Short-course Therapy Research Articles

Population-level utilisation of neoadjuvant radiotherapy for the treatment of rectal cancer.

International clinical guidelines recommend long- or short-course neoadjuvant radiotherapy for locally advanced rectal cancer. This study aims to examine variation in the use of neoadjuvant radiotherapy for rectal cancer and identify patient and hospital factors that underpin this variation. We conducted a retrospective, consecutive cohort study using statewide hospitalisation and radiotherapy data from New South Wales, Australia, 2013-2018. Included participants had a primary rectal adenocarcinoma and underwent surgical resection. Factors associated with the use or not of any neoadjuvant radiotherapy, and short versus long-course were explored using multilevel logistic regression models. Of the 2912 people included in the study, 43% received neoadjuvant radiotherapy. There was significant variation in the use of neoadjuvant radiotherapy depending on geographic location. Abdominoperineal excision (odds ratio [OR] = 1.87, 95% confidence interval [CI] = 1.53-2.28) and having surgery in a public hospital (OR = 2.34, 95% CI = 1.92-2.87) were both predictors of use. Among those receiving neoadjuvant radiotherapy, 17% received short-course therapy, with short-course declining over the study period. The use of neoadjuvant radiotherapy for rectal cancer is highly variable, with differences only partially explained by assessable patient-or hospital-level factors. Understanding neoadjuvant radiotherapy utilisation patterns may assist in identifying barriers and opportunities to improve adherence to clinical guidelines.

The Evolving Neoadjuvant Treatment Paradigm for Patients with Locoregional mismatch Repair Proficient Rectal Cancer.

The standard of care for locally advanced rectal cancer (LARC) has included preoperative chemoradiation, total mesorectal excision surgery and post operative adjuvant chemotherapy based on histopathology. The current therapeutic landscape in LARC has many different options with different directions of travel - depending on the goal of treatment. Enthusiasm for delivering total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer (LARC) is increasing in the light of recently published randomised phase III trials - RAPIDO and PRODIGE-23. There is a wide diversity of different potential schedules and a multitude of approaches, which include induction neoadjuvant chemotherapy (NACT) with a range of chemotherapy options (CAPEOX, FOLFOX, FOLFOXIRI) and a varying duration of 6-18 weeks, or consolidation NACT. These schedules either precede or follow short-course preoperative radiation therapy (SCPRT) using 5 × 5Gy or long-course chemoradiation (LCCRT) using 45-60Gy respectively. The different strategies of induction and consolidation neoadjuvant chemotherapy have been compared and have similar long-term outcomes, but consolidation chemotherapy may facilitate organ-sparing. The results are driving novel paradigms with both intensification and de-intensification treatment strategies. The ideal combination, sequence or duration of such a TNT approach remains undefined. As yet, there are no robust clinical, genetic, molecular, immune or imaging features (alone or integrated), which either direct or aid these choices. Currently, the selection of neoadjuvant treatment is driven by the impact on avoidance or feasibility of surgery or reducing the risk of metastases rather than prevention of local recurrence. Most believe that TNT will improve overall survival, despite the present lack of evidence. Both the inherent heterogeneity in LARC and the observed range of different responses underline the need for response biomarkers to individually tailor therapy rather than 'a one size fits all' approach.

New Frontiers in Management of Early and Advanced Rectal Cancer.

Simple SummaryRectal cancer has the capacity to present in a variety of forms. Depending on subtle differences in the characteristics of the tumor, it is possible for the treatment protocol to vary drastically. There are many tools available to optimize patients’ outcomes when treating rectal cancer of these various stages. Advances in early-stage, local presentation of rectal cancer focus on minimally invasive endoluminal surgery. Lesions completely responding to neoadjuvant chemoradiation non-operative surveillance have been explored. For rectal cancers patients with problematic pelvic anatomy, new platforms for resection, such as transanal total mesorectal excision and robotic total mesorectal excision, have been introduced. Late solid organ and peritoneal metastasis, originally thought to be a terminal disease, have undergone recent advances in hepatic and pulmonary metastasectomy, cytoreductive surgery, and intraperitoneal chemotherapy. Understanding these various therapeutic interventions will pave the way for improved patient outcomes.It is important to understand advances in treatment options for rectal cancer. We attempt to highlight advances in rectal cancer treatment in the form of a systematic review. Early-stage rectal cancer focuses on minimally invasive endoluminal surgery, with importance placed on patient selection as the driving factor for improved outcomes. To achieve a complete pathologic response, various neoadjuvant chemoradiation regimens have been employed. Short-course radiation therapy, total neoadjuvant chemotherapy, and others provide unique advantages with select patient populations best suited for each. With a clinical complete response, a “watch and wait” non-operative surveillance has been introduced with preliminary equivalency to radical resection. Various modalities for total mesorectal excision, such as robotic or transanal, have advantages and can be utilized in select patient populations. Tumors demonstrating solid organ or peritoneal spread, traditionally defined as unresectable lesions conveying a terminal diagnosis, have recently undergone advances in hepatic and pulmonary metastasectomy. Hepatic and pulmonary metastasectomy has demonstrated clear advantages in 5-year survival over standard chemotherapy. With the peritoneal spread of colorectal cancer, HIPEC with cytoreductive therapy has emerged as the preferred treatment. Understanding the various therapeutic interventions will pave the way for improved patient outcomes.

