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Purpose:In this first-in-human study (NCT03564691) in advanced solid tumors, we investigated a novel first-in-class human IgG4 monoclonal antibody targeting the immunoglobulin-like transcript 4 (ILT4) receptor, MK-4830, as monotherapy and in combination with pembrolizumab.Patients and Methods:Patients with histologically/cytologically confirmed advanced solid tumors, measurable disease by RECIST v1.1, and evaluable baseline tumor sample received escalating doses of intravenous MK-4830 every 3 weeks as monotherapy (parts A and B) and in combination with pembrolizumab (part C). Safety and tolerability were the primary objectives. Pharmacokinetics, objective response rate per RECIST v1.1, and molecular biomarkers were also evaluated.Results:Of 84 patients, 50 received monotherapy and 34 received combination therapy. No dose-limiting toxicities were observed; maximum tolerated dose was not reached. MK-4830 showed dose-related target engagement. Eleven of 34 patients in the dose-escalation phase who received combination therapy achieved objective responses; 5 previously had progressive disease on anti–PD-1/PD-L1 therapies. Exploratory evaluation of the association between response and pretreatment gene expression related to interferon-gamma signaling in tumors suggested higher sensitivity to T-cell inflammation with combination therapy than historically expected with pembrolizumab monotherapy, with greater response at more moderate levels of inflammation.Conclusions:This first-in-class MK-4830 antibody dosed as monotherapy and in combination with pembrolizumab was well tolerated with no unexpected toxicities, and demonstrated dose-related evidence of target engagement and antitumor activity. Inflammation intrinsic to the ILT4 mechanism may be facilitated by alleviating the myeloid-suppressive components of the tumor microenvironment, supporting the target of ILT4 as a potential novel immunotherapy in combination with an anti–PD-1/PD-L1 agent.

Objectives Dolutegravir/lamivudine (DTG/3TC) is indicated for treatment-naive and experienced people with HIV; however, questions remain about its utility in a test-and-treat setting because of potential transmitted resistance and baseline hepatitis B virus (HBV) co-infection. We present feasibility and efficacy of DTG/3TC in newly diagnosed individuals in a test-and-treat setting. Design The single-arm STAT study evaluated DTG/3TC in a US test-and-treat setting. Methods Eligible adults initiated DTG/3TC 14 days or less after HIV-1 diagnosis without availability of baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance less than 30 ml/min per 1.73 m2, participants remained on study with treatment modification. Efficacy endpoints included proportions of participants with HIV-1 RNA less than 50 copies/ml at Week 24, regardless of antiretroviral regimen, among all participants (intention-to-treat exposed) and those with available HIV-1 RNA data (observed). Results Of 131 participants enrolled, 8% were female and 50% were non-white. Through Week 24, treatment was modified in eight participants [five with HBV co-infection, one with baseline M184V, one for adverse event (rash), one participant decision]. At Week 24, 78% (102/131) of all participants and 92% (102/111) of those with available data achieved HIV-1 RNA less than 50 copies/ml. Incidence of drug-related adverse events was low (7%); no drug-related serious adverse events occurred. Conclusion These data demonstrate the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting, with therapy adjustments for baseline resistance or HBV co-infection occurring safely via routine clinical care as needed [ClinicalTrials.gov, NCT03945981; see Supplemental Digital Content 1, video abstract (Video abstract summarizing the STAT study design and results), http://links.lww.com/QAD/C189].

Supplemental Digital Content is Available in the Text., Background: With the highest rates of HIV/AIDS in the United States, Black Americans are still underrepresented in HIV medical research. Setting: BRAAVE (NCT03631732) is a randomized, phase 3b, multicenter, open-label US study. Methods: Adults identifying as Black or African American and virologically suppressed on 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus third agent were randomized (2:1) to switch to open-label bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) once daily or stay on baseline regimen (SBR) for 24 weeks, after which SBR had delayed switch to B/F/TAF. Resistance to non-NRTIs, protease inhibitors, and/or NRTIs was permitted; integrase strand transfer inhibitor resistance was exclusionary. Primary endpoint was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 24 (snapshot algorithm; noninferiority margin of 6%). Results: Of 558 screened, 495 were randomized/treated (B/F/TAF n = 330; SBR n = 165). Overall, 32% were ciswomen, 2% transwomen, and 10% had an M184V/I mutation. At week 24, 0.6% on B/F/TAF vs 1.8% on SBR had HIV-1 RNA ≥50 copies/mL (difference −1.2%; 95% confidence interval −4.8% to 0.9%), demonstrating noninferiority of B/F/TAF vs SBR. Proportions with HIV-1 RNA

