A Deep Learning Model for Markerless Pose Estimation Based on Keypoint Augmentation: What Factors Influence Errors in Biomechanical Applications?

In biomechanics, movement is typically recorded by tracking the trajectories of anatomical landmarks previously marked using passive instrumentation, which entails several inconveniences. To overcome these disadvantages, researchers are exploring different markerless methods, such as pose estimation networks, to capture movement with equivalent accuracy to marker-based photogrammetry. However, pose estimation models usually only provide joint centers, which are incomplete data for calculating joint angles in all anatomical axes. Recently, marker augmentation models based on deep learning have emerged. These models transform pose estimation data into complete anatomical data. Building on this concept, this study presents three marker augmentation models of varying complexity that were compared to a photogrammetry system. The errors in anatomical landmark positions and the derived joint angles were calculated, and a statistical analysis of the errors was performed to identify the factors that most influence their magnitude. The proposed Transformer model improved upon the errors reported in the literature, yielding position errors of less than 1.5 cm for anatomical landmarks and 4.4 degrees for all seven movements evaluated. Anthropometric data did not influence the errors, while anatomical landmarks and movement influenced position errors, and model, rotation axis, and movement influenced joint angle errors.

PRPH2 mutation c.582-1G>A causing adult-onset macular dystrophy with a benign concentric annular macular dystrophy phenotype in a family / Mutação c.582-1G>A do gene PRPH2 causando distrofia macular de início adulto com fenótipo de distrofia macular anular concêntrica benigna em uma família

ABSTRACT The peripherin gene (PRPH2) mutation is associated with photoreceptor cell dysfunction as well as in several inherited retinal dystrophies. The PRPH2 mutation c.582-1G>A is a rare variant reported in retinitis pigmentosa and pattern dystrophy. Here Case 1 was of a 54-year-old woman with bilateral atrophy of the perifoveal retinal pigmentary epithelium and choriocapillaris with central foveolar respect. Autofluorescence and fluorescein angiography revealed perifoveal atrophy of the retinal pigmentary epithelium with an annular window effect without the "dark choroid" sign. Case 2 (mother of Case 1) presented with extensive atrophy of the retinal pigmentary epithelium and choriocapillaris. PRPH2 was evaluated and the c.582-1G>A mutation was identified in heterozygosity. An advanced adult-onset benign concentric annular macular dystrophy diagnosis was thereby proposed. The c.582-1G>A mutation is poorly known and not present in all common genomic databases. This case report is the first one to report a c.582-1G>A mutation associated with benign concentric annular macular dystrophy.

RESUMO Mutações do gene da periferina (PRPH2) estão associadas à disfunção das células fotorreceptoras e estão envolvidas em várias distrofias retinianas hereditárias. A mutação c.582-1G>A do gene PRPH2 é uma variante rara, relatada na retinite pigmentosa e nas distrofias em padrão. O caso 1 foi de uma mulher de 54 anos com atrofia bilateral do epitélio pigmentar da retina perifoveal e da coriocapilar, com acometimento foveolar central. A autofluorescência e a angiofluoresceinografia revelaram atrofia perifoveal do epitélio pigmentar da retina, com efeito de janela anular, sem o sinal da "coroide escura". O caso 2 (mãe) apresentava extensa atrofia do epitélio pigmentar da retina e da coriocapilar. Foi feito um estudo do gene PRPH2, que identificou a mutação c.582-1G>A em heterozigose. Foi proposto um diagnóstico de distrofia macular anular concêntrica benigna de início adulto em estágio avançado. A mutação c.582-1G>A é pouco conhecida e não está presente em todos os bancos de dados genômicos usuais. Este é o primeiro relato de caso publicado de uma mutação c.582-1G>A associada à distrofia macular anular concêntrica benigna.

PRPH2 mutation c.582-1G>A causing adult-onset macular dystrophy with a benign concentric annular macular dystrophy phenotype in a family.

