Aggressive Treatment Of Infection Research Articles

The Impact on Parents of Diagnosing PCD in Young Children.

Primary ciliary dyskinesia (PCD) is an incurable, rare, inherited, chronic condition. Treatment includes the regular clearing of airway mucus, aggressive treatment of infections and management of hearing loss. Caregiver burden has not been explored, hence we interviewed 18 mothers and 6 fathers of children under 6 years to understand the impact of diagnostic testing and implications of a positive diagnosis. Interviews were transcribed and thematically analysed and five key themes were identified. These included the parents’ experiences following child’s diagnosis, impact of child’s treatment regimen on parent, impact of child’s health status on parent, parent’s coping strategies, and parental concerns for the future. Parents described their diagnostic journey, with the findings revealing how a lack of awareness among clinicians of the PCD symptom pattern can lead to a delayed diagnosis. Parents discussed the emotional and practical impact of a PCD diagnosis and the coping strategies employed to deal with challenges arising following a diagnosis. Parents use a variety of different lifestyle changes to accommodate their child’s treatment regimen and to cope with disruptive life events such as the COVID-19 pandemic. This study provides valuable insights into parental adjustment and adaptation to a PCD diagnosis and management regimen. Going forward, this research highlights the need for integrated social care for PCD patients and their families.

Palliative care infections and antibiotic cost: a vicious circle

Aim: In this study our aim was to evaluate the nosocomial infections and to understand factors affecting the cost of used antibiotics in palliative care unit.Materials and methods: Between 2016 and 2017, 113 patients were included in the study in palliative care unit of University of Health Sciences Bursa Yuksek Ihtisas Research and Training Hospital. Patients medical records were analyzed retrospectively for nosocomial infections, chronic diseases, presence of decubitis ulcers, opioid use, enteral, parenteral feedings, mortality and antibiotic cost.Results: Nosocomial infections were observed in 74.3% of the cases and 92.0% of patients used antibiotics. The mean duration of antibiotic use was 23.13 ± 18.06 days; and the average antibiotic cost was 2009.72 ± 2153.37 TL. Length of stay, male sex, presence of decubitus ulcers, tracheostomy, enteral and parenteral nutrition significantly increased antibiotic cost. Antibiotic cost and mortality were not related statistically.Conclusions: A vicious circle in palliative care involves the following order: length of stay, increased rate of infection, use of antibiotics, infection with resistant microorganisms, use of broad spectrum antibiotics, increased length of stay; all affecting each other. Therefore, using antibiotics for aggressive treatment of infections in palliative care is contraindicated as it opposes to real philosophy of palliative care.

Bronchoscopy in the diagnosis and treatment of children with bronchiectasis

Objective To analyze the clinical features and the application of bronchoscopy in diagnosis and treatment of children with bronchiectasis. Methods All cases with bronchiectasis were collected from in-patient department of the Children′s Hospital Affiliated to Nanjing Medical University from December 2011 to November 2015.Clinical manifestations, results of bronchoscopy examination were retrospectively analyzed. Results Of the 33 children, 32 cases (97.0%) had chronic cough and sputum.Lung infection was the main cause (50%, 16/33 cases). High resolution CT signet ring sign and/or double-track sign in lungs, and bronchiectatic lesions were most commonly found in the lower lobes(60.6%). Eighteen cases underwent bronchoscope ciliary biopsy, and the number of cilia decrease was found in 2 cases, and cilia ultrastructure abnormalities were found in 6 cases, with 2 cases diagnosed as Kartagener syndrome.The treatment included the following: treatment of the underlying disease, aggressive treatment of infections, promotion of mucociliary clearance, and bronchoscopy.The symptoms of the most patients were relieved through the symptomatic treatment.Follow-ups after discharge, showed that 15 cases had a slight cough without obvious sputum, 11 cases with recurrent lung infections, regular bronchoscope lavage treatment; 4 cases underwent surgical lung resection and recovered well postoperative, and 2 cases died. Conclusion The bronchoscopy should be performed early in the children with bronchiectasis, which can clearly detect pathogens and causes, so as to undertake lavage treatment to improve clinical symptoms. Key words: Bronchiectasis; Child; Bronchoscopy; Cilia

The era of comparable life expectancy between thalassaemia major and intermedia: Is it time to revisit the major-intermedia dichotomy?