Despite numerous publications emphasizing the value of dose finding, drug development in oncology is dominated by the mindset that higher dose provides higher efficacy. Examples of dose finding implemented by biopharmaceutical firms can change this mindset. The purpose of this article is to outline a pragmatic dose selection strategy for immuno-oncology (IO) and other targeted monoclonal antibodies (mAbs). The approach was implemented for pembrolizumab. Selecting a recommended phase II dose (RP2D) with a novel mechanism of action is often challenging due to uncertain relationships between pharmacodynamics measurements and clinical end points. Additionally, phase I efficacy and safety data are generally inadequate for RP2D selection for IO mAbs. Here, the RP2D was estimated based on phase I (clinical study KN001 A and A2) pharmacokinetics data as the dose required for target saturation, which represents a surrogate for maximal pharmacological effect for antagonist mAbs. Due to limitations associated with collecting and analyzing tumor biopsies, characterizing intratumoral target engagement (TE) is challenging. To overcome this gap, a physiologically-based pharmacokinetic model was implemented to predict intratumoral TE. As tumors are spatially heterogeneous, TE was predicted in well-vascularized and poorly vascularized tumor regions. Additionally, impact of differences in target expression, for example, due to interindividual variability and cancer type, was simulated. Simulations showed that 200 mg every 3 weeks can achieve ≥ 90% TE in clinically relevant scenarios, resulting in the recommendation of 200 mg every 3 weeks as the RP2D. Randomized dose comparison studies (KN001 B2 and D) showing similar efficacy over a fivefold dose/exposure range confirmed the RP2D as the pivotal dose.

Ankle arthrodesis (AA) provides reliable pain relief, good patient satisfaction scores, and improved overall function. However, this procedure has been associated with numerous complications and sequelae, such as pseudoarthrosis, malunion, gait abnormalities, increased demand on surrounding joints, and a long period of convalescence. Conversion to total ankle arthroplasty (TAA) is a potential option in the management of these complex and challenging situations. The purpose of this study is to investigate the outcomes of AA conversion to TAA. A systematic review of electronic databases was performed. Six studies involving 172 ankles met inclusion criteria. The weighted mean preoperative Visual Analogue Scale (VAS) score at the time of TAA conversion was 7.8 and the weighted mean postoperative VAS score at the time of final follow-up was 2.5. The weighted mean preoperative AOFAS score at the time of TAA conversion was 32 and the weighted mean postoperative AOFAS score at the time of final follow-up was 72.4. The rate of salvage tibiotalocalcaneal arthrodesis was 2.3% and rate of transtibial amputation was also 2.3% after attempted conversion from initial AA to TAA. Conversion of AA to TAA appears to be a viable option to improve patient outcomes and prevent extensive hindfoot arthrodesis and transtibial amputation. More prospective studies with consistent reporting of outcomes, complications, and revision rates with long-term follow-up are needed.

Total ankle replacement has become a viable alternative to ankle arthrodesis in the surgical management of advanced ankle arthritis. Total ankle replacement has generally been reserved for patients who are older and for those who will have a lower demand on the replacement. The purpose of the current study is to review patient outcomes, complications, and implant survival in patients younger than 55 years who underwent total ankle replacement at a single institution. A single-center chart and radiographic review was performed of consecutive patients who underwent total ankle replacement for treatment of end-stage ankle arthritis. All surgeries were performed by 1 of 5 fellowship-trained foot and ankle surgeons at a single institution. A total of 51 patients met inclusion criteria with a mean follow-up of 31.2 months (SD = 16.2). Implant survival was 94%, There were 7 major complications (13%) requiring an unplanned return to the operating room and 8 minor complications (15%) that resolved with conservative care. The results of this study show that total ankle replacement is a viable treatment option for patients younger than 55 years. Levels of Evidence: A retrospective case series

