Hydrochlorothiazide-Induced Exfoliative Rash and Sepsis.

Hydrochlorothiazide is a diuretic agent commonly used to treat hypertension, chronic edema from congestive heart failure or cirrhosis, and nephrogenic diabetes insipidus. Diuretics work by increasing urine output and are classified based on the specific renal segments they act on. As with all medications, they are not without their side effects. The most significant and serious include hypovolemia and electrolyte disturbances. Other more rare adverse effects include dermatitis and hypersensitivity reactions. We discuss an 86-year-old male who presented to the emergency room with complaints of lightheadedness and progressive exfoliating rash that began shortly after starting hydrochlorothiazide in an outpatient setting.

FInCH: FIJI plugin for automated and scalable whole-image analysis of protein expression and cell morphology.

Study of morphogenesis and its regulation requires analytical tools that enable simultaneous assessment of processes operating at cellular level, such as synthesis of transcription factors (TF), with their effects at the tissue scale. Most current studies conduct histological, cellular and immunochemical (IHC) analyses in separate steps, introducing inevitable biases in finding and alignment of areas of interest at vastly distinct scales of organization, as well as image distortion associated with image repositioning or file modifications. These problems are particularly severe for longitudinal analyses of growing structures that change size and shape. Here we introduce a python-based application for automated and complete whole-slide measurement of expression of multiple TFs and associated cellular morphology. The plugin collects data at customizable scale from the cell-level to the entire structure, records each data point with positional information, accounts for ontogenetic transformation of structures and variation in slide positioning with scalable grid, and includes a customizable file manager that outputs collected data in association with full details of image classification (e.g., ontogenetic stage, population, IHC assay). We demonstrate the utility and accuracy of this application by automated measurement of morphology and associated expression of eight TFs for more than six million cells recorded with full positional information in beak tissues across 12 developmental stages and 25 study populations of a wild passerine bird. Our script is freely available as an open-source Fiji plugin and can be applied to IHC slides from any imaging platforms and transcriptional factors.

Herpes Zoster Ophthalmicus Secondary to Periorbital Cellulitis.

Varicella zoster virus (VZV) infection, also commonly known as chickenpox, is a communicable disease most often contracted in childhood via contact, airborne, or droplet transmission. After about a two-week incubation period, patients can experience a prodromal phase, which includes a pruritic vesicular blistering rash with associated constitutional symptoms such as fever, headache, malaise, muscle aches, fatigue, and sore throat. Symptoms are often self-limiting and only require supportive care and observation. We report a case of a 54-year-old female who presented with an unusual background history and was found to have a rare manifestation of herpes zoster virus, presenting as herpes zoster ophthalmicus (HZO).

Evolving or immutable - phase I solid tumor trials in the era of precision oncology.

In the era of precision oncology (PO), systemic therapies for patients (pts) with solid tumors have shifted from chemotherapy (CT) to targeted therapy (TT) and immunotherapy (IO). This systematic survey describes features of trials enrolling between 2010 and 2020, focusing on inclusion criteria, type of dose escalation scheme (DES) utilized, and use of expansion cohorts (ECs). A literature search identified phase I studies in adults with solid tumors published January 1, 2000- December 31, 2020 from 12 journals. We included only studies enrolling between 2010 and 2020 to better capture the PO era. Two reviewers abstracted data; a third established concordance. Of 10,744 studies, 10,195 were non-topical or enrolled prior to 2010; 437 studies were included. The most common drug classes were TT (47.6%), IO (22%), and CT (6.9%). In studies which reported race, patients were predominantly white (61.7%) or Asian (25.7%), followed by black (6.5%) or other (6.1%). Heterogeneity was observed in the reporting and specification of study inclusion criteria. Only 40.1% of studies utilized ECs, and among the studies which used ECS, 46.6% were defined by genomic selection. Rule-based DES were used in 89% of trials; a 3+3 design was used in 80.5%. Of all drugs tested, 37.5% advanced to phase II, while 10.3% garnered regulatory licensure (for an indication tested in phase I). In the era of PO, TT and IO have emerged as the most studied agents in phase I trials. Rule-based DES, which are more relevant for escalating CT, are still chiefly utilized.

