bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogen/Progesterone Receptor Loss, CTNNB1 and KRAS Mutations Are Associated With Local Recurrence or Distant Metastasis in Low-Grade Endometrial Endometrioid Carcinoma
Authors: Chibbar Rajni , Foerstner Sabrina , Suresh Janarathnee , Chibbar Richa , Piche Alexandre , Kundapur Deeksha , Kanthan Rani , Kundapur Vijayanand , Lee Cheng Han , Agrawal Anita , Lai Raymond
Published: January 2023

A subset of endometrial endometrioid carcinomas (EECs) with low-grade histology recur with poor outcomes. Published evidence suggests that poor outcomes may be associated with loss of expression of ER-alpha (ER-α) as well as with β-Catenin-1 (CTNNB1) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. This study reports on institutional experience with the incidence of recurrence in low-grade EEC and their association with CTNNB1 and KRAS mutations as well as estrogen/progesterone receptor (ER/PR) expression. Forty-eight (8.5%) out of 568 cases of low-grade EEC with biopsy-proven recurrence were identified; and were analyzed by immunohistochemistry for ER, PR, p53, MMR protein, and mutation analysis for exon 3 of the CTNNB1 and exon 2 of KRAS in relation to recurrence type, local or distant metastasis/recurrence. Twenty-three patients (4%) developed local, and 25 patients (4.4%) developed distant metastases/recurrence. Decreased expression or loss of ER/PR was found in 17/44 (38.6%) patients with recurrence. Eighty-four percent of patients with low-grade EEC and local recurrence had CTNNB1 mutations. Seventy-three percent of patients with distant metastasis/recurrence had KRAS mutations. The association of these mutations with the type of recurrence was statistically significant for both. Five cases with the morphology of low-grade EEC were reclassified as mesonephric-like carcinoma and were universally characterized by distant metastasis/recurrence, loss of ER/PR expression, large tumor size, absence of CTNNB1 mutations, and the presence of KRAS mutations. In low-grade EEC, CTNNB1 and KRAS mutations are associated with local recurrence and distant metastasis/recurrence, respectively, suggesting that these 2 different progression types may be conditioned by tumor genotype. ER/PR immunohistochemistry may be helpful in identifying poor performers in low-grade EEC. Furthermore, identification of the decreased expression or loss of ER/PR in tumors with low-grade histology should prompt consideration of mesonephric-like carcinoma, which is a more aggressive tumor than the low-grade EEC. KRAS mutations were associated with distant metastasis/recurrence in tumors with and without mesonephric-like phenotype.
Reporting of Social Determinants of Health in Pediatric Sepsis Studies*
Authors: Menon Kusum , Sorce Lauren R. , Argent Andrew , Bennett Tellen D. , Carrol Enitan D. , Kissoon Niranjan , Sanchez-Pinto L. Nelson , Schlapbach Luregn J. , de Souza Daniela C. , Watson R. Scott , Wynn James L. , Zimmerman Jerry J. , Ranjit Suchitra ,   on behalf of the Pediatric Sepsis Definition Taskforce
Published: January 2023

OBJECTIVE:

Standardized, consistent reporting of social determinants of health (SDOH) in studies on children with sepsis would allow for: 1) understanding the association of SDOH with illness severity and outcomes, 2) comparing populations and extrapolating study results, and 3) identification of potentially modifiable socioeconomic factors for policy makers. We, therefore, sought to determine how frequently data on SDOH were reported, which factors were collected and how these factors were defined in studies of sepsis in children.

DATA SOURCES AND SELECTION:

We reviewed 106 articles (published between 2005 and 2020) utilized in a recent systematic review on physiologic criteria for pediatric sepsis.

DATA EXTRACTION:

Data were extracted by two reviewers on variables that fell within the World Health Organization’s SDOH categories.

DATA SYNTHESIS:

SDOH were not the primary outcome in any of the included studies. Seventeen percent of articles (18/106) did not report on any SDOH, and a further 36.8% (39/106) only reported on gender/sex. Of the remaining 46.2% of articles, the most reported SDOH categories were preadmission nutritional status (35.8%, 38/106) and race/ethnicity (18.9%, 20/106). However, no two studies used the same definition of the variables reported within each of these categories. Six studies reported on socioeconomic status (3.8%, 6/106), including two from upper-middle-income and four from lower middle-income countries. Only three studies reported on parental education levels (2.8%, 3/106). No study reported on parental job security or structural conflict.

CONCLUSIONS:

We found overall low reporting of SDOH and marked variability in categorizations and definitions of SDOH variables. Consistent and standardized reporting of SDOH in pediatric sepsis studies is needed to understand the role these factors play in the development and severity of sepsis, to compare and extrapolate study results between settings and to implement policies aimed at improving socioeconomic conditions related to sepsis.
Geospatial Prioritization to Reach Hispanic or Latino and Other Priority Populations Through HIV Home Testing Services
Authors: Rosenthal Elizabeth M. , Tesoriero James M. , Flavin Susan M. , Yuan Yingchao , Sullivan Thomas T. , Johnson Megan C.
Published: January 2023

Context:

Hispanic or Latino men who have sex with men (HLMSM) are disproportionately affected by the HIV/AIDS epidemic in New York State (NYS) and nationally. In 2019, HLMSM comprised 13% of all new diagnoses and 21% of new diagnoses among men who have sex with men (MSM) in NYS excluding New York City. HIV home testing programs are effective methods for increasing HIV testing.