Objectives Burden of illnesses has been described in the literature using the health-related quality of life (HRQoL) in people with chronic conditions. However, the studies reporting trends of burden are sparse. The aim of this study was to explore the trends of burden of chronic illness from the perspective of HRQoL. Study design This was a secondary analysis of administrative database. Methods Seven data sets of the Canadian Community Health Survey from 2001 to 2014 were obtained for the analysis. Multiple linear and logistic regression models were used on each data set to assess the burden of illness on the Health Utilities Index Mark III (HUI3), life satisfaction (LS), and perceived health (PH). Results People with the effect of stroke constantly had low scores on the HUI3, LS, and PH. Regression analyses revealed that arthritis, back problem, and mood disorder have greater impact on the HUI3 score. Effect of stroke, mood disorder, and anxiety disorder stably had the largest negative impact on LS, while chronic obstructive pulmonary disease (COPD), effect of stroke, and cancer had the largest effect on PH. Conclusion This study identified that arthritis, back pain, mood disorder, effect of stroke, and COPD constantly have high burden on health outcomes compared with other chronic condition over the past decade.

Naviculocuneiform (NC) joint arthrodesis is an effective procedure to treat pain and provide stability to the medial column. Various forms of fixation have been described for NC arthrodesis. Despite this, the available literature is scant and questions remain regarding nonunion rate and contributory factors. A systematic review of the literature was undertaken to determine the rate of nonunion for NC joint arthrodesis. Seven studies involving 139 NC joint arthrodeses met inclusion criteria. The nonunion rate was 6.5% at a weighted mean follow-up of 73.2 months. There is insufficient evidence to provide a practice guideline based on the current literature. Adequately powered prospective clinical trials comparing well-matched patient groups with long-term follow-up are required to limit systematic error and enhance external validity. Specific outcomes measures should include union, functional assessment, complications, and cost-benefit analysis.

Social distancing protocols during the COVID-19 pandemic have resulted in a rapid expansion of telemedicine. It has allowed patients to save time and money on clinic visits, and physicians to communicate with patients who live remotely. Telemedicine has also been valuable in plastic surgery during initial consultations, transfers, and follow up visits. However, given the often-sensitive nature of plastic surgery, the professionalism and expectations of telemedicine have to be reviewed. A comprehensive literature search of the MEDLINE, PubMed, Google Scholar, EMBASE, and Cochrane Central Register of Controlled Trials was conducted for studies published through October 2020 with multiple search terms related to telemedicine and its use in plastic surgery. Data on the effectiveness, challenges, and professionalism of telemedicine were collected. Our review suggests that telemedicine can be an effective mode of communication in many realms of plastic surgery, including cleft care and craniofacial deformities. However, many plastic surgeons are unfamiliar with the existing platforms, and there are no clear guidelines on the most optimal platforms. Physicians have to recognize that patients might have low digital health literacy or may not even possess digital device for telemedicine. There also needs to be an overall improvement in patient education. Given that telemedicine use will continue to increase after the COVID-19 pandemic, regulations on Health Insurance Portability and Accountability Act-compliant platforms and specific guidelines on telemedicine visits, such as undressing, chaperones, privacy matters, need to be established while maintaining a professional relationship between the patient and the physician.

The Scandinavian Total Ankle Replacement (STAR, DJO, Dallas, TX) is a three-part, mobile-bearing ankle implant that has been approved by the Food and Drug Administration for implantation in the United States. Due to the prevalent usage and length of time that the STAR implant has been available, it is one of the most reviewed and researched TAR prostheses. The three-piece design of the STAR prosthesis consists of a flat metallic tibial component with two dorsal dowels, a cylindrical metallic talar component with a small central ridge and a central component composed of high-density polyethylene gliding core. As we become more sophisticated with our techniques and implants, we may find that certain indications are evolving. Currently, implantation of the STAR may be used for the treatment of end-stage ankle arthritis in adult patients. Contraindications include active ankle infection, neuropathic joint, significant areas of avascular osteonecrosis of the talus or distal tibia, complete paralysis of the operative limb, inadequate soft tissue coverage, vascular insufficiency, severe deformity that cannot be corrected, and skeletal immaturity. In this chapter, we provide an in-depth description of the procedure technique including surgical pearls from the authors. To date, a number of studies have reviewed the long-term results and 15-year survivorship of the STAR. Additional long-term studies are needed to further understand the survivability of this implant.

