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Chronic airways infection with methicillin-resistant Staphylococcus aureus (MRSA) is associated with worse respiratory disease cystic fibrosis (CF) patients. Ceftaroline is a cephalosporin that inhibits the penicillin-binding protein (PBP2a) uniquely produced by MRSA. We analyzed 335 S. aureus isolates from CF sputum samples collected at three US centers between 2015–2018. Molecular relationships demonstrated that high-level resistance of preceding isolates to carbapenems were associated with subsequent isolation of ceftaroline resistant CF MRSA. In vitro evolution experiments showed that pre-exposure of CF MRSA to meropenem with further selection with ceftaroline implied mutations in mecA and additional mutations in pbp1 and pbp2, targets of carbapenems; no effects were achieved by other β-lactams. An in vivo pneumonia mouse model showed the potential therapeutic efficacy of ceftaroline/meropenem combination against ceftaroline-resistant CF MRSA infections. Thus, the present findings highlight risk factors and potential therapeutic strategies offering an opportunity to both prevent and address antibiotic resistance in this patient population., Varela, Roch et al. find that resistance of preceding isolates to carbapenems is associated with the subsequent isolation of methicillin-resistant Staphylococcus aureus (MRSA) resistant to ceftaroline. Addition of meropenem reduces the cystic fibrosis MRSA’s resistance to ceftaroline in a pneumonia mouse model, suggesting a strategy to control antibiotics resistance.

Background Chronic obstructive pulmonary disease patients have been shown in orthopedic literature to have poorer outcomes and higher rates of complications from surgery. In this retrospective review, medical complications, length of stay, and costs were obtained to explore the effects of chronic obstructive pulmonary disease on patients undergoing primary total shoulder arthroplasty. Methods Total shoulder arthroplasty cases from January 2005 to March 2014 were queried and analyzed from a nationwide database. Study patients were matched 1:5 to controls by age, sex, and medical comorbidities associated with chronic obstructive pulmonary disease. In-hospital length of stay, 90-day medical complications, day of surgery, and total global 90-day episode of care costs were obtained for comparison. Results Chronic obstructive pulmonary disease patients were found to have higher incidence and odds (53.91 vs. 11.95%; OR: 3.58, 95%CI: 3.18–3.92, p Discussion Chronic obstructive pulmonary disease patients undergoing primary total shoulder arthroplasty have higher rates of medical complications, in-hospital length of stay, and costs of care. This represents an important factor that will allow orthopedic surgeons to adequately manage expectations and educate chronic obstructive pulmonary disease patients of the potential complications which may occur following total shoulder arthroplasty.

Background Tedizolid is a protein synthesis inhibitor in clinical use for the treatment of Gram-positive infections. Pulmonary MRSA infections are a growing problem in patients with cystic fibrosis (CF) and the efficacy of tedizolid-based therapy in CF pulmonary infections is unknown. Objectives To evaluate the in vitro and in vivo activity of tedizolid and predict the likelihood of tedizolid resistance selection in CF-background Staphylococcus aureus strains. Methods A collection of 330 S. aureus strains (from adult and paediatric patients), either of normal or small colony variant (SCV) phenotypes, gathered at three CF centres in the USA was used. Tedizolid activity was assessed by broth microdilution, Etest and time–kill analysis. In vivo tedizolid efficacy was tested in a murine pneumonia model. Tedizolid in vitro mutants were obtained by 40 days of exposure and progressive passages. Whole genome sequencing of clinical S. aureus strains with reduced susceptibility to tedizolid was performed. Results MRSA strain MIC90s were tedizolid 0.12–0.25 mg/L and linezolid 1–2 mg/L; for MSSA strains, MIC90s were tedizolid 0.12 mg/L and linezolid 1–2 mg/L. Two strains, WIS 441 and Seattle 106, with tedizolid MICs of 2 mg/L and 1 mg/L, respectively, had MICs above the FDA tedizolid breakpoint (0.5 mg/L). Tedizolid at free serum concentrations exhibited a bacteriostatic effect. Mean bacterial burdens in lungs (log10 cfu/g) for WIS 423-infected mice were: control, 11.2±0.5; tedizolid-treated (10 mg/kg), 3.40±1.87; linezolid-treated (40 mg/kg), 4.51±2.1; and vancomycin-treated (30 mg/kg), 5.21±1.93. For WIS 441-infected mice the (log10 cfu/g) values were: control, 9.66±0.8; tedizolid-treated, 3.18±1.35; linezolid-treated 5.94±2.19; and vancomycin-treated, 4.35±1.7. Conclusions These results suggest that tedizolid represents a promising therapeutic option for the treatment of CF-associated MRSA/MSSA infections, having potent in vivo activity and low resistance potential.

Purpose: Studies have shown the prevalence of iron deficiency anemia (IDA) increasing worldwide, and currently the literature is limited on the impact of IDA on outcomes following revision total hip arthroplasty (RTHA). Therefore, the purpose of this study was to determine whether IDA patients undergoing RTHA have longer: 1) in-hospital lengths of stay (LOS); 2) medical complications; and 3) costs of care. Materials and Methods: A retrospective query of a nationwide administrative claims database was performed. Using Boolean command operations, the study group consisted of all patients in the database undergoing RTHA with IDA; whereas, patients without IDA served as controls. To reduce the effects of confounding, study group patients were matched to controls in a 1:5 ratio by age, sex, and medical comorbidities yielding 92,948 patients with (n=15,508) and without (n=77,440) IDA undergoing revision THA. A P-value less than 0.001 was considered statistically significant. Results: IDA patients were found to have significantly longer in-hospital LOS (5 days vs. 4 days, P

Klebsiella pneumoniae strains producing K. pneumoniae carbapenemase (KPC) cause serious infections in debilitated and immunocompromised patients and are associated with prolonged hospital stays and increased mortality rates. Daptomycin is a lipopeptide used against Staphylococcus aureus infection and considered inactive against Gram-negative bacteria. We investigated the effectiveness of a daptomycin-meropenem combination by synergy kill curve and a pharmacokinetic/pharmacodynamic model. The combination may represent a novel therapeutic strategy against infections caused by KPC-producing K. pneumoniae strains.

