Psychological review of hemodialysis patients and kidney transplant recipients during the COVID-19 pandemic.

BACKGROUND: Kidney transplantation (KT) and end-stage renal disease (ESRD) requiring hemodialysis (HD) increase the incidence of morbidity and mortality associated with coronavirus disease 2019 (COVID-19) infection. The COVID-19 pandemic has had a negative effect on the psychological well-being of COVID-19 patients, especially those with a high-risk of infectious complications. The prevalence of anxiety and depression is known to be higher in ESRD patients undergoing HD than in the general population. On the other hand, KT recipients have different treatment requirements compared to HD patients, including adherence to complex immunosuppressive regimens and compliance with follow-up appointments. We hypothesized that psychosocial difficulties and stressors would differ between ESRD patients undergoing HD and KT recipients during the COVID-19 pandemic. If so, each group may require different interventions to maintain their psychosocial well-being. AIM: To measure and compare the levels of stress, anxiety, depression, concerns related to the pandemic, and coping skills in ESRD patients undergoing HD and KT recipients during the COVID-19 pandemic. METHODS: This cross-sectional study was performed at a training and research hospital. The study included ESRD patients undergoing HD (HD group) and KT recipients (with stable graft function for ≥ 6 mo prior to the study) (KT group). Patients completed a demographics form, the impact of events scale, the hospital anxiety and depression scale, and the Connor-Davidson resilience scale. Laboratory findings at the last clinical follow-up were recorded. The χ2 test was used to assess the relationship between the HD and KT groups and the categorical variables. The relationships between the scale scores were analyzed using Pearson's correlation test, and differences between the groups were analyzed using the independent groups t-test. RESULTS: The study included 125 patients, of which 89 (71.2%) were in the HD group and 36 (28.8%) were in the KT group. The levels of anxiety and depression were higher in the HD group than in the KT group [9.36 ± 4.38 vs 6.89 ± 4.06 (P = 0.004) and 8.78 ± 4.05 vs 6.42 ± 4.26 (P = 0.004), respectively], whereas the post-traumatic stress score was higher in the KT group [46.75 ± 13.98 vs 37.66 ± 18.50 (P = 0.009)]. The concern with the highest intensity in the HD group was transmission of COVID-19 to family and friends (93.3%) and in the KT group was loss of caregiver and social support (77.8%). Concerns regarding financial hardship, stigmatization, loneliness, limited access to health care services, failure to find medical supplies, and transmission of COVID-19 to family and friends were more prevalent in the HD group. Connor-Davidson resilience scale tenacity and personal competence, tolerance, and negative affect scores were higher in the KT group than in the HD group [43.47 ± 11.39 vs 33.72 ± 12.58, 15.58 ± 4.95 vs 11.45 ± 5.05, and 68.75 ± 17.39 vs 55.39 ± 18.65 (P < 0.001), respectively]. Biochemical parameters, such as creatine, urea, phosphorus, parathyroid hormone, and calcium, were lower, and the albumin and hemoglobin values were higher in the KT group than in the HD group (P < 0.001). CONCLUSION: Psychosocial difficulties and the level of stress differ in ESRD patients undergoing HD and KT recipients; therefore, psychosocial interventions should be tailored for each patient group.

Current practice of live donor nephrectomy in Turkey.

