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Objective: The aim of the study was to report outcomes of a thoraco-abdominal, custom made, low profile (outer diameter 20 Fr) four branched endograft used as an off the shelf (OTS) solution for urgent juxta/pararenal abdominal aortic aneurysms (J/P-AAAs) and thoraco-abdominal aortic aneurysms (TAAAs) in the presence of hostile femoral/iliac access., Methods: Data for patients who underwent endovascular repair for urgent J/P-AAAs and TAAAs with hostile femoral/iliac access by a low profile, four branched endograft in four European aortic centres between 2019 and 2023 were prospectively collected and retrospectively analysed. The investigated device was a custom made endograft with the configuration of a standard T-branch, used as an OTS solution for urgent cases with hostile femoral/iliac access. Access related complications, spinal cord ischaemia (SCI), and 30 day mortality were assessed as primary outcomes. Survival, freedom from re-interventions (FFRs), and iliac limb occlusion (ILO) were evaluated as secondary outcomes., Results: Fifty five cases were enrolled: ruptures, n = 14 (25%); symptomatic, n = 12 (22%); and asymptomatic TAAAs with diameter ≥ 80 mm, n = 29 (53%). The were seven (13%) J/P-AAAs and 48 (87%) TAAAs. The median right and left external iliac artery diameters were 6.7 (interquartile range [IQR] 5.5, 7.9) mm and 7.1 (IQR 6.5, 8.7) mm, respectively. Bilateral hostile femoral/iliac access was reported in 39 patients (71%). Access related complications occurred in five cases (9%). There were four cases (7%) of SCI with two permanent paraplegias. Four patients (7%) died within 30 days. The median follow up was 22 (IQR 11, 33) months. Overall, eight patients (15%) required re-interventions: four within 30 days and four during follow up. No ILO occurred. Estimated one year FFRs and survival was 91% and 87%, respectively., Conclusion: Low profile OTS thoraco-abdominal endograft seems safe and effective to manage urgent J/P-AAAs and TAAAs in the presence of hostile femoral/iliac access. Further larger studies with long term follow up are needed to validate this preliminary experience., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To report outcomes of urgent juxtarenal/pararenal aneurysms (J/P-AAAs) managed by off-the-shelf multibranched thoracoabdominal endografts (Cook, T-branch)., Methods: In this observational, multicenter, retrospective study, patients with J/P-AAAs treated by urgent endovascular repair by T-branch in 23 European aortic centers, from 2013 to 2023, were analyzed. Contained J/P-AAAs rupture, presence of related symptoms, and aneurysm diameter of >70 mm were considered as indication for urgent repair. Technical success (TS), spinal cord ischemia (SCI), and 30-day/hospital mortality were assessed as early outcomes. Survival, freedom from reinterventions, and target artery instability (TAI) were evaluated during follow-up., Results: Overall, 197 patients (J-AAAs, n = 64 [33%]; P-AAAs, n = 95 [48%]; previous failed endovascular aneurysm repair (EVAR), n = 38 [19%]) were analyzed. The mean age and aneurysm diameter was 75 ± 8 years and 76 ± 4 mm, respectively. The American Society of Anesthesiologists score was 3 and 4 in 118 (60%) and 79 (40%) patients. Rupture, symptoms, and diameter of >70 mm were present in 51 (26%), 110 (56%), and 53 (27%) patients, respectively. An adjunctive proximal thoracic endograft was used in 28 cases (14%). The mean aortic coverage between the upper portion of the endograft and the lowest renal artery was 154 ± 49 mm. Single-stage repair and cerebrospinal fluid drainage were reported in 144 (73%) and 53 (27%) cases, respectively. TS was achieved in 182 (92%) cases (rupture, 84% vs no rupture, 95%; P = .02). Failures consist of TA loss (11 [6%]: renal artery, 9; celiac trunk, 2), type I to III endoleaks (2 [1%]), and 24-h mortality (2 [1%]). Rupture was a risk factor for technical failure (P = .02; odds ratio [OR], 3.8; 95% confidence interval [CI], 1.1-12.1). Overall, 15 patients (8%) had persistent SCI (rupture, 14% vs no rupture, 5%) with 11 (6%) , of paraplegia (rupture, 10% vs no rupture, 5%; P = .001). Rupture (P = .04; OR, 3.1; 95% CI, 1.1-8.9) and adjunctive proximal thoracic endograft (P = .01; OR, 4.1; 95% CI, 1.3-12.9) were risk-factors for SCI. Twenty-two patients (11%) died within 30 days or during a prolonged hospitalization. Previous failed EVAR (P = .04; OR, 3.6; 95% CI, 1.1-12.3), paraplegia (P < .001; OR, 9.9; 95% CI, 1.6-62.2) and postoperative mesenteric complications (P = .03; OR, 10.4; 95% CI, 1.2-93.3), as well as cardiac (P = .03; OR, 8.2; 95% CI, 2.0-33.0) and respiratory (P < .001; OR, 10.1; 95% CI, 2.9-35.2) morbidities were associated with 30-day/hospital mortality. The mean follow-up was 19 ± 5 months. The estimated 3-year survival and freedom from reinterventions was 58% and 77%, respectively. TAI occurred in 27 patients (14%) (occlusion, 15; endoleak, 14) with an estimated 3-year freedom from TAI of 72%., Conclusions: Urgent repair of J/P-AAAs