The peripherin gene (PRPH2) mutation is associated with photoreceptor cell dysfunction as well as in several inherited retinal dystrophies. The PRPH2 mutation c.582-1G>A is a rare variant reported in retinitis pigmentosa and pattern dystrophy. Here Case 1 was of a 54-year-old woman with bilateral atrophy of the perifoveal retinal pigmentary epithelium and choriocapillaris with central foveolar respect. Autofluorescence and fluorescein angiography revealed perifoveal atrophy of the retinal pigmentary epithelium with an annular window effect without the "dark choroid" sign. Case 2 (mother of Case 1) presented with extensive atrophy of the retinal pigmentary epithelium and choriocapillaris. PRPH2 was evaluated and the c.582-1G>A mutation was identified in heterozygosity. An advanced adult-onset benign concentric annular macular dystrophy diagnosis was thereby proposed. The c.582-1G>A mutation is poorly known and not present in all common genomic databases. This case report is the first one to report a c.582-1G>A mutation associated with benign concentric annular macular dystrophy.

PRPH2 mutation c.582-1G>A causing adult-onset macular dystrophy with a benign concentric annular macular dystrophy phenotype in a family.

The peripherin gene (PRPH2) mutation is associated with photoreceptor cell dysfunction as well as in several inherited retinal dystrophies. The PRPH2 mutation c.582-1G>A is a rare variant reported in retinitis pigmentosa and pattern dystrophy. Here Case 1 was of a 54-year-old woman with bilateral atrophy of the perifoveal retinal pigmentary epithelium and choriocapillaris with central foveolar respect. Autofluorescence and fluorescein angiography revealed perifoveal atrophy of the retinal pigmentary epithelium with an annular window effect without the "dark choroid" sign. Case 2 (mother of Case 1) presented with extensive atrophy of the retinal pigmentary epithelium and choriocapillaris. PRPH2 was evaluated and the c.582-1G>A mutation was identified in heterozygosity. An advanced adult-onset benign concentric annular macular dystrophy diagnosis was thereby proposed. The c.582-1G>A mutation is poorly known and not present in all common genomic databases. This case report is the first one to report a c.582-1G>A mutation associated with benign concentric annular macular dystrophy.

Body Condition of Reproductive and Non-Reproductive Broad-Snouted Caiman Females.

In this work, we calculated the body condition indices, K-Fulton and scaled mass index (SMI), of reproductive and non-reproductive Caiman latirostris adult females as an indication of stored energy. We considered 87 adult females captured from 2001 to 2018, both reproductive and non-reproductive. The body condition was calculated considering two scenarios: (a) only the weight of the female, and (b) the sum of the weight of the female and the average dry weight of her nest. We tested the difference in body condition between reproductive and non-reproductive females. We also evaluated the minimal body condition required to guarantee that females above it are reproductive by drawing a line that separated the body condition of strictly reproductive individuals from those that may or may not be reproductive. Reproductive females had better body condition than non-reproductive ones. Our SMI.S line separated almost 70% of the reproductive females. Based on our results, we can guarantee that a female whose body condition is above the line will reproduce, although not all those females below the line are non-reproductive, as a few of those under the line will nest. With this information, we have one more biological indicator to take into account when making management and conservation decisions.

Yolk corticosterone and progesterone levels in Greater Rhea (Rhea americana) eggs vary in a changing social environment.

Maternal hormones in avian egg yolks may signal and prepare offspring for the prevailing conditions. However, this adjustment requires some degree of flexibility in regulating yolk hormone deposition. The Greater Rhea (Rhea americana) has a particular mating system that combines mixed polygyny and polyandry, communal nesting, and exclusive paternal care of chicks. In this species, we previously found that yolk hormone deposition varies among eggs of different captive populations and could influence chicks' physiology and behavior. However, it is still unknown whether females can modify yolk hormone deposition in a changing social environment. Using a captive population of Greater Rheas, in this study, we quantified yolk hormone levels before and after a reduction in the number of females present in the population. We found that females deposited on average higher yolk corticosterone and lower yolk progesterone after the change in their social environment. Since corticosterone deposited into the yolk comes exclusively from the female's plasma, our results suggest that females had, on average, higher plasma corticosterone levels. The change in the number of females may increase the events of male-male competitions, courtships, and matings, leading to an increase of corticosterone in the females' plasma and then into their eggs. Since we previously found that higher yolk corticosterone and lower yolk progesterone were associated with the production of chicks that have an attenuated stress response, the present study results suggest that yolk hormone deposition is mediated by flexible mechanisms that could adjust development to the prevailing conditions.

Immunologic Abnormalities Associated With Health Status of Heart Recipients Long Term After Transplantation.

