Showing papers by "Rambam Health Care Campus published in 2015"

Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation

Abstract: Purpose Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) –associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers. Patients and Methods This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with ≥ three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. Olaparib was administered at 400 mg twice per day. The primary efficacy end point was tumor response rate. Results A total of 298 patients received treatment and were evaluable. The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to...

Internal mammary and medial supraclavicular irradiation in breast cancer

Abstract: BACKGROUND The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown. METHODS We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracic-wall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer. RESULTS Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P = 0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P = 0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P = 0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P = 0.02). Acute side effects of regional nodal irradiation were modest. CONCLUSIONS In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds Cancer; ClinicalTrials.gov number, NCT00002851.)

A prospective randomized evaluation of the TriGuard™ HDH embolic DEFLECTion device during transcatheter aortic valve implantation: results from the DEFLECT III trial

Abstract: Aims To evaluate the safety, efficacy, and performance of the TriGuard™ HDH Embolic Deflection Device (TriGuard) compared with no cerebral protection in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results From February 2014 to March 2015, 85 subjects undergoing TAVI at 13 centres in Europe and Israel were randomized to TriGuard protection vs. no protection. Subjects underwent neurologic and cognitive evaluation at baseline, pre-discharge and 30 days; cerebral diffusion-weighted magnetic resonance imaging was performed at 4 ± 2 days post-procedure and at 30 days. Technical success, which included complete 3-vessel cerebral coverage, was achieved in 88.9% (40/45) of cases. The primary in-hospital procedural safety endpoint (death, stroke, life-threatening or disabling bleeding, stage 2 or 3 acute kidney injury, or major vascular complications) occurred in 21.7% of TriGuard and 30.8% of control subjects ( P = 0.34). In the Per Treatment population (subjects with complete three-vessel cerebral coverage), TriGuard use was associated with greater freedom from new ischaemic brain lesions (26.9 vs. 11.5%), fewer new neurologic deficits detected by the National Institutes of Health Stroke Scale (3.1 vs. 15.4%), improved Montreal Cognitive Assessment (MoCA) scores, better performance on a delayed memory task ( P = 0.028) at discharge, and a >2-fold increase in recovery of normal cognitive function (MoCA score >26) at 30 days. Conclusion TriGuard cerebral protection during TAVI is safe and complete cerebral vessel coverage was achieved in 89% of subjects. In this exploratory study, subjects undergoing protected TAVI had more freedom from ischaemic brain lesions, fewer neurologic deficits, and improved cognitive function in some domains at discharge and 30 days compared with controls.

Role of endogenous pain modulation in chronic pain mechanisms and treatment.

Abstract: Development and application of psychophysical test paradigms to assess endogenous pain modulation in healthy controls and in patients yielded large body of data over the last 2 decades. These tests can assist in predicting pain acquisition, in characterizing pain syndromes and related dysfunctions of pain modulation, and in predicting response to treatment. This chapter reviews the development of thought on pain modulation in the clinical setup, focusing on conditioned pain modulation, and update on accumulated data regarding the mechanism, protocols of administration, and applications in the clinic.

Developmental dysplasia of the hip: What has changed in the last 20 years?

Abstract: Developmental dysplasia of the hip (DDH) describes the spectrum of structural abnormalities that involve the growing hip. Early diagnosis and treatment is critical to provide the best possible functional outcome. Persistence of hip dysplasia into adolescence and adulthood may result in abnormal gait, decreased strength and increased rate of degenerative hip and knee joint disease. Despite efforts to recognize and treat all cases of DDH soon after birth, diagnosis is delayed in some children, and outcomes deteriorate with increasing delay of presentation. Different screening programs for DDH were implicated. The suspicion is raised based on a physical examination soon after birth. Radiography and ultrasonography are used to confirm the diagnosis. The role of other imaging modalities, such as magnetic resonance imaging, is still undetermined; however, extensive research is underway on this subject. Treatment depends on the age of the patient and the reducibility of the hip joint. At an early age and up to 6 mo, the main treatment is an abduction brace like the Pavlik harness. If this fails, closed reduction and spica casting is usually done. After the age of 18 mo, treatment usually consists of open reduction and hip reconstruction surgery. Various treatment protocols have been proposed. We summarize the current practice for detection and treatment of DDH, emphasizing updates in screening and treatment during the last two decades.

The role of the open abdomen procedure in managing severe abdominal sepsis: WSES position paper.