BACKGROUND: Over the last few years, the deceased donor organ donation rate was declined or remained stable, whereas the live donor organ donation rate has increased to compensate for the demand. Minimally invasive techniques for live donor nephrectomy (LDN) have also improved the live donor kidney donation rates. This increase has led to an interest in the surgical procedures used for LDN. AIM: To evaluate the LDN techniques performed in Turkey, the structure of surgical teams, and the training received. Additionally, the number of kidney transplantations at different centers, the surgeon experience level, differences in surgical approach during donor surgeries, and outcomes were assessed. METHODS: A questionnaire was sent to the Turkish Ministry of Health-accredited transplant centers. It inquired of the number of LDN surgeries, surgical techniques, complications, optimization protocols, the experience of surgeons, and the training. Descriptive statistics were outlined as follows: Discrete numeric variables were expressed as medians (minimum-maximum), while categorical variables were shown as numbers and percentages. As a result of the goodness-of-fit tests, if the significance of the differences between the groups in discrete numerical variables for which the parametric test statistical assumptions were not met, data were analyzed with the Mann Whitney U test and the χ 2 test. RESULTS: The questionnaire was sent to 72 transplant centers, all of which replied. Five centers that reported not performing LDN procedures were excluded. Responses from the remaining 67 centers were analyzed. In 2019, the median number of kidney transplants performed was 45, and the median number of kidney transplants from living donors was 28 (1-238). Eleven (16.5%) centers performed 5-10, while 34 (50.7%) centers performed more than 100 live donor kidney transplants in 2019. While 19 (28.4%) centers performed the LDN procedures using the open technique, 48 (71.6%) centers implemented minimally invasive techniques. Among the centers preferring minimally invasive techniques for LDN, eight (16.6%) used more than one surgical technique. The most and the least common surgical techniques were transperitoneal laparoscopic (43 centers, 89.6%) and single port laparoscopic LDN (1 center, 2.1%) techniques, respectively. A positive association was found between the performance of minimally invasive techniques and the case volume of a transplant center, both in the total number and live donor kidney transplants (15 vs 55, P = 0.001 and 9 vs 42, P ≤ 0001 respectively). The most frequently reported complication was postoperative atelectasis (n = 33, 49.2%). There was no difference between the techniques concerning complications except for the chyle leak. CONCLUSION: Turkish transplant centers performed LDN surgeries successfully through various techniques. Centers implementing minimally invasive techniques had a relatively higher number of live donor kidney transplants in 2019.

Burned-out germ cell tumor presenting with acute abdomen.

Acute abdomen is a serious condition frequently encountered in the emergency departments (ED). There are various etiologies causing acute abdomen, most common being acute appendicitis; however, there are rare causes of acute abdomen as well and one should keep them in mind while handling a patient with unusual clinical features. We herein present a 26-year-old male, with no past medical or surgical history, presenting with acute abdominal pain and distension to the ED. He was found to have a large vascular retroperitoneal mass on computed tomography which had invaded and perforated the duodenum thus causing the acute presentation. Repair of the duodenal perforation and sampling of the mass were performed in terms of surgical management. Pathology results revealed the mass originating from a burned out testis yolk sac tumor with embryonal carcinoma component. Although the original tumor had regressed at the testis, its metastasis at the retroperitoneal area had caused the clinical condition. This entity is described as the retroperitoneal metastasis of a burned-out testicular tumor. Few cases presenting with gastrointestinal bleeding secondary to invasion of the retroperitoneal metastasis have been reported. However, this is the first case in the literature presenting with duodenal perforation and acute abdomen. Sampling of the retroperitoneal tumor for histopathological diagnosis during the immediate surgical intervention facilitates the diagnostic management in these cases. Although scrotal examination combined with testis tumor marker assessments is essential for optimal patient management, the possibility of a burned-out testicular tumor with normal scrotal examination should always be kept in mind.

An isolated traumatic renal artery pseudoaneurysm treated by renal artery stent insertion: a case report presenting a nephron-sparing approach.

Penetrating or blunt traumas can rarely lead to renal artery pseudoaneurysms (RAPs). Renal parenchymal lacerations usually accompany them, and nephrectomy is performed in these cases. Although angioembolization of the renal artery can negate the need for nephrectomy while treating the RAP, it is not a nephron-sparing procedure. Herein, we present a case of isolated (i.e. without accompanying renal laceration) left RAP. During conservative follow-up, the RAP enlarged, and subsequently, it was treated by renal artery stent insertion. An expandable covered stent was used during this procedure. The renal function was preserved without experiencing any complications.

Vitamin D deficiency may predispose patients to increased risk of kidney transplant rejection.

