bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal follow-up schedule for patients taking PCSK9 monoclonal antibodies in a health system: Analysis of specialty pharmacy clinical interventions
Authors: Avlasevich Viktoriya , Pilat Stephanie , Reindel Kristin , Manou Katherine , Trawinski Allison , Rightmier, Elizabeth
Published: February 2024

Purpose

The objective of this study was to determine if and when it is clinically appropriate to consider a reduction in the frequency of health-system specialty pharmacy (HSSP) clinical pharmacist assessments for patients taking a proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody (mAb) after they are deemed clinically stable on therapy.

Methods

A single-center, retrospective, observational study of adult patients on PCSK9 mAb therapy enrolled in the University of Rochester Specialty Pharmacy Cardiology Patient Management Program was performed between October 24, 2016, and April 30, 2022. The primary outcome was the number of clinical pharmacist interventions per interval within the baseline 12 months compared to 12-month intervals for up to 72 months after initiation of PCSK9 mAb therapy.

Results

A total of 368 patients on PCSK9 mAb therapy were included in the study. A significantly lower percentage of patients had more than 2 interventions during the 12- to 24-month interval (24.3%) as compared to the baseline 12-month interval (80.2%) (P < 0.001); this represented a 70% reduction in the chance of a patient requiring more than 2 interventions (relative risk, 0.30; 95% CI, 0.24-0.38). A similar trend was demonstrated in the 24- to 36-month and 36- to 48-month intervals when compared to the first year of therapy. The most commonly documented clinical pharmacist interventions were in the categories of safety (29.2%), effectiveness (28.4%), and adherence (19.9%).

Conclusion

Patients beyond 1 year of PCSK9 mAb therapy required less clinical pharmacist interventions. Therefore, stable patients receiving a PCSK9 mAb may be considered for less frequent clinical assessments to allow for HSSP growth to nontraditional clinical areas.
Subspecies inflation hampers conservation efforts: a case study on wall lizards
Authors: Berrilli Emanuele , Gambioli Benedetta , Bombi Pierluigi , Garzia Matteo , Muraro Martina , Pardo Claudio , Reale Marco , Sherpa Stéphanie , Ficetola Gentile Francesco , Vignoli Leonardo , Salvi Daniele
Published: February 2024

The common practice of using subspecies as conservation targets raises the question of whether efforts are focused on preserving conspicuous components of the species’ phenotypic variability rather than evolutionarily significant units. To address this question, in this study we performed a comprehensive morphological and genetic assessment on all the subspecies of wall lizard described for the Aeolian Archipelago (Italy) to determine whether they represent distinct evolutionary lineages and/or discrete phenotypic partitions. Further, we applied a monophyly test to 70 subspecies belonging to seven wall lizard species occurring in Italy, based on our results and on previous phylogeographic studies. We found that none of the Aeolian subspecies represents a distinct evolutionary lineage, despite some morphological differentiation of island populations across the archipelago, suggesting a very recent origin of island populations and of the observed phenotype variation. Across seven wall lizard species, tests revealed that lizard subspecies rarely (< 9% of cases) match evolutionary units. This study demonstrates that intraspecific taxonomy of wall lizards is a poor predictor of phylogeographic partitions and evolutionary units, and therefore of limited use (if not dangerous) for defining conservation and management units. A better approach would be relying on the integration of genomic and phenotypic data to assess the evolutionary significance and conservation value of phenotypic and genetic units within species.
Platelet-Rich Plasma Injections for the Treatment of Degenerative Orthopedic Conditions
Authors: Means Gary E , Muench Peter
Published: February 2024

Platelet-rich plasma injections for the treatment of degenerative orthopedic conditions have good evidence for safety, pain relief, and functional improvement. The U.S. Military is providing platelet-rich plasma services for military services members and TRICARE beneficiaries. The use of this safe and effective treatment should be continued and expanded.
Association of Nirmatrelvir/Ritonavir Treatment and COVID-19-Neutralizing Antibody Titers in a Longitudinal Health Care Worker Cohort
Authors: Decker Slade , Xiao Shaoming , Dillen Carly , Schumacher Christina M , Milstone Aaron M , Frieman Matthew , Debes Amanda K
Published: February 2024

Nirmatrelvir/ritonavir (NMV/r) is used for the treatment of coronavirus disease 2019 (COVID-19) infection. However, rebound COVID-19 infections can occur after taking NMV/r. We examined neutralizing antibodies to the severe acute respiratory syndrome coronavirus 2 spike protein before and after infection in people who did and did not take NMV/r to determine if NMV/r impedes the humoral immune response.
Impact of Increasing PD-L1 Levels on Outcomes to PD-1/PD-L1 Inhibition in Patients With NSCLC: A Pooled Analysis of 11 Prospective Clinical Trials
Authors: Vallejo Jonathon , Singh Harpreet , Larkins Erin , Drezner Nicole , Ricciuti Biagio , Mishra-Kalyani Pallavi , Tang Shenghui , Beaver Julia A , Awad Mark M
Published: February 2024

Background

Programmed death ligand 1 (PD-L1) expression is recognized as a key biomarker in the treatment of non–small cell lung cancer (NSCLC) with anti-PD(L)1 inhibitors. Previous work has highlighted that outcomes in patients with NSCLC treated with anti-PD(L)1 inhibitors generally improve with increasing PD-L1 expression. The objectives of these analyses are to quantitate the effect of PD-L1 expression on outcomes, to characterize the potentially nonlinear relationship between PD-L1 expression and outcomes, and to assess potential differences in these relationships across subgroups.

