Endoscopic therapy for Bouveret syndrome, illustrated by a case report.

Bouveret syndrome is an exceptionally rare form of gallstone ileus secondary to a bilioenteric fistula, through which a voluminous gallstone can migrate into the pylorus or duodenum, thereby causing gastric outlet obstruction. In order to increase awareness, we reviewed the clinical features, diagnostic tools and management options for this uncommon entity. We specifically focus on endoscopic therapeutic options, illustrated by a case of a 73 year old woman with Bouveret syndrome, where endoscopic electrohydraulic lithotripsy was successful in relieving gastroduodenal obstruction.

Evaluating the neutrophil-to-lymphocyte ratio as an indicator for early referral of patients with COVID-19 pneumonia to a high-care facility.

BACKGROUND: Early identification of patients at high risk of severe disease requiring referral and treatment at a high-care facility is imperative in the management of COVID-19 pneumonia in a limited-resource setting, as transfer of unstable patients can be detrimental. OBJECTIVES: To examine the value of the neutrophil-to-lymphocyte ratio (NLR) calculated on admission to a healthcare facility as a predictor of the need for early referral to a high-care facility for further treatment. METHODS: We designed a cohort analytical study of 198 patients with COVID-19 pneumonia admitted to the COVID-19 unit at Universitas Academic Hospital in Bloemfontein, South Africa, between 20 May and 30 September 2021. RESULTS: Of the 198 patients enrolled in the study, 134 (67.7%) were admitted to high care and 93 (46.9%) died. The median (interquartile range (IQR)) NLR measured on admission to the hospital was 8.09 (4.90 - 14.86), and the NLR ranged from 0.26 to 136.7. The admission NLR was statistically significantly higher in the high-care group v. the general ward group (p<0.001). After converting the NLR to log scale, to bring it closer to conditional normality, logistic regression analysis identified log NLR (odds ratio (OR) 4.089; 95% confidence interval (CI) 2.464 - 6.787; p<0.001) and age (OR 1.029; 95% CI 1.004 - 1.056; p=0.024) as significant in determining who will require high care. The area under the receiver operating characteristic curve for the combined model of NLR and age was 0.829 (95% CI 0.767 - 0.891). An NLR cut-off value of 7.5 (sensitivity 0.7462, specificity 0.7968) has been calculated as the optimal cut-off value to determine who will need high care. Admission log NLR and age were significant in determining who died (OR 2.067; 95% CI 1.404 - 3.045; p<0.001, and OR 1.043; 95% CI 1.018 - 1.068; p=0.001, respectively). CONCLUSION: The NLR measured on admission and age can be used to predict whether a patient with COVID-19 pneumonia will require high care.

Umbilical hernia repair in patients with cirrhosis: who, when and how to treat.

PURPOSE: Hernia management in patients with cirrhosis is a challenging problem, where indication, timing and type of surgery have been a subject of debate. Given the high risk of morbidity and mortality following surgery, together with increased risk of recurrence, a wait and see approach was often advocated in the past. METHODS: The purpose of this review was to provide an overview of crucial elements in the treatment of patients with cirrhosis and umbilical hernia. RESULTS: Perioperative ascites control is regarded as the major factor in timing of hernia repair and is considered the most important factor governing outcome. This can be accomplished by either medical treatment, ascites drainage prior to surgery or reduction of portal hypertension by means of a transjugular intrahepatic portosystemic shunt (TIPS). The high incidence of perioperative complications and inferior outcomes of emergency surgery strongly favor elective surgery, instead of a "wait and see" approach, allowing for adequate patient selection, scheduled timing of elective surgery and dedicated perioperative care. The Child-Pugh-Turcotte and MELD score remain strong prognostic parameters and furthermore aid in identifying patients who fulfill criteria for liver transplantation. Such patients should be evaluated for early listing as potential candidates for transplantation and simultaneous hernia repair, especially in case of umbilical vein recanalization and uncontrolled refractory preoperative ascites. Considering surgical techniques, low-quality evidence suggests mesh implantation might reduce hernia recurrence without dramatically increasing morbidity, at least in elective circumstances. CONCLUSION: Preventing emergency surgery and optimizing perioperative care are crucial factors in reducing morbidity and mortality in patients with umbilical hernia and cirrhosis.