Evolving or Immutable - Phase I Solid Tumor Trials in the Era of Precision Oncology.

Purpose: In the era of precision oncology (PO), systemic therapies for patients (pts) with solid tumors have shifted from chemotherapy (CT) to targeted therapy (TT) and immunotherapy (IO). This systematic survey describes features of trials enrolling between 2010-2020, focusing on inclusion criteria, type of dose escalation scheme (DES) utilized, and use of expansion cohorts (ECs). Methods: A literature search identified phase I studies in adults with solid tumors published January 1, 2000 - December 31, 2020 from 12 journals. We included only studies enrolling between 2010-2020 to better capture the PO era. Two reviewers abstracted data; a third established concordance. Results: Of 10,744 studies, 10,195 were non-topical or enrolled prior to 2010; 437 studies were included. The most common drug classes were TT (47.6%), IO (22%), and CT (6.9%). In studies which reported race, patients were predominantly white (61.7%) or Asian (25.7%), followed by black (6.5%) or other (6.1%). Heterogeneity was observed in the reporting and specification of study inclusion criteria. Only 40.1% of studies utilized ECs, and among the studies which used ECS, 46.6% were defined by genomic selection. Rule-based DES were used in 89% of trials; a 3+3 design was used in 80.5%. Of all drugs tested, 37.5% advanced to phase II, while 10.3% garnered regulatory licensure (for an indication tested in phase I). Conclusion: In the era of PO, TT and IO have emerged as the most studied agents in phase I trials. Rule-based DES, which are more relevant for escalating CT, are still chiefly utilized.

Forgetting the Frail: National Trends in Vitamin D Prescription After Fragility Fracture-A Large Insurance Claims Database Study.

INTRODUCTION: Vitamin D plays a critical role in bone health, affecting bone mineral density and fracture healing. Insufficient serum vitamin D levels are associated with increased fracture rates. Despite guidelines advocating vitamin D supplementation, little is known about the prescription rates after fragility fractures. This study aims to characterize vitamin D prescription rates after three common fragility fractures in patients older than 50 years and explore potential factors influencing prescription rates. METHODS: The study used the PearlDiver Database, identifying patients older than 50 years with hip fractures, spinal compression fractures, or distal radius fractures between 2010 and 2020. Patient demographics, comorbidities, and vitamin D prescription rates were analyzed. Statistical methods included chi-square analysis and univariate and multivariable analyses. RESULTS: A total of 3,214,294 patients with fragility fractures were included. Vitamin D prescriptions increased from 2.50% to nearly 6% for all fracture types from 2010 to 2020. Regional variations existed, with the Midwest having the highest prescription rate (4.25%) and the West the lowest (3.31%). Patients with comorbidities such as diabetes, tobacco use, obesity, female sex, age older than 60 years, and osteoporosis were more likely to receive vitamin D prescriptions. DISCUSSION: Despite a notable increase in vitamin D prescriptions after fragility fractures, the absolute rates remain low. Patient comorbidities influenced prescription rates, perhaps indicating growing awareness of the link between vitamin D deficiency and these conditions. However, individuals older than 60 years, a high-risk group, were markedly less likely to receive prescriptions, possibly because of practice variations and concerns about polypharmacy. Educational initiatives and revised guidelines may have improved vitamin D prescription rates after fragility fractures. However, there is a need to raise awareness about the importance of vitamin D for bone health, particularly in older adults, and additional study variations in prescription practices. These findings emphasize the importance of enhancing post-fracture care to reduce morbidity and mortality associated with fragility fractures. LEVEL OF EVIDENCE: III.

Corticosteroid injection of the knee within one month prior to meniscus repair increases the risk of repair failure requiring meniscectomy.

