A2/A2B to B kidney transplantation outcomes: A single center 7-year experience.

INTRODUCTION: Data on long-term outcomes following A2/A2B to B kidney transplants since the 2014 kidney allocation system (KAS) changes are few. The primary aim of this study is to report our 7-year experience with A2/A2B to B kidney transplants and to compare post-transplant outcomes of A2/A2B to a concurrent group of B to B kidney transplants. Additionally, the study evaluates the impact of pre-transplant anti-A1 titers on survival outcomes in A2/A2B transplants. METHODS: This retrospective, single-center analysis included all adults who received A2/A2B to B deceased donor kidney transplants from December 2014 to June 2021 compared to B to B recipients. The effects of pre-transplant IgM/IgG titers, stratified as ≤1:8 and ≥1:16, on death-censored, rejection-free, and overall graft survival were tested. RESULTS: Fifty-three A2/A2B and 114 B to B adults were included with a median follow-up time of 32 months. Overall graft survival, patient survival, and rejection-free graft survival did not differ between the two groups. There were no differences between the groups' overall kidney function values (p > .80) or their temporal trajectories (time by group interaction p > .11). Unadjusted death-censored graft survival was lower in A2/A2B to B compared to B recipients (p = .03), but the effect was not significant (p = .195) after adjusting for any readmissions (p = .96), rejection episodes (p < .001) or BK infection (p = .76). We did not detect an effect of pre-transplant titer group on death-censored (p = .59), rejection-free (p = .61), or overall graft survival (p = .26) CONCLUSIONS: A2/A2B to B kidney transplants have comparable overall patient and graft survival, rejection-free graft survival, and longitudinal renal function compared to B to B transplants at our center. Allograft survival outcomes were not significantly different between patients with low and high pre-transplant anti-A1 IgM/IgG titers.

Disseminated Nocardiosis in Kidney Transplant Recipients: A Report of 2 Cases.

Nocardiosis is a rare, life-threatening opportunistic infection caused by bacteria in the environment that predominantly affects immunocompromised patients. Nocardiosis most commonly involves the lungs but can disseminate to other organs. Disseminated nocardiosis, defined as Nocardia infection involving 2 or more organ systems, requires early detection and treatment because of high morbidity and mortality. We report 2 cases of disseminated nocardiosis with pulmonary and central nervous system involvement in kidney transplant recipients. Nocardiosis should be suspected in immunocompromised patients with fever and lung mass, although atypical presentations involving almost any organ can be seen. Solid organ transplant recipients are at greatest risk for Nocardia infection within the first 1 to 2 years after transplantation. However, the patients presented here developed disseminated nocardiosis several years after transplantation, which has important implications. Nocardiosis is treated with 2 to 6 weeks of empiric induction antibiotics, followed by 6 to 12 months of maintenance antibiotics based on antimicrobial susceptibility testing.

Role of Ultrastructural Study in the Diagnosis of Medical Renal Diseases: A Tertiary Medical Center Experience and Review of the Literature.

The 20th century unfolded many mysteries regarding renal pathology with the advent of ancillary techniques such as immunofluorescence (IF) and electron microscopy (EM) studies. EM plays a major role in confirming the routine and IF findings or may uncover new and unsuspected features. The aim of the study is to elucidate the role of ultrastructural findings in patients with medical kidney diseases on whom kidney biopsy was performed at the American University of Beirut Medical Center, between November 2018 and June 2019. A total of 188 renal biopsies were examined during the study period. EM confirmed the light microscopy diagnosis in 54% of the cases while completely changed the diagnosis in 23% of the cases. In 23% of the sample, EM provided additional features and a secondary diagnosis. Our study emphasizes the important diagnostic role of EM and its significance, particularly in minimal change disease, basement membrane abnormalities, and glomerulopathies.

Monoclonal antibody treatment for COVID-19 in solid organ transplant recipients.

Solid organ transplant (SOT) recipients are at high risk for severe coronavirus disease 2019 (COVID-19). Studies suggest that early intervention with monoclonal antibody (MAB) treatment directed against the SARS-CoV-2 spike protein may reduce the risk of emergency department visits or hospitalization for COVID-19, especially in high-risk patients. Herein, we describe our single-center experience of 93 SOT (50 kidney, 17 liver, 11 lung, nine heart, and six dual-organ) recipients with mild to moderate COVID-19 who were treated with bamlanivimab or casirivimab-imdevimab per emergency use authorization guidelines. Median age of recipients was 55 [(Interquartile range) 44-63] years, and 41% were diabetic. Median time from transplant to MAB was 64 (IQR 24-122) months and median time from the onset of COVID-19 symptoms to the infusion was 6 (IQR 4-7) days. All patients had a minimum 30 days of study follow-up. The 30-day hospitalization rate for COVID-19-directed therapy was 8.7%. Infusion-related adverse events were rare and generally mild. Biopsy-proven organ rejection occurred in two patients, and there were no graft losses or deaths. A comparator group of 72 SOT recipients diagnosed with COVID-19 who were eligible but did not receive MAB treatment had a higher 30-day hospitalization rate for COVID-19-directed therapy (15.3%), although this difference was not statistically significant, after adjustment for age (Odds Ratio 0.49 [95% Confidence Interval 0.18-1.32], p = 0.16). Our experience suggests that MAB treatment, with respect to the available MAB formulations and circulating viral variants present during our study period, may provide favorable outcomes for mild to moderate COVID-19 in SOT recipients.

