provide a needed advance for the development of comprehensive mental health systems. However, definitions of stepped care lack consistency, resulting in differing interpretations reflected in variable implementation, ultimately limiting its replicability, utility and potential for impact. To help foster greater alignment in research and practice, we propose a set of principles for stepped care which can provide guidance on how to bridge multiple mental health services together, reduce fragmentation, and respond to the full breadth of mental health needs along a continuum of care in diverse settings. We hope that articulating these principles will foster discussion and spur mental health stakeholders to translate them into actionable standards.

Metformin pretreatment potentiates the antiproliferative action of doxorubicin against breast cancer.

OBJECTIVES: The present study aimed to evaluate the effect of metformin pretreatment on the potentiation of antiproliferative action of doxorubicin against breast cancer. MATERIAL AND METHODS: Female Wistar rats were administered with 7,12-Dimethylbenz(a)anthracene (DMBA) (35mg) in 1mL olive oil subcutaneously beneath the mammary gland. Animals were pretreated with metformin (Met) 200mg/kg two weeks before DMBA administration. DMBA control groups received doxorubicin (Dox) (4mg/kg and 2mg/kg), Met (200mg/kg) alone and in combination with Dox (4mg/kg). Met pre-treated DMBA control groups received Dox 4mg/kg and 2mg/kg. RESULTS: Met pre-treated groups treated with Dox exhibited a decrease in tumor incidence, tumor volume and increased survival rate than the DMBA group. Organ-to-body weight ratios and histopathology of heart, liver and lungs of Met pre-treated groups treated with Dox showed lesser toxicity than Dox treated DMBA control groups. There was a noteworthy decrease in malondialdehyde levels and a substantial increase in the levels of reduced glutathione together with a significant decrease in the levels of inflammatory markers like IL-6, IL-1ß and NF-κB in Met pre-treated groups treated with Dox. Histopathology of breast tumors revealed better control of tumors in Met pre-treated groups treated with Dox than DMBA control group. Immunohistochemistry and real-time PCR data revealed a significant reduction in Ki67 expression in Met pre-treated groups treated with Dox as compared to the DMBA control group. CONCLUSION: The present study suggests that metformin pretreatment potentiates the antiproliferative action of doxorubicin against breast cancer.

A design concept of big data analytics model for managers in hospitality industries.

The hospitality and tourism sector has long played a significant role in Australia's economy, especially in regional areas. Due to the onslaught of COVID-19, numerous businesses have experienced lockdowns, restrictions, and closures due to the fact that people's activity in restaurants, shopping centers, and recreational destinations was restricted, and many other places went into hibernation. After about 2 years since the outbreak, businesses in this sector are gradually starting to reopen and revitalize themselves, but in order to have better decision support about the future of this sector, thus being able to plan, businesses are suffering from an effective analytics solution due to the lack of broken data trends. Starting from fresh day-to-day real-time big data, the study aims to develop a new data analytics model, adopting the design science research methodology, which can provide invaluable options and techniques to make prediction easier from immediate past datasets. This study introduces an innovative design artifact as a big data solution for hospitality managers to utilize analytics for predictive strategic decision-making in post-COVID situation. The artifact can also be generalized for other sectors with tailoring aspects which are subject to further studies. The proposed artifact is then compared with other design artifacts related to big data solutions where it outperforms them in terms of comprehensiveness. The proposed artifact also shows promises for primarily available UGC in managers' decision support aids.

Characterization and virulence factors distribution of blaCTX-M and mcr-1carrying Escherichia coli isolates from bovine mastitis.