In the last few decades, the life expectancy of regularly transfused β-thalassaemia major (TM) patients has dramatically improved following the introduction of safe transfusion practices, iron chelation therapy, aggressive treatment of infections and improved management of cardiac complications. How such changes, especially those attributed to the introduction of iron chelation therapy, improved the survival of TM patients to approach those with β-thalassaemia intermedia (TI) remains unknown. Three hundred and seventy-nine patients with TM (n=284, dead 40) and TI (n=95, dead 13) were followed retrospectively since birth until 30 June 2015 or death. Kaplan-Meir curves showed statistically significant differences in TM and TI survival (P<0·0001) before the introduction of iron chelation in 1965, which were no longer apparent after that date (P=0·086), reducing the Hazard Ratio of death in TM compared to TI from 6·8 [95% confidence interval (CI) 2·6-17·5] before 1965 to 2·8 (95% CI 0·8-9·2). These findings suggest that, in the era of iron chelation therapy and improved survival for TM, the major-intermedia dichotomy needs to be revisited alongside future directions in general management and prevention for both conditions.

Survival Comparability Between Thalassemia Major Versus Thalassemia Intermedia

▪Introduction. In the last few decades, the life expectancy of Thalassemia Major (TM) patients has progressively been increasing. The improvement can be due to several factors, including introduction of chelation treatment (Deferoxamine 1965, Deferiprone 1987, Deferasirox 2006), screening of blood for the most common viral agents, aggressive treatment of infection and improved treatment of cardiac complications. However, no comparative survival curves between TM versus Thalassemia Intermedia (TI) have been so far reported. Moreover, no data on life expectancy, after introduction of chelation treatment have been described.Methods. Data coming from several randomized clinical trials, carried ahead by Campus of Hematology Franco and Piera Cutino-A.O.O.R Villa Sofia-V. Cervello, Palermo (Italy), were retrospectively considered for this study. Primary goal of the study was to provide evidence of possible differences in survival curves between TM versus TI. Survival curves in TM versus TI patients were compared using Kaplan-Meier method and the log-rank test before and after the introduction of Deferoxamine (DFO) (1965). Moreover, Cox regression model was even used to explore risk of death between the two diagnoses. Each dead patient was observed from its birth to its death, and each alive patient was observed from its birth to June 30, 2015.Results. Three hundred seventy-nine patients with TM (n=284, dead 40) and TI (n=95, dead 13) entered into the study. Males were 50.7% of this cohort of patients. Among the cohort of dead patients, 15% (6/40) TM and 76.9% (10/13) TI patients were born before introduction of DFO (1965) . The mean age survival was 50.6 (SE 0.9) and 70.6 (SE 1.7) for TM and TI, respectively. Table 1 shows the main causes of death. In TM patients the most common causes of death were heart damage (16 cases, 40%, Tab. 1), followed by cancer (3 cases, 7.5%, Tab. 1), liver cirrhosis (3 cases, 7.5%, Tab. 1) and infections (3 cases, 7.5%, Tab. 1). In TI patients the most common causes of death were cancer (2 cases, 38.5%, Tab. 1), followed by infections (3 cases, 23.1% , Tab. 1), heart damage (2 case, 15.4%, Tab. 1). Kaplan-Meir curves showed statistically significant difference in TM versus TI survival (log-rank test, p- value<0.0001; Figure 1A). Survival was higher for TI subjects (median age was 73.6 years). Cox regression models of TM versus TI suggested that risk of death for TM patients was 6.8 times higher than TI patients (HR 6.8 (3.3), p- value<0.0001). However, the introduction of chelation treatment (DFO, 1965), changed the Kaplan-Meier curves showing that there was not statistically significant difference between TM versus TI patients in life expectancy ( log-rank test, p- value=0.086; Fig. 1B).Conclusion. These results suggest as TM survival, after the introduction of chelation treatment, improved so much that nowadays it is not different in comparison with TI one's. Moreover, the TM risk of death has been decreased from 6.8 to 2.8 (Cox Model HR 2.8 (1.7), p- value=0.099).These findings, if further confirmed, suggest as, in Western countries, our approach for genetic counselling of "at risk couples" for TM should be reconsidered.Table 1Causes of death in Thalassemia Major and Thalassemia Intermedia patients.DiagnosisCauses of DeathTM n (%)TI n (%)Cancer3 (7,5)5 (38,5)Heart Damage16 (40,0)2 (15,4)Infection3 (7,5)3 (23,1)Multi Organ Failure1 (2,5)0 (0,0)Stroke1 (2,5)0 (0,0)Liver Failure3 (7,5)1 (7,7)Not Available11 (27,5)1 (7,7)Other complications not related to Thalassemia2 (5,0)1 (7,7)Total1340 [Display omitted] DisclosuresPepe:Chiesi: Speakers Bureau; ApoPharma Inc: Speakers Bureau; Novartis: Speakers Bureau.

