Perceived transition readiness among adolescents and young adults with neurofibromatosis type 1 and plexiform neurofibromas: a cross-sectional descriptive study.

OBJECTIVES: Neurofibromatosis type 1 (NF1) is a genetic cancer predisposition syndrome that can impact multiple organ systems and is associated with plexiform neurofibroma tumors, requiring care from birth through adulthood. Adolescents and young adults (AYAs) with NF1 face several barriers to transition from pediatric to adult care. This cross-sectional study aimed to assess transition readiness in this population and to evaluate relationships between specific NF1 symptoms and transition readiness. METHODS: AYAs (aged 16-24) enrolled in existing studies related to NF1 were eligible. AYAs and their parents completed measures of transition readiness (Transition Readiness Assessment Questionnaire version 4 [TRAQ-4]), and AYAs also completed a transition readiness interview (UNC TRxANSITION). RESULTS: Thirty-eight AYAs (mean age = 19.95 ± 2.68 years) participated in the study. Average TRAQ scores indicated that AYAs were still learning Self-Management skills (M = 3.37, SD = 1.08) and Self-Advocacy skills (M = 3.98, SD = 0.67). Older AYAs had higher TRAQ scores for Self-Management (r = 0.70, p < .001) and Self-Advocacy (r = 0.41, p = .011) than younger AYAs. Parents and AYAs had similar TRAQ scores. About one third of AYAs (37.8%, n = 14) expressed uncertainty about how NF1 might affect them in the future. The remaining AYAs mostly expressed concerns regarding tumor growth, pain, or cancer. CONCLUSIONS: In this small study, preliminary findings suggest that AYAs with NF1 express confidence in many areas of transition readiness but continue to require support, particularly with Self-Management skills. Given the gaps in understanding of future health risks, AYAs with NF1 would benefit from early assessment, psychoeducation, and support for transition readiness to adult care.

Perspectives of adults with neurofibromatosis regarding the design of psychosocial trials: Results from an anonymous online survey.

BACKGROUND/AIMS: Individuals with neurofibromatosis, including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2)-related schwannomatosis (SWN), and other forms of SWN, often experience disease manifestations and mental health difficulties for which psychosocial interventions may help. An anonymous online survey of adults with neurofibromatosis assessed their physical, social, and emotional well-being and preferences about psychosocial interventions to inform clinical trial design. METHODS: Neurofibromatosis clinical researchers and patient representatives from the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration developed the survey. Eligibility criteria included age ≥ 18 years, self-reported diagnosis of NF1, NF2, or SWN, and ability to read and understand English. The online survey was distributed internationally by the Neurofibromatosis Registry and other neurofibromatosis foundations from June to August 2020. RESULTS: Surveys were completed by 630 adults (18-81 years of age; M = 45.5) with NF1 (78%), NF2 (14%), and SWN (8%) who were mostly White, not Hispanic/Latino, female, and from the United States. The majority (91%) reported that their neurofibromatosis symptoms had at least some impact on daily life. In the total sample, 51% endorsed a mental health diagnosis, and 27% without a diagnosis believed they had an undiagnosed mental health condition. Participants indicated that neurofibromatosis affected their emotional (44%), physical (38%), and social (35%) functioning to a high degree. Few reported ever having participated in a drug (6%) or psychosocial (7%) clinical trial, yet 68% reported they "probably" or "definitely" would want to participate in a psychosocial trial if it targeted a relevant concern. Top treatment targets were anxiety, healthier lifestyle, and daily stress. Top barriers to participating in psychosocial trials were distance to clinic, costs, and time commitment. Respondents preferred interventions delivered by clinicians via individual sessions or a combination of group and individual sessions, with limited in-person and mostly remote participation. There were no significant group differences by neurofibromatosis type in willingness to participate in psychosocial trials (p = 0.27). Regarding interest in intervention targets, adults with SWN were more likely to prefer psychosocial trials for pain support compared to those with NF1 (p < 0.001) and NF2 (p < 0.001). CONCLUSION: This study conducted the largest survey assessing physical symptoms, mental health needs, and preferences for psychosocial trials in adults with neurofibromatosis. Results indicate a high prevalence of disease manifestations, psychosocial difficulties, and untreated mental health problems in adults with neurofibromatosis and a high degree of willingness to participate in psychosocial clinical trials. Patient preferences should be considered when designing and implementing psychosocial interventions to develop the most feasible and meaningful studies.