AIM: To investigate the occurrence of ESBL and colistin-resistant E. coli and its genotypic characterization and identification of virulence determinants in cases of bovine mastitis in three provinces of China. MATERIALS AND METHODS: Five hundred and thirty-five milk samples presenting mastitis symptoms were screened for the presence of ESBL, colistin-resistant and different virulence genes. Susceptibility testing was identified by the micro-dilution method. Escherichia coli isolates were used to detect ESBL genes (blaCTX-M , blaSHV and blaTEM ) and colistin-resistant genes mcr-(1-9). Multiplex PCR approach was used for the detection of major blaCTX-M groups, different phylogroups and virulence genes. The clonal relationship was then evaluated with MLST, MLSA and PFGE. RESULTS: Multi-drug resistance (MDR) was found in more than 85% of ESBL and colistin-resistant E. coli isolates. Genotypic characterization showed a dominance of the blaCTX-M-1 group, and the most prevalent alleles observed were blaCTX-M-28 (38·37%), blaCTX-M-14 (17·44%), blaCTX-M-66 (13·95%) and blaCTX-M-55 (10·46%). The targeted virulence genes were detected in 97·89% of isolates. Sequence types ST58 and ST410 were the most predominant (2/20 = 20%). The majority of the E. coli isolates carrying ESBL and mcr-1 were clonally unrelated. CONCLUSION: High level of association was observed between ESBL-producing and COL-resistance in E. coli of bovine mastitis. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this is the first report which shows the genetic diversity of ESBL and mcr-1, and various virulent features of E. coli strains isolated from bovine clinical mastitis in three different provinces of China. The major carriers of the blaCTX-M-1 and blaCTX-M-9 were blaCTX-M-28 and blaCTX-M-14 alleles respectively. The association of ESBL-producing E. coli with mcr-1 is of particular concern.

Age differences in the association of comorbid burden with adverse outcomes in SARS-CoV-2.

BACKGROUND: Older age and comorbid burden are both associated with adverse outcomes in SARS-CoV-2, but it is not known whether the association between comorbid burden and adverse outcomes differs in older and younger adults. OBJECTIVE: To compare the relationship between comorbid burden and adverse outcomes in adults with SARS-CoV-2 of different ages (18-64, 65-79 and ≥ 80 years). DESIGN, SETTING, AND PARTICIPANTS: Observational longitudinal cohort study of 170,528 patients who tested positive for SARS-CoV-2 in the US Department of Veterans Affairs (VA) Health Care System between 2/28/20 and 12/31/2020 who were followed through 01/31/2021. MEASUREMENTS: Charlson Comorbidity Index (CCI); Incidence of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death within 30 days of a positive SARS-CoV-2 test. RESULTS: The cumulative 30-day incidence of death was 0.8% in cohort members < 65 years, 7.1% in those aged 65-79 years and 20.6% in those aged ≥80 years. The respective 30-day incidences of hospitalization were 8.2, 21.7 and 29.5%, of ICU admission were 2.7, 8.6, and 11% and of mechanical ventilation were 1, 3.9 and 3.2%. Median CCI (interquartile range) ranged from 0.0 (0.0, 2.0) in the youngest, to 4 (2.0, 7.0) in the oldest age group. The adjusted association of CCI with all outcomes was attenuated at older ages such that the threshold level of CCI above which the risk for each outcome exceeded the reference group (1st quartile) was lower in younger than in older cohort members (p < 0.001 for all age group interactions). LIMITATIONS: The CCI is calculated based on diagnostic codes, which may not provide an accurate assessment of comorbid burden. CONCLUSIONS: Age differences in the distribution and prognostic significance of overall comorbid burden could inform clinical management, vaccination prioritization and population health during the pandemic and argue for more work to understand the role of age and comorbidity in shaping the care of hospitalized patients with SARS-CoV-2.

Frass produced by the primary pest Rhyzopertha dominica supports the population growth of the secondary stored product pests Oryzaephilus surinamensis, Tribolium castaneum, and T. confusum.

