Relationship Between Immune Response to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines and Development of Breakthrough Infection in Solid Organ Transplant Recipients: The CONTRAST Cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients is associated with poorer antibody response (AbR) compared with non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) has yet to be assessed. METHODS: Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV-2 vaccination during a 1-year period (February 2021 - January 2022), end of follow-up April 2022. Patients were tested for AbR at multiple time points. The primary end-point was BI (laboratory-confirmed SARS-CoV-2 infection ≥14 days after the second dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization, and BI states were obtained for each type of graft and vaccination sequence using multistate survival analysis. Then, multivariable logistic regression was performed to analyze the risk of BI related to AbR levels. RESULTS: 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received 3 vaccine doses. The first 2 consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively. For the third dose, mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed the lowest probability of immunization (0.418) and the highest of BI (0.323); all mRNA-1273 vaccine sequences showed the highest probability of immunization (0.732) and the lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age, and shorter time from transplant. CONCLUSIONS: SOT patients with non-high-level AbR and shorter time from transplantation and heart recipients are at highest risk of BI.

Fabry Disease Nephropathy: Histological Changes With Nonclassical Mutations and Genetic Variants of Unknown Significance.

RATIONALE & OBJECTIVE: Fabry disease (FD) is an X-linked genetic disorder that causes lysosomal storage of glycosphingolipids, primarily globotriaosylceramide (Gb3) and its derivative globotriaosylsphingosine (lyso-Gb3), with multiorgan dysfunction including chronic kidney disease. Affected individuals may be carriers of gene variants that are of uncertain significance (GVUS). We describe kidney pathology at the early stages of FD-related kidney disease to gain insights into its association with GVUS and sex. STUDY DESIGN: Single-center, case series. SETTING & PARTICIPANTS: Thirty-five consecutively biopsied patients (aged 48.1±15.4 years, 22 females) from among 64 patients with genetically diagnosed FD. Biopsies were retrospectively screened using the International Study Group of Fabry Nephropathy Scoring System. OBSERVATIONS: Genetic mutation type, p.N215S and D313Y, sex, age, estimated glomerular filtration rate (eGFR), plasma lyso-Gb3 (pLyso-Gb3) levels, and histological parameters, including Gb3 deposits were recorded. Genetic analyses showed mostly missense mutations, p.N215S variant in 15, and the "benign polymorphism" D313Y in 4 of the biopsied patients. Morphological lesions were similar for men and women except for interstitial fibrosis and arteriolar hyalinosis being more common in men. Early in their clinical course, patients with normal/mild albuminuria had podocyte, tubular, and peritubular capillary vacuoles/inclusions, and evidence of chronicity, i.e., glomerulosclerosis, interstitial fibrosis, tubular atrophy. These findings appeared to be associated with pLyso-Gb3, eGFR, and age. LIMITATIONS: Retrospective design and inclusion of outpatients partially based on family pedigree. CONCLUSIONS: In early stages of kidney disease in the setting of FD, numerous histological abnormalities are present. These observations suggest that kidney biopsies early in FD may reveal activity of kidney involvement that may inform clinical management.

Insight in cognitive impairment assessed with the Cognitive Assessment Interview in a large sample of patients with schizophrenia.

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative.

Trust in science, medicine and medical providers and its relations to vaccine beliefs: A latent class analysis.

AIM: People may differ in their vaccine-related beliefs (i.e. efficacy, safety, purpose), with a host of factors influencing these differences. This can produce homogeneous groups of individuals who share certain beliefs, attitudes and opinions not only towards vaccines but science and medicine in general. This study aims to characterise distinct subgroups and identify ideal targets for tailored public health interventions to reinforce favourable vaccine beliefs. METHODS: Latent class analysis was used to derive unique profiles using the 2019 Gallup survey of 140 countries. We modelled a composite of vaccine beliefs and regressed this on class membership and relevant covariates. RESULTS: Patterns of item endorsement indicated a well-fitting five-class model, with classes distinguished based on whether individuals sought personal knowledge about science, medicine and health; trusted science and scientists; and reported confidence in the health care system. The lowest levels of vaccine beliefs were reported by a class lacking trust and confidence and the highest levels were reported by a class endorsing trust, confidence and desiring medical and scientific knowledge. Country-level income was moderately related to class membership, and vaccine beliefs were higher in lower-income countries. CONCLUSIONS: Findings suggest that public health campaigns can focus on improving trust in science and medical providers. Efforts to improve vaccination rates can only be achieved when individuals trust science, view the work of scientists as beneficial and hold favourable views towards health care providers. Individuals will then accrue the necessary wisdom to make good health care decisions that affect not only themselves but also their fellow citizens.