by T-branch is feasible and effective with satisfactory TS and 30-day/hospital mortality in high-risk patients. However, extensive aortic coverage is necessary, leading to a non-negligible SCI rate, especially in case of aortic rupture or when adjunctive thoracic endografts are necessary. Previous failed EVAR and postoperative mesenteric complications, as well as cardiac and respiratory morbidities were associated with 30-day/hospital mortality and should be subjected to more research for the purposes of improving outcomes., Competing Interests: Disclosures E.G., G.F., M.A., N.T., G.M., G.S., A.K., K.O., K.M., L.M.P., and M.G. are proctors for Cook Medical and received travel, educational grants, or speaker's fees. T.K., N.D., and S.H. are consultants for Cook Medical and they have intellectual property with Cook Medical and received speaking fees, and research, travel, and educational grants., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) has rapidly spread to every country around the world taking on pandemic proportions. Since 8 March 2020, the Italian government ordered a nationwide lockdown with unavoidable social isolation. Healthcare professionals (HCPs) represent the most physically and emotionally involved category. The aim of this study is to assess the social distress among HCPs in Italy., Patients and Methods: In this online, totally anonymous survey, 24 multiple choice questions were posed to medical staff employed in the Italian Healthcare System during the COVID-19 pandemic. Data collection was performed from 30 March to 24 April 2020., Results: A total of 600 HCPs completed the questionnaire. The majority of respondents expressed the fear of being at higher risk of contagion than the general population (83.3%) and the weighty concern of infecting their families (72.5%). An insufficient supply of personal protective equipment (PPE; P = 0.0003) and inadequate training about procedures to follow (P = 0.0092) were seen to significantly coincide with these worries. More than two-thirds declared a change in family organisation, which showed a significant correlation with the concern of infecting their relatives (P < 0.0001)., Conclusions: This is the first Italian survey on social distress among HCPs during the COVID-19 pandemic. The unavailability of PPE, screening procedures and adequate training strongly affected HCPs' emotional status. Although there was a predominance of oncologists (especially from the North of Italy), which impairs the generalisation of our findings, this survey underlined the social impact that this health emergency has had on HCPs., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Platinum-based therapy, combined or not with immune checkpoint inhibitors, represents a front-line choice for patients with non-small-cell lung cancer (NSCLC). Despite the improved outcomes in the last years for this malignancy, only a sub-group of patients have long-term benefit. Excision repair cross-complementation group 1 (ERCC1) has been considered a potential biomarker to predict the outcome of platinum-based chemotherapy in NSCLC. However, the ERCC1 gene is transcribed in four splice variants where the isoform 202 was described as the only one active and able to complex Xeroderma pigmentosum group F-complementing protein (XPF). Here, we prospectively investigated if the active form of ERCC1, as assessed by the ERCC1/XPF complex (ERCC1/XPF), could predict the sensitivity to platinum compounds., Patients and Methods: Prospectively enrolled, patients with advanced NSCLC treated with a first-line regimen containing platinum were centrally evaluated for ERCC1/XPF by a proximity ligation assay. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were analyzed., Results: The absence of the ERCC1/XPF in the tumor suggested a trend of worst outcomes in terms of both OS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 0.67-2.94, P = 0.373] and PFS (HR 1.61, 95% CI 0.88-3.03, P = 0.123). ORR was marginally influenced in ERCC1/XPF-negative and -positive groups [odds ratio (stable disease + progressive disease versus complete response + partial response) 0.87, 95% CI 0.25-3.07, P = 0.832]., Conclusion: The lack of ERCC1/XPF complex in NSCLC tumor cells might delineate a group of patients with poor outcomes when treated with platinum compounds. ERCC1/XPF absence might well identify patients for whom a different therapeutic approach could be necessary., Competing Interests: Disclosure MCG reported personal fees from Merck, Bristol-Myers Squibb, AstraZeneca, Roche, Takeda, Celgene, Pfizer, and GlaxoSmithKline. No other disclosures were reported. Data sharing All datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate The study was approved by Fondazione IRCCS Istituto Nazionale dei Tumori Institutional Review Board (INT18/13) and conducted according to the ethical principles for medical research involving human subjects adopted in the Declaration of Helsinki. All patients signed a written informed consent., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

