NobleBlocks

Memorial Hospital of South Bend

Hospital / health systemSouth Bend, Indiana, United States

Research output, citation impact, and the most-cited recent papers from Memorial Hospital of South Bend (United States). Aggregated across the NobleBlocks index of 300M+ scholarly works.

Total works
10.0K
Citations
587.7K
h-index
238
i10-index
10.4K
Also known as
Memorial Hospital of South Bend

Top-cited papers from Memorial Hospital of South Bend

Lamivudine for Patients with Chronic Hepatitis B and Advanced Liver Disease
Yun‐Fan Liaw, Joseph J.�Y. Sung, Wan Cheng Chow, Geoffrey C. Farrell +4 more
2004· New England Journal of Medicine2.3Kdoi:10.1056/nejmoa033364

BACKGROUND: The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown. METHODS: Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were randomly assigned in a 2:1 ratio to receive lamivudine (100 mg per day) or placebo for a maximum of five years. Of 651 patients, 436 were assigned to receive lamivudine and 215 to receive placebo. The primary end point was time to disease progression, defined by hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal varices, or death related to liver disease. An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data. RESULTS: We randomly assigned 651 patients (98 percent Asian and 85 percent male) to receive lamivudine or placebo. The study was terminated after a median duration of treatment of 32.4 months (range, 0 to 42) owing to a significant difference between treatment groups in the number of end points reached. End points were reached by 7.8 percent of the patients receiving lamivudine and 17.7 percent of those receiving placebo (hazard ratio for disease progression, 0.45; P=0.001). The Child-Pugh score increased in 3.4 percent of the patients receiving lamivudine and 8.8 percent of those receiving placebo (hazard ratio, 0.45; P=0.02), whereas hepatocellular carcinoma occurred in 3.9 percent of those in the lamivudine group and 7.4 percent of those in the placebo group (hazard ratio, 0.49; P=0.047). Genotypic resistance YMDD mutations developed in 49 percent of the patients treated with lamivudine, and the Child-Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine (7 percent vs. <1 percent). Overall, 12 percent of the patients in the lamivudine group and 18 percent of the patients in the placebo group reported serious adverse events. CONCLUSIONS: Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma.

2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infectionsa
Benjamin A. Lipsky, Anthony R. Berendt, Paul B. Cornia, James C. Pile +4 more
2012· Clinical Infectious Diseases1.7Kdoi:10.1093/cid/cis346

Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.

Have We Found an Ideal Soft-Tissue Flap? An Experience with 672 Anterolateral Thigh Flaps
Fu‐Chan Wei, Vivek Jain, Naci Çelik, Hung‐Chi Chen +2 more
2002· Plastic & Reconstructive Surgery1.2Kdoi:10.1097/00006534-200206000-00007