Primary synovial sarcoma of bone: a retrospective analysis of 25 patients.

AIMS: To evaluate the diagnostic accuracy of SSX and SSX::SS18 antibodies in decalcified surgical specimens and outcome of synovial sarcomas (SS) of bone. METHODS AND RESULTS: Twenty-five cases were classified as bone SS (prevalence 0.32% among malignant primary bone sarcoma). Median age was 34 years (range = 9-79). Twenty-four of 25 patients presented with non-metastatic tumours, one with lung metastases. The majority of tumours involved the long bones of extremities with metaphyseal origin. Mean size of the tumour was 7.1 cm. Twenty cases (80%) were monophasic and five (20%) were biphasic. SS18::SSX fusion-specific antibody had 92% sensitivity and 99% specificity for primary bone SS, whereas SSX C-terminus antibody had 100% sensitivity and 94% specificity. Fluorescence in-situ hybridisation (FISH) analysis was feasible in nine (36%) cases and detected SS18 rearrangement in all nine cases. All patients underwent surgical removal of their primary tumour, with adequate margins in 18 (72%) patients. Chemotherapy with metothrexate, cisplatin, doxorubicin and ifosfamide was used in the seven patients. Two patients with inadequate surgical margins received radiotherapy. With a median follow-up of 80 months (range = 6-428), 5- and 10-year overall survival (OS) was 66.6% and 47.9%, respectively, and 5 and 10 years' disease-free survival (DFS) was 36.8% [95% confidence interval (CI) = 18.0-55.7%] and 32.2% (95% CI = 14.6-51.2%), respectively. A significant improvement in 10 years' DFS in patients undergoing chemotherapy compared with patients who did not was observed (P = 0.039). CONCLUSIONS: Our series highlights the utility of SS18::SSX fusion-specific and SSX C-terminus antibodies to support the diagnosis of SS. Adjustment chemotherapy was associated with improved prognosis in this series.

The relationship between depression with anxious distress DSM-5 specifier and mixed depression: a network analysis.

INTRODUCTION: Epidemiological, clinical, and treatment response characteristics of major depression with anxious distress (ADS) are quite similar to those of mixed depression, but no study investigated the symptom interplay of these conditions. OBJECTIVE: To analyze the correlations among symptom criteria for major depression with ADS and for mixed depression using a network analysis. METHODS: Two hundred and forty-one outpatients with major depression were consecutively recruited. DSM-5 criteria for major depression with ADS or with mixed features (MF) and Koukopoulos' criteria for mixed depression (MXD) were assessed using a structured clinical interview. RESULTS: A total of 58.9% of patients met DSM-5 criteria for major depression with ADS, 48.5% for MXD, and 2.5% for major depression with MF, so that the symptoms of this specifier were excluded from the network analysis. The most frequent symptoms were difficulty concentrating due to worries (57.7%), feeling keyed up or on edge (51%) (major depression with ADS), and psychic agitation or inner tension (51%) (MXD). Psychic agitation or inner tension had a central position in the network and bridged MXD to major depression with ADS through feeling keyed up or on edge. CONCLUSIONS: Criteria for major depression with ADS and for MXD are partially overlapping, with psychic agitation or inner tension and feeling keyed up or on edge that feature in both conditions and are difficult to distinguish in clinical practice. The clarification of the relationship between these two psychopathological conditions could bring important implications for diagnosis, prognosis, and treatment of depressive episodes.

A practical algorithm to predict postsurgical recurrence and progression of pituitary neuroendocrine tumours (PitNET)s.