ZBTB2 is a protein belonging to the BTB/POZ zinc-finger family whose members typically contain a BTB/POZ domain at the N-terminus and several zinc-finger domains at the C-terminus. Studies have been carried out to disclose the role of ZBTB2 in cell proliferation, in human cancers and in regulating DNA methylation. Moreover, ZBTB2 has been also described as an ARF, p53 and p21 gene repressor as well as an activator of genes modulating pluripotency. In this scenario, ZBTB2 seems to play many functions likely associated with other proteins. Here we report a picture of the ZBTB2 protein partners in U87MG cell line, identified by high-resolution mass spectrometry (MS) that highlights the interplay between ZBTB2 and chromatin remodeling multiprotein complexes. In particular, our analysis reveals the presence, as ZBTB2 candidate interactors, of SMARCA5 and BAZ1B components of the chromatin remodeling complex WICH and PBRM1, a subunit of the SWI/SNF complex. Intriguingly, we identified all the subunits of the NuRD complex among the ZBTB2 interactors. By co-immunoprecipitation experiments and ChIP-seq analysis we definitely identify ZBTB2 as a new partner of the NuRD complex., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier B.V.)

Background: Beyond progression after tyrosine kinase inhibitor in EGFR-positive non-small-cell lung cancer patients (BE-POSITIVE) was the first Italian multicenter observational study that reported the outcomes of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in a "real-life" Caucasian EGFR-mutated non-small-cell lung cancer (NSCLC) population. The sharing of multi-institutional experiences represents a crucial strategy to enrich knowledge about uncommon EGFR mutations. Therefore, we performed a post hoc analysis of the BE-POSITIVE study., Patients and Methods: Data of advanced NSCLC patients with uncommon EGFR mutations who received first-line first-generation EGFR-TKIs in 24 Italian Hospitals were collected. In this analysis we aimed to evaluate overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) of EGFR-TKIs in NSCLC patients harboring uncommon EGFR mutations., Results: Thirty-five patients harboring uncommon EGFR mutations (any mutation other than deletion 19 or substitution of leucine by arginine at codon 858) were included of the original 312 EGFR-mutated cases. Most of them were female (n = 20, 57.1%), former smokers (n = 23, 65.7%), with adenocarcinoma (n = 31, 88.6%). The most frequent EGFR mutations were G719X (n = 6, 17.2%) and L861Q (n = 5, 14.2%). The population presented an ORR of 25.7%, a median PFS of 5.19 months, and a median OS of 14.49 months. When stratified according to type of EGFR mutation, median OS ranged from 3.65 months for unspecified mutations to 21.29 for double EGFR mutations. Median PFS ranged from 1.77 months for unspecified mutations to 20.83 months for concomitant EGFR-anaplastic lymphoma kinase alteration. ORR varied from 0% in exon 18, 20 and double gene alteration to 66.6% in exon 19., Conclusion: Our study supports the existence of a strong outcome heterogeneity within patients harboring uncommon EGFR mutations, which needs to be clarified to achieve a real personalized treatment strategy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: TAS-102 improves overall survival (OS) in patients with metastatic colorectal cancer (mCRC) refractory to standard treatments. However, predictive biomarkers of efficacy are currently lacking., Patients and Methods: We treated a cohort of 43 chemorefractory mCRC patients treated with TAS-102, in a single institution expanded access, compassionate use programme. We stratified patients in two groups according to number of cycles received (<6 cycles and ≥6 cycles). OS, progression-free survival (PFS) and safety were evaluated., Results: Thirteen out of 43 patients (30%) obtained a clinically relevant disease control with TAS-102 therapy. Eleven of them were treated for ≥6 cycles with TAS-102, reaching a median PFS of 7.5 months (95% CI 5.8 to 9.2 months) and a median OS of 11.2 months (95% CI range not reached yet). A trend towards significance (p=0.08) between a good performance status and response to TAS-102 was observed. Further, 7 out of the 11 TAS-102 long-treated patients achieved a clinical benefit from a previous treatment with regorafenib. A significant correlation between regorafenib and TAS-102 clinical efficacy was observed (p=0.008). Six out 13 regorafenib-naïve patients were treated with regorafenib after progression from TAS-102. All these patients achieved SD with a median duration of treatment with regorafenib of 6.1 months (range, 1.6-6.7)., Conclusion: Patients with mCRC in good clinical conditions, even though having been heavily pretreated with all the available treatment options, could obtain a significant clinical benefit from treatment with TAS-102. Moreover, a previous clinical benefit obtained with regorafenib is potentially predictive of clinical efficacy of subsequent TAS-102 treatment., Competing Interests: Competing interests: None declared.

