Septic Failure Research Articles

Impact of Age on Septic Shock and Multiple Organ Failure

Impact of Age on Septic Shock and Multiple Organ Failure

Streptococcal M1 protein induces hyporesponsiveness and cytokine release from human arteries in a fibrinogen-dependent manner: a translational study

BackgroundStreptococcus pyogenes is a Gram positive bacterial species commonly involved in sepsis. Invasive strains express virulence factors such as the M1 protein. M1 protein forms complexes with fibrinogen leading to a cytokine storm in plasma contributing to the development of septic shock and organ failure. In experimental animals M1 protein causes vascular nitric oxide production and hyporesponsiveness to pressors, but it is not known whether it affects the human vascular wall.MethodsHuman omental arteries obtained during surgery were incubated in vitro with M1 protein or lipopolysaccharide (LPS) as positive control, with or without plasma. After 48 h, contractile response to noradrenaline was measured, and levels of nitrite/nitrate and the cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in the incubation medium were measured. A second set of arteries were incubated with or without main components of plasma (immunoglobulin G, albumin or fibrinogen), in the presence of M1 protein followed by cytokine measurement.ResultsArtery segments incubated with M1 protein and plasma contracted weaker in response to noradrenaline, and levels of IL-6 and IL-8 were significantly higher compared to after incubation with M1 protein alone. Incubation with M1 protein and fibrinogen resulted in elevated levels of IL-6 and IL-8, while incubation with M1 protein and albumin or immunoglobulin G did not affect the levels. Neither any of the other cytokines nor nitrite/nitrate was detected in the medium in any of the incubation conditions.ConclusionsThe study shows that M1 protein of Streptococcus pyogenes has a direct effect on the human vascular wall in the presence of plasma, demonstrated both as a diminished contractile response to noradrenaline and increased cytokine production. The effect of plasma was attributed to fibrinogen. The findings suggest that M1 protein contributes to the development of septic shock through impairment of the contractility of the vascular wall.

Proinflammatory biomarkers' level and functional genetic polymorphisms in periprosthetic joint infection

ObjectiveThe aims of this study were 1) to identify the level of inflammatory biomarkers interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-17, C-reactive protein (CRP), granulocyte colony-stimulating factor (GCSF), ferritin, and tumor necrosis factor (TNF)-α in serum and synovial fluid samples of patients who underwent revision arthroplasty surgery; 2) to establish the relationship between serum and synovial fluid levels; 3) to determine if any of the 11 genetic polymorphisms of TNFα, IL-1, IL-6, IL-8, IL-17, and GCSF on the encoding genes was associated with periprosthetic joint infection (PJI). MethodsSynovial fluid and serum was collected from 88 patients who underwent revision arthroplasty surgery. The Musculoskeletal Infection Society definition was used to classify these patients into 2 groups: 36 PJIs and 52 aseptic failures. Synovial fluid and serum samples were tested for 9 biomarkers using a micro enzyme-linked immunosorbent assay. Genetic polymorphisms were evaluated with polymerase chain reaction and restriction endonuclease analysis. ResultsSynovial fluid-derived IL-1α, IL-1β, IL-8, IL-17, CRP, GCSF, TNFα, and serum-derived IL-6, IL-17, ferritin, CRP were found suitable to classify PJI and aseptic failure. In addition, IL-17 and CRP levels demonstrated a positive correlation between synovial fluid and serum. TNFα-238, IL6-174, GCSF3R, and IL1 RN-VNTR genetic polymorphisms occurred more frequently in individuals with septic failure. ConclusionSignificant differences between the two groups were observed in the functional polymorphisms of the genes encoding the cytokines investigated. These differences could be interpreted as indicating that there is an association between PJI and genetic polymorphisms. Level of evidenceLevel III, diagnostic study.

