Postoperative Acute Kidney Injury and Long-Term Outcomes After Lung Transplantation.

BACKGROUND: This study sought to characterize perioperative risk factors of acute kidney injury (AKI) and report outcomes associated with its development in the immediate postoperative setting after lung transplantation. METHODS: Study investigator performed a retrospective analysis of all adult patients undergoing primary lung transplantation at a single institution from January 1, 2011 to December 31, 2021 AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria after lung transplantation and was stratified on the basis of whether patients required renal replacement therapy (RRT; AKI-no RRT vs AKI-RRT). RESULTS: Of the 754 patients included, 369 (48.9%) any AKI developed in the postoperative period (252 AKI-no RRT vs 117 AKI-RRT). Risk factors for postoperative AKI included higher preoperative creatinine levels (odds ratio [OR], 5.15; P < .001), lower preoperative estimated glomerular filtration rate (OR, 0.99; P < 0.018), delayed chest closure (OR, 2.72; P < .001), and higher volumes of postoperative blood products (OR, 1.09; P < .001) in the multivariable analysis. On univariate analysis, both AKI groups were also associated with higher rates of pneumonia (P < .001), reintubation (P < .001), mortality on index admission (P < 0.001), longer ventilator duration (P < .001), longer intensive care unit length of stay (P < .001), and longer hospital length of stay (P < .001), with the highest rates in the AKI-RRT group. In a multivariable survival analysis, postoperative AKI-no RRT (hazard ratio [HR], 1.50; P = .006) and AKI-RRT (HR, 2.70; P < .001) were associated with significantly worse survival independent of severe grade 3 primary graft dysfunction at 72 hours (HR, 1.45; P = .038). CONCLUSIONS: The development of postoperative AKI was associated with numerous preoperative and intraoperative factors. Postoperative AKI remained significantly associated with poorer posttransplantation survival. Severe cases of AKI necessitating RRT portended the worst survival after lung transplantation.

TIP60 is required for tumorigenesis in non-small cell lung cancer.

Histone modifications play crucial roles in transcriptional activation, and aberrant epigenetic changes are associated with oncogenesis. Lysine (K) acetyltransferases 5 (TIP60, also known as KAT5) is reportedly implicated in cancer development and maintenance, although its function in lung cancer remains controversial. Here we demonstrate that TIP60 knockdown in non-small cell lung cancer cell lines decreased tumor cell growth, migration, and invasion. Furthermore, analysis of a mouse lung cancer model with lung-specific conditional Tip60 knockout revealed suppressed tumor formation relative to controls, but no apparent effects on normal lung homeostasis. RNA-seq and ChIP-seq analyses of inducible TIP60 knockdown H1975 cells relative to controls revealed transglutaminase enzyme (TGM5) as downstream of TIP60. Investigation of a connectivity map database identified several candidate compounds that decrease TIP60 mRNA, one that suppressed tumor growth in cell culture and in vivo. In addition, TH1834, a TIP60 acetyltransferase inhibitor, showed comparable antitumor effects in cell culture and in vivo. Taken together, suppression of TIP60 activity shows tumor-specific efficacy against lung cancer, with no overt effect on normal tissues. Our work suggests that targeting TIP60 could be a promising approach to treating lung cancer.

Timeliness of Lung Cancer Care From the Point of Suspicious Image at an Urban Safety Net Hospital.

BACKGROUND: Timeliness of care is an important metric for lung cancer patients, and care delays in the safety-net setting have been described. Timeliness from the point of the suspicious image is not well-studied. Herein, we evaluate time intervals in the workup of lung cancer at an urban, safety net hospital and assess for disparities by demographic and clinical factors. PATIENTS AND METHODS: We performed a retrospective analysis of lung cancer patients receiving some portion of their care at Boston Medical Center between 2015 and 2020. A total of 687 patients were included in the final analysis. Median times from suspicious image to first treatment (SIT), suspicious image to diagnosis (SID), and diagnosis to treatment (DT) were calculated. Nonparametric tests were applied to assess for intergroup differences in time intervals. RESULTS: SIT, SID, and DT for the entire cohort was 78, 34, and 32 days, respectively. SIT intervals were 87 days for females and 72 days for males (p < .01). SIT intervals were 106, 110, 81, and 41 days for stages I, II, III, and IV, respectively (p < .01). SID intervals differed between black (40.5) and Hispanic (45) patients compared to white (28) and Asian (23) patients (p < .05). CONCLUSION: Advanced stage at presentation and male gender were associated with more timely treatment from the point of suspicious imaging while white and Asian were associated with more timely lung cancer diagnosis. Future analyses should seek to elucidate drivers of timeliness differences and assess for the impact of timeliness disparities on patient outcomes in the safety net setting.

Efficacy and utility of robotic single-access bilateral nephrectomy (r-SABN) in end-stage renal disease patients.

