31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Unusual Causes of Abrupt Anuria Early Post-Renal Transplantation

Renal transplantation using living donors has superior outcomes in comparison to deceased donor transplantation and results in immediate allograft function in a majority of cases. Rarely may allograft be nonfunctional from the beginning, or anuria is noted after a period of good urine output. Surgical causes for anuria should be high on the differential diagnosis in immediate-to-early posttransplant period, especially in an unsensitized recipient. We present two unusual causes of early onset anuria after living related renal transplantation where early surgical reexploration salvaged renal allografts with excellent long term outcomes

A comparative study of acute nonemphysematous pyelonephritis in diabetics and nondiabetics from a tertiary care hospital in South India

AIM: The aim of this study is to analyze the clinical, biochemical, and microbiological characteristics of patients with acute nonemphysematous pyelonephritis in diabetics and nondiabetics from Indian subcontinent. MATERIALS AND METHODS: It is a retrospective study conducted at a tertiary care hospital from January 2012 to August 2016. The hospital medical records were searched electronically for clinical, biochemical, and microbiologic data. RESULTS: A total of 177 patients were enrolled for the study. in the diabetic group (51.9 years) was slightly higher than the nondiabetic patients (45.7 years). Nondiabetic patients presented late when compared to diabetics (6.38 days against 4.7 days). About 11.5% in diabetics against 5.8% in nondiabetics had recurrent urinary tract infection. The urine culture in the diabetics and nondiabetics showed positive growth in 43.8% and 43.2% of cases, respectively, with Escherichia coli, extended-spectrum β-lactamase, and Klebsiella being commonly identified organisms. Blood culture specimens in both the groups had high negative results with 86.5% in diabetics and 98.8% in nondiabetics. Over 90% of patients in either group responded to treatment with either antibiotic alone or in combination with double-J stenting. Temporary hemodialysis was required in 8% in diabetic group and 6% in nondiabetic group. Maintenance hemodialysis was required in approximately 3% of diabetic patients. CONCLUSION: In our study, the incidence of acute pyelonephritis was found to be higher in patients in their fifth decade of life. Diabetics had more severe infection at presentation and consequently had poorer outcomes in terms of residual renal function and need for dialysis

Emphysematous Pyelonephritis Case Series From South India

Introduction: Emphysematous pyelonephritis (EPN) is a rare, life-threatening necrotizing infection of the kidney. The mortality rate for EPN is as high as 25%. We conducted a retrospective study at MS Ramaiah Hospital between January 2011 and May 2016 to observe the clinical, biochemical, and microbiological patterns of EPN at our institute. Methods: The clinical and laboratory data, imaging findings, and microbiological patterns of 51 patients chosen for the study were recorded. The data were analyzed to identify the prognostic variables that could predict the morbidity and mortality of patients with EPN, and the focus of this study was to determine risk factors for and outcomes of patients who presented with EPN and who required hemodialysis. Primary endpoints were successful treatment and all-cause mortality. Secondary endpoints included need for hemodialysis and the need for a specific treatment. Results: There was an equal incidence among both sexes (median age: 59 years). Common symptoms were abdominal pain (94.11%), fever (83.2%), dysuria (74.5%), vomiting (72.54%), frequency of micturition (68.62%), oliguria, generalized weakness (66.67%), and breathlessness (66.67%); 98.03% (n = 50) of the patients had diabetes. The most common organism cultured was Escherichia coli (37.2%). Nineteen patients (37.2%) required dialysis; their mean age was 60.25 ± 11.74 years. Male sex, diabetes mellitus, shock, high serum creatinine at presentation, and uremic symptoms showed no statistically significant association. Indefinite hemodialysis was required by 12.5% of patients. The antibiotic-treated group had a 100% success rate, whereas the Double J (DJ) stenting group (Double J stent, Biorad, India) had 96.42% success rate. Conclusion: Early diagnosis and broad spectrum antibiotics, together with an appropriately timed intervention, resulted in decreased mortality. Pain in the abdomen and renal angle tenderness were the most common clinical finding. E coli was the most found organism, and early use of broad spectrum antibiotics decreased mortality. Keywords: emphysematous pyelonephritis, necrotizing renal infectio

Renal transplantation in HIV-positive patients – No more a scare!

