Limitations of antifungal prophylaxis in preventing invasive Candida surgical site infections after liver transplant surgery.

Invasive primary Candida surgical site infections (IP-SSIs) are a common complication of liver transplantation, and targeted antifungal prophylaxis is an efficient strategy to limit their occurrence. We performed a retrospective single-center cohort study among adult single liver transplant recipients at Duke University Hospital in the period between 1 January 2015 and 31 December 2020. The study aimed to determine the rate of Candida IP-SSI according to the peri-transplant antifungal prophylaxis received. Of 470 adult single liver transplant recipients, 53 (11.3%) received micafungin prophylaxis, 100 (21.3%) received fluconazole prophylaxis, and 317 (67.4%) did not receive systemic antifungal prophylaxis in the peri-transplant period. Ten Candida IP-SSIs occurred among 5 of 53 (9.4%) micafungin recipients, 1 of 100 (1.0%) fluconazole recipients, and 4 of 317 (1.3%) recipients who did not receive antifungal prophylaxis. Our study highlights the limitations of antifungal prophylaxis in preventing invasive Candida IP-SSI after liver transplant surgery. We hypothesize that pathogen, host, and pharmacokinetic-related factors contributed to the occurrence of Candida IP-SSI despite antifungal prophylaxis. Our study reinforces the need for a risk-based, multi-pronged approach to fungal prevention, including targeted antifungal administration in patients with risks for invasive candidiasis and close monitoring, especially among patients with surgically complex procedures, with timely control of surgical leaks.

Integrated solutions to manage new normals in healthcare-lessons from corona virus disease 2019.

Global outbreak of the corona virus disease 2019 (COVID19) has not only challenged the existing healthcare systems but is also a threat to the world economy and stability. In the recent times the world has seen the best healthcare systems collapsing due to the overwhelming burden. Thus, it shows that there have been major lacunae in the pandemic preparedness across the globe. Hence, there is an urgent need to identify the problems, learn from failures and to prepare for future pandemics to reduce the loss of lives and livelihood. In the modern era, blend of public healthcare systems, medical sciences and technology can be put to use to provide solutions. In this article, the authors propose a developmental model of international integrated database software which would connect all the players involved in the management of a pandemic. Better networking and warning system is a key to successful containment of a new viral outbreak.

Development of a Telehealth Intervention to Improve Access to Live Donor Kidney Transplantation.

BACKGROUND: Live donor kidney transplantation (LDKT) is underutilized by patients with end-stage kidney disease due to knowledge, communication, and logistical barriers. MATERIAL AND METHODS: The Talking About Live Kidney Donation Social Worker Intervention (TALK-SWI) is a previously validated intervention demonstrated to improve patients' access to and pursuit of LDKT through in-person delivery of education and social support. To help overcome logistical barriers to LDKT, we adapted TALK-SWI into a telehealth intervention employing digital (ie, tablet, smartphone) and telephone technologies. We studied the usability and acceptability of both the mobile device and telephone counseling portions of the intervention among people with kidney disease. For the digital portion, we assessed critical (ie, inability to complete a task) and non-critical (ie, ability to complete a task utilizing an alternative method) errors participants encountered when using the program and their preferences regarding digital materials. Simultaneously, we assessed participants' satisfaction with telephone-adapted counseling compared to the original, in-person counseling. RESULTS: The 15 participants testing the digital technology made 25 critical errors and 29 non-critical errors, while they easily completed 156 tasks (out of 210). A majority of participants (73%) preferred the tablet/smart phone education application over traditional materials, and most (80%) indicated they would be more likely to utilize the mobile platform over traditional materials. Participants testing the telephone-adapted (n = 45) and in-person (n = 125) social worker counseling all reported high satisfaction with the intervention. CONCLUSION: We successfully adapted a validated educational and behavioral intervention to improve access to LDKT into a usable and acceptable telehealth intervention.

The Incremental Cost of Incompatible Living Donor Kidney Transplantation: A National Cohort Analysis.

Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p < 0.0001 for all). ILDKT was associated with longer median length of stay (12.9 vs. 7.8 days), higher Medicare payments ($91 330 vs. $63 782 p < 0.0001), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplantation.

The current state of intestine transplantation: indications, techniques, outcomes and challenges.

