Characteristics and outcomes of COVID-19 in heart transplantation recipients in the Netherlands.

BACKGROUND: Immunocompromised patients are at high risk of complicated severe acute respiratory coronavirus 2 infection. The aim of this retrospective study was to describe the characteristics and outcomes of heart transplantation (HTx) recipients with coronavirus disease 2019 (COVID-19) in the Netherlands. METHODS: HTx patients from one of the three HTx centres in the Netherlands with COVID-19 (proven by positive reverse-transcription polymerase chain reaction or serology test result) between February 2020 and June 2021 were included. The primary endpoint was all-cause mortality and the secondary endpoint was disease severity. RESULTS: COVID-19 was diagnosed in 54/665 HTx patients (8%), with a mean (±â€¯standard deviation (SD)) time after HTx of 11 ± 8 years. Mean (±â€¯SD) age was 53 ± 14 years and 39% were female. Immunosuppressive therapy dosage was reduced in 37% patients (20/54). Hospitalisation was required in 39% patients (21/54), and 13% patients (7/54) had severe COVID-19 (leading to intensive care unit (ICU) admission or death). In-hospital mortality was 14% (3/21), and all-cause mortality was 6%. Compared with patients with moderate COVID-19 (hospitalised without ICU indication), severe COVID-19 patients tended to be transplanted earlier and had a significantly higher mean (±â€¯SD) body mass index (26 ± 3 vs 30 ± 3 kg/m2, p = 0.01). Myocardial infarction, cellular rejection and pulmonary embolism were observed once in three different HTx patients. CONCLUSION: HTx patients were at increased risk of complicated COVID-19 with frequent hospitalisation, but the all-cause mortality was substantially lower than previously described (7-33%).

Enthesis: not the same in each localisation - a molecular, histological and biomechanical study.

The interphase between tendon and bone consists of a highly specialised tissue called enthesis. Typically, the enthesis is described as a succession of four different zones: tendon, non-mineralised fibrocartilage, mineralised fibrocartilage and bone. However, the microstructure of the entheses, cellular composition and mechanical properties vary depending on their anatomical location. The present study aimed to characterise three of the most relevant sites of enthesis injury in a rat model: the patellar tendon, the Achilles tendon and the supraspinatus enthesis, in terms of biomechanics, histology and genetic expression. The patellar enthesis presented the highest ultimate load and lowest stiffness of the three, while the supraspinatus was the weakest and stiffest. The histological characterisation revealed key differences at the insertion site for each enthesis. The patellar enthesis showed a large cartilaginous area at the tendon-to-bone interphase whilst this interphase was smaller in the supraspinatus entheses samples. Furthermore, the Achilles tendon enthesis displayed a more abrupt transition from tendon to bone. Additionally, each enthesis exhibited a particular and distinct pattern of expression of tenogenic, chondrogenic and osteogenic markers. This study provided valuable insights for a better understanding of the three entheses at relevant anatomical sites. Moreover, the larger cross-sectional area of the patellar enthesis, the strong mechanical properties and the easier surgical access to this location led to the conclusion that the patellar tendon enthesis site could be most suitable for the development of a preclinical model for general enthesis regeneration studies in rats.

Mechanical and strain behaviour of human Achilles tendon during in vitro testing to failure.

The Achilles tendon is the strongest tendon in the human body but its mechanical behaviour during failure has been little studied and the basis of its high tensile strength has not been elucidated in detail. In the present study, healthy, human, Achilles tendons were loaded to failure in an anatomically authentic fashion while the local deformation and strains were studied in real time, with very high precision, using digital image correlation (DIC). The values determined for the strength of the Achilles tendon were at the high end of those reported in the literature, consistent with the absence of a pre-existing tendinopathy in the samples, as determined by careful gross inspection and histology. Early in the loading cycle, the proximal region of the tendon accumulated high lateral strains while longitudinal strains remained low. However, immediately before rupture, the mid-substance of the Achilles tendon, its weakest part, started to show high longitudinal strains. These new insights advance the understanding of the mechanical behaviour of tendons as they are stretched to failure.

