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Seroma is a common problem following abdominoplasty surgery. Both compressive garments with drains and progressive tension sutures have their advocates to minimise seroma formation. This is a retrospective study in which patients underwent an identical surgical procedure, except for use of drains and garments in comparison to progressive tension sutures between 2005 and 2020. Two hundred thirty-two patients were included in the study 61 in the drains and garment group (DG group), and 171 with progressive tension sutures (PTS group) alone. There was a lower incidence of seroma formation in the PTS group (X

Background: Patients receiving in-centre haemodialysis (ICHD) are highly vulnerable to COVID-19. Objective: We created a quality improvement (QI) project aimed to eliminate outbreaks of COVID-19 in haemodialysis units and evaluated the utility of surveillance rRT-PCR test and SARS-CoV-2 serum antibodies for prompt identification of patients infected with COVID-19. Methods: A multifaceted QI programme including a bundle of infection prevention control (IPC) measures was implemented across 5 ICHD units following the first wave of the pandemic in June 2020. Primary outcomes evaluated before and after QI implementation were incidence of outbreaks and severe COVID-19 illness defined as COVID-19-related death or hospitalization. Secondary outcomes included the proportion of patients identified in the pre-symptomatic/asymptomatic phase on surveillance rRT-PCR screening and the incidence and longevity of SARS-CoV-2 antibody response. Results: Following the implementation of the QI project, there were no further outbreaks. Pre- and post-implementation comparison showed a significant reduction in COVID-19-related mortality and hospitalization (26 vs. 13 events, respectively, p < 0.001). Surveillance rRT-PCR screening identified 39 asymptomatic or pre-symptomatic cases out of a total of 59 rRT-PCR-positive patients (39/59, 66%). SARS-CoV-2 antibody levels were detected in 72/74 (97%) rRT-PCR-positive patients. Amongst rRT-PCR-positive patients diagnosed before August 2020, 96% had detectable antibodies until January 2021 (days from the rRT-PCR test to last antibody testing, 245–280). Conclusions: Systematic implementation of a bundle of IPC measures using QI methodology and surveillance rRT-PCR eliminated outbreaks in HD facilities. Most HD patients mount and sustain antibody response to COVID-19 for over 8 months.

There are numerous measuring systems that practitioners employ as part of their presurgical assessment for breast implant surgery. These range from direct measurements of patients using a tape measure, to assessment of standardized photographs and 3-dimensional scanning technologies. This personal view describes the authors system, developed over 20 years. The data yielded have assisted in assessing breast symmetry, ptosis, and match of implant to patient, with proven benefits for managing patient outcomes and expectations. It is simple, rapid to undertake, and requires inexpensive measuring equipment to provide useful data.

The importance of measuring breast firmness reproducibly to monitor postsurgical progress has been appreciated for many years. This study ascertains whether a durometer can be used to quantify capsular contraction and to provide an objective, reproducible measure of fibrosis around an implant. Patients with clinically detected Baker 3 or 4 capsules following breast augmentation underwent firmness measurements using a durometer prior to corrective surgery. Durometry was undertaken on both breasts by an operator who was blinded to the clinical diagnosis. Firmness measurements were taken in each breast quadrant and directly over the nipple-areolar complex on each side. In the study, 16 patients were included. Capsules presented 16 to 714 weeks following surgery (mean 217, standard deviation (STD) 205.4 weeks). Differences in pressure were demonstrated in all quadrants of the breast and at the nipple-areolar complex except the lower inner quadrant. All significant differences demonstrated a higher pressure in the encapsulated breast. The mean pressure in an encapsulated breast was 0.66 kPa (STD 0.25) and 0.46 kPa (STD 0.16) in the normal breast. The durometer can reproducibly describe changes in pressure associated with capsular contraction compared with the contralateral breast. It provides a means of objectively describing capsular contraction following breast augmentation surgery for research and patient care.

Summary: COVID-19 infection rates in haemodialysis (HD) facilities are extremely high and are attributed to the high burden of comorbidities of HD patients coupled with inability to self-isolate needing thrice weekly attendance for HD treatment. Healthcare workers (HCW) in HD facilities are at risk of occupational exposure to COVID-19. Infection prevention control (IPC) measures were introduced during the pandemic aiming at reducing transmission and occupational exposure risk of COVID-19. Here we describe the results of our baseline and follow up occupational exposure audit in a renal centre in the North West of England following the implementation of a multifaceted IPC bundle.