OBJECTIVE: Pituitary neuroendocrine tumours (PitNET)s can be aggressive, thus presenting local invasion, postsurgical recurrence and/or resistance to treatment, responsible for significant morbidity. The study aimed at identifying prognostic factors of postsurgical outcome using data-driven classification of patients. DESIGN: Retrospective observational study. METHODS: Clinicopathological and radiological data of patients with PitNET treated via endoscopic endonasal surgery were collected. Tumour recurrence/progression and progression-free survival were assessed by classification tree analysis (CTA) and Kaplan-Meier curves, respectively. Histological subtype, cavernous/sphenoid sinus invasion, mitosis, Ki-67, p53, Trouillas' grading, degree of tumour exeresis and postsurgery disease activity were also evaluated. RESULTS: A total of 1066 (466 gonadotroph, 287 somatotroph, 148 lactotroph, 157 corticotroph and 8 thyrotroph) tumours were included; 21.7% invaded the cavernous/sphenoid sinus. Based on Trouillas' classification, 64.3% were grade 1a, 14.2% 1b, 16.1% 2a, and 5.4% 2b; 18.3% had >2/10 HPF mitoses, 24.9% had Ki-67 ≥3%; 15.8% were positive for p53. Exeresis was radical in 81.2% of the cases. Median follow-up was 59.2 months. At last evaluation, 79.4% of the patients were cured; 20.6% had disease persistence, controlled by medical treatment in 18.3% of them. Disease recurrence/progression was recorded in 10.9% of the cases. CTA identified 5 distinct patient subgroups with different risk of disease recurrence/progression. Grade 2 of the Trouillas' grading, >2/10 HPF mitoses, Ki-67 ≥3%, p53 protein expression (P < .001), tumour invasion (P = .002) and ACTH-subtype (P = .003) were identified as risk factors of disease recurrence/progression. CONCLUSIONS: The combined evaluation of Trouillas' grading, proliferation indexes and immunohistochemistry appears promising in the prediction of surgical outcome in PitNET.

Peculiar pathological, radiological and clinical features of skull-base de-differentiated chordomas. Results from a referral centre case-series and literature review.

AIMS: De-differentiated chordoma is an uncommon and incompletely characterised aggressive neoplasm. Only a few cases originating from the skull base have been reported. METHODS AND RESULTS: All consecutive cases of skull-base de-differentiated chordomas treated surgically in a referral centre from January 1990 to June 2019 were retrospectively evaluated to assess peculiar pathological, radiological and clinical features. Patient data were retrieved from paper and electronic records. Six cases (two male, four female; mean age at surgery = 46 years, range = 35-64), treated surgically at our institution were identified. Transformation to de-differentiated chordomas occurred after radiation therapy in three cases (mean = 13.6 years after treatment, range = 5-25), two during tumour progression, while one was de-novo. Magnetic resonance imaging and surgical examination revealed the presence of two different tumour components, corresponding to the conventional and de-differentiated portion on histological examination. The de-novo case presented a PIK3CA mutation. DNA methylation analysis revealed consistent epigenetic changes in TERT, MAGEA11 and UXT. Prognosis was poor, as five of six patients died after surgery and radiation therapy, with a mean overall survival of 29 months (range = 11-52). CONCLUSIONS: Skull-base de-differentiated chordomas are extremely rare and aggressive neoplasms with characteristic magnetic resonance imaging, surgical and histological features. Therefore, an early and accurate histological diagnosis is of paramount relevance. Molecular analysis appears promising to define mechanisms involved in tumour de-differentiation.

Red blood cell transfusions alter splanchnic oxygenation response to enteral feeding in preterm infants: an observational pilot study.

BACKGROUND: Preterm infants often require red blood cell (RBC) transfusions, which may impair splanchnic hemodynamics, thus predisposing to necrotizing enterocolitis (NEC). The aim of this study was to evaluate whether RBC transfusions alter splanchnic oxygenation patterns in response to enteral feeding in this population. MATERIALS AND METHODS: Preterm neonates (gestational age < 32 weeks and/or birth weight < 1500 g) requiring RBC transfusions for anemia underwent a 12-hour Near Infrared Spectroscopy monitoring of splanchnic (SrSO2 ) and cerebral (CrSO2 ) oxygenation, including the transfusion period, one feed before and one after. Splanchnic-cerebral oxygenation ratio (SCOR) was also calculated. Patterns of CrSO2 , SrSO2 , and SCOR changes from baseline (Δ) in response to feed before and after transfusion were analyzed. RESULTS: Twenty neonates were enrolled; none of them developed any gastrointestinal complication within 48 hours after transfusion. Pre-transfusion ΔSrSO2 and ΔSCOR increased significantly in response to feeding; on the contrary, a significant post-prandial decrease of ΔSrSO2 and ΔSCOR occurred after transfusion (p < 0.05). No difference in pre- and post-transfusion ΔCrSO2 patterns was observed. CONCLUSIONS: In preterm infants, RBC transfusions may alter splanchnic oxygenation response to enteral feeds. Whether these changes are involved in the pathogenesis of transfusion-associated NEC has to be evaluated in further larger trials.