Karnataka, a state in south India, reported its first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on March 8, 2020, more than a month after the first case was reported in India. We used a combination of contact tracing and genomic epidemiology to trace the spread of SARS-CoV-2 in the state up until May 21, 2020 (1578 cases). We obtained 47 full genomes of SARS-CoV-2 which clustered into six lineages (Pangolin lineages-A, B, B.1, B.1.1, B.4, and B.6). The lineages in Karnataka were known to be circulating in China, Southeast Asia, Iran, Europe and other parts of India and are likely to have been imported into the state both by international and domestic travel. Our sequences grouped into 12 contact clusters and 11 cases with no known contacts. We found nine of the 12 contact clusters had a single lineage of the virus, consistent with multiple introductions and most (8/12) were contained within a single district, consistent with local spread. In most of the twelve clusters, the index case (9/12) and spreaders (8/12) were symptomatic. Of the 47 sequences, 31 belonged to the B/B.6 lineage, including seven of eleven cases with no known contact, this is consistent with the ongoing transmission of this lineage in the state. Genomic epidemiology of SARS-CoV-2 in Karnataka is consistent with multiple introductions of the virus followed by local transmission in parallel with ongoing viral evolution. This is the first study from India combining genomic data with epidemiological information emphasizing the need for an integrated approach to outbreak response.

Background Life Goals Programme (LGP) was developed as a psychological intervention for bipolar disorder, with its structured 6-session psychoeducation phase (Phase 1) targeting understanding of the disorder, medication adherence, early warning signs, and coping with symptoms and triggers. The present study tested the efficacy of Phase 1 of the LGP on symptom recovery and moment-by-moment mood stability, as well as medication adherence and quality of life. Methods Adults with bipolar disorder were randomly allocated to the LGP condition (six weekly group sessions) or the waitlist condition (six weeks of standard care, followed by the same LGP intervention). Participants were assessed before and after treatment, and at 6-month follow up. Waitlist participants were additionally assessed at baseline. Assessment included a clinical interview (SCID, MADRS, YMRS, and HAM-A), self-reported questionnaires, and 6-day experience sampling assessment on a mobile device. Results 64 out-patients with bipolar disorder (44 Bipolar I and 20 Bipolar II subtypes) participated in this study. LGP was well received and attended. Following LGP, there were significant improvements in knowledge about illness and level of anxiety, which were of large effect sizes and sustained at 6-month follow-up. Experience sampling assessment revealed small but significant improvements in moment-by-moment mood stability. Improvement in medication adherence was significant at 6 months and was of a moderate-to-large effect size. Changes in anxiety and mood stability were significantly greater following LGP than standard care. Limitations Our results warrant further testing against active control. Conclusions There was a robust improvement in emotional regulation following the 6-week LGP.

Ankle fractures are common orthopedic injuries. Although operative indications and subsequent stabilization of these fractures have not significantly changed, postoperative protocols remain highly variable. Effects of early weight bearing (EWB) on fracture characteristics in operatively stabilized bimalleolar and bimalleolar equivalent ankle fractures remain poorly publicized. This study seeks to clarify postoperative fracture union rates, rates of hardware loosening or failure, and radiographic medial clear space changes when comparing EWB to late weight bearing (LWB) following open reduction and internal fixation (ORIF). A total of 95 patients with either bimalleolar (66%) or bimalleolar equivalent (34%) fractures who underwent ORIF were retrospectively reviewed. Weight bearing was allowed at three weeks in the EWB group and when signs of radiographic union were noted in the LWB group. Postoperatively, patients were evaluated at regular intervals for fracture union, signs of implant failure, and evidence of medial clear space widening radiographically. There were 38 patients (40%) in the EWB group and 57 patients (60%) comprising the LWB cohort. There were no significant demographic differences between groups. The EWB group on average began to weight bear at 3.1 + 1.4 weeks postoperatively, whereas the LWB group began at 7.2 + 2.1 weeks postoperatively (p0.1 at all time intervals) were not notably different between groups. No differences in medial clear space were detected at any postoperative interval between groups (p>0.1 at all time intervals). This study suggests that EWB at three weeks postoperatively does not increase markers of radiographic failure compared to six weeks of non-weight bearing (NWB), which has been regarded as the gold standard of treatment to allow for healing; this may represent an improvement to rehabilitation protocols after bimalleolar ankle ORIF of unstable ankle fractures.