Abstract: The open abdomen (OA) procedure is a significant surgical advance, as part of damage control techniques in severe abdominal trauma. Its application can be adapted to the advantage of patients with severe abdominal sepsis, however its precise role in these patients is still not clear. In severe abdominal sepsis the OA may allow early identification and draining of any residual infection, control any persistent source of infection, and remove more effectively infected or cytokine-loaded peritoneal fluid, preventing abdominal compartment syndrome and deferring definitive intervention and anastomosis until the patient is appropriately resuscitated and hemodynamically stable and thus better able to heal. However, the OA may require multiple returns to the operating room and may be associated with significant complications, including enteroatmospheric fistulas, loss of abdominal wall domain and large hernias. Surgeons should be aware of the pathophysiology of severe intra-abdominal sepsis and always keep in mind the option of using open abdomen to be able to use it in the right patient at the right time.

The phylogenetic and geographic structure of Y-chromosome haplogroup R1a.

Abstract: R1a-M420 is one of the most widely spread Y-chromosome haplogroups; however, its substructure within Europe and Asia has remained poorly characterized. Using a panel of 16 244 male subjects from 126 populations sampled across Eurasia, we identified 2923 R1a-M420 Y-chromosomes and analyzed them to a highly granular phylogeographic resolution. Whole Y-chromosome sequence analysis of eight R1a and five R1b individuals suggests a divergence time of ∼25 000 (95% CI: 21 300–29 000) years ago and a coalescence time within R1a-M417 of ∼5800 (95% CI: 4800–6800) years. The spatial frequency distributions of R1a sub-haplogroups conclusively indicate two major groups, one found primarily in Europe and the other confined to Central and South Asia. Beyond the major European versus Asian dichotomy, we describe several younger sub-haplogroups. Based on spatial distributions and diversity patterns within the R1a-M420 clade, particularly rare basal branches detected primarily within Iran and eastern Turkey, we conclude that the initial episodes of haplogroup R1a diversification likely occurred in the vicinity of present-day Iran.

Heparanase Enhances Tumor Growth and Chemoresistance by Promoting Autophagy

Abstract: Heparanase is the only enzyme in mammals capable of cleaving heparan sulfate, an activity implicated in tumor inflammation, angiogenesis, and metastasis. Heparanase is secreted as a latent enzyme that is internalized and subjected to proteolytic processing and activation in lysosomes. Its role under normal conditions has yet to be understood. Here, we provide evidence that heparanase resides within autophagosomes, where studies in heparanase-deficient or transgenic mice established its contributions to autophagy. The protumorigenic properties of heparanase were found to be mediated, in part, by its proautophagic function, as demonstrated in tumor xenograft models of human cancer and through use of inhibitors of the lysosome (chloroquine) and heparanase (PG545), both alone and in combination. Notably, heparanase-overexpressing cells were more resistant to stress and chemotherapy in a manner associated with increased autophagy, effects that were reversed by chloroquine treatment. Collectively, our results establish a role for heparanase in modulating autophagy in normal and malignant cells, thereby conferring growth advantages under stress as well as resistance to chemotherapy. Cancer Res; 75(18); 3946-57. ©2015 AACR.

The role of the open abdomen procedure in managing severe abdominal sepsis: WSES position paper.

Abstract: The open abdomen (OA) procedure is a significant surgical advance, as part of damage control techniques in severe abdominal trauma. Its application can be adapted to the advantage of patients with severe abdominal sepsis, however its precise role in these patients is still not clear. In severe abdominal sepsis the OA may allow early identification and draining of any residual infection, control any persistent source of infection, and remove more effectively infected or cytokine-loaded peritoneal fluid, preventing abdominal compartment syndrome and deferring definitive intervention and anastomosis until the patient is appropriately resuscitated and hemodynamically stable and thus better able to heal. However, the OA may require multiple returns to the operating room and may be associated with significant complications, including enteroatmospheric fistulas, loss of abdominal wall domain and large hernias. Surgeons should be aware of the pathophysiology of severe intra-abdominal sepsis and always keep in mind the option of using open abdomen to be able to use it in the right patient at the right time.