BACKGROUND: Vitamin D deficiency occurs in more than 80% of kidney transplant recipients. Its immunomodulatory effects can predispose transplant recipients to rejection and chronic allograft nephropathy (CAN). This study determined the association between serum 25 (OH) vitamin D, biopsy-proven allograft rejection, and CAN rates. AIM: To determine the relationship between serum 25 (OH) vitamin D level and biopsy-proven allograft rejection and CAN rate in renal transplant recipients. METHODS: Adult renal transplant recipients followed at the clinic between January 2013 and 2018 were included. Recipients requiring graft biopsy due to declined function, hematuria, and proteinuria were reviewed. The two groups were compared regarding collected data, including the biopsy results, immunologic parameters, vitamin D, parathyroid hormone (PTH), phosphorus, albumin levels, and graft function tests. RESULTS: Fifty-two recipients who underwent graft biopsy met the inclusion criteria. In all, 14 recipients had a vitamin D level > 15 ng/mL (group 1) vs ≤ 15 ng/mL (group 2) in 38. In total, 27 patients had biopsy-proven rejection, and 19 had CAN. There was only 1 recipient with biopsy-proven rejection in group 1, whereas there were 24 patients with rejection in group 2. The rejection rate was significantly higher in group 2 than in group 1 (P < 0.001). Four patients were diagnosed with CAN in group 1 vs fifteen in group 2. There was no significant difference in the CAN rate between the two groups. PTH was higher at the time of graft biopsy (P = 0.009, P = 0.022) in group 1 with a mean of 268 pg/mL. Donor-specific antibodies were detected in 14 (56.0%) of the recipients with rejection. Vitamin D level was 9.7 ± 3.4 ng/mL in the rejection group vs 14.7 ± 7.2 in the non-rejection group; this difference was statistically significant (P = 0.003). The albumin levels were significantly lower in patients with rejection than in those without rejection (P = 0.001). In univariate regression analysis of risk factors affecting rejection, sex, serum vitamin D, phosphorus and albumin were found to have an impact (P = 0.027, P = 0.007, P = 0.023, P = 0.008). In multivariate regression analysis, the same factors did not affect rejection. CONCLUSION: The serum 25 (OH) vitamin D level in kidney transplant recipients remained low. Although low serum vitamin D level emerged as a risk factor for rejection in univariate analysis, this finding was not confirmed by multivariate analysis. Prospective studies are required to determine the effect of serum vitamin D levels on allograft rejection.

Utilization of Internet Resources by Surgeons for Continuous Professional Development in the Era of Prevailing COVID-19 Pandemic: Trends and Obstacles.

Background: To investigate the use of internet resources by surgeons for continuing professional development (CPD). Results: This cross-sectional study was carried out between July 1, 2021, to October 31, 2021, at the Department of Medicine, Health Sciences University Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey, with participants from nine surgical specialties: General surgery, neurosurgery, orthopedics, urology, plastic surgery, ear-nose-throat surgery, cardiovascular surgery, ophthalmology, and anesthesiology. All study participants were asked to complete a questionnaire comprising 23 questions regarding their age, duration of work experience, appointment status, venue, and time spent on internet resources and preferred online resources for CPD purposes. In addition, participants were divided into two groups according to their appointment status: academic faculty and staff surgeons. Data analysis was performed using IBM SPSS Statistics version 17.0. The target population consisted of 216 specialists. The survey was completed by 204 (94.4%) surgical specialists. The majority of the specialists (n = 137, 67.2%) reported using the internet for work-related purposes every day. Daily time spent on internet resources was reported to be 30-60 min by 39.2% (n = 80) participants, whereas 52 (25.5%) reported spending less than 30 min. The participants wished to spend more time on internet resources. The majority of surgeons found the hospital and home equally effective in using the internet and preferred to engage alone. The mean age, English language level, usage of online resources, and the attitude score toward the perceived credibility and usefulness of e-resources were significantly higher in the academic faculty group than staff surgeons (p < 0.005). On the other hand, the use of Google/Google scholar was similar between the two groups (p = 0.192). Technical difficulties such as slow internet, need for website registration, and article fees were considered drawbacks for internet resources among all the participants. Conclusions: This study showed that most surgeons use internet resources daily for CPD and stated they would like to engage longer despite technical difficulties. Institutions should address these technical difficulties.

The impact of lymph node ratio on overall survival in patients with colorectal cancer.

