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Antiretroviral agents with novel mechanisms and dosing intervals could expand treatment options for people with HIV. Lenacapavir, an inhibitor of capsid protein that makes use of a unique mechanism, can be administered orally or subcutaneously. We sought to explore the efficacy of lenacapavir in various combination regimens as initial and maintenance therapy for HIV.In a phase 2, randomised, open-label, ongoing study at 41 investigational sites in the USA and Dominican Republic, we randomly assigned adults with HIV who had not previously received antiretrovirals to four groups (2:2:2:1). Randomisation was stratified by plasma HIV-1 RNA load (≤100 000 or100 000 copies per mL) at screening. Groups 1 and 2 both received lenacapavir (927 mg) subcutaneously every 26 weeks (after 2 weeks of oral loading [600 mg on days 1 and 2, followed by 300 mg on day 8]) with oral daily emtricitabine (200 mg) and tenofovir alafenamide (25 mg) for 28 weeks followed by subcutaneous lenacapavir (927 mg) plus oral daily tenofovir alafenamide (25 mg, group 1) or bictegravir (75 mg, group 2). Group 3 received oral daily lenacapavir (600 mg on days 1 and 2, followed by 50 mg daily) with emtricitabine (200 mg) and tenofovir alafenamide (25 mg). Group 4 received oral daily bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg). Participants and investigators were not masked to group assignment. The primary endpoint was the percentage of participants with virological suppression (HIV-1 RNA50 copies per mL) at week 54, analysed in the full analysis set (all randomly assigned participants who received at least one dose of study drug) using only on-treatment data. The safety outcome measures were incidences of treatment-emergent adverse events and graded laboratory abnormalities, analysed in the full analysis set. This study is registered at ClinicalTrials.gov, NCT04143594.Between Nov 22, 2019, and Aug 27, 2020, 249 people with HIV were screened, 183 participants were randomly assigned and 182 received a dose of antiretroviral drugs (52 in group 1, 53 in group 2, 52 in group 3, and 25 in group 4). 22 participants did not complete the full study course (five in group 1, 12 in group 2, four in group 3, and one in group 4). At week 54, virological suppression was 90% (47 of 52 patients) for group 1 (difference vs group 4: -2·6%, 95% CI -18·4 to 13·2), 85% (45 of 53) for group 2 (-7·1%, -23·4 to 9·3), 85% (44 of 52) for group 3 (-7·2%, -23·5 to 9·1), and 92% (23 of 25) for group 4. The most frequent non-injection-site adverse events with lenacapavir (subcutaneous or oral) were headache (13%, 21 of 157) and nausea (13%, 21 of 157). The most common lenacapavir-related injection-site reactions were erythema (27%, 28 of 105), swelling (23%, 24 of 105), and pain (19%, 20 of 105), which were generally mild or moderate. No serious adverse event related to study treatment occurred. Three participants discontinued subcutaneous lenacapavir because of grade 1 injection-site reactions (two for induration and one for erythema or swelling).Lenacapavir warrants further investigation as a potential antiretroviral used orally and as injection in combination with other antiretroviral drugs.Gilead Sciences.

Salted napa cabbage is the most important ingredient of kimchi. Currently, people have started to prepare ready-to-use salted napa cabbage at home. This study focused on this trend by investigating consumers' beliefs, opinions, and actual use of the products by conducting a telephone survey (895 female consumers) and face-to-face interviews (n = 514) in 2016 and a telephone survey (n = 200) in 2021. Most respondents (93 and 91% in 2016 and 2021, respectively) answered that convenience was the main reason for using salted napa cabbage. Regarding consumption behavior, 22 and 16% of the respondents in each year used salted napa cabbage after storing it for more than 24 h. In particular, 85 and 91% of consumers stored the product at room temperature, and 60 and 58% used it without washing, which could affect the quality of the food, as microorganisms could multiply during the storage. Inappropriate handling increased by age group, especially in 2021 (P0.05). In the query on satisfaction after using the products, 85 and 80% of respondents were satisfied because the product was convenient (54%) and hygienic (17%). Conversely, the respondents who were not satisfied with the products did not like the degree of salting and unhygienic status of the products. The majority (93 and 80%) of consumers preferred buying salted napa cabbage again because of its convenience. Although consumers thought that hygiene and quality were important factors, many respondents (83 and 72%) were not aware of foodborne illnesses associated with kimchi. Nevertheless, consumers intended to pay more for safe, salted napa cabbage (72 and 76%). The results of this study provide useful and credible data for understanding the factors affecting consumers' consumption and general beliefs and opinions on the use of salted napa cabbage, especially for food safety management.