AAOA allergy primer: immunodeficiency.

Primary immunodeficiency is rare but should be considered in patients who present to the otolaryngologist with recurrent, severe, or treatment refractory infections. Recent literature and consensus statements on immunodeficiency were reviewed for clinically important information of relevance to otolaryngologists. The most common and most relevant immunodeficiencies are humoral deficiencies with inadequate antibody production or an impairment in the production of specific antibody after antigen exposure. For otolaryngologists the most important immunodeficiencies include immunoglobulin A (IgA) deficiency, common variable immunodeficiency (CVID), and specific antibody deficiency. Simple screening tests can be used by the otolaryngologist to exclude the most common immunodeficiencies. The general treatment approach to patients with these immunodeficiencies includes airway hygiene, early and aggressive treatment of infections, immunization, and antibody replacement therapy. By virtue of their scope of practice, otolaryngologists are in a position to recognize and initiate the diagnostic workup of patients with immunodeficiency. Patients with a diagnosed primary immunodeficiency are best managed in a multidisciplinary manner with close cooperation among the otolaryngologist, immunologist, and other specialists that are involved in treating these multisystem diseases.

Long-term Outcomes of 1,263 Patients with Mycosis Fungoides and Sézary Syndrome from 1982 to 2009

The purpose of this prospectively collected single center study cohort of 1,263 patients with mycosis fungoides (MF)/Sézary syndrome (SS) is to evaluate the significance of stage and risk of disease progression from initial presentation and to examine other prognostic factors. The prognostic variables effecting overall survival (OS) were examined in a unique prospective cohort of 1,263 patients with MF and SS seen by one investigator at MD Anderson Cancer Center (Houston, TX) from 1982 to 2009. Kaplan-Meier estimates were used to determine median OS, progression-free survival (PFS), and disease-specific survival (DSS). Cox proportional hazards regression model assessed prognostic factors. Mean age at diagnosis was 55.33 years. Early mycosis fungoides (stage IA-IIA) represented 71.5% (903 of 1,263) and advanced (stage IIB-IVB) 28.5% (360 of 1,263) patients. Progression to a higher stage occurred in 147 patients (11.6%) of whom 112 (12%) were early and 35 (9.7%) advanced. Death from disease occurred in 102 of 1,263 (8.1%) patients. Median OS was 24.44 years, PFS was 16 years, and median DSS was not reached. OS and PFS were significantly better for early-stage patients with patches (T1a/T2a) than with patches/plaques (T1b/T2b). The PFS analyzed in 1,241 patients found that only 337 (27.2%) had disease progression or had died from disease. Risk factors associated with progression or deaths were advanced age, plaque stage, lactate dehydrogenase (LDH) level, and tumor area. Improved outcome of MF/SS, reflected by OS and PFS for all stages, may result from earlier diagnosis, new therapies, and aggressive treatment of infections.