BACKGROUND: Lymph node metastasis is a predominant prognostic indicator in colorectal cancer. Number of lymph nodes removed surgically was demonstrated to correlate with staging accuracy and oncological outcomes. However, number of lymph nodes removed depends on uncontrolled variables. Therefore, a more reliable prognostic indicator is needed. Calculation of ratio of positive lymph nodes to total number of removed lymph nodes may be an appealing solution. MATERIALS AND METHODS: We retrospectively analyzed data of 156 Stage III colorectal cancer patients whom underwent surgery between 2008 and 2015. Patients' demographic characteristics, tumor grade, location, vascular-perineural invasion status, number of removed lymph nodes, and ratio of positive lymph nodes to number of removed lymph nodes were recorded. Spearman correlation analysis was used to determine the correlation coefficient while Kaplan-Meier method and Cox proportional hazard regression model were performed for the prediction of survival and multivariate analysis, respectively. RESULTS: Number of removed lymph nodes did not correlate with survival, but it was inversely correlated with number of positive lymph nodes. Multivariate analysis showed that ratio of removed positive lymph nodes to the total number of lymph nodes was a significant prognostic factor for survival for a ratio equal or above 0.31 was a poor prognostic indicator (108 months vs. 34 months, hazard ratio: 4.24 [95% confidence interval: 2.15-8.34]; P < 0.019). Tumor characteristics failed to demonstrate any prognostic value. CONCLUSIONS: This study showed that positive lymph node ratio (PLNR) is an important prognostic factor for Stage III colorectal cancer. Although 0.31 can be taken as threshold for "PLNR," prospective trials including larger patient groups are needed to validate its role as a prognostic indicator.

COVID-19 infection in a kidney transplant recipient-special emphasis on pharmacokinetic interactions: A case report.

BACKGROUND: Solid organ transplant recipients are considered to be at high-risk of developing coronavirus disease 2019 (COVID-19)-related complications. The optimal treatment for this patient group is unknown. Consequently, the treatment of COVID-19 in kidney transplant recipients should be determined individually, considering patient age and comorbidities, as well as graft function, time of transplant, and immunosuppressive treatment. Immunosuppressive treatments may give rise to severe COVID-19. On the contrary, they may also lead to a milder and atypical presentation by diminishing the immune system overdrive. CASE SUMMARY: A 50-year old female kidney transplant recipient presented to the transplant clinic with a progressive dry cough and fever that started three days ago. Although the COVID-19 test was found to be negative, chest computed tomography images showed consolidation typical of the disease; thus, following hospital admission, anti-bacterial and COVID-19 treatments were initiated. However, despite clinical improvement of the lung consolidation, her creatinine levels continued to increase. Ultrasound of the graft showed no pathology. The tacrolimus blood level was determined and the elevation in creatinine was found to be related to an interaction between tacrolimus and azithromycin. CONCLUSION: During the COVID-19 pandemic, various single or combination drugs have been utilized to find an effective treatment regimen. This has increased the possibility of drug interactions. A limited number of studies published in the literature have highlighted some of these pharmacokinetic interactions. Treatments used for COVID-19 therapy; azithromycin, atazanavir, lopinavir/ritonavir, remdesivir, favipiravir, chloroquine, hydroxychloroquine, nitazoxanide, ribavirin, and tocilizumab, interact with immunosuppressive treatments, most importantly with calcineurin inhibitors. Thus, their levels should be frequently monitored to prevent toxicity.

Surgical Drains After Laparoscopic Donor Nephrectomy: Needed or Not?