Objective:

This pilot sought to determine whether the NYS HIV Home Test Giveaway (HHTG) can effectively reach priority populations, specifically HLMSM/transgender/gender nonconforming persons who have sex with men, to increase uptake of HIV home testing services and identify new HIV infections.

Design/Setting:

We recruited participants using media campaigns linked to a brief self-administered eligibility survey. Eligible participants provided their e-mail address to receive a code for a free HIV home test and were sent a self-administered follow-up survey 4 to 11 weeks after eligibility survey completion.

Participants:

The 2018 and 2019 NYS HHTG reached 1214 and 1340 participants, respectively. A total of 606 participants in 2018 and 736 participants in 2019 were eligible to receive the HHTG home test kit.

Main Outcome Measure(s):

HHTG utilization and test results.

Results:

Hispanic or Latino persons participated at higher rates (34.8% and 25.4% in 2018 and 2019, respectively) than the percentage of Hispanic men in prioritized zip codes (15.7% and 15.6% in 2018 and 2019, respectively). The majority of participants who received HHTG test kits used them to test themselves (87.5% in 2018 and 90.6% in 2019). Across both rounds, 4 participants reported new HIV-positive results, for a seropositivity rate of approximately 1%.

Conclusion:

Geospatial prioritization was successful in reaching Hispanic or Latino priority populations for HIV testing. HIV self-testing programs such as the HHTG are beneficial methods to reach priority populations for state and national Ending the HIV Epidemic initiatives.
Impact of High-Deductible Health Plans on Breast Reconstruction: Considerations for Financial Toxicity
Authors: Shamsunder Meghana G. , Sheckter Clifford C. , Sheinin Avraham , Rubin David , Parikh Rajiv P. , Rose John , Momoh Adeyiza O. , Offodile Anaeze C. , Matros Evan
Published: January 2023

Background:

High-deductible health plans (HDHPs) are used within the United States to curb unnecessary health care spending; however, the resulting increased out-of-pocket (OOP) costs may be associated with financial toxicity. The aim was to assess the impact of HDHPs on use and seasonality of mastectomy and breast reconstruction procedures. The hypothesis is that the high OOP costs of HDHPs will lead to decreased overall service use and greater fourth-quarter use after the deductible has been met.

Methods:

MarketScan was queried from 2014 to 2017 for episodes of mastectomy, breast reconstruction (immediate and delayed), breast revision, and reduction. Only patients continuously enrolled for the full calendar year after the index operation were included. HDHPs and low-deductible health plans (LDHPs) were compared based on OOP cost sharing. Outcomes included surgery use rates, seasonality of operations, and median/mean OOP costs.

Results:

Annual mastectomy and breast reconstruction use rates varied little between LDHPs and HDHPs. Mastectomies, delayed breast reconstruction, and elective breast procedures (P < 0.001) all showed significant increases in fourth-quarter use, whereas immediate breast reconstruction did not. Regardless of timing and reconstruction method, HDHPs had significantly greater median OOP costs compared to LDHPs (all P < 0.001).

Conclusions:

Mastectomy and breast reconstruction rates did not differ between LDHPs and HDHPs, but seasonality for all breast procedures was measured with the exception of immediate breast reconstruction, suggesting that women are rational economic actors. Regardless of service timing and reconstruction modality, HDHP patients had greater OOP costs compared to LDHP patients, which serves as a good starting point for provider engagement in financial toxicity.
Association between Immediate Breast Reconstruction and the Development of Breast Cancer–Related Lymphedema
Authors: Jeon Hong Bae , Jung Ji Hyuk , Im Sang Hee , Kim Yong Bae , Chang Jee Suk , Song Seung Yong , Lew Dae Hyun , Roh Tai Suk , Lee Won Jai , Lee Dong Won
Published: January 2023

Background:

With the increasing number of patients undergoing immediate breast reconstruction after mastectomy, the impact of immediate breast reconstruction on the risk of breast cancer–related lymphedema has become an emerging area of interest. This study aimed to identify the association between immediate breast reconstruction and postoperative lymphedema.

Methods:

A retrospective cohort study was conducted from 2006 to 2016 with 5900 consecutive patients who underwent mastectomy for primary breast cancer with or without immediate breast reconstruction. After excluding patients with synchronous contralateral breast cancer, lymphedema before mastectomy, history of procedures performed in the axillary region, and follow-up data of less than 1 year, the cumulative incidence of lymphedema after immediate breast reconstruction and after no reconstruction was calculated and compared using multivariate Cox regression analysis.

Results:

Overall, 5497 patients (mean age, 51.7 years) were included, and 630 developed lymphedema. The 5-year cumulative incidence rate of lymphedema was significantly reduced in patients who underwent immediate breast reconstruction versus control patients (9.6% versus 12.2%; P = 0.02). In the multivariate analysis, immediate breast reconstruction status (hazard ratio, 0.75; 95% confidence interval, 0.56 to 0.99; P = 0.042) was an independent predictor for lymphedema. Similar significant associations were observed in the subgroup analyses of patients with a body mass index less than 30 kg/m2 (P = 0.024), in those with fewer than 10 dissected lymph nodes (P = 0.042), or in those with adjuvant radiotherapy (P = 0.048).