Vaping-associated lung illness (VALI) in Canada: a descriptive analysis of VALI cases reported from September 2019 to December 2020. / La maladie pulmonaire associée au vapotage (MPAV) au Canada : une analyse descriptive des cas de MPAV signalés entre septembre 2019 et décembre 2020.

INTRODUCTION: The aim of this study was to explore demographic and clinical characteristics of vaping-associated lung illness (VALI) cases reported in Canada from September 2019 to December 2020; compare the epidemiology of VALI cases in Canada to e-cigarette or vaping product use-associated lung injury (EVALI) cases in the US; and examine possible explanations for differences between the two countries. METHODS: A federal/provincial/territorial task group developed a national outbreak definition, minimum dataset and case report form for identification and surveillance of VALI cases in Canada. Descriptive analysis explored the characteristics and epidemiology of reported VALI cases. RESULTS: Of the 20 VALI cases reported, none resulted in a death. Of all cases, 5 (25%) involved youth aged 15 to 19 years, 10 (50%) adults aged 20 to 49 years and 5 (25%) aged 50 years and older. Sixty percent of patients were men. Half (50%) required breathing assistance. Three-quarters (75%) reported using nicotine-containing vaping products, and 40% reported use of cannabis-containing vaping products; of those who reported frequency of vaping, most (71%) reported vaping daily. VALI cases were reported at a lower prevalence (0.9 per million) than EVALI (8.5 per million). Demographics and vaping behaviour also differed. CONCLUSION: VALI cases were reported in Canada between September 2019 and December 2020; however, there was a much lower prevalence and they may have been caused by different factors from the EVALI outbreak in the US. The factors influencing VALI in Canada are complex and multifactorial. Research is needed to understand the short- and long-term health effects of nicotine and cannabis vaping.

Impact of the coronavirus pandemic on mental health and health care in adults with neurofibromatosis: Patient perspectives from an online survey.

The coronavirus pandemic increased anxiety and stress and prevented access to health care worldwide; it is unclear how COVID-19 affected adults with a multisystem genetic disorder such as neurofibromatosis (NF). An anonymous online survey was distributed through an international registry and foundations to adults with NF (June-August 2020) to assess the impact of the pandemic on mental health and NF health care. Six hundred and thirteen adults (18-81 years; M = 45.7) with NF1 (77.8%), NF2 (14.2%), and schwannomatosis (7.8%) provided complete responses. Respondents rated moderate-to-high amounts of worry about the impact of COVID-19 on their emotional (46.3%) and physical health (46.7%), and 54.8% endorsed moderate-to-high pandemic-related stress. Adults with diagnosed/suspected mental health disorders or moderate-to-severe NF symptom impact as well as females endorsed higher COVID-19 stress (ps < 0.01). Less than half who missed a doctor's appointment for their NF care (43.4%) used telehealth. Of these, 33.3% and 46.2% reported that telehealth met their needs to a moderate or high degree, respectively. Results indicated that subgroups of adults with NF experience higher COVID-19-related worries and stress and may need additional support. Furthermore, telehealth is under-utilized and could help NF providers connect with patients, although improved delivery and patient training may facilitate expanded use of these services.

Prevalence of alcohol use among women of reproductive age in Canada. / Fréquence de la consommation d'alcool chez les Canadiennes en âge de procréer.

INTRODUCTION: Reporting on alcohol use among women of reproductive age in Canada addresses a major gap in evidence. METHODS: We assessed the prevalence of weekly and heavy alcohol consumption among women aged 15 to 54 years by sociodemographic characteristics, province of residence and concurrent use of other substance(s) using data from the 2019 Canadian Community Health Survey. RESULTS: Of the target population, 30.5% reported weekly and 18.3% reported heavy alcohol consumption in the past year. Prevalence varied by sociodemographic characteristics, province and substance use. The most notable and significant differences were to do with cannabis use and smoking. CONCLUSION: This information can guide health care providers in assessing alcohol consumption and in promoting low-risk alcohol drinking to prevent alcohol exposure during pregnancy.

Morality is relative: Anger, disgust, and aggression as contingent responses to sibling versus acquaintance harm.

