Innate Allorecognition in Transplantation: Ancient Mechanisms With Modern Impact.

Through the effective targeting of the adaptive immune system, solid organ transplantation became a life-saving therapy for organ failure. However, beyond 1 y of transplantation, there is little improvement in transplant outcomes. The adaptive immune response requires the activation of the innate immune system. There are no modalities for the specific targeting of the innate immune system involvement in transplant rejection. However, the recent discovery of innate allorecognition and innate immune memory presents novel targets in transplantation that will increase our understanding of organ rejection and might aid in improving transplant outcomes. In this review, we look at the latest developments in the study of innate allorecognition and innate immune memory in transplantation.

Comparative analysis of partial versus radical nephrectomy for renal cell carcinoma: Is oncologic safety compromised during nephron sparing in higher stage disease?

Objectives: Over the past 20 years, the utility of partial nephrectomy (PN), compared to radical nephrectomy (RN), for the management of localized renal cell carcinoma (RCC) has progressively increased, particularly for larger and more complex masses. We sought to compare the recurrence-free survival (RFS) outcomes of PN versus RN in a single-institution cohort. Methods: Between 2002 and 2017, 228 patients underwent RN or PN for lcT1a-T2b, N0M0 RCC at a single tertiary referral center, performed by five surgeons. The clinical end point result was (local or distant) RFS. Univariate and multivariate (cox regression) models were used to evaluate the association between type of surgery (PN vs. RN) and RFS, in the overall cohort and in a subgroup of patients with cT1b. Results: The median age was 59 (interquartile range [IQR] 48-66), and the median tumor size was 4.5 cm (IQR 3-7). There were 128 PN and 100 RN. Over a median follow-up of 4.2 years (IQR 2.2-6.9), the Kaplan-Meier analysis showed no significant RFS difference between PN and RN (logrank P = 0.53). On multivariate analysis, pathologic stage ≥T2a, Fuhrman Grade ≥3, and chromophobe histology were associated with a worse RFS. PN was not significantly associated with diminished RFS (Hazard ratio [HR] 1.78, 95% confidence interval [CI] 0.74-4.3, P = 0.199) in the overall cohort compared to RN. However, in the cT1b subgroup, PN was associated with a significant increase in recurrence compared to RN (HR = 12.4, 95% CI 1.45-133.4, P = 0.038). Conclusions: Our institutional data highlight the possibility of compromise in RFS for clinically localized RCC treated with PN compared to RN, particularly for larger and more complex masses. These data raise concern, especially in light of the nonproven association of survival benefit of PN over RN, warranting future randomized prospective studies for further evaluation.

Non-cytotoxic functions of CD8 T cells: "repentance of a serial killer".

Cytotoxic CD8 T cells (CTLs) are classically described as the "serial killers" of the immune system, where they play a pivotal role in protective immunity against a wide spectrum of pathogens and tumors. Ironically, they are critical drivers of transplant rejection and autoimmune diseases, a scenario very similar to the famous novel "The strange case of Dr. Jekyll and Mr. Hyde". Until recently, it has not been well-appreciated whether CTLs can also acquire non-cytotoxic functions in health and disease. Several investigations into this question revealed their non-cytotoxic functions through interactions with various immune and non-immune cells. In this review, we will establish a new classification for CD8 T cell functions including cytotoxic and non-cytotoxic. Further, we will discuss this novel concept and speculate on how these functions could contribute to homeostasis of the immune system as well as immunological responses in transplantation, cancer, and autoimmune diseases.

Epidemiology and composition of nephrolithiasis in a Lebanese tertiary care center: A descriptive study.

Introduction: Nephrolithiasis is a common affliction with a prevalence of 12% in men and 7% in women. The incidence rate diverges with geographic location. Arab countries report high nephrolithiasis prevalence rates, with Saudi Arabia being the highest (20.1%). To date, there is little knowledge about the demographics and composition of stones in Lebanon. Methods: A retrospective chart review was performed on stone composition at the American University of Beirut Medical Center, between 2005 and 2018. Patients' demographics and stone characteristics were obtained from electronic medical records. Analysis of frequencies and Chi-square test were adopted for potential risk factor correlations by the Statistical Package for the Social Sciences (SPSS). Results: A total of 626 stone analyses were performed. Male patients predominated (69%). The mean age was 46.58 ± 16.5 years, and mean body mass index was 28.63 ± 5.6, for both sexes. Calcium oxalate was the most predominant stone in both sexes (70%). Uric acid stones followed (~16%), and calcium oxalate phosphate stones were the third most common (5%). Incidence of kidney stones peaks in the summer, with 11.86% presenting in July. Around 60% presented with flank pain to the Emergency Department, and 32% ended up with spontaneous passage of stones by medical expulsive therapies alone, with no further surgical intervention. Diabetes and hypertension were significantly correlated with stone recurrence in our cohort. Conclusion: There is a significant gender disparity in stone prevalence in Lebanon. Calcium oxalate is the most common type in both sexes. Future investigations of dietary and environmental factors are recommended from our region.

Activated-memory T cells influence naïve T cell fate: a noncytotoxic function of human CD8 T cells.