Evaluating the accuracy of three international guidelines in identifying the risk of malignancy in pancreatic cysts: a retrospective analysis of a surgical treated population.

BACKGROUND AND STUDY AIMS: The international consensus Fukuoka guideline (Fukuoka ICG), The European evidence-based guideline on pancreatic cystic neoplasms (European EBG) and the American Gastroenterological Association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts (AGA IG) are 3 frequently cited guidelines for the risk stratification of neoplastic pancreatic cysts. The aim of this study was to assess the accuracy of detecting malignant cysts by strictly applying these guidelines retrospectively to a cohort of surgically resected pancreatic cysts. PATIENTS AND METHODS: 72 resected cysts were included in the analysis. Invasive carcinoma, high grade dysplasia and neuro-endocrine tumour were considered as "malignant cysts" for the purpose of the study. RESULTS: 32% of the resected cysts were malignant. The analysis showed that the Fukuoka ICG, European EBG and AGA IG had a sensitivity of 66,8%, 95,5%, 80%; a specificity of 26,8%, 11,3%, 43,8%; a positive predictive value of 31,8%, 35%, 47,1% and a negative predicted value of 61,1%, 83,3%, 77,8% respectively. The missed malignancy rate was respectively 11,3%, 1,5%, 7,7% and surgical overtreatment was respectively 48,4%, 59,1%, 34,6%. CONCLUSION: In this retrospective analysis, the European EBG had the lowest rate of missed malignancy at the expense of a high number of "unnecessary" resections. The Fukuoka ICG had the highest number of missed malignancy. The AGA IG showed the lowest rate of unnecessary surgery at the cost of a high number of missed malignancy. There is need to develop better biomarkers to predict the risk of malignancy.

The epidemiology and orthopaedic burden of civilian gunshot injuries over a four-year period at a level one trauma unit in Cape Town, South Africa.

PURPOSE: The aim of this study was to quantify the overall burden of orthopaedic gunshot-related injuries at our institution over a four year period. Secondary aims included identifying complications from gunshot-related injuries and the additional burden it places on healthcare services. METHODS: A retrospective review was conducted on all patients with gunshot injuries presenting to our hospital's trauma unit between January 2014 and December 2017. Patient data was recorded, and demographic data, number and type of implants, blood products used, duration of hospital admission, duration of ICU admission, radiological studies performed, and prevalence of complications were analysed. RESULTS: A total of 1449 patients with a mean age of 28.2 ± 9.7 years (range 2.0-71.0) were included in this study. The majority of these gunshot-related orthopaedic injuries were sustained to the lower extremities and were treated non-operatively. The median duration of hospital stay was 7.0 (IQR 4.0-12.0). The most common complications identified were nerve injury (8.3%), vascular injury (6.5%), fracture-related infection (3.2%), non-union (3.1%), and compartment syndrome (1.6%). The total cost of care was ZAR 53,568,537 (USD 4,320,043) with an average cost per patient of ZAR 37,031 (USD 2986). CONCLUSION: This study highlighted the burden of gunshot injuries presenting to our hospital and the strain it places on its healthcare resources. The prevalence of complications was comparable to international studies on the subject. With improved understanding of this burden, more healthcare resources can be allocated to this problem and better prevention strategies can be planned.

Zero-order and prolonged release of atenolol from microporous FAU and BEA zeolites, and mesoporous MCM-41: Experimental and theoretical investigations.

The potential of microporous zeolites FAU and BEA, and mesoporous MCM-41, for prolonged release of atenolol in drug delivery systems was investigated both experimentally, using drug release studies, and theoretically using classical molecular dynamics simulations. Remarkably, zero-order release of atenolol was achieved from FAU (SiO2:Al2O3 = 80:1) into phosphate buffer for 24 h followed by prolonged release for at least another 48 h. Experimental data also demonstrate the ability for all of the drug-zeolite combinations investigated to achieve prolonged release of atenolol, with the release rates determined by the combination of framework topology, aluminium content and drug release study media. Molecular dynamics simulations give an insight into the reasons for the different release rates observed for FAU and BEA. The results of this work emphasise the need for sophisticated models in order to explain subtle differences in release, such as those observed at different SiO2:Al2O3 ratios.