Gastrointestinal tuberculosis following renal transplantation accompanied with septic shock and acute respiratory distress syndrome: a survival case presentation

BackgroundPost-transplant tuberculosis (PTTB) is a serious opportunistic infection in renal graft recipients with a 30-70 fold higher incidence compared to the general population. PTTB occurs most frequently within the first years after transplantation, manifesting as pulmonary or disseminated TB. Gastrointestinal TB (GITB) is a rare and potentially lethal manifestation of PTTB and may show delayed onset in renal transplant recipients due to the use of lower doses of immunosuppressants. Further, non-specificity of symptoms and the common occurrence of GI disorders in transplant recipients may delay diagnosis of GITB.Case presentationHere we report a rare survival case of isolated GITB in a renal transplant recipient, occurring seven years after transplantation. The patient’s condition was complicated by severe sepsis with positive blood culture Staphylococcus haemolyticus, septic shock, multiple organ failure including acute respiratory distress syndrome (ARDS) and acute renal failure, requiring mechanical ventilation, vasopressor circulatory support and intermittent hemodialysis. Furthermore, nosocomial infections such as invasive aspergillosis and Pseudomonas aeruginosa occurred during hospitalization. Antituberculosis therapy (rifampicin, isoniazid, ethambutol and pyrazinamide) was initiated upon Mycobacterium confirmation. Moreover, treatment with voriconazole due to the Aspergillus flavus and meropenem due to the Pseudomonas aeruginosa was initiated, the former necessitating discontinuation of rifampicin. After 34 days, the patient was weaned from mechanical ventilation and was discharged to the pulmonary ward, followed by complete recovery.ConclusionThis case offers a guideline for the clinical management towards survival of GITB in transplant patients, complicated by septic shock and multiple organ failure, including acute renal injury and ARDS.

Knee arthrodesis versus above-the-knee amputation after septic failure of revision total knee arthroplasty: comparison of functional outcome and complication rates

BackgroundAfter septic failure of total knee arthroplasty (TKA) and multiple revision operations resulting in impaired function, bone and/or soft-tissue damage a reconstruction with a revision arthroplasty might be impossible. Salvage procedures to regain mobility and quality of life are an above-the-knee amputation or knee arthrodesis. The decision process for the patient and surgeon is difficult and data comparing arthrodesis versus amputation in terms of function and quality of life are scarce. The purpose of this study was to analyse and compare the specific complications, functional outcome and quality of life of above-the-knee amputation (AKA) and modular knee-arthrodesis (MKA) after septic failure of total knee arthroplasty.MethodsEighty-one patients treated with MKA and 32 patients treated with AKA after septic failure of TKA between 2003 and 2012 were included in this cohort study. Demographic data, comorbidities, pathogens and complications such as re-infection, implant-failure or revision surgeries were recorded in 55MKA and 20AKA patients. Functional outcome with use of the Lower-Extremity-Functional-Score (LEFS) and the patients reported general health status (SF-12-questionnaire) was recorded after a mean interval of 55 months.ResultsA major complication occurred in more than one-third of the cases after MKA and AKA, whereas recurrence of infection was with 22% after MKA and 35% after AKA the most common complication. Patients with AKA and MKA showed a comparable functional outcome with a mean LEFS score of 37 and 28 respectively (p = 0.181). Correspondingly, a comparable physical quality of life with a mean physical SF-12 of 36 for AKA patients and a mean score of 30 for MKA patients was observed (p = 0.080). Notably, ten AKA patients that could be fitted with a microprocessor-controlled-knee-joint demonstrated with a mean LEFS of 56 a significantly better functional outcome than other amputee patients (p < 0.01) or MKA patients (p < 0.01).ConclusionNaturally, the decision process for the treatment of desolate situations of septic failures following revision knee arthroplasty is depending on various factors. Nevertheless, the amputation should be considered as an option in patients with a good physical and mental condition.

Two-stage knee arthrodesis with a modular intramedullary nail due to septic failure of revision total knee arthroplasty with extensor mechanism deficiency

BackgroundPeriprosthetic joint infection is a serious complication and reconstruction after failed revision total knee arthroplasty with significant bone loss and compromised soft-tissues can be challenging. Objective of this study was to assess clinical and functional results, implant survival and infection recurrence rates in patients treated with two-stage arthrodesis after failed revision TKA with extensor mechanism deficiencies due to PJI, and to identify the factors that affect outcomes after surgery. MethodsThirty seven patients with PJI treated within a two-stage exchange and reimplantation of an arthrodesis nail between 2008 and 2014 were included. Systemic and local risk factors were graded preoperatively according to McPherson et al. All patients were treated according to a structured treatment algorithm. Clinical and functional evaluation was performed using the Oxford Knee Score and the Visual Analogue Scale. ResultsThirty two of 37 patients (86.5%) were graded as free of infection. Five patients (13.5%) had recurrent infection after arthrodesis with the need of revision surgery. Mean leg-length discrepancy was 2.2cm. The mean VAS for pain was three, the mean Oxford Knee Score was 38±9. Total implant survival at a 74month follow-up was 74.3% (95% CI: 45.4 to 91.1%), as determined by Kaplan–Meier survival curves. Local McPherson Score, as well as number of revisions was found to be of significant influence to the survival rate. ConclusionsSeptic failure of revision knee arthroplasty can be effectively treated with two-stage arthrodesis using a modular intramedullary nail, providing a stable and painless limb with satisfactory functional results and acceptable infection eradication rates.