Angry reactions to moral violations should be heightened when wrongs befall oneself in comparison with when wrongs befall acquaintances, as prior research by Molho, Tybur, Güler, Balliet, and Hofmann (2017) demonstrates, because aggressive confrontation is inherently risky and therefore only incentivized by natural selection to curtail significant fitness costs. Here, in 3 preregistered studies, we extend this sociofunctional perspective to cases of wrongs inflicted on siblings. We observed equivalently heightened anger in response to transgressions against either oneself or one's sibling relative to transgressions against acquaintances across studies, whereas transgressions against acquaintances evoked greater disgust and/or fear (both associated with social avoidance) in 2 of the 3 studies. Studies 2 and 3, which incorporated measures of tendencies to confront the transgressor, confirmed that the elevated anger elicited by self or sibling harm partially mediated heightened inclinations toward direct aggression. Finally, in Study 3 we compared tendencies to experience anger and to directly aggress on behalf of siblings and close friends. Despite reporting greater affiliative closeness for friends than for siblings, harm to friends failed to evoke heightened anger relative to acquaintance harm, and participants were inclined to directly aggress against those who had harmed their sibling to a significantly greater extent than when the harm befell their friend. These overall results broadly replicate Molho et al.'s (2017) findings and theoretically extend the sociofunctionalist account of moral emotions to kinship. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Pre-meal active video game playing increased subjective appetite but not food intake in children and adolescents.

OBJECTIVE: Sedentary video game playing (VGP) and caloric preloads in the pre-meal environment have been shown to influence short-term food intake (FI) regulation in children. Other factors that may affect FI control include physical activity and/or heightened emotion. Therefore, we examined the effects of a glucose preload and 30 min of active VGP (aVGP) on subjective appetite, short-term FI, and subjective emotions in 9-14 year-old children. METHODS: On four test mornings approximately one-week apart, twenty-seven children (sex: 15M, 12F; age: 11.3 ± 0.3 years; BMI percentile: 55.3 ± 6.1%) consumed a standardized breakfast two hours prior to consuming 250 mL of either a 50 g glucose preload or Sucralose® control. Following the preload, participants participated in 30 min of quiet sitting or aVGP. Energy expenditure was measured during aVGP via indirect calorimetry. FI from an ad libitum pizza meal was measured after each test condition. Subjective appetite and emotions were measured at baseline (0 min), during treatment (15min), and immediately before the test meal (30 min). RESULTS: aVGP did not affect FI, but the glucose preload decreased FI compared with the sucralose control (∆ = 157 kcal, <0.001). Although not statistically significant (p=0.12), caloric compensation was lower following the glucose preload in the aVGP condition. Subjective appetite increased with time, and was higher in the sucralose control + aVGP condition (p=0.05). Change from baseline subjective emotion scores of anger and excitement were higher (p=0.03) and lower (p=0.02) after aVGP, respectively. CONCLUSIONS: Neither short-term FI nor net energy balance were affected by low-intensity aVGP (energy expenditure of 34 kcal). These findings suggest that a short bout of low-intensity aVGP does not alter energy balance during the study measurement period, and may not support achieving or maintaining healthy weights in children. However, future longitudinal studies are needed to confirm such advice.

An update on positive mental health among youth in Canada. / Mise à jour sur la santé mentale positive chez les jeunes au Canada.

The Positive Mental Health Surveillance Indicator Framework (PMHSIF) provides estimates of positive mental health outcomes and associated risk and protective factors for youth aged 12 to 17 years in Canada. This study explored the relationship between sociodemographic factors and psychological and social well-being among youth in Canada using data from the Canadian Student Tobacco, Alcohol and Drugs Survey 2016-2017. Grade and province were significantly associated with psychological and social well-being.

The Quick Stats table presents recent estimates of positive mental health outcomes and determinants among youth in Canada. Over three-quarters of youth have high relatedness (81.8%), a high level of happiness (79.3%), high competence (78.4%) and high self-rated mental health (75.9%). The majority of youth reported high autonomy (73.0%) and life satisfaction (61.0%). Students in middle school (Grades 7­8) were more likely to have higher psychological and social well-being compared to students in high school (Grades 9­12).

Le tableau Statistiques rapides pré- sente des estimations récentes des résultats et des déterminants de la santé mentale positive chez les jeunes au Canada. Plus des trois quarts des jeunes indiquent avoir un niveau élevé d'appartenance (81,8 %), de bonheur (79,3 %), de compétence (78,4 %) et de santé mentale auto- évaluée (75,9 %). La majorité des jeunes ont déclaré jouir d'une grande autonomie (73,0 %) et d'une grande satisfaction à l'égard de leur vie (61,0 %). Les élèves du niveau intermédiaire (de 7e et 8e années) étaient davantage susceptibles de ressentir un bien-être psychologique et social plus élevé que les élèves du secondaire (de la 9e à la 12e année).