Conclusions:

Immediate breast reconstruction was associated with a reduced risk of lymphedema. These results may be used for predicting the development of lymphedema following breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
The Objective Stretch Marks Photonumeric Assessment Scale: A New and Complete Method to Assess Striae Distensae
Authors: La Padula Simone , Hersant Barbara , Pizza Chiara , Chesné Christophe , Jamin Agnes , Ben Mosbah Ismail , D’Andrea Francesco , Persichetti Paolo , Rega Umberto , Pensato Rosita , Meningaud Jean Paul
Published: January 2023

Background:

Striae distensae evaluation criteria have been recently described, but none is focused on objective striae assessment. With the purpose of better and objectively estimating the severity of striae distensae, the Objective Stretch Marks Assessment Scale has been developed by the authors’ team.

Methods:

Seven hundred White patients were included in the study and assessed. To assess the severity of striae distensae, abdomen, breasts, hips, gluteal area, back area, thighs, calves, and upper limbs photonumeric grading scales were developed. The Rasch model was used as part of the validation process. A score was attributed to each patient, based on the scales we developed. The interrater reliability and test-retest reliability were analyzed.

Results:

Eight photonumeric scales for striae distensae treatment outcomes assessment were developed. All scales exceeded criteria for acceptability, reliability and validity. The interrater and intrarater reliabilities were good, with a substantial or virtually perfect interrater reliability for the total score (P = 0.16).

Conclusions:

The authors’ results allowed them to validate the Objective Stretch Marks Assessment Scale as a reliable and reproducible tool to assess striae distensae treatment outcomes. This scale could be also considered as an important new metric that can be used in clinical research.
The Middle Temporal Vein on Computed Tomographic Angiography: Implications for Filler Injection and Reconstructive Surgery
Authors: Wang Dawei , Xiong Shixuan , Zeng Ning , Wu Yiping
Published: January 2023

Background:

Detailed knowledge of middle temporal vein (MTV) anatomy would benefit health care professionals when performing filler injection and reconstructive surgery. The purpose of this study was to assess the variation and course of the MTV using computed tomographic angiography.

Methods:

Computed tomographic angiography images of 300 MTVs from 150 Asian patients were evaluated in this study. The course and branching pattern of the MTVs were evaluated, as well as the relationship between the location of the MTV and the frontal branch of the superficial temporal artery. The diameter of the MTV and the distances between anatomic landmarks and temporal vessels were measured.

Results:

The MTV was identified in all images, with an average diameter of 2.98 ± 0.80 mm. All MTVs had at least one major trunk; 12.3% had two major trunks. According to the landmarks, the MTV ran 16.3 ± 8.1 mm, 24.8 ± 4.5 mm, and 24.2 ± 4.6 mm above bony lateral canthus, jugale, and zygion point, respectively. Regarding the relationship between the MTV and the frontal branch of the superficial temporal artery, most of the superficial temporal arteries (81.7%) were located above the MTVs, whereas only 9.0% of the superficial temporal arteries crossed the MTVs. The superficial temporal artery was located 43.5 ± 9.6 mm, 44.3 ± 11.9 mm, and 37.0 ± 11.9 mm above the bony lateral canthus, jugale, and zygion point, respectively.

Conclusion:

Detailed knowledge of MTV anatomy will provide a valuable reference for safe filler injection and reconstructive surgery in the temporal region.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
A Simplified Treatment for Mild to Moderate Epicanthal Folds
Authors: Fagien Steven
Published: January 2023

Surgical treatments to the upper eyelid have evolved along with a better understanding of the aging upper eyelid anatomy and development of solutions that are aesthetically pleasing and that defy detection. It is not uncommon for patients to present before or after upper blepharoplasty with perceived deformities of the medial canthus. Epicanthal folds are sometimes a concern. Approaches to the varied presentations of epicanthal folds have derived from the belief that they relate to a dermal or orbicular (muscle) issue, and solutions have primarily involved traditional approaches to altering skin and muscle tension by means of complex flaps. Complications or unfavorable outcomes that relate to this approach mainly involve scarring or nonresolution. The author describes a novel and simple surgical approach for the treatment of mild to moderate epicanthal folds or medial canthal webbing that is in line with the goals of the balance of aesthetics, resolution, and undetectability.
Guidelines for Wide-Awake Local Anesthesia Surgery with No Tourniquet in the Office Setting Using Field Preparation Sterility
Authors: Schank Kyle J. , Engwall Abigail J. , Kuhns Benjamin W. , Oakes Tannur C. , Bray Stephanie M. , Clarkson James H. W.
Published: January 2023

Wide-awake local anesthesia surgery with no tourniquet, or WALANT, has become popular in surgery, especially among hand surgeons. With the increasing number of surgeons performing office-based procedures, this article provides guidelines that may be used in the office setting to help transition more traditional hospital operating room–based procedures to the office setting. This article outlines the benefits of performing office-based wide-awake local anesthesia surgery with no tourniquet and provides a step-by-step guide to performing procedures that can be easily incorporated into any hand surgeon’s practice successfully and safely.
Optimizing the Psychosocial Function Measures in the International Consortium for Health Outcomes Measurement Standard Set for Cleft
Authors: Apon Inge , van Leeuwen Nikki , Koudstaal Maarten J. , Allori Alexander C. , Rogers-Vizena Carolyn R. , Wolvius Eppo B. , Klassen Anne F. , Versnel Sarah L.
Published: January 2023

Background:

To ensure the feasibility of implementing PROMs in clinical practice, they must be continually appraised for undue burden placed on patients and clinicians and their usefulness for decision-making. This study assesses correlations between the CLEFT-Q psychosocial scales in the International Consortium for Health Outcomes Measurement Standard Set for cleft and explores their associations with patient characteristics and psychosocial care referral.

