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Cancer can evade destruction by the immune system if aided by immunosuppressive regulatory T cells. These cells depend on a lipid-production pathway in the tumour environment, a vulnerability that might be used to target them. Lipid factory marks regulatory T cells found in tumours.

To examine metabolic differences between renal allograft acute cellular rejection (ACR) and ischemic-reperfusion injury (IRI), we transplanted MHC-mismatched kidneys and induced 28 minutes warm-IRI, and collected the ACR and IRI kidneys as well as their respective native and collateral control kidneys. We extracted metabolites from the kidney tissues and found the lysine catabolite saccharopine 12.5-fold enriched in IRI kidneys, as well as the immunometabolites itaconate and kynurenine in ACR kidneys. Saccharopine accumulation is known to be toxic to mitochondria and may contribute to IRI pathophysiology, while itaconate and kynurenine may be reflective of counterregulatory responses to immune activation in ACR.

Background Intestinal Ultrasound (IUS) has been gaining momentum in the management of patients with inflammatory bowel disease (IBD). Underutilized in the United States(U.S.), we present the impact of IUS in management decisions in a cohort of IBD patients seen at a tertiary center. Methods This retrospective study analyzed all IBD patients seen at our institution undergoing IUS as part of routine clinical evaluation. Patient demographics, disease type, clinical activity, laboratory markers, and therapy was obtained. Patients with evidence of inflammation based on IUS characteristics of bowel wall thickening, with additional parameters of mural stratification, mesenteric fat, doppler flow, lymph nodes, dilated bowel, free fluid used as adjunct measures were compared to those without IUS features of activity. Subsequent management plan based on findings were evaluated. Results Of 148 patients seen for IUS (median age 41 (range 18–81), 67% female), 108(73%) had Crohn’s disease (CD), 39(26.4%) had ulcerative colitis (UC), 1(0.7%) had IBD-undetermined (IBD-U) with 111(75%) Caucasians, 9.5% Blacks, 8.8% Asians, and 6.8% Hispanics. Median disease duration was 8 years, range (0–43) with 113(94.1%) on biologic/small molecule therapy and 7(5.8%) on mesalamines. No differences in BMI were noted in those with active disease vs. those in remission. However, we noted 29(19.3%) had fatty liver on ultrasound, which correlated highly with high BMI (31 vs. 24) in those with normal liver (p On IUS, 110(66%) of our patients had evidence of disease activity and 56(34%) were in remission. Inflammatory markers ESR and CRP did not correlate to IUS activity. In our UC patients Mayo score correlated to IUS findings but not Harvey Bradshaw Index (HBI) for CD. For those with positive findings on IUS, 29.5% escalated therapy for their IBD, and 13.3% required change in drug mechanism. For those in remission, the majority of patients 43(84.3%) continued their therapy while 3(5.9%) successfully de-escalated therapy. Conclusion In our study, IUS was useful in providing management decisions in those with active disease especially as there was a lack of correlation to inflammatory markers and HBI scores.

Objective There are limited data on using more than one biologic or small molecule drug combined to treat patients with inflammatory bowel disease. The aim of our study was to determine the effectiveness and safety of combination biologic use in inflammatory bowel disease. Methods We identified patients with Crohn's disease or ulcerative colitis who received treatment with a combination of two biologics or a biologic and a small molecule drug from 2015 to 2019 for persistent disease activity or concomitant rheumatological or dermatological disease. The primary end-point was effectiveness, based on improvements in inflammatory markers, clinical, and endoscopic remission. The secondary end-point was safety. Results Of the 50 patients treated with combination therapy there were significantly more patients in clinical and endoscopic remission at follow-up compared to baseline (50% vs 14%, P = 0.0018, delta 36%, 95% confidence interval [CI] 0.13-0.53; and 34% vs 6%, P = 0.0039, delta 28%, 95% CI 0.09-0.47), respectively. Median erythrocyte sedimentation rate (17 mm/h vs 13 mm/h, P = 0.002) and C-reactive protein (5.00 mg/dL vs 2.35 mg/dL, P = 0.002) also decreased posttreatment. There were eight serious adverse events and no deaths CONCLUSIONS: Combination biologic therapy appears to be an effective option for patients with refractory inflammatory bowel disease or concomitant autoimmune disease that is inadequately controlled by biologic monotherapy. There was an increased risk of serious infection compared with biologic monotherapy; however, this risk might be minimized by discontinuing immunomodulators prior to initiating combination therapy. Large prospective studies are needed to confirm these findings.