Effectiveness of Short-Course Antibacterial Therapy on Acute Cholecystitis after Successful Percutaneous Transhepatic Gallbladder Drainage: A Retrospective Study.

Background: The aim of this study was to evaluate the outcome of short- and long-course antibacterial therapy after successful percutaneous transhepatic gallbladder drainage in patients with mild to moderate acute cholecystitis. Patients and Methods: We compared the effect of short-course antibacterial therapy retrospectively (SCT; ≤3 days) and long-course antibacterial therapy (LCT; ≥4 days) after successful drainage of acute cholecystitis. The study outcomes involved three-month recurrence and 30-day mortality rates, as well as hospital stay length. Results: We included 132 patients with acute cholecystitis who underwent successful percutaneous transhepatic gallbladder drainage (PTGBD) and excluded 174 patients. We then grouped these patients (78 males and 54 females), according to the duration of antibacterial therapy. Short- and long-course antibacterial therapy groups comprised 54 (40.9%) and 78 (59.1%) patients, respectively. We did not observe significant differences in the three-month recurrence (p = 0.761) and 30-day mortality (p = 0.151) rates between these groups and observed only two deaths in the LCT group. The median hospital stay for the SCT group was six days (interquartile range [IQR], 5-7 days), compared with nine days (IQR, 8-10 days) for the LCT group (p < 0.001). Conclusions: A duration of three days or less of antibacterial therapy may be adequate for patients with mild to moderate acute cholecystitis after successful PTGBD.

Comparative Analysis of Short-Course Vs Long Course Antibiotic Therapy among Patients with Complicated Intra-Abdominal Infections

Background: Complicated intra-abdominal infections have become a major health challenge that merits safe and efficacious therapy. Antibiotic therapy is the treatment of choice, however the duration of antibiotic use is debatable.&#x0D; Objective: To compare the safety and efficacy of the short course and long course antibiotic therapy towards the treatment and the progressive outcome of patients presented with complicated intra-abdominal infections.&#x0D; Methodology: This comparative study was carried out on 94 subjects (chosen via non-probability, consecutive sampling), who presented with complicated intra-abdominal infections, had signs and symptoms of infection along with ultrasound abdomen examination consistent with infective foci and routine blood test showing raised total leukocyte count, at the Department of Surgery - Liaquat University Hospital, Hyderabad. Subjects were divided into two groups (47 in each) through a random assignments. Group-A was kept on a short course (5-7-days) while Group-B was kept on a long course (7-10 days) antibiotic therapy. Data were documented using a structured questionnaire, including inquiries related to sociodemographic details, disease specifics, and observed for the outcome variables (mainly postoperative early resolution of infection and long hospital stay).&#x0D; Results: In Group A, resolution of infection was achieved in 59.57%, 29.79% and 10.64% patients on day 5, 6 and 7, espectively. In Group B, esoluation of infection was only reported as 42.55%, 36.17% and 21.28% on day 5, 6 and 7, respectively. The median duration of taking antibiotic was almost half in short course group than the long. Surgical site infections were commonly observed in Group B patients. There was no mortality observed in both groups. There is no significance difference observed in primary outcome of clinical cure among the groups.&#x0D; Conclusion: It can be concluded that the short course antibiotic therapy has good efficacy to treat CIAI when the primary foci of infection are surgically extracted with adequate source control.

