Application of Combined Donor-Derived Cell-Free DNA and Transcriptome in Diagnosis of Kidney Transplant Rejection.

BACKGROUND: Transcriptomic kidney profile testing and donor-derived cell-free DNA (dd-cfDNA) testing are new methods shown to provide early markers of graft inflammation during the post-transplant period. This study focused on utilizing clinical data to evaluate the application of these tests in detecting transplant rejection by comparing tests results to biopsy reports. MATERIAL AND METHODS: We conducted a retrospective analysis of a prospectively collected database of all adult kidney transplant patients at SUNY Upstate Medical Hospital from 1 January 2014 to 1 December 2022. Inclusion criteria were patients with concurrent transcriptomic kidney profile test and kidney biopsy results. RESULTS: Biopsies identified 33 kidney transplant rejections. For diagnosis of kidney rejection, transcriptomic kidney profile testing had a 52.83% positive predictive value and 92.77% negative predicative value, while dd-cfDNA testing had a 54.83% positive predictive value and 86.45% negative predictive value. Transcriptomic kidney profile testing showed an 82.35% sensitivity and 75.49% specificity, while dd-cfDNA testing showed a 56.66% sensitivity and 85.56% specificity. Positive transcriptomic kidney profile and dd-cfDNA tests detected 51.51% of rejections. Combined negative tests were observed in 70.21% of biopsies without rejection. CONCLUSIONS: Despite certain discrepancies and limitations, we believe transcriptomic profile testing and dd-cfDNA testing are useful for detecting early-stage rejections and can guide patient care. Additionally, dd-cfDNA testing avoids invasive screening biopsies. Following negative test results, the probability patients are not having rejection is 86.45%. The transcriptomic profile test's high sensitivity and specificity allow possible detection of transplant rejections that may have otherwise not been identified by biopsy.

Phytochemical evaluation, embryotoxic, and teratogenic effects of Buwakan (Decalobanthus peltatus (L.) A.R.Simões & Staples) leaf extracts on duck embryo.

Decalobanthus peltatus is a woody vine that is commonly utilized in traditional Southeast Asian medicinal preparations. Despite the documented therapeutic uses of D. peltatus, there is hardly any information regarding its toxic effects on its consumers. In this study, crude leaf extracts (aqueous, methanol, ethyl acetate, and hexane) from D. peltatus were prepared and evaluated for their embryotoxicity and teratogenic effects. Phytochemical screening of bioactive compounds from the plants showed the presence of alkaloids, flavonoids, saponins, steroids, and tannins. In addition, investigations on the toxicity of the crude leaf extracts were determined using brine shrimp lethality assay, in which the LC50 was calculated. Results showed that the ethyl acetate leaf extract was the most toxic among the crude leaf extracts, with an LC50 of 14.54 ppm. Based on this result, ethyl acetate leaf extract was treated on duck embryos, and the alteration of vascular branching patterns in the chorioallantoic membrane was quantified. Gross morphological and histological analysis of the skin tissues from the treated duck embryos were also examined. We found significant reduction of primary and tertiary vessel diameters in the duck embryos treated with ethyl acetate leaf extracts in both concentrations compared to the control group. Treated duck embryos exhibited gross malformations, growth retardation, and hemorrhages on the external body surfaces at 1000 ppm. Histopathological analysis of the skin tissues from the 14-day-old treated duck embryos showed a reduced number of feather follicles compared to the control group. These results suggest that D. peltatus crude leaf extracts present risks when taken in significant dosages and comprehensive toxicity testing on therapeutic herbs should be performed to ensure their safety on the consumers.

Pancreas after kidney transplantation, is it the time to overcome the stigma?