Histamine-mediated potentiation of transient receptor potential (TRP) ankyrin 1 and TRP vanilloid 4 signaling in submucosal neurons in patients with irritable bowel syndrome.

Previously, we showed histamine-mediated sensitization of transient receptor potential (TRP) vanilloid 1 (TRPV1) in patients with irritable bowel syndrome (IBS). Sensitization of TRP ankyrin 1 (TRPA1) and TRP vanilloid 4 (TRPV4) are also involved in aberrant pain perception in preclinical models of somatic pain. Here, we hypothesize that in parallel with TRPV1, histamine sensitizes TRPA1 and TRPV4, contributing to increased visceral pain in patients with IBS. Rectal biopsies were collected from patients with IBS and healthy subjects (HS) to study neuronal sensitivity to TRPA1 and TRPV4 agonists (cinnamaldehyde and GSK1016790A) using intracellular Ca2+ imaging. In addition, the effect of supernatants of rectal biopsies on patients with IBS and HS was assessed on TRPA1 and TRPV4 responses in murine dorsal root ganglion (DRG) sensory neurons. Finally, we evaluated the role of histamine and histamine 1 receptor (H1R) in TRPA1 and TRPV4 sensitization. Application of TRPA1 and TRPV4 agonists evoked significantly higher peak amplitudes and percentage of responding submucosal neurons in biopsies of patients with IBS compared with HS. In HS, pretreatment with histamine significantly increased the Ca2+ responses to cinnamaldehyde and GSK1016790A, an effect prevented by H1R antagonism. IBS supernatants, but not of HS, sensitized TRPA1 and TRPV4 on DRG neurons. This effect was reproduced by histamine and prevented by H1R antagonism. We demonstrate that the mucosal microenvironment in IBS contains mediators, such as histamine, which sensitize TRPV4 and TRPA1 via H1R activation, most likely contributing to increased visceral pain perception in IBS. These data further underscore H1R antagonism as potential treatment for IBS. NEW & NOTEWORTHY We provide evidence for histamine-mediated transient receptor potential (TRP) ankyrin 1 and TRP vanilloid 4 sensitization in irritable bowel syndrome (IBS) via histamine 1 receptor (H1R) activation, most likely contributing to increased visceral pain perception. Our results reveal a general role of sensory TRP channels as histamine effectors in the pathophysiology of IBS and provide novel mechanistic insights into the therapeutic potential of H1R antagonism in IBS.

Improved survival after LTx-associated acute GVHD with mAb therapy targeting IL2RAb and soluble TNFAb: Single-center experience and systematic review.

Acute graft-versus-host disease (GVHD) after liver transplant (LTx) is a rare complication with a high mortality rate. Recently, monoclonal antibody (mAb) treatment, specifically with anti-interleukin 2 receptor antibodies (IL2RAb) and anti-tumor necrosis factor-α antibodies (TNFAb), has gained increasing interest. However, evidence is mostly limited to case reports and the efficacy remains unclear. Here, we describe 5 patients with LTx-associated GVHD from our center and provide the results of our systematic literature review to evaluate the potential therapeutic benefit of IL2RAb/TNFAb treatment. Of the combined population of 155 patients (5 in our center and 150 through systematic search), 24 were given mAb (15.5%)-4 with TNFAb (2.6%) and 17 with IL2RAb (11%) ("mAb group")-and compared with patients who received other treatments (referred to as "no-mAb group"). Two-sided Fisher exact tests revealed a better survival when comparing treatment with mAb versus no-mAb (11/24 vs 27/131; P = .018), TNFAb versus no-mAb (3/4 vs 27/131; P = .034), and IL2RAb versus no-mAb (8/17 vs 27/131; P = .029). This systematic review suggests a beneficial effect of mAb treatment and a promising role for TNFAb and IL2RAb as a first-line strategy to treat LTx-associated acute GVHD.

Nutritional supplements for people being treated for active tuberculosis: A technical summary.