BACKGROUND Routine placement of prophylactic drains after laparoscopic donor nephrectomy has been suggested and has become common practice in some centers. However, there is a lack of evidence proving the surgical benefits of routine drain placement in laparoscopic donor nephrectomy. Here, we assessed the effect of surgical drain placement on recovery, length of hospital stay, and complication rates of live kidney donors. MATERIAL AND METHODS This retrospective study included all live donor nephrectomies performed at a single institution from January 2010 to January 2017. Surgeries were performed by 2 surgeons; one routinely placed a closed suction drain after LDN whereas the other did not. Patients operated on by these 2 surgeons were enrolled in either the drain or no drain group. Demographic data, preoperative and postoperative creatinine levels, estimated blood loss (EBL), surgical time, surgical complications, and length of hospital stay were compared. RESULTS The study included 272 patients. Three were converted to open donor nephrectomy and were excluded (1.1%). Among the 269 patients, 156 (57.9%) had surgical drains and 113 (42.1%) did not. Mean surgical time, estimated blood loss, and duration of hospital stay did not significantly differ between groups. Postoperative complications were encountered in 17 of the patients, but the overall complication rate did not differ between patients with vs. those without surgical drains. CONCLUSIONS There was no significant difference between the drain and no drain groups in terms of length of hospital stay, complication rates, or postoperative creatinine levels. Thus, placement of a surgical drain in the setting of an LDN is not justified based on our single-center experience.

Listening to music during arteriovenous fistula surgery alleviates anxiety: A randomized single-blind clinical trial.

BACKGROUND: Both end-stage renal disease and being wait-listed for a kidney transplant are anxiety-causing situations. Wait-listed patients usually require arteriovenous fistula surgery for dialysis access. This procedure is performed under local anesthesia. We investigated the effects of music on the anxiety, perceived pain and satisfaction levels of patients who underwent fistula surgery. AIM: To investigate the effect of music therapy on anxiety levels and perceived pain of patients undergoing fistula surgery. METHODS: Patients who were on a waiting list for kidney transplants and scheduled for fistula surgery were randomized to control and music groups. The music group patients listened to music throughout the fistula surgery. The State-Trait Anxiety Inventory was performed to assess anxiety, additionally visual analog scale was used to evaluate perceived pain, willingness to repeat the procedure and patient satisfaction. Demographic features, comorbidities, surgical history, basic surgical data (location of fistula creation, duration of surgery, incision length) and intra-operative hemodynamic parameters were recorded by an investigator blinded to the study group. An additional trait anxiety assessment was performed following the surgery. RESULTS: There was a total of 55 patients included in the study. However, 14 patients did not fulfill the criteria due to requirement of sedation during surgery or uncompleted questionnaires. The remaining 41 patients were included in the analysis. There were 26 males and 15 females. The control and music groups consisted of 20 and 21 patients, respectively. With regard to basic surgical and demographic data, there was no difference between the groups. Overall patient satisfaction was significantly higher and intra-operative heart rate and blood pressure were significantly lower in the music group (P < 0.05). Postoperative state anxiety levels were significantly lower in the music group. CONCLUSION: Music therapy can be a complimentary treatment for patients undergoing fistula surgery. It can reduce anxiety and perceived pain, improve intraoperative hemodynamic parameters and enhance treatment satisfaction, thus may contribute to better compliance of the patients.

Transcatheter embolization in pediatric blunt renal trauma: Case report and review of the literature.

This study aims to evaluate the clinical use and outcomes of transcatheter embolization in the setting of pediatric blunt renal trauma cases using an index case and review of the literature. Although the treatment method selection depends on the grade of the trauma and the hemodynamic status of the patient, conservative methods are considered initially in the setting of pediatric blunt renal trauma. Transcatheter embolization, which is a relatively conservative treatment option, is commonly utilized in adult blunt renal trauma patient population; however, experience in the pediatric population is scarce. A seven-year-old male patient was admitted due to grade IV renal injury secondary to blunt abdominal trauma. He was conservatively followed until -on the post-trauma day 15- he developed gross hematuria and an unstable hemodynamic status. A renal angiogram was performed, which revealed right-sided renal inferior segmental artery pseudoaneurysm and arterio-venous fistula. Subsequently, a transcatheter embolization was performed. There were no complications and no permanent renal injury. Review of the literature revealed that the success rate of transcatheter embolization is 89.47% in the setting of pediatric blunt abdominal trauma-related renal injury regardless of the renal trauma grade. Four patients underwent nephrectomy due to a failed transcatheter embolization procedure. There are not any patients who suffered from embolization-related complications. These results suggest that transcatheter embolization can be safely performed in children with renal injuries due to blunt abdominal trauma with high success and low complication rates and preservation of renal function.