Extracorporeal liver support-albumin dialysis with the Molecular Adsorbent Recirculating System (MARS)

Extracorporeal liver support has been a much studied topic throughout the last 50 years. Albumin dialysis as a therapeutic option for patients with acute liver failure or acute decompensation of chronic liver disease was introduced in the mid-nineties. The Molecular Adsorbent Recirculating System (MARS) is based on the concept of albumin dialysis and allows for the removal of protein-bound as well as water-soluble toxins. Besides its role as a sufficient volume expander human serum albumin is an important scavenger for molecules with pathophysiological relevance in liver failure. Albumin dialysis enables the selective regeneration of patient’s albumin resulting in an increase of albumin binding capacity. Clinically, an improvement of central and local hemodynamics as well as liver-, brain-, and kidney-functions were observed. Thus, the treatment can contribute to liver regeneration and stabilization of vital organ functions and thus help to bridge patients to liver transplantation or to recovery of native liver function. Proper patient selection is critical for clinical success. Aggressive treatment of infections and sepsis seems to be a decisive pre-requisite for its safe and efficient use. Cautious anticoagulation with heparin is the common standard. Citrate use is recommended for patients prone to bleeding. Today, albumin dialysis MARS is among the best studied liver support methods. It appears as a valuable therapeutic tool for the treatment of various complications of of liver failure, especially hemodynamic instability and hepatic encephalopathy. Further studies will need to help defining the optimal patient selection and technical process parameters such as session-length and frequency of treatment.

Long-Term Outcomes of Diabetic Patients With Critical Limb Ischemia Followed in a Tertiary Referral Diabetic Foot Clinic

OBJECTIVEWe describe the long-term outcomes of 510 diabetic patients with critical limb ischemia (CLI) and an active foot ulcer or gangrene, seen at the University Hospital of Rome Tor Vergata, a tertiary care clinic.RESEARCH DESIGN AND METHODSThese patients were seen between November 2002 and November 2007 (mean follow-up 20 ± 13 months [range 1–66 months]). The Texas Wound Classification was used to grade these wounds that were either class C (ischemia) and D (ischemia+infection) and grade 2–3 (deep–very deep). This comprehensive treatment protocol includes rapid and extensive initial debridement, aggressive use of peripheral percutaneous angioplasty, empirical intravenous antibiotic therapy, and strict follow-up.RESULTSThe protocol was totally applied (with percutaneous angioplasty [PA+]) in 456 (89.4%) patients and partially (without percutaneous angioplasty [PA−]) in 54 (10.6%) patients. Outcomes for the whole group and PA+ and PA− patients are, respectively: healing, n = 310 (60.8%), n = 284 (62.3%), and n = 26 (48.1%); major amputation, n = 80 (15.7%), n = 67 (14.7%), and n = 13 (24.1%); death, n = 83 (16.25%), n = 68 (14.9%), and n = 15 (27.8%); and nonhealing, n = 37 (7.25%), n = 37 (8.1%), and n = 0 (0%) (χ2 <0.0009). Predicting variables at multivariate analysis were the following: for healing, ulcer dimension, infection, and ischemic heart disease; and for major amputation, ulcer dimension, number of minor amputations, and age. Additional predicting variables for PA+ patients were the following: for healing, transcutaneous oxygen tension [ΔTcPo2]; and for major amputation, basal TcPo2, basal A1C, ΔTcPo2, and percutaneous angioplasty technical failure.CONCLUSIONSEarly diagnosis of CLI, aggressive treatment of infection, and extensive use of percutaneous angioplasty in ischemic affected ulcers offers improved outcome for many previously at-risk limbs. Ulcer size >5 cm2 indicates a reduced chance of healing and increased risk of major amputation. It was thought that all ulcers warrant aggressive treatment including percutaneous angioplasty and that treatment should be considered even for small ischemic ulcers.