Tuberculosis and nutrition are intrinsically linked in a complex relationship. Altered metabolism and loss of appetite associated with tuberculosis may result in undernutrition, which in turn may worsen the disease or delay recovery. We highlight an updated Cochrane review assessing the effects of oral nutritional supplements in people with active tuberculosis who are receiving antituberculosis drug therapy. The review authors conducted a comprehensive search (February 2016) for all randomised controlled trials comparing any oral nutritional supplement, given for at least 4 weeks, with no nutritional intervention, placebo or dietary advice only in people receiving antituberculosis treatment. Of the 35 trials (N=8 283 participants) included, seven assessed the provision of free food or high-energy supplements, six assessed multi-micronutrient supplementation, and 21 assessed single- or dual-micronutrient supplementation. There is currently insufficient evidence to indicate whether routinely providing free food or high-energy supplements improves antituberculosis treatment outcomes (i.e. reduced death and increased cure rates at 6 and 12 months), but it probably improves weight gain in some settings. Plasma levels of zinc, vitamin D, vitamin E and selenium probably improve with supplementation, but currently no reliable evidence demonstrates that routine supplementation with multi-, single or dual micronutrients above the recommended daily intake has clinical benefits (i.e. reduced death, increased cure rate at 6 and 12 months, improved nutritional status) in patients receiving antituberculosis treatment. In South Africa, most provinces implement a supplementation protocol based on nutritional assessment and classification of individuals rather than on disease diagnosis or treatment status.

Budd-Chiari syndrome: reassessment of a step-wise treatment strategy.

BACKGROUND AND STUDY AIMS: The Budd-Chiari syndrome is a rare disorder characterized by hepatic venous outflow obstruction. A step-wise management was recently proposed. The aim of this study is to reassess our treatment approach and long-term outcome. PATIENTS AND METHODS: The data of 37 Budd-Chiari patients, seen in our unit, were critically analyzed and compared with the ENVIE (European Network For Vascular Disorders of the Liver) data. RESULTS: Most patients had multiple prothrombotic conditions (41%), of which an underlying myeloproliferative neoplasm was the most frequent (59%). The JAK2V617F mutation was associated with more complete occlusion of all hepatic veins (JAK2 mutation +: 70% vs JAK2 mutation -: 23% and a higher severity score. The step-wise treatment algorithm used in our unit, in function of the severity of the liver impairment and the number and the extension of hepatic veins occluded, resulted in the following treatments: only anticoagulation (n = 7.21%), recanalization procedure (n = 4.21%), portosystemic shunts (n = 9.26%) and liver transplantation (n = 14.44%). This resulted in a 10 year survival rate of 90%. Treatment of the underlying hemostatic disorder offered a low recurrence rate. None of the 21 patients with a myeloproliferative neoplasm died in relation to the hematologic disorder. CONCLUSIONS: An individualized treatment regimen consisting of anticoagulation and interventional radiology and/or transplantation when necessary and strict follow-up of the underlying hematologic disorder, provided an excellent long-term survival, which confirm the data of the ENVIE study.

Electrohydrodynamic Preparation of Nanomedicines.

The preparation of nanomedicines can be achived using a host of methods ranging from wet-chemical approaches to more engineering related techniques. As a maturing branch of nanotechnology, nanomedcines are being tailored to serve multiple pharmaceutic and biomedical related funcitons (e.g. targeted delivery, imaging, healing, sensing which may require the utilisaiton of one or more actives or excipients. In some instances, handling of materials (such as sensitive biomolecules or active pharmaceutical ingredient) becomes a limiting factor along with issues related to fabrication steps (loss or degradation of active components and functional materials, deposition location & procedure (removal of formed structures, process environment sensitivity and scale-up potential. This short review focuses on the electrohydrodynamic preparation of emerging nanomedicines that have potential to serve as therapeutic platforms. An insight into the underpinning process (jet-formation, related paramerts (material and process and strucutral outcomes (particles and fibres is given in relation to highlighted research. The ambient temperature processing, user friendly preparation and present industrial scale up potential (now in kg/hr make such processes valuable in the preparation of future nano-scaled and sensitive dosage forms.

Combined liver and lung transplantation with extended normothermic lung preservation in a patient with end-stage emphysema complicated by drug-induced acute liver failure.