Interleukin 13 (IL-13)-regulated expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging cartilage.

OBJECTIVE: The adamalysin metalloproteinase 15 (ADAM15) has been shown to protect against development of osteoarthritis in mice. Here, we have investigated factors that control ADAM15 levels in cartilage. DESIGN: Secretomes from wild-type and Adam15 -/- chondrocytes were compared by label-free quantitative mass spectrometry. mRNA was isolated from murine knee joints, either with or without surgical induction of osteoarthritis on male C57BL/6 mice, and the expression of Adam15 and other related genes quantified by RT-qPCR. ADAM15 in human normal and osteoarthritic cartilage was investigated similarly and by fluorescent immunohistochemistry. Cultured HTB94 chondrosarcoma cells were treated with various anabolic and catabolic stimuli, and ADAM15 mRNA and protein levels evaluated. RESULTS: There were no significant differences in the secretomes of chondrocytes from WT and Adam15 -/- cartilage. Expression of ADAM15 was not altered in either human or murine osteoarthritic cartilage relative to disease-free controls. However, expression of ADAM15 was markedly reduced upon aging in both species, to the extent that expression in joints of 18-month-old mice was 45-fold lower than in that 4.5-month-old animals. IL-13 increased expression of ADAM15 in HTB94 â€‹cells by 2.5-fold, while modulators of senescence and autophagy pathways had no effect. Expression of Il13 in the joint was reduced with aging, suggesting this cytokine may control ADAM15 levels in the joint. CONCLUSION: Expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging human and murine joints, possibly due to a concomitant reduction in IL-13 expression. We thus propose IL-13 as a novel factor contributing to increased osteoarthritis risk upon aging.

Effects of FK506 on the healing of diaphyseal, critical size defects in the rat femur.

There is much interest in understanding the influence of the immune system on bone healing, including a number of reports suggesting a beneficial effect of FK506 (tacrolimus) in this regard. The influence of FK506 in a rat, femoral, critical size defect was examined using locally implanted, recombinant, human (rh) BMP-2 and adenovirally-transduced, autologous, adipose-derived mesenchymal stromal cells (AD-MSCs) expressing BMP-2. FK506 was delivered systemically using an implanted osmotic pump. Empty defects and those implanted with unmodified AD-MSCs did not heal in the presence or absence of FK506. Defects treated with rhBMP-2 healed with a large callus containing thin cortices and wispy trabeculae; this, too, was unaffected by FK506. A third of defects implanted with adenovirally-transduced AD-MSCs healed, but this improved to 100 % in the presence of FK506. New bone formed in response to BMP-2 synthesised endogenously by the genetically modified cells had a slimmer callus than those healed by rhBMP-2, with improved cortication and advanced reconstitution of marrow. These results suggest that FK506 may have had little effect on the intrinsic biology of bone healing, but improved healing in response to adenovirally-transduced cells by inhibiting immune responses to the first-generation adenovirus used here. Because the genetically modified cells produced bone of higher quality at far lower doses of BMP-2, this approach should be explored in subsequent research.

Implementation of the WHO hand hygiene strategy in Faranah regional hospital, Guinea.