Methicillin-resistant Staphylococcus aureus (MRSA) acquisition in cystic fibrosis (CF) patients confers a worse clinical outcome with increased rate of declined lung function. Telavancin, an approved lipoglycopeptide used to treat infections due to S. aureus has a dual mode of action causing inhibition of the peptidoglycan synthesis and membrane depolarization. CF-associated MRSA infections remain an important problem with no foreseeable decline in prevalence rates. Although telavancin is currently in clinical use for complicated skin infections and hospital-acquired pneumonia, the activity against CF-associated S. aureus infections has not been investigated. In this work, we studied the activity of telavancin against CF S. aureus strains collected from diverse geographical CF centers in the USA. We found that telavancin-MIC90 was 0.06 μg/ml, 8-fold lower than ceftaroline or daptomycin and 25-fold lower than linezolid and vancomycin. We demonstrate that telavancin at serum-free concentrations has rapid bactericidal activity with a decrease of more than 3 log10 CFU/ml during the first 4 to 6 hours of treatment, performing better in this assay than vancomycin and ceftaroline, including S. aureus resistant to ceftaroline.Telavancin resistance was infrequent (0.3%), although we found that it can occur in-vitro in both CF-and non-CF S. aureus strains by progressive passages with sub-inhibitory concentrations. Genetic analysis of telavancin in-vitro mutants showed gene polymorphisms in cell wall and virulence genes, and increased survival in a Galleria mellonella infection model. Thus, we conclude that telavancin represents a promising therapeutic option for CF infections with potent in-vitro activity and low resistance potential.

Methicillin-resistant Staphylococcus aureus (MRSA) acquisition in cystic fibrosis (CF) patients confers a clinical outcome worse than that in non-CF patients with an increased rate of declined lung function. Telavancin, an approved lipoglycopeptide used to treat infections due to S. aureus, has a dual mode of action causing inhibition of peptidoglycan synthesis and membrane depolarization. MRSA infections in CF patients remain an important problem with no foreseeable decline in prevalence rates. Although telavancin is currently in clinical use for the treatment of complicated skin infections and hospital-acquired pneumonia, the activity against S. aureus infections in CF patients has not been investigated. In this work, we studied the activity of telavancin against CF patient-derived S. aureus strains collected from geographically diverse CF centers in the United States. We found that the telavancin MIC90 was 0.06 μg/ml, 8-fold lower than the ceftaroline or daptomycin MIC90 and 25-fold lower than the linezolid and vancomycin MIC90 We demonstrate that telavancin at serum free concentrations has rapid bactericidal activity, with a decrease of more than 3 log10 CFU/ml being achieved during the first 4 to 6 h of treatment, performing better in this assay than vancomycin and ceftaroline, including against S. aureus strains resistant to ceftaroline. Telavancin resistance was infrequent (0.3%), although we found that it can occur in vitro in both CF- and non-CF patient-derived S. aureus strains by progressive passages with subinhibitory concentrations. Genetic analysis of telavancin-resistant in vitro mutants showed gene polymorphisms in cell wall and virulence genes and increased survival in a Galleria mellonella infection model. Thus, we conclude that telavancin represents a promising therapeutic option for infections in CF patients with potent in vitro activity and a low resistance development potential.

This chapter will review the types of surgical drains and tubes available to the modern general and thoracic surgeon, with a brief mention of those available to the interventional radiologist. Proper drain care and management are also discussed with a focus on individual drain types and indications for use. Negative-pressure wound therapy (NPWT) is also reviewed. These modern drainage tools for managing wounds, fluid collections, abscesses, and enteric fistulae have significantly reduced the need for both initial and re-operative surgeries. This has led to decreased morbidity and mortality in the surgical population and has reduced the need for emergent interventions, thereby reducing the associated debilitating inflammatory response, unanticipated “collateral damage,” and stress to both the patient and operating surgeon.

Antimicrobial resistance is recognized as one of the principal threats to public health worldwide, yet the problem is increasing. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains are among the most difficult to treat in clinical settings due to the resistance of MRSA to nearly all available antibiotics. The cyclic anionic lipopeptide antibiotic daptomycin (DAP) is the clinical mainstay of anti-MRSA therapy. The decreased susceptibility to DAP (DAP resistance [DAP r ]) reported in MRSA is frequently accompanied by a paradoxical decrease in β-lactam resistance, a process known as the “seesaw effect.” Despite the observed discordance in resistance phenotypes, the combination of DAP and β-lactams has been proven to be clinically effective for the prevention and treatment of infections due to DAP r MRSA strains. However, the mechanisms underlying the interactions between DAP and β-lactams are largely unknown. In the study described here, we studied the role of mprF with DAP-induced mutations in β-lactam sensitization and its involvement in the effective killing by the DAP-oxacillin (OXA) combination. DAP-OXA-mediated effects resulted in cell wall perturbations, including changes in peptidoglycan insertion, penicillin-binding protein 2 (PBP 2) delocalization, and reduced membrane amounts of PBP 2a, despite the increased transcription of mecA through mec regulatory elements. We have found that the VraSR sensor-regulator is a key component of DAP resistance, triggering mutated mprF -mediated cell membrane (CM) modifications that result in impairment of PrsA location and chaperone functions, both of which are essential for PBP 2a maturation, the key determinant of β-lactam resistance. These observations provide for the first time evidence that synergistic effects between DAP and β-lactams involve PrsA posttranscriptional regulation of CM-associated PBP 2a.