Isolated lung transplantation (LuTx) and liver transplantation are established treatments for irreversible lung and liver failure. Combined liver and lung transplantation (cLiLuTx) is a less common, but approved therapy of combined organ failure, mostly applied in patients suffering from progressive cystic fibrosis and advanced liver disease. We report a patient who was listed for LuTx due to end-stage chronic obstructive pulmonary disease and who developed drug-induced acute hepatic failure. The only therapeutic option was hyper-urgent cLiLuTx. To correct the poor coagulation in order to reduce the per-operative risk of bleeding, the liver was transplanted first. In anticipation of the longer lung preservation time, cold flushed lungs were preserved on a portable lung perfusion device for ex vivo normothermic perfusion for 11 h 15 min, transplanted sequentially off-pump, and reperfused after a total ex vivo time of 13 h 32 min and 16 h for the first and second lung, respectively. Ten months later, the patient is doing well and no rejection occurred. Normothermic ex vivo lung perfusion may help to prolong preservation time, facilitating long-distance transport and combined organ transplantation.

Sex-related trends in non-conversion of new smear-positive tuberculosis patients in the Free State, South Africa.

SETTING: Free State Province, South Africa. OBJECTIVE: To examine sex-specific trends in 2-month sputum smear non-conversion in new sputum smear-positive tuberculosis (TB) cases during a period when the DOTS strategy was operative. DESIGN: A retrospective cohort study of TB cases registered between 2003 and 2009 was conducted. Non-conversion was indicated by a positive 2-month sputum smear result. Descriptive and generalised linear model analyses were performed and sex-specific trends in 2-month sputum smear non-conversion rates estimated. RESULTS: Overall, 2-month sputum smear non-conversion rates were 12.5% in males and 9.3% in females. Non-conversion was significantly associated with age in males (P < 0.001). Non-conversion rates declined significantly between 2003 and 2009: from 15.9% to 10.8% in males (P < 0.001) and from 12.0% to 6.6% in females (P < 0.001). The average rate of decline of non-conversion was higher among females (1.0%, 95%CI 0.8-1.2) than among males (0.8%, 95%CI 0.5-1.0). By 2009, males had a 60% higher risk of non-conversion than females (RR 1.60, CI 1.37-1.86). CONCLUSION: The decline in the trend of 2-month sputum smear non-conversion confirms the relative success of the DOTS strategy in TB control, with better performance among females than males. Interventions should consider the sex and age of patients to improve the 2-month sputum smear-conversion rate.

Contexte : Province de l'Etat Libre, Afrique du Sud.Objectif : Examiner les tendances en fonction du sexe de la nonconversion des frottis de crachats après 2 mois chez des nouveaux cas de tuberculose (TB) à frottis positifs pendant une période où la stratégie DOTS opérait.Schéma : Réalisation d'une étude rétrospective de cohorte des cas de TB enregistrés entre 2003 et 2009. La non-conversion était définie par un résultat de frottis positif après 2 mois de traitement. Des analyses descriptives et de modèles linéaires généralisés ont été réalisées et les tendances de non conversion à 2 mois en fonction du sexe ont été estimées.Résultats : Le taux d'ensemble de non conversion était de 12,5% chez les hommes et de 9,3% chez les femmes. La non conversion était significativement associée à l'âge chez les hommes (P < 0,001). Le taux de non conversion a significativement diminué entre 2003 et 2009 de 15,9% à 10,8% chez les hommes (P < 0,001) et de 12% à 6,6% chez les femmes (P < 0,001). Le taux moyen de déclin de la non-conversion était plus élevé chez les femmes à 1% (IC95% 0,8­1,2%) que chez les hommes à 0,8% (IC95% 0,5­1%). En 2009, le risque de non conversion était plus élevé de 60% chez les hommes (RR 1,60; IC95% 1,37­1,86).Conclusion : Le déclin de la tendance à la non-conversion du frottis de crachats après 2 mois de traitement a mis en évidence le succès relatif de la stratégie DOTS dans la lutte contre la TB, avec un meilleur résultat chez les femmes que chez les hommes. Les interventions devraient tenir compte du sexe et de l'âge des patients afin d'améliorer le taux de conversion du frottis de crachats à 2 mois.