Cross-Reactivity with Self-Antigen Tunes the Functional Potential of Naive B Cells Specific for Foreign Antigens.

Upon Ag exposure, naive B cells expressing BCR able to bind Ag can undergo robust proliferation and differentiation that can result in the production of Ab-secreting and memory B cells. The factors determining whether an individual naive B cell will proliferate following Ag encounter remains unclear. In this study, we found that polyclonal naive murine B cell populations specific for a variety of foreign Ags express high levels of the orphan nuclear receptor Nur77, which is known to be upregulated downstream of BCR signaling as a result of cross-reactivity with self-antigens in vivo. Similarly, a fraction of naive human B cells specific for clinically-relevant Ags derived from respiratory syncytial virus and HIV-1 also exhibited an IgMLOW IgD+ phenotype, which is associated with self-antigen cross-reactivity. Functionally, naive B cells expressing moderate levels of Nur77 are most likely to proliferate in vivo following Ag injection. Together, our data indicate that BCR cross-reactivity with self-antigen is a common feature of populations of naive B cells specific for foreign Ags and a moderate level of cross-reactivity primes individual cells for optimal proliferative responses following Ag exposure.

Total Hip Arthroplasty in Patients With Avascular Necrosis After Hematopoietic Stem Cell Transplantation.

The immunosuppressive regimens required for hematopoietic stem cell transplantation predispose recipients to complications, including avascular necrosis. Cancer-related comorbidities, immunosuppression, and poor bone quality theoretically increase the risk for perioperative medical complications, infection, and implant-related complications in total joint arthroplasty. This study reviewed 20 primary total hip arthroplasties for avascular necrosis in 14 patients. Outcomes were assessed at routine clinical visits and Harris hip scores were calculated. Follow-up radiographs were evaluated for component malposition, loosening, polyethylene wear, and osteolysis. Average follow-up was 44.5 months for all patients. Postoperative clinical follow-up revealed good to excellent outcomes, with significant improvement in functional outcome scores. There were no periprosthetic infections or revisions for aseptic loosening. There was 1 dislocation on postoperative day 40, which was treated successfully with a closed reduction. Two patients with a prior history of venous thromboembolism developed a pulmonary embolus on postoperative day 13 and 77, respectively. Four patients died several months to years after arthroplasty of complications unrelated to the surgical procedure. Total hip arthroplasty can both be safely performed and greatly improve quality of life in recipients of hematopoietic stem cell transplantation who develop avascular necrosis. However, prolonged venous thromboembolism prophylaxis should be carefully considered in this high-risk patient population. [Orthopedics. 2018; 41(2):e257-e261.].

Comparative Outcomes after Haploidentical or Unrelated Donor Bone Marrow or Blood Stem Cell Transplantation in Adult Patients with Hematological Malignancies.

Most patients eligible for allogeneic hematopoietic stem cell transplantation will require identification of an alternate (unrelated or mismatched related) donor. We explored the transplantation outcomes for a sequential series of 54 patients undergoing haploidentical donor transplantation (HAPLO) compared to those from a control group of patients receiving cells from matched or mismatched unrelated donors (URD) selected by diagnosis and stem cell source. Patients undergoing HAPLO transplantations received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (Cy). Day 15 neutrophil recovery was lower after HAPLO than in URD recipients (43% versus 77%, P < .001), as was day 30 platelet recovery (67% versus 84%, P = .043). HAPLO patients receiving bone marrow achieved neutrophil engraftment at a median of 17 days and platelet engraftment at a median of 29 days, compared with 16 days and 24 days, respectively, for recipients of peripheral blood stem cells. The incidence of graft failure was similar for both HAPLO and URD recipients (P = .42). HAPLO recipients were more likely to reach donor CD3 chimerism >95% by day 28 after transplantation (88% versus 62%, P = .003). The cumulative incidence of grades II to IV acute GVHD (aGVHD) at 6 months after transplantation did not differ for these 2 groups (63% for HAPLO and 53% for URD recipients; P = .269), nor did the cumulative incidence of severe grade III/IV aGVHD (13% for HAPLO and 8% for URD recipients; P = .44). The cumulative incidence of moderate or severe chronic GVHD at 2 years did not differ, with probabilities of 24% for HAPLO and 18% for URD recipients (P = .43). The cumulative incidence of cytomegalovirus reactivation by day 100 after transplantation did not differ (45% for HAPLO and 46% for URD recipients; P = .96). The HAPLO recipients experienced a lower incidence of Epstein-Barr virus reactivation by day 100 (6% versus 32%, P < .001) but a higher incidence of Human Herpesvirus-6 reactivation (35% versus 10%, P = .001). Relapse risk, regimen-related mortality, progression-free survival, and overall survival probabilities did not differ between these 2 groups. These data support the use of HAPLO transplantation with post-transplantation Cy as an alternate transplantation technique for patients lacking HLA-matched sibling donors. Transplantation of peripheral blood stem cells does not appear to enhance the speed of neutrophil recovery. The different patterns of viral reactivation require additional studies to explain.