Background.The impact of antimicrobial scrubs on healthcare worker (HCW) bacterial burden is unknown.Objective.To determine die effectiveness of antimicrobial scrubs on hand and apparel bacterial burden.Design.Prospective, crossover trial.Setting and Participants.Thirty HCWs randomized to study versus control scrubs in an intensive care unit.Methods.Weekly microbiology samples were obtained from scrub abdominal area, cargo pocket, and hands. Mean log colony-forming unit (CFU) counts were calculated. Compliance with hand hygiene practices was measured. Apparel and hand mean log CFU counts were compared.Results.Adherence measures were 78% (910/1,173) for hand hygiene and 82% (223/273) for scrubs. Culture compliance was 67% (306/460). No differences were observed in bacterial hand burden or in HCWs with unique positive scrub cultures. No difference in vancomycin-resistant enterococci (VRE) and gram-negative rod (GNR) burden was observed. A difference in mean log mediicillin-resistant Staphylococcus aureus (MRSA) CFU count was found between study and control scrubs for leg cargo pocket (mean log CFUs, 11.84 control scrub vs 6.71 study scrub; P = .0002), abdominal area (mean log CFUs, 11.35 control scrub vs 7.54 study scrub; P = .0056), leg cargo pocket at die beginning of shift (mean log CFUs, 11.96 control scrub vs 4.87 study scrub; P = .0028), and abdominal area pocket at die end of shift (mean log CFUs, 12.14 control scrubs vs 8.22 study scrub; P = .0054).Conclusions.Study scrubs were associated witfi a 4–7 mean log reduction in MRSA burden but not VRE or GNRs. A prospective trial is needed to measure die impact of antimicrobial impregnated apparel on MRSA transmission rates.Infect Control Hosp Epidemiol 2012;33(3):268-275

Background We studied risk factors for nasal colonization with inducible dormant methicillin-resistant Staphylococcus aureus (ID-MRSA) and community-associated MRSA (CA-MRSA) in a cohort of predominantly university students. Methods Nasal surveillance cultures were performed in student health and ambulatory clinics. Molecular features were identified and risk factors for CA-MRSA and ID-MRSA colonization were determined by logistic regression. Results Of the 1000 participants, 89% ( n = 890) were university students. Sixty-four percent were female, 59% Caucasian. The mean age was 23.5 years; 1.6% ( n = 16) were CA-MRSA and 1.4% ( n = 14) were ID-MRSA colonized. Fifteen (94%) of the CA-MRSA strains were PFGE type IV. pvl (Panton–Valentine leukocidin gene) positivity was 75% in CA-MRSA and 57% in ID-MRSA. ID-MRSA isolates were pulsed-field gel electrophoresis (PFGE) type I, 7%; type II, 14%; type V, 7%; and type IV, 71%. CA-MRSA SCC mec classification was 94% type IV and 6% type V. Risk factors for carriage of CA-MRSA were older age (OR 1.046, p =0.040) and dog ownership (OR 1.450, p =0.019). Single family home (OR 0.040, p =0.007) was a protective factor. There were no significant variables of association found for ID-MRSA colonization. Conclusions ID-MRSA/CA-MRSA colonization was low. Most isolates were PFGE types IV and II, pvl -positive and susceptible to several antibiotics. Older age and dog ownership were risk factors for CA-MRSA. Future studies are needed to assess the impact of ID-MRSA carriage.

Objective.To compare the efficacy of universal gloving with emollient-impregnated gloves with standard contact precautions for the control of multidrug-resistant organisms (MDROs) and to measure the effect on healthcare workers' (HCWs') hand skin health.Design.Prospective before-after trial.Setting.An 18-bed surgical intensive care unit.Methods.During phase 1 (September 2007 through March 2008) standard contact precautions were used. During phase 2 (March 2008 through September 2008) universal gloving with emollient-impregnated gloves was used, and no contact precautions. Patients were screened for vancomycin-resistantEnterococcus(VRE) and methicillin-resistantStaphylococcus aureus(MRSA). HCW hand hygiene compliance and hand skin health and microbial contamination were assessed. The incidences of device-associated infection andClostridium difficileinfection (CDI) were determined.Results.The rate of compliance with contact precautions (phase 1) was 67%, and the rate of compliance with universal gloving (phase 2) was 78% (P= .01). Hand hygiene compliance was higher during phase 2 than during phase 1 (before patient care, 40% vs 35% of encounters;P= .001; after patient care, 63% vs 51% of encounters;P< .001). No difference was observed in MDRO acquisition. During phases 1 and 2, incidences of device-related infections, in number of infections per 1,000 device-days, were, respectively, 3.7 and 2.6 for bloodstream infection (P= .10), 8.9 and 7.8 for urinary tract infection (P= .10), and 1.0 and 1.1 for ventilator-associated pneumonia (P= .09). The CDI incidence in phase 1 and in phase 2 was, respectively, 2.0 and 1.4 cases per 1,000 patient-days (P= .53). During phase 1, 29% of HCW hand cultures were MRSA positive, compared with 13% during phase 2 (P= .17); during phase 1, 2% of hand cultures were VRE positive, compared with 0 during phase 2 (P= .16). Hand skin health improved during phase 2.Conclusions.Compared with contact precautions, universal gloving with emollient-impregnated gloves was associated with improved hand hygiene compliance and skin health. No statistically significant change in the rates of device-associated infection, CDI, or patient MDRO acquisition was observed. Universal gloving may be an alternative to contact precautions.

Malignant tumors of the small bowel account for less than 10% of all gastrointestinal neoplasms. The majority of these tumors are secondary neoplasms metastatic from either an intra- or extra-abdominal site. Symptoms related to these tumors include bleeding, obstruction, and perforation, although the great majority of these metastases remain asymptomatic and are only discovered at autopsy. Outcomes remain poor and most interventions are palliative. We review the current surgical recommendations for management of this challenging clinical scenario.

Background Intralumenal full-thickness gastric resection (FTGR) could be useful as a biopsy technique or in the management of gastric neoplasms. SurgASSIST is a cutting and stapling device delivered on a steerable shaft to which interchangeable stapling units are affixed. Objective This feasibility study assessed the applicability of the SurgASSIST to perform intralumenal FTGR in a swine model. Design Descriptive analysis; no statistical tests were applied. Setting Animal laboratory. Methods Four nonsurvival swine under general anesthesia were studied. An oroesophageal overtube was placed. A balloon trocar was inserted into the stomach under endoscopic guidance and served as a port for instruments and imaging. Under direct visualization, the SurgASSIST with a 55-mm straight-linear cutter and stapler unit (SLCS55) was advanced via the overtube into the stomach. We evaluated the safety and efficacy of overtube placement, SLCS55 insertion and maneuverability in the stomach, parallel versus perpendicular optics, and various tissue grasping devices to achieve FTGR. Results Overtube insertion produced limited esophageal mucosal tears in 2 subjects and a severe tear in 1 subject. Maneuverability of the SLCS55 was limited. Endoscopic guidance for FTGR via both peroral (parallel) and per gastrostomy port (perpendicular) orientations was satisfactory. FTGR was successful in 2 of 4 subjects. Resected specimens measured 6.0 × 0.6 cm and 6.0 × 0.7 cm. There were no operative complications. In the remaining 2 subjects, the depth of resection was submucosa. Limitations Animal model. Conclusions Peroral intralumenal FTGR is feasible. A gastrostomy port facilitates triangulation for optics and tissue manipulation. Further refinements are needed to yield reliable results.