The free anterolateral thigh flap is becoming one of the most preferred options for soft-tissue reconstruction. Between June of 1996 and August of 2000, 672 anterolateral thigh flaps were used in 660 patients at Chang Gung Memorial Hospital. Four hundred eighty-four anterolateral thigh flaps were used for head and neck region recontruction in 475 patients, 58 flaps were used for upper extremity reconstruction in 58 patients, 121 flaps were used for lower extremity reconstruction in 119 patients, and nine flaps were used for trunk reconstruction in nine patients. Of the 672 flaps used in total, a majority (439) were musculocutaneous perforator flaps. Sixty-five were septocutaneous vessel flaps. Of these 504 flaps, 350 were fasciocutaneous and 154 were cutaneous flaps. Of the remaining 168 flaps, 95 were musculocutaneous flaps, 63 were chimeric flaps, and the remaining ten were composite musculocutaneous perforator flaps with the tensor fasciae latae. Total flap failure occurred in 12 patients (1.79 percent of the flaps) and partial failure occurred in 17 patients (2.53 percent of the flaps). Of the 12 flaps that failed completely, five were reconstructed with second anterolateral thigh flaps, four with pedicled flaps, one with a free radial forearm flap, one with skin grafting, and one with primary closure. Of the 17 flaps that failed partially, three were reconstructed with anterolateral thigh flaps, one with a free radial forearm flap, five with pedicled flaps, and eight with primary suture, skin grafting, and conservative methods. In this large series, a consistent anatomy of the main pedicle of the anterolateral thigh flap was observed. In cutaneous and fasciocutaneous flaps, the skin vessels (musculocutaneous perforators or septocutaneous vessels) were found and followed until they reached the main pedicle, regardless of the anatomic position. There were only six cases in this series in which no skin vessels were identified during the harvesting of cutaneous or fasciocutaneous anterolateral thigh flaps. In 87.1 percent of the cutaneous or fasciocutaneous flaps, the skin vessels were found to be musculocutaneous perforators; in 12.9 percent, they were found as septocutaneous vessels. The anterolateral thigh flap is a reliable flap that supplies a large area of skin. This flap can be harvested irrespective of whether the skin vessels are septocutaneous or musculocutaneous. It is a versatile soft-tissue flap in which thickness and volume can be adjusted for the extent of the defect, and it can replace most soft-tissue free flaps in most clinical situations. (Plast. Reconstr. Surg. 109: 2219, 2002.)

The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis
Daniel I. Swerdlow, Michael V Holmes, Karoline B Kuchenbaecker, Jorgen E L Engmann +4 more
2012· The Lancet1.2Kdoi:10.1016/s0140-6736(12)60110-x

BACKGROUND: A high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation. However, whether IL6R blockade also reduces risk of coronary heart disease is unknown. METHODS: Applying the mendelian randomisation principle, we used single nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease. We compared genetic findings with the effects of tocilizumab reported in randomised trials in patients with rheumatoid arthritis. FINDINGS: In 40 studies including up to 133,449 individuals, an IL6R SNP (rs7529229) marking a non-synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased circulating log interleukin-6 concentration (increase per allele 9·45%, 95% CI 8·34-10·57) as well as reduced C-reactive protein (decrease per allele 8·35%, 95% CI 7·31-9·38) and fibrinogen concentrations (decrease per allele 0·85%, 95% CI 0·60-1·10). This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4-8 mg/kg every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials. In 25,458 coronary heart disease cases and 100,740 controls, the IL6R rs7529229 SNP was associated with a decreased odds of coronary heart disease events (per allele odds ratio 0·95, 95% CI 0·93-0·97, p=1·53×10(-5)). INTERPRETATION: On the basis of genetic evidence in human beings, IL6R signalling seems to have a causal role in development of coronary heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials. Genetic studies in populations could be used more widely to help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses. FUNDING: UK Medical Research Council; British Heart Foundation; Rosetrees Trust; US National Heart, Lung, and Blood Institute; Du Pont Pharma; Chest, Heart and Stroke Scotland; Wellcome Trust; Coronary Thrombosis Trust; Northwick Park Institute for Medical Research; UCLH/UCL Comprehensive Medical Research Centre; US National Institute on Aging; Academy of Finland; Netherlands Organisation for Health Research and Development; SANCO; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Agentschap NL; European Commission; Swedish Heart-Lung Foundation; Swedish Research Council; Strategic Cardiovascular Programme of the Karolinska Institutet; Stockholm County Council; US National Institute of Neurological Disorders and Stroke; MedStar Health Research Institute; GlaxoSmithKline; Dutch Kidney Foundation; US National Institutes of Health; Netherlands Interuniversity Cardiology Institute of the Netherlands; Diabetes UK; European Union Seventh Framework Programme; National Institute for Healthy Ageing; Cancer Research UK; MacArthur Foundation.

Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic
Zahra Belhadjer, Mathilde Méot, Fanny Bajolle, Diala Khraiche +4 more
2020· Circulation1.1Kdoi:10.1161/circulationaha.120.048360

BACKGROUND: Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention. METHODS: Over a 2-month period, contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. RESULTS: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range, 2-16 years). Comorbidities were present in 28%, including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was <30% in one-third; 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation. Inflammation markers were suggestive of cytokine storm (interleukin-6 median, 135 pg/mL) and macrophage activation (D-dimer median, 5284 ng/mL). Mean BNP (B-type natriuretic peptide) was elevated (5743 pg/mL). Thirty-one of 35 patients (88%) tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. All patients received intravenous immunoglobulin, with adjunctive steroid therapy used in one-third. Left ventricular function was restored in the 25 of 35 of those discharged from the intensive care unit. No patient died, and all patients treated with extracorporeal membrane oxygenation were successfully weaned. CONCLUSIONS: Children may experience an acute cardiac decompensation caused by severe inflammatory state after SARS-CoV-2 infection (multisystem inflammatory syndrome in children). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring
Gianfranco Parati, George S. Stergiou, Eoin O’Brien, Roland Asmar +4 more
2014· Journal of Hypertension1.0Kdoi:10.1097/hjh.0000000000000221

Given the increasing use of ambulatory blood pressure monitoring (ABPM) in both clinical practice and hypertension research, a group of scientists, participating in the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability, in year 2013 published a comprehensive position paper dealing with all aspects of the technique, based on the available scientific evidence for ABPM. The present work represents an updated schematic summary of the most important aspects related to the use of ABPM in daily practice, and is aimed at providing recommendations for proper use of this technique in a clinical setting by both specialists and practicing physicians. The present article details the requirements and the methodological issues to be addressed for using ABPM in clinical practice, The clinical indications for ABPM suggested by the available studies, among which white-coat phenomena, masked hypertension, and nocturnal hypertension, are outlined in detail, and the place of home measurement of blood pressure in relation to ABPM is discussed. The role of ABPM in pharmacological, epidemiological, and clinical research is also briefly mentioned. Finally, the implementation of ABPM in practice is considered in relation to the situation of different countries with regard to the reimbursement and the availability of ABPM in primary care practices, hospital clinics, and pharmacies.

Reconstruction of Damaged Corneas by Transplantation of Autologous Limbal Epithelial Cells
Ray Jui-Fang Tsai, Lien-Min Li, Jan-Kan Chen
2000· New England Journal of Medicine932doi:10.1056/nejm200007133430202

BACKGROUND: Stevens-Johnson syndrome, ocular pemphigoid, and thermal or chemical burns can cause scarring and opacification of the cornea and loss of vision. Transplantation of epithelial cells from the limbus of the contralateral cornea can restore useful vision. However, this procedure requires a large limbal graft from the healthy eye and is not possible in patients who have bilateral lesions. METHODS: We took specimens of limbal epithelial cells from the healthy contralateral eyes of six patients with severe unilateral corneal disease. The epithelial cells were cultured and expanded on amniotic membrane. The amniotic membrane, together with the sheet of limbal epithelial cells, was transplanted to the denuded corneal surface of the damaged eye after superficial keratectomy to remove fibrovascular ingrowth. The mean (+/-SD) follow-up period was 15+/-2 months. RESULTS: Complete reepithelialization of the corneal surface occurred within two to four days of transplantation in all six eyes receiving transplants. By one month, the ocular surface was covered with corneal epithelium, and the clarity of the cornea was improved. In five of the six eyes receiving transplants (83 percent), the mean visual acuity improved from 20/112 to 20/45. In one patient with a chemical burn who had total opacification of the cornea, the acuity improved from the ability to count fingers at 40 cm to 20/200. No patient had recurrent neovascularization or inflammation in the transplanted area during the follow-up period. CONCLUSIONS: Transplantation of autologous limbal epithelial cells cultured on amniotic membrane is a simple and effective method of reconstructing the corneal surface and restoring useful vision in patients with unilateral deficiency of limbal epithelial cells.