Monitoring Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes with Genetically Encoded Calcium and Voltage Fluorescent Reporters

Abstract: The advent of the human-induced pluripotent stem cell (hiPSC) technology has transformed biomedical research, providing new tools for human disease modeling, drug development, and regenerative medicine. To fulfill its unique potential in the cardiovascular field, efficient methods should be developed for high-resolution, large-scale, long-term, and serial functional cellular phenotyping of hiPSC-derived cardiomyocytes (hiPSC-CMs). To achieve this goal, we combined the hiPSC technology with genetically encoded voltage (ArcLight) and calcium (GCaMP5G) fluorescent indicators. Expression of ArcLight and GCaMP5G in hiPSC-CMs permitted to reliably follow changes in transmembrane potential and intracellular calcium levels, respectively. This allowed monitoring short- and long-term changes in action-potential and calcium-handling properties and the development of arrhythmias in response to several pharmaceutical agents and in hiPSC-CMs derived from patients with different inherited arrhythmogenic syndromes. Combining genetically encoded fluorescent reporters with hiPSC-CMs may bring a unique value to the study of inherited disorders, developmental biology, and drug development and testing.

Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial.

Abstract: ObjeCtive To show non-inferiority of trimethoprimsulfamethoxazole compared with vancomycin for the treatment of severe infections due to meticillin resistant Staphylococcus aureus (MRSA). Design Parallel, open label, randomised controlled trial. s etting Four acute care hospitals in Israel. PartiC iPants Adults with severe infections caused by MRSA susceptible to trimethoprim-sulfamethoxazole and vancomycin. Patients with left sided endocarditis, meningitis, chronic haemodialysis, and prolonged neutropenia were excluded. interventiOns

Multicenter, randomized, tandem evaluation of EndoRings colonoscopy - Results of the CLEVER study

Abstract: Background and study aims: Adenoma miss rate during colonoscopy has become a widely acknowledged proxy measure for post-colonoscopy colorectal cancer. Among other reasons, this can happen because of inadequate visualization of the proximal aspects of colonic folds and flexures. EndoRings (EndoAid Ltd., Caesarea, Israel) is a silicone-rubber device that is fitted onto the distal end of the colonoscope. Its flexible circular rings engage and mechanically stretch colonic folds during withdrawal. The primary aim of this study was to compare adenoma miss rates between standard colonoscopy and colonoscopy using EndoRings. Methods: In this multicenter, randomized, tandem colonoscopy study, we performed same-day, back-to-back colonoscopies with EndoRings followed by standard colonoscopy, or vice versa. Results: After exclusion of 10 patients for protocol violations, 116 patients (38.8 % female; mean age 58.7) remained for analysis. The adenoma miss rate of EndoRings colonoscopy (7/67; 10.4 %) was significantly lower (P Conclusions: This study demonstrates that colonoscopy with EndoRings has lower adenoma and polyp miss rates than standard colonoscopy, which may improve the efficacy particularly of screening and surveillance colonoscopies. ClinicalTrials.gov NCT01955122.

MRI Guided Focused Ultrasound Thalamotomy for Moderate-to-Severe Tremor in Parkinson's Disease.

Abstract: Background. Thalamotomy is effective in alleviating tremor in Parkinson's disease (PD). Methods. Seven PD patients, mean age 59.4 ± 9.8 years (range, 46-74) with a mean disease duration of 5.4 ± 2.8 years (range, 2-10) suffering from severe refractory tremor, underwent ventral intermediate nucleus thalamotomy using MRI guided focused ultrasound (MRgFUS), an innovative technology that enables noninvasive surgery. Results. Tremor stopped in the contralateral upper extremity in all patients immediately following treatment. Total UPDRS decreased from 37.4 ± 12.2 to 18.8 ± 11.1 (p = 0.007) and PDQ-39 decreased from 42.3 ± 16.4 to 21.6 ± 10.8 (p = 0.008) following MRgFUS. These effects were sustained (mean follow-up 7.3 months). Adverse events during MRgFUS included headache (n = 3), dizziness (n = 2), vertigo (n = 4), and lip paresthesia (n = 1) and following MRgFUS were hypogeusia (n = 1), unsteady feeling when walking (n = 1, resolved), and disturbance when walking tandem (n = 1, resolved). Conclusions. Thalamotomy using MRgFUS is safe and effective in PD patients. Large randomized studies are needed to assess prolonged efficacy and safety.