Retrospective Cohort Analysis of the Effect of Antimicrobial Stewardship on Postoperative Antibiotic Therapy in Complicated Intra-Abdominal Infections: Short-Course Therapy Does Not Compromise Patients’ Safety

Background: Recent evidence suggests that short-course postoperative antibiotic therapy (PAT) of intra-abdominal infections is non-inferior considering clinical outcomes. The aim of this study was to compare the outcome of short vs. long PAT in complicated intra-abdominal infections (cIAIs) without sepsis. Methods: We performed a single center-quality improvement study at a 1500 bed sized university hospital in Bavaria, Germany, with evaluation of the length of antibiotic therapy after emergency surgery on cIAIs with adequate source control during 2016 to 2018. We reviewed a total of 260 cases (160 short duration vs. 100 long duration). The antibiotic prescribing quality was assessed by our in-house antimicrobial stewardship team (AMS). Results: No significant differences of patient characteristics were observed between short and long PAT. The frequency of long PAT declined during the observation period from 48.1% to 26.3%. Prolongation of PAT was not linked with any clinical benefits, on the contrary clinical outcome of patients receiving longer regimes were associated with higher postoperative morbidity. AMS identified additional educational targets to improve antibiotic prescribing quality on general wards like unnecessary postoperative switches of antibiotic regimes, e.g., unrequired switches to oral antibiotics as well as prolongation of PAT due to elevated CRP. Conclusion: Short-course antibiotic therapy after successful surgical source control in cIAIs is safe, and long-duration PAT has no beneficial effects.

Are short courses of antibiotic therapy as effective as standard courses for COPD exacerbations? A systematic review and meta-analysis

BackgroundThe best duration of antibiotic treatment for chronic obstructive pulmonary disease (COPD) exacerbations is uncertain. ObjectiveTo evaluate whether a short course of antibiotic therapy is as effective as the standard longer treatment for exacerbations of patients with COPD. MethodsWe searched Pubmed/MEDLINE and trials in relevant systematic reviews from the inception up to March 2021, with no language restrictions. Randomised controlled trials comparing short-course antibiotic therapy (≤5 days) with standard antibiotic therapy (≥6 days) for exacerbations of patients aged ≥40 with spirometrically-confirmed COPD were included. Three outcomes were considered: end-of-therapy clinical cure, bacterial eradication and adverse events. Statistical analyses included random effects meta-analyses using odds ratios and assessment of heterogeneity. ResultsOf 1274 citations found, eight were eligible for inclusion, seven of which recruited outpatients. Overall, short-course antibiotic treatments were not significantly different from those of long-course treatments for clinical cure (odds ratio [OR] 1.14, 95% CI 0.91; 1.44) and for bacterial eradication (OR 1.16, 95% CI 0.91; 1.48). Adverse events were observed in 379 (21.1%) patients receiving short-term antibiotic regimens, while 412 (22.8%) patients receiving the standard regimens reported adverse events (OR 0.83, 95% CI 0.62; 1.11). The heterogeneity of the studies was low. ConclusionIn relation to clinical and bacteriological efficacy, a short course of antibiotic treatment is equivalent to longer conventional treatment in mainly outpatients with exacerbations of COPD. Moreover, shorter exposure to antibiotics may decrease the risk developing antimicrobial resistance and, hence, might become first-line therapy for the management of ambulatory COPD patients.

Nonrandomized Comparison of Efficacy and Side Effects of Bicalutamide Compared With Luteinizing Hormone-Releasing Hormone (LHRH) Analogs in Combination With Radiation Therapy in the CHHiP Trial

PurposeCHHiP is a randomized trial evaluating moderately hypofractionated radiation therapy for treatment of localized prostate cancer. Of all participants, 97% of them had concurrent short-course hormone therapy (HT), either luteinizing hormone-releasing hormone analog (LHRHa) or 150 mg of bicalutamide daily. This exploratory analysis compares efficacy and side effects in a nonrandomized comparison. Methods and MaterialsIn our study, 2700 patients received LHRHa and 403 received bicalutamide. The primary endpoint was biochemical/clinical failure. Groups were compared with Cox regression adjusted for various prognostic factors and stratified by radiation therapy dose. A key secondary endpoint was erectile dysfunction (ED) assessed by clinicians (using scores from Late Effects on Normal Tissues: Subjective/Objective/Management [LENT-SOM] subjective erectile function for vaginal penetration) and patients (single items within the University of California-Los Angeles Prostate Cancer Index [UCLA PCI] and Expanded Prostate Cancer Index Composite [EPIC]-50 questionnaires) at 2 years and compared between HT regimens by χ2 trend test. ResultsBicalutamide patients were significantly younger (median 67 vs 69 years LHRHa). Median follow-up was 9.3 years. There was no difference in biochemical or clinical failure with an adjusted hazard ratio or 0.97 (95% confidence interval, 0.77-1.23; P = .8). At 2 years, grade ≥2 LENT-SOM ED was reported in significantly more LHRHa patients (313 out of 590; 53%) versus bicalutamide (17 out of 68; 25%) (P < .0001). There were no differences in ED seen with UCLA-PCI and EPIC-50 questionnaires. ConclusionsIn this nonrandomized comparison, there was no evidence of a difference in efficacy according to type of HT received. Bicalutamide preserved clinician assessed (LENT-SOM) erectile function at 2 years but patient-reported outcomes were similar between groups.