Red blood cell transfusion in the resuscitation of septic patients with hematological malignancies

BackgroundIndications for red blood cell (RBC) transfusion in septic acute circulatory failure remain unclear. We addressed the practices and the prognostic impact of RBC transfusion in the early resuscitation of severe sepsis and septic shock in patients with hematological malignancies.MethodsWe performed a retrospective analysis of a prospectively collected database of patients with hematological malignancies who required intensive care unit (ICU) admission in 2010–2011. Patients with a main admission diagnosis of severe sepsis or septic shock were included in the present study. We assessed RBC transfusion during the first two days as part of initial resuscitation.ResultsAmong the 1011 patients of the primary cohort, 631 (62.4%) were admitted to the ICU for severe sepsis (55%) or septic shock (45%). Among them, 210 (33.3%) patients received a median of 2 [interquartile 1–3] packed red cells during the first 48 h. Hemoglobin levels were lower in transfused patients at days 1 and 2 and became similar to those of non-transfused patients at day 3. Early RBC transfusion was more likely in patients with myeloid neoplasms and neutropenia. Transfused patients displayed more severe presentations as assessed by higher admission SOFA scores and blood lactate levels and the further requirements for organ failure supports. RBC transfusion within the first two days was associated with higher day 7 (20.5 vs. 13.3%, p = 0.02), in-ICU (39 vs. 25.2%, p < 0.001) and in-hospital (51 vs. 36.6%, p < 0.001) mortality rates. RBC transfusion remained independently associated with increased in-hospital mortality in multivariate logistic regression (OR 1.52 [1.03–2.26], p = 0.03) and propensity score-adjusted (OR 1.64 [1.05–2.57], p = 0.03) analysis.ConclusionsRBC transfusion is commonly used in the early resuscitation of septic patients with hematological malignancies. Although it was preferentially provided to the most severe patients, we found it possibly associated with an increased risk of death.

Role of mitral valve repair in active infective endocarditis: long term results

BackgroundAlthough mitral valve repair is at present the technique of choice in mitral regurgitation (MR) due to degenerative valve disease, long term results in patients with active mitral infective endocarditis (IE) are still under evaluation.MethodsIn the study were included 34 consecutive patients (22 males; mean age, 60 years; range 32–84 years) referred to our institution between January 1, 2005 to December 31, 2011 who were treated with valve repair for mitral valve (MV) active infective endocarditis. Eighteen patients underwent isolated MV repair. Aortic valve replacement and respectively repair were performed in 9 and 2 patients with concomitant aortic involvement. Blood cultures were positive in 30 (17 Staphylococcus, 13 Streptococcus, 1 g negative, 2 enterococcus).ResultsFour patients died during hospital stay (11%) due to multi system organ failure as a consequence of severe septic shock (2 patients), cardiogenic shock (1 case) and respiratory failure (1 patient). At an average follow up of 48 months in patients discharged alive from hospital survival was 96.7% (29 out of 30). None developed more than mild- to moderate mitral valve regurgitation during follow-up and we found a significant improvement in functional capacity and left ventricular ejection fraction associated with a significant decrease of pulmonary artery pressure. The only recurrence of endocarditis occurred in a drug addict patient.ConclusionsPresent investigation suggest that in patients with active mitral valve endocarditis MV repair, when technically feasible, is associated with a favorable clinical long term outcome. None of the patients alive at the end of follow-up developed severe mitral regurgitation. Moreover mortality and reinfection rate are uncommon and functional improvement.