Methods:

Spearman correlation coefficients were calculated for CLEFT-Q psychological function, social function, school function, face, speech function, and speech-related distress scales. Logistic regressions were used to assess the association of cleft phenotype, syndrome, sex, and adoption status on scale scores and clinical referral to psychosocial care for further evaluation and management.

Results:

Data were obtained from 3067 patients with cleft lip and/or palate at three centers. Strong correlations were observed between social function and psychological function (r > 0.69) and school function (r > 0.78) scales. Correlation between school function and psychological function scales was lower (r = 0.59 to 0.68). Genetic syndrome (OR, 2.37; 95% CI, 1.04 to 5.41), psychological function (OR, 0.92; 95% CI, 0.88 to 0.97), school function (OR, 0.94; 95% CI, 0.90 to 0.98), and face (OR, 0.96; 95% CI, 0.94 to 0.98) were significant predictors for referral to psychosocial care.

Conclusions:

Because social function as measured by the CLEFT-Q showed strong correlations with both school and psychological function, its additional value for measuring psychosocial function within the Standard Set is limited, and it is reasonable to consider removing this scale from the International Consortium for Health Outcomes Measurement Standard Set for cleft.
Artificial Intelligence–Enabled Evaluation of Pain Sketches to Predict Outcomes in Headache Surgery
Authors: Chartier Christian , Gfrerer Lisa , Knoedler Leonard , Austen William G.
Published: January 2023

Background:

Recent evidence has shown that patient drawings of pain can predict poor outcomes in headache surgery. Given that interpretation of pain drawings requires some clinical experience, the authors developed a machine learning framework capable of automatically interpreting pain drawings to predict surgical outcomes. This platform will allow surgeons with less clinical experience, neurologists, primary care practitioners, and even patients to better understand candidacy for headache surgery.

Methods:

A random forest machine learning algorithm was trained on 131 pain drawings provided prospectively by headache surgery patients before undergoing trigger-site deactivation surgery. Twenty-four features were used to describe the anatomical distribution of pain on each drawing for interpretation by the machine learning algorithm. Surgical outcome was measured by calculating percentage improvement in Migraine Headache Index at least 3 months after surgery. Artificial intelligence predictions were compared with clinician predictions of surgical outcome to determine artificial intelligence performance.

Results:

Evaluation of the data test set demonstrated that the algorithm was consistently more accurate (94%) than trained clinical evaluators. Artificial intelligence weighted diffuse pain, facial pain, and pain at the vertex as strong predictors of poor surgical outcome.

Conclusions:

This study indicates that structured algorithmic analysis is able to correlate pain patterns drawn by patients to Migraine Headache Index percentage improvement with good accuracy (94%). Further studies on larger data sets and inclusion of other significant clinical screening variables are required to improve outcome predictions in headache surgery and apply this tool to clinical practice.
A Contemporary Review of the Role of Facial Prostheses in Complex Facial Reconstruction
Authors: Slijepcevic Allison A. , Afshari Azadeh , Vitale Ann E. , Couch Steven M. , Jeanpierre Latoya M. , Chi John J.
Published: January 2023

Background:

Maxillofacial prostheses provide effective rehabilitation of complex facial defects as alternatives to surgical reconstruction. Although facial prostheses provide aesthetically pleasing reconstructions, multiple barriers exist that prevent their routine clinical use. The accessibility of facial prostheses is limited by the scarce supply of maxillofacial prosthodontists, significant time commitment and number of clinic appointments required of patients during prosthesis fabrication, short lifespan of prostheses, and limited outcomes data.

Methods:

A literature review was completed using PubMed and Embase databases, with search phrases including face and maxillofacial prostheses. Patient cases are included to illustrate the use of facial prostheses to reconstruct complex facial defects.

Results:

The clinical use of facial prostheses requires a multidisciplinary team including a reconstructive surgeon, a maxillofacial prosthodontist, and an anaplastologist, if available, to provide patients with aesthetically appropriate facial prostheses. Developing technology including computer-aided design and three-dimensional printing may improve the availability of facial prostheses by eliminating multiple steps during prosthesis fabrication, ultimately decreasing the time required to fabricate a prosthesis. In addition, enhanced materials may improve prosthesis durability. Long-term outcomes data using validated measures is needed to support the continued use of facial prostheses.

Conclusions:

Facial prostheses can be used to reconstruct complex facial defects, and bone-anchored prostheses are associated with high patient satisfaction. Multiple barriers prevent prostheses from being used for facial reconstruction. New technologies to assist the design and fabrication of prostheses, and cost reduction measures, may allow their use in the appropriately selected patient.
Lymphatic Microsurgical Preventive Healing Approach for the Primary Prevention of Lymphedema: A 4-Year Follow-Up
Authors: Levy Adam S. , Murphy Alexander I. , Ishtihar Sherene , Peysakhovich Anya , Taback Bret , Grant Robert T. , Ascherman Jeffrey A. , Feldman Sheldon , Rohde Christine H.
Published: January 2023

Background:

Axillary lymph node dissection (ALND) remains the leading cause of lymphedema nationally, and there is still no cure for the disease. The lymphatic microsurgical preventive healing approach (LYMPHA) is a promising option for lymphedema prophylaxis in patients undergoing ALND, but long-term outcomes of the LYMPHA are not well established.