Patients and Methods

We performed a retrospective, pooled analysis of 11 clinical trials submitted to the US FDA between 2015 and 2022 that included patients with advanced NSCLC treated with anti-programmed death 1 or anti-PD-L1 immune checkpoint inhibitor (ICI) monotherapy in the first-line (1L) or second-line (2L) treatment setting. The clinical outcomes explored were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

Results

The primary analysis population included 3806 patients with advanced NSCLC, of which 2040 were treated in 1L and 1766 in 2L. For patients with a PD-L1 score of 100% in the 1L setting, the hazard ratio versus a patient with 1% PD-L1 was 0.55 (95% CI, 0.43 to 0.70) for OS and 0.50 (95% CI, 0.41 to 0.61) for PFS. For patients with a PD-L1 score of 100% in the 2L setting, the hazard ratio versus a patient with 0% PD-L1 was 0.55 (95% CI, 0.43 to 0.71) for OS and 0.51 (95% CI, 0.41 to 0.63) for PFS. Subgroup analyses suggested that this relationship may vary by subgroup, particularly by region.

Conclusions

These analyses suggest PD-L1 expression has an appreciable impact on clinical outcomes for patients with NSCLC treated with ICI. As the impact of PD-L1 expression on outcomes may vary across regions, it is critical that future trials are multiregional and enroll a diverse patient population.
Inquiry in Action: A Problem-Oriented Account of Agency
Authors: Dyck Nathan
Published: February 2024

In this paper, I argue that it is not a necessary condition of intentional agency that agents act on intentions with antecedently clear content. That is, some actions proceed on the basis of intentions which do not initially provide necessary conditions for performing those actions, and instead involve discovering at least some of these conditions in the course of performing them. To do this, I develop an account of problem-oriented agency, according to which agents may act in relation to problems which at first resist adequate representation. This pushes us to recognize a dimension of open-ended inquiry in agency often neglected in rationalist accounts. Lastly, I argue that paradigmatically rational actions on determinate intentions which are not sensitive to potentially transformative feedback in the course of their execution can fall short of full agency in important ways.
Complex geohistory of continental islands advanced allopatric evolution even for the highly dispersive generalist red fox (Vulpes vulpes): multiple phylogenetic groups in the Japanese Archipelago
Authors: Watanabe Takumi , Yamazaki Yuji
Published: February 2024

The red fox (Vulpes vulpes) plays a key role as an apex-generalist predator in terrestrial ecosystems. We estimated the phylogeographic structure, time to most recent common ancestor (tMRCA), and demographic dynamics based on the mitochondrial DNA cytochrome b gene and partial D-loop region sequences of 182 red foxes in the Japanese Archipelago, and discussed the geohistory and biotic interactions that influenced them. The Hondo red fox (Vulpes vulpes japonica), distributed on Honshu, Shikoku, and Kyushu islands, was supported as a monophyletic group. The tMRCA of the Hondo clade was ~0.148 (95% highest posterior density: 0.236–0.080) Ma. The Hondo clade diverged into two subclades, and each was roughly distributed on the eastern or western area of the Japanese Archipelago. The effective population size of the Hondo red fox remained nearly constant until ~0.03–0.02 Ma; thereafter, it grew ~10-fold. The Kita red fox (Vulpes vulpes schrencki) distributed on Hokkaido Island formed a polyphyletic group, not including the Hondo clade. The completely different phylogenetic structures of the Hondo and Kita red fox indicate that they have independent evolutionary backgrounds. These findings provide crucial insights into the formation mechanisms of diversity and endemism of mammals on continental islands.
Improving clinician communication to increase adolescent HPV vaccination rates
Authors: Meachum Chelsey
Published: February 2024

Despite the proven effectiveness of human papillomavirus (HPV) vaccination, this vaccine is underused in the United States and is associated with many disparities and barriers to acceptance. Adolescent HPV vaccination rates failed to meet the Healthy People 2020 goal of 80% vaccine coverage when nearly all other routine adolescent vaccines met or were near this goal. When introducing the HPV vaccine series, many clinicians use a conversational approach, although years of research show that an announcement approach is more effective at increasing HPV vaccination rates. This article reviews current HPV vaccine communication practices used by clinicians and recommends evidence-based best practices to improve adolescent HPV vaccination rates in the United States.
Angiogenic Biomarkers in Preeclampsia
Authors: Burwick Richard M. , Rodriguez M. Hellen
Published: February 2024

Preeclampsia contributes disproportionately to maternal and neonatal morbidity and mortality throughout the world. A critical driver of preeclampsia is angiogenic imbalance, which is often present weeks to months before overt disease. Two placenta-derived angiogenic biomarkers, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), have proved useful as diagnostic and prognostic tests for preeclampsia. Recently, the U.S. Food and Drug Administration approved the sFlt-1/PlGF assay to aid in the prediction of preeclampsia with severe features among women with hypertensive disorders of pregnancy at 24–34 weeks of gestation. In this narrative review, we summarize the body of work leading to this approval and describe how the sFlt-1/PlGF ratio may be implemented in clinical practice as an adjunctive measure to help optimize care and to reduce adverse outcomes in preeclampsia.
Cheilectomy and the Shortening PelCO for the Treatment of Low-grade Hallux Rigidus
Authors: Del Vecchio Jorge J. , Dealbera Eric D. , Ferraz Ferreira Gabriel , Dalmau-Pastor Miki
Published: February 2024