PURPOSE: Bilateral native nephrectomies are needed in ESRD patients with select indications in a pre-transplant setting. Yet, the perioperative morbidity is significant in this population. Herein we evaluate the efficacy and utility of r-SABN. METHOD: A total of 12 patients were consented at a single center. Of 12 patients, 3 patients did not meet study criteria and were excluded. Preoperative, perioperative, and postoperative data were prospectively collected from 9 patients from electronic health records and administered postoperative surveys. Patients were assessed at 30-180 days postoperatively for follow-up. RESULTS: Mean operative time was 204.3 ± 59.7 min (142.0-314.0) and estimated blood loss during operation was 94.4 ± 87.3 ml (25.0-300.0). The mean length of hospital stay was 2 ± 0.7 days (1-3) for all patients. Total post-operative opioid usage was normalized to morphine dose equivalents (MDE) and calculated to be 56.1 ± 30.4 mg (30.8-101.8). Patients experienced a fourfold and tenfold respective increase in weekly structural and incidental physical activity from 30 to 180 days postoperatively. There were no procedure related intraoperative or postoperative complications reported in the cohort. CONCLUSION: Overall, r-SABN afforded the patients low morbidity. Longitudinal studies are in progress to further assess the efficacy and outcome of this procedure. In a single-center study, we demonstrate r-SABN is viable and provides a novel tool for treatment of ESRD patients requiring this procedure.

One-Year Post Hoc Analysis of Renal Function for Live Kidney Donors That Were Enrolled in an Enhanced Recovery After Surgery Pathway With Ketorolac.

Background and Objective Opioid exposure is a concern after live donation for kidney transplants (LDKT). We previously theorized that an enhanced recovery after surgery (ERAS) pathway for LDKT will reduce perioperative narcotic use. The aim of this post hoc analysis of merged data from two ERAS trials was to review the one-year follow-up to determine if the exposure to ketorolac versus placebo had any significant impact on long-term kidney function after LDKT. Methods One-year post hoc analysis of merged data from two ERAS LDKT, prospective, double-blind, randomized clinical trials were combined involving a total of 72 patients undergoing nephrectomy for LDKT. Kidney functions of both the ERAS groups' versus placebo were compared prospectively and blinded at one year using estimated glomerular filtration rate (eGFR) and total protein (TP) in the urine in compliance with United Network for Organ Sharing (UNOS) live donor requirements. Results There was no significant difference in postoperative eGFR at one year between ERAS and placebo groups. TP urine at one-year post-operative was significantly lower in the ERAS cohort by 4.7 mg/dl (95% CI 0.48 ~ 8.82, p = 0.025). Conclusions The ERAS groups' exposure to ketorolac did not negatively affect kidney function at one year after LDKT.

Small bowel obstruction caused by a bezoar following an adult simultaneous liver-kidney transplantation: A case report.

BACKGROUND: Small bowel obstructions (SBOs) are common following a large intra-abdominal operation; however, SBOs caused by bezoars are unreported in patients following liver-kidney transplantation procedures, particularly in adults. CASE SUMMARY: A 65-year-old Caucasian female presented with nausea and nonbilious emesis during her postoperative course following a simultaneous liver-kidney transplantation. She developed worsening nausea and vomiting with significant abdominal distension and obstipation. Computed tomography imaging showed a marked abnormal dilation of multiple small bowel loops with a distinct transition point that was suggestive of a small bowel obstruction. An exploratory laparotomy revealed a foreign body in the intestinal track approximately 30 cm from the ileocecal valve. The foreign body was extracted and identified as a bezoar with hair follicles and old digestive contents. Following the operation, the patient demonstrated rapid clinical improvement with resolution of nausea, emesis, and progress in bowel motility. CONCLUSION: SBOs caused by bezoars can occur immediately following a liver-kidney transplantation and should not be discounted as a diagnosis.

Page kidney phenomenon in kidney allograft following abdominal trauma.

The page kidney phenomenon is often associated in patients with abdominal trauma. External compression from a renal hematoma can cause hypertension, and presentation can be delayed following the initial injury. For patients who have a kidney allograft, page kidneys may lead to renal insufficiency and acute renal failure due to the absence of a contralateral kidney to compensate. This case report discusses the identification and management of a page kidney in a kidney allograft recipient within three months following transplantation.

Alternative splicing of APOBEC3D generates functional diversity and its role as a DNA mutator.