Undetectable anti‐TNF drug levels in patients with long‐term remission predict successful drug withdrawal

Abstract: Summary Background Low drug levels are associated with emerging loss of response to anti-TNF. However, this may not be the case in patients with long-term remission. Aim To investigate the outcome of anti-TNF discontinuation in patients with long-term remission and incidental undetectable drug levels. Methods A retrospective cohort study examining the duration of relapse-free survival in IBD patients in remission who discontinued infliximab or adalimumab having undetectable drug levels. Results Forty eight patients who discontinued anti-TNF while in remission and had available drug levels were identified in two centres in France and Israel (infliximab-treated 35, adalimumab-13, Crohn's disease 30, ulcerative colitis 18, mean treatment duration of 22.7 ± 12.4 months). Endoscopy/MRE before stopping showed absence of active inflammation in 40/42 (95%) of evaluated patients, while inflammatory biomarkers (CRP and/or Calprotectin) were completely normal in only 31/48 (65%) of patients. During 12 months median follow-up, relapse occurred in 16/20 (80%) of patients who stopped anti-TNF while having measurable drug levels compared with 9/28 (32%) of patients who had undetectable drug levels (OR: 8.4, 95% CI: 2.2–32, P = 0.002). Relapse-free survival after anti-TNF cessation was significantly longer in patients with absent drug compared to those with detectable drug (P < 0.001, log rank test). On multivariate analysis, a patient's decision to stop therapy was weakly associated and abnormal inflammatory biomarkers and detectable drug levels were both strongly and independently associated with a higher risk of relapse after drug discontinuation. Conclusion Incidental finding of undetectable anti-TNF drug levels in patients with stable long-term deep remission may identify a subset of patients whose clinical remission is no longer dependent on anti-TNF treatment.

A proposal for a CT driven classification of left colon acute diverticulitis

Abstract: Computed tomography (CT) imaging is the most appropriate diagnostic tool to confirm suspected left colonic diverticulitis. However, the utility of CT imaging goes beyond accurate diagnosis of diverticulitis; the grade of severity on CT imaging may drive treatment planning of patients presenting with acute diverticulitis. The appropriate management of left colon acute diverticulitis remains still debated because of the vast spectrum of clinical presentations and different approaches to treatment proposed. The authors present a new simple classification system based on both CT scan results driving decisions making management of acute diverticulitis that may be universally accepted for day to day practice.

Functional abnormalities in iPSC-derived cardiomyocytes generated from CPVT1 and CPVT2 patients carrying ryanodine or calsequestrin mutations

Abstract: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia characterized by syncope and sudden death occurring during exercise or acute emotion. CPVT is caused by abnormal intracellular Ca2+ handling resulting from mutations in the RyR2 or CASQ2 genes. Because CASQ2 and RyR2 are involved in different aspects of the excitation-contraction coupling process, we hypothesized that these mutations are associated with different functional and intracellular Ca²+ abnormalities. To test the hypothesis we generated induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CM) from CPVT1 and CPVT2 patients carrying the RyR2R420Q and CASQ2D307H mutations, respectively, and investigated in CPVT1 and CPVT2 iPSC-CM (compared to control): (i) The ultrastructural features; (ii) the effects of isoproterenol, caffeine and ryanodine on the [Ca2+]i transient characteristics. Our major findings were: (i) Ultrastructurally, CASQ2 and RyR2 mutated cardiomyocytes were less developed than control cardiomyocytes. (ii) While in control iPSC-CM isoproterenol caused positive inotropic and lusitropic effects, in the mutated cardiomyocytes isoproterenol was either ineffective, caused arrhythmias, or markedly increased diastolic [Ca2+]i. Importantly, positive inotropic and lusitropic effects were not induced in mutated cardiomyocytes. (iii) The effects of caffeine and ryanodine in mutated cardiomyocytes differed from control cardiomyocytes. Our results show that iPSC-CM are useful for investigating the similarities/differences in the pathophysiological consequences of RyR2 versus CASQ2 mutations underlying CPVT1 and CPVT2 syndromes.

Foregut caustic injuries: results of the world society of emergency surgery consensus conference