Primary pests such as Rhyzoperta dominica may increase the contents of dockage, dust, and frass in grain mass. Although it has been suggested that frass can affect the population growth of stored product pests and ecological interactions among primary and secondary pests in stored grain, this has not been validated experimentally. Therefore, this work experimentally tested the hypothesis that R. dominica wheat frass may support population increases in secondary pests such as Tribolium confusum, T. castaneum, and Oryzaephilus surinamensis for the first time. The effect of frass on secondary pest performance was compared with the effects of various physical qualities of wheat grain (i.e., intact grain kernels, grain fragments, flour, grain + frass) and an artificially enriched control diet (milled wheat kernels, oat flakes, and yeast). The results showed that the clean intact grain kernels did not support the population growth of any tested species, and the nutrient-rich control diet provided the best support. Frass was a significantly better food medium for O. surinamensis and T. castaneum than flour or cracked grain, while T. confusum performed equally well on flour and frass. Our results showed that in terms of food quality and suitability for the tested species, frass occupied an intermediate position between the optimized breeding diet and simple uniform cereal diets such as cracked grain or flour. The results suggest that (i) the wheat frass of primary pest R. dominica is a riskier food source for the development of the tested secondary pests than intact or cracked wheat grain or flour; (ii) frass has the potential to positively influence interspecific interactions between R. dominica and the tested secondary pests; and (iii) wheat grain should be cleaned if increases in R. dominica populations and/or accumulated frass are detected.

Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies.

BACKGROUND: Selinexor is an oral inhibitor of the nuclear export protein Exportin 1 (XPO1) with demonstrated antitumor activity in solid and hematological malignancies. We evaluated the efficacy and safety of selinexor in heavily pretreated, recurrent gynecological malignancies. METHODS: In this phase 2 trial, patients received selinexor (35 or 50 mg/m2 twice-weekly [BIW] or 50 mg/m2 once-weekly [QW]) in 4-week cycles. Primary endpoint was disease control rate (DCR) including complete response (CR), partial response (PR) or stable disease (SD) ≥12 weeks. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: 114 patients with ovarian (N = 66), endometrial (N = 23) or cervical (N = 25) cancer were enrolled. Median number of prior regimens for ovarian, endometrial and cervical cancer was 6 (1-11), 2 (1-5), and 3 (1-6) respectively. DCR was 30% (ovarian 30%; endometrial 35%; cervical 24%), which included confirmed PRs in 8%, 9%, and 4% of patients with ovarian, endometrial, and cervical cancer respectively. Median PFS and OS for patients with ovarian, endometrial and cervical cancer were 2.6, 2.8 and 1.4 months, and 7.3, 7.0, and 5.0 months, respectively. Common Grade 3/4 adverse events (AEs) were thrombocytopenia (17%), fatigue (14%), anemia (10%), nausea (9%) and hyponatremia (9%). Patients with ovarian cancer receiving 50 mg/m2 QW had fewer high-grade AEs with similar efficacy as BIW treatment. CONCLUSIONS: Selinexor demonstrated single-agent activity and disease control in patients with heavily pretreated ovarian and endometrial cancers. Side effects were a function of dose level and treatment frequency, similar to previous reports, reversible and mitigated with supportive care.

COVID-19 Pandemic: What is Known Till June 2020 and What is Yet to Know?

Since first cluster of unknown pneumonia from China reported in December 2019 to World Health Organization, more than 10.5 million new cases and more than 0.513 million deaths have been reported till June 30, 2020 in six months' time. World got to know lot of facts about COVID-19 within short period of six months and success stories too concerning its containment. The situation has constantly been unfolding every moment educating people regarding public health and clinical aspects of the infection and disease and its impact on countries and communities. But still lot of information and evidences are required with regard to pharmacological interventions including effective drugs and efficacious vaccine to mitigate the impact of COVID-19 pandemic at all levels. It seems that we have to live with COVID-19 months-years as the virus is going to stay for longer period of time. The option is to continue practice of effective non-pharmacological interventions as to minimize spread of COVID-19 and ensure adequate provision of PPE to healthcare workforce and testing of health-care workers (HCWs) as to alleviate the anxiety of HCW and lessen their depletion by unnecessary quarantine thereby protect their health and reduce in hospital transmission.

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.

Short duration of untreated psychosis enhances negative symptom remission in extended early intervention service for psychosis.

