Classification of dry eye disease subtypes.

PURPOSE: The current subclassifications of dry eye disease (DED) are aqueous deficient (ADDE) and evaporative (EDE) forms, but there lacks consistency in the clinical characteristics used to define each of these. This study used clinical data to inform cut-off values for the subclassification of ADDE and EDE, to allow more consistent study of the epidemiology of both DED subtypes. METHODS: The study enrolled 261 residents from the UK, extracted from a cohort with demographics representing the population (mean 42.4 ± 18.7 years, 56 % females). The TFOS DEWS II diagnostic criteria were used to identify those with DED. Meibomian gland loss/drop-out (from meibography), lipid layer thickness (LLT - from interferometry graded on the Guillon-Keeler scale), and tear meniscus height (TMH - Keratograph 5M) along with tear evaporation (Delfin Vapometer) were used to characterise the subclassification. The Dry Eye Risk Factor Survey was used to assess risk factors associated with each DED subtype. RESULTS: Compared to individuals who were not diagnosed with DED, EDE was characterized by signs of meibomian gland loss of > 28 %, LLT grade < 3 and tear evaporation > 46 g/m2/h. In contrast, ADDE was best characterized by a reduced TMH < 0.2 mm. Based on these criteria, the prevalence of ADDE was 6.2 %, EDE was 64.2 %, and 11.1 % exhibited features of both ADDE and EDE, with 18.5 % unclassified despite having a DED diagnosis. Contact lens wear and computer use were risk factors for ADDE (p < 0.05), whereas age was a positive risk factor for EDE (p < 0.01). Meibomian gland loss (occurring in 27.9 %) was the most commonly observed sign in EDE. CONCLUSIONS: Data driven-classification of DED confirms that the evaporative form is most prevalent and identified that in a generalisable UK population, ADDE alone occurs only in approximately 1 in 16 cases of DED.

The epidemiology of dry eye disease in the UK: The Aston dry eye study.

PURPOSE: Cross-sectional studies on dry eye disease (DED) have relied on different diagnoses hindering conclusions about the disease epidemiology. This study offers an insight into DED epidemiology in the UK using prior and recent diagnostic recommendations. METHODS: Study participants comprised 282 volunteers from Birmingham, UK (median 40 years, range 18-88 years, 56% females). DED was defined by the Tear Film Ocular Surface Dry Eye Workshop II (TFOS DEWS II) criteria, based on a positive symptom score with the Dry Eye Questionnaire (DEQ-5) and Ocular Surface Disease Index (OSDI), and one of the following homeostasis markers: non-invasive tear break-up time of < 10 s (Oculus Keratograph 5M); the highest osmolarity value of ≥ 308 mOsm/L among eyes or an interocular osmolarity difference of > 8 mOsm/L (TearLab Osmolarity System); or > 5 corneal spots, >9 conjunctival spots or lower/upper lid-wiper-epitheliopathy staining of ≥ 2 mm length and ≥ 25% width (Oculus Keratograph 5 M). In addition, the Women's Health Study (WHS) criteria, based on symptoms or a prior dry eye diagnosis, was assessed. DED risk factors were gathered using a self-administered questionnaire. RESULTS: DED prevalence by the TFOS DEWS II criteria was 32.1% (95% confidence interval 25.5-37.7% and 29.5% (95% confidence interval 24.4-35.1% by the WHS criteria. Female sex, systemic and/or ocular health conditions, short sleep duration and prolonged outdoor leisure time spent were significant DED risk factors (p ≤ 0.05). CONCLUSIONS: Approximately one-third of the adult UK population have DED, aligning with the prevalence reported in multiple counties globally. Female sex, systemic/ocular health conditions, short sleep duration and prolonged outdoor leisure time are positive predictors of DED.

Piloting an ICU follow-up clinic to improve health-related quality of life in ICU survivors after a prolonged intensive care stay (PINA): study protocol for a pilot randomised controlled trial.