Intestine transplantation is the least common form of organ transplantation in the United States and often deemed one of the most difficult. Patient and graft survival have historically trailed well behind other organ transplants. Over the past 5-10 years registry reports and single center series have demonstrated improvements to patient survival after intestinal transplantation that now match patient survival for those without life-threatening complications on parenteral nutrition. For various reasons including improvements in medical care of patients with intestinal failure and difficulty accessing transplant care, the actual number of intestine transplants has declined by 25% over the past 6 years. In light of the small numbers of intestine transplants, many physicians and the lay public are often unaware that this is a therapeutic option. The aim of this review is to describe the current indications, outcomes and advances in the field of intestine transplantation and to explore concerns over future access to this important and life-saving therapy.

Quantifying the risk of incompatible kidney transplantation: a multicenter study.

Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti-HLA donor-specific antibody (DSA). Program-specific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15-2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71-6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28-3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98-7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal-quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19-, 1.33- and 1.73-fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22-, 4.09- and 10.72-fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life-saving treatment in jeopardy of regulatory intervention.

Liver transplantation in an adolescent with acute liver failure from acute lymphoblastic leukemia.

The most common identifiable causes of acute liver failure in pediatric patients are infection, drug toxicity, metabolic disease, and autoimmune processes. In many cases, the etiology of acute liver failure cannot be determined. Acute leukemia is an extremely rare cause of acute liver failure, and liver transplantation has traditionally been contraindicated in this setting. We report a case of acute liver failure in a previously healthy 15-yr-old male from pre-B-cell acute lymphoblastic leukemia. He underwent liver transplantation before the diagnosis was established, and has subsequently received chemotherapy for pre-B-cell acute lymphoblastic leukemia. He is currently alive 31 months post-transplantation. The published literature describing acute lymphoblastic leukemia as a cause of acute liver failure is reviewed.

Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study.

In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m(2) (97.5% CI 1.9, 11.4 mL/min/1.73 m(2), p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m(2) in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m(2) in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant.

Posterior reversible encephalopathy syndrome independently associated with tacrolimus and sirolimus after multivisceral transplantation.

Posterior reversible encephalopathy syndrome (PRES) is a small vessel microangiopathy of the cerebral vasculature that occurs in 0.5-5% of solid organ transplant recipients, most commonly associated with tacrolimus (Tac). Clinical manifestations include hypertension and neurologic symptoms. We report an adult multivisceral transplant recipient who experienced recurrent PRES initially associated with Tac and subsequently with sirolimus. A 49-year-old woman with short bowel syndrome underwent multivisceral transplantation due to total parenteral nutrition-related liver disease. She was initially maintained on Tac, mycophenalate mofetil (MMF) and prednisone. Three months after transplantation, she developed renal dysfunction, leading to a reduction in Tac and the addition of sirolimus. Eight months after transplantation, she developed PRES. Tac was discontinued and PRES resolved. Sirolimus was increased to maintain trough levels of 12-15 ng/mL. Fourteen months after transplant, she experienced recurrent PRES which resolved after discontinuing sirolimus. Currently 3 years posttransplant, she is maintained on cyclosporine, MMF and prednisone with no PRES recurrence. In addition to calcineurin inhibitors, sirolimus may also be associated with PRES after solid organ transplantation. Ours is the first report of sirolimus-associated PRES in the setting of multivisceral transplantation. Identifying a safe alternative immunosuppression regimen was challenging but ultimately successful.

Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial.

In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (-3.0%; 95% CI -8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m(2) , 97.5% CI 3.74, 13.27 mL/min/1.73 m(2) , p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation.

Use of vascularized posterior rectus sheath allograft in pediatric multivisceral transplantation--report of two cases.

Restoring abdominal wall cover and contour in children undergoing bowel and multivisceral transplantation is often challenging due to discrepancy in size between donor and recipient, poor musculature related to birth defects and loss of abdominal wall integrity from multiple surgeries. A recent innovation is the use of vascularized posterior rectus sheath to enable closure of abdomen. We describe the application of this technique in two pediatric multivisceral transplant recipients--one to buttress a lax abdominal wall in a 22-month-old child with megacystis microcolon intestinal hypoperistalsis syndrome and another to accommodate transplanted viscera in a 10-month child with short bowel secondary to gastoschisis and loss of domain. This is the first successful report of this procedure with long-term survival. The procedure has potential application to facilitate difficult abdominal closure in both adults and pediatric liver and multivisceral transplantation.

Long-term management of the liver transplant patient: recommendations for the primary care doctor.