Laparoscopic repair of duodenal atresia in neonates has gained popularity among some pediatric surgeons. Single-center studies suggest comparable short-term outcomes to open surgery. The purpose of this study was to utilize a large, multi-institutional pediatric dataset to examine 30-day post-operative outcomes by operative approach for newborns who underwent duodenal atresia repairs.We identified neonates aged ≤1 wk in the 2016-2018 National Surgical Quality Improvement Program-Pediatric -database that underwent a laparoscopic or open repair for duodenal atresia. Preoperative characteristics were compared between operative approaches. Postoperative complications, operative time, postoperative length of stay (LOS), and supplemental nutrition at discharge were assessed using multivariate regressions.There were 267 neonates who met inclusion criteria. There were 233 (87%) infants who underwent open repairs and 34 (13%) who underwent laparoscopic repairs. Ten (29%) children who had laparoscopy were converted to open. After adjusting for confounding, laparoscopy was associated with an increase in operative time by 65 min (95% confidence interval 45-87 min, P 0.001) but a five-day shorter LOS (95% confidence interval -9 to -2, P = 0.006) when compared to laparotomy. There were no significant differences in postoperative complications or supplemental nutrition at discharge.Our findings suggest that laparoscopic repairs of duodenal atresia are associated with shorter postoperative LOS but longer operative times when compared to open repairs. Although the conversion rate to laparotomy remained relatively high, the laparoscopic approach was associated with comparable 30-day postoperative outcomes.

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Supplemental Figure 1 shows the tumor masses of the subcutaneous tumors shown in Figure 1, as well as the flow cytometry gating strategy of M/OCP populations and the osteoclast differentiation assay experimental schematic. Supplemental Figure 2 shows representative images and the flow cytometry gating strategy for the in vitro osteoclast differentiation assay demonstrated in Figure 2. Supplemental Figure 3 shows that ZA inhibits breast cancer metastasis in a manner that is counteracted by G-CSF in intratibial injections, subcutaneous bone marrow functional assays, and with intracardiac injections of the B1 cell line following pre-treatment with Ctl or ZA and/or recombinant G-CSF. Supplemental Figure 4 shows the tumor masses of the subcutaneous tumors shown in Figure 4, as well as the plasma ALP and NTX concentrations in nude mice with and without ZA treatment. Supplemental Figure 5 shows the representative images and quantifications of the in vitro osteoclast differentiation assay with whole bone marrow from Ctl- or ZA- donors. Supplemental Figure 6 shows the volcano plots, heatmaps of differentially expressed genes, and gene ontology categories for the RNA-sequencing analysis of whole bone marrow from mice treated with Ctl, ZA, G-CSF, or ZA+G-CSF. Supplemental Figure 7 shows the determination of cut point analyses for the plasma G-CSF concentrations and patient outcome data shown in Figure 7.

Functionally enriched gene ontology (GO) terms and differentially enriched genes for the RNA-sequencing tables and heatmaps included in the manuscript text.