Role of accredited social health activists in treatment of persons with severe mental illness in the community.

Role of accredited social health activists in treatment of persons with severe mental illness in the community.

Development of an Orthotopic Murine Model of Rectal Cancer in Conjunction With Targeted Short-Course Radiation Therapy

PurposeOrthotopic tumors more closely recapitulate human cancers than do ectopic models; however, precision targeting of such internal tumors for radiation therapy (RT) without inducing systemic toxicity remains a barrier. We developed an innovative murine orthotopic rectal tumor model where the insertion of clinical grade titanium fiducial clips on opposing sides of the rectal tumor allowed for targeted administration of short-course radiation therapy (SCRT). With this novel approach, clinically relevant RT regimens can be administered to orthotopic tumors to explore the biology and efficacy of radiation alone or as a combination therapy in a murine model that closely recapitulates human disease. Methods and MaterialsMurine Colon 38-luciferase tumor cells were injected into the rectal wall of syngeneic mice, and fiducial clips were applied to demarcate the tumor. An SCRT regimen consisting of 5 consecutive daily doses of 5 Gy delivered by an image-guided conformal small animal irradiator was administered 9 days after implantation. Tumor burden and survival were monitored along with histological and flow cytometric analyses on irradiated versus untreated tumors at various time points. ResultsSCRT administered to orthotopic rectal tumors resulted in a reduction in tumor burden and enhanced overall survival with no apparent signs of systemic toxicity. This treatment paradigm resulted in significant reductions in tumor cellularity and increases in fibrosis and hyaluronic acid production, recapitulating the SCRT-induced effects observed in human cancers. ConclusionsWe have established a means to target murine orthotopic rectal tumors using fiducial markers with a fractionated and clinically relevant SCRT schedule that results in an RT response similar to what is observed in human rectal cancer. We also validated our model through examining various parameters associated with human cancer that are influenced by irradiation. This model can be used to further explore RT doses and scheduling, and to test combinatorial therapies.

1126. Short-Course Therapy and Transition to Enteral Antibiotics for Uncomplicated Bacteremia Due to Enterobacterales Species

Abstract Background Gram-negative bacteremia historically has been treated with 10-14 days of parenteral antibiotics. However, data supporting this practice are lacking, and recent evidence shows equivalent outcomes for short-course (SC) therapy (7 days) and early (by day 5) conversion to highly bioavailable enteral (PO) antibiotics for Enterobacterales bacteremia. Methods Under a QI framework, we used PDSA cycles to reduce treatment duration and increase use of PO levofloxacin or trimethoprim-sulfamethoxazole for uncomplicated Enterobacterales bacteremia among Infectious Diseases (ID) clinicians at a children’s hospital in Boston, MA. We conducted an education session on evidence to support these practices for ID faculty and fellows in October 2020. In December 2020, we implemented standardized recommendations for a 7-day duration and early PO transition for eligible patients (≥ 3-months-old, ≤ 2 days monomicrobial bacteremia, with source control and return to baseline clinical status) that could be inserted automatically into electronic consult notes. In February 2021, we reinforced this practice to ID providers. We collected data before and after these interventions on ID recommendations and on patients’ actual antibiotic management. Results From 11/01/20 to 05/31/21, mean recommended treatment decreased from 10.6 to 9.5 days; however, mean duration received was similar (11.2 vs 11.7 days) (Figure 1). The percentage of patients for whom ID recommended PO conversion and in whom transition to PO agents by day 5 occurred increased from 27% to 37.5%. Figure 1. Change in average duration of antibiotics recommended and received, in days Conclusion Education and creation of automated standardized recommendations led to decreased recommended treatment durations and increased PO conversions for Enterobacterales bacteremia, but only modestly. This quality improvement initiative demonstrates the potential benefits of education and electronic documentation tools to facilitate evidence-based practice changes, but also highlights the difficulty in changing practice even amongst ID clinicians. Further PDSA cycles will be targeted at increasing more consistent awareness among a large ID division in addition to other stakeholders. Disclosures Gabriella S. Lamb, MD, MPH, Nothing to disclose