BACKGROUND: Healthcare-associated infections are the most frequent adverse events in healthcare worldwide, with limited available evidence suggesting highest burden in resource-limited settings. Recent Ebola epidemics emphasize the disastrous impact that spread of infectious agents within healthcare facilities can have, accentuating the need for improvement of infection control practices. Hand hygiene (HH) measures are considered to be the most effective tool to prevent healthcare-associated infections. However, HH knowledge and compliance are low, especially in vulnerable settings such as Guinea. The aim of PASQUALE (Partnership to Improve Patient Safety and Quality of Care) was to assess knowledge and compliance with HH and improve HH by incorporating the WHO HH Strategy within the Faranah Regional Hospital (FRH), Guinea. METHODS: In a participatory approach, a team of FRH staff and leadership was invited to identify priorities of the hospital prior to the start of PASQUALE. The local hygiene committee was empowered to increase its activities and take ownership of the HH improvement strategy. A baseline assessment of knowledge, perception and compliance was performed months before the intervention. The main intervention consisted of local alcohol-based-hand-rub (ABHR) production, with final product efficacy testing, in conjunction with a training adapted to the needs identified in the baseline assessment. A follow-up assessment was conducted directly after the training. Effectiveness of the intervention was assessed via uncontrolled before-and-after comparison. RESULTS: Baseline knowledge score (13.0/25) showed a significant increase to 19.0/25 in follow-up. Baseline-Compliance was 23.7% and increased significantly to 71.5% in follow-up. Compliance rose significantly across all professional groups except for midwifes and in all indications for HH, with the largest in the indication "Before aseptic tasks". The increase in compliance was associated with the intervention and remained significant after adjusting for confounders. The local pharmacy successfully supplies the entire hospital. The local supply resulted in a ten-fold increase of monthly hospital disinfectant consumption. CONCLUSION: The WHO HH strategy is an adaptable and effective method to improve HH knowledge and compliance in a resource-limited setting. Local production is a feasible method for providing self-sufficient supply of ABHR to regional hospitals like the FRH. Participatory approaches like hygiene committee ownership builds confidence of sustainability.

Effects of freeze-thaw on the biomechanical and structural properties of the rat Achilles tendon.

Rodent models are commonly used to investigate tendon healing, with the biomechanical and structural properties of the healed tendons being important outcome measures. Tendon storage for later testing becomes necessary when performing large experiments with multiple time-points. However, it is unclear whether freezing rodent tendons affects their material properties. Thus the aim of this study was to determine whether freezing rat Achilles tendons affects their biomechanical or structural properties. Tendons were frozen at either -20 °C or -80 °C directly after harvesting, or tested when freshly harvested. Groups of tendons were subjected to several freeze-thaw cycles (1, 2, and 5) within 3 months, or frozen for 9 months, after which the tendons were subjected to biomechanical testing. Additionally, fresh and thawed tendons were compared morphologically, histologically and by transmission electron microscopy. No major differences in biomechanical properties were found between fresh tendons and those frozen once or twice at -20 °C or -80 °C. However, deterioration of tendon properties was found for 5-cycle groups and both long-term freezing groups; after 9 months of freezing at -80 °C the tear resistance of the tendon was reduced from 125.4 ±â€¯16.4N to 74.3 ±â€¯18.4N (p = 0.0132). Moreover, tendons stored under these conditions showed major disruption of collagen fibrils when examined by transmission electron microscopy. When examined histologically, fresh samples exhibited the best cellularity and proteoglycan content of the enthesis. These properties were preserved better after freezing at -80 °C than after freezing at -20 °C, which resulted in markedly smaller chondrocytes and less proteoglycan content. Overall, the best preservation of histological integrity was seen with tendons frozen once at -80 °C. In conclusion, rat Achilles tendons can be frozen once or twice for short periods of time (up to 3 months) at -20 °C or -80 °C for later testing. However, freezing for 9 months at either -20 °C or -80 °C leads to deterioration of certain parameters.

Improved tendon healing using bFGF, BMP-12 and TGFß1 in a rat model.