OBJECTIVE: To test whether duration of untreated psychosis (DUP) < 3 months, recommended by the World Health Organization/International Early Psychosis Association, enhances the effects of an extended early intervention service (EEIS) on symptom remission. METHOD: We examined data from a randomized controlled trial in which patients who received 2 years of treatment in EIS for psychosis were subsequently randomized to either 3 years of EEIS or 3 years of regular care (RC). Using a DUP cut-off ≤ 12 weeks (approximately < 3 months), patients were split into two groups. Length of positive, negative and total symptom remission were the outcomes. RESULTS: Patients (N = 217) were mostly male (68%) with schizophrenia spectrum disorder (65%); 108 (50%) received EEIS (58 had DUP ≤12 weeks; 50 had DUP >12 weeks). Interaction between treatment condition (EEIS vs. RC) and DUP cut-off ≤ 12 weeks was only significant in multiple linear regression model examining length of negative symptom remission as the outcome (adjusted ß = 36.88 [SE = 15.88], t = 2.32, P = 0.02). EEIS patients with DUP ≤12 weeks achieved 25 more weeks of negative symptom remission than EEIS patients with DUP >12 weeks. CONCLUSION: Having a short DUP may be critical in deriving long-term benefits from EIS for psychosis, including EEIS settings. This work empirically supports policy recommendations of reducing DUP <3 months.

Medication adherence in first episode psychosis: the role of pre-onset subthreshold symptoms.

OBJECTIVE: The experience of pre-onset subthreshold psychotic symptoms (STPS, signifying a clinical high-risk state) in first episode psychosis (FEP) predicts poorer outcomes during treatment, possibly through differential adherence to medication. We explored whether adherence differs between FEP patients with and without pre-onset STPS. METHODS: Antipsychotic medication adherence was compared in 263 STPS+ and 158 STPS- subjects in a specialized early intervention program for FEP. Data were gathered from a larger observational study conducted between 2003 and 2016. STPS status, sociodemographic, and baseline clinical variables were tested as predictors of non-adherence using univariate and multivariate logistic regressions. Time to onset of non-adherence was analyzed using Kaplan-Meier curves. The same predictors were tested as predictors of time to onset of non-adherence using Cox regression models. RESULTS: Medication non-adherence was higher in STPS+ participants (78.9% vs. 68.9%). STPS status (OR 1.709), substance use disorder (OR 1.767), and milder positive symptoms (OR 0.972) were significant baseline predictors of non-adherence. Substance use disorder (HR 1.410), milder positive symptoms (HR 0.990), and lack of contact between the clinical team and relatives (HR 1.356) were significant baseline predictors of time to non-adherence. CONCLUSION: FEP patients who experience pre-onset STPS are more likely to be non-adherent to antipsychotic medication over 2 years of intervention. FEP programs should routinely evaluate pre-onset symptomatology to deliver more personalized treatments, with emphasis on engaging both patients and family members from the beginning of care.

Smartphone geospatial apps for dengue control, prevention, prediction, and education: MOSapp, DISapp, and the mosquito perception index (MPI).

India has the largest number of dengue cases in the world, contributing approximately 34% of the global burden. The framework for a geospatially enabled early warning and adaptive response system (EWARS) was first proposed in 2008. It was meant to be a decision support system for enhancing traditional surveillance methods for preventing mosquito-borne diseases in India by utilizing remote sensing data and fuzzy logic-based mathematical predictive modeling. This conceptual paper presents a significant evolution of EWARS such that it synthesizes inputs from not only traditional surveillance and reporting systems for dengue but also from the public via participatory disease surveillance. Two smartphone-based applications have been developed to support EWARS. The first-MOSapp-allows field health workers to upload surveillance data and collect key data on environmental parameters by both direct observation and via portable microclimate stations. The second-DISapp-collects relevant information directly from the community to support participatory disease surveillance. It also gives the user a real-time estimate of the risk of exposure to dengue in proximity to their home and has an educational component that provides information on relevant preventive measures. Both applications utilize a new mosquito abundance measure-the mosquito perception index (MPI)-as reported by the user. These data streams will feed into the EWARS model to generate dynamic risk maps that can guide resource optimization and strengthen disease surveillance, prevention, and response. It is anticipated that such an approach can assist in addressing gaps in the current system of dengue surveillance and control in India.