An important role for natural killer (NK) cells in the regulation of T-cell responses is emerging, although the receptor pairs regulating the NK-T-cell interaction have still not been identified. We found that superantigen-stimulated T cells express Nectin-2 (CD112) and poliovirus receptor (PVR; CD155), the ligands of the activating NK receptor DNAX accessory molecule-1 (DNAM-1; CD226). Interestingly, only PVR was present at the T cell surface, particularly on cells in the S and G(2)/M phases of the cell cycle. The up-regulation of PVR expression involves DNA-damage response (DDR)-dependent pathways, because we found that pharmacologic inhibition of ATM and ATR kinases reduced PVR expression and that PVR was almost exclusively induced on cells expressing the DDR marker γH2AX. Oxidative stress contributed to DDR activation, and our results showed impaired PVR levels in the presence of the reactive oxygen species (ROS) scavenger N-acetyl-cysteine (NAC), being monocytes the main ROS source needed for optimal PVR expression on activated T cells. Interestingly, in accordance with ligand expression, NK cells lysed allogeneic proliferating more efficiently than nonproliferating T lymphocytes, with a mechanism requiring the cooperation between DNAM-1 and NKG2D. These results could contribute to unraveling the role of NK cells in the down-regulation of T-cell responses in physiologic and pathologic processes such as autoimmunity or GVHD.

Type I mucopolysaccharidosis (MPS I) is a lysosomal storage disorder caused by the deficiency of α-L-iduronidase, which results in glycosaminoglycan accumulation in tissues. Clinical manifestations include skeletal dysplasia, joint stiffness, visual and auditory defects, cardiac insufficiency, hepatosplenomegaly, and mental retardation (the last being present exclusively in the severe Hurler variant). The available treatments, enzyme-replacement therapy and hematopoietic stem cell (HSC) transplantation, can ameliorate most disease manifestations, but their outcome on skeletal and brain disease could be further improved. We demonstrate here that HSC gene therapy, based on lentiviral vectors, completely corrects disease manifestations in the mouse model. Of note, the therapeutic benefit provided by gene therapy on critical MPS I manifestations, such as neurologic and skeletal disease, greatly exceeds that exerted by HSC transplantation, the standard of care treatment for Hurler patients. Interestingly, therapeutic efficacy of HSC gene therapy is strictly dependent on the achievement of supranormal enzyme activity in the hematopoietic system of transplanted mice, which allows enzyme delivery to the brain and skeleton for disease correction. Overall, our data provide evidence of an efficacious treatment for MPS I Hurler patients, warranting future development toward clinical testing.