Several growth factors (GFs) are expressed as tendons heal, but it remains unknown whether their combined application enhances the healing process. This matter was addressed by applying a combination of basic fibroblast growth factor (bFGF), bone morphogenetic protein 12 (BMP-12) and transforming growth factor beta 1 (TGFß1) in a rat Achilles tendon transection model. GFs were applied in one of the three following ways: i) direct application of all three factors at the time of surgery; ii) sequential, tiered percutaneous injection of individual factors immediately after surgery, 48 h and 96 h later; iii) load of all three factors onto a collagen sponge implanted at the time of surgery. After 1, 2, 4 and 8 weeks, healing was assessed based on tendon length and thickness, mechanical strength, stiffness and histology. Best results were achieved when GFs were loaded onto a collagen sponge - with a rapid increase in mechanical strength (load to failure, 71.2 N vs. 7.7 N in controls), consistent tendon length over time (9.9 mm vs. 16.2 mm in controls) and faster tendon remodelling, as measured by histology - followed by tiered injection therapy over 96 h. In conclusion, implantation of a GF-loaded collagen sponge could provide a promising treatment, especially in high-performance athletes and revision cases prone to re-rupture. For conservative treatment, tiered percutaneous GF application could be an option for improving clinical outcome.

Randomized clinical trial on the effect of coffee on postoperative ileus following elective colectomy.

BACKGROUND: Postoperative ileus is a common problem after abdominal surgery. It was postulated that coffee intake would decrease postoperative ileus after colectomy. METHODS: This was a multicentre parallel open-label randomized trial. Patients with malignant or benign disease undergoing elective open or laparoscopic colectomy were assigned randomly before surgery to receive either coffee or water after the procedure (100 ml three times daily). The primary endpoint was time to first bowel movement; secondary endpoints were time to first flatus, time to tolerance of solid food, length of hospital stay and perioperative morbidity. RESULTS: A total of 80 patients were randomized, 40 to each group. One patient in the water arm was excluded owing to a change in surgical procedure. Patient characteristics were similar in both groups. In intention-to-treat analysis, the time to the first bowel movement was significantly shorter in the coffee arm than in the water arm (mean(s.d.) 60·4(21·3) versus 74·0(21·6) h; P = 0·006). The time to tolerance of solid food (49·2(21·3) versus 55·8(30·0) h; P = 0·276) and time to first flatus (40·6(16·1) versus 46·4(20·1) h; P = 0·214) showed a similar trend, but the differences were not significant. Length of hospital stay (10·8(4·4) versus 11·3(4·5) days; P = 0·497) and morbidity (8 of 40 versus 10 of 39 patients; P = 0·550) were comparable in the two groups. CONCLUSION: Coffee consumption after colectomy was safe and was associated with a reduced time to first bowel action.

Long-term in vitro culture of hamster pancreatic ß-cells and induction of adenocarcinoma by treatment with N-nitrosobis(2-oxopropyl)amine.

OBJECTIVES: Earlier studies indicated that hamster pancreatic ductal adenocarcinoma not only derives from ductal/ductular structures but also from cells within the islet. So far unidentified cells within the islet are responsive to the carcinogenic effect of N-nitrosobis (2-oxopropyl) amine (BOP) forming poorly differentiated ductal adenocarcinoma. However, studies indicated a major role of ß-cells during carcinogenesis. To find out, if ß-cells are the primary target cells of BOP and if they are capable to form ductal adenocarcinoma after malignant transformation, we established a long-term culture of undifferentiated cells deriving from isolated ß-cells and treated them with BOP. METHODS: Langerhans' islets from pancreata of Syrian golden hamsters were isolated and dispersed into single cells by dispase digestion. Cells were labeled with a highly specific ß-cell surface antibody (K14D10) and these K14D10+ cells were extracted from the suspension by paramagnetic Dynabeads. Cells were cultured in vitro and treated with BOP. Untreated cells served as control. RESULTS: K14D10+ cells formed a monolayer and produced insulin over a period of 28 days in culture. However, with time in culture they became undifferentiated with a higher proliferation rate and after about 60 days in culture BOP treated cells showed anchorage independent growth. These cells autotransplanted s.c. formed a well-differentiated ductal adenocarcinoma. CONCLUSIONS: Pancreatic ß-cells are the primary target of BOP without necessarily being embedded in the compound of the Langerhans' islet. With time in culture, they give rise to undifferentiated cells and after malignant transformation they are able to form ductal adenocarcinoma.