BACKGROUND: With improvements in survival rates, health-related quality of life is an important outcome parameter to evaluate the effectiveness of transplantation. We aimed to identify potential immunologic abnormalities as factors associated with poorer health-related quality of life at distinct scales of the 36-Item Short Form Health Survey in heart transplant recipients long term after transplantation. METHODS: One hundred heart transplant recipients were evaluated in a single center. Short-form 36 questionnaires were sent by mail to participants. All patients were clinically and immunologically evaluated after the first year of heart transplantation. RESULTS: A high prevalence of several immunologic abnormalities persisted even after the first year of transplantation, including IgG hypogammaglobulinemia, low IgG-specific antipneumococcal antibodies, C4 hypocomplementemia, CD8 T-cell lymphocytopenia, and CD19 B-cell lymphocytopenia. Older recipients (>55 years), posttransplant diabetes, digestive complications, and posttransplant infections were associated with lower physical functioning scores (scale < 60). Older recipients (>55 years), pretransplant diabetes, pretransplant arterial hypertension, posttransplant digestive complications, and lower CD8 counts were associated with lower physical role scores (scale <25). CONCLUSION: In a single center study, lower CD8 cell counts were found to be associated with poorer health status in heart recipients after the first year of transplantation.

Multifocal pyoderma gangrenosum secondary to subclinical diverticulitis: case report and brief literature review.

Pyoderma gangrenosum is characteristically associated with inflammatory bowel disease. However, the association between this neutrophilic dermatosis and diverticular disease is scarcely mentioned in the literature. Diverticulitis should be included in the differential diagnosis in patients with pyoderma gangrenosum and gastrointestinal complaints, or even in asymptomatic patients, particularly in the elderly. Misdiagnosis can lead to inadequate treatments and serious complications.

First assessment of persistent organic pollutants in the Greater rhea (Rhea americana), a near-threatened flightless herbivorous bird of the Pampas grasslands.

Persistent organic pollutants (POPs) are still globally distributed and can exert different effects on ecosystems. Little is known about the occurrence of these contaminants in terrestrial birds from South America. In this study, POPs were assessed for the first time in a flightless herbivorous species from the Pampas grasslands, the Greater rhea (Rhea americana). Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) were determined in 18 samples of feathers from free-ranging and captive individuals inhabiting four sites with different land uses in central Argentina. Among the 16 POPs tested in those feathers, 6 PCBs (28, 52, 101, 138, 153, and 180) and 8 OCPs (α-HCH, ß-HCH, γ-HCH, p,p'-DDE, p,p'-DDD, o,p'-DDT, p,p'-DDT, and HCB) were quantified. No PBDEs were detected. The total concentration of POPs was higher in populations living in an intensive crop production area (agriculture 159 ng g -1 and farm: 97.53 ng g-1) compared with the population in an urban area (zoo 45.86 ng g-1) and an agroecosystem with extensive rearing of livestock (cattle rearing 36.77 ng g-1). PCBs were the most abundant pollutants in all the populations studied. Lower chlorinated CB 52 and CB 101 were the principal PCB congeners detected, representing at least 70% of the total quantified. All populations studied showed a DDE + DDD/DDT ratio > 1, indicating a historical application of this insecticide. This study provides a new contribution to the scarce data on POP concentrations in South American bird species. Further investigations are needed to evaluate their potential effects on the health of individuals and populations.

Secondary antibody deficiency is associated with development of infection in kidney transplantation: Results of a multicenter study.

BACKGROUND: We performed a multicenter study to assess the association between secondary antibody deficiency (immunoglobulin G [IgG] hypogammaglobulinemia combined with low levels of specific antibodies) and development of infection in kidney transplantation. METHODS: We prospectively analyzed 250 adult kidney recipients at four centers. The assessment points were before transplantation and 7 and 30 days after transplantation. The immune parameters were as follows: IgG, IgA, and IgM and complement factors C3 and C4 tested by nephelometry; specific IgG antibodies to cytomegalovirus (CMV) and IgG and IgG2 antibodies to pneumococcal polysaccharide (anti-PPS) determined using enzyme-linked immunosorbent assay. The clinical follow-up period lasted 6 months. The clinical outcomes were CMV disease and recurrent bacterial infections requiring antimicrobial therapy. STATISTICS: Multivariate logistic regression. RESULTS: At day 7, IgG hypogammaglobulinemia (IgG levels < 700 mg/dL) combined with low IgG anti-CMV antibody titers (defined as levels < 10 000 units) was present in 12% of kidney recipients. IgG hypogammaglobulinemia combined with low IgG anti-PPS antibody titers (defined as levels < 10 mg/dL) at 1 month after kidney transplantation were recorded in 16% of patients. At day 7 the combination of IgG hypogammaglobulinemia and low anti-CMV titers was independently associated with the development of CMV disease (odds ratio [OR], 6.95; 95% confidence interval [CI], 1.17-41.31; P = .033). At day 30 after transplantation, the combination of IgG < 700 mg/dL and IgG anti-PPS < 10 mg/dL, was independently associated with recurrent bacterial infection (OR, 5.942; 95% CI, 1.943-18.172; P = .002). CONCLUSION: In a prospective multicenter study, early immunologic monitoring of secondary antibody deficiency proved useful for the identification of kidney recipients who developed severe infection.