BACKGROUND: Pancreas transplantation is the most effective treatment to improve quality of life and overcome complications in patients with end-stage renal disease and diabetes mellitus. One of the main approaches for concurrent renal disease and diabetes mellitus which has been underutilized during the past decade is a pancreas transplant after kidney transplantation. Our study aimed to quantify outcomes following pancreas after kidney transplants (PAKs) in the United States from 2001 to 2020 with an emphasis on graft and patient survival. METHODS AND MATERIALS: A retrospective registry analysis was performed by accessing the OPTN/UNOS database for PAKs that were performed in the United States from January 2001 to April 2020. The study population was divided into two subgroups: patients receiving a pancreas transplant between 2001 and 2010 and those receiving a pancreas transplant between 2011 and 2020. RESULTS: The study examined a total number of 3706 PAK recipients; patients who received a PAK from January 2001 through December 2010 (n = 2892) and those who received a PAK from January 2011 to April 2020 (n = 814). The selection process of transplant recipients did not drastically change throughout the 2001-2010 and 2011-2020 periods. Length of stay at the hospital after the transplantation improved significantly in the 2011-2020 group relative to the 2001-2010 group (8.48 vs. 10.08 days, mean, p < 0.01). Additionally, more transplantation with 4-6 human leukocyte antigen mismatch occurred in the 2011-2020 group than in the 2001-2010 group (80.6% vs. 71.4%, p < 0.01). The pancreas preservation time of 13.35 h in the 2001-2010 group decreased significantly to 11.17 h in the 2011-2020 group (p < 0.001). The mean donor's amylase and lipase also decreased significantly in the 2011-2020 cohort. Significant graft survival improvement was observed in the 2011-2020 group compared to the 2001-2010 group after a long-term follow-up (p < 0.001). The mean Calculated Pancreas Donor Risk Index was 1.08 for the 2001-2010 group and 0.99 for the 2011-2020 group with a significant difference (p < 0.001). CONCLUSION: The beneficial results and improved outcomes observed in PAK patients demonstrate the effectiveness of the operation for individuals in need of a pancreas transplant. PAKs can prove to be a meaningful solution to overcome long waiting times, decrease the donor-recipient imbalance, expand the donor pool, and overcome the current underutilization in order to improve the short- and long-term quality of life in the groups of interest.

Early conversion to belatacept-based immunosuppression regimen promotes improved long-term renal graft function in kidney transplant recipients.

BACKGROUND: Belatacept has been demonstrated as an effective alternative immunosuppressant in kidney transplant recipients. This study focuses on outcomes of early and late conversion to Belatacept-based immunosuppression after kidney transplant. MATERIALS AND METHODS: This retrospective analysis of a prospectively collected database included all adult kidney transplants patients at SUNY Upstate Medical Hospital from 1 January 2014 to 30 December 2022. Early conversion was defined as all conversions done at <6 months after kidney transplantation, and late conversion to belatacept was defined as conversion at >6 months after kidney transplantation. RESULTS: Out of 61 patients included in this study, 33 patients (54%) were in the early conversion group, and 28 patients (46%) were in the late conversion group. The mean eGFR in the early conversion group was 26.73 ± 16.26 ml/min/1.73 m2 before conversion to belatacept, which improved to 45.3 ± 21.01 ml/min/1.73 m2 at one-year post-conversion (p = 0.0006). Furthermore, eGFR changes in the late conversion group were insignificant, with 46.30 ± 15.65 ml/min/1.73 m2 before conversion to belatacept, and 44.76 ± 22.91 ml/min/1.73 m2 after one year of follow-up (p = 0.72). All four biopsy-proven allograft rejections in the early conversion group were acute T-cell-mediated rejections (ATMR). In the late conversion group, out of three biopsy-proven rejections, one was chronic antibody-mediated rejection (CAMR), one was ATMR, and one was mixed ATMR/CAMR. All four patients with ATMR rejection received mycophenolic acid (MPA) as part of their immunosuppressive regimen, and none received tacrolimus. The one-year post-conversion allograft survival rate in early and late conversion groups was 100%. However, the one-year post-conversion patient survival rate was 90.9% in the early conversion group and 100% in the late conversion group (P = 0.11). CONCLUSIONS: Early post-transplant conversion to belatacept can improve the eGFR more meaningful when compared to late conversion. Patients who receive belatacept and MPA rather than tacrolimus may have increased rates of T-cell-mediated rejection.

Immunosuppression regimen modification during COVID-19 infection in kidney transplant recipients.