Methods:

The authors conducted a retrospective review of patients undergoing ALND at their center from November of 2012 to November of 2016 and assembled two cohorts, those who received the LYMPHA and those who did not (non-LYMPHA). Patient data were collected to evaluate lymphedema risk and long-term lymphedema incidence of each group.

Results:

Forty-five women were included in both our LYMPHA and non-LYMPHA cohorts. Mean body mass index (27.7 kg/m2 versus 29.9 kg/m2; P = 0.15) and radiation therapy rates (60.0% versus 68.9%; P = 0.51) did not differ between groups. Non-LYMPHA patients underwent complete mastectomy more frequently than LYMPHA patients (97.8% versus 77.8%; P = 0.007), but had a similar number of nodes removed during ALND (14.4 versus 15.8; P = 0.32). Median follow-up time was greater than 4 years for both LYMPHA and non-LYMPHA groups (57.0 months versus 63.0 months; P = 0.07). Overall, lymphedema incidence was 31.1% in the LYMPHA group and 33.3% in the non-LYMPHA group (P > 0.99). No significant differences in lymphedema incidences were observed between the LYMPHA and non-LYMPHA groups for patients with obesity, patients who received radiation therapy, or patients with obesity who also received radiation therapy (P > 0.05 for all subgroups).

Conclusions:

The LYMPHA may not prevent lymphedema long-term in patients who undergo ALND. More long-term studies are needed to determine the true potential of the procedure.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Correlation between Relative Value Units and Operative Time for Flap-Based Reconstruction Procedures
Authors: Dibbs Rami P. , Skochdopole Anna , Reul Ross M. , Beh Han Z. , Ferry Andrew M. , Conlon Christopher J. , O’Neill Rebecca , Reece Edward , Winocour Sebastian
Published: January 2023

Background:

Procedures performed by plastic surgeons tend to generate lower work relative value units (RVUs) compared to other surgical specialties despite their major contributions to hospital revenue. The authors aimed to compare work RVUs allocated to all free flap and pedicled flap reconstruction procedures based on their associated median operative times and discuss implications of these compensation disparities.

Methods:

A retrospective analysis of deidentified patient data from the American College of Surgeons National Surgical Quality Improvement Program was performed, and relevant CPT codes for flap-based reconstruction were identified from 2011 to 2018. RVU data were assessed using the 2020 National Physician Fee Schedule Relative Value File. The work RVU per unit time was calculated using the median operative time for each procedure.

Results:

A total of 3991 procedures were included in analysis. With increased operative time and surgical complexity, work RVU per minute trended downward. Free-fascial flaps with microvascular anastomosis generated the highest work RVUs per minute among all free flaps (0.114 work RVU/minute). Free-muscle/myocutaneous flap reconstruction generated the least work RVUs per minute (0.0877 work RVU/minute) among all flap reconstruction procedures.

Conclusions:

Longer operative procedures for flap-based reconstruction were designated with higher work RVU. Surgeons were reimbursed less per operative unit time for these surgical procedures, however. Specifically, free flaps resulted in reduced compensation in work RVUs per minute compared to pedicled flaps, except in breast reconstruction. More challenging operations have surprisingly resulted in lower compensation, demonstrating the inequalities in reimbursement within and between surgical specialties. Plastic surgeons should be aware of these discrepancies to appropriately advocate for themselves.
Hospitalization among infants who initiate antiretroviral therapy before 3 months of age
Authors: Anderson Kim , Iyun Victoria , Eley Brian S. , Rabie Helena , Ferreira Thalia , Nuttall James , Frigati Lisa , Van Dongen Nicola , Davies Mary-Ann
Published: January 2023

Introduction:

Studies examining hospitalization among infants with HIV in resource-limited settings, in the context of early infant diagnosis and early antiretroviral therapy (ART) initiation, are limited.

Methods:

We used routinely collected data on infants who initiated ART aged <3 months (Western Cape province, South Africa; 2013–2017) to describe hospitalization from birth until 12 months post-ART initiation. Record reviews were additionally performed at three tertiary-level facilities. We used mixed-effects Poisson regression to examine factors associated with hospitalization.

Results:

Among 840 infants, 579 (69%) were hospitalized; 36% had >1 hospitalization. Median age at ART initiation decreased from 57 days (interquartile range [IQR] 22–74; 2013–2015) to 19 days (IQR 5–54; 2016–2017). Early neonatal hospitalization (age <7 days) occurred in 271 infants (32%) and represented 24% of hospitalizations (272/1131). Overall, 443 infants (53%) were hospitalized at age ≥7 days, including 13% with hospitalizations pre-ART initiation, 15% pre and post-ART initiation and 25% post-ART initiation. Excluding early neonatal hospitalizations, initiating ART at older age vs. age <1 week was associated with higher hospitalization rates: adjusted incidence rate ratios (95% confidence interval) were 1.86 (1.31–2.64); 2.31 (1.62–3.29) and 2.47 (1.76–3.46) if ART initiation age was 1–4 weeks; 5–8 weeks and 9–12 weeks respectively. Among infants whose hospital records were reviewed, reasons for early neonatal hospitalizations mostly related to prematurity or low birthweight (n = 46/60; 77%) whereas hospitalizations at age ≥7 days were mostly due to infections (n = 206/243; 85%).