Purpose:Clinical trials with immune checkpoint inhibition in sarcomas have demonstrated minimal response. Here, we interrogated the tumor microenvironment (TME) of two contrasting soft-tissue sarcomas (STS), rhabdomyosarcomas and undifferentiated pleomorphic sarcomas (UPS), with differing genetic underpinnings and responses to immune checkpoint inhibition to understand the mechanisms that lead to response.Experimental Design:Utilizing fresh and formalin-fixed, paraffin-embedded tissue from patients diagnosed with UPS and rhabdomyosarcomas, we dissected the TME by using IHC, flow cytometry, and comparative transcriptomic studies.Results:Our results demonstrated both STS subtypes to be dominated by tumor-associated macrophages and infiltrated with immune cells that localized near the tumor vasculature. Both subtypes had similar T-cell densities, however, their in situ distribution diverged. UPS specimens demonstrated diffuse intratumoral infiltration of T cells, while rhabdomyosarcomas samples revealed intratumoral T cells that clustered with B cells near perivascular beds, forming tertiary lymphoid structures (TLS). T cells in UPS specimens were comprised of abundant CD8+ T cells exhibiting high PD-1 expression, which might represent the tumor reactive repertoire. In rhabdomyosarcomas, T cells were limited to TLS, but expressed immune checkpoints and immunomodulatory molecules which, if appropriately targeted, could help unleash T cells into the rest of the tumor tissue.Conclusions:Our work in STS revealed an immunosuppressive TME dominated by myeloid cells, which may be overcome with activation of T cells that traffic into the tumor. In rhabdomyosarcomas, targeting T cells found within TLS may be key to achieve antitumor response.

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The presence of disseminated tumor cells in breast cancer patient bone marrow aspirates predicts decreased recurrence-free survival. Although it is appreciated that physiologic, pathologic, and therapeutic conditions impact hematopoiesis, it remains unclear whether targeting hematopoiesis presents opportunities for limiting bone metastasis. Using preclinical breast cancer models, we discovered that marrow from mice treated with the bisphosphonate zoledronic acid (ZA) are metastasis-suppressive. Specifically, ZA modulated hematopoietic myeloid/osteoclast progenitor cell (M/OCP) lineage potential to activate metastasis-suppressive activity. Granulocyte-colony stimulating factor (G-CSF) promoted ZA resistance by redirecting M/OCP differentiation. We identified M/OCP and bone marrow transcriptional programs associated with metastasis suppression and ZA resistance. Analysis of patient blood samples taken at randomization revealed that women with high-plasma G-CSF experienced significantly worse outcome with adjuvant ZA than those with lower G-CSF levels. Our findings support discovery of therapeutic strategies to direct M/OCP lineage potential and biomarkers that stratify responses in patients at risk of recurrence.Significance: Bone marrow myeloid/osteoclast progenitor cell lineage potential has a profound impact on breast cancer bone metastasis and can be modulated by G-CSF and bone-targeting agents. Cancer Res; 78(18); 5300–14. ©2018 AACR.

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This review summarizes available data for lenacapavir, an investigational first-in-class agent that disrupts functioning of HIV capsid protein across multiple steps in the viral life cycle.Lenacapavir demonstrated picomolar potency in vitro with no cross resistance to existing antiretroviral classes and potent antiviral activity in persons with HIV-1. In persons with HIV-1, there was no preexisting resistance to lenacapavir regardless of treatment history. Lenacapavir can be administered orally either daily or weekly and subcutaneously up to every 6 months. In heavily treatment-experienced persons with multidrug-resistant HIV-1 and in treatment-naive persons with HIV-1, lenacapavir in combination with other antiretroviral agents led to high rates of virologic suppression and was well tolerated.Ongoing studies are evaluating long-acting dosing of lenacapavir for treating HIV-1 in combination with other antiretrovirals and preventing HIV-1 as a single agent.

Background Pulmonary arterial hypertension (PAH) is a chronic and progressive disease associated with impaired health-related quality of life and survival. Palliative care (PC) is patient- and family-centered care provided by an interdisciplinary team with an overarching goal of alleviating suffering and improving quality of life for patients with advanced illness. PC in other chronic diseases is associated with improved quality of life, symptom management, illness understanding, and reduced caregiver burden, but there is limited data regarding PC in PAH. Despite limited evidence, there is strong rationale for involving PC specialists in the longitudinal management of PAH. Implications for Clinicians There are currently no guidelines to help clinicians determine the most appropriate timing for referral of PAH patients to PC specialty teams. Consequently, referrals are limited and often delayed. Adoption of a standardized approach to PC referrals based on clinical or patient triggers could facilitate earlier involvement of PC as an adjunct to ongoing PAH disease-directed care. Conclusions Incorporation of PC in the longitudinal management of PAH may be beneficial to address the multidimensional aspects of living with a chronic and life-limiting illness.