BACKGROUND The objective of this study was to evaluate the usefulness of resection of metastatic uveal melanoma and to analyze the characteristics of patients who may benefit from surgical intervention. PATIENTS AND METHODS Twelve patients underwent surgical removal of metastasis between 1976 and 1998. Data regarding primary uveal melanoma, systemic metastasis, surgical procedures, and outcomes were reviewed retrospectively. RESULTS There were seven patients with liver metastases, two with lung metastases, one with brain metastasis, and two patients with metastases in the liver and other organs. Median time to systemic metastasis was 8 years. Seven of 12 patients were asymptomatic when they were found to have metastasis. Ten patients underwent complete resection of metastasis. No significant surgical complications were experienced. Median recurrence free and overall survival periods after complete resection were 19 months (range, 6–78 months) and greater than 27 months (range, 11–86 months), respectively. Recurrence free and overall 5-year survival rates of those patients were 15.6% and 53.3%, respectively. Three of these patients had no further systemic recurrence. All patients whose time to systemic metastasis was within 5 years developed further systemic recurrence within 2 years after surgery. In contrast, in 8 patients whose time to systemic metastases was greater than 5 years, 4 patients either were recurrence free or developed second metastasis more than 4 years after surgery. CONCLUSIONS Complete surgical removal of metastatic uveal melanoma provided unexpectedly long survival without significant morbidity for the selected patients. These results are encouraging and justify a trial in which patients eligible for resection are randomized between standard treatment and surgery. Cancer 2000;89:1561–8. © 2000 American Cancer Society.

OBJECTIVE: The objective of the study was to analyze a single center's experience in the treatment of pancreatic carcinoma with a combination of pancreatic resection and intraoperative radiation therapy (IORT). SUMMARY BACKGROUND DATA: Pancreatic cancer is the most lethal form of gastrointestinal malignancy. Historically, it carries a 20% 1-year survival and a 5-year survival of 3% to 5%. Since 1987, patients at Thomas Jefferson University Hospital have been offered IORT in an attempt to improve their survival. METHODS: The authors reviewed all patients treated at Thomas Jefferson University Hospital with pancreatic adenocarcinoma from 1987 to 1994. From this population, 14 patients were identified who received IORT in conjunction with curative surgery. Duration of hospital stay, perioperative complications, duration of postoperative ileus, and survival were assessed by retrospective review. RESULTS: Of the 14 patients, 6 were male and 8 were female. Patient median age was 61. Six patients had stage I disease, 2 had stage II, 6 had stage III. Two patients had total pancreatectomy, 2 had distal pancreatectomy, and the remaining had pancreaticoduodenectomy (Whipple resection). Median survival was 16 months with a 15.5% 5-year survival. Postoperative complications, duration of hospital stay, and duration of postoperative ileus were not adversely affected by the addition of IORT when compared to in-house control subjects. CONCLUSIONS: Intraoperative radiation therapy is a useful adjunct to surgical resection as treatment of pancreatic cancer. The authors' data suggested it can prolong median survival and long-term survival without adding significant morbidity.

Background Intraoperative ultrasound has been shown to provide significant assistance in operative staging and management of patients with liver tumors during open surgery. The availability of the 5.0–7.5 Mhz semiflexible ultrasound transducer with gray-scale, color and spectral Doppler capabilities can provide similar information laparoscopically. Methods Twenty-four consecutive patients with liver tumors (18 metastatic and six primary), in technically resectable locations determined by a variety of conventional imaging studies, were brought to the operating room. There was no known extrahepatic disease, and there was no recurrence at the primary site in the metastatic subgroup. These patients were evaluated intraoperatively with laparoscopy and intraoperative laparoscopic ultrasound to assess resectability prior to performing a major laparotomy. Laparoscopy was successful in 23 of the patients and in 19 of 23, laparoscopic ultrasound was also employed, using the 5.0–7.5 MHz semi-flexible transducer. The use of the open entry technique, selection of alternate entry sites, coupled with expertise in laparoscopic lysis of adhesions, has allowed safe laparoscopic tumor staging. Results The laparoscopic evaluation was aborted only once due to dense adhesions, despite the fact that 67% of the patients had undergone previous abdominal surgery. There was only one complication: bleeding from a liver biopsy in an unresectable cirrhotic patient, necessitating laparotomy. Laparoscopy and ultrasound together predicted nonresectability in six of eight unresectable patients, all of whom were spared an unnecessary laparotomy. Conclusions Laparoscopic ultrasonographic evaluation for the staging of liver tumors should be a prerequisite to definitive laparotomy, with the objective of avoiding unncessary surgery. J. Surg. Oncol. 64: 63–67 © 1997 Wiley-Liss, Inc.

Laparoscopic surgery has been accepted as the surgery of choice for many diagnostic and therapeutic abdominal procedures because of decreased morbidity, reduced cost, and improvement in long-term outcomes compared with open procedures. However, this approach has inherent limitations in the evaluation of diseases concealed within solid organs, hollow viscera, or the retroperitoneum. Laparoscopic ultrasound, which evolved from the concepts of intraoperative and endoscopic ultrasound, opens a whole new dimension to accurately diagnose and treat conditions laparoscopically. This technique shows promise of becoming a valuable new adjunct to a variety of laparoscopic procedures for the diagnosis and treatment of various abdominal and pelvic abnormalities.