Introduction Gonorrhoea is currently the second most common bacterial sexually transmitted infection and represents a serious public health threat. The increasing antimicrobial resistance in Neisseria gonorrhoeae (GC) to currently available therapies is driving an urgent need for new novel agents. Gepotidacin (GEP) is a novel, first in class triazaacenaphthylene antibacterial which inhibits bacterial DNA replication. This multicenter (11 US and 1 UK) trial evaluated GEP as a single oral dose in men and women. Methods Patients with signs and symptoms of urogenital gonorrhoea, a prior culture or nucleic acid amplification test (NAAT) positive for GC, a urethral Gram stain with intracellular diplococci, or who had sexual contact with an individual diagnosed with gonorrhoea in the past 14 days were eligible for enrollment. Participants were randomised 1:1 to receive either 1.5g or 3g GEP orally. The primary efficacy endpoint was culture confirmed microbiological eradication at test-of-cure (TOC) visit 3–7 days post dose. Results 106 patients (101 men and 5 women) were randomised and 105 received treatment. Baseline GC isolates were identified in 69 (65%) urogenital, 3 (3%) pharyngeal, and 4 (4%) rectal specimens. Microbiological success was achieved by 97% and 95% of subjects with urogenital GC in the 1.5g and 3g treatment groups, respectively. Isolates from 2 subjects developed resistance to GEP between baseline and TOC. The most common GEP-related AEs were gastrointestinal (diarrhoea, flatulence, abdominal pain and nausea) with the majority being mild or moderate in intensity. Treatment-related AEs of moderate intensity occurred with a higher incidence in the 3g treatment group than the 1.5g treatment group (15% and 10%, respectively). There were no AEs that led to study withdrawal and no SAEs were reported. Conclusions Both the GEP 1.5g and 3g single doses eradicated urogenital GC with microbiological success rates of 29/30 (97%) and 37/39 (95%), respectively. The data support further development of GEP in this indication. Support: This study was supported by GSK (BTZ116576; NCT02294682). This project was funded in whole or in part with Federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced. Research and Development Authority (BARDA), under agreement # HHSO100201300011C

Combination therapy regimens appear to be one of the next logical strategies for treating individuals with HIV infection. At the 10th International Conference on AIDS [Yokohama, Japan; August 1994] promising findings from several combination therapy studies were reported. In the words of leading AIDS researcher Professor Neil Graham from Johns Hopkins University, Baltimore, Maryland, US, ‘the era of monotherapy[for HIV disease]is rapidly drawing to a close; the way forward is with combination therapy’.

The eagerly-awaited results of the Concorde trial were revealed last week in theLancet [9 April].1Preliminary findings that were published just over a year ago in a letter to theLancet [April 3, 1993]* caused considerable controversy at the time. However, the original conclusions from the Concorde study remain unchanged, despite any minor differences in figures that may have emerged. According to the investigators, the results of the Concorde trial are sufficient to discourage the early use of zidovudine in symptom-free HIV-infected adults. Furthermore, in their view, doubt has now been cast on the‘uncritical use of CD4 counts as “surrogate endpoints” in trials’.Inevitably, controversy will continue to reign, especially in view of a number of criticisms that have been levelled at the study.

US researchers are moving closer towards using gene therapy to treat patients with HIV infection. At the 10th International Conference on AIDS [Yokohama, Japan; August 1994] Dr Flossie Wong-Staal discussed her group’s work on gene therapy. A particular focus was research into the use of a hairpin ribozyme gene.