Hallux rigidus is a degenerative condition of the first metatarsophalangeal joint resulting in stiffness and pain. Surgical treatments can be divided into joint-sparing and joint-sacrificing procedures. Cheilectomy has been recommended as an isolated procedure for the treatment of low-grade hallux rigidus (I and II, even III in some articles). First metatarsal shortening osteotomies are indicated in low-grade hallux rigidus. The Shortening Percutaneous, Intra-articular, Chevron Osteotomy resembles the Green-Watermann procedures regarding shortening and decompression. Shortening Percutaneous, Intra-articular, Chevron Osteotomy provides excellent clinical and functional results and represents a viable treatment option to decrease pain, improve function, and maintain motion for hallux rigidus grade I and II.

Level of Evidence: Diagnostic level IV.
Serum Bicarbonate Levels Among Patients on Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome With and Without Kidney Replacement Therapy
Authors: Adkisson Wren S. , Gannon Whitney D. , Qian Edward T. , Bacchetta Matthew , Siew Edward D. , Ford Daniel J. , Landsperger Janna S. , Rice Todd W. , Casey Jonathan D. , Semler Matthew W. ,   for the Pragmatic Critical Care Research Group
Published: February 2024

OBJECTIVES:

For patients with acute respiratory distress syndrome (ARDS) receiving venovenous extracorporeal membrane oxygenation (ECMO) who develop acute kidney injury (AKI) requiring kidney replacement therapy (KRT), the inability to renally compensate for respiratory acidosis could result in increased sweep gas flow to normalize arterial pH. Our objective was to examine the relationship of serum bicarbonate levels, arterial pH, sweep gas flow, and Paco
2.

DESIGN:

This is a retrospective cohort study. We compared patients who received KRT while undergoing venovenous ECMO to patients who did not.

SETTING:

Vanderbilt University Medical Center, February 2019 to February 2022.

PATIENTS:

We examined data from adult patients receiving venovenous ECMO for ARDS.

INTERVENTIONS:

Values for serum bicarbonate, arterial pH, Paco
2, and sweep gas flow were collected daily from time of cannulation until the earlier of decannulation, 30 days, or death.

MEASUREMENTS AND MAIN RESULTS:

Of the 126 patients included, 53 (42.1%) received KRT and 73 (57.9%) did not. In patients who received KRT, mean serum bicarbonate levels remained between 22 and 28 mmol/L throughout the study period. Patients who did not receive KRT experienced an increase in mean serum bicarbonate levels over time up to 40 mmol/L (mean difference = –4.4 mmol/L [95% CI, –6.3 to –2.5 mmol/L]; p < 0.0001). Mean values for Paco
2 (–5.2 [95% CI, –8.8 to –1.7]; p = 0.004) and pH (–0.03 [95% CI, –0.03 to –0.02]; p < 0.0001) were lower in patients who received KRT than in patients who did not, despite higher sweep gas flow rates in patients who received KRT than in patients who did not (mean difference = 1.5 [95% CI, 0.8–2.3]; p < 0.001).

CONCLUSIONS:

ARDS patients on venovenous ECMO with preserved kidney function experience an increase in bicarbonate concentration over time, compared to patients with AKI on KRT. Whether this increase in bicarbonate concentration increases pH, decreases sweep gas flow requirements, and facilitate weaning from venovenous ECMO requires examination in future research.
Association of Neighborhood Opportunity with Infant Brain Activity and Cognitive Development
Authors: Elansary Mei , Wei Wendy S. , Pierce Lara J. , McCoy Dana C. , Nelson Charles A.
Published: February 2024

Background and objectives:

Neighborhood socioeconomic disadvantage is associated with lower neurocognitive scores and differences in brain structure among school-age children. Associations between positive neighborhood characteristics, infant brain activity, and cognitive development are underexplored. We examined direct and indirect associations between neighborhood opportunity, brain activity, and cognitive development.

Methods:

This longitudinal cohort study included infants from 2 primary care clinics in Boston and Los Angeles. Using a sample of 65 infants, we estimated path models to examine associations between neighborhood opportunity (measured by the Child Opportunity Index), infant electroencephalography (EEG) at 6 months, and infant cognitive development (measured using the Mullen Scales of Early Learning) at 12 months. A mediation model tested whether EEG power explained associations between neighborhood opportunity and infant cognition.

Results:

Neighborhood opportunity positively predicted infant absolute EEG power across multiple frequency bands: low

(b = 0.12, 95% CI 0.01–0.24, p = 0.04,

= 0.21); high

(b = 0.11, 95% CI 0.01–0.21, p = 0.03,

= 0.23);

(b = 0.10, 95% CI 0.00–0.19, p = 0.04,

= 0.20); and

(b = 0.12, 95% CI 0.02–0.22, p = 0.02,

= 0.24). The results remained statistically significant after applying a Benjamini-Hochberg false discovery rate of 0.10 to adjust for multiple comparisons. No significant associations emerged between neighborhood opportunity, relative EEG power, and infant cognition. Mediation was not significant.