Marco de referencia: La Provincia del Estado Libre en África del Sur.Objetivo: Examinar las tendencias específicas de sexo, con respecto a la falta de conversión de la baciloscopia del esputo a los 2 meses de tratamiento, en los casos nuevos de tuberculosis (TB) con baciloscopia positiva, durante un período de aplicación de la estrategia DOTS.Métodos: Se llevó a cabo un estudio retrospectivo de cohortes de los casos de TB registrados entre el 2003 y el 2009. La falta de conversión se definió como la obtención de un resultado positivo de la baciloscopia del esputo a los 2 meses. Se practicaron análisis con modelos generales lineales y se calculó la tendencia de la falta de conversión a los 2 meses, según las tasas específicas de sexo.Résultados: En general, las tasas de falta de conversión fueron 12,5% en los hombres y 9,3% en las mujeres. La falta de conversión se asoció de manera significativa con la edad en los hombres (P < 0,001). El índice de falta de conversión disminuyó de manera considerable entre el 2003 y el 2009, de 15,9% a 10,8% en los hombres (P < 0,001) y de 12,0% a 6,6% en las mujeres (P < 0,001). La tasa promedio de disminución de la falta de conversión en las mujeres de 1,0 % (IC95% de 0,8% a 1,2%) fue más alta que la tasa de 0,8% en los hombres (IC95% de 0,5% a 1,0%). En el 2009, los hombres exhibieron un riesgo de falta de conversión superior en 60,0 % a las mujeres (RR 1,60; IC95% de 1,37 a 1,86).Conclusión: La tendencia a la disminución de la falta de conversión de la baciloscopia a los 2 meses de tratamiento define la eficacia relativa de la estrategia DOTS en el control de la TB y ofrece un mejor rendimiento en las mujeres que en los hombres. Con el propósito de mejorar las tasas de conversión, las intervenciones deben tener en cuenta el sexo y la edad de los pacientes.

South African guideline for the management of chronic hepatitis B: 2013.

Hepatitis B remains a significant yet preventable health issue in South Africa. The introduction of the hepatitis B vaccine into the country some 18 years ago has demonstrated benefit, but the exposure to, and prevalence of chronic HBsAg positivity remain unacceptably high. Those with chronic hepatitis B virus infection have an elevated risk of developing cirrhosis with end-stage liver disease and a markedly elevated risk of hepatocellular carcinoma, independent of the presence of cirrhosis. The challenge in South Africa remains prevention through the universal vaccination coverage of all children and the identification of those with chronic hepatitis B virus infection. Over the last decade our understanding of hepatitis B and its behaviour and natural history in those with chronic infection has significantly improved. This understanding is key to identifying those who warrant further evaluation and therapy. A number of global societies have updated their guidelines in recent years. This document draws on these guidelines and serves to contextualise, for South Africa, practice guidelines for the management of chronic hepatitis B.

Prevalence of and risk factors for retinopathy of prematurity in a cohort of preterm infants treated exclusively with non-invasive ventilation in the first week after birth.

OBJECTIVES: To determine the current prevalence of retinopathy of prematurity (ROP) in premature babies treated with non-invasive ventilation at Tygerberg Children's Hospital, Parow, Cape Town, South Africa, and to identify risk factors associated with the development of ROP. METHODS: A retrospective medical records review of infants screened for ROP during a 2-year period (January 2009 - December 2010). Infants who did not receive invasive ventilation during the first week of life were included. Twenty-four previously reported risk factors for the development of ROP were identified for use in a multivariate logistic regression (MLR) analysis. RESULTS: A total of 356 patients were included. The overall prevalence of ROP was 21.8% and that of clinically significant ROP (CSROP) 4.4%. The risk factors with a statistically significant association with the development of ROP on MLR analysis were severe apnoea (p=0.0005) and decreasing birth weight (p=0.0382). CONCLUSIONS: There is a low prevalence of ROP in the cohort of preterm infants treated exclusively with non-invasive ventilation in the first week of life. The risk factors of importance in our population were severe apnoea and lower birth weight. Birth weight is a practical and reproducible variable that can be used to aid development of ROP screening criteria.

A once-a-day dosage form for the delivery of insulin through the nasal route: in vitro assessment and in vivo evaluation.

