Showing papers by "Rambam Health Care Campus published in 2014"
Harvard University1, Broad Institute2, University of Tübingen3, Max Planck Society4, University of Mainz5, University of Washington6, University of California, Berkeley7, Massachusetts Institute of Technology8, Stockholm University9, University of Adelaide10, The Heritage Foundation11, National Museum of Natural History12, Sultan Qaboos University13, University of Edinburgh14, University of Costa Rica15, University of Antioquia16, Rambam Health Care Campus17, University of Pécs18, Al Akhawayn University19, Catholic University of the Sacred Heart20, University of Oxford21, Belgorod State University22, University of Toronto23, University of Buenos Aires24, University of Bern25, Russian Academy of Sciences26, Paul Sabatier University27, North-Eastern Federal University28, University of Chicago29, University of Arizona30, Stony Brook University31, University of Bergen32, Illumina33, Sofia Medical University34, Bashkir State University35, University of Cambridge36, Vilnius University37, Estonian Biocentre38, University of Strasbourg39, Amgen40, University College London41, Gladstone Institutes42, University of Tartu43, University of Oulu44, Muhimbili University of Health and Allied Sciences45, University of Palermo46, University of Tarapacá47, University of Chile48, Academy of Sciences of Uzbekistan49, Armenian National Academy of Sciences50, University of North Texas51, University of Santiago de Compostela52, University of Kharkiv53, Higher University of San Andrés54, Novosibirsk State University55, Leidos56, Lebanese American University57, University of Split58, University of Pennsylvania59, Banaras Hindu University60, Centre for Cellular and Molecular Biology61, Estonian Academy of Sciences62, Pompeu Fabra University63, Howard Hughes Medical Institute64
TL;DR: It is shown that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians; and early European farmers, who were mainly of Near Eastern origin but also harboured west Europeanhunter-gatherer related ancestry.
Abstract: We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
1,077 citations
TL;DR: Twelve weeks of treatment with ABT-450/r-ombitasvir and dasabuvir without ribavirin was associated with high rates of sustained virologic response among previously untreated patients with HCV genotype 1 infection.
Abstract: Background The interferon-free regimen of ABT-450 with ritonavir (ABT-450/r), ombitasvir, and dasabuvir with or without ribavirin has shown efficacy in inducing a sustained virologic response in a phase 2 study involving patients with hepatitis C virus (HCV) genotype 1 infection. We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. Methods We randomly assigned 419 patients with HCV genotype 1b infection (PEARL-III study) and 305 patients with genotype 1a infection (PEARL-IV study) to 12 weeks of ABT-450/r–ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight or to matching placebo for ribavirin. The primary efficacy end point was a sustained virologic response (an HCV RNA level of <25 IU per milliliter) 12 weeks after the end of treatment. Results The study regimen resulted in high rates of sustained virologic response among patients with HCV genotype 1b infection (99.5% with ribavirin and 99.0% without ribavirin) and among those with genotype 1a infection (97.0% and 90.2%, respectively). Of patients with genotype 1b infection, 1 had virologic failure, and 2 did not have data available at post-treatment week 12. Among patients with genotype 1a infection, the rate of virologic failure was higher in the ribavirin-free group than in the ribavirin group (7.8% vs. 2.0%). In both studies, decreases in the hemoglobin level were significantly more common in patients receiving ribavirin. Two patients (0.3%) discontinued the study drugs owing to adverse events. The most common adverse events were fatigue, headache, and nausea. Conclusions Twelve weeks of treatment with ABT-450/r–ombitasvir and dasabuvir without ribavirin was associated with high rates of sustained virologic response among previously untreated patients with HCV genotype 1 infection. Rates of virologic failure were higher without ribavirin than with ribavirin among patients with genotype 1a infection but not among those with genotype 1b infection. (Funded by AbbVie; PEARL-III and PEARL-IV ClinicalTrials.gov numbers, NCT01767116 and NCT01833533.)
694 citations
University of Nottingham1, King Saud Medical City2, International Centre for Diarrhoeal Disease Research, Bangladesh3, Government Medical College, Thiruvananthapuram4, Centers for Disease Control and Prevention5, Ljubljana University Medical Centre6, Kantonsspital St. Gallen7, Institut de veille sanitaire8, Children's Hospital at Westmead9, Mexican Social Security Institute10, Medical University of Vienna11, Capital Medical University12, University of Barcelona13, University of Colorado Denver14, State University of West Paraná15, Sheba Medical Center16, University of Manitoba17, Peking University18, National Institutes of Health19, Hospital General Universitario Gregorio Marañón20, Statens Serum Institut21, Imperial College London22, Boston Children's Hospital23, Peking Union Medical College Hospital24, Dhaka Medical College and Hospital25, Universidade Federal de Ciências da Saúde de Porto Alegre26, Gold Coast Hospital27, Tehran University of Medical Sciences28, University of Oxford29, University of Zagreb30, Pamela Youde Nethersole Eastern Hospital31, Stellenbosch University32, Shiraz University of Medical Sciences33, Tan Tock Seng Hospital34, University of Helsinki35, China Medical University (PRC)36, King Hussein Cancer Center37, University of Toronto38, Alfaisal University39, Erciyes University40, Lithuanian University of Health Sciences41, Military Medical Academy42, Haukeland University Hospital43, University of Bergen44, Shahid Beheshti University of Medical Sciences and Health Services45, Johns Hopkins University School of Medicine46, University of Birmingham47, Rambam Health Care Campus48, Vanderbilt University49, Charité50, University of Bristol51, Yüzüncü Yıl University52, Oswaldo Cruz Foundation53, Rzeszów University54, University Hospital of Basel55, Medical University of Warsaw56, University of Alberta57, University of Alberta Hospital58, University of Hong Kong59, National Center for Immunization and Respiratory Diseases60, VU University Medical Center61
TL;DR: There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset, and early treatment versus no treatment was also associated with a reduction in mortality risk.