Reduction of periprosthetic infection with silver‐coated megaprostheses in patients with bone sarcoma

The placement of megaprostheses in patients with bone sarcoma is associated with high rates of infection, despite prophylactic antibiotic administration. In individual cases, secondary amputation is unavoidable in the effort to cure infection. The infection rate in 51 patients with sarcoma (proximal femur, n = 22; proximal tibia, n = 29) who underwent placement of a silver-coated megaprosthesis was assessed prospectively over a 5-year period, along with the treatment administered for infection. The infection rate was compared with the data for 74 patients in whom an uncoated titanium megaprosthesis (proximal femur, n = 33; proximal tibia, n = 41) was implanted. The infection rate was substantially reduced from 17.6% in the titanium to 5.9% in the silver group. Whereas 38.5% of patients in the titanium group ultimately had to undergo amputation when periprosthetic infection developed, these mutilating surgical procedures were not necessary in the study group. The use of silver-coated prostheses reduced the infection rate in the medium term. In addition, less aggressive treatment of infection was possible in the group with silver-coated prostheses. Further studies with longer term follow-up periods and larger numbers of patients are warranted in order to confirm these encouraging results.

The Clinical Approach to Lung Disease in Patients with Cystic Fibrosis

There is strong evidence that early, aggressive therapy of lung disease leads to improved quality and quantity of life for patients with cystic fibrosis (CF). The treatment of pulmonary disease associated with CF is multifactorial, encompassing prophylaxis, aggressive treatment of infection, use of antiinflammatory agents, and treatment of severe complications. Chest physiotherapy on a regular basis, perhaps using new modalities that allow patient autonomy, is also crucial. This review covers the pathogenesis of CF lung disease and current approaches to therapy, highlighting guidelines recently published by the Cystic Fibrosis Foundation. Clinicians caring for patients with CF should maximize current therapies with the goal of preserving lung function until the time a more definitive curative or controller medication is developed. Empowering patients in the process of providing their own care is a key to achieving this goal.

Albumin Dialysis MARS: Knowledge from 10 Years of Clinical Investigation

A decade ago, albumin dialysis was introduced as a new extracorporeal detoxification method for patients with liver failure. Today, the molecular adsorbent recirculating system is the most frequently used type of albumin dialysis and most studied liver-support technique. Numerous preclinical and clinical studies demonstrated the importance of albumin as a scavenger for molecules with pathophysiological relevance in liver failure. Albumin dialysis enables the selective regeneration of albumin. The resulting increase of albumin binding capacity is paralleled by improvement of central and local hemodynamics and liver, brain, and kidney functions. The treatment can contribute to liver regeneration and prolongation of patient survival in the context of acute liver failure, decompensated chronic liver disease, and bridging of patients to liver transplantation. Proper patient selection is critical for clinical success. Aggressive treatment of infections and sepsis seems to be a decisive prerequisite for its safe and efficient use. Cautious anticoagulation with heparin is the common standard. Citrate use is recommended for patients prone to bleeding. Taken together, albumin dialysis represents a valuable therapeutic tool for the treatment of various types of liver failure. Ongoing and future studies will help define the optimal patient selection and technical process parameters such as session length and frequency of treatment.