Streptococcus G leading to septic abortion and multiple organ failure

The authors report a patient admitted at 12 weeks of pregnancy with an acute infectious syndrome, leading to abortion, sepsis, and multiple organ failure. Admission to intensive care unit (ICU) was needed after curettage for incomplete abortion complicated by uterine atony, hemorrhage, and septic shock. The patient had multiple organ failure and required non-invasive ventilation. Hemoculture showed streptococcus G bacteremia. She had no evidence of concurrent infection, mainly genital or urinary, except amygdalitis few days before. Hematogenous spread to the gestational sac could have possibly been the cause of her sepsis. Streptococcus G infection during pregnancy can lead to severe consequences.

Septic Shock and Multiple Organ Failure : Treatment with Cytokine Removal Continous Hemofiltration

Septic Shock and Multiple Organ Failure : Treatment with Cytokine Removal Continous Hemofiltration

Traumatic Perforation of the Small Intestine in General Surgery of the CHU Gabriel Tour&amp;#233;

Goal: To determine hospital frequency, to describe the clinical and therapeutic aspects and to determine the prognosis. Patients and Methods: This was a retrospective and prospective study carried out in the General Surgery Department from 1 January 1999 to 31 December 2015. Inclusion criteria: 1) open or closed trauma of the abdomen with perforation of the small bowel; 2) clinical examination (abdominal pain, vomiting, fever, abdominal contracture, evisceration, intraoperative findings); 3) paraclinical examinations: pneumoperitoneum on the abdominal X-ray without preparation (ASP) and CT scan. Exclusion Criteria: Abdominal trauma without perforation of the small bowel. We selected 128 patients operated for traumatic perforation of the small bowel. The data was entered and analyzed using Word, Excel 2007 and Statistical Package and Social Science Windows 16.0. The statistical analysis consisted in the calculation of the different frequencies of the variables studied. We used the Khi2 test with significance level P < 0.05. Results: We recorded 119 men versus 9 women and the sex ratio was 13.22. The mean age was 25 years with extremes varying between 15 and 70 years. The majority of patients 57.7% (74 cases) came from the capital, 46.1% (59 cases) were workers, 26.6% (34 cases) of the students. The average time to admission was 29 hours. The main etiologies were road traffic accidents 36.7% (47 cases), stabbing 21.9% (28 cases), firearm 14.8% (19 cases), and sports accidents 10.1% (13 cases). The main clinical signs were abdominal pain 48.44% (62 cases), abdominal contracture 60% (76 cases), disappearance of pre-liver dullness 66.36% (84 cases), and Douglas painful 74.4% (94 cases). The abdominal X-ray without preparation (A.S.P) allowed to objectify a pneumoperitoneum in 45.31% and the scanner a liquid effusion in 45.31% with the associated lesions in 37.5% (48 cases). The surgical treatment consisted of 60.15% suture excision (77 cases), 25% anastomosis resection (32 cases) and a 15% stoma (19 cases). The average length of hospital stay was 9 days with extremes of 1 to 60 days. The morbidity was 10.15% at the site of surgical site (OS) infection 17.4% (8 cases), postoperative peritonitis 3.1% (4 cases) and evisceration 0.8% (1 case). Mortality was 17.18% due to septic shock and multivisceral failure. Conclusion: Traumatic perforation of the small bowel is an emergency. Young people are more victims. The prognosis depends on the speed of diagnosis and management. Emphasis should be placed on prevention.

Pelvic Abscess with Initial Presentation of Crohn’s Disease in Pregnancy Leading to Maternal Sepsis

Background: A new diagnosis of Crohn disease during pregnancy is uncommon. Intra-abdominal abscess as an initial feature of Crohn disease during pregnancy is rare. Case: A 26-year-old healthy primigravida woman at 33 weeks of gestation presented with abdominal pain and an abdominal mass. Labor was induced at 37 weeks to expedite postpartum evaluation. On postpartum day 2 she developed septic shock and multiorgan failure. Emergent exploratory laparotomy revealed an intra-abdominal abscess involving the right colon and terminal ileum. Pathology was consistent with Crohn’s disease. Conclusion: Intra-abdominal abscess from Crohn’s disease is a rare occurrence during pregnancy and may be associated with significant maternal morbidity. When diagnosis in the postpartum period is uncertain and the differential diagnosis includes Crohn’s disease or abscess, early postpartum evaluation may prevent complications.