High rates of advanced prostate cancer in the Middle East: Analysis from a tertiary care center.

OBJECTIVES: Prostate cancer incidence is increasing in the Middle East (ME); however, the data of stage at the diagnosis and treatment outcomes are lacking. In developed countries, the incidence of de novo metastatic prostate cancer ranges between 4% and 14%. We hypothesized that the rates of presentation with advanced disease are significantly higher in the ME based on clinical observation. This study aims to examine the stage at the presentation of patients with prostate cancer at a large tertiary center in the ME. METHODS: After Institutional Review Board approval, we identified the patients diagnosed with prostate adenocarcinoma and presented to a tertiary care center between January 2010 and July 2015. Clinical, demographic, and pathological characteristics were abstracted. Patients with advanced disease were stratified according to tumor volume based on definitions from practice changing clinical trials. Descriptive and Kaplan-Meier survival analysis was used. RESULTS: A total of 559 patients were identified, with a median age at the diagnosis of 65 years and an age range of 39-94 years. Median prostate-specific antigen (PSA) at the presentation was 10 ng/ml, and almost a quarter of the men (23%) presented with metastatic disease. The most common site of metastasis was the bone (34/89, 38%). High-volume metastasis was present in 30.3%, 9%, and 5.2% of the cohort based on STAMPEDE, CHAARTED, and LATITUDE trial criteria, respectively. CONCLUSION: This is the first report showing the high proportion of men from ME presenting with de novo metastasis. This could be due to many factors, including the highly variable access to specialist multidisciplinary management, lack of awareness, and lack of PSA screening in the region. There is a clear need to raise the awareness about prostate cancer screening and early detection and to address the rising burden of advanced prostate cancer affecting men in the ME region.

Genitourinary Interventions in Autosomal Dominant Polycystic Kidney Disease: Clinical Recommendations for Urologic and Transplant Surgeons.

Autosomal dominant polycystic kidney disease is the fourth most common single cause of end-stage renal disease worldwide with both renal and extrarenal manifestations, resulting in significant morbidity. Approaches to the management of this disease vary widely, with no broadly accepted practice guidelines. Herein, we reviewed the various surgical and interventional management options that are targeted toward treating the symptoms or addressing the resulting kidney failure. Novel treatment modalities such as celiac plexus blockade and renal denervation appear to be promising in pain relief; however, further studies are lacking. Renal cyst decortication seems to have a higher success rate in targeting cyst-related pain compared with aspiration only. In terms of requiring major surgical intervention, such as need and timing of native nephrectomy, there are several considerations when deciding on transplantation with or without a pretransplant native nephrectomy. Patients who are not candidates for native nephrectomy may consider transcatheter arterial embolization. Based on our review of the contemporary indications for genitourinary interventions in the management of autosomal dominant polycystic kidney disease, we propose an algorithm that depicts the decision-making process on assessing the indications and timing of native nephrectomy in patients with end-stage renal disease awaiting transplant.

SuPAR, an emerging biomarker in kidney and inflammatory diseases.

Soluble urokinase plasminogen activator receptor (suPAR) is a circulating form of a physiological and pathophysiological important cell surface receptor, implicated in inflammation. Recent studies showed that suPAR is a promising biomarker, useful for diagnosis, assessment and prognosis of several diseases. This review summarises the majority of preliminary studies and analyses the significance and the clinical application of suPAR in various clinical conditions. SuPAR seems to have a significant value in the diagnosis as well as prognosis of many diseases; nonetheless, it merits large-scale studies to set cut-off values that help physicians in following up their patients and accordingly tailor their treatment plans.