Human immunodeficiency virus (HIV) infection has posed as a major global health epidemic for almost three decades. With the advent of highly active antiretroviral therapy in 1996 and the application of prophylaxis and management of opportunistic infections, acquired immunodeficiency syndrome mortality has decreased markedly. The most aggressive HIV-related renal disease is end-stage renal disease due to HIV-associated nephropathy. Presence of HIV infection used to be viewed as a contraindication to renal transplantation for multiple reasons; concerns for exacerbation of an already immunocompromised state by administration of additional immunosuppressants; the use of a limited supply of donor organs with unknown long-term outcomes. Multiple studies have reported promising outcomes at three to five years after kidney transplantations in patients treated with highly active antiretroviral therapy, and HIV is no longer a contraindication for renal transplant. Hence, we present eight HIV-positive patients who received live-related renal transplantation at our center and their follow-up

Spectrum of renal injury in pregnancy-induced hypertension: Experience from a single center in India

Pregnancy-induced hypertension (PIH) is a known complication of late pregnancy and is an important cause of maternal and fetal morbidity and mortality. Data on clinical profile, especially renal profile of preeclampsia and eclampsia in Indian women are lacking. The aim of our study was to examine the renal profile and clinical outcomes of patients diagnosed with PIH in our institution with a focus on the spectrum of acute kidney injury (AKI). In this prospective, observational study, 347 patients with a diagnosis of preeclampsia-eclampsia, who were undergoing treatment at the M. S. Ramaiah Medical College, were included in the study. The study duration was from 2010 to 2014. Details regarding epidemiologic data, obstetric data, laboratory parameters as well as maternal, renal, and fetal outcomes were noted. Patients with preexisting hypertension, diabetes mellitus, or chronic kidney disease were excluded from analysis. The overall incidence of preeclampsia was 3.4%. Hemolysis, elevated liver enzymes, and low platelets syndrome was seen in 31 patients (9%); 56 patients (19%) had AKI with a mean serum creatinine of 3.2 mg/dL and mean proteinuria of 2.8 g/24 h. Nineteen patients required dialysis. Persistent renal failure was seen in 2.5% of the cohort. Maternal mortality was 2.5%, largely secondary to sepsis. Primiparity was a major risk factor. In this study, we found a low rate of preeclampsia in a low-to-moderate risk cohort, with an incidence of AKI and maternal mortality consistent with reported literature

Histologic patterns of primary adult onset nephrotic syndrome and their clinical characteristics; a single center study from South India

Background: The histologic pattern causing nephrotic syndrome (NS) and their clinical outcome varies depending on age, sex, race, socioeconomic status and geographic location. There has been a changing trend in the histologic spectrum of NS in the last few decades, in India as well as worldwide. Objectives: The objective of the present study was to see the histologic spectrum of adult NS in our institution and to compare it with data from other centers. Patients and Methods: All adults (≥ 18 years) with nephrotic range proteinuria who underwent renal biopsy from August 2012 to February 2015, were consecutively included in this prospective study. NS caused by diabetes and other secondary glomerular diseases were excluded. Results: Eighty (65.4%) patients were males and 42 (34.4%) were females. The median age at the time of biopsy was 36 years (interquartile range [IQR]: 24.8–45). The most common lesions were minimal change disease (MCD) in 40.2%, membranous nephropathy (MN) in 24.6% and focal segmental glomerulosclerosis (FSGS) in 16.4% of the patients. MCD was observed mostly commonly in the age group 18-35 years and MN was seen mostly commonly in age group 36-55 years. Conclusions: MCD still continues to be leading cause of NS in south Indian adults as evidenced from previous studies from this region. Other common causes include MN and FSGS. The incidence of MPGN is on the decline

Unusual Fungal Infections in Renal Transplant Recipients

Fungal infections are an important cause of morbidity and mortality in renal transplant recipients. The causative agent and the risk factors differ depending on the period after the kidney transplant. Also the incidence varies according to the geographical area. We are reporting three cases of fungal infections in renal transplant recipients. Two of them have etiological agents which are common among immunosuppressed patients, but with an atypical clinical presentation, while one of them is a subcutaneous infection caused by a less frequent dematiaceous fungus, Aureobasidium pullulans. These cases highlight how a high index of clinical suspicion and prompt diagnosis is very much essential for better outcome. The emerging fungal infections and paucity of data regarding their management pose a challenge to the transplant physicians