Immunoserologic Detection and Diagnostic Relevance of Cross-Reactive Autoantibodies in Coronavirus Disease 2019 Patients.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, we detected a new immunofluorescence (IF) pattern in serum autoantibody (autoAb) screening of laboratory-confirmed COVID-19 patients. METHODS: The IF pattern was composed of liver and gastric mucosa staining on rat kidney/liver/stomach sections. RESULTS: We describe 12 patients positive for the cross-reactive antibody, compared with a negative group of 43 hospitalized COVID-19 patients, finding association with either neurologic or thrombotic complications. In sequential pre- and post-COVID-19 serum samples, we confirmed autoAb seroconversion. CONCLUSIONS: Our data indicate that autoAb screening in COVID-19 patients may be easily performed by IF and alert for autoreactive-mediated complications such as thrombotic or neurologic events.

Genetic identification of the ciliates from greater rheas (Rhea americana) and lesser rheas (Rhea pennata) as Balantioides coli.

The ciliate species Balantioides coli can be cross-transmitted between humans and several animal species. Usually harmless, sometimes it can be pathogenic and cause the death of the host. In birds, B. coli has been confirmed in ostriches by genetic analysis, but the identification from South American greater rheas (Rhea americana) and lesser rheas (Rhea pennata pennata) is tentative. Since these species are reared for commercial purposes and for reintroduction into the wild, it is necessary to elucidate whether the ciliate from rheas is B. coli to minimize health risks for humans and for other domestic and wild animals. Individual parasite cells are collected from Argentinean isolates of reared greater rheas and of wild and reared lesser rheas, and their ITS region was PCR amplified; the cloning products were sequenced and compared with sequences available in public databases. The results have shown that several sequence types are expressed at the same time in the parasite cells, and all correspond to B. coli, confirming the possibility of cross-transmission of the parasite between wild and reared South American rheas and several mammal species and humans.

Developing High Medical Technology, a Challenge for Developing Countries: The Percutaneous Closure of Atrial Septal Defects Using Nit-Occlud ASD-R: Early and Mid-term Results.

OBJECTIVE: To assess the efficacy and safety of the Nit-Occlud ASD-R (PFM S.R.L, La Paz, Bolivia) in the percutaneous closure of secundum atrial septal defects (ASD). PATIENTS AND METHODS: Fifty-three consecutive patients with median age of 11 years (range 3-67) and mean weight 27.1 kg (range 13-75 kg), treated in two cardiology centers between May 2007 and March 2011. RESULTS: Mean fluoroscopy time was 14 minutes (5-53), mean procedure time was 70 minutes (45-150), mean defect size, as measured by the stop-flow technique, was 17.8 mm (5.6-31), and mean stent size of the implanted device was 18 mm (6-28), which is 0.98 times the defect size. Successful closure of the ASD without major complications was achieved in 49 of 53 patients. In 71.4% of patients in whom device implantation was accomplished, there was no evidence of a persistent shunt at the completion of the procedure. This closure rate increased to 91.7% after 24 hours, with 95.8% closure after three months and 100% closure after six months. Device embolization occurred in one patient within 24 hours of implantation and required surgical device removal and ASD closure. There were no other major complications and no deaths during the period of follow-up (average 72 months; range 59-105 months). CONCLUSION: The Nit-Occlud ASD-R device is safe and effective with very good closure rates.

Effect of maternal environment on yolk immunoreactive corticosterone and its influence on adrenocortical and behavioral activity in chicks of Greater Rhea (Rhea americana).