We sought to evaluate the impact of thoracoscopic repair on perioperative outcomes in infants with esophageal atresia and tracheoesophageal fistula (EA/TEF).The American College of Surgeons National Surgical Quality Improvement Program pediatric database from 2014 to 2018 was queried for all neonates who underwent operative repair of EA/TEF. Operative approach based on intention to treat was correlated with perioperative outcomes, including 30-day postoperative adverse events, in logistic regression models.Among 855 neonates, initial thoracoscopic repair was performed in 133 (15.6%) cases. Seventy (53%) of these cases were converted to open. Those who underwent thoracoscopic repair were more likely to be full-term (p = 0.03) when compared to those in the open repair group. There were no significant differences in perioperative outcome measures based on surgical approach except for operative time (thoracoscopic: 217 min vs. open: 180 min, p0.001). A major cardiac comorbidity (OR 1.6, 95% CI 1.2-2.1; p = 0.003) and preoperative ventilator requirement (OR 1.4, 95% CI 1.0-1.9; p = 0.034) were the only risk factors associated with adverse events.Thoracoscopic neonatal repair of EA/TEF continues to be used sparingly, is associated with high conversion rates, and has similar perioperative outcomes when compared to open repair.III.

Surgery for nasal airway obstruction (NAO) has a high failure rate, with up to 50% of patients reporting persistent symptoms postoperatively. Virtual surgery planning has the potential to improve surgical outcomes, but current manual methods are too labor-intensive to be adopted on a large scale. This manuscript introduces an automatic atlas-based approach for performing virtual septoplasties. A cohort of 47 healthy subjects and 26 NAO patients was investigated. An atlas of healthy nasal geometry was constructed. The automatic virtual septoplasty method consists of a multi-stage registration approach to fit the atlas to a target NAO patient, automatically segment the patient’s septum and airway, and deform the patient image to have a non-deviated septum. Our automatic virtual septoplasty method straightened the septum successfully in 18 out of 26 NAO patients (69% of cases). In these cases, the ratio of the higher to the lower airspace cross-sectional areas in the left and right nasal cavities improved from 1.47 ± 0.45 to 1.16 ± 0.33 in the region surrounding the septal deviation, showing that the nasal airway became more symmetric after virtual septoplasty. This automated virtual septoplasty technique has the potential to greatly reduce the effort required to perform computational fluid dynamics (CFD) analysis of nasal airflow for NAO surgical planning. Future studies are needed to investigate if virtual surgery planning using this method is predictive of subjective symptoms in NAO patients after septoplasty.

Children with cancer often develop leukopenia which may impair wound healing and increase surgical complication rates. When leukopenic children with cancer develop an acute surgical condition, the optimal management strategy remains unclear. This study examined the effect of preoperative leukopenia on postoperative outcomes in children with cancer who underwent an appendectomy or cholecystectomy.We retrospectively identified cancer patients undergoing an appendectomy or cholecystectomy from the National Surgical Quality Improvement Program-Pediatric database from 2012-2018. Demographics and perioperative characteristics were compared by leukopenia status (WBC4 vs. ≥4 × 10^3/mL). Postoperative length of stay (LOS) and 30-day composite complications, including infections, reoperations, and readmissions, were analyzed for each procedure using multivariate regression.There were 227 children who underwent an appendectomy and 101 children who underwent a cholecystectomy. Leukopenia was seen in 93 (41.0%) appendectomy and 57 (56.4%) cholecystectomy cases. Nineteen (8.4%) appendectomy patients and six (5.9%) cholecystectomy patients developed a postoperative complication. The median postoperative LOS was 2 days (IQR 1-6 days) for appendectomy and 1 day (IQR 1-2.5 days) for cholecystectomy cases. After multivariate analyses, leukopenia was not associated with increased postoperative complications after an appendectomy (OR 0.55, P = 0.36) or cholecystectomy (OR 0.39, P = 0.37). There was no significant difference in postoperative LOS based on leukopenia status for children who underwent an appendectomy (P = 0.82) or cholecystectomy (P = 0.37).In pediatric cancer patients, leukopenia was not associated with increased short-term postoperative complications or longer postoperative LOS after either an appendectomy or cholecystectomy. These results support that operative management can be performed safely in pediatric appendicitis and cholecystitis in leukopenic cancer patients.