Crohn’s disease exacerbations can often be associated with bacterial infections causing gastroenteritis. We report a child who experienced exacerbation of his Crohn’s disease associated with a positive stool culture forEdwardsiella tarda (E. tarda). Endoscopy showed features of moderate inflammation similar to exacerbation of Crohn’s disease. The patient was treated simultaneously with intravenous steroids and antibiotics, and his symptoms resolved. This case report highlights the importance of clinicians being able to promptly recognize and treat concurrent bacterial infections in Crohn’s disease exacerbations.

There is a lack of consensus in the literature regarding optimal treatment methods for Lisfranc injuries, and recent literature has emphasized the need to compare open reduction and internal fixation (ORIF) with primary arthrodesis (PA). The purpose of the current study is to compare reoperation and complication rates between ORIF and PA following Lisfranc injury in a private, outpatient, orthopaedic practice. A retrospective chart review was performed on patients undergoing operative intervention for Lisfranc injury between January 2009 and September 2015. A total of 196 patients met the inclusion criteria (130 ORIF, 66 PA), with a mean follow-up of 61.3 and 81.7 weeks, respectively. The ORIF group had a higher reoperation rate than the PA group, due to hardware removal. When hardware removals were excluded, the reoperation rate was similar. Postsurgical complications were compared between the 2 groups with no significant difference. In conclusion, ORIF and PA had similar complication rates. When hardware removals were excluded, the reoperation rates were similar, although hardware removals were more common in the ORIF group compared with the PA group. Levels of Evidence: Level III

Background Black Americans are disproportionately impacted by HIV. The BRAAVE 2020 study, evaluated the safety and efficacy of switching to the guidelines-recommended single-tablet regimen bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) in Black adults through week (W) 48. Methods Adults with HIV who self-identified as Black or African American and were virologically suppressed on 2 NRTIs plus a 3rd agent were randomized (2:1) to switch to open-label B/F/TAF once daily or stay on their baseline regimen (SBR). Prior virologic failure was allowed except failure on an INSTI. Prior resistance to NNRTIs, PIs and/or NRTIs was permitted except K65R/E/N, ≥3 thymidine analog mutations or T69-insertions. Primary INSTI-resistance was excluded. SBR participants switched to B/F/TAF at W24. Efficacy was assessed at the W24 (1○ endpoint, noninferiority margin 6%) and at W48 as the proportion with HIV-1 RNA ≥ 50 c/mL by FDA Snapshot and by changes in CD4 count. Safety was assessed by adverse events (AE) and lab results. Results 495 were randomized and treated (B/F/TAF n=330, SBR n=165): 32% cis women, 2% transgender women, median age 49 y (range 18-79), 10% had pre-existing M184V/I mutation (Table 1), and 62% lived in the US South. At W24, 1% (2/328) on B/F/TAF vs 2% (3/165) on SBR had HIV-1 RNA ≥50 c/mL (difference -1.2%; 95% CI -4.8% to 0.9%) demonstrating noninferiority of B/F/TAF; 2 with pre-existing primary INSTI resistance were excluded from analysis. 163 assigned to SBR completed W24 and switched to B/F/TAF (SBR to B/F/TAF). At W48 1% (3/328) originally randomized to B/F/TAF and 0 SBR to B/F/TAF had HIV-1 RNA ≥ 50 c/mL (Table 2). The presence of baseline NRTI resistance did not affect the efficacy of B/F/TAF. No treatment emergent resistance was detected. The mean (SD) changes in CD4 were +7 cells/mm3 (189) for B/F/TAF and -8 cells/mm3 (159) for SBR to B/F/TAF. Median (IQR) weight increased 0.9 kg (-1.5, 4.1) and 0.6 kg (-1.0, 3.1) for B/F/TAF and SBR to B/F/TAF groups, respectively. Study drug-related AEs occurred in 10% of participants while on B/F/TAF; most were grade 1. Table 1. Table 2. Conclusion Switching to B/F/TAF was highly effective for Black adults regardless of baseline regimen or pre-existing NRTI resistance and was associated with few treatment related AEs or discontinuations. Disclosures Debbie Hagins, MD, Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Janssen (Grant/Research Support)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member)Viiv Healthcare (Consultant, Grant/Research Support, Advisor or Review Panel member) Princy Kumar, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Michael Saag, MD, Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator)Merck (Consultant, Grant/Research Support)Proteus (Grant/Research Support)Viiv Healthcare (Consultant, Grant/Research Support) Anson K. Wurapa, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)GlaxoSmithKline (Grant/Research Support)Janssen (Grant/Research Support, Advisor or Review Panel member)Pfizer (Grant/Research Support) Indira Brar, MD, Gilead (Speaker’s Bureau)janssen (Speaker’s Bureau)ViiV (Speaker’s Bureau) Daniel Berger, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Olayemi Osiyemi, M.D, GlaxoSmithKline (Advisor or Review Panel member, Speaker’s Bureau)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Corrilynn Hileman, MD, Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator) Moti Ramgopal, MD FACP FIDSA, AbbVie (Speaker’s Bureau)Allergan (Speaker’s Bureau)Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Speaker’s Bureau)Janssen (Speaker’s Bureau)Merck (Consultant)Viiv Healthcare (Consultant) Cheryl McDonald, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen (Grant/Research Support)Merck (Grant/Research Support, Speaker’s Bureau)Viiv Healthcare (Grant/Research Support) Christiana Blair, MS, Gilead Sciences (Employee, Shareholder) Kristen Andreatta, MSc, Gilead Sciences (Employee, Shareholder) Sean E. Collins, MD, MS, Gilead Sciences (Employee) Diana M. Brainard, MD, Gilead Sciences (Employee) Hal Martin, MD, MPH, Gilead Sciences Inc. (Employee, Shareholder)