Conclusions:

Earlier ART initiation is associated with lower hospitalization rates. High hospitalization rates, despite initiation age <3 months, is concerning.
Not all clusters are equal: dynamics of molecular HIV-1 clusters in a statewide Rhode Island epidemic
Authors: Novitsky Vlad , Steingrimsson Jon , Howison Mark , Dunn Casey W. , Gillani Fizza S. , Fulton John , Bertrand Thomas , Howe Katharine , Bhattarai Lila , Ronquillo Guillermo , MacAskill Meghan , Bandy Utpala , Hogan Joseph , Kantor Rami
Published: January 2023

Objectives:

Molecular epidemiology is a powerful tool to characterize HIV epidemics and prioritize public health interventions. Typically, HIV clusters are assumed to have uniform patterns over time. We hypothesized that assessment of cluster evolution would reveal distinct cluster behavior, possibly improving molecular epidemic characterization, towards disrupting HIV transmission.

Design:

Retrospective cohort.

Methods:

Annual phylogenies were inferred by cumulative aggregation of all available HIV-1 pol sequences of individuals with HIV-1 in Rhode Island (RI) between 1990 and 2020, representing a statewide epidemic. Molecular clusters were detected in annual phylogenies by strict and relaxed cluster definition criteria, and the impact of annual newly-diagnosed HIV-1 cases to the structure of individual clusters was examined over time.

Results:

Of 2153 individuals, 31% (strict criteria) – 47% (relaxed criteria) clustered. Longitudinal tracking of individual clusters identified three cluster types: normal, semi-normal and abnormal. Normal clusters (83–87% of all identified clusters) showed predicted growing/plateauing dynamics, with approximately three-fold higher growth rates in large (15–18%) vs. small (∼5%) clusters. Semi-normal clusters (1–2% of all clusters) temporarily fluctuated in size and composition. Abnormal clusters (11–16% of all clusters) demonstrated collapses and re-arrangements over time. Borderline values of cluster-defining parameters explained dynamics of non-normal clusters.

Conclusions:

Comprehensive tracing of molecular HIV clusters over time in a statewide epidemic identified distinct cluster types, likely missed in cross-sectional analyses, demonstrating that not all clusters are equal. This knowledge challenges current perceptions of consistent cluster behavior over time and could improve molecular surveillance of local HIV epidemics to better inform public health strategies.
Cystatin C in addition to creatinine for better assessment of glomerular renal function decline in people with HIV receiving antiretroviral therapy
Authors: Mondesert Etienne , Reynes Jacques , Makinson Alain , Bargnoux Anne-Sophie , Plawecki Maëlle , Morquin David , Cristol Jean-Paul , Badiou Stéphanie
Published: January 2023

Objective:

To compare the estimated glomerular filtration rate (eGFR) using the creatinine equation (eGFRcreat) or the cystatin C equation (eGFRcys) in people with HIV (PWH) under antiretroviral drugs. We specifically included patients with an eGFRcreat around 60 ml/min per 1.73 m2 to evaluate agreement on stage 2 and 3 chronic kidney disease (CKD) classification.

Design:

eGFRcreat, eGFRcys and resulting CKD staging were determined in 262 consecutive patients with HIV-1 (PWH) with a suppressed viral load (<200 copies/ml) under antiretroviral drugs and having impaired renal function (eGFRcreat between 45 and 80 ml/min per 1.73 m2). Antiretroviral drugs regimens were classified into eight groups: cobicistat (COBI)+elvitegravir (EVG), ritonavir (RTV)+protease inhibitor, dolutegravir (DTG), DTG+rilpivirine (RPV), RPV, raltegravir (RAL), bictegravir (BIC), and other antiretroviral drugs.

Results:

Mean eGFRcys was higher than mean eGFRcreat (77.7 ± 0.5 vs. 67.9  ± 7.9 ml/min per 1.73 m2, P < 0.0001). The differences were significant in five treatment groups with COBI/EVG; DTG; DTG+RPV; RPV; RAL. CKD classification was modified for 51% of patients when using eGFRcys instead of eGFRcreat, with reclassification to less severe stages in 37% and worse stages in 14%.

Conclusion:

This study highlighted significant differences in eGFR depending on the renal marker used in PWH, having a significant impact on CKD classification. eGFRcys should be an additive tool for patients having eGFRcreat around 60 ml/min per 1.73 m2 for better identification of renal impairment.
Longitudinal comparison of insulin resistance and dyslipidemia in children with and without perinatal HIV infection in South Africa
Authors: Davies Claire , Vaida Florin , Otwombe Kennedy , Cotton Mark F. , Browne Sara , Innes Steve
Published: January 2023

Introduction:

HIV infection is associated with insulin resistance and dyslipidaemia driven by HIV-associated immune dysregulation and antiretroviral therapy (ART). Children living with perinatally acquired HIV (CHIV) face many decades of exposure to these factors. We evaluated the longitudinal trajectory of insulin resistance and dyslipidaemia in CHIV and HIV-exposed uninfected children (CHEU), compared with children HIV-unexposed (CHU).

Methods:

Four hundred and eighty-five children (141 CHIV, 169 CHEU, 175 CHU) aged 5–16 years, previously part of CHER and P1060 trials, were followed annually at Tygerberg Children's Hospital, South Africa. The primary outcome was Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Secondary outcomes included low-density lipoprotein (LDL) cholesterol, triglyceride-to-HDL ratio, android fat mass and SBP. Outcomes were evaluated using linear mixed effects models, adjusting for potential confounders.