BACKGROUND: COVID-19 pandemic had tremendously affected all the aspects of human life during the past 3 years. In this study, we focused on kidney transplant patients' course from the COVID-19 diagnosis, immunosuppressive medication modification, hospitalization, and COVID-19 complications and how the COVID-19 infection affected the kidney and patients' quality of life during the hospitalization and after the discharge. MATERIAL AND METHOD: A retrospective analysis of a prospectively collected database of all kidney transplants adult patients who had a positive COVID-19 PCR from 1 January 2020 to 30 December 2022, and had a history of kidney transplant at the SUNY Upstate Medical Hospital was done to identify the cases. RESULTS: 188 patients met the inclusion criteria and were included in the study. Based on the immunosuppressive regimen modification during COVID-19 infection, patients divided into two groups; in 143 (76%) patients, the immunosuppressive medication was reduced, and in 45 (24%) of patients, the immunosuppressive regimen continued as before during the COVID-19 infection. The mean time from the transplant to the diagnosis of COVID-19 was 67 months in the group we reduced the IM regimen, and 77 months in the group without changes in IM regimen. The mean recipients' age was 50.7 ± 12.9 years in the group we reduced the IM regimen, and 51.8 ± 16.4 years in the group without changes in IM regimen (P = 0.64). The vaccination rate against COVID-19 with at least 2 doses of either the CDC recommended Moderna or Pfizer vaccines was 80.2% in the group we reduced the IM regimen, and 84.8% in the group without changes in IM regimen (P = 0.55). The hospitalization rate due to COVID-19 related symptoms was 22.4% % in the group we reduced the IM regimen, and 35.5% in the group without changes in IM regimen (P = 0.12). However, the ICU admission rate was higher in the group we reduced the IM regimen, but the difference was not significant (26.5% Vs.6.25%, P = 0.12). 6 episodes of biopsy-proven rejection in the group with IM reduction was observed, which were 3 episodes of acute antibody-mediated rejections (ABMR) and 3 episodes of acute T-Cell-mediated rejections (TCMR), and 3 episodes in the group without any change in IM regimen, which were 2 episodes of ABMR and 1 episode of TCMR (P = 0.51). No significant difference was mentioned in the eGFR and serum creatinine after the comparison between the groups after 12 months of follow up. 124 patients responded to the post-COVID-19 questionnaires and were included in the data analysis. The response rate was 66%. Fatigue and exertion were the most reported symptom with a 43.9% prevalence. CONCLUSIONS: We found that immunosuppressive regimen minimization did not impact the kidney function in the long-term and it might be a helpful strategy to minimize the effect of COVID-19 infection on patients' condition during the hospital stay. With all the treatments, vaccinations, and precautions, still some patients did not achieve the complete recovery compared to their pre-COVID-19 health status. Fatigue was the main reported symptom amongst all the reported symptoms.

Deceased Donor Kidney Transplantation From Donors With Acute Kidney Injury: Realities and Costs.

OBJECTIVES: Transplant of kidneys from donors with acute kidney injury has shown favorable outcomes. We investigated the outcomes of kidney transplant recipients with deceased donors who developed acute kidney injury before organ procurement. MATERIALS AND METHODS: We retrospectively reviewed the medical records of recipients from January 2016 to December 2021 in a single center. Outcomes in recipients of kidney grafts from donors with and without acute kidney injury were compared. RESULTS: The mean follow-up time was 40 months. Our study included 129 (34%) kidneys transplanted from donors with acute kidney injury and 251 (66%) kidneys from donors without acute kidney injury. Delayed graft function rate in recipients was 33% in the acute kidney injury group and 25.5% in the group without acute kidney injury (P = .099). Readmission rate at 30 days was significantly higher among recipients of kidneys with acute kidney injury compared with recipients of kidneys without acute kidney injury (45% vs 33.5%; P = .02). The mean overall costs of transplant in the acute kidney injury group were comparable to the group without acute kidney injury ($253 865 vs $253 611; P = .97). The acute rejection rate was comparable between the 2 groups (4% in both groups; P = .96). Delayed graft function rate was increased with increased stage of acute kidney injury (18% stage 1, 45% stage 2, 36% stage 3; P = .03). However, the overall length of hospital stay and costs were comparable among recipients of different stages of acute kidney injury. CONCLUSIONS: Our study showed that kidney transplants from donors with acute kidney injury have early and late outcomes comparable to kidney transplants from donors without acute kidney injury. Allografts from donors with acute kidney injury can be used safely and can expand the donor pool in kidney transplant without increasing perioperative resource utilization.