The most forward ring (2 ≤ θ ≤ 3°) of the INDRA multidetector has been equipped with 12 plastic phoswich detectors able to withstand the high counting rates encountered at very small angles. Each phoswich detector is composed of a 500 μm thick fast scintillator and a 25 cm thick slow scintillator. Elemental identification is achieved on a fairly large domain, ranging from Z = 1 up to Z = 37. A new method of Z separation, using an identification function technique, is described.

Background. One thousand seventy patients treated conservatively for Stages I and II breast cancer between the years 1982 and 1994 were reviewed. The median follow-up was 40 months with a maximum follow-up of 152 months. Methods. All patients had a wide local excision and lower lymph axillary node dissection followed by radiation therapy. The entire breast received an external beam dose of 4500 cGy at 180 cGy/5 days/week. An additional boost dose of 2000 cGy to the tumor bed was given at the time of lumpectomy (perioperative) with an Ir-192 implant or with electron beam therapy after the external beam therapy. Results. The 5- and 10-year disease specific survival results were 97 and 90%, respectively for Stage I and 87 and 69% for patients with Stage II disease. The 5- and 10-year local control rates were 93 and 85% for Stage I and 92 and 87% for Stage II, respectively. The risk factors for local failure were premenopausal status and estrogen receptor-negative status at the univariate level but at the multivariate level the premenopausal and margins status were significant. Conclusion. These 10-year results were at least equivalent to reported series of similarly staged patients treated by mastectomy. This should encourage more surgeons to offer conservative treatment as an alternative to mastectomy to patients with Stage I and II breast cancer. Cancer 1995 ; 75 :2328-36.

To evaluate a semiflexible ultrasound (US) transducer inserted through a laparoscopic port to image abdominal structures.Laparoscopic US with a 9.6-mm-diameter, 5.0-7.5-MHz semiflexible transducer with gray-scale, color, and spectral Doppler capabilities was performed in three miniature swine and in 25 patients with a variety of abdominal abnormalities.This miniature US probe was used to locate normal structures such as blood vessels, allowing the surgeon to decide the best approach for dissection. Color and spectral Doppler US proved especially useful in differentiating vascular from nonvascular structures. The presence or absence of stones in the gallbladder and common bile duct was readily determined. It was possible to detect masses and to provide guidance for their aspiration or biopsy within abdominal organs. In 10 cases (40%), laparoscopic US helped the surgeon make the decision for clinical management and altered the surgical procedures.Laparoscopic US was useful in assisting laparoscopic evaluation of abnormalities in the abdomen.

Nontumorous perfusion defects occur during CT arterial portography (CTAP) as normal variants or in cirrhosis, focal fatty infiltration, and portal vein obstruction. The purpose of this study was to determine whether delayed CT 4-6 hr after CTAP improves sensitivity to hepatic tumors and differentiates them from other hepatic perfusion defects.CTAP was done at 1-cm increments on 26 patients for evaluation of hepatic tumors. Delayed CT scans were obtained 4-6 hr later in all patients. Two observers retrospectively reviewed the CT scans obtained during CTAP and recorded size, shape, and location of suspected hepatic tumors. Confidence levels were assigned for each tumor. The delayed CT scan was then interpreted in conjunction with the CT scans obtained during CTAP, and confidence levels were reassigned. Surgical correlation was obtained for all patients. In the 26 patients, 86 masses were found at surgery. The sensitivity and number of false-positives for both CTAP alone and CTAP combined with delayed CT were compared with a two-tailed Student t-test. Receiver-operating-characteristic analysis also was performed.CTAP detected 73 (85%) of the 86 hepatic masses. Delayed CT had no effect on the sensitivity of CTAP. However, adding delayed CT decreased the total number of false-positives by 11, a statistically significant difference (p.05). Receiver-operating-characteristic analysis revealed a significantly greater (p.05) area under the curve (Az index) of 0.927 +/- 0.025 for CTAP combined with delayed CT compared with 0.886 +/- 0.032 for CTAP alone. Delayed CT was most useful for larger (1 cm) wedge-shaped perfusion defects and least useful for smaller (1 cm) round defects.Delayed CT has no effect in detecting tumors but may be useful for differentiating tumors from other hepatic perfusion defects seen on CTAP. The greatest benefit of delayed CT is in evaluating regions obscured by large wedge-shaped perfusion defects on CT scans obtained during CTAP.

Median arcuate ligament syndrome results from external compression of the celiac axis by attachments of the diaphragmatic crura. It has been treated with open or laparoscopic surgical decompression of the celiac axis with neurolysis. We describe our initial experience treating three patients using a robotic-assisted technique with median arcuate ligament release and celiac neurolysis. Average operative time was 2.2 hours. No intraoperative complications occurred. At an average of 11 months postoperative (14, 11, and 8 months), two patients continue with resolution of preoperative symptoms. Our experience affirms that further study using the robotic approach appears warranted.

Over the past 10 years, minimally invasive esophagectomy has become an accepted approach to the management of esophageal and gastroesophageal benign and malignant neoplasms. There are many interpretations of the minimally invasive esophagectomy. Currently, the most frequently performed surgeries include combined thoracoscopic esophageal mobilization and laparoscopic gastric mobilization with creation of a cervical esophagogastrostomy anastomosis (“3-hole” esophagectomy); laparoscopic Ivor-Lewis technique, utilizing a laparoscopic mobilization of the stomach followed by a thoracoscopic intrathoracic esophagogastrostomy anastomosis; laparoscopic transhiatal esophagectomy, utilizing a laparoscopic mobilization of the stomach and a trans-abdominal laparoscopic mediastinal esophageal dissection, combined with a cervical esophageal blunt dissection and creation of an esophagogastrostomy anastomosis in the neck.

Recent technical innovations have made MR imaging a useful technique for imaging the pancreas. The potential impact of MR imaging on the management and outcome of cases can be determined only by controlled prospective comparative studies; however, these cannot be performed adequately until the normal and abnormal appearances of the pancreas on state-of-the-art MR images are understood. This pictorial essay is presented to further this intermediate goal.

