Belatacept Conversion Protocols and Outcomes in Kidney Transplant Recipients

BackgroundConversion from calcineurin inhibitor (CNI)-based to belatacept-based immunosuppression has become common; however, numerous protocols have emerged in lieu of a standardized protocol. The purpose of this study was to characterize belatacept conversion protocols from multiple centers and observe outcomes.MethodsThis was a retrospective study that included Kaiser Permanente Southern California members. The primary outcome was rejection 6 months after conversion and secondary outcomes included change in serum creatinine and graft loss.ResultsSeventy-eight patients were included. Thirteen distinct protocols were identified from 8 different transplant centers. Protocols varied by initial dose, induction schedule, and CNI taper. The observed rate of rejection was 6%. There was a trend toward an association of rejection with lower tacrolimus exposure at the time of conversion and lower mycophenolic acid dosing postconversion. Graft survival was 88% and patient survival was 94%. There was a significant improvement in creatinine after conversion. Those with early conversions and creatinine >2.0 mg/dL at the time of conversion had the best response.ConclusionsA large variety of belatacept conversion protocols were identified. Protocols were defined by the initial dose, induction regimen, and CNI taper. Rejection rates were low and may be influenced by exposure to maintenance immunosuppression during and after conversion. Most patients showed stabilization and improvement in creatinine postconversion, with the largest effect in those with an early conversion and serum creatinine >2.0 mg/dL.     

ASO Visual Abstract: Association of Obesity with Worse Operative and Oncologic Outcomes Among Patients Undergoing Gastric Cancer Resection

Annals of Surgical Oncology -     

Risk factors for postoperative ileus after oblique lateral interbody fusion: a multivariate analysis

Background ContextOblique lateral interbody fusion (OLIF)–has become a widely used, efficient surgical tool for various degenerative lumbar conditions. Postoperative ileus (POI) is a relatively common complication after anterior lumbar interbody fusion due to the manipulation of the intestine during the surgical approach. However, to our knowledge, little is known about POI following OLIF even though it also involves bowel manipulation during a surgical procedure.PurposeTo assess the incidence of POI and identify independent risk factors for POI development after OLIF.Study Design/SettingRetrospective cohort study.Patient SampleAll consecutive patients who underwent OLIF and percutaneous pedicle screw instrumentation from August 2012 until October 2019 at a single institutionOutcome MeasuresPatient demographics (sex, age, body weight, height, and body mass index), comorbidities (diabetes mellitus, gastroesophageal reflux disease, antithrombotic medication, previous abdominal surgery, and previous lumbar surgery), and perioperative details (preoperative diagnosis, number of levels fused, inadvertent endplate fracture during cage insertion, type of interbody graft, intraoperative estimated blood loss, duration of surgery and anesthesia, the amount of intraoperative remifentanil and propofol used as anesthetic agents, the total postoperative retroperitoneal closed-suction drainage output, and the cumulative opioid dosage administered in the first 72 hours postoperatively).MethodsPOI was defined as 2 or more of the following at 72 hours postoperatively: (1) ongoing nausea or vomiting postoperatively, (2) the absence of flatus over last 24-hour period, (3) inability to tolerate an oral diet over last 24-hour period, (4) ongoing abdominal distention postoperatively, and (5) radiological confirmation. The subjects were divided into 2 groups: patients with POI and those without POI. Binary logistic regression analyses were performed on demographics, comorbidities, and perioperative factors to identify independent risk factors for POI.ResultsEighteen (3.9%) of 460 patients experienced POI after OLIF and percutaneous pedicle screw instrumentation. Patients with POI had a significantly longer postoperative length of hospital stay than those without POI (8.61 ± 2.66 vs 6.48 ± 2.64, p = .001). Multivariate logistic regression analysis identified inadvertent endplate fracture (adjusted odds ratio = 6.017, p = .001) and the amount of intraoperative remifentanil (adjusted odds ratio = 1.057, p = .024) as independent risk factors for the occurrence of POI following OLIF.ConclusionThis study identified inadvertent endplate fracture and the amount of intraoperative remifentanil as independent risk factors for the development of POI after OLIF.     