Conversion to Belatacept in kidney transplant recipients with chronic antibody-mediated rejection (CAMR).

BACKGROUND: The costimulatory inhibitor Belatacept (Bela) has been shown to be an effective alternative in several clinical situations, including chronic antibody-mediated rejection, calcineurin toxicity, and de novo alloantibody formation. To further explore the usefulness of Belatacept under various clinical scenarios, we performed a retrospective analysis of a prospective database of all recipients who had a BPAR diagnosis of CAMR and were converted to a Belatacept maintenance immunosuppression regimen after kidney transplantation. MATERIAL AND METHOD: We conducted a retrospective analysis of a prospectively collected database of all kidney transplants adult patients at SUNY Upstate Medical Hospital from 1 January 2013 to 31 December 2021. Our inclusion criteria were the patients who have been diagnosed with CAMR according to their renal biopsy based on the 2013 Banff criteria. The primary objective was to compare the kidney viability and function using GFR between the two interest groups and finally compare the outcomes. RESULTS: A total of 48 patients met our inclusion criteria based on the kidney biopsy result, which showed chronic antibody-mediated graft rejection (CAMR). Nineteen patients (39.6%) were converted to the Belatacept, and we continued the previous immunosuppression regimen in 29 patients (60.4%). The mean time from the transplant date to the diagnosis of CAMR was 1385 days in the Belatacept group and 914 days for the non-Belatacept group (P = 0.15). The mean GFR comparison at each time point between the groups did not show a significant difference, and Belatacept did not show superiority compared to the standard immunosuppression regimen in terms of kidney function preservation. 1 (5.2%) patient from the Belatacept group and 1 (3.4%) patient from the non-Belatacept group had a biopsy-proven acute rejection (BPAR) after CAMR confirmation, and it was comparable (P = 0.76). De novo synthesis of the DSA rate was 12.5% in the Belatacept group and 15% In the non-Belatacept group, which was comparable. (P = 0.90). The patient survival rate was 100% in both groups. CONCLUSIONS: We conclude that compared to the standard Tacrolimus/MMF/Prednisone regimen, Belatacept did not significantly benefit in preserving the GFR in long-term follow-ups and stabilizing the DSA production, which is one of the main factors resulting in chronic graft failure.

BosR: A novel biofilm-specific regulator in Pseudomonas aeruginosa.

Biofilms are the most common cause of bacterial infections in humans and notoriously hard to treat due to their ability to withstand antibiotics and host immune defenses. To overcome the current lack of effective antibiofilm therapies and guide future design, the identification of novel biofilm-specific gene targets is crucial. In this regard, transcriptional regulators have been proposed as promising targets for antimicrobial drug design. Therefore, a Transposon insertion sequencing approach was employed to systematically identify regulators phenotypically affecting biofilm growth in Pseudomonas aeruginosa PA14 using the TnSeq analysis tools Bio-TraDIS and TRANSIT. A screen of a pool of 300,000 transposon insertion mutants identified 349 genes involved in biofilm growth on hydroxyapatite, including 47 regulators. Detection of 19 regulatory genes participating in well-established biofilm pathways validated the results. An additional 28 novel prospective biofilm regulators suggested the requirement for multiple one-component transcriptional regulators. Biofilm-defective phenotypes were confirmed for five one-component transcriptional regulators and a protein kinase, which did not affect motility phenotypes. The one-component transcriptional regulator bosR displayed a conserved role in P. aeruginosa biofilm growth since its ortholog in P. aeruginosa strain PAO1 was also required for biofilm growth. Microscopic analysis of a chromosomal deletion mutant of bosR confirmed the role of this regulator in biofilm growth. Overall, our results highlighted that the gene network driving biofilm growth is complex and involves regulators beyond the primarily studied groups of two-component systems and cyclic diguanylate signaling proteins. Furthermore, biofilm-specific regulators, such as bosR, might constitute prospective new drug targets to overcome biofilm infections.

Piperacillin/Tazobactam and Meropenem Use Increases the Risks for Acute Graft Rejection Following First Kidney Transplantation.