Elevated preoperative CEA is associated with worse survival in stage I-III rectal cancer patients.

BACKGROUND: The objective of this investigation was to assess whether preoperative carcinoembryonic antigen (CEA) level is an independent predictor of overall survival in rectal cancer patients. METHODS: All patients (n=504) undergoing a resection for stage I-III rectal cancer at the Kantonsspital St Gallen were included into a database between 1991 and 2008. The impact of preoperative CEA level on overall survival was assessed using risk-adjusted Cox proportional hazard regression models and propensity score methods. RESULTS: In risk-adjusted Cox proportional hazard regression analyses, preoperative CEA level (hazard ratio (HR): 1.98, 95% confidence interval (CI): 1.36-2.90, P<0.001), distance from anal verge (<5 cm: HR: 1.93, 95% CI: 1.11-3.37; P=0.039), older age (HR: 1.07, 95% CI: 1.05-1.09; P<0.001), lower body mass index (HR: 0.94, 95% CI: 0.89-0.98; P=0.006), advanced tumour stage (stage II HR: 1.41, 95% CI: 0.85-2.32; stage III HR: 2.08, 95% CI: 1.31-3.31; P=0.004), R 1 resection (HR: 5.65, 95% CI: 1.59-20.1; P=0.005) and chronic kidney disease (HR: 2.28, 95% CI: 1.03-5.04; P=0.049) were all predictors for poor overall survival. CONCLUSION: This is one of the first investigations based on a large cohort of exclusively rectal cancer patients demonstrating that preoperative CEA level is a strong predictor of decreased overall survival. Preoperative CEA should be used as a prognostic factor in the preoperative assessment of rectal cancer patients.

The role of an interdisciplinary transplant team on living donation kidney transplantation program.

During the last decades, the disparity between the organ supply and the demand for kidney transplantation in Europe has led to consider living donors as a more acceptable option. In the last 7 years, we have established an interdisciplinary supporting transplant team to increase the rate of living donation. After 2001, the new interdisciplinary transplant team consisted of a transplant surgeon, a nephrologist, a pediatrician, a radiologist, a psychologist, a transplant coordinator, and a transplant nurse. We performed a prospective analysis to examine the effect of implementing this team on our living donation program. Demographic data, the annual number of procedures, the duration of waiting, and the cold ischemia time were evaluated among brain-dead and living donors. From January 2002 until December 2008, the number of patients who were annually on the waiting list increased 42% (from 377 to 536 patients). Consequently, the number of the total kidney transplants increased from 81 to 120 with an annual median of 98 cases. By implementing the interdisciplinary transplant team, a significant increase of living kidney donors was observed: from 18 to 42 cases; median = 27). In the last 7 years, a total number of 796 kidney transplants have been performed: 567 from brain-dead and 229 from living donors. In 2001, the waiting list times for recipients who received grafts from brain-dead versus living donors were 1356 versus 615 days respectively. Compared with 2008, the duration on the waiting list decreased significantly for patients receiving a living donor graft, whereas there was a slight increase for the patients in the brain-dead group: brain death versus living donors: 1407 versus 305 days. The interdisciplinary approach has also reduced the cold ischemia time for the living donor recipients: 3 hours and 42 minutes in 2001 versus 2 hours and 50 minutes in 2008. During the last years, by implementing an interdisciplinary transplant team, supporting living donor procedures has produce a gradual increase in the number of kidney transplants from living donors with a remarkable decrease in waiting and cold ischemia times, the latter presumably influencing graft quality.

A single center experience of combined liver kidney transplantation.