The Multidisciplinary Diabetic-Foot Clinic

need easy access to this system, which should provide specialized care. Such clinics were set up in the United Kingdom in 1980s. The main principles of care were regular debridement, early and aggressive treatment of infection, custom-made footwear, and education. The clinics were permanent bases for clinical assessment, investigation and regular treatment, and a focal point for patients who were seen by several members of the team at one visit. The clinics were easily accessible for both urgent consultations and regular outpatient treatment. They quickly reduced amputations by approximately 50%. Indeed, this benchmark of improvement was incorporated into the St Vincent Declaration in Europe as one of the proposed targets of improved health care in diabetes. In United Kingdom, a working party between the department of health and the then British Diabetic Association provided a strategy document supporting the development of multidisciplinary foot clinics in hospitals, as well as stressing the importance of education and screening in the community. Throughout the 1990s, the number of hospital multidisciplinary diabetic-foot clinics increased as did the challenges they faced. Provision was made for open access so that patients could attend quickly when they developed lesions. It was important for diabetic-foot care to be coordinated and not fragmented. At King’s College Hospital, the post of hospital diabetic-foot practitioner was set up to coordinate care of the diabetic-foot inpatient between various hospital specialities and also to link community services when patients were discharged. The multidisciplinary clinics also faced increasing clinical challenges, stretching into the 21st century, including the ischemic foot, the Charcot foot, and the renal foot. Patients with diabetes were surviving longer, and distal arterial disease posed a major problem for management. However, multidisciplinary clinics embraced the skills and technologies of the interventional radiologists, and the vascular surgeon and numbers of amputations continued to The diabetic-foot patient is very vulnerable. There is a rapidly progressive and complex natural history that demands easily accessible, specialized multidisciplinary and coordinated care. This is necessary both in the short term and in the long term. It is important to understand this vulnerability and devastating natural history so as to organize efficient care. Three major pathologies come together in the diabetic foot, neuropathy, immunopathy, and ischemia. The impact of neuropathy in the diabetic foot is immense. Signs and symptoms of disease may be minimal; however, the pathology proceeds rapidly, and the end stage of tissue death is quickly reached. Therefore, the window of opportunity is limited. Furthermore, the immune system, which serves as a sixth sense, is also deficient. An intact inflammatory response notifies the nervous system of the presence of bacteria. In diabetes, both the immune system and the nervous system are deficient, and the body is unaware of bacterial invasion. Peripheral arterial disease occurs distally, is difficult to treat, and is accompanied by coronary artery and cerebrovascular disease. In diabetes, there is also microvascular component of ischemia leading to nephropathy and retinopathy. Such vulnerability is also increased by poor socioeconomic circumstances and poverty. This overwhelming vulnerability leads to devastating natural history with rapid progression from ulceration to infection, leading to gangrene both in the neuropathic and neuroischemic foot. To detect this problem and intervene early and also reverse the natural history, a unique special form of health care is necessary. This is the multidisciplinary team working together in a dedicated diabetic-foot clinic. Patients The International Journal of Lower Extremity Wounds Volume 7 Number 2 June 2008 66-67 © 2008 Sage Publications 10.1177/1534734608317638 http://ijlew.sagepub.com hosted at http://online.sagepub.com

Hyper IgE syndrome: review and future directions

Hyper IgE syndrome, or Job’s syndrome, is an immunodeficiency syndrome characterized by eczema, recurrent infections and elevated serum immunoglobulin E levels. Individuals tend to have frequent staphylococcal abscesses and pneumonias early in life, often developing pneumatocoeles that predispose them to later fungal and Gram-negative bacterial infections. In addition to the immunologic abnormalities, hyper IgE syndrome is now recognized as a multisystem disorder with skeletal and morphologic features such as characteristic facies, osteopenia, scoliosis, fractures and retention of the primary teeth. Therapy of hyper IgE syndrome involves careful skin care, antimicrobial prophylaxis and aggressive treatment of infections, as well as treatment of some of the complicating abnormalities, such as scoliosis. The genetic etiology of hyper IgE syndrome remains unknown, however, it continues to be investigated. Identification of the genetic etiology or etiologies of this syndrome will allow for targeted therapies as well as great advances in understanding the connections between immunologic function and connective tissue.