Colonic anastomosis can be protected from ischemia reperfusion injury with intra-peritoneal Montelukast treatment.

BACKGROUND: Ischemia reperfusion injury is unavoidable in the setting of transplantation and may lead to primary dysfunction of the transplanted organ. Similarly, intestinal ischemia reperfusion injury may have deleterious effects causing intestinal failure. Montelukast is a selective reversible cysteinyl-leukotriene type 1 receptor antagonist used in clinical practice for its anti-inflammatory effects. In this study, we investigated the effects of Montelukast on colon anastomosis performed after intestinal ischemia reperfusion injury. METHODS: 40 adult male Wistar Albino rats were used. All rats underwent intestinal ischemia reperfusion injury. Afterwards, the entire group was divided into two for either right or left colonic resection and anastomosis. Rats in the control groups were given intra-peritoneal normal saline for 1 week while the animals in the treatment groups were given intra-peritoneal Montelukast (10 mg/kg; 1 ml). All animals were subjected to ischemia reperfusion injury followed by either right or left colonic segmental resection and anastomosis in the first day of the experiment. On postoperative day 7 adhesion scoring, anastomotic bursting pressure, anastomotic tissue hydroxyproline content were assessed for all groups. RESULTS: Significant differences were detected in adhesion scores between the treatment and control groups regardless of the colonic resection site. Anastomotic bursting pressures and hydroxyproline content of the anastomotic sites were significantly higher in the treatment groups when compared with the control groups. Anastomotic tissues treated with Montelukast showed more prominent vascularization in histopathological examinations. CONCLUSION: Montelukast has a potential to attenuate the detrimental effects of ischemia reperfusion injury on intestinal anastomosis.

Challenges of pancreas transplantation in developing countries, exploring the Turkey example.

Pancreas transplantation significantly improves the quality of life for people with type 1 diabetes, primarily by eliminating the need for insulin and frequent blood glucose measurements. Despite the growing numbers of solid organ transplantations worldwide, number of pancreas transplantations in the developing countries` remain significantly low. This difference of pancreas transplantation practices was striking among the participating countries at the 1st International Transplant Network Meeting which was held in Turkey on 2018. In this meeting more than 40 countries were represented. Most of these counties were developing countries located in Africa, Middle East or Asia. The aim of this article is to identify the challenges and limiting factors for pancreas transplantations in these developing countries, by exploring the Turkish example. The challenges faced by the developing countries are broadly classified in four categories; wait-listing, donor pool, team work and follow up. Under these categorical titles, issues are further discussed in detail, giving examples from Turkish practice of pancreas transplantation. Additionally, several solutions to these challenges have been proposed- some of which have already been undertaken by the Turkish Ministry of Health. With the insight and methods presented in this article, pancreas transplantation should be made possible for the potential recipients in the developing countries.

Bilateral intra-abdominal testicular tumor: Case report.

INTRODUCTION: Bilateral intra-abdominal testis is a very rare clinical entity. These testes may develop cancer in an adult patient with empty scrotum. CASE PRESENTATION: A case of a huge intra-abdominal solid mass in a 32-year-old gentleman is presented. Physical examination revealed an empty scrotum. Laboratory investigations, imaging studies, laparotomy and histopathological examination showed that the solid mass was a mixed germ cell tumor of the left testis. The contra-lateral testis also had a tumor. Resection of the solid mass and contra-lateral orchiectomy was performed. Adjuvant chemotherapy was given. Six months after surgery, his follow-up parameters were all within normal limits. DISCUSSION: Since bilateral intra-abdominal testis tumor is a very rare clinical entity, there are no patient management guidelines available. Management strategies differ significantly among groups and they are based mainly on the experience reflected in the context of anecdotal case reports. CONCLUSION: Surgical exploration and adjuvant chemotherapy seems as a reasonable treatment option in the setting of bilateral intra-abdominal testis tumor in an adult patient.

Delivery of Soluble Heme Oxygenase 1 Cell-Penetrating Peptide into Liver Cells in in vitro and ex vivo Models of Cold Ischemia.