527 citations
Harvard University1, Broad Institute2, University of Tübingen3, Max Planck Society4, University of Mainz5, University of Washington6, University of California, Berkeley7, Massachusetts Institute of Technology8, Stockholm University9, University of Adelaide10, The Heritage Foundation11, National Museum of Natural History12, University of Edinburgh13, Sultan Qaboos University14, University of Costa Rica15, University of Antioquia16, Rambam Health Care Campus17, University of Pécs18, Al Akhawayn University19, Catholic University of the Sacred Heart20, University of Oxford21, Belgorod State University22, University of Toronto23, University of Buenos Aires24, University of Bern25, Russian Academy of Sciences26, Paul Sabatier University27, North-Eastern Federal University28, University of Chicago29, University of Arizona30, Stony Brook University31, University of Bergen32, Illumina33, Sofia Medical University34, Bashkir State University35, University of Cambridge36, Vilnius University37, Estonian Biocentre38, University of Strasbourg39, Amgen40, University College London41, Gladstone Institutes42, University of Tartu43, University of Oulu44, Muhimbili University of Health and Allied Sciences45, University of Palermo46, University of Chile47, University of Tarapacá48, Academy of Sciences of Uzbekistan49, Armenian National Academy of Sciences50, University of North Texas51, University of Santiago de Compostela52, University of Kharkiv53, Higher University of San Andrés54, Novosibirsk State University55, Leidos56, Lebanese American University57, University of Split58, University of Pennsylvania59, Banaras Hindu University60, Centre for Cellular and Molecular Biology61, Estonian Academy of Sciences62, Pompeu Fabra University63, Howard Hughes Medical Institute64
TL;DR: The authors showed that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunters-gatherer related ancestry.
Abstract: We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
442 citations
TL;DR: Given an event rate of 7.5% as in included trials' control group, prophylaxis for PCP using TMP/SMX is highly effective among non-HIV patients, with a number needed to treat of 15 patients (95% CI 13 to 20).
Abstract: Background
Pneumocystis pneumonia (PCP) is a disease affecting immunocompromised patients. PCP among these patients is associated with significant morbidity and mortality.
Objectives
To assess the effectiveness of PCP prophylaxis among non-HIV immunocompromised patients; and to define the type of immunocompromised patient for whom evidence suggests a benefit for PCP prophylaxis.
Search methods
Electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE and EMBASE (to March 2014), LILACS (to March 2014), relevant conference proceedings; and references of identified trials.
Selection criteria
Randomised controlled trials (RCTs) or quasi-RCTs comparing prophylaxis with an antibiotic effective against PCP versus placebo, no intervention, or antibiotic(s) with no activity against PCP; and trials comparing different antibiotics effective against PCP among immunocompromised non-HIV patients. We only included trials in which Pneumocystis infections were available as an outcome.
Data collection and analysis
Two review authors independently assessed risk of bias in each trial and extracted data from the included trials. We contacted authors of the included trials to obtain missing data. The primary outcome was documented PCP infections. Risk ratios (RR) with 95% confidence intervals (CI) were estimated and pooled using the random-effects model.
Main results
Thirteen trials performed between the years 1974 and 2008 were included, involving 1412 patients. Four trials included 520 children with acute lymphoblastic leukemia and the remaining trials included adults with acute leukemia, solid organ transplantation or autologous bone marrow transplantation. Compared to no treatment or treatment with fluoroquinolones (inactive against Pneumocystis), there was an 85% reduction in the occurrence of PCP in patients receiving prophylaxis with trimethoprim/sulfamethoxazole, RR of 0.15 (95% CI 0.04 to 0.62; 10 trials, 1000 patients). The evidence was graded as moderate due to possible risk of bias. PCP-related mortality was also significantly reduced, RR of 0.17 (95% CI 0.03 to 0.94; nine trials, 886 patients) (low quality of evidence due to possible risk of bias and imprecision), but in trials comparing PCP prophylaxis against placebo or no treatment there was no significant effect on all-cause mortality (low quality of evidence due to imprecision). Occurrence of leukopenia or neutropenia and their duration were not reported consistently. No significant differences in overall adverse events or events requiring discontinuation were seen comparing trimethoprim/sulfamethoxazole to no treatment or placebo (four trials, 470 patients, moderate quality evidence). No differences between once daily versus thrice weekly trimethoprim/sulfamethoxazole were seen (two trials, 207 patients).
Authors' conclusions
Given an event rate of 6.2% in the control groups of the included trials, prophylaxis for PCP using trimethoprim/sulfamethoxazole is highly effective among non-HIV immunocompromised patients, with a number needed to treat to prevent PCP of 19 patients (95% CI 17 to 42). Prophylaxis should be considered for patients with a similar baseline risk of PCP.
367 citations
TL;DR: Superior OS was observed for advanced-disease BRCA-associated PDAC with platinum exposure, observed for patients with stage 3/4 treated with platinum vs those treated with non-platinum chemotherapies.
Abstract: The BRCA1/2 proteins are involved in regulation of cellular proliferation by DNA damage repair via homologous recombination. Therefore, BRCA1/2 mutation carriers with pancreatic cancer may have distinct biologic outcomes. Patients with BRCA1/2-associated pancreatic ductal adenocarcinoma (PDAC) diagnosed between January 1994 and December 2012 were identified from databases at three participating institutions. Clinical data were collected. Disease-free survival and overall survival (OS) were analysed. Overall, 71 patients with PDAC and BRCA1 (n=21), BRCA2 (n=49) or both (n=1) mutations were identified. Mean age at diagnosis was 60.3 years (range 33–83), 81.7% (n=58) had any family history of malignancy; 30% (n=21) underwent primary resection. Out of 71 participants, 12 received experimental therapy; one patient had missing data, these 13 cases were excluded from OS analysis. Median OS for 58 patients was 14 months (95% CI 10–23 months). Median OS for patients with stage 1/2 disease has not been reached with 52% still alive at 60 months. Median OS for stage 3/4 was 12 months (95% CI 6–15). Superior OS was observed for patients with stage 3/4 treated with platinum vs those treated with non-platinum chemotherapies (22 vs 9 months; P=0.039). Superior OS was observed for advanced-disease BRCA-associated PDAC with platinum exposure.