The article offers a brief history of pitted keratolysis (PK), research regarding PK etiology, evaluation of PK, and current treatment modalities. The main objective of this article focuses on the current literature on PK, its presentation and symptomatology, prevalence, and available therapeutic options. We present a case report and review on PK of a patient treated with an over the counter antiperspirant, topical erythromycin, oral erythromycin, and proper education on hygiene, with complete resolution and without recurrence after a follow up of greater than 12 months.

Since the inception of the first surgical training system by Sir William Stewart Halsted, resident surgical skill development has been promulgated in teaching hospitals. Currently, the Council on Podiatric Medical Education does not mandate the availability of a cadaver lab as a residency curriculum requirement. The purpose of the present study is to assess the structure of the cadaver lab and availability in the current podiatric surgical training programs. A survey was sent electronically to 229 American Association of Colleges of Podiatric Medicine–approved residency programs, excluding OhioHealth, across all residency programs. A total of 173 (6.9%) residents from 74 (32.3%) residency programs completed the survey. This survey analyzed the characteristics and perception of the current state of cadaver lab in podiatric residency. The most reported type of cadaver labs available were medical company sponsored and hospital sponsored. Other hands-on training, including inanimate simulators (n = 24) and animal models (n = 5), was also reported. Overall, 87.9% of the surveyed residents found that cadaver lab is either extremely beneficial (57.8%) or somewhat beneficial (30.1%). The most important factors perceived in a successful cadaver lab were faculty instruction (n = 78), accessibility of lab (n = 46), and availability of instrumentation/hardware (n = 26). This qualitative survey is the first study to address the uniformity, perception, and potential value of the cadaver lab in a podiatric surgical residency.