Locoregional recurrence (LRR) is an important factor after pancreaticoduodenectomy (PD) for pancreatic cancer. Intraoperative radiation therapy (IORT) administered to the resection bed may improve local tumor control. We performed a retrospective analysis of patients who underwent PD at Thomas Jefferson University Hospital (TJUH) between 1995 and 2005 to identify patients who underwent resection with and without IORT. Data collected included age, gender, complications, margin status, stage, survival, and recurrence. Unadjusted analyses of the IORT and non-IORT groups were performed using Fisher’s chi-square method for discrete variables and Wilcoxon rank sum test for continuous variables. To account for biases in patient selection for IORT, a propensity score was calculated for each patient and adjusted statistical analyses were performed for survival and recurrence outcomes. Between January 1995 and November 2005, 122 patients underwent PD for periampullary tumors, including 99 pancreatic cancers. Of this group, 37 patients were treated with IORT, and there was adequate follow-up information for a group of 46 patients who underwent PD without IORT. The IORT group contained a higher percentage of Stage IIB or higher tumors (65%) than in the non-IORT group (39.1%), though differences in stage did not reach significance (P = .16). There was a nonsignificant decrease in the rate of LRR in patients who had IORT (39% non-IORT vs. 23% IORT, P = .19). The median survival time of patients who received IORT was 19.2 months, which was not significantly different than patients managed without IORT, 21.0 months (P = .78). In the propensity analyses, IORT did not significantly influence survival or recurrence after PD. IORT can be safely added to management approaches for resectable pancreatic cancer, with acceptable morbidity and mortality. IORT did not improve locoregional control and did not alter survival for patients with resected pancreatic cancer. IORT is an optional component of adjuvant chemoradiation for pancreatic cancer. In the future, IORT may be combined with novel therapeutic agents in the setting of a clinical trial in order to attempt to improve outcomes for patients with pancreatic cancer.

This study was designed to identify quantifiable parameters to track performance improvements brought about by the implementation of a critical pathway for complex alimentary tract surgery. Distal pancreatectomy is among the more complex general surgical procedures. This is primarily due to the possibility of blood loss from visceral vessels, splenic injury, and significant postoperative complications. The introduction of the laparoscopic approach to the distal pancreas has introduced a further level of surgical expertise required to fully address the clinical needs of this diverse patient population. Critical pathways have been one of the key tools used to achieve consistently excellent outcomes at high-quality, high-volume institutions. It remains to be determined if implementation of a critical pathway at an academic institution with prior moderate experience with distal pancreatectomy will result in performance gains and improved outcomes. Between January 1, 2003 and August 15, 2007, 111 patients underwent distal pancreatectomy. Forty patients underwent resection during the 34-month period before the implementation of a critical pathway on October 15, 2005 and 71 during the 20 months after pathway implementation. Patients undergoing both open and laparoscopic procedures were included. Peri- and postoperative parameters were analyzed retrospectively to identify those that could be used to track performance improvement and outcomes. The two groups were not significantly different with respect to age, sex, race, diagnosis, operative blood loss, or mean operative duration. Postoperative length of hospital stay was significantly shorter when comparing pre- to postpathway implementation (10.2 days versus 6.7 days, P ≤ 0.037). The rate of readmission to the hospital after discharge was significantly lower post pathway (25% versus 7%, P ≤ 0.027). Hospital costs were also reduced. Implementation of a critical pathway for a complex procedure can be demonstrated to improve short-term outcomes at an academic institution. This improvement can be quantified and tracked and has implications for better utilization of resources and overall cost containment while maintaining or improving upon an already high level of care.

Community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) infections are becoming increasingly frequent, and cutaneous disease with this organism is often seen in otherwise healthy organized sports participants. A case of CA-MRSA skin and soft tissue infection in a female collegiate basketball player is presented, and screening and management of her team is discussed. Interestingly, multiple MRSA strains were discovered on testing of the team, raising concern that the prevalence of colonization in this population may be high.

We present an unusual case of sarcoidosis in which the clinical presentation is best explained by an inflammatory mass in the region of the ampulla of Vater causing obstruction of the bile duct and pancreatic duct as well as intermittent duodenal obstruction. It is clear from previous reports that gastrointestinal exacerbations of sarcoidosis may occur during quiescent pulmonary disease. We are confident of the diagnosis because (1) the patient had a well-documented history of systemic sarcoidosis; (2) the obstruction responded to high-dose steroids promptly on two separate occasions; (3) biopsy of peripancreatic lymph nodes in the inflammatory mass was consistent with sarcoidosis; and (4) there was no clinical or radiographic evidence for Crohn's disease or any other granulomatous disorder. Our report indicates that small bowel obstruction must be added to the list of rare intra-abdominal complications of sarcoidosis.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are a heterogeneous collection of clonal disorders of bone marrow disorders that lead to clonal expansion and ineffective hematopoiesis. Patients with higher-risk MDS subtypes often experience rapid disease progression towards AML, facing a life expectancy of less than 1 year. AML remains incurable in the majority of adult patients. The physiopathology of these diseases involves impaired epigenetic regulation in the progression of MDS to AML and resistance to conventional treatment. Such epigenetic marks can be reversed by nucleoside analogs (NA) DNA methyltransferase inhibitors (DNMTis) such as azacitidine (AZA) and decitabine, currently the standard treatment for MDS, and histone tails modifiers histone deacetylase inhibitors (HDACis). These agents synergistically induce re-expression of silenced genes resulting in cell growth arrest, differentiation and apoptosis. Furthermore, we have demonstrated that synergistic effects of combining nucleosides analogs (e.g. fludarabine, AZA, cytarabine) with HDACIs both in vitro and in vivo relied also on mechanisms modulating activation of pro-survival NA-mediated NF-κB signaling. Based on this mechanism centered on NF-κB signaling, we analyzed several original transcriptional expression datasets related to the treatment of AZA or HDACis in AML cell lines, xenografts and MDS/AML patients. A list of possible repositioned drugs was predicted. Upon a detailed comparison among the drugs, Dexamethasone (DEX), an inexpensive medication sporadically used during MDS and AML therapy to treat fever, nausea and allergic reactions, stood out as supported by the following emanating results: 1) DEX could suppress the VEGFA gene set, STAT5 gene set and inflammatory cytokines, chemokines and their cognate receptors gene set in primary human bone marrow progenitor cells, which is significantly activated in MDS/AML patients resistant to AZA+HDACi treatment; 2) DEX could inhibit the alternative activated signaling molecules responsible for the resistance to AZA; 3) two clusters of aberrantly methylated (hypo and hyper) genes were examined significantly enriched in blasts from MDS patients comparing with healthy people, and DEX is able to “normalize” these genes' expression; 4) DEX could suppress the elevated target genes of P210 BCR-ABL gene fusion in MDS patients; and, importantly 5) DEX has a wide inhibitory effects on the NF-κB pathway-targeted cytokines, chemokines, and their modulators on human bone marrow CD34+ cells compared to untreated cells. To validate the repositioning performance of DEX, preliminary assays were performed where human leukemia cells were exposed to HDACi/NA, a situation where exists a marked reduction in the synergism because of strong NF-kB activation. In the presence of DEX, either the drugs alone or in combination displayed a significant increase in lethality, notably in the case of HDACi/NA. Importantly, co-administering HDACi/NA with DEX had a major impact on the outcome of the drug combination, notably since AML cells that remain alive after HDACi/NA treatment may constitute one of the main sources of chemo-resistance. This new concept is critically relevant for therapies involving NA and HDACIs. In this context, by adding DEX to the therapeutic intervention which results in almost 100% cell death, we may be directly affecting this small percentage of cells that display increased survival capacity, thereby reducing/delaying the probability of relapse. Citation Format: Hong Zhao, Rui Zhu, Jaime Mejia, Adriana E. Rosato, Swaminathan Iyer, Roberto R. Rosato. Drug repositioning improves synergistic interactions between HDAC inhibitors and nucleoside analogs in AML and MDS models. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr B11.