No official document has been published for primary care physicians regarding the management of liver transplant patients. With no official source of reference, primary care physicians often question their care of these patients. The following guidelines have been approved by the American Society of Transplantation and represent the position of the association. The data presented are based on formal review and analysis of published literature in the field and the clinical experience of the authors. These guidelines address drug interactions and side effects of immunosuppressive agents, allograft dysfunction, renal dysfunction, metabolic disorders, preventive medicine, malignancies, disability and productivity in the workforce, issues specific to pregnancy and sexual function, and pediatric patient concerns. These guidelines are intended to provide a bridge between transplant centers and primary care physicians in the long-term management of the liver transplant patient.

Robotically assisted biliary pancreatic diversion with a duodenal switch: a new technique.

BACKGROUND: Minimally invasive surgical techniques decrease the length of hospitalization and the morbidity for general surgery procedures. Application of minimally invasive techniques to obesity surgery had previously been limited to stapled techniques used primarily for the Roux-en-Y gastric bypass and laparoscopic band placement. The authors present the technique for totally intracorporeal robotically assisted biliary pancreatic diversion with a duodenal switch (BPD/DS) using five ports. METHODS: After development of the technique in animal and human cadaver models, the da Vinci robot was first used in October 2000 to perform BPD/DS using five ports and a totally intracorporeal technique. Patient selection was based on standard surgery guidelines for the morbidly obese. RESULTS: This technique was applied for 47 patients with a mean body mass index (BMI) of 45 kg/m2 and a mean age of 38 +/- 10 years. The median operating time was 514 min (range, 370-931 min). The median operative time for the last 10 patients was 379 min (range, 370-582 min). Three patients underwent conversion to open surgery, and four patients experienced postoperative leaks with no mortality. CONCLUSION: The safety, feasibility, and reproducibility of a minimally invasive robotic surgical approach to complex abdominal operations such as BPD/DS is demonstrated. The BPD/DS allows for a sutured bowel anastomosis similar to the open technique using a minimal number of small access ports.

Predicting outcome of procedures to slow intestinal transit.

Procedures designed to slow intestinal transit in patients with the short-bowel syndrome (SBS) have unpredictable outcomes. Our aim was to evaluate the outcome and predictive factors for this complication in SBS patients. Ten patients (37-61 years) underwent reversed segment (n = 9) or nipple valve creation (n = 1). All patients had remnant lengths over 90 cm and rapid intestinal transit times. All subjects had benign diseases, including Crohn's (n = 3). Six patients had a colon remnant. SBS had been present for 8 to 150 months. Nine (90%) required parental nutrition (PN) preoperatively. A procedure was performed either alone (n = 5) or concurrently with an ostomy closure (n = 3), an ostomy revision (n = 1), or a fundoplication (n = 1). There was one postoperative complication (urinary tract infection) and no deaths. Two patients developed bacterial overgrowth. One required repair of an ileocolonic stricture. One reversed segment was taken down 12 months later. Five (50%) patients improved (off PN), five remained on PN or had persistent diarrhea. Patients with a successful outcome were more likely to have had ostomy takedown (60% vs 0%). The duration of SBS; presence of Crohn's disease, a colon remnant, or type 1 anatomy; and the transit times were similar in both groups. Adjusted remnant length (small intestine +30 cm for type 2 anatomy and +60 cm for type 3) was similar (136 +/- 20 vs 154 +/- 25 cm). Procedures may benefit half of selected SBS patients with adequate remnant length and rapid transit. Successful patients are more likely to have an ostomy takedown, but the outcome is less determined by transit time or intestinal length if over 90 cm.

Inflammatory bowel disease after liver transplantation: risk factors for recurrence and de novo disease.

Inflammatory bowel disease (IBD) is associated with primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) and can recur or develop de novo after orthotopic liver transplantation (OLT). The aim of this study was to investigate the incidence and severity of IBD after liver transplantation and to perform a multivariate analysis for possible risk factors. In this retrospective study, 91 patients transplanted for PSC or AIH, without prior colectomy, were included. Sixty patients were transplanted for PSC, 31 for AIH. IBD activity before and after OLT and other possible risk factors were analysed in a multivariate model. Forty-nine patients (54%) had IBD before OLT. Forty patients (44%) had active IBD after transplantation: recurrence in 32 and de novo in 8. Cumulative risk for IBD after OLT was 15, 39 and 54% after 1, 5 and 10 years, respectively. In 59% of patients with IBD prior to OLT the disease was more active after transplantation. Risk factors for recurrent disease were: symptoms at time of OLT, short interval of IBD before OLT and use of tacrolimus. 5-aminosalicylates were protective. A cytomegalovirus positive donor/negative recipient combination increased the risk for de novo IBD.