323 citations
University College London1, Rambam Health Care Campus2, University of Oxford3, Hammersmith Hospital4, Mayo Clinic5, Case Western Reserve University6, University of Pennsylvania7, National Health Service8, Nottingham University Hospitals NHS Trust9, Newcastle University10, Yeshiva University11, Memorial Sloan Kettering Cancer Center12
TL;DR: Adding imatinib to standard therapy improves CR rate and long-term OS for adults with ALL and a proportion of the OS benefit derives from the fact that imatinIB facilitates alloHSCT.
299 citations
TL;DR: Serial measurements showed that ATI development often preceded the onset of clinical flare, and survival free of clinical loss of response was enjoyed by 51% of patients, and serial measurements showed this incidence is reduced by concomitant immunomodulator even in scheduled-therapy patients.
Abstract: Objective To characterise the temporal evolution of antibodies to infliximab (ATI). Design Prospective observational study of infliximab-treated patients with inflammatory bowel disease between 2009 and 2012. Interventions Trough levels of infliximab and ATI were measured before each infusion by anti-λ ELISA. Patients were monitored for disease activity by clinical activity indexes and for dose-intensification or infliximab cessation. The occurrence of transient ATI disappearing spontaneously without intervention was recorded separately. Results 125 patients were included (98 Crohn9s disease, 27 ulcerative colitis, median follow-up 11.5±22 months) and 1119 sera were analysed for infliximab and ATI levels. Kaplan-Meier analysis showed that 42% of patients remained ATI-free by 4 years of treatment. Most (90%) of the patients who developed ATI did so within the first 12 months of therapy, whereas transient ATI were detected throughout the duration of infliximab therapy (p Conclusions When followed prospectively, most patients who develop ATI do so within the first 12 months of therapy. This incidence is reduced by concomitant immunomodulator even in scheduled-therapy patients. In contrast, transient ATI, which are of little clinical significance, can appear haphazardly at any time during treatment. The onset of clinical loss of response may lag behind the appearance of anti-infliximab antibodies.
272 citations
Denver Health Medical Center1, American Board of Surgery2, Harvard University3, UC San Diego Health System4, Kyoto University5, University of Newcastle6, Rambam Health Care Campus7, Adria Airways8, Virginia Commonwealth University9, Memorial Hospital of South Bend10, Hadassah Medical Center11, Tianjin Medical University12, University of Health Sciences Antigua13, Sher-I-Kashmir Institute of Medical Sciences14, Ahmadu Bello University15, Mansoura University16, Victoria University, Australia17, University of Nice Sophia Antipolis18, Yonsei University19, University of Ulsan20, Siriraj Hospital21, Thammasat University Hospital22, Tokyo Medical and Dental University23, Nippon Medical School24, Our Lady of Lourdes Hospital25, Obafemi Awolowo University26, Chiba University27, Jichi Medical University28, Mayo Clinic29
TL;DR: The CIAOW study (Complicated intra-abdominal infections worldwide observational study) is a multicenter observational study underwent in 68 medical institutions worldwide during a six-month study period (October 2012-March 2013).
Abstract: The CIAOW study (Complicated intra-abdominal infections worldwide observational study) is a multicenter observational study underwent in 68 medical institutions worldwide during a six-month study period (October 2012-March 2013). The study included patients older than 18 years undergoing surgery or interventional drainage to address complicated intra-abdominal infections (IAIs). 1898 patients with a mean age of 51.6 years (range 18-99) were enrolled in the study. 777 patients (41%) were women and 1,121 (59%) were men. Among these patients, 1,645 (86.7%) were affected by community-acquired IAIs while the remaining 253 (13.3%) suffered from healthcare-associated infections. Intraperitoneal specimens were collected from 1,190 (62.7%) of the enrolled patients. 827 patients (43.6%) were affected by generalized peritonitis while 1071 (56.4%) suffered from localized peritonitis or abscesses. The overall mortality rate was 10.5% (199/1898). According to stepwise multivariate analysis (PR = 0.005 and PE = 0.001), several criteria were found to be independent variables predictive of mortality, including patient age (OR = 1.1; 95%CI = 1.0-1.1; p < 0.0001), the presence of small bowel perforation (OR = 2.8; 95%CI = 1.5-5.3; p < 0.0001), a delayed initial intervention (a delay exceeding 24 hours) (OR = 1.8; 95%CI = 1.5-3.7; p < 0.0001), ICU admission (OR = 5.9; 95%CI = 3.6-9.5; p < 0.0001) and patient immunosuppression (OR = 3.8; 95%CI = 2.1-6.7; p < 0.0001).
216 citations
TL;DR: An international, multicentre, randomised trial to compare the adenoma miss rates of full-spectrum endoscopy colonoscopy with those of standard forward-viewing Colonoscopy.