Conclusion:

Neighborhood opportunity is positively associated with some forms of infant brain activity, suggesting that positive neighborhood characteristics may play a salient role in early development.
A Review of Aesthetic Considerations for Treating the Transgender Patient
Authors: Cattelan Leila , Dayan Steven , Aguilera Shino Bay , Viscomi Bianca , Fabi Sabrina G.
Published: February 2024

BACKGROUND

As gender diversity becomes increasingly embraced by society, and despite growing recognition of the unique needs of transgender patients, the literature remains devoid of guidelines for gender affirming facial feminization or masculinization techniques.

OBJECTIVE

The authors seek to identify and discuss target feminine and masculine facial features, as well as an armamentarium of surgical and nonsurgical strategies to effectively address and achieve them in the transgender population.

METHODS

A search of the National Library of Medicine database (PubMed) was undertaken to identify the existing literature on gender-affirming facial feminization and masculinization techniques.

RESULTS

The importance of assessing proportional relationships between the bitemporal, bizygomatic, and bigonial distances is discussed; ideal masculine faces possess a rectangular face shape, with ratios for these 3 areas tending toward 1:1:1. Conversely, the ideal female face is heart shaped with projection at the zygoma and a tapered jawline. Strategic positioning of the cheek apex serves as an anchor in sculpting a distinctly masculine or feminine face. Other considerations include the enhancement of skin quality and implications of hormonal therapy.

CONCLUSION

The aesthetic considerations provided in this study can serve as a valuable guidance for aesthetic physicians seeking to deliver optimal care for their transitioning patients.
Lacrimal Sac Characteristics in Patients With Punctal and Canalicular Agenesis: Punctum Update (PUP) Study—Paper 3
Authors: Bothra Nandini , Mishra Dilip , Ali Mohammad Javed
Published: February 2024

Purpose:

To explore the endoscopic and histopathologic characteristics of the lacrimal sac (LS) and the nasolacrimal duct in cases with punctal agenesis presenting with LS swellings.

Methods:

This is a prospective, interventional study of 13 LSs of 8 patients presenting with punctal agenesis and LS swellings over a 5-year study period (June 2018–July 2023). Complete ophthalmic examination was performed along with CT scans of the orbits. The LS was exposed with an anterior lacrimal crest incision and explored. The exterior and interior of the sac swelling were examined and LS flaps were sent for histopathological analysis.

Results:

The mean age of the patients was 23 years with a male:female ratio of 5:3. All patients presented with swelling in the LS region. Occasional epiphora was the presenting feature in 6 patients. All patients had both upper and lower punctal agenesis on the affected side with associated LS swelling. CT scans showed a hypodense cystic swelling with expansion of the LS fossa and bony nasolacrimal duct ending abruptly short of the inferior meatus. Intraoperatively, the LS had thin, translucent walls with mucoid secretion and an absence of common canalicular opening. Histopathological analysis showed epithelium consistent with LS with less robust development of the sac walls and poorly structured lacrimal drainage-associated lymphoid tissue with scanty stromal inflammation.

Conclusions:

The development of LS and the nasolacrimal duct is structurally affected in patients with punctal agenesis. Retrograde approaches for epiphora resolution are not logical in such cases but conjunctivodacryocystorhinostomy with Jones tube can be a feasible option.
Antisynthetase Syndrome Causing Necrotizing Myositis Involving Extraocular Muscles
Authors: Lin Lisa Y. , Azad Amee D. , Chiou Carolina A. , Kozanno Liana , Stemmer-Rachamimov Anat , Stone John , Lee Nahyoung Grace
Published: February 2024

The authors describe the clinical, histologic, and serologic findings of a patient with necrotizing myositis of the extraocular muscles in the setting of antisynthetase syndrome, as well as subsequent management. This is the first case in the literature of a systemic necrotizing myositis to have associated ophthalmic findings.
Gestational Diabetes Mellitus, Obstetric Data, and Simple Congenital Ptosis
Authors: Gushansky Konstantin , Nemet Achia , Tuuminen Raimo
Published: February 2024

Purpose:

This retrospective cohort study aimed to identify obstetric risk factors for simple congenital ptosis and propose an underlying pathophysiological mechanism.

Methods:

Newborns diagnosed with simple congenital ptosis (n = 51) were compared with existing population data in terms of obstetric parameters.

Results:

Positive associations were found between simple congenital ptosis and gestational diabetes mellitus (11.8% vs. 5%, p = 0.026), preterm delivery (15.7% vs. 0.05%, p < 0.001), and lower birth weight (2,998 ± 506 vs. 3,255 ± 484, p < 0.001).