Microbial Contamination of Medical Staff Clothing During Patient Care Activities: Performance of Decontamination of Domestic Versus Industrial Laundering Procedures.

The efficacy of domestic laundering of healthcare staff clothing is still debated. This study aimed to compare the performance of decontamination of different domestic laundering with that of industrial laundering. Fourteen naturally contaminated white coats of healthcare workers (5 fabric squares from each coat) and fabric squares of artificially contaminated cotton cloth (30 fabric squares per each bacterial strain used) were included. Four domestic laundering procedures were performed; two different washing temperatures (40 °C and 90 °C) and drying (tumble dry and air dry) were used. All fabric squares were ironed. Presence of bacterial bioburden on the fabric squares after domestic and industrial laundering was investigated. None of the naturally contaminated fabric squares resulted completely decontaminated after any of the domestic washes. At 24, 48, and 72 h of incubation, bacterial growth was observed in all the laundered fabric squares. Besides environmental microorganisms, potentially pathogenic bacteria (i.e., Acinetobacter lwoffii, Micrococcus luteus, coagulase-negative staphylococci) were isolated. On the artificially contaminated fabric squares, the bioburden was reduced after the domestic laundries; nevertheless, both Gram-negative and -positive pathogenic bacteria were not completely removed. In addition, a contamination of the fabric squares by environmental Gram-negative bacteria was observed. In both the naturally and artificially contaminated fabric squares, no bacterial growth at all the time-points analyzed was observed after industrial laundering, which provided to be more effective in bacterial decontamination than domestic washes. For those areas requiring the highest level of decontamination, the use of specialized industrial laundry services should be preferred.

Developing and validating an algorithm to identify incident chronic dialysis patients using administrative data.

BACKGROUND: Administrative healthcare databases are widespread and are often standardized with regard to their content and data coding, thus they can be used also as data sources for surveillance and epidemiological research. Chronic dialysis requires patients to frequently access hospital and clinic services, causing a heavy burden to healthcare providers. This also means that these patients are routinely tracked on administrative databases, yet very few case definitions for their identification are currently available. The aim of this study was to develop two algorithms derived from administrative data for identifying incident chronic dialysis patients and test their validity compared to the reference standard of the regional dialysis registry. METHODS: The algorithms are based on data retrieved from hospital discharge records (HDR) and ambulatory specialty visits (ASV) to identify incident chronic dialysis patients in an Italian region. Subjects are included if they have at least one event in the HDR or ASV databases based on the ICD9-CM dialysis-related diagnosis or procedure codes in the study period. Exclusion criteria comprise non-residents, prevalent cases, or patients undergoing temporary dialysis, and are evaluated only on ASV data by the first algorithm, on both ASV and HDR data by the second algorithm. We validated the algorithms against the Emilia-Romagna regional dialysis registry by searching for incident patients in 2014 and performed sensitivity analyses by modifying the criteria to define temporary dialysis. RESULTS: Algorithm 1 identified 680 patients and algorithm 2 identified 676 initiating dialysis in 2014, compared to 625 patients included in the regional dialysis registry. Sensitivity for the two algorithms was respectively 90.8 and 88.4%, positive predictive value 84.0 and 82.0%, and percentage agreement was 77.4 and 74.1%. CONCLUSIONS: Algorithms relying on retrieval of administrative records have high sensitivity and positive predictive value for the identification of incident chronic dialysis patients. Algorithm 1, which showed the higher accuracy and has a simpler case definition, can be used in place of regional dialysis registries when they are not present or sufficiently developed in a region, or to improve the accuracy and timeliness of existing registries.

PD-1 (PDCD1) promoter methylation in Merkel cell carcinoma: prognostic relevance and relationship with clinico-pathological parameters.