Background: Current treatment for HIV-infected individuals with renal failure on haemodialysis frequently requires complex regimens with multiple pills. A daily single-tablet regimen of coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide is approved in Europe, the USA, and in other regions for use in HIV-1-infected individuals with mild-to-moderate chronic kidney disease (creatinine clearance 30–69 mL/min). We aimed to assess the safety, efficacy, and pharmacokinetics of this regimen in HIV-infected adults with end-stage renal disease on chronic haemodialysis. Methods: We did an open-label, single-arm, multicentre, phase 3b trial at 26 outpatient clinics in Austria, France, Germany, and the USA. Participants were HIV-1-infected adults with end-stage renal disease (creatinine clearance

The development of hallux interphalangeal joint (IPJ) arthritis after an arthrodesis of the first metatarsophalangeal joint has been established in the literature. However, the significance has not been well reported. A retrospective, radiographic review of patients who had undergone a first metatarsophalangeal joint arthrodesis was performed. The Coughlin classification for degree of arthritic degeneration, hallux abductus angle, and hallux interphalangeus angle were measured in 107 radiographs of 103 patients preoperatively and postoperatively. Postoperative angles were measured immediately following surgery at approximately 6 weeks, 3 months, 6 months, 12 months, and 24 months. We found that the hallux abductus angle had decreased in the patients postoperatively; however, the hallux abductus interphalangeus angle increased on average after first metatarsophalangeal fusion. The majority of patients started with a Coughlin classification I of the hallux IPJ, which remained unchanged over the postoperative period, with no statistically significant difference in IPJ degeneration in the patients with or without fusion of the first metatarsophalangeal joint. In addition, no patients had a symptomatic hallux IPJ postoperatively within our limited study period. Further prospective studies would be beneficial with longer follow-up times to assess IPJ degeneration following first metatarsophalangeal joint fusions. Levels of Evidence: Level III: Retrospective, comparative study

Hallux interphalangeal joint arthrodesis is an effective procedure to treat pain and provide stability and is often performed for intrinsic pain to the hallux interphalangeal joint. Additionally, this procedure is typically used in concert with the Jones tenosuspension. Although this as an accepted technique, the available data are scant, and questions remain regarding nonunion rates and contributory factors to poor healing. A systematic review of the reported data were undertaken to determine the rate of nonunion for hallux interphalangeal joint arthrodesis. Seven studies involving 313 hallux interphalangeal joint arthrodeses met the inclusion criteria. The nonunion rate was 28.3% at a weighted mean follow-up period of 8.4 months. The overall complication rate was 33.0%. Considering the increased rate of complications and nonunion rate for this commonly used procedure, additional prospective comparative analyses are needed regarding this topic to identify important patient demographic data and determine superior fixation constructs.

Background HIV treatment for individuals with end-stage renal disease (ESRD) on hemodialysis (HD) has previously required complex dose-adjusted regimens. We evaluated the safety and efficacy of single-tablet, once-daily elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) in people living with HIV (PLH) and ESRD on chronic HD. Methods Virologically suppressed adult PLH with ESRD on chronic HD for ≥ 6 months were switched to open-label E/C/F/TAF 150/150/200/10 mg once daily for 96 weeks. Efficacy was assessed as the proportion of participants who maintained virologic suppression (HIV RNA < 50 copies/mL) using the snapshot algorithm. Safety and participant satisfaction were assessed throughout the study. Results We enrolled 55 participants with median age 51 years (range 23–64) with median time on HD 6 years (range 1–17). In the per protocol analysis set, virologic suppression was maintained in 30 of 31 participants (96.8%, 95% CI [83.3%, 99.9%]) at week 96. In the full analysis set, virologic suppression was maintained in 30 of 55 participants (54.5%; 95% CI [40.6%, 68.0%]); one discontinued therapy due to lack of efficacy, and W96 data were unavailable for 24. Of the 24 participants lacking W96 data, 17 discontinued study drug early and 7 had missing data while on study drug; all had HIV RNA < 50 copies/mL at the last pre-week 96 check. Treatment-emergent AEs occurred in 53 (96.4%) participants, and study-drug-related AEs occurred in 7 (12.7%). Treatment-emergent AEs leading to premature study drug discontinuation occurred in 4 (7.3%) participants; two were considered study-drug-related (allergic pruritus and peripheral neuropathy in one participant each). No study-drug-related serious AEs were observed. 85.7% (30/35) of responding participants reported they were ‘much more satisfied’ with their regimen. Conclusion Single-tablet, once-daily E/C/F/TAF was effective in maintaining virologic suppression in PLH on chronic HD over 96 weeks of follow-up. E/C/F/TAF was well tolerated and was associated with improved participant satisfaction. These data demonstrate that E/C/F/TAF is a safe and effective alternative to more complicated regimens in PLH on chronic HD, with the potential to improve patient satisfaction and quality of life. Disclosures All authors: No reported disclosures.