Abstract: Lesions of the upper digestive tract due to ingestion of caustic agents still represent a major medical and surgical emergency worldwide. The work-up of these patients is poorly defined and no clear therapeutic guidelines are available. The aim of this study was to provide an evidence-based international consensus on primary and secondary prevention, diagnosis, staging, and treatment of this life-threatening and potentially disabling condition. An extensive literature search was performed by an international panel of experts under the auspices of the World Society of Emergency Surgery (WSES). The level of evidence of the screened publications was graded using the Oxford 2011 criteria. The level of evidence of the literature and the main topics regarding foregut caustic injuries were discussed during a dedicated meeting in Milan, Italy (April 2015), and during the 3rd Annual Congress of the World Society of Emergency Surgery in Jerusalem, Israel (July 2015). One-hundred-forty-seven full papers which addressed the relevant clinical questions of the research were admitted to the consensus conference. There was an unanimous consensus on the fact that the current literature on foregut caustic injuries lacks homogeneous classification systems and prospective methodology. Moreover, the non-standardized definition of technical and clinical success precludes any accurate comparison of therapeutic modalities. Key recommendations and algorithms based on expert opinions, retrospective studies and literature reviews were proposed and approved during the final consensus conference. The clinical practice guidelines resulting from the consensus conference were approved by the WSES council. The recommendations emerging from this consensus conference, although based on a low level of evidence, have important clinical implications. A world registry of foregut caustic injuries could be useful to collect a homogeneous data-base for prospective clinical studies that may help improving the current clinical practice guidelines.

WSES guidelines for management of Clostridium difficile infection in surgical patients

Abstract: In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.

Molecular Characterization of Choroid Plexus Tumors Reveals Novel Clinically Relevant Subgroups

Abstract: Purpose To investigate molecular alterations in choroid plexus tumors (CPT) using a genome-wide high-throughput approach to identify diagnostic and prognostic signatures that will refine tumor stratification and guide therapeutic options. Experimental design One hundred CPTs were obtained from a multi-institutional tissue and clinical database. Copy-number (CN), DNA methylation, and gene expression signatures were assessed for 74, 36, and 40 samples, respectively. Molecular subgroups were correlated with clinical parameters and outcomes. Results Unique molecular signatures distinguished choroid plexus carcinomas (CPC) from choroid plexus papillomas (CPP) and atypical choroid plexus papillomas (aCPP); however, no significantly distinct molecular alterations between CPPs and aCPPs were observed. Allele-specific CN analysis of CPCs revealed two novel subgroups according to DNA content: hypodiploid and hyperdiploid CPCs. Hyperdiploid CPCs exhibited recurrent acquired uniparental disomy events. Somatic mutations in TP53 were observed in 60% of CPCs. Investigating the number of mutated copies of p53 per sample revealed a high-risk group of patients with CPC carrying two copies of mutant p53, who exhibited poor 5-year event-free (EFS) and overall survival (OS) compared with patients with CPC carrying one copy of mutant p53 (OS: 14.3%, 95% confidence interval, 0.71%-46.5% vs. 66.7%, 28.2%-87.8%, respectively, P = 0.04; EFS: 0% vs. 44.4%, 13.6%-71.9%, respectively, P = 0.03). CPPs and aCPPs exhibited favorable survival. Discussion Our data demonstrate that differences in CN, gene expression, and DNA methylation signatures distinguish CPCs from CPPs and aCPPs; however, molecular similarities among the papillomas suggest that these two histologic subgroups are indeed a single molecular entity. A greater number of copies of mutated TP53 were significantly associated to increased tumor aggressiveness and a worse survival outcome in CPCs. Collectively, these findings will facilitate stratified approaches to the clinical management of CPTs.

WSES guidelines for management of Clostridium difficile infection in surgical patients

Abstract: In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.

Delayed contrast extravasation MRI: a new paradigm in neuro-oncology

Abstract: Background Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing tissues. We have applied delayed-contrast MRI for calculating high resolution treatment response assessment maps (TRAMs) clearly differentiating tumor/nontumor tissues in brain tumor patients.

The human microbiome and the great obstetrical syndromes: a new frontier in maternal-fetal medicine.

Abstract: The emergence of the concept of the microbiome, together with the development of molecular-based techniques, particularly polymerase chain reaction (PCR) amplification using the 16S ribosomal RNA (rRNA) gene, has dramatically increased the detection of microorganisms, the number of known species, and the understanding of bacterial communities that are relevant to maternal–fetal medicine in health and disease. Culture-independent methods enable characterization of the microbiomes of the reproductive tract of pregnant and nonpregnant women, and have increased our understanding of the role of the uterine microbiome in adverse obstetric outcomes. While bacterial ascent from the vaginal tract is recognized as the primary cause of intrauterine infection, the microbiomes of the gastrointestinal, oral, and respiratory tracts are shown to be involved by means of hematogenous spread. The transmission of maternal microbiomes to the neonate, by vaginal delivery or cesarean section, is shown to affect health from birth to adulthood.