Knee arthrodesis by the Ilizarov method in the treatment of total knee arthroplasty failure

BackgroundCurrently, the main indication for knee arthrodesis is septic failure of a total knee arthroplasty (TKA). The purpose of this study was to evaluate the results of knee arthrodesis by circular external fixation performed in the treatment of TKA failure in which revision arthroplasty was not indicated. MethodsThe study involved 19 patients who underwent knee arthrodesis by the Ilizarov method. Clinical and functional assessments were performed, including Knee Society Score (KSS). A postoperative clinical and radiographic evaluation was conducted every three months until the end of the treatment. Postoperative complications and eventual leg shortening were recorded. ResultsKSS results showed a significant improvement with respect to the preoperative condition. Of the 16 patients in the final follow-up, 15 patients (93.7%) achieved complete bone fusion. Major complications occurred in patients treated for septic failure of TKA and most occurred in patients over 75years of age; the mean final leg shortening was four centimeters. ConclusionIn our experience, the Ilizarov method is effective for performing a knee arthrodesis in the case of extensive bone loss. At the same time, it is possible to correct the associated leg deformities or limb length difference. In addition, only the Ilizarov method provides a mechanical stimulus for bone formation and improves the quality of the bone and of the microcirculation, which enhances the host response against infection. Despite these attributes, knee arthrodesis by the Ilizarov method must be considered a ‘salvage procedure’ in cases of severe outcomes from knee surgery in which revision arthroplasty is not indicated.

Venovenous Extracorporeal Membrane Oxygenation in Pediatric Respiratory Failure

Conventional treatment of respiratory failure involves positive pressure ventilation that can worsen lung damage. Extracorporeal membrane oxygenation (ECMO) is typically used when conventional therapy fails. In this study, we evaluated the use of venovenous (VV)-ECMO for the treatment of severe pediatric respiratory failure at our institution. A retrospective analysis of pediatric patients (age 1-18) placed on ECMO in the last 15 years (1999-2014) by the pediatric surgery team for respiratory failure was performed. Five pediatric patients underwent ECMO (mean age 10 years; range, 2-16). All underwent VV-ECMO. Diagnoses were status asthmaticus (2), acute respiratory distress syndrome due to septic shock (1), aspergillus pneumonia (1), and respiratory failure due to parainfluenza (1). Two patients had severe barotrauma prior to ECMO initiation. Average oxygenation index (OI) prior to cannulation was 74 (range 23-122). No patients required conversion to VA-ECMO. The average ECMO run time was 4.4 days (range 2-6). The average number of days on the ventilator was 15 (range 4-27). There were no major complications due to the procedure. Survival to discharge was 100%. Average follow up is 4.4 years (range 1-15). A short run of VV-ECMO can be lifesaving for pediatric patients in respiratory failure. Survival is excellent despite severely elevated oxygen indices. VV-ECMO may be well tolerated and can be considered for severe pediatric respiratory failure.

Extracorporeal Life Support in Multiple Trauma Patients with Refractory Cardiopulmonary Failure: Predictors of Procedural Suitability and Success Rate

Background: Major trauma is a leading cause of death, particularly amongst young patients. New strategies in management are needed to improve the poor outcome of severe trauma. We report our initial experience with extracorporeal life support (ECLS) as a rescue therapy in severe multiple trauma patients with refractory cardiopulmonary failure. Objectives: The purpose of this study was to identify the pre-ECLS patient characteristics predicting appropriateness ECLS treatment. Methods: From December 2008 to May 2013, 420 multiple trauma patients were treated at our tertiary level referral trauma center. Our ECLS team was alerted on 35 and applied ECLS in 20 adult trauma patients. In 16 patients with cardiopulmonary failure with refractory shock, we adopted a veno-arterial ECLS; in 4 patients with isolated refractory acute respiratory failure, we used venovenous ECLS. Results: ECLS was initiated at a mean of 324.15 ± 197.8 (110 - 950) min from initial trauma. In 4 patients, ECLS treatment failed due to an incapability to maintain adequate ECLS flow and patient perfusion. In the other 16 patients efficiently supported by ECLS, the Cardiac Index, mean arterial pressure, lactate concentration, PaO2, PaCO2, and pH showed significant improvement with normal values reached at 3.2 ± 1.5 hours. Seven (43.7%) patients in the ECLS-Success Group donated organs, 2 patients (22.2%) died due to septic multi organ failure (MOF), and 7 (77.7%) patients were discharged from the hospital. ECLS was suitable and successful in patients with a significantly lower injury severity score, lower blood lactate level, lower number of blood units given, and significantly higher pH and Hb. Conclusions: From our data, ECLS seems to be a valuable option to resuscitate severe trauma patients when conventional therapies are insufficient: it is safe, feasible and effective in providing hemodynamic support and blood gas exchange. Our data permitted us to identify strong predictors of ECLS non-suitability and success in multiple trauma patients; these might be helpful in deciding whether ECLS should be used or not. Future improvements in materials and techniques are expected to make ECLS even easier and safer to manage, leading to a further extension of its use in disastrously injured patients