The graft-versus-myeloma effect: chronic graft-versus-host disease but not acute graft-versus-host disease prolongs survival in patients with multiple myeloma receiving allogeneic transplantation.

We conducted a study of patients with multiple myeloma (MM) undergoing allogeneic transplantation to evaluate outcome parameters. Fifty-seven consecutive patients with MM received an allogeneic transplantation between 2004 and 2011 at our institution. Patients who had received at least 1 prior autologous transplantation were included. Twenty-six patients underwent allogeneic transplantation for consolidation after a response to their first autograft, and 30 patients received an allogeneic transplantation as salvage therapy. Donor source was evenly distributed between related and unrelated. The median follow-up was 52 months. Thirty-two (57.1%) patients achieved a complete response (CR). At 5 years, 49.2% of all patients were in CR. Sixteen patients received either donor lymphocyte infusions or immune suppression withdrawal for disease progression, with a 62.5% response rate. The 5-year overall survival (OS) for all patients was 59%. The 5-year OS for the 30 patients in the consolidation group was 82% compared with 38% for those in the salvage group. In multivariate analysis, 3 factors remained significantly associated with OS. These include being in the salvage group (hazard ratio [HR], 4.05; P = .0196), acute graft-versus-host disease (aGVHD) (HR, 2.99; P = .034), and chronic graft-versus-host disease (cGVHD), which was highly protective, with a 5-year OS of 78.8% for patients with cGVHD versus 42.6% for patients without cGVHD (HR .17, P = .008). Our data show that allogeneic transplantation for MM can lead to sustained remissions. aGVHD is significantly deleterious to OS and progression-free survival, whereas cGVHD is strongly favorable, supporting an important role for the graft-versus-myeloma effect.

Structural variations in articular cartilage matrix are associated with early-onset osteoarthritis in the spondyloepiphyseal dysplasia congenita (sedc) mouse.

Heterozgyous spondyloepiphyseal dysplasia congenita (sedc/+) mice expressing a missense mutation in col2a1 exhibit a normal skeletal morphology but early-onset osteoarthritis (OA). We have recently examined knee articular cartilage obtained from homozygous (sedc/sedc) mice, which express a Stickler-like phenotype including dwarfism. We examined sedc/sedc mice at various levels to better understand the mechanistic process resulting in OA. Mutant sedc/sedc, and control (+/+) cartilages were compared at two, six and nine months of age. Tissues were fixed, decalcified, processed to paraffin sections, and stained with hematoxylin/eosin and safranin O/fast green. Samples were analyzed under the light microscope and the modified Mankin and OARSI scoring system was used to quantify the OA-like changes. Knees were stained with 1C10 antibody to detect the presence and distribution of type II collagen. Electron microscopy was used to study chondrocyte morphology and collagen fibril diameter. Compared with controls, mutant articular cartilage displayed decreased fibril diameter concomitant with increases in size of the pericellular space, Mankin and OARSI scores, cartilage thickness, chondrocyte clustering, proteoglycan staining and horizontal fissuring. In conclusion, homozygous sedc mice are subject to early-onset knee OA. We conclude that collagen in the mutant's articular cartilage (both heterozygote and homozygote) fails to provide the normal meshwork required for matrix integrity and overall cartilage stability.

Acinar dysplasia of the lungs: variation in the extent of involvement and clinical features.