BACKGROUND/PURPOSE: Liver transplantation is the treatment of choice in patients with end-stage liver disease. During liver transplantation, ischemia-reperfusion injury (IRI) occurs, which is an inevitable consequence of the transplantation process. To reduce the extent of cellular injury, one of the proteins that have been extensively investigated is heme oxygenase 1 (HO-1), which plays an important role in protecting the organs against IRI. The aim of this study was to introduce an active and functional HO-1 protein conjugated to a cell-penetrating peptide (CPP) in vitro and ex vivo into liver cells in hypothermic and anoxic conditions and to assert its cytoprotective effects. METHODS: We generated an enzymatically active soluble (s)HO-1-CPP recombinant protein. The ability of the sHO-1-CPP protein to penetrate McA-RH7777, Clone 9, and Hep G2 cells, primary hepatocytes, and Kupffer and human umbilical vein endothelial cells in vitro, as well as its ability to penetrate a whole liver ex vivo under hypothermic and anoxic conditions, was assessed. An in vitro hypoxia-reoxygenation (HR) model was used to determine the cytoprotective effect of the sHO-1-CPP protein. RESULTS: We showed that our recombinant protein sHO-1-CPP can cross cell membranes into rodent and human liver cells in vitro, and the results were further validated ex vivo, where rodent livers were perfused with an organ preservation solution supplemented with sHO-1-CPP under anoxic and hypothermic conditions. Immunohistochemistry revealed an intracellular localization of sHO-1-CPP in zones 1-3 of the perfused livers. The CPP did not exert any significant toxicity on the cells. Treating cells with sHO-1-CPP showed significant cytoprotection in the in vitro HR model. CONCLUSIONS: Our findings show that the recombinant protein sHO-1-CPP can be successfully delivered to cells of a whole organ in an ex vivo hypothermic and anoxic perfusion model and that it provides cytoprotection to hepatocytes in an in vitro HR model. These results hold great potential for future repair and protection of donor organs. Future experiments are planned to confirm these data in in vivo models of IRI.

Mitochondrial Damage-Associated Molecular Patterns (MTDs) Are Released during Hepatic Ischemia Reperfusion and Induce Inflammatory Responses.

Ischemia / reperfusion injury (IRI) during the course of liver transplantation enhances the immunogenicity of allografts and thus impacts overall graft outcome. This sterile inflammatory insult is known to activate innate immunity and propagate organ damage through the recognition of damage-associate molecular pattern (DAMP) molecules. The purpose of the present study was to investigate the role of mitochondrial DAMPs (MTDs) in the pathogenesis of hepatic IRI. Using in vitro models we observed that levels of MTDs were significantly higher in both transplantation-associated and warm IR, and that co-culture of MTDs with human and rat hepatocytes significantly increased cell death. MTDs were also released in an in vivo rat model of hepatic IRI and associated with increased secretion of inflammatory cytokines (TNF-α, IL-6, and IL-10) and increased liver injury compared to the sham group. Our results suggest that hepatic IR results in a significant increase of MTDs both in vitro and in vivo suggesting that MTDs may serve as a novel marker in hepatic IRI. Co-culture of MTDs with hepatocytes showed a decrease in cell viability in a concentration dependent manner, which indicates that MTDs is a toxic mediator participating in the pathogenesis of liver IR injury.

A gastrointestinal stromal tumour with pulmonary metastases mimicking unilateral gynaecomastia.

Gastrointestinal stromal tumours (GISTs) represent 1% of primary gastrointestinal cancers. These neoplasms most frequently metastasise to the liver and peritoneum and rarely to the lungs and bones. Treatment of unresectable GISTs involves systemic chemotherapy with tyrosine kinase inhibitors, imatinib and sunitinib being first-line and second-line drugs. We report the case of a 52-year-old man with GIST who developed a right-sided subareolar breast swelling and subsequently discovered to be an invasive metastatic pulmonary GIST. Given that gynaecomastia is a known adverse effect of imatinib and sunitinib, this case report illustrates the importance of including metastatic disease in the differential diagnosis of patients with GIST and with the new onset of soft tissue masses.