Merkel cell carcinoma is an aggressive neuroendocrine skin tumor, for which several non-conclusive prognostic factors of adverse clinical behavior have been reported. As promoter methylation of the immune checkpoint receptor CD279/PD-1/PDCD1(mPDCD1) has been shown to be a prognostic factor in different cancers, we investigated its role in Merkel cell carcinoma. mPDCD1was assessed retrospectively in a cohort of 69 Merkel cell carcinoma patients from the University of Bologna, University of Turin and University of Insubria. Kaplan-Meier curves and log-rank tests were calculated for all variables. To assess the influence of mPDCD1, the Cox proportional hazards model and different Royston-Parmar models were evaluated. High PDCD1 methylation (mPDCD1high) was associated with a higher overall mortality at both the univariate analysis (log rank test: χ2 = 5.17, p = 0.023; permutation test: p = 0.023) and the multivariate analysis (HR = 2.111, p = 0.042). The other variables associated with a higher overall mortality at the multivariate analysis were clinical stage III-IV (HR = 2.357, p = 0.008), size > 2 cm (HR = 2.248, p = 0.031) and Merkel cell polyomavirus (HR = 0.397, p = 0.015). Further, mPDCD1high was strongly associated with older age (81 vs 76 years, p = 0.042), absence of immune cells (92.6%, p < 0.001), no expression of PD-L1 by immune cells (70.4%, p = 0.041) and by both immune and tumor cells (70.4%, p = 0.001). mPDCD1 is a valid prognostic parameter in patients affected by Merkel cell carcinoma. In addition, it could provide an estimate of the global PD-1/PD-L1 expression with potentially relevant implications from a therapeutic point of view.

Osteoblastoma-like osteosarcoma: high-grade or low-grade osteosarcoma?

AIMS: Osteoblastoma-like osteosarcoma is a rare variant of osteosarcoma (1% of all osteosarcomas), histologically similar to osteoblastoma. In the current World Health Organisation (WHO) classification, osteoblastoma-like osteosarcoma is classified within the group of conventional (high-grade) osteosarcomas. However, several published cases have been actually regarded as low-grade malignant tumours. As strict morphological criteria to distinguish between low- and high-grade lesions are not available, we reviewed our series of osteoblastoma-like osteosarcomas in the attempt to identify clinical and morphological features predictive of aggressiveness. METHODS AND RESULTS: We retrieved 15 cases of osteoblastoma-like osteosarcoma from the files of the Istituto Ortopedico Rizzoli. Patients received various treatments. Five patients developed metastasis and five patients developed local recurrences (all after incomplete surgery). Eleven patients were alive without disease, while four patients died of their disease. Statistical analysis revealed a statistically significant (P = 0.048) lower disease-free survival in patients with areas of conventional (high-grade) osteosarcoma. CONCLUSIONS: With the important limitation of a small cohort of patients, the presence of areas of conventional (high-grade) osteosarcoma is the only parameter to predict the aggressiveness of osteoblastoma-like osteosarcoma.

Clinical utility of measuring Epstein-Barr virus-specific cell-mediated immunity after HSCT in addition to virological monitoring: results from a prospective study.

Lack of virus-specific cell-mediated immunity (CMI) is associated with worse viral infection outcome in hematopoietic stem cell transplantation (HSCT). We aimed to evaluate the role of immunological monitoring of Epstein-Barr virus (EBV) infection in addition to virological one in 33 adult and 18 pediatric allogeneic HSCT recipients. Virological monitoring of infection was performed on whole blood samples by a quantitative real-time PCR assay. Immunological monitoring was performed by Enzyme-linked ImmunoSPOT assay, evaluating EBV-specific CMI, at fixed time-points and when EBV DNAemia was ≥ 10,000 copies/mL. Fifty-one percent of patients developed a post-transplant EBV infection and reduced-intensity conditioning regimen was the only factor associated to infection (P = 0.023). Lack of EBV-specific CMI during active EBV infection was associated with a greater severity of infection. Patients without EBV-specific CMI showed higher median peak level of EBV DNAemia than patients with EBV-specific CMI (P = 0.014), and consequently received more frequently, at EBV DNAemia peak, anti-CD20 therapy (0 versus 54.5%, P = 0.002). No patients with EBV-specific CMI versus 27.2% without EBV-specific CMI developed EBV-related complications (P = 0.063), including two lethal EBV-related post-transplant lymphoproliferative disorders. Combined immunological and virological measurements could improve EBV infection management in HSCT, anticipating the beginning of preemptive treatment from the EBV DNAemia peak to the finding of the lack of EBV-specific CMI.

Temporal validation of the CT-PIRP prognostic model for mortality and renal replacement therapy initiation in chronic kidney disease patients.