Background Lenacapavir (LEN), a potent first-in-class inhibitor of HIV-1 capsid function, is in development as a long-acting agent for treatment and prevention of HIV-1. Methods CAPELLA is an ongoing, phase 2/3 study in heavily treatment-experienced (HTE) people with HIV-1 (PWH) with multidrug-resistance. 36 participants were randomized (2:1) to add oral LEN or placebo to their failing regimen. At D15, those on oral LEN received subcutaneous (SC) LEN 927 mg (Q6M); those on placebo started the oral LEN lead-in, followed by SC Q6M. All randomized participants initiated an investigator-selected, optimized background regimen (OBR) at D15. An additional 36 participants started OBR concurrent with LEN (oral lead-in → SC) in a non-randomized cohort. We report the Week (W) 52 efficacy and safety results from both cohorts. Results Of 72 participants enrolled, 25% were female, 38% Black, median age 52 years, 64% had CD4 < 200 cells/µL, 46% had HIV-1 resistant to all 4 major classes (NRTI, NNRTI, PI, INSTI), and 53% had OBR with 1 or no fully active agents. At W52, 78% (56/72) achieved VL< 50 c/mL and 82% (59/72) achieved VL< 200 c/mL via FDA Snapshot algorithm. CD4 count increased by a median 84 cells/µL (Q1 to Q3: 21 to 153) and the proportion of participants with CD4 count ≥200 cells/ul increased from 36% at baseline to 68% at W52. Ten participants had emergent LEN resistance (8 previously reported); 4 of 10 subsequently suppressed. The median (range) duration of follow up on LEN was 71 (13–111) weeks. One participant discontinued due to injection site nodule (Grade 1). The most common injection site reaction (ISR) was swelling (28% [20/72] and 17% [12/70] after the 1st and 2nd SC doses, respectively). Most ISRs were mild or moderate. The most common AEs (excluding injection site reactions) were nausea and diarrhea (14% each). Conclusion In HTE PWH, subcutaneous LEN was well tolerated and in combination with OBR led to high and sustained rate of virologic suppression at W52. These results support the potential role for LEN for treatment of multi-drug resistant HIV-1 infection. Disclosures Sorana Segal-Maurer, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|JANSSEN THERAPEUTICS: Honoraria|ViiV: Honoraria Benoit Trottier, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Jason Brunetta, M.D., Gilead Canada: Advisor/Consultant|Gilead Canada: Honoraria|Gilead Canada: Conference Attendance Sponsorship|Viiv Canada: Advisor/Consultant Hui Wang, PhD, Gilead Sciences: Employment|Gilead Sciences: Stocks/Bonds Nicolas A. Margot, MA, Gilead Sciences: Employment|Gilead Sciences: Stocks/Bonds Hadas Dvory-Sobol, PhD, Gilead Sciences: Employment|Gilead Sciences: Stocks/Bonds Martin S Rhee, MD, Gilead Sciences: Stocks/Bonds Jared Baeten, MD, PhD, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Jean-Michel Molina, MD; PhD, GIlead: Board Member|GIlead: Grant/Research Support|Merck: Board Member|Merck: Expert Testimony|ViiV: Board Member.