BACKGROUND: Intensive care unit (ICU) survivors often suffer from cognitive, physical and mental impairments, known as post-intensive care syndrome (PICS). ICU follow-up clinics may improve aftercare of these patients. There is a lack of evidence whether or which concept of an ICU follow-up clinic is effective. Within the PINA study, a concept for an ICU follow-up clinic was developed and will be tested in a pilot randomised controlled trial (RCT), primarily to evaluate the feasibility and additionally the potential efficacy. METHODS/DESIGN: Design: Pilot RCT with intervention and control (usual care) arms plus mixed-methods process evaluation. PARTICIPANTS: 100 ICU patients (50 per arm) of three ICUs in a university hospital (Regensburg, Germany), ≥ 18 years with an ICU stay of > 5 days, a sequential organ failure assessment (SOFA) score > 5 during the ICU stay and a life expectancy of more than 6 months. INTERVENTION: The intervention will contain three components: information, consultation and networking. Information will be available in form of an intensive care guide for patients and next of kin at the ICU and phone support during follow-up. For consultation, patients will visit the ICU follow-up clinic at least once during the first 6 months after discharge from ICU. During these visits, patients will be screened for symptoms of PICS and, if required, referred to specialists for further treatment. The networking part (e.g. special referral letter from the ICU follow-up clinic) aims to provide a network of outpatient care providers for former ICU patients. Feasibility Outcomes: Qualitative and quantitative evaluation will be used to explore reasons for non-participation and the intervention´s acceptability to patients and caregivers. Efficacy Outcomes: Health-related quality of life (HRQOL) will be assessed as primary outcome by the physical component score (PCS) of the Short-Form 12 Questionnaire (SF-12). Secondary outcomes encompass further patient-reported outcomes. All outcomes are assessed at 6 months after discharge from ICU. DISCUSSION: The PINA study will determine feasibility and potential efficacy of a complex intervention in a pilot RCT to enhance follow-up care of ICU survivors. The pilot study is an important step for further studies in the field of ICU aftercare and especially for the implementation of a pragmatic multi-centre RCT. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04186468 . Submitted 2 December 2019.

Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity in healthy adults: a phase I, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Protection induced by acellular vaccines can be short, requiring novel immunization strategies. Objectives of this study were to evaluate safety and capacity of a recombinant pertussis toxin (PTgen) -coated Viaskin® epicutaneous patch to recall memory responses in healthy adults. METHODS: This double-blind, placebo-controlled randomized trial (Phase I) assessed the safety and immunogenicity of PTgen administered on days 0 and 14 to healthy adults using Viaskin® patches applied directly or after epidermal laser-based skin preparation. Patch administration was followed by Boostrix®dTpa on day 42. Antibodies were assessed at days 0, 14, 28, 42 and 70. RESULTS: Among 102 volunteers enrolled, 80 received Viaskin-PT (Viaskin-PT 25 µg (n = 25), Viaskin-PT 50 µg (n = 25), laser + Viaskin-PT 25 µg (n = 5), laser + Viaskin-PT 50 µg (n = 25)), Viaskin-placebo (n = 10) or laser + Viaskin-placebo (n = 2). Incidence of adverse events was similar across groups (any local event: 21/25 (84.0%), 24/25 (96.0%), 4/5 (80.0%), 24/25 (96.0%), 8/10 (80.0%), 10/12 (83.0%), respectively). Direct application induced no detectable response. On day 42, PT-IgG geometric mean concentrations were significantly higher following laser + Viaskin-PT 25 µg and 50 µg (139.87 (95% CI 87.30-224.10) and 121.76 (95% CI 95.04-156.00), respectively), than laser + Viaskin-placebo (59.49, 95% CI 39.37-89.90). Seroresponse rates were higher following laser + Viaskin-PT 25 µg (4/5 (80.0%), 95% CI 28.4-99.5) and 50 µg (22/25 (88.0%), 95% CI 68.8-97.5) than laser + Viaskin-placebo (0/12 (0.0%), 95% CI 0.0-26.5). CONCLUSIONS: Viaskin-PT applied after laser-based epidermal skin preparation showed encouraging safety and immunogenicity results: anti-PT booster responses were not inferior to those elicited by Boostrix®dTpa. This study is registered at ClinicalTrials.gov (NCT03035370) and was funded by DBV Technologies.

Spectral and Structural Variations of Biomimetic Light-Harvesting Nanotubes.

Bioinspired, self-assembled nanotubes have been investigated by low-temperature, polarization-resolved single-tube spectroscopy. These assemblies are based on zinc chlorin monomers and are considered as model systems that resemble the secondary structural elements in the natural light-harvesting systems of green (non)sulfur bacteria. Compared to the natural systems, the spectral parameters extracted from the single-nanotube spectra feature distributions with significantly smaller widths, which is ascribed to a tremendous reduction of structural heterogeneity in the artificial systems. Employing quantum chemical molecular modeling the spectra of individual nanotubes can be explained consistently only for a molecular packing model that is fundamentally different from those considered so far for the natural systems. Subsequent theoretical simulations reveal that the remaining spectral variations between single nanotubes can be traced back to small variations of the mutual orientations of the monomer transition dipole moments that are far beyond the resolving power of high-resolution electron microscopy imaging techniques.