COMBINED ELECTROHYDRAULIC AND HOLMIUM:YAG LASER URETEROSCOPIC NEPHROLITHOTRIPSY FOR 20 TO 40 MM RENAL CALCULI

Percutaneous nephrolithotripsy is standard treatment for renal calculi greater than 2 cm. Modern flexible ureteroscopes using the complementary effects of electrohydraulic (EHL) and Ho:YAG laser lithotrites can treat 2 to 4 cm renal calculi in minimally invasive fashion with similar or superior results. We evaluated the safety and efficacy of ureteroscopic nephrolithotripsy for the management of 2 to 4 cm renal calculi in a community setting. Between January 2001 and November 2002 all 15 patients presenting with renal calculi 22 to 42 mm long (mean 33) and 275 to 650 mm in area (mean 396), of whom 40% had infection, underwent flexible ureteroscopic nephrolithotripsy. A total of 13 patients had 3-month followup data. Hard stone components, namely calcium oxalate monohydrate and/or apatite, were present in 13 cases (87%). Treatment principles were the aggressive treatment of infection, EHL stone debulking, Ho:YAG laser lithotripsy to weaken hard stones structurally, manual piston irrigation to maintain visibility, bladder drainage to maintain low intrarenal pressures, minimum 6-hour postoperative observation and physiological passage of stone fragments. In the 13 patients with 3-month followup data the stone clearance rate was 92% for complete stone free status and 100% for fragments less than 4 mm. This result was achieved at 1 stage in 10 cases 13 (77%) and at 2 to 4 stages in 1 each. Mean procedure time per stage was 47 minutes (range 25 to 90) and total procedure time per patient was 66 minutes (range 25 to 240). There was no significant change in mean preoperative and postoperative hemoglobin (p = 0.87) and creatinine (p = 0.85) in the 16 of 21 procedures for which data were available. Procedures were done on an outpatient basis except in 1 patient, who was hospitalized overnight for the management of preexisting pulmonary problems. One rehospitalization for colic management but no other unplanned emergency department or clinic visits occurred. All patients were rendered infection-free and symptom-free. Combined EHL and Ho:YAG laser flexible ureteroscopic lithotripsy can be an effective treatment with low morbidity. As such, it provides an attractive, minimally invasive alternative to percutaneous nephrolithotripsy or open surgery in patients with 2 to 4 cm renal calculi.

O0052 ANTECEDENTS AND OUTCOMES OF 755 PATIENTS WITH BILIARY ATRESIA LISTED FOR LIVER TRANSPLANT IN THE UNITED STATES AND CANADA

Introduction: Biliary Atresia (BA) is a progressive cholangiopathy which, if untreated, leads to death by 2yrs of age. Liver transplant (LT) remains the only ultimate treatment for most patients. Once BA patients have been listed for LT, limited data exist regarding their potential for dying on the waiting list, waiting time, antecedents of early post-LT morbidity and survival. Methods: We analyzed data from 755 cases of BA listed for first LT (1995–2003) from the Studies of Pediatric Liver Transplantation (SPLIT) database, a 39 center North American consortium. Results: Most patients were female with 70% <1yr at the time of listing. Of the 755 patients listed, 567 have had LT and 24 have died while waiting. The probability of survival on an intent-to-treat basis from listing was 93% and 86% at 6m and 3yr, respectively. The overall probability of receiving a LT was 44% and 80% at 3 and 12 months post-listing, respectively. Between listing and LT, nutrition and growth declined. Once receiving a LT, patient and graft survival were 92% and 86%, respectively, at 6m. Tacrolimus was superior to cyclosporine in univariate analyses. Multivariate analysis revealed 3 significant risk factors for death, including recipient age<1yr, ht/wt<−2SD and donor age>50yr. Graft failure risks included ht/wt <−2SD, , the use of cadaveric partial donor organs, and donor age >50yr. 86% had a KP prior to transplant; however, KP was not a predictor for survival. Rejection occurred in 34% by 1m and 48% by 6m. Bacterial, viral and fungal infection occurred <30d following LT in 40%, 12% and 9%, respectively. Conclusion: In conclusion, aggressive pre-LT management of complications of BA should be pursued, particularly in infants. Patient and graft survival improvements may come from enhanced pre-LT nutrition and growth, care with donor selection, use of tacrolimus and prevention or aggressive treatment of infection. Further analysis of the outcomes of specific BA subtypes, the influence of KP timing and the intent-to-treat data is warranted.