OBJECTIVE: Meniscal tears are common knee injuries with limited endogenous healing capacity. This study aimed to investigate the association between the timing and administration of preoperative intra-articular corticosteroid injections (CSIs) and the risk of subsequent meniscectomy following meniscus repair. METHODS: Using a national insurance claims database, patients aged 18-40 years undergoing meniscus repair within six months of tear diagnosis were studied. Patients were categorized based on whether they received preoperative CSIs within three intervals prior to repair. Multivariable logistic regression was used to analyze the risk of follow-up meniscectomy while controlling for various patient-related variables. RESULTS: Among 5,390 patients meeting inclusion criteria, 201 received preoperative CSIs. The CSI group was older and had higher rates of diabetes, obesity, and knee osteoarthritis. The overall rate of follow-up meniscectomy did not differ between groups. However, CSIs performed within one month prior to repair were associated with significantly higher odds of subsequent meniscectomy compared to CSIs performed between three and six months prior. Obesity, tobacco use, and knee osteoarthritis were also independently associated with higher risk, while increasing age was associated with lower risk. CONCLUSION: The study highlights an increased risk of repair failure requiring follow-up meniscectomy for patients receiving intra-articular CSIs within one month prior to meniscus repair. These findings suggest caution when considering CSIs as a treatment option for patients scheduled for meniscus repair. Further research is needed to establish optimal timing guidelines for CSIs in relation to meniscus repair and to understand the underlying mechanisms.

Efficacy and toxicity of anti-vascular endothelial growth receptor tyrosine kinase inhibitors in patients with neuroendocrine tumours - A systematic review and meta-analysis.

AIM: Although anti-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (RTKIs) have been tested in patients with neuroendocrine tumours (NETs) over the last two decades, no study to date has benchmarked efficacy and toxicity of these drugs in this patient population. METHODS: All phase II and phase III studies of anti-VEGF RTKIs in patients with NETs, published between January 1, 2000 andJuly 31, 2021, across major trial databases, were searched in August 2021 for relevant studies. The primary objectives of the meta-analysis were to compare objective response rate (ORR) and progression-free survival (PFS) between patients with pancreatic NETs (pNETs) and extra-pancreatic NETs (epNETs), and the incidence rate ratio (IRR) of adverse events between patients receiving anti-VEGF RTKIs and control. RESULTS: 1611 patients were available for the meta-analysis; 1194 received anti-VEGF RTKIs. ORR in pNETs was 18% (95% confidence interval (CI) 13-25%), while ORR in epNETs was 8% (95% CI 5-12%); test for differences between pNETs and epNETs (x12 = 8.38, p < .01). Median PFS in pNETs was 13.9 months (95% CI 11.43-16.38 months), while median PFS in epNETs was 12.71 months (95% CI 9.37-16.05 months); test for differences between pNETs and epNETs (x12 = .35, p = .55). With regards to common grade 3/4 adverse events , patients who received anti-VEGF RTKIs were more likely to experience hypertension (IRR 3.04, 95% CI 1.63-5.65) and proteinuria (IRR 5.79, 95% CI 1.09-30.74) in comparison to those who received control. CONCLUSIONS: Anti-VEGF RTKIs demonstrate anti-tumour effect in both pNETs and epNETs, supporting their development in both populations. These agents also appear to be safe in patients with NETs.

Long Head of the Biceps Autograft Performs Biomechanically Similar to Human Dermal Allograft for Superior Capsule Reconstruction After Rotator Cuff Tear.

PURPOSE: To provide a biomechanical comparison between human dermal (HD) allograft and long head of biceps tendon (LHBT) autograft with and without posterior side-to-side suturing for superior capsule reconstruction. METHODS: Eight fresh-frozen cadaveric shoulder specimens were tested in 5 conditions: (1) intact, (2) complete supraspinatus tear, (3) LHBT, (4) LHBT with side-to-side suturing, and (5) HD allograft with side-to-side suturing. Functional abduction force, superior translation of humeral head, translational range of motion, and rotational range of motion were tested at 0°, 30°, 60°, and 90° of abduction within each condition. Data were analyzed using analysis of variance with post-hoc Tukey testing for pairwise comparison, with a significance value set at .05. RESULTS: Functional abduction force in the LHBT, LHBT + suture, and HD + suture conditions was significantly increased compared with the supraspinatus tear condition at abduction angles of 30° (P = .011, .001, and .017, respectively), 60° (P = .004, .001, and .002, respectively), and 90° (P = .013, .001, and .038, respectively). In addition, superior translation of the humeral head in the LHBT, LHBT + suture, and HD + suture conditions was significantly decreased compared with the tear condition at abduction angles of 30° (P = .03, .049, .03, respectively) and 60° (P = .02, .04, .03, respectively). All 3 reconstructive techniques were statistically identical to the intact rotator cuff condition in regard to translational and rotational range of motion. CONCLUSIONS: Superior capsule reconstruction with LHBT autograft without side-to-side suturing, LHBT with posterior side-to-side suturing, and HD allograft with posterior side-to-side suturing all equivalently restore functional abduction force and decrease superior translation of the humeral head after a complete supraspinatus tear. CLINICAL RELEVANCE: Superior capsule reconstruction with long head of the biceps tendon autograft and human dermal allograft both restore functional abduction force and decrease superior translation of the humeral head, while displaying no losses in the range of motion in a cadaveric model.