A randomized controlled trial evaluating combination detection of HIV in Malawian sexually transmitted infections clinics

IntroductionHIV diagnosis is the necessary first step towards HIV care initiation, yet many persons living with HIV (PLWH) remain undiagnosed. Employing multiple HIV testing strategies in tandem could increase HIV detection and promote linkage to care. We aimed to assess an intervention to improve HIV detection within socio‐sexual networks of PLWH in two sexually transmitted infections (STI) clinics in Lilongwe, Malawi.MethodsWe conducted a randomized controlled trial to evaluate an intervention combining acute HIV infection (AHI) screening, contract partner notification and social contact referral versus the Malawian standard of care: serial rapid serological HIV tests and passive partner referral. Enrolment occurred between 2015 and 2019. HIV‐seropositive persons (two positive rapid tests) were randomized to the trial arms and HIV‐seronegative (one negative rapid test) and ‐serodiscordant (one positive test followed by a negative confirmatory test) persons were screened for AHI with HIV RNA testing. Those found to have AHI were offered enrolment into the intervention arm. Our primary outcome of interest was the number of new HIV diagnoses made per index participant within participants’ sexual and social networks. We also calculated total persons, sexual partners and PLWH (including those previously diagnosed) referred per index participant.ResultsA total of 1230 HIV‐seropositive persons were randomized to the control arm, and 561 to the intervention arm. Another 12,713 HIV‐seronegative or ‐serodiscordant persons underwent AHI screening, resulting in 136 AHI cases, of whom 94 enrolled into the intervention arm. The intervention increased the number of new HIV diagnoses made per index participant versus the control (ratio: 1.9; 95% confidence interval (CI): 1.2 to 3.1). The intervention also increased the numbers of persons (ratio: 2.5; 95% CI: 2.0 to 3.2), sexual partners (ratio: 1.7; 95% CI: 1.4 to 2.0) and PLWH (ratio: 2.3; 95% CI: 1.7 to 3.2) referred per index participant.ConclusionsCombining three distinct HIV testing and referral strategies increased the detection of previously undiagnosed HIV infections within the socio‐sexual networks of PLWH seeking STI care. Combination HIV detection strategies that leverage AHI screening and socio‐sexual contact networks offer a novel and efficacious approach to increasing HIV status awareness.     

Schedule dependent potentiation of antitumor drug effects by α-difluoromethylornithine in human gastric carcinoma cells in vitro

A clone of human gastric cancer cells (AGS-6) and the parental line (AGS-P) from which it was isolated were used in cell survival studies to determine whether pretreatment for 24, 48 or 72h with -difluoromethylornithine (DFMO, 5mM) would increase the cell's sensitivity to 5-Fluorouracil (5FU), Adriamycin (Adria), 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (MeCCNU), or Bleomycin (Bleo). Generally, the AGS parental cells were most sensitive to the anticancer agents after exposures to DFMO. However, there was no way to predict in advance from DFMO-induced changes in ornithine decarboxylase (ODC), polyamine or cell kinetics values, how long an exposure to DFMO was required before sensitization to an anticancer agent occurred. The degree of potentiation for a single drug was variable from time to time during exposure to DFMO, and broad differences in the sensitizations were demonstrated among the four anticancer drugs. The AGS-6 clone exhibited little or no increased sensitivity as a result of pretreatment with DFMO, even though the DFMO-induced reductions in ODC and polyamine values in these cells were similar to those produced in the more sensitive parental line.     

A rubrofusarin gentiobioside isomer from roastedCassia tora

From the roasted seeds ofCassia tora L., a new naphthopyrone glycoside was isolated and characterized as 10-[(β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranosyl)oxyl-5-hydroxy-8-methoxy-2-methyl-4H-naphtho [1,2-b]pyran-4-one(isorubrofusarin gentiobioside). Along with isorubrofusarin gentiobioside, alaternin and adenosine were isolated and identified.