61. Short- versus prolonged-courses of antimicrobial therapy for patients with uncomplicated Pseudomonas aeruginosa bloodstream infection

BackgroundThe optimal duration of antimicrobial therapy for uncomplicated Pseudomonas aeruginosa bloodstream infection (BSI) is unknown. We compared the outcomes of short and prolonged courses of antimicrobial therapy in adults with uncomplicated pseudomonal BSI.MethodsAll patients with uncomplicated P. aeruginosa BSI admitted at a tertiary-care hospital from May 2016 to September 2020 were included. We compared the rate of recurrent P. aeruginosa infection and 30-day mortality among patients who underwent short (7‒11 days) and prolonged (12‒21 days) courses of antimicrobial therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. ResultsWe evaluated 1,477 patients with uncomplicated P. aeruginosa BSI; of them, 290 met the eligibility criteria, including 97 (33%) who underwent short-course therapy (9 [interquartile range (IQR), 8‒11] days) and 193 (67%) who underwent prolonged-course therapy (15 [IQR, 14‒18] days). We found no significant difference in the risk of recurrence or 30-day mortality between the prolonged-course and short-course groups (n=10, 11% vs. n=32, 16%; IPTW-adjusted hazard ratio (HR) 0.61; 95% confidence interval (CI) 0.30−1.24; p=0.17). The recurrence of P. aeruginosa infection at any site within 180 days of completing therapy occurred significantly more in the prolonged-course group (n=10, 10% vs. n=38, 20%; IPTW-adjusted HR 0.48; 95% CI 0.24−0.96, p=0.04). The resistance acquisition in subsequent P. aeruginosa isolates was more frequent in the prolonged-course group, although the difference was not statistically significant (n=2, 20% vs. n=12, 32%; p=0.70). ConclusionShort-course antimicrobial therapy could be as effective as prolonged-course therapy for uncomplicated P. aeruginosa bloodstream infection.Disclosures All Authors: No reported disclosures

Trends in the use of short-course radiation therapy for rectal cancer in New South Wales, Australia.

Trends in the use of short-course radiation therapy (RT) for rectal cancer in Australia are unknown. The purpose of this study was to compare short-course RT and long-course chemoradiation (CRT) utilisation in the neoadjuvant treatment of rectal cancer in New South Wales (NSW). Patients who received neoadjuvant RT (2009-2014) for rectal cancer were identified from the NSW Central Cancer Registry. Univariate and multivariable analyses were performed to investigate factors associated with receipt of short-course RT. A total of 1196 (81%) patients received long-course CRT, and 274 (19%) patients received short-course RT. Receipt of short-course RT was associated with older age: 54% in patients ≥80 years, and 11% in patients <50 years (P < 0.0001). Patients with T2 disease (30%) were more likely to receive short-course RT, compared with T3 (19%) or T4 (8%) disease (P = 0.002). Patients with N0 (23%) disease were more likely to be treated with short-course RT, compared with N+ (16%) (P = 0.03). The proportion of short-course RT delivered to patients with Charlson Comorbidity Index (CCI) ≥ 2 (28%) was higher than patients with CCI = 0 (17%) (P = 0.002). There was wide variation in the proportion of short-course RT used across residence local health districts (5-29%) (P < 0.0001). In rectal cancer patients treated with neoadjuvant RT in NSW, 19% received short-course RT. The use of short-course RT was associated with older age, comorbidities and less advanced disease. Wide variation across NSW was identified and future research investigating factors for the variation will be useful.

The clinical utility and safety of short-course immune checkpoint inhibitors in multiple tumours-A real-world multicentric study from India.

The real-world data on short course of immune checkpoint inhibitor (ICI) use are sparse and merit exploration. A multicentric observational study on the safety and efficacy of ICI in oncology patients between August 2014 and October 2020 involves 1011 patients across 13 centers in India. The median age was 59 (min 16-max 98) years with male preponderance (77.9%). The predominant cohort received short-course ICI therapy; the median number of cycles was 5 (95% confidence interval [CI] 1-27), and the median duration of therapy was 3 (95% CI 0.5-13) months. ICIs were used commonly in the second and third line setting in our study (66.4%, n=671). Objective response rate (complete or partial response) was documented in 254 (25.1%) of the patients, 202 (20.0%) had stable disease, and 374 (37.0%) had progressive disease. The clinical benefit rate was present in 456 (45.1%). Among the patients whom ICI was stopped (n=906), the most common reason for cessation of ICI was disease progression (616, 68.0%) followed by logistic reasons like financial constraints (234, 25.82%). With a median follow-up of 14.1 (95% CI 12.9-15.3) months, there were 616 events of progression and 443 events of death, and the median progression free survival and overall survival were 6.4 (95% CI 5.5-7.3) and 13.6 (95% CI 11.6-15.7) months, respectively, in the overall cohort. Among the immune-related adverse events, autoimmune pneumonitis (29, 3.8%) and thyroiditis (24, 2.4%) were common. Real-world multicentric Indian data predominantly with short-course ICI therapy have comparable efficacy/safety to international literature with standard ICI therapy.