Background: Contact precautions are recommended to reduce the transmission of multidrug-resistant organisms. However, the optimal method for control of multidrug-resistant organisms remains unclear. Methods: A controlled trial was conducted in a medical intensive care unit. Phase 1 was a 3-month period of standard practice in which patients were placed in contact precautions per Centers for Disease Control and Prevention guidelines. In the second 3 months, phase 2, gloves were required for all patient contact, and no patients were placed in contact precautions. Results: Compliance with contact precautions in phase 1 versus universal gloving in phase 2 was 75.7% versus 87.0%, respectively (P , .001). Hand hygiene compliance before patient care was significantly higher in phase 1 when compared with phase 2 (18.7% vs 11.4%, respectively, P , .001). Hand hygiene compliance after patient care was 57.7% in phase 1 versus 52.5% in phase 2 (P 5 .011). Nosocomial infection rates per 1000 device-days in phase 1 versus phase 2 were as follows: bloodstream infection, 6.2 versus 14.1, respectively (P , .001); urinary tract infection, 4.3 versus 7.4, respectively (P , .001); and ventilatorassociated pneumonia, 0 versus 2.3, respectively (P , .001). There were no differences in vancomycin-resistant enterococci or methicillin-resistant Staphylococcus aureus acquisition in the 2 study phases; however, in both phases, the majority of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus conversions were clonal. Conclusion: Compliance with universal gloving was significantly greater than compliance with contact precautions. However, greater compliance with hand hygiene was observed in the contact precautions phase. Measures must be in place to both increase and sustain hand hygiene compliance so as to minimize the risk of nosocomial cross transmission before reevaluating the concept of replacing contact precautions with universal gloving. (Am J Infect Control 2007;35:650-5.)

The following is a case report of left breast necrosis following coronary artery bypass grafting (CABG) in a woman previously treated for a stage I breast carcinoma. To our knowledge this is the first such report of its kind in the literature. We believe that breast tumor extirpation and internal mammary artery utilization in combination are not sufficient insults on the vascularity of the breast to account for necrosis, but rather we feel that a variety of conditions are necessary for vascular compromise to occur.

Nosocomial bloodstream infections (BSIs) are important causes of morbidity and mortality, and coagulase-negative staphylococci (CNS) are the most common pathogens. Second generation, central venous catheters impregnated with chlorhexidine and silver sulfadiazine were recently introduced for the prevention of catheter-related infections and appear to be effective in reducing the incidence of both colonization and catheter related BSI. 1 However, the potential for emergence to biocides has been a concern. A recent study evaluating the in vitro susceptibility of epidemiologically important pathogens found a statistically significant inverse correlation between intensity of chlorhexidine use and the overall susceptibility of all organisms tested to this agent. 2 Because of an increase in the incidence of CNS BSIs in our 12-bed medical intensive care unit (MICU) from 6.6/1000 catheter days in 2000 to 12.7/1000 catheter days in 2003, we evaluated changes in the epidemiology and susceptibility of CNS following the

Bile duct injury is perhaps the most feared complication of laparoscopic cholecystectomy. The focus of this study was on the immediate and short-term outcome of patients who have undergone repair of major bile duct injuries with respect to hospital stay, perioperative interventions, and reoperations. The records of patients who underwent surgery at three academic hospitals in Philadelphia (Hospital of the University of Pennsylvania, Thomas Jefferson University Hospital, and Graduate Hospital) from 1990 to 1995 for repair of a major biliary injury following laparoscopic cholecystectomy were reviewed. A major biliary injury was defined as any disruption (including ligation, avulsion, or resection) of the extrahepatic biliary system. Small biliary leaks not requiring surgery were excluded. Thirty-two patients sustained major bile duct injuries. The injury was recognized immediately in 10 patients. The remaining 22 patients had pain (59%), jaundice (50%), and/or fever (32%) as the symptom heralding the injury. Bismuth classification was as follows: 13% of patients were class I, 63% were class II, 7% were class III, 7% were class IV, and 10% were class V. Biliary reconstruction included a Roux-en-Y hepaticojejunostomy in 30 patients and two were primary repairs. There was one postoperative death from multiorgan system failure. The mean length of hospital stay after repair was 17 +/- 8 days. Over a mean follow-up period of 11.5 +/- 10.5 months, 11 patients (38%) required 19 emergency readmissions, most commonly for cholangitis. Five patients (17%) required postoperative balloon dilatation for biliary stricture. At follow-up 18 patients (62.0%) remain asymptomatic with normal liver function, eight (28%) are experiencing episodic cholangitis, and three (10%) are asymptomatic with persistently elevated liver function values. The consequences of a major biliary tract injury following laparoscopic cholecystectomy include a complex operative repair resulting in a lengthy postoperative stay with an increased risk of death, an excessive number of perioperative diagnostic and therapeutic studies, frequent readmissions (often as emergencies), and a lifelong risk of restricture. The "cost" to these patients remains enormous.