Objective The rate of transmission of SARS-CoV-2 from mothers to infants in the peri- and post-natal period remains an area of ongoing investigation. This study aims to determine rates of development of clinically significant COVID-19 disease within 1 month among infants born to symptomatic and asymptomatic SARS-CoV-2 positive mothers. Materials and methods This was a single-center, retrospective cohort study of all infants born to SARS-CoV-2 positive mothers who were admitted to the Well Baby Nursery (WBN) at New York University Langone Hospital-Brooklyn from 23 March–23 September 2020. Infants born to asymptomatic mothers were allowed to room-in, while infants born to mothers with symptoms of SARS-CoV-2 were isolated and discharged home to an alternate primary caregiver. A phone follow-up program contacted mothers at 2 weeks and 1 month post discharge to inquire about newborn symptoms, maternal symptoms, personal protective equipment (PPE) usage, and any presentations to care. Medical records were also reviewed for clinic and hospital visits to determine if exposed infants developed any symptoms following discharge. Results Of 1903 deliveries during the study period, 131 mothers (21 symptomatic, 110 asymptomatic) tested positive for SARS-CoV-2 and had infants admitted to the WBN. 57 infants (21 born to symptomatic mothers, 36 born to asymptomatic mothers) were tested prior to discharge, and none were positive. 121 of 133 infants had at least 1 follow up call in the study period. Of these, 31 had symptoms potentially concerning for SARS-CoV-2 infection or Multisystem Inflammatory Syndrome in Children, and 19 presented to medical care for these symptoms. 4 infants had SARS- CoV-2 testing after discharge, and none were positive. 2 infants were admitted to the hospital for fever but neither had a positive SARS-CoV-2 result. 65% of mothers reported always adhering to PPE recommendations. Conclusion Our results suggest that infants born both to symptomatic and asymptomatic mothers are unlikely to develop clinically significant COVID-19 disease in the peri- and post-natal periods.

No studies exist comparing various femoral artery cannula sizes in children on ECMO. We hypothesize that smaller arterial cannulas provide adequate flow in children while decreasing vascular complications.We performed a retrospective review of the ELSO database from 2012-2017. We included children undergoing femoral venoarterial ECMO between ages 12 and 18 years and weighing more than 30 kg. Arterial cannula sizes were grouped as: 15-16Fr, 17-18Fr, 19-20Fr and ≥21Fr. Arterial pump flow, bleeding complications, limb ischemia, and mechanical complications were compared by cannula size. Distal perfusion catheter and percutaneous placement were also compared for complications.A total of 429 patients were included with 28.2% 15-16Fr, 32.2% 17-18Fr, 22.8% 19-20Fr, and 16.8% ≥ 21Fr arterial femoral cannulas. Median age was lower in the 15-16Fr group compared to the largest cannula group (14.7 years vs 15.5 years, p 0.01). The overall mean arterial flow was 57.4 +/- 17.0 mL/kg/min with no difference in mean arterial flow rates among the cannula size groups (p = 0.85). There were no significant differences in all complications, bleeding or mechanical complications by arterial cannula size group. However, there was an increased risk of limb ischemia in the ≥21Fr group compared to the 15-16Fr group (OR 4.38, 95% CI 1.24-15.43; p = 0.02). Distal perfusion catheter was shown to increase the risk of mechanical complications (OR 1.78; 95% CI 1.03-3.07; p = 0.04) but did not make a statistically significant difference in limb ischemia (OR 0.37; 95% CI 0.12-1.11; p = 0.07).Review of the ELSO database demonstrates that the use of larger arterial cannulas compared to 15-16Fr cannulas are not needed to achieve similar pump flows for hemodynamic support but the largest cannula sizes may increase the risk of ischemic complications.

BACKGROUND The American Academy of Dermatology and Food and Drug Administration recommend consultation with a dermatologist prior to undergoing laser tattoo removal. However, non-healthcare professionals offer tattoo removals. Understanding the information available on the Internet for patients regarding tattoo removal is important given that individuals are increasingly consulting digital sources to make decisions regarding skin care. Prior research has identified that YouTube contains misinformation on dermatologic health. OBJECTIVE Here, we present a cross-sectional study that determines that sources of information in YouTube videos that discuss tattoo removals and describe the content presented to viewers METHODS Using the query “tattoo removal”, we reviewed English-language YouTube videos that explicitly discussed tattoo removals. RESULTS We analyzed 162 YouTube videos and show that majority are presented by non-healthcare professionals (77%), with only 4 records of this subset recommending viewers to seek consultation from a dermatologist to ensure safe and adequate tattoo removals. CONCLUSIONS Based on our findings, we recommend dermatologists and other healthcare professionals to provide high-quality, evidence-based information to viewers regarding tattoo removals. CLINICALTRIAL N/A