Severe ketoacidosis in a patient with spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disease characterized by progressive muscle weakness and atrophy. We report a case of a 36-year-old man with SMA type 3 who presented to our emergency department with epigastric pain and vomiting. He was found to have severe ketoacidosis on laboratory evaluation. The patient's symptoms and ketoacidosis resolved after dextrose infusion and a relatively small amount of sodium bicarbonate infusion. Given the severity of the ketosis that seemed inconsistent with moderate starvation alone, we postulate that there must have been other contributing factors besides moderate starvation that might explain the severity of acidosis in this particular patient. These factors include low muscle mass, disturbed fatty acid metabolism, hormonal imbalances and defective glucose metabolism. Ketoacidosis is an under-recognized entity in patients with neuromuscular diseases and requires a high index of suspicion for prompt diagnosis and management.

Primary synovial sarcoma of the kidney: a case report of complete pathological response at a Lebanese tertiary care center.

BACKGROUND: Primary synovial sarcoma of the kidney is a rare type of soft tissue sarcoma. Its presenting features can resemble those of other renal tumors; rendering its early diagnosis, a dilemma. Several cases of renal synovial sarcoma have been reported in the literature with varying treatment options and outcomes. This article describes a rare case of primary renal synovial sarcoma and reviews all cases in the literature. CASE PRESENTATION: A 26-year-old male presented with flank pain and hematuria. Initially diagnosed with Wilm's tumor, revision of pathology and histology, along with the immunohistochemical profile, confirmed, nevertheless, the diagnosis of primary monophasic synovial sarcoma of the kidney with the SYT-SSX2 fusion transcript. Follow-up, post nephrectomy, revealed recurrence within the lungs and at the surgical bed. Surgical resection followed by adjuvant chemotherapy regimen constituting of Doxorubicin and Ifosfamide, achieved complete pathological response. CONCLUSION: In this case report, we emphasize the need for accurate diagnosis and prompt treatment. We propose multimodality treatment approach including surgery along with anthracycline-based chemotherapy to induce complete remission.

Increase in spleen volume as a predictor of oxaliplatin toxicity.

BACKGROUND: Oxaliplatin is a nonconventional third-generation platinum compound. It is an important chemotherapeutic agent in regimens used in gastrointestinal carcinomas as well as other malignancies. Oxaliplatin toxicity profile includes neurotoxicity, hepatotoxicity, and splenomegaly. The primary aim of this study was to measure the spleen volume of patients on oxaliplatin therapy before and during chemotherapy to detect any increase in splenic size as a biomarker for early oxaliplatin toxicity. METHODS: This was a prospective pilot study conducted at the American University of Beirut-Medical Center. Fifty patients newly started on oxaliplatin were included. The spleen volume was measured from the patients' baseline CT scan using the IntelliSpace Portal upgraded system (using Response Evaluation Criteria In Solid Tumors [RECIST]), for each follow-up CT scan. Side effects were evaluated at each patient visit and graded according to the severity. RESULTS: Thirty-seven (74%) patients developed an increase in spleen size. Thirty-three (66%) sampled patients developed peripheral neuropathy (all grades) at 3 months, whereas only two (4%) patients developed grade 3 neuropathy. Only one (3%) patient who developed an increase in spleen size also developed grade 3 peripheral neuropathy - a result that is significantly different (p<0.001) when comparing patients with an increase in spleen size who also developed peripheral neuropathy of other grades. CONCLUSION: An increase in spleen volume possibly precedes a significant peripheral neuropathy which could be a potential marker for oxaliplatin-induced toxicity.

Pancreaticoduodenal Artery Aneurysm Associated with Celiac Trunk Stenosis: Case Illustration and Literature Review.

Pancreaticoduodenal artery aneurysms (PDA) are rare visceral aneurysms. Celiac trunk stenosis represents a common attributable aetiology for those aneurysms. Therefore, an alternative treatment approach, which differs from those isolated aneurysms, is recommended. We hereby present a 77-year-old male patient who was admitted with sudden onset of severe abdominal pain and significant drop in haemoglobin, occurring within a 24-hour interval. Contrast-enhanced computed tomography revealed a ruptured visceral aneurysm arising from the anterior branch of the inferior pancreaticoduodenal artery. A severe stenosis was also noted at the take-off of the celiac trunk. Selective catheterization of the supplying branch of the superior mesenteric artery, followed by coil embolization of the aneurysm, was performed, resulting in cessation of flow within the aneurysm, with preservation of the posterior branch, supplying the celiac territory. PDAs are usually asymptomatic and discovered incidentally at rupture. The risk of rupture is independent of the aneurysmal size and is associated with a 50% mortality rate. The consensus on coping with aneurysms is to treat them whenever they are discovered. Selective angiography followed by coil embolization represents a less invasive, and frequently definitive, approach than surgery. The risk for ischemia mandates that the celiac territory must not be compromised after embolization.

Optimizing tumor immune response through combination of radiation and immunotherapy.