A clinical and pathological staging system for soft tissue sarcomas
William O. Russell, Jonathan Cohen, Franz M. Enzinger, Steven I. Hajdu +4 more
1977· Cancer765doi:10.1002/1097-0142(197710)40:4<1562::aid-cncr2820400428>3.0.co;2-6

A system for staging the clinical status of patients with soft tissue sarcomas is presented, based on the clinical characteristics of the primary tumor (size, extension), the involvement of lymph nodes, the presence of metastases, and the grade of the tumor. This represents the TNM system with grade of tumor (G) added. The system evolved was based on examination of 1215 cases of 13 types of soft tissue sarcomas, primarily in the extremities (fibrosarcoma, liposarcoma, etc.). Nine stages are described, and they are correlated with survival in the cases reviewed. The staging system now can be used for case evaluation for therapy determination and for intercomparison of series of patients as to incidence of different kinds of tumors, effects of treatment, and survival.

Benign solitary schwannomas (neurilemomas)
Tapas K. Das Gupta, Richard D. Brasfield, Elliót W. Strong, Steven I. Hajdu
1969· Cancer695doi:10.1002/1097-0142(196908)24:2<355::aid-cncr2820240218>3.0.co;2-2

Three hundred and three patients with benign solitary neurilemomas, or schwannomas, not associated with the classical type of von Recklinghausen's disease were studied. One hundred and seventy-two were women and 131 were men. Forty-five percent of the tumors were seen in the extremities, and no specific area could be related to the development of these tumors. Approximately 9% of the tumors occurred in the soft tissues of the trunk and 14% in various unusual sites. Most patients were seen initially because of a painless mass; only 10 complained of pain radiating along the course of a peripheral nerve. One documented case of a malignant degeneration in a benign schwannoma has been reported. The treatment of a benign solitary neurilemoma is enucleation. Excision of a segment of a major peripheral nerve is contraindicated. The histologic features of benign peripheral nerve tumors were briefly described. The confusion regarding terminology has been discussed, and it is suggested that the term schwannoma be more frequently used. The lack of neurologic deficit in schwannomas arising in major peripheral nerves has been pointed out, and further studies have been suggested. The high association of malignant tumors in these patients has been discussed, and it is proposed that a further study be undertaken to ascertain whether these patients are more prone to develop unrelated cancers.

A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study
Dae‐Hyun Yoo, Paweł Hrycaj, Pedro C. Miranda, Edgar Ramiterre +4 more
2013· Annals of the Rheumatic Diseases653doi:10.1136/annrheumdis-2012-203090

OBJECTIVES: To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. METHODS: Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5-25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. RESULTS: At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI -6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28-CRP, ACR-EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. CONCLUSIONS: CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. CLINICALTRIALS.GOV IDENTIFIER: NCT01217086.

Shock wave therapy induces neovascularization at the tendon–bone junction. A study in rabbits
Ching‐Jen Wang, Feng‐Sheng Wang, Kuender D. Yang, Lin‐Hsiu Weng +3 more
2003· Journal of Orthopaedic Research®629doi:10.1016/s0736-0266(03)00104-9

Despite the success in clinical application, the exact mechanism of shock wave therapy remains unknown. We hypothesized that shock wave therapy induces the ingrowth of neovascularization and improves blood supply to the tissues. The purpose of this study was to investigate the effect of shock wave therapy on neovascularization at the tendon-bone junction. Fifty New Zealand white rabbits with body weight ranging from 2.5 to 3.5 kg were used in this study. The right limb (the study side) received shock wave therapy to the Achilles tendon near the insertion to bone. The left limb (the control side) received no shock wave therapy. Biopsies of the tendon-bone junction were performed in 0, 1, 4, 8 and 12 weeks. The number of neo-vessels was examined microscopically with hematoxylin-eosin stain. Neovascularization was confirmed by the angiogenic markers including vessel endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expressions and endothelial cell proliferation determined by proliferating cell nuclear antigen (PCNA) expression examined microscopically with immunohistochemical stains. The results showed that shock wave therapy produced a significantly higher number of neo-vessels and angiogenesis-related markers including eNOS, VEGF and PCNA than the control without shock wave treatment. The eNOS and VEGF began to rise in as early as one week and remained high for 8 weeks, then declined at 12 weeks; whereas the increases of PCNA and neo-vessels began at 4 weeks and persisted for 12 weeks. In conclusion, shock wave therapy induces the ingrowth of neovascularization associated with early release of angiogenesis-related markers at the Achilles tendon-bone junction in rabbits. The neovascularization may play a role to improve blood supply and tissue regeneration at the tendon-bone junction.