The Multidisciplinary Approach to Limb Salvage

There is considerable morbidity and mortality associated with ulcerations of the lower limbs in patients with diabetes as well as non-diabetic patients. The role of the primary care physician and podiatrist in the evaluation, diagnosis, and management of lower extremity wounds is critical. Careful assessment and management of vascular disease by vascular surgeons and interventionalists, biomechanical foot abnormalities by the podiatrist, wound coverage by the plastic surgeons and aggressive treatment of infections and metabolic derangements by the physicians are required. The multidisciplinary approach provides a comprehensive treatment protocol and significantly increases the chances of successfully healing the ulcer and prevents recurrence. It also provides for increased academic output through publications, participation in clinical trials and educational venues.

PRIMARY PHAGOCYTIC DISORDERS OF CHILDHOOD

Primary phagocytic disorders are rare and usually first manifest during childhood. A phagocytic disorder should be considered in patients with unusually severe or recurrent infections by common pathogens or an infection by certain opportunistic pathogens. Common manifestations of primary phagocytic disorders include recurrent soft-tissue infections requiring incision and drainage, severe dental infections leading to premature tooth loss, recurrent pneumonias, and perirectal infections. Primary phagocytic disorders are caused by defects of neutrophil number or function, and the latter, in turn, can be divided into disorders of oxidative and nonoxidative pathways. Certain phagocytic disorders have unique characteristics apart from the immune defect that may facilitate diagnosis. Early diagnosis of phagocytic disorders can be life-saving or lead to a significant reduction in morbidity and relies on a compatible clinical (or family) history and appropriate laboratory diagnostic studies. Key principles of management of such patients involve early recognition and aggressive treatment of infections and appropriate surgical débridement of localized disease. Prophylactic antibiotics, BMT, and the use of exogenous cytokines, such as IFN-gamma and G-CSF, are appropriate for specific phagocytic disorders. Gene therapy is a promising strategy for several of the phagocytic disorders.

The Genetic Basis of Chronic Granulomatous Disease

Chronic granulomatous disease is a serious clinical entity. The disease is caused by the failure of NADPH oxidase in phagocytic leukocytes to generate superoxide, needed for the killing of micro-organisms. The patients need careful management aimed at prevention and aggressive treatment of infections. CGD is a heterogeneous syndrome, both clinically and genetically. This disease is caused by a diversity of mutations, and multiple genes are affected. In fact, in the A22 and X91 subtypes of CGD, in which the alpha subunit and the beta subunit of cytochrome b558 are affected, respectively, the mutations are virtually unique for each CGD family tested. The results of these studies provide a better understanding of the mechanism of action of the various components of the superoxide-generating enzyme. Although treatment of CGD patients has improved considerably over the past 30 years, death caused by overwhelming infections is still a serious threat. Prenatal diagnosis now provides the relatives of a CGD patient with the possibility to choose for first-trimester abortion of an affected fetus. Moreover, genetic correction of the disease is now a goal within reach.

Reconstruction Of The Pharynx And Cervical Esophagus Using Free Jejunal Transfer

Although FJT has been perceived as unreliable, current FJT survival rates of 94% or greater, FJT salvage rates of up to 100%, and perioperative mortality of 6% or less demonstrate that FJT is a safe, reliable, one-stage method of reconstructing partial and circumferential pharyngoesophageal defects. FJT is associated with some morbidity; however, the procedure is well tolerated, and swallowing function is restored in 80% or more of patients within an average of 9 to 12 days after surgery. The success of the technique requires careful attention to details, such as designing the flap to avoid vein grafts, selecting large recipient vessels with high blood flow, careful in setting of the flap, meticulous microvascular anastomotic technique, close postoperative monitoring, and early, aggressive treatment of infection. If FJT failure should occur, a repeat FJT should be performed in the immediate postoperative period to increase the possibility of salvage and to decrease the risk of infection and mortality.