Radiation therapy and immunotherapy are two highly evolving modalities for the treatment of solid tumors. Immunotherapeutic drugs can either stimulate the immune system via immunogenic pathways or target co-inhibitory checkpoints. An augmented tumor cell recognition by host immune cells can be achieved post-irradiation, as irradiated tissues can release chemical signals which are sensed by the immune system resulting in its activation. Different strategies combining both treatment modalities were tested in order to achieve a better therapeutic response and longer tumor control. Both regimens act synergistically to one another with complimentary mechanisms. In this review, we explore the scientific basis behind such a combination, starting initially with a brief historical overview behind utilizing radiation and immunotherapies for solid tumors, followed by the different types of these two modalities, and the biological concept behind their synergistic effect. We also shed light on the common side effects and toxicities associated with radiation and immunotherapy. Finally, we discuss previous clinical trials tackling this multimodality combination and highlight future ongoing research.

Younger age is an independent predictor of worse prognosis among Lebanese nonmetastatic breast cancer patients: analysis of a prospective cohort.

BACKGROUND: Several retrospective studies have reported that younger age at presentation is associated with a worse prognosis for nonmetastatic breast cancer patients. In this study, we prospectively assessed the association between different baseline characteristics (age, tumor characteristics, mode of treatment, etc) and outcomes among newly diagnosed nonmetastatic Lebanese breast cancer patients. METHODS: We recruited a sample of 123 women newly diagnosed with nonmetastatic breast cancer presenting to American University of Beirut Medical Center. Immunohistochemical, molecular (vitamin D receptor, methylene tetrahydrofolate reductase polymorphisms), and genetic assays were performed. Patient characteristics were compared by age group (<40 and ≥40 years). A Cox regression analysis was performed to evaluate the variables affecting the disease-free survival (DFS). Outcome data were obtained, and DFS was estimated. RESULTS: Among the 123 patients, 47 were 40 years of age or younger, and 76 were older than 40 years. Median follow-up duration was 58 months. Nine out of 47 patients <40 years (19.1%) experienced disease relapse in contrast to four out of 76 patients >40 years (5.2%). A wide immunohistochemical panel included Ki-67, cyclin B1, p53, platelet-derived growth factor receptor, and vascular endothelial growth factor receptor, and did not reveal any significant difference in these markers between the two age groups. Older patients had a larger percentage of Luminal A than younger patients. On multivariate analysis including age, stage, grade, and subtype, only age <40 and stage were significantly associated with shorter DFS with hazard ratios of 4 (p=0.03, 95% confidence interval [CI]: 1.1-13.5) and 3 (p=0.03, 95% CI: 0.8-14.9), respectively. The estimated 5-year DFS for patients >40 years was 90%, and for patients <40 years was 37%. CONCLUSION: Being <40 years old was an independent risk factor for recurrence in this cohort of patients.

Pregnancy Outcomes in Women with Preeclampsia Superimposed on Chronic Hypertension with and without Severe Features.

Objective The American Congress of Obstetricians and Gynecologists (ACOG) task force on hypertension in pregnancy introduced a new definition of superimposed preeclampsia (SIP) adding severe features (SF) as new criteria to define severe disease. They also recommended that those with SIP be delivered ≥ 37 weeks, whereas those with SF be delivered ≤ 34 weeks. Our aim was to investigate the validity of this new definition by comparing adverse pregnancy outcomes in SIP with (SIP-SF) and without SF (SIP). Study Design Women with chronic hypertension (CHTN) enrolled in a multicenter trial were studied. SIP was reclassified according to the new definition to SIP and SIP-SF (persistent systolic blood pressure [BP] > 160 or diastolic BP > 110, platelets < 100 K, liver function tests > 70, creatinine > 1.1, or persistent central nervous system/abdominal symptoms). Composite adverse outcomes including rates of indicated preterm birth, abruptio placentae, postpartum hemorrhage, and maternal death were compared by chi-square. Adjustment was done with a multivariate logistic-regression analysis and all statistical tests were two-sided. Results A total of 216 women (28%) out of 774 with CHTN developed SIP, 87 (11%) had SIP-SF, and 129 (17%) didn't have SF. Baseline characteristics including maternal age, baseline BP, and assignment to low-dose aspirin were similar between groups. Using univariate analysis, the composite adverse outcome was higher among the SIP-SF group (p = 0.04), as well as indicated preterm birth (p = 0.02), cesarean section (p = 0.02), and SGA (p = 0.02). After adjustment, composite adverse outcomes were not significantly different between groups. The rate of SGA, however, was higher among SIP-SF (adjusted odds ratio: 3.12, p = 0.02). Conclusion The rate of SIP-SF in this study was 11% of all women with CHTN. Surprisingly, pregnancy outcomes were not significantly different in those with and without SF. We suggest a prospective observational study to determine the optimal timing for delivery in those with SIP using new ACOG diagnostic criteria.