Effect of Everolimus on Survival in Advanced Hepatocellular Carcinoma After Failure of Sorafenib
Andrew X. Zhu, Masatoshi Kudo, Eric Assénat, Stéphane Cattan +4 more
2014· JAMA569doi:10.1001/jama.2014.7189

IMPORTANCE: Aside from the multikinase inhibitor sorafenib, there are no effective systemic therapies for the treatment of advanced hepatocellular carcinoma. OBJECTIVE: To assess the efficacy of everolimus in patients with advanced hepatocellular carcinoma for whom sorafenib treatment failed. DESIGN, SETTING, AND PARTICIPANTS: EVOLVE-1 was a randomized, double-blind, phase 3 study conducted among 546 adults with Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma and Child-Pugh A liver function whose disease progressed during or after sorafenib or who were intolerant of sorafenib. Patients were enrolled from 17 countries between May 2010 and March 2012. Randomization was stratified by region (Asia vs rest of world) and macrovascular invasion (present vs absent). INTERVENTIONS: Everolimus, 7.5 mg/d, or matching placebo, both given in combination with best supportive care and continued until disease progression or intolerable toxicity. Per the 2:1 randomization scheme, 362 patients were randomized to the everolimus group and 184 patients to the placebo group. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. Secondary end points included time to progression and the disease control rate (the percentage of patients with a best overall response of complete or partial response or stable disease). RESULTS: No significant difference in overall survival was seen between treatment groups, with 303 deaths (83.7%) in the everolimus group and 151 deaths (82.1%) in the placebo group (hazard ratio [HR], 1.05; 95% CI, 0.86-1.27; P = .68; median overall survival, 7.6 months with everolimus, 7.3 months with placebo). Median time to progression with everolimus and placebo was 3.0 months and 2.6 months, respectively (HR, 0.93; 95% CI, 0.75-1.15), and disease control rate was 56.1% and 45.1%, respectively (P = .01). The most common grade 3/4 adverse events for everolimus vs placebo were anemia (7.8% vs 3.3%, respectively), asthenia (7.8% vs 5.5%, respectively), and decreased appetite (6.1% vs 0.5%, respectively). No patients experienced hepatitis C viral flare. Based on central laboratory results, hepatitis B viral reactivation was experienced by 39 patients (29 everolimus, 10 placebo); all cases were asymptomatic, but 3 everolimus recipients discontinued therapy. CONCLUSIONS AND RELEVANCE: Everolimus did not improve overall survival in patients with advanced hepatocellular carcinoma whose disease progressed during or after receiving sorafenib or who were intolerant of sorafenib. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01035229.

High Frequency of Epidermal Growth Factor Receptor Mutations with Complex Patterns in Non–Small Cell Lung Cancers Related to Gefitinib Responsiveness in Taiwan
Shiu‐Feng Huang, Hui-Ping Liu, Ling-Hui Li, Yuan-Chieh Ku +4 more
2004· Clinical Cancer Research553doi:10.1158/1078-0432.ccr-04-1245

PURPOSE: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. EXPERIMENTAL DESIGN: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. RESULTS: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. CONCLUSIONS: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.