Many broad-spectrum antibiotics (BSA) alter the intestinal microbiome that regulates adaptive immune responses. We hypothesized that BSA use before and early after kidney transplant may affect acute graft rejection (AGR). We carried out a retrospective cohort study on all patients who underwent kidney transplants in our institution. Patient demographics, clinical data, diagnosis, and treatment history were collected. Antibiotic use within 2 months prior to transplant and during the hospital admissions for transplant, as well as antibiotic types were recorded. A total of 357 consecutive first transplants were included for analysis. Median age was 52 years (range 7-76). A total of 67 patients received living donor and 290 deceased donor kidneys. A total of 19 patients received BSA within two months prior to transplant and 55 patients during the hospital admission for the transplant. With a median follow-up of 1270 days, 38 episodes of biopsy-proven AGR were recorded. There was no difference in the AGR rates during the first year between patients who received BSA and those who did not. However, the use of piperacillin/tazobactam or meropenem (PM) was associated with increased risks for the development of AGR, irrespective of the source of the donor grafts. Time to development of AGR was also shorter. Our data, therefore, suggest that the use of PM BSA prior to and immediately after kidney transplant increases the risks for AGR.

Utilization of Treg Cells in Solid Organ Transplantation.

Organ transplants have been a life-saving form of treatment for many patients who are facing end stage organ failure due to conditions such as diabetes, hypertension, various congenital diseases, idiopathic diseases, traumas, and other end-organ failure. While organ transplants have been monumental in treatment for these conditions, the ten year survival and long-term outcome for these patients is poor. After receiving the transplant, patients receive a multi-drug regimen of immunosuppressants. These drugs include cyclosporine, mTOR inhibitors, corticosteroids, and antibodies. Polyclonal antibodies, which inhibit the recipient's B lymphocytes, and antibodies targeting host cytokine inhibitors which prevent activation of B cells by T cells. Use of these drugs suppresses the immune system and increases the risk of opportunistic pathogen infections, tumors, and further damage to the transplanted organs and vasculature. Many regulatory mechanisms are present in organs to prevent the development of autoimmune disease, and Tregs are central to these mechanisms. Tregs secrete suppressive cytokines such as IL-10, TGF-B, and IL-35 to suppress T cells. Additionally, Tregs can bind to target cells to induce cell cycle arrest and apoptosis and can inhibit induction of IL-2 mRNA in target T cells. Tregs also interact with CTLA-4 and CD80/CD86 on antigen presenting cells (APCs) to prevent their binding to CD28 present on T cells. Due to their various immunosuppressive capabilities, Tregs are being examined as a possible treatment for patients that receive organ transplants to minimize rejection and prevent the negative outcomes. Several studies in which participants were given Tregs after undergoing organ transplantations were reviewed to determine the efficacy and safety of using Tregs in solid organ transplantation to prevent adverse outcomes.

Changes in immune profile affect disease progression in hepatocellular carcinoma.

Objective: Hepatocellular carcinoma (HCC) as a chronic liver condition is largely associated with immune responses. Previous studies have revealed that different subsets of lymphocytes play fundamental roles in controlling or improving the development and outcome of solid tumors like HCC. Hence, this study aimed to investigate whether immune system changes were related to disease development in HCC patients. Methods: Peripheral blood mononuclear cells were isolated from 30 HCC patients and 30 healthy volunteers using Ficoll density centrifugation. The isolated cells were stained with different primary antibodies and percentages of different immune cells were determined by flow cytometry. Results: HCC patients indicated significant reductions in the numbers of CD4+ cells, Tbet+IFNγ+cells, and GATA+IL-4+cells in peripheral blood in comparison with healthy individuals (p < 0.05). There was no significant change in IL-17+RORγt+cells between patient and healthy groups. In contrast, Foxp3+CD127lowcell frequency was significantly higher in patients than healthy subjects (p < 0.0001). The numbers of Th1, Th2, and Th17 cells were significantly lower in HCC patients than healthy control (p < 0.0001), although the reduction in Th2 cell numbers was not statistically significant. On the contrary, Treg percentage showed a significant increase in patients compared to healthy subjects (p < 0.0001). Other data revealed that Th1, Th2, and Th17 cell frequencies were significantly higher in healthy individuals than patients with different TNM stages of HCC, with the exception of Th2 in patients with stage II HCC (p < 0.01-0.05). Treg percentage was significantly increased in patients with different TNM stages (p < 0.0001). Among all CD4+ T cells, the frequency of Th2 cell was significantly associated with TNM stages of HCC (p < 0.05). Conclusion: Our data provide further evidence to show that immune changes may participate in determining HCC progression and disease outcome. However, it should be mentioned that more investigations are needed to clarify our results and explain possible impacts of other immune cells on the pathogenesis of HCC.