Lower Extremity Stress Fractures in the National Basketball Association, 2013-2014 Through 2018-2019.

Background: Players in the National Basketball Association (NBA) are at risk for lower extremity stress fractures, partly because of the sport's high-intensity demand on the lower body. Purpose: To provide insight on the identification and management of potential risk factors associated with lower extremity stress fractures in NBA athletes. Study Design: Case series; Level of evidence, 4. Methods: A retrospective study was conducted using the NBA electronic medical record database for all players who were on an NBA roster for ≥1 game from the 2013-2014 through 2018-2019 seasons. Player characteristics, games missed, and treatment methodology were independently analyzed. Results were presented as incidence per 1000 player-games. Results: There were 22 stress fractures identified in 20 NBA players over the course of 6 years, with an average of 3.67 stress fractures per year and an incidence of 0.12 stress fractures per 1000 player-games. Most stress fractures occurred in the foot (17/22), and 45% (10/22) of stress fractures were treated surgically, with the most common site of operation being the navicular. On average, approximately 37 games and 243 days were missed per stress fracture injury. There was no significant difference in time to return to play between high-risk stress fractures treated operatively versus nonoperatively (269.2 vs 243.8 days; P = .82). Conclusion: The overall incidence of stress fractures in NBA players was 0.12 per 1000 player-games, and a high percentage of players returned to NBA activity after the injury. There was a relatively even distribution between high-risk stress fractures treated operatively and nonoperatively. When comparing high-risk stress fractures treated operatively to ones treated nonoperatively, no significant difference in average time to return to play in the NBA was found.

Concussions Increase the Odds of Lower-Extremity Injuries in National Football League Players: Four-Year Review of Publicly Available Data.

Objective: To investigate the effect of multiple concussions on the risk of lower-extremity injuries in National Football League (NFL) players. Methods: All active NFL players from September 2016 to January 2017 through September 2019 to January 2020 regular seasons were eligible for inclusion. All players who sustained multiple concussions during the study period were identified using publicly available data and included in the multiple concussion (MC) cohort. Players who sustained a single concussion (SC) as well as controls were age and position matched to the MC cohort using MEDCALC case-control. Lower-extremity injuries were then documented for the players included in all 3 cohorts. Results: The odds of sustaining a lower-extremity injury were significantly greater in the MC as well as the SC cohort when compared with the no concussion (NC)-matched cohort (odds ratio 2.92, standard deviation [SD] 1.7-4.9) and 2.28 (SD 1.5-3.6), respectively. However, we found no significant difference in the odds of sustaining a lower-extremity injury when comparing the SC with the MC cohort (odds ratio 1.00, SD 0.7-1.3). The time to lower-extremity injury after return to play from a concussion was significantly shorter in the SC group when compared with the MC group, within 1 year following a concussion injury (P = .01). Conclusions: There was a significant increase in the odds of suffering a lower-extremity injury after return to play in NFL players exposed to SC or MC when compared with age- and position-matched controls who did not sustain a concussion within the study period. There was no significant difference in the odds of suffering a lower-extremity injury after return to play for NFL players exposed to MC when compared with players exposed to a SC during our study period. Our findings suggest a potential need for injury-prevention protocols following concussion injuries. Level of Evidence: Level III, retrospective comparative prognostic trial.

The Relationship Between Preoperative Opioid Use and Adverse Events Following Total Knee Arthroplasty.