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) protein family members have cytidine deaminase activity and can induce cytosine to uracil transition in nucleic acid. The main function of APOBEC3 (A3) proteins is to trigger an innate immune response to viral infections. Recent reports have shown that several APOBEC family proteins such as A3B can induce somatic mutations into genomic DNA and thus promote cancer development. However, the role of A3D on somatic mutations is unclear. Here, we identified the alternative splicing of A3D, and investigated each splice variant's subcellular localization and role in DNA mutagenesis. We identified four A3D variants, which all have one or two cytidine deaminase domains. The full-length form of A3D (variant 1) and truncated forms of A3D (variant 2, 6, 7) showed the ability to induce C/G to T/A transitions in foreign DNA and genomic DNA and retained antiretroviral activity. Furthermore, we demonstrated that A3D and A3B could induce deletions that are possibly repaired by microhomology-mediated end joining (MMEJ). Taken together, our experiments illustrated that alternative splicing generates functional diversity of A3D, and some variants can act as DNA mutators in genomic DNA.

Successful Utilization of a Live Donor Kidney with Angiomyolipoma.

The gap between the kidney transplant recipient list and the number of organs available for transplantation continues to grow. Kidneys from living donors are a major source of high-quality organs. However, they commonly have benign conditions such as cysts and benign tumors that present as operative challenges. This case presents a donor kidney that had a benign angiomyolipoma. The kidney was donated in a standard, minimally invasive fashion. The tumor was then removed on the back table and transplanted without an issue. Both donor and recipient enjoyed a speedy recovery with no significant complications.

Atypical Hemolytic Uremic Syndrome After Kidney Transplantation: Lessons Learned From the Good, the Bad, and the Ugly. A Case Series With Literature Review.

Atypical hemolytic uremic syndrome (aHUS) after kidney transplantation is rare and carries a grave outcome. We present a single-center experience of all aHUS cases since the program's inception. Six patients were diagnosed with aHUS, all after kidney transplants, except for 1 patient. All had nonreactive crossmatches. Delayed graft function (DGF) occurred in 2 patients. Five patients developed aHUS after transplant; 4 (80%) of these patients manifested aHUS ≤ 14 days. All were confirmed by allograft biopsy. Genetic testing was abnormal in all patients except for 1 patient. Actual patient and graft survival during the first year was 100% and 83.3%, respectively. A single graft was lost early in the study secondary to aHUS (eculizumab was not used in the treatment process). Prophylactic and therapeutic use of eculizumab salvaged all other cases. At 1 year, mean creatinine level was 1.9 mg/dL (range, 1.3-2.5). After 6 months of eculizumab treatment (halted in 2 cases) 1 patient had recurrence 2 months later and eculizumab was restarted. However, graft function continued to worsen, and the graft was ultimately lost at 20 months after kidney transplantation. High index of suspicion, prompt diagnosis, and utilization of eculizumab are key to successful salvage of allografts in cases of aHUS after kidney transplantation. aHUS can be prevented by prophylactic use of eculizumab. It still needs to be determined when and if eculizumab therapy can be safely discontinued.

Renal Auto-Transplantation for Loin Pain Hematuria Syndrome Using a Multidisciplinary Team Model: Intermediate-Term Results.

Background Patients with loin pain hematuria syndrome (LPHS) can find relief via multiple modalities, few provide long-term pain control like renal auto-transplantation (RAT). This study evaluates the intermediate effectiveness of the RAT procedure's ability to achieve long-term pain control and quality of life improvement. Methods All patients with suspected LPHS were seen by a multi-disciplinary team (MDT) composed of urologists, interventional radiologists, and transplant surgeons. Clinical history and physical exam, lab values, imaging findings, and response to renal hilar block (RHB) were used to determine LPHS and candidacy for potential RAT. Preoperative, one-year, three-year, and five-year postoperative pain assessment scores and quality of life surveys were administered to each LPHS and potential RAT patient. Results Eighty-four LPHS patients were referred for the evaluation of and consultation for the option of RAT. Sixty-four of these patients underwent RHB of which 60 (93.8%) had a positive response, defined as a temporary reduction of pain score by >50%. Forty-six of the 60 patients who responded favorably proceeded to RAT. At the one-year follow-up, there was a 75% reduction in pain with 88.9% of patients experiencing a 50% reduction in pain. At one year, the mean Beck Depression Inventory (BDI) decreased by 65.4%, from an average of 23.7 to 8.2. Similarly, at three years (n = 5) and five years (n = 3), the mean pain scores were 2 and 1. Conclusions The MDT evaluation of potential LPHS patients with our protocol and treatment results in an improvement in pain and depression scores in these selected patients.

Two-stage Enteric Exclusion to Salvage a Pancreas Transplant After an Early Post-transplant Leak.

Early technical complications after pancreas transplantation are almost always unsalvageable. The two most common complications are vascular thrombosis and duodenal anastomotic leaks. We present a case of a duodenal stump leak that led to a large abscess and severe sepsis. The pancreas was salvaged by repairing the leak and creating a proximal diverting ileostomy. Several months later, the ileostomy was reversed. This was done by creating a defunctionalized Roux limb to exclude the pancreas. The patient healed well and continued to enjoy excellent glucose control.