Agitation and Sugar Craving Related to Epilepsy Seizure.

INTRODUCTION: Epilepsy is a chronic central nervous system disorder characterized by the recurrence of unprovoked seizures and can affect people of all ages. Seizure symptoms can vary widely in patients. Many papers have been published about agitation and epileptic seizures, but almost nothing about sugar cravings and agitation related to epilepsy. The purpose of this case report is to shed light on possibly a hidden symptom within the epilepsy field, in fact sugar cravings. Case presentation. A 12-year-old boy was referred to the children and adolescent psychiatric outpatient clinic with suspicion of ADHD. The boy has struggled with anxiety, concentration, and impulsivity. Because of intense agitation and sugar cravings, the patient was referred to EEG. The EEG shows pathological activity with bilatero-temporal to central epileptiform activity, not synchronized. After pathological EEG findings, the patient started treatment with Lamotrigine. Great improvement when it comes to agitation, moodiness, and reduction of sugar craving after starting with Lamotrigine. CONCLUSION: We consider inexplicable behavior or symptoms such as agitation and sugar craving may be related to epilepsy seizure. Therefore, it is important that these patients should be examined more closely with EEG to confirm or deny epilepsy.

Liver Resection Promotes (Regulates) Proinflammatory Cytokines in Patients with Hepatocellular Carcinoma.

Background: Several animal studies have shown the roles of cytokines in regulating liver regeneration following liver resection (LR), which is a type of surgery designed to remove cancerous tumors from the liver. This study investigated how the expressions and serum levels of some pro- and anti-inflammatory cytokines in patients with hepatocellular carcinoma (HCC) were changed during LR. Methods: Liver tissues from 15 patients with HCC were collected and the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), IL-1α, IL-1 ß, IL-10, and transforming growth factor-beta1 (TGF-ß1) were assessed using real-time PCR assay at different times before and after LR. The serum values of TNF-α and IL-6 were also measured by ELISA. Results: After 60 and 90 minutes of LR, IL-6 gene expression was significantly increased (P < 0.001 - 0.05). The same trend was also observed in TNF-α expression after 90 minutes of LR (P < 0.01). No significant changes were observed in the expressions of IL-1α, IL-1ß, IL-10, and TGF-ß1 before and after LR. In addition, LR had significant effects on TNF-α and IL-6 serum levels (P < 0.05 - 0.0001). Conclusion: Our data provided further evidence to reveal that IL-6 and TNF-α cytokines are critical to improve liver regeneration.

Sitagliptin Modulates the Response of Ovarian Cancer Cells to Chemotherapeutic Agents.

The strong association between diabetes mellitus type 2 and cancer is observed. The incidence of both diseases is increasing globally due to the interaction between them. Recent studies suggest that there is also an association between cancer incidence and anti-diabetic medications. An inhibitor of dipeptidyl-peptidase 4 (DPP-4), sitagliptin, is used in diabetes treatment. We examined the influence of sitagliptin alone or in combination with a cytostatic drug (paclitaxel) on the development of epithelial ovarian cancer cells and the process of metastasis. We examined migration, invasiveness, apoptosis, and metalloproteinases (MMPs) and their inhibitors' (TIMPs) production in two human ovarian cancer cell lines. Sitagliptin induced apoptosis by caspase 3/7 activation in paclitaxel-treated SKOV-3 and OVCAR-3 cells. Sitagliptin maintained paclitaxel influence on ERK and Akt signaling pathways. Sitagliptin additionally reduced migration and invasiveness of SKOV-3 cells. There were distinct differences of metalloproteinases production in sitagliptin-stimulated ovarian cancer cells in both cell lines, despite their identical histological classification. Only the SKOV-3 cell line expressed MMPs and TIMPs. SKOV-3 cells co-treated with sitagliptin and paclitaxel decreased concentrations of MMP-1, MMP-2, MMP-7, MMP-10, TIMP-1, TIMP-2. The obtained data showed that sitagliptin used with paclitaxel may be considered as a possibility of pharmacological modulation of intracellular transmission pathways to improve the response to chemotherapy.