A Statewide Collaborative Quality Initiative to Improve Antibiotic Duration and Outcomes in Patients Hospitalized With Uncomplicated Community-Acquired Pneumonia.

BackgroundCommunity-acquired pneumonia (CAP) is a common cause for hospitalization and antibiotic overuse. We aimed to improve antibiotic duration for CAP across 41 hospitals participating in the Michigan Hospital Medicine Safety Consortium (HMS).MethodsThis prospective collaborative quality initiative included patients hospitalized with uncomplicated CAP who qualified for a 5-day antibiotic duration. Between 23 February 2017 and 5 February 2020, HMS targeted appropriate 5-day antibiotic treatment through benchmarking, sharing best practices, and pay-for-performance incentives. Changes in outcomes, including appropriate receipt of 5 ± 1–day antibiotic treatment and 30-day postdischarge composite adverse events (ie, deaths, readmissions, urgent visits, and antibiotic-associated adverse events), were assessed over time (per 3-month quarter), using logistic regression and controlling for hospital clustering.ResultsA total of 41 hospitals and 6553 patients were included. The percentage of patients treated with an appropriate 5 ± 1–day duration increased from 22.1% (predicted probability, 20.9% [95% confidence interval: 17.2%–25.0%]) to 45.9% (predicted probability, 43.9% [36.8%–51.2%]; adjusted odds ratio [aOR] per quarter, 1.10 [1.07–1.14]). Thirty-day composite adverse events occurred in 18.5% of patients (1166 of 6319) and decreased over time (aOR per quarter, 0.98 [95% confidence interval: .96–.99]) owing to a decrease in antibiotic-associated adverse events (aOR per quarter, 0.91 [.87–.95]).ConclusionsAcross diverse hospitals, HMS participation was associated with more appropriate use of short-course therapy and fewer adverse events in hospitalized patients with uncomplicated CAP. Establishment of national or regional collaborative quality initiatives with data collection and benchmarking, sharing of best practices, and pay-for-performance incentives may improve antibiotic use and outcomes for patients hospitalized with uncomplicated CAP.

Carotid Artery Stenting in Patients with Atrial Fibrillation: Direct Oral Anticoagulants, Brief Double Antiplatelets, and Testing Strategy.

Carotid endarterectomy is usually preferred over carotid artery stenting (CAS) for patients with atrial fibrillation (AF). We present our experience with short-course periprocedural triple antithrombotic therapy in 32 patients aged >18 years with nonvalvular AF undergoing CAS. There were no deaths, cardiac events, embolic strokes, hyperperfusion syndrome, intracranial hemorrhage, or stent thrombosis within 30 days. Transient intraprocedural hemodynamic instability in 15/32 (47%) and prolonged instability in 4/32 (13%) was managed conservatively. At a mean 16-month follow-up, there were no new neurological events or deterioration. Mean stenosis was reduced from 78.0% ± 9.7% to 17.3% ± 12.2%. This retrospective study included patients AF who were symptomatic (minor stroke (NIHSS ≤ 5)/TIA) with ICA stenosis >50%, or asymptomatic under DOAC therapy with carotid stenosis >80%, who underwent CAS from 6/2014–10/2020. Patients received double antiplatelets and statins. Antiplatelet therapy effectiveness was monitored. Stenting was performed when P2Y12 reaction units (PRU) were <150. DOACs were discontinued 48 h before angioplasty; one 60 mg dose of subcutaneous enoxaparin was administered in lieu. DOAC was restarted 12–24 h after intervention. Patients were discharged under DOAC and one nonaspirin antiplatelet. 32 patients on DOAC were included (26 male, mean age 71). 19 (59.4%) presented with stroke (ICA stenosis-related in 14); 13 (40.6%) were asymptomatic. Stents were deployed under filter protection following pre-angioplasty; post-angioplasty was performed at least once in 12 patients (37.5%). Our experience suggests that CAS can be safely performed in selected patients with CAS and AF requiring DOAC. The role of CAS in AF patients under DOAC warrants study in rigorous trials.