This study aims to compare perioperative events following total knee arthroplasty (TKA) amongst various degrees of preoperative opioid use. In total, 84,569 patients undergoing TKA were identified from a Humana Claims Dataset, and stratified by their preoperative opioid use based on number of prescriptions filled within 6 months of surgery (naïve 0 [50,561]; sporadic 1 [12,411]; chronic 2 or greater [21,687]). Outcomes of interest included Center for Medicare and Medicaid Services (CMS)-reportable complications, need for postoperative supplemental oxygen, 90-day readmission, and hospital length of stay. Complication rates (9.8% vs 8.9% vs 12.6%; p < 0.01), need for supplemental oxygen (3.0% vs 3.1% vs 5.3%; p = 0.03), mean length of stay (2.1 vs 2.8 vs 3.5; p < 0.01), and 90-day readmission (9.7% vs 10.8% vs 16.4%; p < 0.01) significantly differed amongst groups. On logistic regression, only the chronic opioid use group was associated with significantly increased likelihood of complications, need for supplemental oxygen, and readmission. (Journal of Surgical Orthopaedic Advances 31(2):100-103, 2022).

Anal Cancer: Emerging Standards in a Rare Disease.

The social stigma surrounding an anal cancer diagnosis has traditionally prevented open discussions about this disease. However, as recent treatment options and an increasing rate of diagnoses are made worldwide, awareness is growing. In the United States alone, 9,090 individuals were expected to be diagnosed with anal cancer in 2021. The US annual incidence of squamous cell carcinoma of the anus continues to increase by 2.7% yearly, whereas the mortality rate increases by 3.1%. The main risk factor for anal cancer is a human papillomavirus infection; those with chronic immunosuppression are also at risk. Patients with HIV are 19 times more likely to develop anal cancer compared with the general population. In this review, we have provided an overview of the carcinoma of the anal canal, the role of screening, advancements in radiation therapy, and current trials investigating acute and chronic treatment-related toxicities. This article is a comprehensive approach to presenting the existing data in an effort to encourage continuous international interest in anal cancer.

The Injury Rate in NBA Players Did Not Increase Following Return to Play After the COVID-19 Stay-at-Home Order.

OBJECTIVE: The purpose of this study was to investigate the injury rate in NBA players following return to play during the post-COVID-19 shutdown 2019-2020 NBA season. METHODS: This study was a retrospective review of all NBA players who were placed on the injury report during the preseason and first 4 weeks of the regular season as well as playoffs from the 2017-2018 through 2020-2021 NBA seasons. The data were compiled using publicly available injury reports. All injuries were recorded, and injury rates were calculated per 1000 athletic exposures. Risk ratio with 95% confidence intervals compared injury rates between the 2 cohorts. RESULTS: Over the course of the study period, 399 injuries were reported. The highest injury rate per athletic exposure was observed to have occurred during the first month of the regular season in the 2 seasons prior to the COVID-19 pandemic. There was no significant difference in the average number of games missed before and after the pandemic for the preseason (P = .95), first month of regular season (P = .62), and playoffs (P = .69). There was no significant difference in the rate of injury when comparing injury rates before and after the pandemic for the preseason (P = .25), first month of the regular season (P = .11), and playoffs (P = .3). CONCLUSION: The rate of injury in NBA players following the COVID-19 pandemic was not significantly higher than 2 recent past NBA seasons.

A contemporary systematic review on liver transplantation for unresectable liver metastases of colorectal cancer.

The 5-year overall survival rate of a patient with unresectable metastatic colorectal cancer is poor at approximately 14%. Similarly, historical data on liver transplantation (LT) in those with colorectal liver metastases (CRLM) showed poor outcomes, with 5-year survival rates between 12% and 21%. More recently, limited data have shown improved outcomes in select patients with 5-year overall survival rates of approximately 60%. Despite these reported survival improvements, there is no significant improvement in disease-free survival. Given the uncertain benefit with this therapeutic approach and a renewed investigational interest, we aimed to conduct a contemporary systematic review on LT for CRLM. A systematic review of the literature was performed according to the preferred reporting items for systematic reviews and meta-analysis statement. English articles reporting on data regarding LT for CRLM were identified through the MEDLINE (via PubMed), Cochrane Library, and ClinicalTrials.gov databases (last search date: December 16th, 2021) by 2 researchers independently. A total of 58 studies (45 published and 13 ongoing) were included. Although early retrospective studies suggest the possibility that some carefully selected patients may benefit from LT, there is minimal prospective data on the topic and LT remains exploratory in the setting of CRLM. Additionally, several other challenges, such as the limited availability of deceased donor organs and defining appropriate selection criteria, remain when considering the implementation of LT for these patients. Further evidence from ongoing prospective trials is needed to determine if and to what extent there is a role for LT in patients with surgically unresectable CRLM.