Venous thromboembolism risk for the contemporary bariatric surgeon.

BACKGROUND: Postoperative venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), are the leading causes of morbidity and mortality after bariatric surgery. Although several studies have examined VTE, few have examined risk factors separately for DVT and PE after contemporary bariatric surgery, including laparoscopic sleeve gastrectomy (LSG). Our objective was to define risk factors for DVT and PE independently for both LSG and laparoscopic Roux-en-Y gastric bypass (LRYGB) patients using the largest validated bariatric surgery database. METHODS: The metabolic and bariatric surgery accreditation and quality improvement program (MBSAQIP) database was queried to identify patients who underwent LSG or LRYGB between January 2015 and December 2017. Perioperative data were compared using bivariate analysis. Risk of DVT and PE after LSG or LRYGB was determined using multivariable logistic regression analysis. RESULTS: During the study period, 369,032 bariatric cases (72% LSG, 28% LRYGB) were performed. The incidence of DVT was similar between LSG and LRYGB (0.2% vs. 0.2%, p = 0.96), while the incidence of PE was decreased for LSG compared to LRYGB (0.1% vs. 0.2%, p < 0.001). Operative length was associated with increased risk of postoperative DVT (OR 1.1, CI 1.01-1.30, p = 0.04) and postoperative PE (OR 1.4, CI 1.16-1.64, p < 0.001) after surgery. The largest independent risk factors for DVT were history of DVT (OR 6.2, CI 4.44-8.45, p < 0.001) and transfusion (OR 4.2, CI 2.48-6.63, p < 0.001). The largest independent risk factors for PE were transfusion (OR 5.0, CI 2.69-8.36, p < 0.001) and history of DVT (OR 2.8, CI 1.67-4.58, p < 0.001). LSG was associated with a decreased risk of PE compared to LRYGB (OR 0.7 CI 0.55-0.91, p = 0.01). CONCLUSIONS: Prolonged operative length is associated with a higher risk of DVT and PE after either LSG or LRYGB. Transfusion and history of DVT are the largest risk factors for developing DVT and PE. There is a decreased risk of PE after LSG compared to LRYGB.

Role of Telemedicine in Multidisciplinary Team Meetings.

We reviewed the role of telemedicine in multidisciplinary team (MDT) meetings, which play an important role in the provision of effective and tailored patient care in diverse clinical settings. This article is based on conducted search in PubMed. Search terms included "telemedicine," "multidisciplinary team," and "(telemedicine) and (multidisciplinary team)." Telemedicine provides an important advantage in the provision of MDT meeting comparing with traditional settings. Those include improved access to and collaboration of medical experts. This resulted in increased levels of medical competence and improved provisions of diagnosis, treatment, and follow-up to patients irrespective of location.

Utilization of Mesenchymal Stem Cells in Kidney Transplantation: From Bench to Bedside.

There has been ample of preclinical and animal studies whichshowed efficacy and safety of using mesenchymal stem cells (MSCs)after transplantation for tissue repair, immunosuppression ortolerance induction. However, there has been a significant progressrecently using MSCs in small clinical trials after transplantation. Recent results using MSCs after transplantation seem to befeasible and safe. However, there are some limitations to show theeffectiveness of these cells including source, dose, timing and routeof infusions. Currently, live donor kidney transplantation has beenespecially considered and development of recent regimes includingimmunosuppression drugs and MSCs administration to kidney andother organs and deceased donor transplantation would be crucial.Therefore, in this review we focused on immunomodulatory effectsof MSCs that have been extensively studied to suppress variousinflammatory responses in kidney transplantation.