Short- Versus Standard-Course Nonmacrolide Antibiotic Treatment in Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Retrospective, Observational Cohort Study

In critically ill patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and without positive microbiological data, the efficacy and tolerability of short-course nonmacrolide antibiotics are ill-described and have pertinent implications in antimicrobial stewardship. This study compared the efficacy and tolerability of nonmacrolide antibiotic strategies in critically ill patients with AECOPD and without pertinent positive microbiological testing. This single-center, retrospective cohort study was conducted in culture-negative critically ill adults admitted to an intensive care unit (ICU) between July 1, 2014, and July 1, 2019, for the treatment of AECOPD. Included patients received treatment with an empiric corticosteroid, azithromycin, and/or a nonmacrolide antibiotic. Patients treated with a nonmacrolide antibiotic for ≤3 and >3 days made up the short- and standard-course groups, respectively. The prevalence of in-hospital mortality, progression to the need for ventilation, and/or readmission for AECOPD within 30 days (primary composite end point) was compared between the two groups. Additional end points included hospital and ICU lengths of stay (LOS), all-cause 30-day readmission, and prevalence of antibiotic-related adverse events. A total of 135 patients were included (short course, 66; standard course, 69). The differences in the primary composite end point (short vs standard, 24.2% vs 39.1%; P=0.06) and its individual components were not significant. The median ICU LOS (2 vs 3 days) and hospital LOS (4 vs 6 days) were shorter in the short-course group (both, P < 0.01). Multivariate logistic regression confirmed no association between group assignment and the primary end point. Short-course nonmacrolide therapy in patients with AECOPD and no positive microbiological testing was not associated with differences in mortality, progression to ventilation, readmission rate, or prevalence of adverse drug events. Larger-scale prospective studies are needed to validate these findings.

Short-course daily isoniazid and rifapentine for latent tuberculosis infection in people living with HIV who received coformulated bictegravir/emtricitabine/tenofovir alafenamide.

IntroductionShort‐course preventive therapy with 1‐month course of daily administration of isoniazid (300‐mg) plus rifapentine (600‐mg) (1HP) and 3‐month course of weekly administration of isoniazid (900‐mg) plus rifapentine (900‐mg) (3HP) has higher completion rates than 9‐month course of daily isoniazid (9H) for individuals with latent tuberculosis infection (LTBI). We aimed to evaluate the effect, safety and tolerability of 1HP in people living with HIV (PLWH) and LTBI who received coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).MethodsPLWH testing positive by interferon‐gamma release assay and having received BIC/FTC/TAF for >2 weeks with plasma HIV RNA load (PVL) <200 copies/ml were enrolled. BIC trough plasma concentrations and cytokine profiles were determined before the first dose (day 1/baseline), 24 h after the 14th (day 15) and 28th (day 29) doses of 1HP. PVL were determined on days 15 and 29 of 1HP and every 3 months subsequently after discontinuation of 1HP.ResultsFrom November 2019 to December 2020, 48 PLWH with LTBI were enrolled. One participant (2.1%) discontinued 1HP on day 15 due to fever and generalized rashes with PVL of 72 copies/ml, which was <50 copies/ml in three subsequent determinations while on BIC/FTC/TAF over the 12 months of follow‐up. The percentages of BIC trough plasma concentrations above the protein‐adjusted 95% effective concentration (paEC95 = 162 ng/ml) were 56.3% and 37.0% on days 15 and 29, respectively. The percentage of PVL <200 copies/ml was 91.7% on day 15, 97.8% on day 29 and 100% at both months 3 and 6. After a median observation of 52 weeks (interquartile range, 51–55), all participants continued BIC/FTC/TAF with a median PVL of 20 copies/ml (range 20–331). Except for the participant who discontinued 1HP because of allergic reactions, none of the participants had relevant symptoms or increases of the cytokine levels assessed between baseline and days 15 and 29 of 1HP.ConclusionsBIC/FTC/TAF in combination with 1HP was well tolerated with a high completion rate. BIC trough plasma concentrations were significantly decreased with concurrent use of 1HP among PLWH with LTBI. While transient viral blips were observed during 1HP without causing subsequent treatment failure, such combination should be applied with caution.

Efficacy and safety of sequential neoadjuvant chemotherapy and short-course radiation therapy followed by delayed surgery in locally advanced rectal cancer: a single-arm phase II clinical trial with subgroup analysis between the older and young patients.