Multicenter methodology comparison of the FDA and ISO standard for measurement of in vitro UVA protection of sunscreen products.

In vitro standard methods are available and accepted worldwide to assess UVA protection of sunscreen products. Though, harmonisation of methods has made progress in the last decade, still two differing methods - one by FDA the other by ISO - are in use. In a multicentre study including 9 centres in Germany, 4 different commercial sunscreen products were assessed using both methods to discover their similarities and differences. UVA protection factor and Critical Wavelength were detected at various substrate type (sandblasted versus moulded PMMA plates), at different surface roughness of the plates as well as at different product application dose using two different irradiation spectra. Results: The strongest influence on UVA protection factor results from the surface roughness of the plates. Depending on the roughness (accepted range of 2 to 7 µm in the FDA method) a variability in the UVA protection factor of up to 25% was observed, while the much narrower definition of plate roughness by ISO (4.5 to 5.2 µm) had no relevant influence on the test results. Sandblasted plates in our assessment led to higher UVA protection factors and produced less scattered results compared to moulded plates. These differences were not pronounced. Application dose and spectra of the irradiation source were of negligible influence on UVA protection factor results for the investigated UV-filter combinations. The UVA protection factor which is the endpoint of the ISO method was found to be a parameter with a high potential to differentiate among different test products. The endpoint of the FDA method - the Critical Wavelength - was found to be an unambitious endpoint. Insensitivity to all described modifications of the method was observed. All investigated products performed similar and passed the Critical Wavelength criteria independent of method and parameters.

[Bilateral pulmonary embolism mimicking acute chest syndrome in an adolescent with sickle cell disease]. / Embolie pulmonaire bilatérale mimant un syndrome thoracique aigu chez un adolescent drépanocytaire.

Pulmonary embolism is a life-threatening and potentially lethal disease. Its incidence in children with sickle cell disease is probably underestimated and pediatric case reports in the literature are rare. Moreover, symptoms can mimic an acute chest syndrome. We report on the case of a 17-year-old boy with SS sickle cell disease, admitted for chest pain with dyspnea and tachycardia. Pulmonary angiography revealed a partial bilateral obstructive pulmonary embolism. We did not find any deep venous thrombosis or thrombophilia. The progression was rapidly favorable with anticoagulant therapy. We recommend a pulmonary angiography for any chest pain that does not evolve favorably in a child with sickle cell disease. Large series of pediatric patients would be useful to establish diagnostic and therapeutic guidelines.

Retroperitoneal anatomy of the iliohypogastric, ilioinguinal, genitofemoral, and lateral femoral cutaneous nerve: consequences for prevention and treatment of chronic inguinodynia.

PURPOSE: Chronic inguinodynia is one of the most frequent complications after groin herniorrhaphy. We investigated the retroperitoneal anatomy of the iliohypogastric, ilioinguinal, genitofemoral, and lateral femoral cutaneous nerve to prevent direct nerve injury during hernia repairs and to find the most advantageous approach for posterior triple neurectomy. METHODS: We dissected the inguinal nerves in 30 human anatomic specimens bilaterally. The distances from each nerve and their entry points in the abdominal wall were measured in relation to the posterior superior iliac spine, anterior superior iliac spine, and the midpoint between the two iliac spines on the iliac crest. We evaluated our findings by creating high-resolution summation images. RESULTS: The courses of the iliohypogastric and ilioinguinal nerve are most consistent on the anterior surface of the quadratus lumborum muscle. The genitofemoral nerve always runs on the psoas muscle. The entry points of the nerves in the abdominal wall are located as follows: the iliohypogastric nerve is above the iliac crest and lateral from the anterior superior iliac spine, the ilioinguinal nerve is with great variability, either above or below the iliac crest and lateral from the anterior superior iliac spine, the genital branch is around the internal inguinal ring, the femoral branch is either cranial or caudal to the iliopubic tract, and the lateral femoral cutaneous nerve is either medial or lateral to the anterior superior iliac spine. CONCLUSION: Nerve injury during inguinal hernia repairs can be avoided by taking the topographic anatomy of the inguinal nerves into consideration. The most advantageous plane to look for the iliohypogastric and ilioinguinal nerve during posterior neurectomy is on the anterior surface of the quadratus lumborum muscle. For the surgical treatment of severe chronic inguinodynia, especially after posterior open or endoscopic mesh repair (TAPP/TEP), the retroperitoneoscopic or open retroperitoneal approach for posterior triple neurectomy can be considered.