Temporal Relationship of Corticosteroid Injection and Open Release for Trigger Finger and Correlation With Postoperative Deep Infections.

PURPOSE: Previous single-institution studies have shown a relationship between corticosteroid injection and infection after surgery if open trigger release occurs within 90 days. We queried an insurance claims database to evaluate the temporal relationship between a corticosteroid injection and the development of a surgical site infection requiring secondary surgery in patients undergoing trigger release. METHODS: The PearlDiver database was queried for adults who underwent unilateral trigger finger release surgery from 2012 to 2018. The total number of injections, time from last injection to surgery, and preoperative antibiotic use were determined, in addition to the rates of postoperative administration of antibiotics and deep infection requiring surgery at 30, 60, and 90 days after surgery. Logistic regression analysis was used to evaluate the odds of deep infection at 30, 60, and 90 days. RESULTS: A total of 14,686 patients were included; at least 1 corticosteroid injection was administered to 5,173 patients prior to surgery. When grouped based on whether a corticosteroid injection was administered prior to surgery, the postoperative infection rates between the groups were similar at 30, 60, and 90 days. When surgery was performed within 1 month of injection, increased odds of deep infection requiring irrigation and debridement were seen at 60 (odds ratio 2.92 [1.01-7.52]) and 90 days (odds ratio 3.01 [1.13-7.25]). Postoperative antibiotic use in the groups with and without a preoperative injection was similar at all queried time points, but patients who underwent open trigger finger release within 1 month of a prior injection had significantly increased odds (odds ratio 5.77 [1.41-22.06]) of using antibiotics after surgery. Male sex, a higher Elixhauser comorbidity index, and rheumatoid arthritis were additional independent risk factors for a deep infection. CONCLUSIONS: Patients who undergo open trigger release within 1 month of a corticosteroid injection are at increased odds of developing a postoperative infection requiring surgical debridement. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

The targeting rule does not increase the rate of lower extremity injuries in NFL players over two seasons.

OBJECTIVES: In 2018 the NFL instituted playing rule article 8, which aimed to help decrease sport related concussion (SRC) by broadening the helmet-hit rule, making it a foul when a player lowers his head to make contact with his helmet against an opponent. Previous studies have demonstrated that the rate of lower extremity injuries increased following the institution of the targeting rule in NCAA football. The objective of this study was to determine if playing rule article 8 unintentionally led to a significant increase in the rate of lower extremity injuries sustained by NFL players during regular season games. METHODS: This study was a retrospective review of all NFL players who were placed on the publically available injury reports for a lower extremity injury from the 2016-2017 through 2019-2020 regular seasons. With article 8 taking effect starting with the 2018-2019 season, players were assigned to a pre- or post-rule cohort based on date of injury for purposes of injury rate comparison. Injury rates were calculated per 1000 athletic exposures (AE). Incidence rate ratio (RR) with 95% confidence intervals (CI) compared injury rates between the two cohorts. RESULTS: There was a 3% decrease in the lower extremity injury rate in 2018-2019 to 2019-2020 compared with 2016-2017 to 2017-2018, however this was not statistically significant (33.6 versus 34.3/1000 AEs, respectively; RR, 0.97; 95% CI 0.92-1.04). There was a 40% decrease in the SRC rate when comparing the post- to the pre-article-8 cohort (3.3 vs. 5.5/1000 AEs, respectively; RR 0.60; 95% CI 0.50-0.73). CONCLUSIONS: The rate of lower extremity injuries and players placed on the injury reserve over the past two NFL seasons following the enactment of playing rule article 8 has not significantly increased. However, the average games missed due to lower extremity injuries significantly increased under playing rule article 8, which suggests that the severity of lower extremity injuries possibly increased. LEVEL OF EVIDENCE: IV Diagnostic.