Exenatide modulates expression of metalloproteinases and their tissue inhibitors in TNF-α stimulated human retinal pigment epithelial cells.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common complications of diabetes and the leading cause of acquired blindness in adults. In diabetic patients hyperglycemia induces complex metabolic abnormalities affecting retinal homeostasis, and promotes retinal inflammation and angiogenesis. Incretin mimetic drugs such exenatide, are a relatively new group of drugs used in the treatment of diabetes. We investigated the potential direct effects of exenatide on human retinal pigment epithelium (HRPE). METHODS: cAMP production was measured after stimulation of HRPE cells with GLP-1 and exenatide. Intracellular signaling pathways were also examined. HRPE cells were stimulated with TNF-α and subsequently incubated with exenatide. The concentration of metalloproteinases, MMP-1, MMP-2 and MMP-9, and tissue inhibitors of metalloproteinases, TIMP-1, TIMP-2, and TIMP-3 were evaluated. Viability, cytotoxicity and caspase 3/7 activation were determined. Activity of dipeptidyl peptidase-4 (DPP-4), an enzyme involved in GLP-1 inactivation, was also determined. RESULTS: Both GLP-1 and exenatide stimulation in HRPE cells caused no effect in cAMP levels suggesting alternative signaling pathways. Signaling pathway analysis showed that exenatide reduced phosphorylation of Akt-Ser473, PRAS40, SAPK/JNK, Bad, and S6 proteins but not Akt-Thr308. Exenatide also decreased MMP-1, MMP-9, and TIMP-2 protein levels whereas MMP-2 level in HRPE cells was increased. Finally, we show that exenatide decreased the activity of DPP-4 in TNF-α stimulated HRPE cells. CONCLUSIONS: These findings indicate that exenatide modulates regulation of extracellular matrix components involved in retinal remodeling.

Complete Routine Remote Digital Pathology Services.

BACKGROUND: Validation studies in digital pathology addressed so far diverse aspects of the routine work. We aimed to establish a complete remote digital pathology service. METHODS: Altogether 2295 routine cases (8640 slides) were reported in our studies on digital versus microscopic diagnostics, remote reporting, diagnostic time, fine-needle aspiration cytology (FNAC) clinics, frozen sections, and diagnostic sessions with residents. The same senior pathologist was involved in all studies. Slides were scanned by ScanScope AT Turbo (Aperio). Digital images were accessed through the laboratory system (LS) on either 14" laptops or desktop computers with double 23" displays for the remote and on-site digital reporting. Larger displays were used when available for remote reporting. First diagnosis was either microscopic, digital, or remote digital only (6 months washout period). Both diagnoses were recorded separately and compared. Turnaround was measured from the registration to sign off or scanning to diagnosis. A diagnostic time was measured from the point slides were made available to the point of diagnosis or additional investigations were necessary, recorded independently in minutes/session, and compared. Jabber Video (Cisco) and Lync (Microsoft) were interchangeably used for the secure, video supervision of activities. Mobile phone, broadband, broadband over Wi-Fi, and mobile broadband were tested for internet connections. Nine autopsies were performed remotely involving three staff pathologists, one autopsy technician, and one resident over the secure video link. Remote and on-site pathologists independently interpreted and compared gross findings. Diverse benefits and technical aspects were studied using logs or information recorded in LS. Satisfaction surveys on diverse technical and professional aspects of the studies were conducted. RESULTS: The full concordance between digital and light microscopic diagnosis was 99% (594/600 cases). A minor discordance, without clinical implications, was 1% (6/600 cases). The instant upload of digital images was achieved at 20 Mbps. Deference to microscopic slides and rescanning were under 1%. Average turnaround was shorter and percentage of cases reported up to 3 days higher for remote digital reporting. Larger displays improved the most user experience at magnifications over ×20. A digital diagnostic time was shorter than microscopic in 13 sessions. Four sessions with shorter microscopic diagnostic time included more cases requiring extensive use of magnifications over ×20. Independent interpretations of gross findings between remote and on-site pathologists yielded full agreement in the remote autopsies. Delays in reporting of frozen sections and FNAC due to scanning were clinically insignificant. Satisfaction levels with diverse technical and/or professional aspects of all studies were high. CONCLUSIONS: Complete routine remote digital pathology services are found feasible in hands of experienced staff. The introduction of digital pathology has improved provisions and organizations of our pathology services in histology, cytology, and autopsy including teaching and interdepartmental collaboration.