HNA antibody-mediated neutrophil aggregation is dependent on serine protease activity.

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is often caused by antibodies against human neutrophil alloantigen-2 (HNA-2) and HNA-3a. Neutrophil aggregation is considered as a major cause of TRALI, but little is known about how HNA antibodies initiate this process. We explored mechanisms involved in neutrophil aggregation induced by HNA-2 and HNA-3a antibodies. MATERIALS AND METHODS: Isolated neutrophils were pretreated with broad-spectrum or specific inhibitors against different cell functions or proteases. Granulocyte agglutination test (GAT) was performed with serially diluted anti-HNA-2 and anti-HNA-3a plasmas or control plasma, and reactivity was evaluated microscopically. Reactive oxygen species (ROS) production in neutrophils was investigated using a lucigenin-based chemiluminescence assay. RESULTS: HNA-2 and HNA-3a antibody-mediated neutrophil aggregation was inhibited by pretreatment with formaldehyde, iodoacetamide and the serine protease inhibitors Pefabloc-SC, N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and Nα-tosyl-L-lysine chloromethyl ketone hydrochloride (TLCK). In contrast, inhibition of actin polymerization, respiratory burst, cysteine proteases, metalloproteases or aspartic proteases did not affect neutrophil aggregation. Furthermore, HNA-3a antibodies did not directly cause ROS production in neutrophils. CONCLUSION: Aggregation of neutrophils induced by HNA-2 and HNA-3a antibodies is an active process and depends on trypsin- or chymotrypsin-like serine proteases but is not dependent on the production of ROS. These findings may open new prospects for the pharmacologic prevention of neutrophil-associated acute lung injury.

Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias (International Endohernia Society (IEHS)-part 1.

Guidelines are increasingly determining the decision process in day-to-day clinical work. Guidelines describe the current best possible standard in diagnostics and therapy. They should be developed by an international panel of experts, whereby alongside individual experience, above all, the results of comparative studies are decisive. According to the results of high-ranking scientific studies published in peer-reviewed journals, statements and recommendations are formulated, and these are graded strictly according to the criteria of evidence-based medicine. Guidelines can therefore be valuable in helping particularly the young surgeon in his or her day-to-day work to find the best decision for the patient when confronted with a wide and confusing range of options. However, even experienced surgeons benefit because by virtue of a heavy workload and commitment, they often find it difficult to keep up with the ever-increasing published literature. All guidelines require regular updating, usually every 3 years, in line with progress in the field. The current Guidelines focus on technique and perioperative management of laparoscopic ventral hernia repair and constitute the first comprehensive guidelines on this topic. In this issue of Surgical Endoscopy, the first part of the Guidelines is published including sections on basics, indication for surgery, perioperative management, and key points of technique. The next part (Part 2) of the Guidelines will address complications and comparisons between open and laparoscopic techniques. Part 3 will cover mesh technology, hernia prophylaxis, technique-related issues, new technologic developments, lumbar and other unusual hernias, and training/education.

Synthesis and Spectroscopic Characterization of Diphenylargentate, [(C6H5)2Ag](.).

We present the structural and optical properties of the isolated diphenylargentate anion, which has been synthesized by multistage mass spectrometry in a quadrupole ion trap. The experimental photodetachment spectrum has been obtained by action spectroscopy. Comparison with quantum chemical calculations of the electronic absorption spectrum allows for a precise characterization of the spectroscopic features, showing that in the low-energy regime, the optical properties of diphenylargentate bear a significant resemblance to those of atomic silver.

Structural and photochemical properties of organosilver reactive intermediates MeAg2(+) and PhAg2(+).

Although there is growing interest in silver promoted carbon-carbon bond formation, a key challenge in developing robust and reliable organosilver reagents is that thermal and photochemical decomposition reactions can compete with the desired coupling reaction. These undesirable reactions have been poorly understood due to complications arising from factors such as solvent effects and aggregation. Here the unimolecular decomposition reactions of organosilver cations, RAg(2)(+), where R = methyl (Me) and phenyl (Ph), are examined in the gas phase using a combination of mass spectrometry based experiments and theoretical calculations to explore differences between thermal and photochemical decompositions. Under collision-induced dissociation conditions, which mimic thermal decomposition, both PhAg(2)(+) and MeAg(2)(+) fragment via formation of Ag(+). The new ionic products, RAg(+•) and Ag(2)(+•), which arise via bond homolysis, are observed when RAg(2)(+) is subject to photolysis using a UV-vis tunable laser OPO. Furthermore, comparisons between the theoretical and experimental UV-vis spectra allow us to unambiguously determine the most stable structures of PhAg(2)(+) and MeAg(2)(+) and to identify the central role of the silver part in the optical absorption of these species. The new photoproducts result from fragmentation in electronic excited states. In particular, potential energy surface calculations together with the fragment charges highlight the role of triplet states in these new fragmentation schemes.