Results:

CHIV had 73% greater HOMA-IR than CHU in ages 6–8 years (95% CI 15.9–158.2%,P < 0.001), and 24.7% greater HOMA-IR than CHU in ages 9–10 years (0.3–55.1%,P = 0.04). By 10–11 years, the difference was not significant (P = 0.161). Longitudinally, triglyceride-to-HDL was 47.94% (34.50–62.73%,P < 0.001) higher in CHIV vs. CHU; LDL was 0.25 mmol/l (0.10–0.39,P = 0.001) higher in CHIV vs. CHU; android fat mass was 11.57% (−21.11 to −0.87%,P = 0.035) lower in CHIV than CHU. No significant difference in SBP was found. CHEU and CHU had similar outcomes.

Conclusion:

Early-treated CHIV have elevated insulin resistance, which resolves with time. Triglyceride-to-HDL ratio and LDL cholesterol were elevated into puberty. CHIV should be monitored for insulin resistance, dyslipidaemia and subclinical cardiovascular disease.
Needs for shelter or housing assistance among people with diagnosed HIV by jurisdiction: United States, 2015–2020
Authors: Dasgupta Sharoda , Beer Linda , Lu Jen-Feng , Weiser John , Yuan Xin , Nair Priya , Banks Lauren , Marcus Ruthanne
Published: January 2023

Objective:

To describe the landscape of needs for housing assistance among people with HIV (PWH) and availability of Housing Opportunities for People with AIDS (HOPWA) funding with respect to housing service needs, nationally and for 17 US jurisdictions.

Design:

The CDC Medical Monitoring Project (MMP) is an annual, cross-sectional survey designed to report nationally and locally representative estimates of characteristics and outcomes among adults with diagnosed HIV in the United States.

Methods:

We analyzed 2015–2020 data from MMP and 2019 funding data from HOPWA. Weighted percentages and 95% confidence intervals (CIs) for national and jurisdiction-level estimates were reported.

Results:

Nationally, 1 in 4 (27.7%) PWH had shelter or housing service needs. Among those who needed housing services, 2 in 5 (40.4%) did not receive them (range: 21.3% in New York to 62.3% in Georgia). Reasons for unmet needs were multifactorial and varied by jurisdiction. Available 2019 HOPWA funding per person in need would cover up to 1.24 months of rent per person nationally (range: 0.53 months in Virginia to 9.54 months in Puerto Rico), and may not have matched housing assistance needs among PWH in certain jurisdictions.

Conclusion:

Addressing housing service needs necessitates a multipronged approach at the provider, jurisdiction, and national level. Locally, jurisdictions should work with their partners to understand and address housing service needs among PWH. Nationally, distribution of HOPWA funding for housing services should be aligned according to local needs; the funding formula could be modified to improve access to housing services among PWH.
The role of oncology pharmacists and comprehensive medication reconciliation in informing treatment plans for older adults with cancer and downstream outcomes
Authors: Whitman Andrew , Fitch Emily , Nightingale Ginah
Published: January 2023

Purpose of review

Proper medication management is an essential part of older adult cancer care. An aging population, an increase in anticancer treatment options, and high rates of comorbid conditions make navigating general medication reconciliation complicated. This review will highlight the recent literature describing the roles of the oncology pharmacist in caring for older adults with cancer.

Recent findings

The body of literature highlighting oncology pharmacist roles in this population is mainly focused on polypharmacy and potentially inappropriate medication assessments, deprescribing nonessential therapies, drug–drug interaction reviews, and immunization optimization. Outcomes associated with oncology pharmacist interventions are still lacking as well as the development of benchmarks for appropriate pharmacy-based care in the older adult oncology population.

Oncology pharmacist interventions in older adults with cancer have the potential to improve patient care. Future randomized studies in this area of practice are warranted in order to clearly define the optimal impact of oncology pharmacists.
Immunotherapy for older patients with cancer
Authors: Araujo Vargas Tatianny P. , Al-Humiqani Abdullah , Giffoni De Mello Morais Mata Danilo , Menjak Ines B.
Published: January 2023

Purpose of the review

The aim of this review is to describe the clinical use and tolerability of immune checkpoint inhibitors in older adults with solid tumors, where there is an abundance of evidence with recent updates including subgroups of older patients.

Recent findings

Studies with updated analyses and subgroups of older patients show that in general older patients benefit as well as younger patients and tolerate immunotherapy very well. However, in some instances of combination therapies which may expose patients to more toxicity, the benefits are reduced, and careful selection of older patients, including adjunctive assessments such as geriatric assessment, can help to identify the appropriate treatment for an individual patient.

Older adults remain underrepresented in clinical trials, including those involving immunotherapy. Therefore, efforts must be made to include more older patients in trials and to assess real-world evidence to inform decision-making.
A shift from simple to sophisticated: using intensity-modulated radiation therapy in conventional nonstereotactic palliative radiotherapy
Authors: Dennis Kristopher , Linden Kelly , Gaudet Marc
Published: January 2023

Purpose of review

The authors aimed to highlight trends in, and evidence underlying the use of highly conformal radiotherapy (RT) techniques in conventional nonstereotactic palliative RT. The authors reviewed palliative-intent and curative-intent studies relevant to the use of intensity-modulated radiation therapy (IMRT) for the delivery of nonstereotactic conventional regimens to the brain, head and neck, thorax, abdomen and pelvis, and bone metastases.