Category: Midfoot/Forefoot Introduction/Purpose: Hallux interphalangeal joint (HIPJ) arthrodesis is an effective procedure to treat pain and provide stability, which is often performed for intrinsic pain to the HIPJ. Additionally, this procedure is typically employed in concert with the Jones tenosuspension. Despite that this is an accepted technique, the available literature is scant and questions remain regarding nonunion rates and contributory factors to poor healing. A systematic review of the literature was undertaken to determine the rate of nonunion for HIPJ arthrodesis. Methods: To acquire the highest quality and most relevant studies available, publications were eligible for inclusion only if they involved patients undergoing HIPJ arthrodesis. Studies additionally required mean follow-up of at least six weeks and inclusion of appropriate detail regarding complications, nonunion rates, and patient demographics. Ultimately, 7 studies involving 313 HIPJ arthrodeses met inclusion criteria. Results: A total of 291 patients with a weighted mean age of 48.9 were included. The nonunion rate was 28.3% at a weighted mean follow-up of 8.4 months. The overall complication rate was 33.0%. Conclusion: Considering the increased rate of complications and nonunions for this commonly employed procedure, additional prospective comparative analyses are needed to identify important patient demographics and to determine superior fixation constructs.

In this study, a pharmacodynamic model is developed, based on calcium-parathyroid hormone (PTH) homeostasis, which describes the concentration-effect relationship of a negative allosteric modulator of the calcium-sensing receptor (CaR) in rats. Plasma concentrations of drug and PTH were determined from plasma samples obtained via serial jugular vein sampling following single subcutaneous doses of 1, 5, 45, and 150 mg/kg to male Sprague-Dawley rats (n = 5/dose). Drug pharmacokinetics was described by a one-compartment model with first-order absorption and linear elimination. Concentration-time profiles of PTH were characterized using a model in which the compound allosterically modulates Ca(+2) binding to the CaR that, in turn, modulates PTH through a precursor-pool indirect response model. Additionally, negative feedback was incorporated to account for tolerance observed at higher dose levels. Model fitting and parameter estimation were conducted using the maximum likelihood algorithm. The proposed model well characterized the data and provided compound specific estimates of the K(i) and cooperativity constant (α) of 1.47 ng/mL and 0.406, respectively. In addition, the estimated model parameters for PTH turnover were comparable to that previously reported. The final generalized model is capable of characterizing both PTH-Ca(+2) homeostasis and the pharmacokinetics and pharmacodynamics associated with the negative allosteric CaR modulator. As such, the model provides a simple platform for analysis of drugs targeting the PTH-Ca(+2) system.

The purpose of this study was to develop a mechanism-based pharmacokinetic/pharmacodynamic model that describes the regulation of the parathyroid hormone (PTH)-Ca(2+) system in rats and humans. Temporal concentration data for endogenous PTH and Ca(2+) were extracted from literature for rats (normal adult males) and humans. In addition, exogenous PTH was administered subcutaneously to male Sprague-Dawley rats with jugular vein catheters, and plasma concentrations were measured over time. A mathematical model was developed and fitted simultaneously to endogenous PTH, Ca(2+), and exogenous PTH concentrations in rats. Ca(2+) concentrations were described using a turnover model, with its depletion being induced by a chelating agent, and PTH concentrations were characterized using a precursor-dependent indirect response model. The same structural model was used for fitting data obtained in humans. PTH stimulation was driven by occupancy of the Ca(2+) sensing receptor, and lowering of physiological Ca(2+) concentrations increased PTH secretion, with PTH profiles being adequately described by the model. PTH stimulatory capacity was baseline-dependent in rats [S(max_rats) = 34.8 x PTH(0)] and humans [S(max_humans) = 392/PTH(0)]. Modeling results suggest that normal rats are twice as sensitive to Ca(2+)-induced PTH stimulation compared with humans. In conclusion, the developed model adequately characterizes the PTH-Ca(2+) regulation across species and may be useful in the development of therapeutic drugs targeting this system.