Adverse effects of polyvinylidene fluoride-coated polypropylene mesh used for laparoscopic intraperitoneal onlay repair of incisional hernia.

BACKGROUND: Polyvinylidene fluoride-coated polypropylene meshes have been developed specifically for intraperitoneal onlay mesh repair. They combine a macroporous design with biomechanical characteristics compatible with the abdominal wall and are reported to have favourable antiadhesive properties. This retrospective study reports complications related to one of these materials, DynaMesh. METHODS: Twenty-nine patients underwent intraperitoneal onlay mesh repair with DynaMesh at one of two hospitals. Patients characteristics, surgical procedures and postoperative analgesia were comparable at both sites. RESULTS: Six patients developed DynaMesh-related complications that required surgical reintervention by laparotomy within 1 year of operation. Surgical reintervention was for adhesions in five patients and the mesh had to be explanted in three. One mesh was explanted because of early infection. Adhesions to DynaMesh were found in two patients who had surgery for unrelated reasons. CONCLUSION: Laparoscopic intraperitoneal onlay DynaMesh repair was associated with a high rate of complications.

Antioxidant efficacy on human skin in vivo investigated by UVA-induced chemiluminescence decay analysis via induced chemiluminescence of human skin.

BACKGROUND/AIMS: Exogenous factors (e.g. physical: UV irradiation; or chemical: hydrogen peroxide) and endogenous metabolic processes (e.g. cellular respiration, oxidative burst, etc.) generate oxidative stress in living tissues which are in balance with enzymatic antioxidative systems and ingested antioxidants under normal conditions. These complex biological reactions are accompanied by chemiluminescence (ultraweak photon emission). However, knowledge about the chemiluminescence decay characteristics of human skin and the modulatory influence of topically applied antioxidants is still scarce. METHODS: Using ICL-S (induced chemiluminescence of human skin), a highly sensitive in vivo method, the decay characteristics of UVA-induced photon emission caused by different UVA doses were investigated in detail. In addition, modulatory properties of topical antioxidant pretreatment were examined for 2 weeks. RESULTS: UVA-induced chemiluminescence signals were generally characterized by two distinct decay phases: an initial burst (0-5 s), contributing approximately 80% of the complete signal with an inverse dose-response relationship (UVA dose vs. chemiluminescence intensity), followed by a second decay phase (delayed chemiluminescence, 5-200 s) showing a direct correlation. Antioxidant pretreatment caused a reduction in signal intensity of approximately 50%, which was calculated by signal integration and confirmed using the modulation of the intersection point of decay curves resulting from irradiation with different UVA doses at constant intensity with and without treatment. CONCLUSION: In addition to the established UVA filter testing (independent from UVB filter content) on human skin in vivo, ICL-S is also a valuable tool for the efficacy testing of topically applied antioxidants under in vivo conditions in humans. The first rapid, but short, decay phase not only provides approximately 80% of the complete chemiluminescence signal, but is also essential for the investigation of antioxidant-mediated effects. Chemiluminescence signal modulations induced by UVA intensity reduction (e.g. UV filters in daily care products) can be clearly distinguished from antioxidant-mediated signal modulations. The probe head dimensions permit comprehensive in vivo testing in humans on practically every skin area (e.g. arms, legs, back, abdomen and face).

In vitro sun protection factor: still a challenge with no final answer.

In the past, several attempts have been made to develop in vitro methods for determining protection against UV radiation. To date however, there is no broadly accepted method. Various known and unknown parameters influence the transmission measurements of scattering films, such as the multifaceted compositions of sunscreens, the technical limitations of measurement devices as well as the difficulty to apply very thin films of sunscreen in a reproducible manner throughout different laboratories. In vitro data were measured in this multicenter study to compare possible methodologies and strategies for an in vitro approach to the sun protection factor (SPF). This publication will not present a final in vitro SPF test method, but it will point out which technical side effects may influence such a method. Influential factors such as the quality of spectrophotometer used, the amount of product applied, pretreatment of samples, time and temperature of equilibration, size of the measured surface, the application process or the calculation on the basis of standardized data are presented and discussed. Finally, a reduction of the standard deviations within single laboratories could be realized for in vitro SPF testing, but no improvement of the interlaboratory comparison was obtained. The development of a valid and reliable SPF in vitro test still remains a challenge, and further work is necessary to develop a satisfactory method.