BACKGROUND: A classification tree model (CT-PIRP) was developed in 2013 to predict the annual renal function decline of patients with chronic kidney disease (CKD) participating in the PIRP (Progetto Insufficienza Renale Progressiva) project, which involves thirteen Nephrology Hospital Units in Emilia-Romagna (Italy). This model identified seven subgroups with specific combinations of baseline characteristics that were associated with a differential estimated glomerular filtration rate (eGFR) annual decline, but the model's ability to predict mortality and renal replacement therapy (RRT) has not been established yet. METHODS: Survival analysis was used to determine whether CT-PIRP subgroups identified in the derivation cohort (n = 2265) had different mortality and RRT risks. Temporal validation was performed in a matched cohort (n = 2051) of subsequently enrolled PIRP patients, in which discrimination and calibration were assessed using Kaplan-Meier survival curves, Cox regression and Fine & Gray competing risk modeling. RESULTS: In both cohorts mortality risk was higher for subgroups 3 (proteinuric, low eGFR, high serum phosphate) and lower for subgroups 1 (proteinuric, high eGFR), 4 (non-proteinuric, younger, non-diabetic) and 5 (non-proteinuric, younger, diabetic). Risk of RRT was higher for subgroups 3 and 2 (proteinuric, low eGFR, low serum phosphate), while subgroups 1, 6 (non-proteinuric, old females) and 7 (non-proteinuric, old males) showed lower risk. Calibration was excellent for mortality in all subgroups while for RRT it was overall good except in subgroups 4 and 5. CONCLUSIONS: The CT-PIRP model is a temporally validated prediction tool for mortality and RRT, based on variables routinely collected, that could assist decision-making regarding the treatment of incident CKD patients. External validation in other CKD populations is needed to determine its generalizability.

Histological Analysis of Term Placentas from Hyperimmune Globulin-Treated and Untreated Mothers with Primary Cytomegalovirus Infection.

BACKGROUND: The Congenital Human Cytomegalovirus Infection Prevention (CHIP) study, a randomized, blinded, placebo-controlled trial, demonstrated that the efficacy of hyperimmune globulin (HIG) was not different from that of placebo regarding transmission of cytomegalovirus (CMV) from mothers to newborns. Our aim was to analyze histologically HIG effects on placentas collected for the CHIP study. MATERIALS AND METHODS: Virological and histological analyses were performed on 40 placentas from transmitter and nontransmitter HIG-treated and untreated mothers by assessing the number of CMV-positive cells, tissue viral load, tissue damage, and compensatory mechanisms. RESULTS: The HIG and placebo groups showed no significant differences in the number of CMV-positive cells (median number in 10 fields at 10 high-power fields: 2.5 vs. 2, p = 0.969) and viral load (median load: 5 copies/5 ng vs. 10.5 copies/5 ng, p = 0.874). Regarding histological examination, the scores of parameters related to tissue damage and hypoxic parenchymal compensation were higher in transmitters except for chorangiosis, with statistically significant differences observed for chronic villitis (p = 0.007), calcification (p = 0.011), and the total score of tissue damage (p < 0.001). The HIG and placebo groups showed no significant differences for all tissue damage and compensation parameters and overall scores. DISCUSSION: HIGs are not able to reduce placental viral load and histological damage, which was significantly associated only with infection.

Different rates of progression and mortality in patients with chronic kidney disease at outpatient nephrology clinics across Europe.

The incidence of renal replacement therapy varies across countries. However, little is known about the epidemiology of chronic kidney disease (CKD) outcomes. Here we describe progression and mortality risk of patients with CKD but not on renal replacement therapy at outpatient nephrology clinics across Europe using individual data from nine CKD cohorts participating in the European CKD Burden Consortium. A joint model assessed the mean change in estimated glomerular filtration rate (eGFR) and mortality risk simultaneously, thereby accounting for mortality risk when estimating eGFR decline and vice versa, while also correcting for the measurement error in eGFR. Results were adjusted for important risk factors (baseline eGFR, age, sex, albuminuria, primary renal disease, diabetes, hypertension, obesity and smoking) in 27,771 patients from five countries. The adjusted mean annual eGFR decline varied from 0.77 (95% confidence interval 0.45, 1.08) ml/min/1.73m2 in the Belgium cohort to 2.43 (2.11, 2.75) ml/min/1.73m2 in the Spanish cohort. As compared to the Italian PIRP cohort, the adjusted mortality hazard ratio varied from 0.22 (0.11, 0.43) in the London LACKABO cohort to 1.30 (1.13, 1.49) in the English CRISIS cohort. These results suggest that the eGFR decline showed minor variation but mortality showed the most variation. Thus, different health care organization systems are potentially associated with differences in outcome of patients with CKD within Europe. These results can be used by policy makers to plan resources on a regional, national and European level.