Conclusions:

This study pioneers an association between simple congenital ptosis and gestational diabetes mellitus, potentially linked to insulin-like growth factor 1 levels. We advocate for early ophthalmology checkups for specific newborn subsets.
All about traumatic cataracts: narrative review
Authors: Soleimani Mohammad , Cheraqpour Kasra , Salari Farhad , Fadakar Kaveh , Habeel Samer , Baharnoori Seyed Mahbod , Banz Soraya , Tabatabaei Seyed Ali , Woreta Fasika A. , Djalilian Ali R.
Published: February 2024

Ocular trauma is an important cause of monocular blindness worldwide. Injury to the lens after blunt or penetrating trauma is common and can result in vision impairment. Selecting the most appropriate therapeutic approaches depends on factors such as patients' age, mechanism of trauma, and underlying clinical conditions. Early management, especially within childhood, is essential because of the difficulties involved in examination; anatomical variations; as well as accompanying intraocular inflammation, amblyopia, or vitreoretinal adhesions. The objective of this study was to provide a comprehensive review of the epidemiology and clinical management of traumatic cataract, highlighting the significance of accurate diagnosis and selection of the optimal therapeutic approach.
ChatGPT’s innovative application in blood morphology recognition
Authors: Yang Wan-Hua , Yang Yi-Ju , Chen Tzeng-Ji
Published: February 2024

Background:

Recently, the rapid advancement in generative artificial intelligence (AI) technology, such as ChatGPT-4, has sparked discussions, particularly in image recognition. Accurate results are critical for hematological diagnosis, particularly for blood morphology identification. Despite advanced hematology analyzers, reliance on professional hematopathologists for manual identification remains in cases of abnormal or rare conditions, a process prone to human subjectivity and potential errors. Consequently, this study aimed to investigate the potential of ChatGPT-4 to assist with blood morphology identification.

Methods:

We conducted a retrospective study using blood images obtained from the American Society of Hematology (ASH). These images comprised a range of normal and abnormal morphologies. Each sample was analyzed by expert technicians (control group) and classified using ChatGPT-4 (test group).

Results:

Preliminary results showed that ChatGPT-4 could identify normal blood cells with an accuracy of 88%, exceeding the accuracy of identifying abnormal blood cells at a rate of 54%. Regarding identifying abnormal cells, the accuracy of ChatGPT-4 was slightly higher than that of the manual method, which was 49.5%.

Conclusion:

This study shows that although generative AI shows the potential for blood type identification, it has not yet reached the point where it can replace the professional judgment of medical staff. The results showed that ChatGPT-4 is excellent for identifying red blood cell morphology, particularly inclusion bodies. It can be used as an auxiliary tool for clinical diagnosis. However, the overall recognition accuracy must be further improved. Our study produced innovative results in this field, establishing a foundation for future studies and highlighting the potential of generative AI in aiding blood morphology recognition. Future research should focus on enhancing the effectiveness of AI to improve overall standards of medical care.
The Impact of Adjustment on Workplace Attitudes and Behaviors Among Health Care Workers During the COVID-19 Pandemic
Authors: Griffin Brandon J. , Coyle Patrick T. , Weber Marcela C. , Benight Charles C. , Morison Margaret , Maguen Shira , Pyne Jeffrey , Duncan Matthew S. , Brady Robert E. , Wright Hannah , Love Tiffany , Langenecker Scott A. , Smith Andrew J.
Published: February 2024

Objective

We examined the impact of health care workers’ (HCWs) adjustment to the COVID-19 pandemic on their work-related attitudes and behaviors.

Methods

HCWs (n = 1468) participated in an observational longitudinal study in which they completed surveys of anxiety and occupational health between 2020 and 2021.

Results

Most HCWs reported anxiety that was consistently below the diagnostic threshold (68%) or fell below the threshold within a year (16%). Others reported consistently high (14%) or increasing (2%) anxiety, especially women, younger HCWs, those with a weakened immune system, and allied health professionals. Consistently high or increasing anxiety was associated with poorer job satisfaction, work engagement, perceived supervisor support, burnout, and turnover intentions.

Conclusions

Resources to support HCWs may be focused on those who report consistently high or increasing anxiety to minimize the effects of crises and disasters on the workforce.
2023 Prentice Medal Award lecture: Ocular surface–related symptoms of discomfort and other stories
Authors: Papas Eric B.
Published: February 2024

I have been fortunate to spend portions of my career in each of private practice, industry, and academia. At some times, these occupations have dictated the research direction, whereas, at others, curiosity has been allowed to dominate. This has resulted in multiple avenues of inquiry (some might say, too many), along which I have traveled with a rich and varied cast of collaborators, who have all taught me a great deal. The privilege of being awarded the Charles F. Prentice medal provides me an opportunity to summarize some of these activities. Beginning with an attempt to use contact lenses to solve a problem for those affected by albinism, the story shifts to addressing some of the wider deficiencies of contact lenses, in particular the consequences of their oxygen permeability and tendency to induce discomfort toward the end of the day. After briefly considering some aspects of meibomian gland function, the narrative concludes with the latest investigations of neurological links between the cornea and migraine.
HIV-1 drug resistance and genetic diversity in people with HIV-1 in Cape Verde
Authors: Gonçalves Paloma , Barreto Jorge , Santos Menilita , Leal Silvania , Marcelino José , Abecasis Ana , Palladino Claudia , Taveira Nuno
Published: February 2024

Objectives:

To characterize the genetic diversity and drug resistance profiles of people with HIV-1 failing ART in Cape Verde (CV).

Design:

Cross-sectional study conducted between January 2019 and December 2021 in 24 health centres on the islands of Santiago and São Vicente.