Galiximab is a primatized monoclonal antibody that targets CD80 expressed on malignant B cells and is being studied in the clinic as a potential treatment for follicular NHL. We have recently reported that galiximab signals B-NHL cells in vitro and inhibits cell growth and sensitizes resistant tumor cells to apoptosis by chemotherapeutic drugs. This study was designed to validate the in vitro findings in in vivo in mice. Thus, we examined in vivo the antitumor activity of galiximab used alone and in combination with chemotherapeutic agents in SCID mice bearing human lymphoma xenografts. The in vivo antitumor effects of galiximab used alone and in combination with fludarabine or doxorubicin were determined in solid and disseminated human B-lymphoma tumors grown in SCID mice. Galiximab monotherapy in vivo demonstrated significant antitumor activity in a Raji lymphoma solid tumor model and in an SKW disseminated lymphoma tumor model. There was significant inhibition in tumor growth and prolongation of survival. In vitro, galiximab sensitized Raji cells to apoptosis by both fludarabine and doxorubicin. Tumor growth inhibition was significantly enhanced when the mice were treated with the combination of galiximab and fludarabine. These findings support the potential clinical application of galiximab in combination with chemotherapeutic drugs for the treatment of CD80-expressing hematological malignancies.

The measurement of soft-tissue firmness has many potential applications in medical practice. This study reports a user-friendly, novel device that is capable of measuring changes in soft-tissue firmness in a reproducible manner. The study reports the development of the equipment and how it has been applied to breast implant surgery. The device was tested for both intra- and inter-observer variability on an in vitro model, using a breast implant. Once reproducibility was confirmed, breast firmness was measured on a series of patients who underwent sub-fascial breast augmentation (n = 50) to examine how it varied post-operatively. Firmness in the upper half of the breast increased to a maximum level two weeks post-surgery (0.44–0.61 Pa), reducing to pre-operative levels by 6 weeks (0.37–0.54 Pa). There was no further significant change at 12 weeks. Firmness in the nipple areolar complex (NAC) and at the lower outer quadrant (LOQ) followed a similar pattern, but remained firmer at 12 weeks. We interpret these patterns as implying that measurements taken at the upper half of the breast are indicative of post-operative oedema, whereas those at the NAC and LOQ represent changes in firmness produced by the breast implant composite. We consider the potential for this novel device in the measurement of soft-tissue firmness in aesthetic breast surgery and would encourage other researchers to explore novel applications. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Therapeutic antibodies directed against the type 1 insulin-like growth factor receptor (IGF-1R) have recently gained significant momentum in the clinic because of preliminary data generated in human patients with cancer. These antibodies inhibit ligand-mediated activation of IGF-1R and the resulting down-stream signaling cascade. Here we generated a panel of antibodies against IGF-1R and screened them for their ability to block the binding of both IGF-1 and IGF-2 at escalating ligand concentrations (>1 μm) to investigate allosteric versus competitive blocking mechanisms. Four distinct inhibitory classes were found as follows: 1) allosteric IGF-1 blockers, 2) allosteric IGF-2 blockers, 3) allosteric IGF-1 and IGF-2 blockers, and 4) competitive IGF-1 and IGF-2 blockers. The epitopes of representative antibodies from each of these classes were mapped using a purified IGF-1R library containing 64 mutations. Most of these antibodies bound overlapping surfaces on the cysteine-rich repeat and L2 domains. One class of allosteric IGF-1 and IGF-2 blocker was identified that bound a separate epitope on the outer surface of the FnIII-1 domain. Using various biophysical techniques, we show that the dual IGF blockers inhibit ligand binding using a spectrum of mechanisms ranging from highly allosteric to purely competitive. Binding of IGF-1 or the inhibitory antibodies was associated with conformational changes in IGF-1R, linked to the ordering of dynamic or unstructured regions of the receptor. These results suggest IGF-1R uses disorder/order within its polypeptide sequence to regulate its activity. Interestingly, the activity of representative allosteric and competitive inhibitors on H322M tumor cell growth in vitro was reflective of their individual ligand-blocking properties. Many of the antibodies in the clinic likely adopt one of the inhibitory mechanisms described here, and the outcome of future clinical studies may reveal whether a particular inhibitory mechanism leads to optimal clinical efficacy.