Bone density and microarchitecture in hepatitis C and HIV-coinfected postmenopausal minority women.

We found that HIV+/HCV+ women had 7-8% lower areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) at the spine, hip, and radius (p < 0.01) and 5-7% lower volumetric BMD (vBMD) by central quantitative computed tomography (cQCT) at the spine and hip (p < 0.05). These data suggest that true deficits in vBMD may contribute to bone fragility and excess fractures reported in HIV+/HCV+ women. INTRODUCTION: aBMD by DXA is lower in persons coinfected with HIV and HCV (HIV+/HCV+) than with HIV monoinfection (HIV+). However, weight is often also lower with HCV infection, and measurement of aBMD by DXA can be confounded by adiposity; we aimed to determine whether true vBMD is also lower in HIV+/HCV+ coinfection. METHODS: We measured aBMD of the lumbar spine (LS), total hip (TH), femoral neck (FN), and ultradistal radius (UDR) by DXA and vBMD of the spine and hip by cQCT and of the distal radius and tibia by high-resolution peripheral QCT (HRpQCT) in 37 HIV+/HCV+ and 119 HIV+ postmenopausal women. Groups were compared using Student's t tests with covariate adjustment by multiple regression analysis. RESULTS: HIV+/HCV+ and HIV+ women were of similar age and race/ethnicity. HIV+/HCV+ women had lower body mass index (BMI) and trunk fat and were more likely to smoke and less likely to have a history of AIDS. In HIV+/HCV+ women, aBMD by DXA was 7-8% lower at the LS, TH, and UDR (p < 0.01). Similarly, vBMD by cQCT was 5-7% lower at the LS and TH (p < 0.05). Between-group differences in LS aBMD and vBMD remained significant after adjustment for BMI, smoking, and AIDS history. Tibial total vBMD by HRpQCT was 10% lower in HIV+/HCV+ women. CONCLUSION: HIV+/HCV+ postmenopausal women had significantly lower spine aBMD and vBMD. These deficits in vBMD may contribute to bone fragility and excess fractures reported in HIV+/HCV+ women.

Correction to: Development of a sensitive PCR-dot blot assay to supplement serological tests for diagnosing Lyme disease.

In the original version of this article, the word "flagellin" is not correct. The correct word should be "P66" throughout the body of the article.

Development of a sensitive PCR-dot blot assay to supplement serological tests for diagnosing Lyme disease.

Laboratory diagnosis of Lyme disease is difficult and presently dependent on detecting Borrelia burgdorferi-specific antibodies in patient serum with the disadvantage that the immune response to B. burgdorferi can be weak or variable, or alternatively, the slow and inefficient culture confirmation of B. burgdorferi. PCR tests have previously shown poor sensitivity and are not routinely used for diagnosis. We developed a sensitive and specific Lyme Multiplex PCR-dot blot assay (LM-PCR assay) applicable to blood and urine samples to supplement western blot (WB) serological tests for detecting B. burgdorferi infection. The LM-PCR assay utilizes specific DNA hybridization to purify B. burgdorferi DNA followed by PCR amplification of p66 [corrected] and OspA gene fragments and their detection by southern dot blots. Results of the assay on 107 and 402 clinical samples from patients with suspected Lyme disease from Houston, Texas or received at the IGeneX laboratory in Palo Alto, California, respectively, were analyzed together with WB findings. The LM-PCR assay was highly specific for B. burgdorferi. In the Texas samples, 23 (21.5%) patients antibody-negative in WB assays by current US Centers for Disease Control (CDC) recommended criteria were positive by LM-PCR performed on urine, serum or whole blood samples. With IGeneX samples, of the 402 LM-PCR positive blood samples, only 70 met the CDC criteria for positive WBs, while 236 met IGeneX criteria for positive WB. Use of the LM-PCR assay and optimization of current CDC serological criteria can improve the diagnosis of Lyme disease.