Infected cystic hygroma resulting in septic shock and respiratory failure: A case report

Abstract Macrocystic lymphatic malformations (cystic hygromas) are a common cause of cystic neck lesions. These lesions are often diagnosed prenatally in children. In cases without airway compromise, these children are discharged from the hospital for elective treatment. Surgical excision is one treatment modality while sclerotherapy has recently shown adequate results as well. While infection is a relatively common problem for lymphatic malformations, the majority can be treated with antibiotics alone. We present a case in which septic shock and respiratory failure resulted from primary infection of a macrocystic lymphatic malformation in a term infant discharged with a lymphatic malformation of the neck. Urgent surgical drainage failed, and complete excision was ultimately required for source control due to numerous small multiloculated small cysts inaccessible via incision and drainage.

The Diagnosis of Infection in Metal-on-Metal Hip Arthroplasties

BackgroundDistinction of aseptic from septic hip arthroplasty failure can be challenging. Some studies report an increased incidence of septic failure with metal-on-metal (MoM) hip arthroplasties. The Musculoskeletal Infection Society (MSIS) have formulated criteria to facilitate the diagnosis of periprosthetic joint infection (PJI). In this study, we determined the prevalence and histologic features of septic MoM hip failure. MethodsOverall, 104 cases of failed MoM hip arthroplasty, classified as septic or aseptic by MSIS microbiological criteria, were analyzed. The overall prevalence of septic failure was determined and the nature of the causative organisms noted. The extent of the neutrophil polymorph (NP) infiltrate in periprosthetic tissue in all cases was analyzed by hematoxylin-eosin and chloroacetate esterase staining. ResultsThe prevalence of septic MoM hip arthroplasty failure was 6.7%. Infective organisms were coagulase-negative Staphylococcus in 4 cases; Staphylococcus aureus, Streptococcus, and Propionibacterium species were isolated in the remaining cases. Chloroacetate esterase staining facilitated identification of NPs. All cases of PJI contained more than 5 NPs per high-power field (HPF) on average. Four cases of aseptic MoM implant failure contained scanty or scattered NPs (less than 5 per HPF on average). ConclusionThe prevalence of PJI as a cause of MoM hip arthroplasty failure was relatively high compared to other hip bearing combinations; however, the organisms responsible were similar. Histologically, a minority of aseptic MoM implant failures contained some NPs, but the MSIS criteria for the histologic diagnosis of PJI (>5 NPs/HPF) correctly identified all microbiologically confirmed cases of septic failure.

Abstract P1-10-19: Skin, and nail, infections associated with the addition of pertuzumab to trastuzumab-based chemotherapy