Influence of applied quantity of sunscreen products on the sun protection factor--a multicenter study organized by the DGK Task Force Sun Protection.

It is often debated that the protection against solar-induced erythema under real conditions is dependent upon the amount of sunscreen applied. It is believed that when too little is applied a lower sun protection than indicated on the label will result. The aim of this study was to quantify this effect. In this multicenter study, the influence of three different amounts (0.5, 1.0, 2.0 mg/cm(2)) of three commercial sunscreen products in three reliable test centers was investigated according to the test protocol of The International Sun Protection Factor Test Method. The main result was a linear dependence of the SPF on the quantity applied. Taking into consideration the volunteer-specific variations, an exponential dependence of confidence interval of the in vivo SPF and amount applied was found. The highest amount applied (2.0 mg/cm(2)) was linked to the lowest confidence intervals. Thus, from the point of view of producing reliable and reproducible in vivo results under laboratory conditions, the recommendation of this multicenter study is an application quantity of 2.0 mg/cm(2).

Successful simultaneous kidney-pancreas transplantation from extreme donors.

UNLABELLED: The purpose of this study was to retrospectively review our experience with "extreme" pancreas donors compared to conventional (CONV) donors. METHODS: "Extreme" (EX) pancreas donors were defined as deceased donors (DDs) age >50 years, <8 years, donation after cardiac death (DCD), and targeted for organ discard. RESULTS: From January 2002 through January 2005, we performed 40 simultaneous kidney-pancreas transplants (SKPT) with Thymoglobulin induction, including 9 (22.5%) from EX and 31 from CONV DDs. Mean DD age was higher in EX DD (41.2 years EX vs 26.0 CONV, P < .05), but mean recipient age and cold ischemia times did not differ between groups. With a mean follow-up of 16.8 months in the EX DD group, patient and kidney graft survival rates are both 100%, and the pancreas graft survival rate is 89%. With a mean follow-up of 21.7 months in the CONV DD group, patient and kidney graft survival rates are both 93.5% and the pancreas graft survival rate is 77.4%. All patients with surviving grafts exhibited good initial (1 case of delayed kidney graft function in a CONV DD) and stable long-term kidney and pancreas graft function. Mean length of initial hospital stay and the incidences of acute rejection, readmissions, operative complications, and infections were similar between groups. CONCLUSIONS: The results of this study suggest that the limits of donor acceptability continue to evolve as excellent outcomes can be achieved in SKPTs from selected EX DDs.

Experience with alternate-day thymoglobulin induction in pancreas transplantation with portal-enteric drainage.

The purpose of this study was to retrospectively review outcomes in patients undergoing pancreas transplantation (PTX) with a novel induction protocol of alternate-day thymoglobulin (rATG) in combination with tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. From January 2002 through January 2005, we performed 55 PTXs in 53 patients. The first dose of rATG (1.5 mg/kg) was given intraoperatively, and subsequent doses were given on alternate days until therapeutic TAC levels (>8 ng/mL) were achieved. All patients underwent PTX with enteric drainage, including 51 with portal and 4 with systemic venous drainage. Patients received a minimum of 2 and maximum of 6 doses of rATG induction (median 3 doses). The patient group had a mean age of 42.8 years and included 40 simultaneous kidney-PTX, 11 sequential PTX after kidney, and 4 PTX-alone transplant recipients. Patient, kidney, and pancreas graft survival rates are 96%, 96%, and 84%, respectively, with a mean follow-up of 21 months. The incidence of acute rejection was 18%; there were no graft losses due to isolated acute rejection. The incidence of infection was 60%, but there were no cases of polyomavirus or Epstein-Barr virus infection and only 6 cases (11%) of cytomegalovirus infection. The composite endpoint of no rejection, graft loss, or mortality was attained by 71% of patients. At present, 94% of surviving patients are both dialysis and insulin-free, including 5 successful PTX retransplants. These findings suggest that PTX with portal-enteric drainage and alternate day rATG induction may result in excellent intermediate-term outcomes.