Abstract: Summary Background Although colonoscopy is the accepted standard for detection of colorectal adenomas and cancers, many adenomas and some cancers are missed. To avoid interval colorectal cancer, the adenoma miss rate of colonoscopy needs to be reduced by improvement of colonoscopy technique and imaging capability. We aimed to compare the adenoma miss rates of full-spectrum endoscopy colonoscopy with those of standard forward-viewing colonoscopy. Methods We did an international, multicentre, randomised trial at three sites in Israel, one site in the Netherlands, and two sites in the USA between Feb 1, 2012, and March 31, 2013. Patients aged 18–70 years referred for colorectal cancer screening, polyp surveillance, or diagnostic assessment underwent same-day, back-to-back tandem colonoscopy with standard forward-viewing colonoscope and the full-spectrum endoscopy colonoscope. The patients were randomly assigned (1:1), via computer-generated randomisation with block size of 20, to which procedure was done first. The endoscopist was masked to group allocation until immediately before the start of colonoscopy examinations; patients were not masked. The primary endpoint was adenoma miss rates. We did per-protocol analyses. This trial is registered with ClinicalTrials.gov, number NCT01549535. Findings 197 participants were enrolled. 185 participants were included in the per-protocol analyses: 88 (48%) were randomly assigned to receive standard forward-viewing colonoscopy first, and 97 (52%) to receive full-spectrum endoscopy colonoscopy first. By per-lesion analysis, the adenoma miss rate was significantly lower in patients in the full-spectrum endoscopy group than in those in the standard forward-viewing procedure group: five (7%) of 67 vs 20 (41%) of 49 adenomas were missed (p Interpretation Full-spectrum endoscopy represents a technology advancement for colonoscopy and could improve the efficacy of colorectal cancer screening and surveillance. Funding EndoChoice.
215 citations
TL;DR: This multicenter phase III trial demonstrated that MRgFUS is a safe and effective, noninvasive treatment for alleviating pain resulting from bone metastases in patients that have failed standard treatments.
Abstract: Bone metastases are common in patients with advanced cancer and are the greatest contributor to cancer-related pain, often severely affecting quality of life (1,2). Many patients with advanced cancer are undertreated for pain (3,4). Radiation therapy (RT), together with systemic therapies and analgesics, is the standard of care for localized metastatic bone pain, although up to two-thirds of patients have residual pain after RT (5,6), leaving them with limited treatment options. These include reirradiation, which results in temporary pain reduction in some patients (7), surgical intervention (8), and percutaneous cryoablation (9). More effective systemic therapies are prolonging survival of cancer patients with metastatic disease, resulting in an increased need for alternative therapies for painful bone metastases.
Focused ultrasound is a noninvasive technique that delivers acoustic energy to heat lesions focally to ablative temperatures of more than 65°C. The combination of focused ultrasound with magnetic resonance (MR) imaging enables physicians to perform precise localized tumor tissue ablation, while using MR thermometry for real-time temperature monitoring (10,11). Preliminary clinical studies on the use of MR-guided focused ultrasound surgery (MRgFUS) for palliation of painful bone metastases demonstrated excellent response rates and safety (12–14).
We report here results of a randomized controlled trial to evaluate safety and efficacy of MRgFUS for treating bone metastases in patients with persistent or recurrent pain after RT, or who were otherwise not candidates for RT, or who declined RT. The primary objective was to evaluate pain reduction after MRgFUS. The secondary objectives of the study included assessment of the treatment’s impact on pain-related interference with patient functioning and treatment-related toxicity.
TL;DR: The results suggest a novel model in which stress may alter hippocampal function by promoting oligodendrogenesis, thereby altering the cellular composition and white matter structure.
Abstract: Stress can exert long-lasting changes on the brain that contribute to vulnerability to mental illness, yet mechanisms underlying this long-term vulnerability are not well understood. We hypothesized that stress may alter the production of oligodendrocytes in the adult brain, providing a cellular and structural basis for stress-related disorders. We found that immobilization stress decreased neurogenesis and increased oligodendrogenesis in the dentate gyrus (DG) of the adult rat hippocampus and that injections of the rat glucocorticoid stress hormone corticosterone (cort) were sufficient to replicate this effect. The DG contains a unique population of multipotent neural stem cells (NSCs) that give rise to adult newborn neurons, but oligodendrogenic potential has not been demonstrated in vivo. We used a nestin-CreER/YFP transgenic mouse line for lineage tracing and found that cort induces oligodendrogenesis from nestin-expressing NSCs in vivo. Using hippocampal NSCs cultured in vitro, we further showed that exposure to cort induced a pro-oligodendrogenic transcriptional program and resulted in an increase in oligodendrogenesis and decrease in neurogenesis, which was prevented by genetic blockade of glucocorticoid receptor (GR). Together, these results suggest a novel model in which stress may alter hippocampal function by promoting oligodendrogenesis, thereby altering the cellular composition and white matter structure.
TL;DR: Adalimumab is an effective treatment for Crohn's disease and anti‐adalimumab antibodies (AAA) and low trough serum drug concentrations have been implicated as pre‐disposing factors for treatment failure.
Abstract: SummaryBackground
Adalimumab is an effective treatment for Crohn's disease (CD). Anti-adalimumab antibodies (AAA) and low trough serum drug concentrations have been implicated as pre-disposing factors for treatment failure.
Aims
To assess adalimumab and AAA serum levels, and to examine their association and discriminatory ability with clinical response and serum C-reactive protein (CRP).
Methods
We performed a cross-sectional study using trough sera from adalimumab-treated CD patients. Demographical data, Montreal classification, treatment regimen and clinical status were recorded. Serum adalimumab, AAA and CRP were measured. Receiver operating characteristic analysis and a multivariate regression model were performed to find drug and antibody thresholds for predicting disease activity at time of serum sampling.
Results
One hundred and eighteen trough serum samples were included from 71 patients. High adalimumab trough serum concentration was associated with disease remission (Area Under Curve 0.748, P < 0.001). A cut-off drug level of 5.85 μg/mL yielded optimal sensitivity, specificity and positive likelihood ratio for remission prediction (68%, 70.6% and 2.3, respectively). AAA were inversely related with adalimumab drug levels (Spearman's r = −0.411, P < 0.001) and when subdivided into categorical values, positively related with disease activity (P < 0.001). High drug levels and stricturing vs. penetrating or inflammatory phenotype, but not AAA levels, independently predicted disease remission in a multivariate logistic regression model.