This study evaluated the ability of laparoscopic ultrasonography to detect, localize, and characterize focal liver masses. Laparoscopic ultrasonography and CT portography of the liver were performed in 13 patients with known or suspected malignancy. Laparoscopic ultrasonography directly influenced surgical management in four (31%) cases ; three by detection of small focal masses and one by exclusion of masses suspected on CT portography. Laparoscopic ultrasonography provide guidance for biopsy or added important anatomic information in three cases. Laparoscopic ultrasonography was complementary to CT portography but added no additional information in three cases, and it failed to provide any information in two cases. Laparoscopic ultrasonography was falsely negative in one case. In this preliminary series, laparoscopic ultrasonography assisted surgeons in critical decision-making by either providing important new information, clarifying questionable areas, or complementing CT pornography.

To assess the efficacy of perioperative implantation of iridium-192 for stage I and II breast cancer.The authors retrospectively reviewed findings from 655 patients with stage I and II cancer treated with conservative surgery and Ir-192 implantation between 1982 and 1992. Hollow plastic tubes were placed in the tumor bed as a single- or double-plane implant at lumpectomy. Ribbons with Ir-192 seeds were inserted into the tubes 4-6 hours later. The Ir-192 was left in place for approximately 50 hours. External-beam irradiation was given to the whole breast 10-14 days later.Follow-up ranged from 2 to 146 months. The local control at 10 years for stage I and II disease was 93% and 87%, respectively. The 10-year actuarial survival rate was 92% +/- 1 for stage I disease and 72% +/- 4 for stage II disease. The rate of survival with no evidence of disease for stage I and II disease combined was 82% +/- 1 at 5 years and 75% +/- 3 at 10 years.Perioperative implantation produced excellent local control equal to that with electron-beam therapy.

OBJECTIVE: Chronic stimulation of a cardiomyoplasty was combined with low-dose infusion of heparin into the arterial supply of the cardiomyoplasty in order to determine if latissimus-derived collateral blood flow could be further enhanced. SUMMARY BACKGROUND DATA: Acute and chronic stimulation of a latissimus dorsi cardiomyoplasty increased extramyocardial collateral blood flow to 35 +/- 9% and 27 +/- 5%, respectively, of normal myocardial blood flow. METHODS: A model of coronary artery disease was created with an ameroid constrictor in goats, and a cardiomyoplasty was performed. Heparin (15 to 50 U/h) was delivered into the left subclavian artery for a period of 4 weeks. Simultaneously, the latissimus dorsi was chronically stimulated at 2 Hz. RESULTS: Chronic ischemic myocardium received a collateral flow per gram from the skeletal muscle equivalent to 11.8 +/- 5.2% of the blood flow to normal myocardium. The extramyocardial collateral flow correlated with the latissimus muscle flow (r = 0.72). CONCLUSIONS: Enhancement of extramyocardial collateral flow was not found with heparin treatment. In view of the correlation of extra-coronary collateral flow with latissimus muscle flow, the lack of a heparin effect may have been due to low latissimus blood flow. These results suggest that extramyocardial collateral blood flow to the myocardium is highest if the blood flow to the latissimus dorsi muscle is maintained.

From 1981 to 1987, 81 patients with localized, unresectable carcinoma of the pancreas were treated at Thomas Jefferson University Hospital with a combination of intraoperative Iodine-125 implantation, external beam radiation, and peri-operative systemic chemotherapy. Fifty patients had Stage II disease and 31 patients had Stage III disease. Radioactive Iodine-125 seeds were implanted intraoperatively into the tumor to deliver a minimum peripheral dose of 12,000 cGy over one year. This was followed by external beam radiation (50-55 Gy) and systemic chemotherapy (5-FU, Mitomycin-C +/- CCNU). Incidence of peri-operative mortality was 5% (4/81). Early morbidity was observed in 34% of patients and late complications in 32%. A median survival of 12 months and 2- and 5-year survival rates of 21% and 7% were observed. The determinate 2- and 5-year survival rates were 28% and 13%, respectively. The overall 2- and 5-year survival rates with Stage II disease were 27% and 8% and for Stage III disease, 13% and 3%, respectively (p less than 0.05). The determinate 2- and 5-year survival rates were 34% and 19% for Stage II and 19% and 5% for Stage III disease, respectively (p = 0.08). Local control of disease was achieved in 71% of patients. This combined modality approach appears to have achieved satisfactory local control of primary cancer and long term survival of selected patients.

Energy and spatial resolution of a HgI2 microstrip detector with six differently spaced (0.05 mm through 1.0 mm interstrip distances) microstrips, have been tested by using a 241Am source by an analog readout and a centroid finding method, with the aim of setting up a high-efficiency position-sensitive detector with spatial resolution of ≈ 50 μm for X-ray energies of ≈ 30 keV, to inserted in a Bragg X-ray spectrometer. Analog readout was preferred with respect to improving the spatial resolution by reducing the strip size, in order to not increase the number of readout channels. The energy resolution observed at a single strip, although worse than the one reported in the literature for HgI2 spectrometers, would allow using the centroid finding technique, but only the regions below the strips appear to be active for detection, i.e. the device is equivalent to one with digital readout for position identification. Thus a microstrip detector with a surface resistive layer between the strips is proposed, in order to enhance the active region of detection and to reach the required spatial resolution. Calculations performed by taking into account the various sources of noise allow getting optimized values for the interstrip distance and resistance.