Methods:

The HIV-1 pol gene was sequenced in individuals with a detectable viral load. HIV-1 genetic diversity was determined by phylogenetic analysis. Drug resistance mutation patterns and resistance phenotypes were estimated using the Stanford algorithm.

Results:

Viral load was detected in 73 of 252 (29%) enrolled participants and sequencing data were produced for 58 (79%) participants. CRF02 AG strains predominated (46.5%), followed by subtype G (22.4%). Most patients (80%) had mutations conferring resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) (67%), nucleoside reverse transcriptase inhibitors (55%), integrase inhibitors (10%) and/or protease inhibitors (7%) used in Cape Verde, a significant increase compared with a study conducted in 2010–2011. The most common mutations were M184V/I (43%), K103N/S (36%) and G190A/S (19%). NNRTI resistance was associated with younger age and exposure to two or more drug regimens.

Conclusion:

The HIV-1 epidemic in Cape Verde is mainly driven by CRF02_AG and subtype G. Resistance to NNRTIs and/or NRTIs is highly prevalent and resistance to LPV/r and DTG is emerging. Our results support the use of DTG-based first-line ART and protease inhibitor-based regimens for patients with virological failure, but emerging resistance to LPV/r and DTG is a concern. Continued monitoring of drug resistance is essential to ensure adequate healthcare for PWH in Cape Verde.
Feasibility of Implementing a Low-Barrier Long-Acting Injectable Antiretroviral Program for HIV Treatment and Prevention for People Experiencing Homelessness
Authors: Mehtani Nicky J. , Strough Alix , Strieff Sarah , Zevin Barry , Eveland Joanna , Riley Elise D. , Gandhi Monica
Published: February 2024

Background:

Long-acting (LA) antiretrovirals may provide meaningful benefit to people who use drugs and people experiencing homelessness (PEH) who face disproportionate structural and psychosocial barriers in adhering to daily oral HIV antiretroviral therapy or pre-exposure prophylaxis (PrEP), but their use in these populations has not been studied.

Setting:

The Maria X. Martinez Health Resource Center is a low-barrier (eg, no appointment) community-based clinic serving San Francisco PEH.

Methods:

A multidisciplinary care model with robust monitoring and outreach support was developed to provide LA antiretroviral therapy (ART) and LA-PrEP to eligible patients experiencing difficulties adhering to oral antiretrovirals. Feasibility was assessed by evaluating the rates of HIV viremia and on-time injections among patients receiving LA antiretrovirals over the first 24 months of program implementation.

Results:

Between November 2021 and November 2023, 33 patients initiated LA-ART or LA-PrEP (median age, 37 years; 27% transgender/nonbinary; 73% non-White; 27% street homeless; 52% sheltered homeless; 30% with opioid use disorder; 82% with methamphetamine use disorder). Among 18 patients with HIV, 14 initiated LA-ART injections with detectable viremia (median CD4 count, 340 cells/mm3; mean log10 viral load, 3.53; SD, 1.62), 8 had never previously been virally suppressed, and all but 1 achieved or maintained virologic suppression (mean, 9.67 months; SD, 8.30). Among 15 LA-PrEP patients, all remained HIV negative (mean, 4.73 months; SD, 2.89). Of 224 total injections administered, 8% were delayed >7 days.

Discussion:

The implementation of LA antiretrovirals is feasible in low-barrier, highly supportive clinical settings serving vulnerable PEH. Expansion of such programs will be critical in ending the HIV epidemic.
Comparative Study of Different Imaging Modalities for Diagnosis of Bone Metastases of Prostate Cancer
Authors: Kim Keunyoung , Ha Mihyang , Kim Seong-Jang
Published: February 2024

Purpose

This study aimed to compare the diagnostic performances of 8 different imaging modalities for preoperative detection of bone metastases in prostate cancer patients by performing a network meta-analysis using direct comparison studies with 2 or more imaging techniques.

Patients and Methods

We searched PubMed, Embase, and Cochrane Library for studies evaluating the performances of 8 different imaging modalities for the preoperative detection of bone metastases in prostate cancer patients. The network meta-analysis was performed in patient-based analysis. The consistency was evaluated by examining the agreement between direct and indirect treatment effects, and the surface under the cumulative ranking curve (SUCRA) values were obtained to calculate the probability of each imaging modality being the most effective diagnostic method.

Results

A total of 999 patients from 13 direct comparison studies using 8 different imaging modalities for preoperative detection or follow-up of bone metastases in prostate cancer patients were included. For the detection of bone metastases of prostate cancer,68Ga-PSMA-11 PET/CT showed the highest SUCRA values of sensitivity, positive predictive value, accuracy, and diagnostic odds ratio. In addition,18F-NaF PET/CT and SPECT/CT showed high SUCRA values.