Abstract Objectives: We have maintained a local registry of skin and nail infections in patients receiving pertuzumab and trastuzumab as treatment for HER2 positive breast cancer. Over the past 16 months, we have continued to observe an increase in infectious complications in patients receiving the combination of pertuzumab and trastuzumab with or without chemotherapy. We expand a series of prospectively identified patients who developed infections while on these regimens. Methods: We became concerned about an increased incidence of infections shortly after the FDA approval of pertuzumab, and created an IRB approved registry of these patients. Results: Twenty-eight women were identified to have 32 separate infections (often at more than one site); 9 after cycle 1; 6 after cycle 2, 9 after cycle 3 and 8 after 4 or more cycles. The median age was 51 (Range 25-67); 14 received pertuzumab, trastuzumab, carboplatin, and docetaxel (PTCH), 5 pertuzumab, trastuzumab, and docetaxel, 7 pertuzumab, trastuzumab, and nab-paclitaxel, and 2 pertuzumab and trastuzumab. Folliculitis of the scalp, abdomen, and/or buttocks was observed in 19 patients, abscesses in 8 patients (4 of whom required incision and drainage) and cellulitis in 2. Severe paronychial infections involving one to 16 digits were observed in 4; 2 pt required surgical removal of 2 nails. Quantitative immunoglobulins were found to be low in 8 of 17 women tested; 2 patient had low total protein but did not have an assessment of quantitative immunoglobulins. All patients were initially treated with oral antibiotics, and 6 required hospitalization. Cultures were obtained in 10 patients; Staphylococcus aureus was identified in 4, methicillin resistant Staphylococcus aureus (MRSA) in 5, Enterococcus faecalis in 1. A 57 year old pt receiving neoadjuvant PTCH died on cycle 2 day 7. Autopsy was consistent with sepsis and gram positive cocci were identified. A 62 year old became septic and developed renal failure. Skin biopsies were performed in 3 patients and are consistent with changes associated with EGFR inhibition. Conclusions: We believe these infections are a result of combining pertuzumab with trastuzumab as 2 pts received no concurrent chemotherapy. An awareness of this complication is critical as some infections may be life-threatening. We have initiated patient education to ensure awareness of this potential complication. Citation Format: Mortimer JE, Yuan Y, Jung J, Kruper L, Stewart D, Chung S, Yu WK, Mendelsohn M, D'Apuzzo M, Tegtmeier B, Dadwal S. Skin, and nail, infections associated with the addition of pertuzumab to trastuzumab-based chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-19.

A Rare Clinical Course of Seronegative Pulmonary-Renal Syndrome.

Purpose. Pulmonary-renal syndrome (PRS) is characterized by diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis mainly due to autoimmune etiologies. Seronegative PRS is a challenging entity to the clinician, since early diagnosis may be missed leading to delayed appropriate treatment. Materials and Methods. We present the clinical course of a 77-year-old patient who was admitted under the suspected diagnosis of pneumogenic sepsis and septic renal failure with fever, dyspnea, and elevated CRP levels. The diagnosis of pulmonary-renal syndrome was initially missed because of the absence of autoantibodies in all serological findings. Results. Despite delayed initiation of immunosuppressive therapy and a prolonged period of dialysis and extracorporeal membrane oxygenation the patient recovered well and was released to a rehabilitation center with nearly normalized creatinine levels. The diagnosis of PRS was established by renal biopsy. Conclusion. This case illustrates the important differential diagnosis of seronegative pulmonary-renal syndrome in patients with pulmonary and renal impairment.

Orthopedic implant infections: Incompetence of Staphylococcus epidermidis, Staphylococcus lugdunensis, and Enterococcus faecalis to invade osteoblasts.

Septic failure is still the major complication of prosthetic implants. Entering host cells, bacteria hide from host immune defenses, shelter from extracellular antibiotics, and cause chronic infection. Staphylococcus aureus, the leading etiologic agent of orthopedic implant infections, is able to enter bone cells and induce osteoblast apoptosis, osteoclast recruitment, and highly destructive osteomyelitis. Staphylococcus epidermidis, Staphylococcus lugdunensis, and Enterococcus faecalis are opportunistic pathogens causative of implant-related infections. This study investigated the ability to internalize into osteoblastic MG63 cells of 22 S. epidermidis, 9 S. lugdunensis, and 21 E. faecalis clinical isolates from orthopedic implant infections. Isolates were categorized in clusters by ribotyping. Internalization assay was carried out by means of a microtiter plate-based method. S. epidermidis, S. lugdunensis, and E. faecalis strains turned out incompetent to enter osteoblasts, exhibiting negligible internalization into MG63 cells, nearly three orders of magnitude lower than that of S. aureus. Osteoblast invasion does not appear as a pathogenetic mechanism utilized by S. epidermidis, S. lugdunensis, or E. faecalis for infecting orthopedic implants. Moreover, it can be inferred that intracellularly active antimicrobials should not be necessary against implant infections caused by the three bacterial species. Finally, implications with the uptake of biomaterial microparticles by nonphagocytic cells are enlightened. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 788-801, 2016.