A Clinical and Experimental Study
Richard M. Peters, W. E. Loring, William H. Sprunt
1958· Annals of Surgery503doi:10.1097/00000658-195812000-00002

PETERS, RICHARD M. M.D.; LORING, WILLIAM E. M.D.; SPRUNT, WILLIAM H. M.D. Author Information

MUCO-EPIDERMOID TUMORS OF SALIVARY GLANDS
Fred W. Stewart, Frank W. Foote, Walter Ferreira Becker
1945· Annals of Surgery477doi:10.1097/00000658-194511000-00005

NEW YORK, N. Y. PATHOLOGY LABORATORIES, MEMORIAL HOSPITAL FOR CANCER AND ALLIED DISEASES. NFW YORK. N. Y., AND DIVISION OF LABORATORIES AND RESEARCH, NEW YORK STATE DEPARTMENT OF HEALTH.

Neonatal Sepsis and Other Infections Due to Group B Beta-Hemolytic Streptococci
Theodore C. Eickhoff, Jerome O. Klein, A Daly, David Ingall +1 more
1964· New England Journal of Medicine465doi:10.1056/nejm196412102712401

BETA-hemolytic streptococci of Lancefield Group B have been implicated in human disease almost from the time when the precipitin-grouping technic first came into use.1 2 3 Since that time additional reports4 5 6 7 8 have established the fact that these organisms occasionally cause severe infection in parturient women, and less frequently in other adult patients and in newborn infants. Streptococcus agalactiae, the species designation9 of Group B streptococcus, has been recognized for many years at the Boston City Hospital from its characteristic colonial morphology on suitable solid mediums10 and observed frequently in primary cultures from obstetric patients and newborn infants. Recently, there appeared to be . . .

Dietary components that regulate serum somatomedin-C concentrations in humans.
W L Isley, Louis E. Underwood, David R. Clemmons
1983· Journal of Clinical Investigation436doi:10.1172/jci110757

Dietary components responsible for the regulation of somatomedin-C in humans were assessed in five adult volunteers of normal weight who were fasted for 5 d on three occasions, then refed three diets of differing composition. The serum somatomedin-C decreased from a mean prefasting value of 1.85 +/- 0.39 U/ml (+/- 1 SD) to 0.67 +/- 0.16 U/ml at the end of fasting (P less than 0.005). After refeeding for 5 d with a normal diet, the mean serum somatomedin-C increased to 1.26 +/- 0.20 U/ml. A protein-deficient (32% of control), isocaloric diet resulted in a significantly smaller increase, to a mean value of 0.90 +/- 0.24 U/ml (P less than 0.05). A diet deficient in both protein and energy led to a further fall 0.31 +/- 0.06 U/ml. The changes in somatomedin-C during fasting and refeeding correlated significantly with mean daily nitrogen balance (r = 0.90). We conclude that both protein and energy intake are regulators of serum somatomedin-C concentrations in adult humans, and energy intake may be of greater importance. The correlation between changes in somatomedin-C and nitrogen balance suggests that the former are directly related to changes in protein synthesis and may be helpful in assessing the response to nutritional therapy.

A global emerging disease of <i>Klebsiella pneumoniae</i> liver abscess: is serotype K1 an important factor for complicated endophthalmitis?
C-P Fung, F-Y Chang, S-C Lee, Bor-Shen Hu +4 more
2002· Gut424doi:10.1136/gut.50.3.420