AIM: This study presents the clinicopathological features in three patients with acinar dysplasia, a very rare developmental abnormality of the lungs, to expand on the spectrum of the disease. METHODS: The clinical and histological features in the biopsies and autopsies were reviewed and compared with those reported in literature and in other diffuse lung diseases in neonates. RESULTS: All three patients presented at birth with severe respiratory distress. Two were siblings, with autopsy in both, and sequential lung biopsies in one. Histology showed spaces lined by ciliated columnar epithelium and separated by mesenchyme, with minimal saccule-like structures. The changes seemed considerably less severe in the biopsy than at autopsy. Both died, one at 6 hours and the other at 24 days with no improvement following ventilation and steroids. The third had a previous sibling who died at a few hours of age following severe respiratory distress. She was given ventilation and extracorporeal membranous oxygenation. Her biopsy showed changes similar to although less uniform than those in the biopsy of the previous patient. She improved slowly and was discharged at 4 months. At 18 months she was without tachypnoea and weaned off supplemental oxygen. CONCLUSIONS: Acinar dysplasia may show more variation in the degree of involvement and clinical outcome than previously recognised, even within families, sometimes compatible with survival.

Demonstration of liver metastases on postmortem whole body CT angiography following inadvertent systemic venous infusion of the contrast medium.

An 86-year-old woman was hospitalized for breathlessness and a large right-sided pleural effusion. Approximately 1 h after thoracentesis, she developed a hemothorax resulting in hypotension and death. Routine postmortem CT scanning showed a large volume right hemothorax and a markedly enlarged liver. In an attempt to determine the origin of bleeding prior to autopsy, a postmortem CT angiogram was performed. Following inadvertent cannulation of the left long saphenous vein and infusion of ∼1,700 mL of a polyethylene glycol 200 and iodine-based radiographic contrast solution into systemic veins using a mechanical pump, CT scanning revealed a dense hepatic "parenchogram" containing multiple large, filling defects indicative of metastases. These were confirmed at autopsy. Microscopic evaluation of the liver using hematoxylin and eosin staining showed marked histological artifact characterized by centrilobular sinusoidal expansion although histology of the adenocarcinoma metastases was typical and apparently unaffected by the contrast solution. Postmortem CT angiography using an aqueous radiographic contrast agent in the so-called venous phase seems to be useful for the identification of hepatic parenchymal metastatic disease although it does cause histological artifact.

Management of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that adversely affects quality of life and clinical outcomes in patients following hematopoietic stem cell transplantation. Conventional treatment of GVHD includes prolonged and high-dose corticosteroids; however, those drugs are associated with multiple side effects. This article describes the ability of extracorporeal photopheresis therapy to exhibit a steroid-sparing effect, which can reduce long-term complications as a consequence of steroid treatment.

Allograft TNFbeta and IL16 polymorphisms influence HCV recurrence and severity after liver transplantation.

Hepatitis C (HCV) recurrence after liver transplantation is universal although severity varies. We explored whether certain donor cytokine gene polymorphisms may be useful markers of susceptibility to severe recurrence. Allograft tumor necrosis factor (TNF) beta and interleukin (IL) 16 gene polymorphisms were correlated with l-yr clinical outcome among HCV+ recipients. Recipients of donor TNFbeta(2,2) (n = 8) experienced less recurrence (50% vs. 71%, P < 0.05), less fibrosis (25% vs. 76%, P < 0.01), and less rejection (25% vs. 71%, P < 0.01) than donor TNFbeta(1,1) (n = 19). Recipients of donor TNFbeta(1,2) (n = 27) demonstrated an intermediate picture with less fibrosis (56%, P < 0.01) and less rejection (37%, P < 0.01) than TNFbeta(1,1). Recipients with donor IL16(TC) (n = 22) showed less recurrence (65% vs. 78%, P = 0.05), less fibrosis (53% vs. 67%, P = 0.06), and less rejection (41% vs. 55%, P = 0.06) than IL16(TT) (n = 32) genotype. Recipients of the combination TNFbeta(2,2)/IL16(TC) donor genotype had the most benign clinical outcome with less recurrence (33% vs. 75%, P < 0.01), no fibrosis (0% vs. 50%, P < 0.001), and fewer rejections (33% vs. 75%, P < 0.01) than donor TNFbeta(1,1)/IL16(TT) genotype. In vitro production of cytokines correlated with genotype. Release of soluble TNFbeta for TNFbeta(1,1) vs. TNFbeta(1,2) and TNFbeta(2,2) was 4803 +/- 2142 pg/mL vs. 5629 +/- 3106 (P = not significant [ns]) and 7180 +/- 3005 (P = ns). Release of soluble IL16 for IL16(TT) vs. IL16(TC) was 437 +/- 86 pg/mL vs. 554 +/- 39 (P = 0.06). In conclusion, allograft TNFbeta and IL16 gene polymorphisms may be useful markers to predict the severity of disease recurrence among HCV+ patients after liver transplantation.