Conclusions

68Ga-PSMA-11 PET/CT showed the highest SUCRA values. Other imaging modalities showed complementary diagnostic roles for preoperative detection of bone metastases in patients with prostate cancer, except bone scintigraphy and MRI.
Exploring Theranostic Avenues in Adrenocortical Carcinoma Using Chemokine Receptor and Prostate-Specific Membrane Antigen–Directed PET/CT
Authors: Hahner Stefanie , Higuchi Takahiro , Serfling Sebastian E. , Samnick Samuel , Fuss Carmina Teresa , Heinze Britta , Buck Andreas K. , Schirbel Andreas , Fassnacht Martin , Werner Rudolf A.
Published: February 2024

We report on an adrenocortical carcinoma (ACC) patient, which has exhausted previous treatment options and was scheduled for prostate-specific membrane antigen (PSMA)- and C-X-C motif chemokine receptor 4 (CXCR4)-targeted PET/CT. We identified PSMA-avid pulmonary metastases exhibiting modest radiotracer accumulation, while chemokine receptor PET/CT provided intense uptake. This dual-tracer molecular imaging approach revealed that chemokine receptor PET appears to be more suitable in patients with advanced ACC, indicating that CXCR4-directed radioligand therapy may be considered in such patients suffering from end-stage disease. Given its dismal prognosis, chemokine receptor-directed theranostics may therefore extend the therapeutic armamentarium as last-line option in advanced ACC.
Granulomatosis With Polyangiitis of Spinal Dura Presenting With “Bottle Brush Sign” on 18F-FDG PET/CT
Authors: Zhang Yue , Wu Chunyan , Shi Qinwen , Su Minggang
Published: February 2024

A 72-year-old man with fever and weakness in both lower limbs underwent thoracolumbar MRI and 18F-FDG PET/CT. The PET/CT scan revealed diffused FDG uptake along the spinal dura mater from T7 to S2 level like a “bottle brush.” Pathologic examination after biopsy of spinal canal lesions manifested granulomatous inflammation. The blood test showed cytoplasmic antineutrophil cytoplasmic antibody (ANCA) and myeloperoxidase-ANCAs were positive, whereas the perinuclear ANCA was negative. Eventually, he was diagnosed with granulomatosis with polyangiitis.
Continued Diabetes Remission Despite Weight Recurrence: Gastric Bypass Long-Term Metabolic Benefit
Authors: Ghanem Omar M , Abi Mosleh Kamal , Kerbage Anthony , Lu Lauren , Hage Karl , Abu Dayyeh Barham K
Published: February 2024

BACKGROUND:

Roux-en-Y gastric bypass (RYGB) demonstrates high rates of type 2 diabetes mellitus (T2DM) remission, a phenomenon hypothesized to be mediated mainly by weight loss. Compared with procedures that do not bypass the proximal small intestines, such as sleeve gastrectomy (SG), RYGB exhibits weight loss–independent intestinal mechanisms conducive to T2DM remission. We investigated continued diabetes remission (CDR) rates despite weight recurrence (WR) after RYGB compared with an SG cohort.

STUDY DESIGN:

A retrospective review of patients who underwent successful primary RYGB or SG with a BMI value of 35 kg/m2 or more and a preoperative diagnosis of T2DM was performed. Patients with less than 5 years of follow-up, absence of WR, or lack of T2DM remission at nadir weight were excluded. After selecting the optimal procedure for glycemic control, rates of CDR were then stratified into WR quartiles and compared.

RESULTS:

A total of 224 RYGB and 46 SG patients were analyzed. The overall rate of CDR was significantly higher in the RYGB group (75%) compared with the SG group (34.8%; p < 0.001). The odds of T2DM recurrence were 5.5 times higher after SG compared with RYGB. Rates of CDR were stratified into WR quartiles (85.5%, <25%; 81.7%, 25% to 44.9%; 63.2%, 45% to 74.9%; and 60%, >75%). Baseline insulin use, higher preoperative glycosylated hemoglobin, and longer preoperative duration of T2DM were associated with T2DM recurrence, whereas WR was not.

CONCLUSIONS:

T2DM remission rates after RYGB are maintained despite WR, arguing for a concurrent weight loss–independent metabolic benefit likely facilitated by bypassing the proximal small intestine.
Characterization of MultidrugResistant serogroup 19 Streptococcus pneumoniae isolated from healthy children below 5 years of age in Indonesia
Authors: Salsabila Korrie , Winarti Yayah , Paramaiswari Wisiva Tofriska , Tafroji Wisnu , Putri Hanifah Fajri Maharani , Daningrat Wa Ode Dwi , Wulandari I Gusti Ayu Inten , Soebandrio Amin , Safari Dodi
Published: February 2024

We investigated the resistance genes, pilus islets, biofilm formation ability and sequence types of multidrug-resistant

Streptococcus pneumoniae

(MDRSP) isolated from healthy children below 5 years of age in Indonesia. In all, 104 archived MDRSP isolates from previous carriage studies in Indonesia in 2016–2019 were screened for the presence of antibiotic resistance genes and the rrgC (pilus islet 1) and pitB (pilus islet 2) genes. Multilocus sequence typing and biofilm formation were determined by PCR sequencing and the ability of cells to adhere to the walls, respectively. Results have shown that the mefA, ermB and tetM genes were found in 93, 52 and 100 % of MDRSP isolates, respectively. Insertions of arginine, proline and Ile-100–Leu were the most common mutations in the folA and folP genes. Pilus islets 1 and 2 were discovered in 93 and 82 % of MDRSP isolates, respectively. The MDRSP isolates showed no biofilm formation ability (64 %), and 5 out of 10 strains of MDRSP strains were ST1464. This finding can be used to provide further considerations in implementing and monitoring pneumococcal vaccination in Indonesia.
Feasibility of Identifying Factors Related to Alzheimer’s Disease and Related Dementia in Real-World Data
Authors: Chen Aokun , Li Qian , Huang Yu , Li Yongqiu , Chuang Yu-neng , Hu Xia , Guo Serena , Wu Yonghui , Guo Yi , Bian Jiang
Published: February 2024