With advancements in the operative techniques, patient survival following liver transplantation (LTx) has increased substantially. This has led to the acceleration of pre-existing kidney disease because of immunosuppressive nephrotoxicity making additional kidney transplantation (KTx) inevitable. On the other hand, in a growing number of patients on the waiting list to receive liver, long waiting time has resulted in adverse effect of decompensated liver on the kidney function. During the last two decades, the transplant community has considered combined liver kidney transplantation (CLKTx) to overcome this problem. The aim of our study is to present an overview of our experience as well as a review of the literature in CLKTx and to discuss the controversy in this regard. All performed CLKTx (n = 22) at our institution as well as all available reported case series focusing on CLKTx are extracted. The references of the manuscripts were cross-checked to implement further articles into the review. The analyzed parameters include demographic data, indication for LTx and KTx, duration on the waiting list, Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, immunosuppressive regimen, post-transplant complications, graft and patient survival, and cause of death. From 1988 to 2009, a total of 22 CLKTx were performed at our institution. The median age of the patients at the time of CLKTx was 44.8 (range: 4.5-58.3 yr). The indications for LTx were liver cirrhosis, hyperoxaluria type 1, polycystic liver disease, primary or secondary sclerosing cholangitis, malignant hepatic epithelioid hemangioendothelioma, cystinosis, and congenital biliary fibrosis. The KTx indications were end-stage renal disease of various causes, hyperoxaluria type 1, polycystic kidney disease, and cystinosis. The mean follow-up duration for CLKTx patients were 4.6 +/- 3.5 yr (range: 0.5-12 yr). Overall, the most important encountered complications were sepsis (n = 8), liver failure leading to retransplantation (n = 4), liver rejection (n = 3), and kidney rejection (n = 1). The overall patient survival rate was 80%. Review of the literature showed that from 1984 to 2008, 3536 CLKTx cases were reported. The main indications for CLKTx were oxalosis of both organs, liver cirrhosis and chronic renal failure, polycystic liver and kidney disease, and liver cirrhosis along with hepatorenal syndrome (HRS). The most common encountered complications following CLKTx were infection, bleeding, biliary complications, retransplantation of the liver, acute hepatic artery thrombosis, and retransplantation of the kidney. From the available data regarding the need for post-operative dialysis (n = 673), a total of 175 recipients (26%) required hemodialysis. During the follow-up period, 154 episodes of liver rejection (4.3%) and 113 episodes of kidney rejection (3.2%) occurred. The cumulative 1, 2, 3, and 5 yr survival of both organs were 78.2%, 74.4%, 62.4%, and 60.9%, respectively. Additionally, the cumulative 1, 2, 3, and 5 yr patient survival were 84.9%, 52.8%, 45.4%, and 42.6%, respectively. The total number of reported deaths was 181 of 2808 cases (6.4%), from them the cause of death in 99 (55%) cases was sepsis. It can be concluded that there is still no definitive evidence of better graft and patient survival in CLKTx recipients when compared with LTx alone because of the complexity of the exact definition of irreversible kidney function in LTx candidates. Additionally, CLKTx is better to be performed earlier than isolated LTx and KTx leading to the avoidance of deterioration of clinical status, high rate of graft loss, and mortality. Shorter graft ischemia time and more effective immunosuppressive regimens can reduce the incidence of graft malfunctioning in CLKTx patients. Providing a model to reliably determine the need for CLKTx seems necessary. Such a model can be shaped based upon new and precise markers of renal function, and modification of MELD system.

Current concepts in transplant surgery: liver transplantation today.