Conclusions
Adalimumab drug levels were inversely related to disease activity. High levels of anti-adalimumab antibodies were positively associated with disease activity, but this association was mediated mostly by adalimumab drug levels.
Book•
United Arab Emirates University1, The Queen's Medical Center2, Ghent University Hospital3, State University of Campinas4, University of Bologna5, Queen Elizabeth Hospital Birmingham6, Tel Aviv University7, Foothills Medical Centre8, Rambam Health Care Campus9, University of Washington10, Vanderbilt University Medical Center11, American Board of Surgery12, St James's University Hospital13, Washington University in St. Louis14, University of Paris15, University of Pittsburgh16, The Catholic University of America17, Stavanger University Hospital18, Université libre de Bruxelles19, University of Colorado Denver20
TL;DR: This paper reports on the consensus conference on the management of intra-abdominal infections which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery meeting.
Abstract: This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.
Harvard University1, Broad Institute2, University of Tübingen3, Max Planck Society4, University of Mainz5, University of Washington6, University of California, Berkeley7, Massachusetts Institute of Technology8, Stockholm University9, University of Adelaide10, The Heritage Foundation11, National Museum of Natural History12, American Museum of Natural History13, University of Edinburgh14, National Scientific and Technical Research Council15, University of Costa Rica16, University of Antioquia17, Rambam Health Care Campus18, University of Pécs19, Al Akhawayn University20, Catholic University of the Sacred Heart21, University of Oxford22, Belgorod State University23, University of Toronto24, University of Buenos Aires25, Russian Academy26, University of Bern27, Paul Sabatier University28, North-Eastern Federal University29, University of Chicago30, Russian Academy of Sciences31, University of Arizona32, Stony Brook University33, University of Bergen34, Illumina35, Sofia Medical University36, University of Illinois at Chicago37, University of Cambridge38, Vilnius University39, Estonian Biocentre40, University of Strasbourg41, Amgen42, Gladstone Institutes43, University of Tartu44, University of Oulu45, Muhimbili University of Health and Allied Sciences46, University of Palermo47, University of Tarapacá48, Academy of Sciences of Uzbekistan49, University of Helsinki50, University of Santiago de Compostela51, University of Kharkiv52, Higher University of San Andrés53, Leidos54, Armenian National Academy of Sciences55, Lebanese American University56, University of Split57, University College London58, University of Pennsylvania59, Centre for Cellular and Molecular Biology60, Pompeu Fabra University61
TL;DR: It is shown that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to Near Easterners; Ancient North Eurasians (ANE); and Early European Farmers (EEF), who were mainly of Near Eastern origin but also harbored WHG-related ancestry.
Abstract: We sequenced genomes from a ~7,000 year old early farmer from Stuttgart in Germany, an ~8,000 year old hunter-gatherer from Luxembourg, and seven ~8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to Near Easterners; Ancient North Eurasians (ANE), who were most closely related to Upper Paleolithic Siberians and contributed to both Europeans and Near Easterners; and Early European Farmers (EEF), who were mainly of Near Eastern origin but also harbored WHG-related ancestry. We model these populations' deep relationships and show that EEF had ~44% ancestry from a "Basal Eurasian" lineage that split prior to the diversification of all other non-African lineages.
TL;DR: Transplant-related mortality has decreased due to improved supportive care, including better strategies to prevent severe infections and with the incorporation of reduced-intensity conditioning protocols that lowered the toxicity and allowed for transplantation in older patients, however, disease relapse and graft-versus-host disease remain the two major causes of mortality with unsatisfactory progress.
Abstract: Hematopoietic stem cell transplantation is a highly specialized and unique medical procedure. Autologous transplantation allows the administration of high-dose chemotherapy without prolonged bone marrow aplasia. In allogeneic transplantation, donor-derived stem cells provide alloimmunity that enables a graft-versus-tumor effect to eradicate residual disease and prevent relapse. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then the field has evolved and expanded worldwide. New indications beside acute leukemia and aplastic anemia have been constantly explored and now include congenital disorders of the hematopoietic system, metabolic disorders, and autoimmune disease. The use of matched unrelated donors, umbilical cord blood units, and partially matched related donors has dramatically extended the availability of allogeneic transplantation. Transplant-related mortality has decreased due to improved supportive care, including better strategies to prevent severe infections and with the incorporation of reduced-intensity conditioning protocols that lowered the toxicity and allowed for transplantation in older patients. However, disease relapse and graft-versus-host disease remain the two major causes of mortality with unsatisfactory progress. Intense research aiming to improve adoptive immunotherapy and increase graft-versus-leukemia response while decreasing graft-versus-host response might bring the next breakthrough in allogeneic transplantation. Strategies of graft manipulation, tumor-associated antigen vaccinations, monoclonal antibodies, and adoptive cellular immunotherapy have already proved clinically efficient. In the following years, allogeneic transplantation is likely to become more complex, more individualized, and more efficient.
TL;DR: The present review focuses on the expression and function of insulin, IGFs and their receptors in the brain in physiological and pathological conditions.
TL;DR: It is suggested that the nonsense mutation identified accounts for the POI phenotype, highlighting the importance of the synaptonemal complex and meiosis in ovarian function.