Maternal corticosterone in avian eggs may modify offspring phenotype in order to increase survival in poor environments. In the Greater Rhea (Rhea americana), we previously found that yolk immunoreactive corticosterone is influenced by the quality of the maternal environment: eggs laid by females of the intensive rearing system (IRS), living in poor captive conditions, had higher yolk immunoreactive corticosterone than those produced by females of the semi-extensive rearing system (SRS), living in better conditions. Here, we evaluate if these different hormone levels are associated with the production of different phenotypes. We collected eggs from the IRS and SRS for hormonal quantification and artificial incubation. Then, half of the chicks selected from each environment were exposed to a capture and restraint protocol, and the rest remained undisturbed and were used as controls. In the IRS, we found that higher yolk immunoreactive corticosterone was associated with the production of chicks that had reduced hatchability, lower hatchling mass and higher baseline fecal glucocorticoid metabolites (FGM) than those produced by SRS females. Moreover, after capture and restraint, IRS chicks did not modify their FGM nor their behaviors compared to their controls, while SRS chicks increased their FGM and spent more time ambulating and less time pecking, compared to their controls. These results indicate that yolk immunoreactive corticosterone could modify offspring phenotype. Although future studies are needed to elucidate their implications for fitness, our results suggest that yolk corticosterone could be mediating an adaptive maternal effect that allows individuals to better cope with poor conditions.

State of the art knowledge in adrenocortical and behavioral responses to environmental challenges in a threatened South American ratite: Implications to in situ and ex-situ conservation.

The Greater Rhea (Rhea americana) is an endemic ratite to South America, whose wild populations have undergone a remarkable decrease due to habitat degradation and fragmentation by the expansion of the agricultural frontier, poaching and predation by dogs. Anthropogenic perturbations in wild environments, as well as the management in captivity, can generate different stress responses in this species, thus, the monitoring of adrenocortical and behavioral activities are considered primary assessment tools with both conservation and welfare implications. In this review we analyze and integrate the different measurements of glucocorticoids (in plasma, feces, and yolk) carried out in different captive and wild populations, taking into account the diverse predictable and unpredictable conditions to which the Greater Rhea responds in each of those environments. In addition, the translocation of this bird is presented as an application of stress physiology in field ecology for conservation purposes, in which we evaluated how this species responds when it is released into a novel environment. Our results indicate that this ratite has a striking high sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis compared to that of other bird species and shows a wide variety of adrenocortical responses depending on the environment in which it lives. This suggests that its HPA axis has a phenotypic plasticity that enables the rhea to cope with the environmental challenges. In this sense, we propose that one of the routes of this plasticity could be mediated by the maternal transfer of steroid hormones to the egg. Finally, we discuss the importance of integrating the monitoring of the adrenocortical response along with the environmental variables that define the life history of the species, in management and conservation programs ex-situ and in situ.

Monitoring of early humoral immunity to identify lung recipients at risk for development of serious infections: A multicenter prospective study.

BACKGROUND: Infection is still a leading cause of death during the first year after lung transplantation. We performed a multicenter study among teaching hospitals to assess monitoring of early humoral immunity as a means of identifying lung recipients at risk of serious infections. METHODS: We prospectively analyzed 82 adult lung recipients at 5 centers in Spain. Data were collected before transplantation and at 7 and 30 days after transplantation. Biomarkers included IgG, IgM, IgA, complement factors C3 and C4, titers of antibodies to pneumococcal polysaccharide antigens (IgG, IgA, IgM) and antibodies to cytomegalovirus (IgG), and serum B-cell activating factor (BAFF) levels. The clinical follow-up period lasted 6 months. Clinical outcomes were bacterial infections requiring intravenous anti-microbial agents, cytomegalovirus (CMV) disease, and fungal infections requiring therapy. RESULTS: We found that 33 patients (40.2%) developed at least 1 serious bacterial infection, 8 patients (9.8%) had CMV disease, and 10 patients (12.2%) had fungal infections. Lower IgM antibody levels against pneumococcal polysaccharide antigens at Day 7 (defined as <5 mg/dl) were a risk factor for serious bacterial infection (adjusted odds ratio [OR] 3.96; 95% confidence interval [CI] 1.39 to 11.26; p = 0.0099). At Day 7 after transplantation, IgG hypogammaglobulinemia (defined as IgG <600 mg/dl) was associated with a higher risk of CMV disease (after adjustment for CMV mismatch: OR 8.15; 95% CI 1.27 to 52.55; p = 0.028) and fungal infection (adjusted OR 8.03, 95% CI 1.51 to 42.72; p = 0.015). Higher BAFF levels before transplantation were associated with a higher rate of development of serious bacterial infection and acute cellular rejection. CONCLUSION: Early monitoring of specific humoral immunity parameters proved useful for the identification of lung recipients who are at risk of serious infections.