Comparison of Design, Eligibility, and Outcomes of Neuroendocrine Neoplasm Trials Initiated From 2000 to 2009 vs 2010 to 2020.

Importance: Neuroendocrine neoplasms (NENs) have historically been grouped homogenously in clinical trials, despite their heterogeneity. Given the adoption of a more advanced pathologic classification system and drug licensure of several targeted therapies over the last decade, information is needed on whether study characteristics of NEN studies have evolved. Objective: To assess changes in study design, eligibility, accrual, sponsorship, and outcomes between phase II or III NEN clinical trials that began enrollment from 2000 to 2009 vs 2010 to 2020. Design, Setting, and Participants: This quality improvement study used a systematic survey of completed studies published between January 1, 2000, and December 31, 2020. Therapeutic phase II and III NEN studies were identified through a database search of Medline (via PubMed), EMBASE (OvidSP), Cumulative Index of Nursing and Allied Health Literature (EBSCOhost), Web of Science (Clarivate), Cochrane Database of Systematic Reviews (Wiley), ClinicalTrials.gov (National Institutes of Health), EU Clinical Trials Register, and National Cancer Institute Clinical Trials. Data were analyzed between March and June 2021. Main Outcomes and Measures: Study characteristic proportions between the 2 enrollment periods. Results: Of 3243 identified studies, 119 studies met criteria for inclusion, of which 117 studies (54 studies that began enrollment between 2000-2009 and 63 studies that began enrollment between 2010-2020) included exact dates of enrollment and were compared. Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were less likely to include all NENs (13 studies [21%] vs 34 studies [63%]; P < .001) and more likely to include select NENs (eg, gastrointestinal neuroendocrine tumors, 25 studies [40%] vs 11 studies [20%]; P = .02; pancreatic neuroendocrine tumors, 32 studies [51%] vs 16 studies [30%]; P = .02). Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were more likely to specify tumor differentiation (59 studies [98%] vs 34 studies [63%]; P < .001) or Ki-67 index (23 studies [38%] vs 5 studies [9%]; P < .001) in inclusion criteria. Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were more likely to use progression-free survival (22 studies [35%] vs 9 studies [18%]; P = .04) rather than objective response rate (19 studies [30%] vs 27 studies [53%]; P = .01) as a primary or coprimary end point. Conclusions and Relevance: These findings suggest that NEN trials enrolling over the last decade were more focused on select tumor populations, compared with studies that began enrollment before 2010. Despite this shift, more than 20% of studies still included all NENs. Studying novel agents in specific disease populations may enhance drug development in the field.

Unicompartmental Knee Arthroplasty Is Associated With a Lower Rate of Periprosthetic Joint Infection Compared to Total Knee Arthroplasty.

BACKGROUND: Several studies have reported lower perioperative complications with unicompartmental knee arthroplasty (UKA) than with total knee arthroplasty (TKA). However, there is a paucity of data analyzing the incidence of periprosthetic joint infection (PJI) in similar patients undergoing UKA and TKA. As such, we sought to analyze the incidence of UKA and TKA PJI in a large matched population. MATERIAL AND METHODS: The Mariner data set of the PearlDiver database was queried for all patients undergoing UKA or TKA during 2010-2017. Included patients were required to have at least 2 years of database inclusion after surgery. Patients were then matched at a 1:3 ratio (UKA:TKA) on age, gender, Elixhauser Comorbidity Index, tobacco use, and obesity. Rates of PJI requiring operative intervention within 90 days and 1 year were calculated. RESULTS: In total, 5636 patients having undergone UKA were matched to 16,890 patients having undergone TKA. Fifteen (0.27%) after UKA and 79 (0.47%) after TKA had a PJI surgically managed within 90 days (risk ratio = 0.57, 95% confidence interval = 0.33-0.99, P = .04). Thirty (0.53%) after UKA and 136 (0.81%) after TKA had a PJI surgically managed within 1 year (risk ratio = 0.66, 95% confidence interval = 0.45-0.98, P = .04). CONCLUSIONS: In a large group of rigorously matched patients, UKA was associated with a significantly lower rate of surgically managed PJI than TKA at 90 days and 1 year; however, the rate of PJI in both groups remained low at <1% at 90 days and 1 year.