Abstract: Context: Primary ovarian insufficiency (POI) is caused by ovarian follicle depletion or follicle dysfunction. The phenotypic spectrum ranges from absence of pubertal maturation to early menopause. Genes involved in essential steps in chromosome synapsis and recombination during meiosis, such as synaptonemal complex central element 1 (SYCE1), have been shown to cause POI in animal models. We describe for the first time a homozygous mutation in SYCE1 in humans. Objective: To identify the genetic cause of POI in an Israeli Arab family with a consanguineous pedigree. Setting and Design: A family-based genetic study conducted at a tertiary medical center. Patients: Two daughters of consanguineous parents (first cousins) from a 13-member family were diagnosed with POI. Genotyping was performed in the index patients, their parents, and four unaffected siblings. Intervention: DNA from the affected sisters was subjected to whole-exome sequencing. The genotypes of interest were confirmed and genotypes of the additi...
TL;DR: The described engineered muscle flap, equipped with an autologous vascular pedicle, constitutes an effective tool for reconstruction of large defects, thereby circumventing the need for both harvesting autologously flaps and postoperative scarification.
Abstract: Large soft tissue defects involve significant tissue loss, requiring surgical reconstruction. Autologous flaps are occasionally scant, demand prolonged transfer surgery, and induce donor site morbidity. The present work set out to fabricate an engineered muscle flap bearing its own functional vascular pedicle for repair of a large soft tissue defect in mice. Full-thickness abdominal wall defect was reconstructed using this engineered vascular muscle flap. A 3D engineered tissue constructed of a porous, biodegradable polymer scaffold embedded with endothelial cells, fibroblasts, and/or myoblasts was cultured in vitro and then implanted around the femoral artery and veins before being transferred, as an axial flap, with its vascular pedicle to reconstruct a full-thickness abdominal wall defect in the same mouse. Within 1 wk of implantation, scaffolds showed extensive functional vascular density and perfusion and anastomosis with host vessels. At 1 wk posttransfer, the engineered muscle flaps were highly vascularized, were well-integrated within the surrounding tissue, and featured sufficient mechanical strength to support the abdominal viscera. Thus, the described engineered muscle flap, equipped with an autologous vascular pedicle, constitutes an effective tool for reconstruction of large defects, thereby circumventing the need for both harvesting autologous flaps and postoperative scarification.
University of Minnesota1, Bristol Royal Hospital for Children2, Medical College of Wisconsin3, Case Western Reserve University4, Alfaisal University5, Emory University6, University of Chicago7, University of Hamburg8, Joseph Fourier University9, Harvard University10, Carolinas Healthcare System11, Imperial College London12, Vanderbilt University13, Princess Margaret Cancer Centre14, Johns Hopkins University15, University of Texas MD Anderson Cancer Center16, Royal Adelaide Hospital17, Alberta Children's Hospital18, University of Rochester19, Mayo Clinic20, University of Pennsylvania21, Baylor University Medical Center22, University of Florida23, University of South Florida24, Rambam Health Care Campus25, Washington University in St. Louis26, Yeshiva University27
TL;DR: RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRDneg status is preferred pre-HCT.
Abstract: The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (P=0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P=0.057), but absence of pre-HCT TKI (HR 1.88; P=0.018), RIC (HR 1.891; P=0.054) and pre-HCT MRD(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.
University of Sydney1, Children's Hospital at Westmead2, Harvard University3, Boston Children's Hospital4, University of Calgary5, University Hospital Bonn6, University of Patras7, George Washington University8, University of Pennsylvania9, Children's Hospital of Philadelphia10, Rambam Health Care Campus11, Yale University12, Indiana University13, Karolinska Institutet14
TL;DR: In this article, a review of clinical and laboratory records of 133 individuals from 27 kindreds, including 5 previously unreported HHRH kindreds and two cases with IH, in which known and novel SLC34A3 mutations (c.1357delTTC [p.F453del]; c.G1369A [p] and c.367delC] were identified.
Abstract: Compound heterozygous and homozygous (comp/hom) mutations in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium (Na(+))-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate wasting resulting in hypophosphatemia, correspondingly elevated 1,25(OH)2 vitamin D levels, hypercalciuria, and rickets/osteomalacia. Similar, albeit less severe, biochemical changes are observed in heterozygous (het) carriers and indistinguishable from those changes encountered in idiopathic hypercalciuria (IH). Here, we report a review of clinical and laboratory records of 133 individuals from 27 kindreds, including 5 previously unreported HHRH kindreds and two cases with IH, in which known and novel SLC34A3 mutations (c.1357delTTC [p.F453del]; c.G1369A [p.G457S]; c.367delC) were identified. Individuals with mutations affecting both SLC34A3 alleles had a significantly increased risk of kidney stone formation or medullary nephrocalcinosis, namely 46% compared with 6% observed in healthy family members carrying only the wild-type SLC34A3 allele (P=0.005) or 5.64% in the general population (P<0.001). Renal calcifications were also more frequent in het carriers (16%; P=0.003 compared with the general population) and were more likely to occur in comp/hom and het individuals with decreased serum phosphate (odds ratio [OR], 0.75, 95% confidence interval [95% CI], 0.59 to 0.96; P=0.02), decreased tubular reabsorption of phosphate (OR, 0.41; 95% CI, 0.23 to 0.72; P=0.002), and increased serum 1,25(OH)2 vitamin D (OR, 1.22; 95% CI, 1.05 to 1.41; P=0.008). Additional studies are needed to determine whether these biochemical parameters are independent of genotype and can guide therapy to prevent nephrocalcinosis, nephrolithiasis, and potentially, CKD.
TL;DR: With knowledge of the presence, patterns, and persistence of 18F-FDG uptake in noninfected vascular prostheses, misinterpretation of PET/CT studies in patients referred for suspected prosthetic infection and in those assessed for diseases unrelated to their graft status can be avoided.