Monitoring of Cytomegalovirus (CMV)-Specific Cell-Mediated Immunity in Heart Transplant Recipients: Clinical Utility of the QuantiFERON-CMV Assay for Management of Posttransplant CMV Infection.

The clinical utility of the QuantiFERON-CMV (QFN-CMV) assay in heart transplant recipients was assessed. Forty-four cytomegalovirus (CMV)-seropositive patients were enrolled: 17 received antiviral prophylaxis, and 27 were managed preemptively. CMV-DNAemia monitoring was performed by the use of a quantitative real-time PCR assay. The QFN-CMV assay was retrospectively performed on blood samples collected at five posttransplant time points. A higher proportion of patients with an indeterminate QFN-CMV result after the suspension of prophylaxis than of patients who showed a global T-cell responsiveness developed CMV infection (P = 0.036). Patients who reconstituted a CMV-specific response following the first CMV-DNAemia-positive result (42.9%) showed a median CMV-DNAemia peak 1 log of magnitude lower than that seen with patients with indeterminate results, and all controlled viral replication spontaneously. The 25% of patients with an indeterminate result developed CMV disease. In the preemptive strategy group, no differences in the development of subsequent infection, magnitude of viral load, and viral control were observed on the basis of QFN-CMV measurements performed before and after the first CMV-DNAemia-positive result. Considering both CMV prevention strategies, viral relapse was associated with the failure to reconstitute CMV-specific cell-mediated immunity (CMI) after the resolution of the first episode of CMV infection (P = 0.032). QFN-CMV measurements can be a useful tool for identifying patients (i) at higher risk of developing infection after discontinuing antiviral prophylaxis, (ii) with late CMV infection who would benefit from appropriate antiviral interventions, and (iii) at higher risk of viral relapses. QFN-CMV measurements taken within 1 month posttransplantation (early period) are not revealing.

Impact of rehabilitation on mortality and readmissions after surgery for hip fracture.

BACKGROUND: Hip fracture in elderly patients is a rising global public health concern because of population ageing, and increasing frailty. Long-term morbidity related to poor management of hip fracture is associated with decreased quality of life, survival, and increase in healthcare costs. Receiving postoperative rehabilitation is associated with better outcomes and a higher likelihood of returning to pre-existing level of functioning. However little is known about which postoperative rehabilitation pathways are more effective to optimize patient outcomes. Few studies have analyzed postoperative rehabilitation pathways in a universal healthcare system. The aim of this study is to analyze the impact of post-acute rehabilitation pathways on mortality and readmission in elderly patients undergoing surgery for hip fracture in a large metropolitan area in Italy. METHODS: In this retrospective cohort study, we analyzed 6-month mortality from admission and 6-month readmission after hospital discharge in patients who underwent surgical repair for hip fracture in the hospitals of the Bologna metropolitan area between 1.1.2013 and 30.6.2014. Data were drawn from the regional hospital discharge records database. Kaplan-Meier estimates and multiple Cox regression were used to analyze mortality as a function of rehabilitation pathways. Multiple logistic regression determined predictors of readmission. RESULTS: The study population includes 2208 patients, mostly women (n = 1677, 76%), with a median age of 83.8 years. Hospital rehabilitation was provided to 519 patients (23.5%), 907 (41.1%) received rehabilitation in private inpatient rehabilitation facilities (IRF) accredited by the National Health System, and 782 (35.4%) received no post-acute rehabilitation. Compared with patient receiving hospital rehabilitation, the other groups showed significantly higher mortality risks (no rehabilitation, Hazard Ratio (HR) = 2.19, 95%CI = 1.54-3.12, p < 0.001; IRF rehabilitation, HR = 1.66, 95%CI = 1.54-1.79, p < 0.001). The risk of readmission did not differ significantly among rehabilitation pathways. CONCLUSIONS: Intensive hospital rehabilitation was significantly associated with a lower risk of mortality compared to IRF rehabilitation and no rehabilitation. Our results may help in the development of evidence-based recommendations aimed to improve resource utilization and quality of care in hip fracture patients. Further research is warranted to investigate the impact of the rehabilitation pathway on other outcomes, such as patients' functional status and quality of life.