An in situ thermogelling, mucoadhesive formulation based on N-trimethyl chitosan chloride has been evaluated for its potential to affect the transmucosal delivery of insulin via the nasal route. In vitro studies at a physiologically relevant temperature (ca. 35 °C) have shown that the formulation releases most of its insulin load (ca. 70%) in a non-Fickian manner during the timescale over which the sol-to-gel transition (ca. 8 min) takes place, and also that, once gelation is complete, the release of the remainder of the therapeutic content follows first order kinetics over at least sixty minutes. Investigations on the effects of the application of the same formulation to a modelled nasal mucosa (Calu-3 cell monolayer) have indicated the capability of the formulation to induce the transient opening of tight junctions. Cytotoxic investigations have shown that the formulation exhibits negligible detrimental effects to the integrity of these monolayers. The in vivo potential of the nasal formulation to act as a once-a-day dosage form for the intranasal delivery of insulin has been demonstrated in a diabetic-rat model.

Septuagenarian and octogenarian donors provide excellent liver grafts for transplantation.

BACKGROUND: Wider utilization of liver grafts from donors ≥ 70 years old could substantially expand the organ pool, but their use remains limited by fear of poorer outcomes. We examined the results at our center of liver transplantation (OLT) using livers from donors ≥ 70 years old. METHODS: From February 2003 to August 2010, we performed 450 OLT including 58 (13%) using donors ≥ 70 whose outcomes were compared with those using donors <70 years old. RESULTS: Cerebrovascular causes of death predominated among donors ≥ 70 (85% vs 47% in donors <70; P < .001). In contrast, traumatic causes of death predominated among donors <70 (36% vs 14% in donors ≥ 70; P = .002). Unlike grafts from donors <70 years old, grafts from older individuals had no additional risk factors (steatosis, high sodium, or hemodynamic instability). Both groups were comparable for cold and warm ischemia times. No difference was noted in posttransplant peak transaminases, incidence of primary nonfunction, hepatic artery thrombosis, biliary strictures, or retransplantation rates between groups. The 1- and 5-year patient survivals were 88% and 82% in recipients of livers <70 versus 90% and 84% in those from ≥ 70 years old (P = .705). Recipients of older grafts, who were 6 years older than recipients of younger grafts (P < .001), tended to have a lower laboratory Model for End-Stage Liver Disease score (P = .074). CONCLUSIONS: Short and mid-term survival following OLT using donors ≥ 70 yo can be excellent provided that there is adequate donor and recipient selection. Septuagenarians and octogenarians with cerebrovascular ischemic and bleeding accidents represent a large pool of potential donors whose wider use could substantially reduce mortality on the OLT waiting list.

Outcomes of liver transplantations using donations after circulatory death: a single-center experience.

INTRODUCTION: Orthotopic liver transplantation (OLT) (LTx) using donation after circulatory death (DCD) donors is increasingly performed, but still considered to risk of poorer outcomes compared with standard donations after brain death (DBD)-OLT. Therefore we reviewed our results of DCD-OLT. PATIENTS AND METHODS: Between 2003 and 2010, we performed 30 DCD-OLT (6% of all OLT). We retrospectively reviewed medical records of donors and recipients after DCD versus DBD-OLT to analyze biliary complications, retransplantation rates, and patient/graft survivals. RESULTS: Median donor age was similar for DCD and DBD-OLT: 51 versus 53 years (P = .244). Median donor warm ischemia time (stop ventilation to cold perfusion in DCD donors) was 24 minutes. Median cold ischemia time was shorter for DCD (6 hours 54 minutes) compared with DBD-OLT (8 hours 36 minutes; P < .0001). Median laboratory model of end-stage liver disease score was 15 for DCD, and 16 for DBD-OLT (P = .59). Median post-OLT Aspartate Aminotransferase (AST) peak was higher after DCD: 1178 versus DBD-OLT 651 IU/L (P = .005). The incidence of nonanastomotic strictures was different: 33.3% for DCD versus 12.5% for DBD-OLT (P = .001). The overall retransplantation rate was 3% after both DCD and DBD-OLT. After DCD-LTx actuarial 1, 3- and 5-year patient survivals were 93, 85 and 85%, and corresponding graft survivals, 90%, 82%, and 82% respectively, and not different compared with DBD-OLT: 88%, 78%, and 72% (P = .348) and 85%, 74%, and 68% (P = .524) respectively. CONCLUSION: Despite substantial ischemic injury (high peak AST and biliary strictures) short- and long-term survival after DCD-OLT was comparable to DBD-OLT. Rapid donor surgery, careful donor and recipient selection, as well as short warm and cold ischemia times are key factors to optimize outcomes after DCD-OLT. However, strategies to reduce biliary complications remain warranted.