T cells are endowed with the capacity to sense their environment including other T cells around them. They do so to set their numbers and activation thresholds. This form of regulation has been well-studied within a given T cell population - i.e., within the naïve or memory pool; however, less is known about the cross-talk between T cell subsets. Here, we tested whether memory T cells interact with and influence surrounding naïve T cells. We report that human naïve CD8 T cells (TN) undergo phenotypic and transcriptional changes in the presence of autologous activated-memory CD8 T cells (TMem). Following in vitro co-culture with activated central memory cells (TCM), ~3% of the TN acquired activation/memory canonical markers (CD45RO and CD95) in an MHC-I dependent-fashion. Using scRNA-seq, we also observed that ~3% of the TN acquired an activated/memory signature, while ~84% developed a unique activated transcriptional profile hybrid between naïve and activated memory. Pseudotime trajectory analysis provided further evidence that TN with an activated/memory or hybrid phenotype were derived from TN. Our data reveal a non-cytotoxic function of TMem with potential to activate autologous TN into the activated/memory pool. These findings may have implications for host-protection and autoimmunity that arises after vaccination, infection or transplantation.

MRI/US fusion transperineal versus transrectral biopsy of prostate cancer: Outcomes and complication rates, a tertiary medical center experience in the Middle East.

OBJECTIVE: To report on the outcomes of transperineal versus transrectal magnetic resonance imaging/ultrasound fusion biopsy of the prostate including detection of clinically significant cancer and complications. This is the first and largest series in the Middle East. MATERIAL AND METHODS: Between May 2019 and June 2020, 145 patients with suspicious lesions on magnetic resonance imaging underwent magnetic resonance imaging/ultrasound fusion prostate biopsy at our center. Transperineal biopsy was performed under light sedation, while transrectal biopsy patients had a periprostatic block for anesthesia. Clinically significant cancer was defined as Gleason ≥3+4 Results: In all, 98 transperineal biopsies and 47 transrectal magnetic resonance imaging/ultrasound fusion prostate biopsies were done. Patients had similar prebiopsy parameters (transperineal vs. transrectal): median age (64.5 vs. 66 years; P=.68), median prostate-specific antigen value (7.5 vs. 7.5; P=.42), and median prostate volume (51 vs. 52.5; P=.83). Those that underwent transperineal biopsy had fewer average total number of cores compared to transrectal ultrasound-guided biopsy (11 vs. 13; P=.025) fewer average number of random cores (3 vs. 6; P < .0001), and the detection rate of clinically significant cancer was similar between the groups (44% vs. 48.9%; P=.57). No difference in hematuria, retention, and sepsis rate requiring admission (1 vs. 2; P=.2) was observed. However, more patients had urinary tract infection in the transrectal ultrasound-guided biopsy group compared to transperineal biopsy group (5 vs. 1; P=.006) that were treated with antibiotics on outside basis. CONCLUSION: Magnetic resonance imaging/ultrasound transperineal fusion biopsy has similar detection rate of clinically significant cancer compared to transrectal ultrasound-guided biopsy with less urinary tract infection post biopsy.

Immunoglobulin-like receptors and the generation of innate immune memory.

Host immunity is classically divided into "innate" and "adaptive." While the former has always been regarded as the first, rapid, and antigen-nonspecific reaction to invading pathogens, the latter represents the more sophisticated and antigen-specific response that has the potential to persist and generate memory. Recent work however has challenged this dogma, where murine studies have successfully demonstrated the ability of innate immune cells (monocytes and macrophages) to acquire antigen-specific memory to allogeneic major histocompatibility complex (MHC) molecules. The immunoreceptors so far identified that mediate innate immune memory are the paired immunoglobulin-like receptors (PIRs) in mice, which are orthologous to human leukocyte immunoglobulin-like receptors (LILRs). These receptor families are mainly expressed by the myelomonocytic cell lineage, suggesting an important role in the innate immune response. In this review, we will discuss the role of immunoglobulin-like receptors in the development of innate immune memory across species.

Comparative analysis of histopathological subtypes of renal cell carcinoma in the Middle East compared to other world regions.

INTRODUCTION: Renal cell carcinoma (RCC) has various histopathological tumor subtypes which have a significant implication on the oncological outcome of these patients. We aimed to evaluate the distribution of RCC subtypes presenting at a tertiary care center in the Middle East, in comparison to the distribution reported in different geographic areas worldwide. METHODS: A retrospective chart review was conducted on all patients who underwent partial or radical nephrectomy for RCC at the American University of Beirut Medical Center between January 2012 and January 2018. Data on histologic subtypes were compiled and compared to representative series from different continents. RESULTS: One hundred and seventy-nine patients with RCC were identified, of whom 122 (68.2%) were classified as clear cell, 30 (16.8%) as papillary, 17 (9.5%) as chromophobe, and 10 (5.6%) as unclassified. When compared to other regions of the world, this Middle Eastern series demonstrated a higher prevalence of the chromophobe subtype compared to Western populations (9.5% in the Middle East vs. 5.3% in the US and 3.1% in Europe) and a lower prevalence of clear cell subtype (68.2% in the Middle East vs. 78.7% in the US and 85.8% in Europe). Conversely, there was a higher prevalence of papillary RCC in the Middle East (16.8%) compared to North America (13.1%, 95% confidence interval [CI]: 12.7-13.6), Europe (11.1%, 95% CI: 10.0-12.1), and Australia (10.2%). The prevalence of chromophobe and clear cell RCC in the Middle East was similar to that reported in South America. CONCLUSIONS: The distribution of RCC subtypes in this Middle Eastern cohort was significantly different from that reported in the Western hemisphere (Europe and the US) but similar to that reported in South America and Australia. These findings may point to a possible genetic predisposition underlying the global variation in distribution.