Prolonged Survival Following Pig-to-Primate Liver Xenotransplantation Utilizing Exogenous Coagulation Factors and Costimulation Blockade.

Since the first attempt of pig-to-primate liver xenotransplantation (LXT) in 1968, survival has been limited. We evaluated a model utilizing α-1,3-galactosyltransferase knockout donors, continuous posttransplant infusion of human prothrombin concentrate complex, and immunosuppression including anti-thymocyte globulin, FK-506, methylprednisone, and costimulation blockade (belatacept, n = 3 or anti-CD40 mAb, n = 1) to extend survival. Baboon 1 remained well until postoperative day (POD) 25, when euthanasia was required because of cholestasis and plantar ulcers. Baboon 2 was euthanized following a seizure on POD 5, despite normal liver function tests (LFTs) and no apparent pathology. Baboon 3 demonstrated initial stable liver function but was euthanized on POD 8 because of worsening LFTs. Pathology revealed C4d positivity, extensive hemorrhagic necrosis, and a focal cytomegalovirus inclusion. Baboon 4 was clinically well with stable LFTs until POD29, when euthanasia was again necessitated by plantar ulcerations and rising LFTs. Final pathology was C4d negative and without evidence of rejection, inflammation, or thrombotic microangiopathy. Thus, nearly 1-mo rejection-free survival has been achieved following LXT in two of four consecutive recipients, demonstrating that the porcine liver can support life in primates for several weeks and has encouraging potential for clinical application as a bridge to allotransplantation for patients with acute-on-chronic or fulminant hepatic failure.

Role of Intrinsic (Graft) Versus Extrinsic (Host) Factors in the Growth of Transplanted Organs Following Allogeneic and Xenogeneic Transplantation.

In our studies of life-supporting α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidneys, we found that some recipients developed increased serum creatinine with growth of the grafts, without histological or immunological evidence of rejection. We hypothesized that the rapid growth of orthotopic pig grafts in smaller baboon recipients may have led to deterioration of organ function. To test this hypothesis for both kidneys and lungs, we assessed whether the growth of outbred (Yorkshire) organ transplants in miniature swine was regulated by intrinsic (graft) or extrinsic (host environment) factors. Yorkshire kidneys exhibited persistent growth in miniature swine, reaching 3.7 times their initial volume over 3 mo versus 1.2 times for miniature swine kidneys over the same time period. Similar rapid early growth of lung allografts was observed and, in this case, led to organ dysfunction. For xenograft kidneys, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm3 /kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are responsible, at least in part, for growth of donor organs and that this property should be taken into consideration for growth-curve-mismatched transplants, especially for life-supporting organs transplanted into a limited recipient space.

The Effects of Exogenous Administration of Human Coagulation Factors Following Pig-to-Baboon Liver Xenotransplantation.

We sought to determine the effects of exogenous administration of human coagulation factors following pig-to-baboon liver xenotransplantation (LXT) using GalT-KO swine donors. After LXT, baboons received no coagulation factors (historical control, n = 1), bolus administration of a human prothrombin concentrate complex (hPCC; 2.5 mL/kg, n = 2), continuous infusion of hPCC (1.0 mL/h, n = 1) or continuous infusion of human recombinant factor VIIa (1 µg/kg per hour, n = 3). The historical control recipient demonstrated persistent thrombocytopenia despite platelet administration after transplant, along with widespread thrombotic microangiopathy (TMA). In contrast, platelet levels were maintained in bolus hPCC recipients; however, these animals quickly developed large-vessel thrombosis and TMA, leading to graft failure with shortened survival. Recipients of continuous coagulation factor administration experienced either stabilization or an increase in their circulating platelets with escalating doses. Furthermore, transfusion requirements were decreased, and hepatic TMA was noticeably absent in recipients of continuous coagulation factor infusions compared with the historical control and bolus hPCC recipients. This effect was most profound with a continuous, escalating dose of factor VIIa. Further studies are warranted because this regimen may allow for prolonged survival following LXT.