INTRODUCTION: The discipline of liver transplantation (LTx) has been developed over the past decades, and LTx is now considered the gold standard for the treatment of patients with end-stage liver diseases and early liver tumors in cirrhotic livers. This procedure is now performed routinely in many transplant centers, and it has provided an enormous technical innovation to the field of hepatobiliary surgery. Allocation decision of liver organs is based on medical need and timing. MATERIALS AND METHODS: The Mayo Model for End Stage Liver Disease based on patient-specific criteria was developed and applied to prioritize patients on the waiting list. From the donor aspects of LTx, sources of organ, excluding xenotransplantation, can be brain-dead donors, living donors, and non-heart-beating donors. Today, the majority of livers are procured from cadaveric donors. In addition to the conventional LTx, other types are living-donor LTx, reuse of grafts as domino transplantation, ex situ as well as in situ split LTx, and reduced-size LTx. The transplantation procedure consists of several steps including donor selection and management, liver procurement and preservation, back-table preparation, recipient operation with liver implantation, postoperative care, immunosuppression, and follow-up. RESULTS: The postoperative complications are divided into surgical, non-surgical, and multifactorial complications. Surgical complications account about 34% of morbidities after LTx and are mainly categorized to vascular and biliary complications. The main medical ones are non-surgical bleeding and infections. The multifactorial complications include primary non- or poor function and small-for-size syndrome. The pretransplant outcome predictors of LTx can be divided into donor, recipient, operative, and postoperative factors. CONCLUSION: LTx is now considered a safe and standardized procedure with a substantially improved graft and patient survival and acceptable morbidity rates. However, the new problems, including recurrence of hepatitis C or hepatocellular carcinoma, chronic biliary complications, opportunistic infections, and development of de-novo malignancies are the major problems affecting the long-term outcome of transplanted patients.

[Orthotopic liver transplantation. Techniques and results]. / Orthotope Lebertransplantation. Technik und Ergebnisse.

Since 1963, orthotopic liver transplantation (OLT) has developed into an established interdisciplinary therapy concept for patients with end-stage liver disease, acute irreversible liver failure, and hepatic malignancies in selected cases. In 26 centers in Germany, around 900 full-size OLTs are performed annually. The classic technique has been replaced by the "piggyback" method, which has become the standard in many centres. Improvements in surgical techniques, anaesthetic protocols, and medical management along with the introduction of new immunosuppressive regimens and early adequate therapy against infections and transplant rejection have increased patient survival. These factors have resulted in 1-year survival rates of 80-90% and led to an increase in indications for OLT. Despite decades of experience, approximately 10% of the mortality in the first 3 months still can be traced to technical complications.

Long-term effects of anal sphincter rupture during vaginal delivery: faecal incontinence and sexual complaints.

OBJECTIVE: To determine the long-term effects of obstetric anal sphincter rupture on the frequency of faecal incontinence and sexual complaints. DESIGN: Retrospective case-control study. SETTING: Department of Gynaecology and Obstetrics, Ikazia Hospital, The Netherlands. POPULATION: All 171 women operated for anal sphincter rupture between 1971 and 1990 and 171 controls matched for parity and date of delivery. METHODS: Postal questionnaires regarding faecal incontinence were sent in 1996 and 2005 to all cases and controls with questions regarding sexual complaints added to the questionnaire in 2005. MAIN OUTCOME MEASURES: Anorectal complaints defined as any form of faecal incontinence including faecal urgency and faecal soiling. Sexual complaints defined as dyspareunia or faecal incontinence during intercourse. RESULTS: Sixty-one percent of the women responded to both questionnaires. Anorectal complaints were reported by 38% of case versus 16% of controls in 1996 (risk difference: 0.22, 95% CI 0.10-0.34) and by 61% of cases versus 22% of controls in 2005 (risk difference: 0.41, 95% CI 0.29-0.53). In contrast to the control group, the increase of anorectal complaints in the case group between 1996 and 2005 was highly significant (P < 0.0001). Postmenopausal state was not associated with an increased risk for faecal incontinence. Dyspareunia was reported by 29% of cases versus 13% of controls (P = 0.01). Faecal incontinence during intercourse was reported by 13% of cases versus 1% of controls (P = 0.005). CONCLUSIONS: Obstetric anal sphincter rupture is an important risk factor for sexual complaints and for faecal incontinence increasing with age irrespective of menopausal state.