Abstract 4873 The non-Hodgkin's lymphomas (NHLs) are a group of lymphoproliferative malignancies with divergent clinical courses. Although the NHLs have historically been treated with radiation therapy and/or chemotherapy, the standard of care has evolved to incorporate the use of rituximab, a mAb that is directed against the CD20 antigen expressed on the surface of transformed B-lymphocytes. However, there are subsets of patients who do not initially respond or become refractory to further treatments. Hence, there is a need for new therapeutic strategies for these patients. CD80 is constitutively expressed on the surface of many B-cell lymphomas. When cell-surface CD80 is cross-linked with anti-CD80 antibodies, cell proliferation is inhibited, proapoptotic molecules are upregulated and antibody-dependent cell cytotoxicity (ADCC) is induced. These findings provide the rationale for using an anti-CD80 mAb to treat lymphoma. Galiximab is a primatized monoclonal antibody that targets CD80 expressed on malignant B cells and is being studied in the clinic as a potential treatment for follicular NHL. Galiximab is a primatized anti-CD80 mAb that has been tested as monotherapy in phase I/II clinical trials involving patients with relapsed/refractory follicular lymphoma (FL), producing an overall response rate of 11% and tumor reductions in 46% of patients. In a recent phase I/II clinical trial involving patients with relapsed or refractory FL, combined therapy with galiximab and rituximab yielded an overall response rate of 66% and a median progression-free survival of 12.1 months at the recommended phase II dose of galiximab (500 mg/m2). We have recently reported that galiximab signals B-NHL cells in vitro and inhibits cell growth and sensitizes resistance tumor cells to apoptosis by chemotherapeutic drugs. The present finding was designed to validate the in vitro findings in in vivo in mice. Thus, we examined in vivo the anti-tumor activity of galiximab used alone and in combination with chemotherapeutic agents in SCID mice bearing human lymphoma xenografts. The in vivo anti-tumor effects of galiximab used alone and in combination with fludarabine or doxorubicin were determined in solid and disseminated human B-lymphoma tumors grown in SCID mice. Galiximab monotherapy in vivo demonstrated significant anti-tumor activity in a Raji lymphoma solid tumor model and in an SKW disseminated lymphoma tumor model. There was significant inhibition in tumor growth and prolongation of survival in both models. In vitro, galiximab sensitized Raji cells to apoptosis by both fludarabine and doxorubicin. Tumor growth inhibition was significantly enhanced when the mice were treated with the combination of galiximab and fludarabine. These findings support the potential clinical application of galiximab in combination with chemotherapeutic drugs for the treatment of CD80-expressing hematologic malignancies. Disclosures: No relevant conflicts of interest to declare.

3040 Background: Galiximab, a primatized monoclonal antibody that binds with high affinity to CD80 and mediates antibody- dependent, cell-mediated cytotoxicity in vitro, is currently under investigation for the treatment of follicular non-Hodgkin’s lymphoma (NHL). In a phase I/II monotherapy study, galiximab produced an overall response rate of 11%, and tumor reductions were observed in 46% of patients. Initial clinical trials also demonstrate that galiximab is well tolerated and suggest that combining galiximab with rituximab (anti-CD20) provides clinical benefit. These results are consistent with preclinical studies in murine lymphoma xenograft model systems, which demonstrate the superiority of combination therapy. Methods: To further define the therapeutic potential of galiximab, the Raji subcutaneous and the SKW disseminated lymphoma murine xenograft models were used to define the in vivo efficacy of galiximab alone or in combination with fludarabine or doxorubicin. Similar studies were performed with rituximab. Results: In the Raji model, both galiximab and rituximab exhibited maximal inhibition of the growth of preestablished (150-mg) tumors at a dose of 3 mg/kg/wk. Interestingly, higher doses of galiximab (but not rituximab) showed reduced inhibition. Galiximab (3 mg/kg/wk) inhibited tumor growth alone (P No significant financial relationships to disclose.