BACKGROUND AND AIMS: Over the past two decades in Taiwan, pyogenic liver abscess has usually been caused by a single microorganism, Klebsiella pneumoniae, and is frequently associated with the serious complication of endophthalmitis, especially in diabetic patients. However, the relationship between the clinical presentation and bacterial factors remains unclear. The aim of this study was to investigate the clinical features of patients and the serotype and ribotype of K pneumoniae liver abscess. METHODS: From July 1991 to June 1998, a total of 134 cases of K pneumoniae liver abscess with 248 K pneumoniae isolates from the same patients were collected from two large medical centres in northern Taiwan. Clinical data were collected from medical records. Serotyping and ribotyping were performed using the countercurrent immunoelectrophoresis method and automated Riboprinter. RESULTS: Serotyping revealed that the most common serotypes were K1 (63.4%) and K2 (14.2%). K1 isolates occurred at a significantly higher frequency (p<0.01) than all other serotypes. Among 134 patients, 105 (78.4%) had suffered from diabetes mellitus for 3-15 years. Fourteen patients (10.4%) had metastatic infection to the eye causing septic endophthalmitis. Liver aspirates, and blood and vitreous pus cultures yielded the same serotype of K pneumoniae in all patients. Among patients with septic endophthalmitis, 92.3% (13/14) were diabetic, and 85.7% (12/14) of the isolates belonged to serotype K1. For molecular typing, different degrees of genetic polymorphism among isolates with the same K1 serotype suggested no particular prevalence of any one strain in K pneumoniae liver abscess. CONCLUSION: K pneumoniae serotype K1 was significantly associated with liver abscess and the complication of endophthalmitis, especially in diabetic patients. Physicians should request an immediate report of serotyping and susceptibility test results simultaneously if a diagnosis of pyogenic liver abscess has been made so that early and appropriate management for possible complications will not be delayed. The use of ceftriaxone because of its higher concentration in the aqueous humor is suggested to decrease the chance of septic endophthalmitis.

Tumors of minor salivary origin
Ronald H. Spiro, Leopold G. Koss, Steven I. Hajdu, Elliót W. Strong
1973· Cancer422doi:10.1002/1097-0142(197301)31:1<117::aid-cncr2820310116>3.0.co;2-7

All cases of minor salivary neoplasm seen at Memorial Hospital during a 25-year period are reviewed. More than 88% had malignant tumors, and adenoidcystic carcinoma was the lesion most frequently encountered. Although the palate was the site most often involved, great diversity in clinical presentation was noted. Neither the symptomatology nor the gross appearance was of assistance in predicting the histology of these lesions. All but 10% of the patients were treated surgically. Elective radical neck dissection was avoided in those with malignant tumors inasmuch as metastases were as likely to appear in distant sites as in regional lymph nodes. The determinate “cure” rate 5, 10, and 15 years after treatment was 44.5, 32.6, and 21.4%, respectively. Histology, anatomic site, and the extent of the disease were the factors which most influenced survival.

Timing of Presentation of the First Signs of Vascular Compromise Dictates the Salvage Outcome of Free Flap Transfers
Kuang-Te Chen, Samir Mardini, David Chwei‐Chin Chuang, Chih‐Hung Lin +4 more
2007· Plastic & Reconstructive Surgery417doi:10.1097/01.prs.0000264077.07779.50

BACKGROUND: Microsurgical free tissue transfer has become a reliable technique. Nevertheless, 5 to 25 percent of transferred flaps require re-exploration due to circulatory compromise. This study was conducted to evaluate the timing of occurrence of flap compromise following free tissue transfer, and its correlation with salvage outcome. METHODS: Between January of 2002 and June of 2003, 1142 free flap procedures were performed and 113 flaps (9.9 percent) received re-exploration due to compromise. All patients were cared for in the microsurgical intensive care unit for 5 days. Through a retrospective review, timing of presentation of compromise was identified and correlated with salvage outcome. RESULTS: Seventy-two flaps (63.7 percent) were completely salvaged and 23 (20.4 percent) were partially salvaged. Eighteen flaps (15.9 percent) failed completely. Ninety-three flaps (82.3 percent) presented with circulatory compromise within 24 hours; 108 (95.6 percent) presented with circulatory compromise within 72 hours, and 92 flaps (85.2 percent) were salvaged within this period. One out of the three flaps presenting with compromise 1 week postoperatively was salvaged. Flaps presenting with compromise upon admission to the microsurgical intensive care unit had significantly lower complete salvage rates as compared with those without immediate abnormal signs (40.9 percent versus 69.2 percent, p = 0.01). CONCLUSIONS: The time of presentation of flap compromise is a significant predictor of flap salvage outcome. Intensive flap monitoring at a special microsurgical intensive care unit by well-trained nurses and surgeons allows for early detection of vascular compromise, which leads to better outcomes.