Precision targeting of liver lesions with a needle-based soft tissue navigation system.

In this study, we assessed the targeting precision of a previously reported needle-based soft tissue navigation system. For this purpose, we implanted 10 2-ml agar nodules into three pig livers as tumor models, and two of the authors used the navigation system to target the center of gravity of each nodule. In order to obtain a realistic setting, we mounted the livers onto a respiratory liver motion simulator that models the human body. For each targeting procedure, we simulated the liver biopsy workflow, consisting of four steps: preparation, trajectory planning, registration, and navigation. The lesions were successfully hit in all 20 trials. The final distance between the applicator tip and the center of gravity of the lesion was determined from control computed tomography (CT) scans and was 3.5 +/- 1.1 mm on average. Robust targeting precision of this order of magnitude would significantly improve the clinical treatment standard for various CT-guided minimally invasive interventions in the liver.

Thymoglobulin and ischemia reperfusion injury in kidney and liver transplantation.

Since the beginning of organ transplantation, graft preservation has been one of the most important concerns. Ischemia reperfusion injury (IRI), which plays an important role in the quality and function of the graft, is a major cause for increased length of hospitalization and decreased long term graft survival. Among numerous attempts which have been made to minimize graft damage associated with IRI, the use of Thymoglobulin (TG) seems to offer potential benefits. TG is a polyclonal antibody which blocks multiple antigens related to IRI, in addition to its better known T cell depleting effects. This review will focus on the use of TG in preventing IRI in kidney transplantation (KTx) and liver transplantation (LTx). Different studies in experimental and clinical transplantation have shown that TG protects renal and liver grafts from IRI. Improvement in early graft function and decreased delayed graft function (DGF) rates are some of the clinical benefits of TG. Additionally, it is used in patients with hepatorenal syndrome to support the recovery of kidney function after LTx, by allowing reduced exposure to nephrotoxic calcineurin inhibitors as well as improving liver graft function by minimizing IRI. TG can reduce acute rejection rates in kidney and liver transplant recipients, decrease the length of hospital stay, and hence reduce transplantation costs. TG can play an important role in expanding the donor pool in both KTx and LTx by improving long-term graft and patient survival rates which increases the possibility of using marginal donors. Although controversial, the development of post-transplant lymphoproliferative disorder is a potential side effect of TG. No single optimal immunosuppressive regimen has given consistent results in decreasing the graft damage following IRI; however, TG usage in KTx and LTx appears to have some benefits in reducing IRI.

C-reactive protein as early predictor for infectious postoperative complications in rectal surgery.

BACKGROUND: This study evaluated the role of the acute phase C-reactive protein (CRP) in the postoperative course of a large series of rectal resections on the basis of a prospective database. Main focus of this study was the early identification of complications. MATERIALS AND METHODS: Three hundred eighty-three rectal resections with primary anastomosis for rectal cancer were screened for infectious postoperative complications. Forty-eight complicated cases were identified and matched with 48 patients with an uneventful postoperative course. RESULTS: In the postoperative setting, CRP peaked on postoperative day (POD) 2 with a median serum CRP of 140 mg/l and gradually declined thereafter in uncomplicated cases. In complicated cases, CRP elevation generally persisted after POD 2, whereas white blood cells and body temperature were within normal range in the early postoperative period. A cutoff CRP value of 140 mg/dl on PODs 3 and 4 resulted in predictive values of 85.7 and 90.5% (adjusted to the prevalence: 37.6 and 50.3%), sensitivities of 80.0 and 54.3%, and specificities of 81.0 and 92.3% for a complicated postoperative course (P<0.001), respectively. CONCLUSION: Persistent CRP elevation and elevation of serum CRP above 140 mg/dl on PODs 3-4 are predictive of infectious postoperative complications and should prompt intense clinical search for an inflammatory process, especially for an anastomotic leak if pneumonia and wound infection are unlikely or excluded.