Aim: Survivin is a member of the inhibitors of apoptosis (IAP) gene family that acts through pathways different from those involving the bcl-2 family. Largely undetectable in normal adult tissues, survivin is deregulated in most human cancers including non-small-cell lung cancer (NSCLC) and may represent a tumor marker with prognostic and therapeutic implications. Aim of our study was to determine the prognostic role of survivin as an apoptosis-related biomarker in a series of resected NSCLC patients., Methods: A retrospective series of resected NSCLC patients were retrieved from the files of the Regina Elena National Cancer Institute. Survivin was detected by immunohistochemistry (IHC) using a polyclonal antibody. Survivin displayed two kinds of immunoreactivity: (i) a diffuse cytoplasmic staining and (ii) a distinct nuclear staining. A score-scale to distinguish positive (score 1-2) vs. negative (score 0) pattern was applied. Clinical and biological (nuclear and cytoplasmic survivin staining) covariables were screened for a prognostic relationship with overall survival (OS) and disease-free survival (DFS) into the univariate and multivariate analyses., Results: Data referring to 116 NSCLC patients who underwent surgery for stage I-IIIA NSCLC were collected. Multivariate analyses identified tumor size, nodal status and nuclear, but not cytoplasmic, expression of survivin as significant independent predictors of OS, with a hazard ratio of 2.40 (95% CI 1.44, 3.99, p=0.001), 2.03 (95% CI 1.26, 3.26, p=0.003) and 1.83 (95% CI 1.01, 3.30, p=0.044), respectively. Median OS for nuclear survivin positive (score 1-2) and negative (score 0) patients were 23 months (95% CI 15, 31) and 36 months (95% CI 1, 76), respectively (p=0.01); five-year survival for score 1-2 and score 0 patients were 20% and 44.5%, respectively. Conversely, no significant impact on survival is found when patients are stratified according to cytoplasmic survivin expression., Conclusions: Data presented herein open the issue that prognosis of stage I-IIIA NSCLC can be linked to the cellular pattern of distribution of survivin.

Background: Customizing chemotherapy on the basis of chemosentitivity prediction may improve outcome in advanced bladder cancer patients. Since DNA damaging agents are the cornerstones of therapy, we hypothesized that levels of DNA repair genes could predict survival., Patients and Methods: Messenger RNA expression levels of excision repair cross complementing 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and caveolin-1 were determined by RT-PCR in tumor DNA from 57 advanced and metastatic bladder cancer patients treated with either gemcitabine/cisplatin or gemcitabine/cisplatin/paclitaxel (Taxol). Levels were correlated with survival, time to disease progression and chemotherapy response., Results: Median survival was significantly higher in patients with low ERCC1 levels (25.4 versus 15.4 months; P = 0.03) (median follow-up 19 months). A trend towards longer time to progression was observed in patients with tumors expressing low levels of all markers. Levels of RRM1, BRCA1 and caveolin-1, however, failed to predict the survival and a clear link with chemotherapy response could not be established. On multivariate analysis with pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for survival., Conclusion: The results of the study indicate that ERCC1 may predict survival in bladder cancer treated by platinum-based therapy.

This review highlights the numerous molecular biology findings in the field of lung cancer with potential therapeutic impact in both the near and distant future. At least six lines of research have recently emerged as potential contributors to changes in clinical practice. Abundant pre-clinical and clinical data indicate that BRCA1 mRNA expression is a differential modulator of chemotherapy sensitivity. Low levels predict cisplatin sensitivity and antimicrotubule drug resistance, and the opposite occurs with high levels. Secondly, single nucleotide polymorphisms in the ERCC1 gene influence survival and toxicity with cisplatin-based chemotherapy. The main core of recent research has centered on EGFR mutations and gene copy numbers. For the first time, EGFR mutations have been shown to predict dramatic responses in metastatic lung adenocarcinomas, with a threefold increase in time to progression and survival in patients receiving EGFR tyrosine kinase inhibitors. In contrast, K-ras mutations confer a negative effect in these patients. Evidence has also been accumulated on the crosstalk between estrogen and EGFR receptor pathways, paving the way for clinical trials of EGFR tyrosine kinase inhibitors plus aromatase inhibitors. microRNAs control the expression of cognate target genes, and downregulation of Dicer has been shown to be a strong predictor of relapse in surgically resected non-small-cell lung cancer patients. Finally, overexpression of the Wingless-type (Wnt) genes and methylation of Wnt antagonists like WIF and secreted frizzled related proteins have been documented in non-small-cell lung cancer and are believed to be an important mechanism of cancer stem cell maintenance.