Recent findings

The use of IMRT has become standard with certain indications for brain metastases such as hippocampus-avoiding/limiting whole brain RT. IMRT in the treatment of bone metastases is increasing at many institutions despite limited data comparing its effectiveness with that of fluoroscopy-based and three-dimensional conformal radiation therapy techniques. There is scant data describing the use of IMRT for palliation in other extracranial anatomic sites; guidance for its use in these settings must be gleaned almost exclusively from curative-intent randomized trials, consensus recommendations and contouring atlases.

Consistent with historical technology shifts in RT practice, the uptake of highly conformal techniques such as IMRT for conventional palliative RT will likely outpace rigorous evaluations of their advantages and disadvantages relative to simpler techniques. Opportunities exist in virtually all anatomic sites for observational and randomized studies to evaluate the clinical impacts of these modern techniques in the palliative setting.
Estradiol provokes hypercoagulability and affects fibrin biology: A mechanistic exploration of sex dimorphisms in coagulation
Authors: Coleman Julia R. , Moore Ernest E. , Schmitt Lauren , Hansen Kirk , Dow Nathan , Freeman Kalev , Cohen Mitchell J. , Silliman Christopher C.
Published: January 2023

BACKGROUND

Sex dimorphisms in coagulation are well established, with female-specific hypercoagulability conferring a survival benefit in the setting of trauma-induced coagulopathy (TIC). The mechanism behind these phenomena remains to be elucidated. We hypothesize that estradiol provokes a hypercoagulable profile and alters clot proteomics and fibrin crosslinking.

METHODS

Whole blood was collected from healthy adult volunteers (n = 30). A battery of thrombelastography (TEG) assays (native, kaolin, platelet-mapping, functional fibrinogen), whole blood thrombin generation, proteomics, and clot structure architecture (via analysis of fibrin crosslinks and fluorescent fibrinogen-visualized clots) were performed after pre-treatment of the blood with physiologic concentrations of beta-estradiol. In addition, a prospective study of coagulation through the menstrual cycle was conducted by collecting blood from women on peak and nadir estrogen days in the standard 28-day menstrual cycle.

RESULTS

On TEG, in females, estradiol provoked a hypercoagulable phenotype, specifically a shorter time to clot formation and greater thrombin generation, greater rate of clot propagation and functional fibrinogen, higher clot strength, and diminished clot fibrinolysis. In both males and females, estradiol increased platelet hyperactivity. Similar changes were seen in time to clot formation and clot strength in vivo during peak estrus of the menstrual cycle. On proteomic analysis, in both males and females, estradiol was associated with increases in abundance of several procoagulant and antifibrinolytic proteins. Crosslinking mass spectrometry analysis showed addition of estradiol increased the abundance of several FXIII crosslinks within the FIBA alpha chain in both sexes. Fluorescent fibrinogen analysis revealed a trend toward increased fiber resolvability index after addition of estradiol.

CONCLUSION

Estradiol provokes a hypercoagulable phenotype, affecting time to clot formation, clot propagation, clot strength, clot fibrinolysis, and clot structure. In sum, these data highlight the role of estradiol is driving female-specific hypercoagulability and highlights its potential role as a therapeutic adjunct in resuscitation of TIC.
Surgical stabilization of critical abdominal injuries in a mature rural trauma system: A retrospective study
Authors: Tinsman Chandler , Lilienthal Michele , Galet Colette , Torner James , Skeete Dionne A.
Published: January 2023

BACKGROUND

Worse outcomes following injuries are more likely in rural versus urban areas. In 2001, our state established an inclusive trauma system to improve mortality. In 2015, the trauma system had a consultation visit from the American College of Surgeons' Committee on Trauma, who made several recommendations. We hypothesized that continued maturation of this system would lead to more laparotomies prior to transfer to a higher level of care and better outcomes.

METHODS

Our trauma registry was queried to identify all patients transferred between January 1, 2010, and December 31, 2020, who underwent laparotomy either before transfer or within 4 hours of arrival. The preconsultation (2010–2015) and postconsultation periods (2016–2020) were compared. Categorical and continuous variables were compared using χ2 and Mann-Whitney U tests, respectively.

RESULTS

We included 213 patients; 63 had laparotomy before transfer and 150 within 4 hours after transfer. Age, injury severity scores, systolic blood pressure, and mechanism of injury were not different between periods. Proportions of laparotomy before and after transfer and outcomes (mortality, hospital length of stay, intensive care unit length of stay, ventilator days) were also similar (p = 0.368 for laparotomy, p = 0.840, 0.124, 0.286, 0.822 for outcomes). Compared with the preconsultation period, the proportion of laparotomy performed before transfer for severe injuries (abdominal Abbreviated Injury Scale score >3) significantly increased postconsultation (57.1% vs. 30.6%, p = 0.011). Incidence of damage-control laparotomies (43.9% vs. 23.6%; p = 0.020) and transfusion of plasma and platelets (33.6% vs. 13.2%; p < 0.001, 22.4% vs. 8.5%, p = 0.007, respectively) significantly increased.

CONCLUSION

Identification and surgical stabilization of critical patients at the non-Level I facilities prior to transfer, as well as blood product use and damage-control techniques, improved postconsultation, suggesting a shift in the approaches to surgical stabilization and resuscitation efforts in our trauma system.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.