Multimarker risk stratification approach at multiple sclerosis onset.

Delay in the diagnosis of multiple sclerosis (MS) stems from the lack of specific clinical and analytical markers to assist in the early diagnosis and prediction of progressive course. We propose a decision-tree model that better defines early at onset MS patients and those with the progressive form by analysing a 12-biomarkers panel in serum and CSF samples of patients with MS, other neurological diseases (OND) and healthy contols. Thus, patients at onset of neurological disease were first classified by serum IL-7 levels <141pg/ml (OR=6.51, p<0.001). Combination of IL-7 and CXCL10 indicated risk for a specific MS clinical form, where IL-7<141 and CXCL10<570pg/ml were associated with the highest risk for PP-MS (OR=22, p=0.01). Unexpectedly, both PP-MS and RR-MS patients shared significantly decreased prototypical biomarkers of inflammation and tissue regeneration in CSF than OND suggesting a defective intrinsic immune response playing a role at the beginning of the disease.

Distribution and concentration of maternal progesterone in the yolk of Greater Rhea eggs (Rhea americana).

Progesterone is the most concentrated maternal yolk steroid characterized to date in birds; however, no information about it is available in ratite eggs. We collected freshly laid eggs from zoo-housed Greater Rhea females (Rhea americana) bred under similar rearing conditions during two breeding seasons to characterize concentration and distribution of maternal yolk progesterone. After high-performance liquid chromatography analysis, yolk hormone was measured using a commercial electrochemiluminescence immunoassay. Progesterone concentrations were found to vary significantly among the yolk layers, supporting a follicular origin for this steroid in Greater Rhea eggs. Additionally, highly similar mean absolute yolk progesterone concentrations were detected between 2013 and 2015 breeding seasons (1,332.98 ± 82.59 and 1,313.59 ± 85.19 ng/g, respectively). These values are also comparable to those found in some domestic carinate species. Findings suggest that at population level, when rearing conditions are similar, mean absolute yolk maternal progesterone concentrations also appear bounded. Future research on the factors and mechanisms that regulate progesterone deposition in Greater Rhea eggs is needed to better understand whether its levels depend on different rearing conditions.

Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study.

BACKGROUND: New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. METHODS: We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection. RESULTS: During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection. CONCLUSION: Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection.

Early intravenous immunoglobulin replacement in hypogammaglobulinemic heart transplant recipients: results of a clinical trial.

BACKGROUND: Immunoglobulin G (IgG) hypogammaglobulinemia (HGG) is a risk factor for development of severe infections after heart transplantation. We performed a clinical trial to preliminarily evaluate the efficacy and safety of early administration of intravenous immunoglobulin (IVIG) for prevention of severe infection in heart recipients with post-transplant IgG HGG. METHODS: Twelve heart recipients with IgG HGG detected in a screening phase of the clinical trial (IgG <500 mg/dL) were recruited. Patients received IVIG (Flebogamma 5%), as follows: 2 doses of 200 mg/kg followed by up to 5 additional doses of 300 mg/kg to maintain IgG >750 mg/dL. IgG and specific antibody titers to distinct microorganisms were tested during follow-up. The primary outcome measure was development of severe infection during the study period. Data on the primary outcome were matched with those of 13 recipients with post-transplant HGG who were not included in the clinical trial and with those of 11 recipients who did not develop HGG during the same study period. RESULTS: Mean time to detection of HGG was 15 days. IgG and specific antibody reconstitution (anti-cytomegalovirus, anti-Haemophilus influenza, and anti-hepatitis B surface antigen antibodies) was observed in IVIG-treated patients. Severe infection was detected in 3 of 12 (25%) IVIG-treated recipients, in 10 of 13 (77%) HGG non-IVIG patients, and in 2 of 11 (18%) non-HGG patients (log-rank, 15.31; P=.0005). No severe IVIG-related side effects were recorded. CONCLUSION: Data from this study demonstrate that prophylactic IVIG replacement therapy safely modulates HGG and specific antimicrobial antibodies. Our data also preliminarily suggest that IVIG replacement therapy might decrease the incidence of severe infection in heart recipients with HGG.