Abstract: 18F-FDG PET/CT is of value in the diagnosis of prosthetic vascular graft infection, but potential pitfalls related to tracer uptake in noninfected implants have been described. The current study assesses the incidence and patterns of 18F-FDG uptake over time in noninfected grafts, in relationship to prosthetic material and location. Methods: A 12-y PET/CT database was retrospectively searched for cancer patients with prosthetic vascular grafts. Data retrieved from patient files included graft location, material, and time from surgery. Images were reviewed by 2 nuclear medicine physicians in consensus, with the presence and patterns (focal, diffuse homogeneous, inhomogeneous) of increased 18F-FDG uptake in grafts recorded. The mean standardized uptake value in grafts (SUV-G) and mediastinum (SUV-M) was measured. The ratio of SUV-G to SUV-M (SUV-G/SUV-M) was calculated for each graft. Results: One hundred seven prostheses were identified in 102 studies in 43 cancer patients. Sixty-seven prostheses were made of Dacron, 33 of Gore-Tex, and 7 were native veins. No increased 18F-FDG uptake was found in 9 grafts (native veins, 4; Gore-Tex, 3; Dacron, 2). There was diffuse homogeneous uptake in 68 and inhomogeneous uptake in 30 grafts. The homogeneous pattern was more prevalent in Gore-Tex whereas the inhomogeneous uptake was seen more in Dacron vascular grafts. None of the grafts demonstrated focal uptake. The SUV-G range was 0.4–6.3 (average, 1.9), and SUV-M range was 0.6–2.4 (average, 1.4). The intensity of uptake was significantly higher in Dacron (SUV-G = 2.35 and SUV-G/SUV-M = 1.72) than in Gore-Tex (SUV-G = 1.09, SUV-G/SUV-M = 0.91) and native vein grafts (SUV-G = 1.07, SUV-G/SUV-M = 0.75) (P
TL;DR: Structural variations occurred in areas associated with the default mode network, attentional direction and shifting, as well as somatosensory processing, which underscore the potential importance of processes related to default mode thought and attention in shaping individual differences in pain sensitivity.
Abstract: Pain is a highly personal experience that varies substantially among individuals In search of an anatomical correlate of pain sensitivity, we used voxel-based morphometry to investigate the relationship between grey matter density across the whole brain and interindividual differences in pain sensitivity in 116 healthy volunteers (62 women, 54 men) Structural magnetic resonance imaging (MRI) and psychophysical data from 10 previous functional MRI studies were used Age, sex, unpleasantness ratings, scanner sequence, and sensory testing location were added to the model as covariates Regression analysis of grey matter density across the whole brain and thermal pain intensity ratings at 49 °C revealed a significant inverse relationship between pain sensitivity and grey matter density in bilateral regions of the posterior cingulate cortex, precuneus, intraparietal sulcus, and inferior parietal lobule Unilateral regions of the left primary somatosensory cortex also exhibited this inverse relationship No regions showed a positive relationship to pain sensitivity These structural variations occurred in areas associated with the default mode network, attentional direction and shifting, as well as somatosensory processing These findings underscore the potential importance of processes related to default mode thought and attention in shaping individual differences in pain sensitivity and indicate that pain sensitivity can potentially be predicted on the basis of brain structure
American Board of Surgery1, Vanderbilt University Medical Center2, University of Texas at Austin3, Denver Health Medical Center4, University of Florida5, University of Pittsburgh6, UC San Diego Health System7, Rambam Health Care Campus8, Kyoto University9, University of Valle10, University of Santiago de Compostela11, State University of Campinas12, Sher-I-Kashmir Institute of Medical Sciences13, University of Health Sciences Antigua14, Hebrew University of Jerusalem15, Mansoura University16, Hamad Medical Corporation17, Universidade Federal de Juiz de Fora18, Tianjin Medical University19, Universidad Nacional de Asunción20, University of Ulsan21, Memorial Hospital of South Bend22
TL;DR: A worldwide international panel of experts developed evidence-based guidelines for management of soft tissue infections, which led to a collaboration among surgeons, intensive care and infectious diseases specialists, who have shared these guidelines, implementing clinical practice recommendations.
Abstract: Skin and soft tissue infections (SSTIs) encompass a variety of pathological conditions ranging from simple superficial infections to severe necrotizing soft tissue infections. Necrotizing soft tissue infections (NSTIs) are potentially life-threatening infections of any layer of the soft tissue compartment associated with widespread necrosis and systemic toxicity. Successful management of NSTIs involves prompt recognition, timely surgical debridement or drainage, resuscitation and appropriate antibiotic therapy. A worldwide international panel of experts developed evidence-based guidelines for management of soft tissue infections. The multifaceted nature of these infections has led to a collaboration among surgeons, intensive care and infectious diseases specialists, who have shared these guidelines, implementing clinical practice recommendations.
TL;DR: Serum levels of certain cytokines, measured immediately after initial injury, can be used as potential biomarkers for predicting the development and the degree of severity of the systemic inflammatory response (SIRS) in patients with moderate and severe trauma, found to be reliable markers for the existence of immune reactivity in trauma patients.
Abstract: Purpose
Much research is now being conducted in order to understand the role of cytokines in the development of the inflammatory response following trauma. The purpose of this study was to evaluate whether serum levels of certain cytokines, measured immediately after initial injury, can be used as potential biomarkers for predicting the development and the degree of severity of the systemic inflammatory response (SIRS) in patients with moderate and severe trauma.
Sichuan University1, University of New Mexico2, University of Florida3, New York University4, Ohio State University5, University of Alabama at Birmingham6, University of Utah7, Mayo Clinic8, University of Chicago9, University of Texas MD Anderson Cancer Center10, Yeshiva University11, Rambam Health Care Campus12, University of Pennsylvania13, Memorial Sloan Kettering Cancer Center14, National Institutes of Health15, University of California, San Francisco16, Pennsylvania State University17, University of Colorado Denver18
TL;DR: The results from this first genome-wide association study of AYA ALL susceptibility point to unique biology underlying leukemogenesis and potentially distinct disease etiology by age group.