PurposeThis study was performed to investigate the efficacy and safety of short-course radiation therapy (SCRT) and sequential chemotherapy followed by delayed surgery in locally advancer rectal cancer with subgroup analysis between the older and young patients.Materials and MethodsIn this single-arm phase II clinical trial, eligible patients with locally advanced rectal cancer (T3–4 and/or N1–2) were enrolled. All the patients received a median three sequential cycles of neoadjuvant CAPEOX (capecitabine + oxaliplatin) chemotherapy. A total dose of 25 Gy in five fractions during 1 week was prescribed to the gross tumor and regional lymph nodes. Surgery was performed about 8 weeks following radiotherapy. Pathologic complete response rate (pCR) and grade 3–4 toxicity were compared between older patients (≥65 years) and younger patients (<65 years).ResultsNinety-six patients with locally advanced rectal cancer were enrolled. There were 32 older patients and 64 younger patients. Overall pCR was 20.8% for all the patients. Older patients achieved similar pCR rate (18.7% vs. 21.8; p = 0.795) compared to younger patients. There was no statistically significance in terms of the tumor and the node downstaging or treatment-related toxicity between older patients and younger ones; however, the rate of sphincter-saving surgery was significantly more frequent in younger patients (73% vs. 53%; p=0.047) compared to older ones. All treatment-related toxicities were manageable and tolerable among older patients.ConclusionNeoadjuvant SCRT and sequential chemotherapy followed by delayed surgery was safe and effective in older patients compared to young patients with locally advanced rectal cancer.

Feasibility of Organ Preservation With Short Course Radiation Therapy as Part of Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer During the COVID-19 Pandemic

Purpose/Objective(s)While long course chemoradiation therapy has been studied as part of a watch-and-wait (WW) strategy for patients with locally advanced rectal cancer, it is unclear whether short-course radiation therapy (SCRT) will be associated with similar rates of organ preservation. We hypothesized that a WW strategy to facilitate organ preservation with SCRT, as part of a total neoadjuvant therapy (TNT) approach during the COVID-19 pandemic, would be both safe and feasible.Materials/MethodsFrom March to June of 2020, due to the COVID-19 pandemic, per institutional policy, all patients undergoing radiation therapy for locally advanced rectal cancer were treated with SCRT. After completion of SCRT-TNT, patients were clinically restaged by exam, endoscopy and MRI and the decision was made to manage the patient surgically or with a WW approach. The decision for WW or surgery was made by the surgeon in conjunction with patient consent. After IRB waiver was obtained, we reviewed consecutive patients treated during our SCRT mandate. The main outcome of interest was total mesorectal excision (TME)-free survival among patients eligible for WW after SCRT-TNT.ResultsOur cohort included 42 patients with a median age of 57 years (Interquartile Range [IQR] 48-67), 24 (57%) of whom were male. Median follow-up from end of SCRT-TNT was 7 months (IQR 6-8). The median tumor cranio-caudal size was 4.1 cm (IQR 3.3-5.2) with a median distance from the anal verge of 7 cm (IQR 5-9). The majority had cT3 (71%) or cN+ (74%) disease. Patients underwent a median of 14 weeks (IQR 13-15) of FOLFOX or CAPEOX chemotherapy, with 32 (76%) patients receiving chemotherapy prior to SCRT and 10 (24%) patients receiving chemotherapy after SCRT. The median time from completion of TNT to endoscopic restaging was 9 weeks (IQR 7-10). Nineteen (45%) patients were recommended to undergo surgical resection, of whom 17 went on to TME and 2 refused TME. Of the 15 patients with pathology available, 2 had a pCR (13%). Notably, one of these patients had a cCR at post-TNT endoscopy, but due to the presence of a stricture, WW was deemed unfeasible. Of the 23 patients managed by a WW strategy after SCRT-TNT completion, 19 had a clinical complete response (cCR), 3 had a near-CR, and 1 had an incomplete response. The 6-month TME-free survival was 85% for patients on WW. Four (17%) patients had a local regrowth at a median of 20 weeks (IQR 17-24), 3 of whom were salvaged with TME and 1 who declined surgery and opted for further surveillance. One of these patients had regrowth confirmed by biopsy, but had a pCR confirmed in the TME specimen. The 6-month TME- free survival of the entire cohort was 52%, and the combined pCR/6-month cCR was 52%.ConclusionOur data suggest WW after SCRT-TNT is feasible. Longer term follow-up is required to confirm the durability and oncologic safety of these results.