Background: Impaired DNA repair capacity may favorably affect survival in cisplatin/gemcitabine-treated non-small-cell lung cancer (NSCLC) patients. We investigated the association of survival with genetic polymorphisms in X-ray repair cross-complementing group 1 and group 3 (XRCC3), xeroderma pigmentosum group D (XPD), excision repair cross-complementing group 1, ligase IV, ribonucleotide reductase, TP53, cyclooxygenase-2, interleukin-6, peroxisome proliferator-activated receptor gamma, epidermal growth factor, methylene-tetra-hydrofolate reductase and methionine synthase., Patients and Methods: One hundred and thirty-five stage IV or IIIB (with malignant pleural effusion) NSCLC patients treated with cisplatin/gemcitabine from different hospitals of the Spanish Lung Cancer Group were genotyped for 14 different polymorphisms in 13 genes. Polymorphisms were detected by the TaqMan method, using genomic DNA extracted from baseline blood samples., Results: Median survival was significantly increased in patients harboring XRCC3 241 MetMet: 16 months versus 10 months for patients with ThrMet and 14 months for those with ThrThr (P = 0.01). The risk of death ratio was significantly lower for MetMet than for ThrMet patients (hazard ratio, 0.43; P = 0.01). In the multivariate Cox model, XRCC3 241 remained an independent prognostic factor (hazard ratio: XRCC3 241 MetMet, 0.44; P = 0.01), and XPD 751 and XRCC1 399 also emerged as significant prognostic factors (hazard ratios: XPD 751 LysGln, 0.46, P = 0.03; XRCC1 399 ArgGln, 0.61, P = 0.04). No other association was observed between genotype and survival., Conclusion: XRCC3 241 MetMet is an independent determinant of favorable survival in NSCLC patients treated with cisplatin/gemcitabine. A simple molecular assay to determine the XRCC3 241 genotype can be useful for customizing chemotherapy.

Recent evidence suggests that young women with estrogen receptor (ER)-positive breast cancer (BC) require additional treatment because of the inadequacy of cyclophosphamide, methotrexate fluorouracil (CMF) alone. Herein we report our findings from 368 premenopausal patients given adjuvant anthracycline alone. Overall, patients had a significantly increasing risk of relapse and dying with decreasing age at diagnosis and ER-negative disease. Interestingly, ER expression was not a negative prognostic factor, even among women <35 years, the 5-year disease-free survival (DFS) tending to be higher in patients with ER-positive rather than -negative BC. The potential of combining anthracyclines and endocrine therapies is reviewed and discussed.

Objective: This study was undertaken to develop a comprehensive risk-assessment approach capable of evaluating maternal and fetal outcomes., Study Design: Data from 10,984 women and 11,066 infants delivered at 79 military treatment facilities in the United States from 1995 to 1997 were used to develop two individual but complementary risk-adjustment models for maternal and, separately, fetal outcomes. A range of maternal and delivery-related risk variables and clinically important outcomes were identified by expert opinion and selected and weighted with ordinal logistic regression analysis. Receiver operating characteristic curves for the maternal and fetal models were determined. Variation across the facilities in risk-adjusted performance was also evaluated., Results: Risk factors and poor outcomes were rare for both mothers and infants, with 96.9% of infants and 97.7% of mothers having good or excellent outcomes (0.7% mortality and 0.01% mortality, respectively). Despite the low frequency of poor outcomes both models performed well, with receiver operating characteristic curves of 0.75 for maternal outcomes and 0.78 for infant outcomes. When the models were applied to the military treatment facilities, there were significant differences among facilities in risk-adjusted outcomes. Twenty-four of the facilities in the study (30%) had outcomes odds ratios that were significantly >1 or significantly <1 (P <.05). There did not appear to be any relationship between the performance of a military treatment facility for maternal outcome and that for infant outcome., Conclusion: Complementary risk models for maternal and infant outcomes were developed that had satisfactory discriminatory power across a variety of facilities within a large health system. With further development and refinement this approach holds promise of being able to detect variations in risk-adjusted performance that could be used to identify best practices. The results might also be used to help coordinate and improve the quality of care for the entire conception-to-delivery process.

The activity of RA is significantly altered by pregnancy with approximately 70 per cent of patients experiencing substantial improvement in symptoms, signs and sometimes extra-articular manifestations. This lessening of disease activity occurs in association with an almost complete cessation of medications. However, whether partial or complete this remission is short-lived with more than 90 per cent of women who improved relapsing by 6 to 8 months postpartum. Further, in approximately 30 per cent of RA patients the course remains unchanged or worsens during gestation and indeed the first symptoms of RA may develop during pregnancy or shortly thereafter. Conversely active rheumatoid arthritis seems to little influence the maternal course or fetal outcome of pregnancy. The multiple and complex immunologic alterations of the pregnant state are designed to ensure survival of the fetal allograft in a foreign host. A number of these alterations particularly involving modulation of cell-mediated immunity, immunoglobulin composition, immune complex generation, or the inflammatory response have the potential to interfere with the pathophysiology of RA. In short, although the specific mechanism remains an enigma, the reason for the amelioration of RA during pregnancy is probably an incidental and fortuitous reaction to one or more of these immunomodulatory factors.