Icahn School of Medicine at Mount Sinai1, New York University2, University of Manchester3, University of Maryland, Baltimore4, Aarhus University5, French Institute of Health and Medical Research6, University of Cambridge7, Cambridge University Hospitals NHS Foundation Trust8, Dresden University of Technology9, German Cancer Research Center10, National Taiwan University11, Maastricht University12, Ghent University13, Katholieke Universiteit Leuven14, Rambam Health Care Campus15, Institute of Cancer Research16, University of Santiago de Compostela17, Autonomous University of Barcelona18, National Institute of Radiological Sciences19, University of Leicester20, University of Texas MD Anderson Cancer Center21, University of Chicago22, Yeshiva University23, University of Alberta24, University of Pennsylvania25, University of California, San Francisco26, Université de Montréal27, University of Arizona28
TL;DR: This work has shown promise in predicting response of esophageal cancer patients to chemoradiation therapy and in doing so has potential to improve the quality of life for patients and their doctors.
Abstract: Reprint requests to: Barry S. Rosenstein,PhD, Department of RadiationOncology, Icahn School of Medicine at Mount Sinai, One Gustave L. LevyPlace, Box 1236, New York, NY 10029. Tel: (212) 824-8960; E-mail:barry.rosenstein@mssm.eduSupported by grants from the National Institutes of Health and theDepartment of Defense (1R01CA134444 and PC074201 to B.S.R. andH.O.), the American Cancer Society (RSGT-05-200-01-CCE to B.S.R.),the Instituto de Salud Carlos III (FIS PI10/00164 and PI13/02030 to A.V.),Fondo Europeo de Desarrollo Regional (FEDER 2007e2013) in Spain, aMiguel Servet contract from the Spanish Carlos III Health Institute (CP10/00617 to S.G.-E.), and in the UK by Cancer Research UK.Conflict of interest: E.Y. Chuang holds a patent on biomarkers forpredicting response of esophageal cancer patients to chemoradiationtherapy. The authors report no other conflict of interest.Int J Radiation Oncol Biol Phys, Vol. 89, No. 4, pp. 709e713, 20140360-3016/$ - see front matter 2014 Elsevier Inc. All rights reserved.http://dx.doi.org/10.1016/j.ijrobp.2014.03.009
TL;DR: Conjoined analysis confirmed that dissociable mechanisms support inhibitory processes engaged during spatial vs temporal filtering of nociceptive information, and suggested that CPM‐related activity did not overlap with that of OA.
Abstract: The role of endogenous analgesic mechanisms has largely been viewed in the context of gain modulation during nociceptive processing. However, these analgesic mechanisms may play critical roles in the extraction and subsequent utilization of information related to spatial and temporal features of nociceptive input. To date, it remains unknown if spatial and temporal filtering of nociceptive information is supported by similar analgesic mechanisms. To address this question, human volunteers were recruited to assess brain activation with functional magnetic resonance imaging during conditioned pain modulation (CPM) and offset analgesia (OA). CPM provides one paradigm for assessing spatial filtering of nociceptive information while OA provides a paradigm for assessing temporal filtering of nociceptive information. CPM and OA both produced statistically significant reductions in pain intensity. However, the magnitude of pain reduction elicited by CPM was not correlated with that elicited by OA across different individuals. Different patterns of brain activation were consistent with the psychophysical findings. CPM elicited widespread reductions in regions engaged in nociceptive processing such as the thalamus, insula, and secondary somatosensory cortex. OA produced reduced activity in the primary somatosensory cortex but was associated with greater activation in the anterior insula, dorsolateral prefrontal cortex, intraparietal sulcus, and inferior parietal lobule relative to CPM. In the brain stem, CPM consistently produced reductions in activity, while OA produced increases in activity. Conjunction analysis confirmed that CPM-related activity did not overlap with that of OA. Thus, dissociable mechanisms support inhibitory processes engaged during spatial vs temporal filtering of nociceptive information.
TL;DR: This work reviews the evidence supporting second hits or modifying factors that affect risk for apolipoprotein L1 gene-associated nephropathy and produce the protean manifestations of this common and complex syndrome.
Abstract: Molecular genetics have revolutionized the understanding of susceptibility to the broad spectrum of kidney diseases with light microscopic appearance of FSGS, particularly in populations with recent African ancestry. These disorders include idiopathic FSGS, HIV-associated nephropathy, severe lupus nephritis, sickle cell nephropathy, and the primary kidney disorder focal global glomerulosclerosis, which had historically been ascribed to systemic hypertension. FSGS was once thought to include a multitude of unrelated disorders with similar histologic appearance. However, variation in the apolipoprotein L1 gene locus is now known to account for the vast majority of such cases in African Americans as well as nearly all the excess risk for FSGS and related forms of progressive nondiabetic nephropathy in populations with recent African ancestry, relative to European ancestry. Inheriting two coding apolipoprotein L1 gene nephropathy risk variants is necessary for susceptibility to CKD; however, these variants alone are insufficient to produce disease. This work reviews the evidence supporting second hits or modifying factors that affect risk for apolipoprotein L1 gene-associated nephropathy and produce the protean manifestations of this common and complex syndrome. Targeting modifiable second factors will lead to preventive therapies for slowing progression of nondiabetic nephropathy in many patients possessing two apolipoprotein L1 gene risk variants. This model of genetic risk coupled with modifiable second hits will serve as a paradigm applicable to patients with CKD of various etiologies as well as a host of other complex disorders.
TL;DR: Although it may be a valuable option for a patient with a completely edentulous ridge(s), the strategic removal of teeth with satisfactory prognosis for the sake of delivering an implant supported full-arch dental hybrid prosthesis should be avoided.