A comprehensive view of factors associated with AD/ADRD will significantly aid in studies to develop new treatments for AD/ADRD and identify high-risk populations and patients for prevention efforts. In our study, we summarized the risk factors for AD/ADRD by reviewing existing meta-analyses and review articles on risk and preventive factors for AD/ADRD. In total, we extracted 477 risk factors in 10 categories from 537 studies. We constructed an interactive knowledge map to disseminate our study results. Most of the risk factors are accessible from structured Electronic Health Records (EHRs), and clinical narratives show promise as information sources. However, evaluating genomic risk factors using RWD remains a challenge, as genetic testing for AD/ADRD is still not a common practice and is poorly documented in both structured and unstructured EHRs. Considering the constantly evolving research on AD/ADRD risk factors, literature mining via NLP methods offers a solution to automatically update our knowledge map.

HIGHLIGHTS

We summarized the risk factors for AD/ADRD by reviewing existing meta-analyses and review articles on risk and preventive factors for AD /ADRD.

Drawing from this literature review and identified AD/ADRD factors, we explored the accessibility of these risk and preventive factors in both structured and unstructured EHR data.

We constructed an interactive knowledge map that can be used to aid in the design of future AD/ADRD studies that aim to leverage large collections of RWD to generate RWE.
Deep learning-based Spatial Feature Extraction for Prognostic Prediction of Hepatocellular Carcinoma from Pathological Images
Authors: Hu Huijuan , Tan Tianhua , Liu Yerong , Liang Wei , Zhang Wei , Cui Ju , Song Jinghai , Li Xuefei
Published: February 2024

The spatial structures of various cell types in tumor tissues have been demonstrated to be able to provide useful information for the evaluation of the disease progression as well as the responsiveness to targeted therapies. Therefore, powered by machine-learning, several image segmentation methods have been developed to identify tumor-cells, stromal, lymphocytes, etc., in hematoxylin and eosin (H&E) stained pathological images. However, the quantitative and systematic characterization of the spatial structures of various cell types is still challenging. In this work, we first developed a robust procedure based on deep learning to precisely recognize cancer cells, stromal and lymphocytes in H&E-stained pathological images of hepatocellular carcinoma (HCC). In order to quantitatively characterize the composition and spatial arrangement of the tumor microenvironment, we then systematically constructed 109 spatial features based on locations of the 3 major types of cells in the H&E images. Interestingly, we discovered that the absolute values of several spatial features are significantly associated with patient overall survival in two independent patient cohorts, such as the cellular diversity around stromal cells (StrDiv), the average distance between stromal cells (StrDis), the coefficient of variation of the tumor-cell polygon area in the Voronoi diagram (TumCV),etc., based on univariate analysis. In addition, multivariate Cox regress analyses further demonstrated that StrDiv and StrDis are independent survival prognostic factors for HCC patient from The Cancer Genome Atlas Program (TCGA). Furthermore, we demonstrated that a combination analysis with cell spatial features,i.e. StrDiv or TumCV, and another important clinical feature,i.e. microvascular invasion (MVI), can further improve the efficacy of prognostic stratification for patients from the Beijing Hospital cohorts. In summary, the spatial features of tumor microenvironment enabled by the digital image analysis pipeline developed in this work can be effective in patient stratification, which holds the promise for its usage in predicting the therapeutic response of patients in the future.
IMPROVING ANTIBIOTICS USE IN PEDIATRIC HOSPITALS IN ARGENTINA: FEASIBILITY STUDY
Authors: Jorro-Baron Facundo , Echave Cecilia , Rodriguez Viviana , Aguilar Maria-Jose , Balboa Romina , Guglielmino Marina , Garcia-Causarano Florencia , Del Negro Veronica , Dondoglio Patricia , Falcon Esteban , Gibbons Luz , Guerrero Celeste , Juarez Ximena , López Analía , Matteucci Erika , Rodriguez Ana Paula , Vitar Emilse , Roberti Javier , Garcia-Elorrio Ezequiel , Falaschi Andrea
Published: February 2024

Background

We aimed to test the feasibility of a multifaceted intervention to enhance the quality of antibiotic prescription by reducing its overuse and increasing the use of narrow-spectrum agents, comprising a range of antimicrobial stewardship strategies in LMIC pediatric hospitals.

Methods

We implemented a quality improvement (QI) initiative for the treatment of three groups of infections: acute lower respiratory infections (ALRI), urinary tract infections (UTI), and skin and soft tissue infections (SSTI) in six units of two academic pediatric hospitals. We used an uncontrolled before-and-after design, preceded by a formative phase, to identify barriers and facilitators. The target population was Healthcare workers (HCWs). The strategy comprised an antibiotic audit and feedback, ward- or pathway-specific treatment guidelines, infection-based interventions focused on improving diagnostic accuracy, tailoring therapy to culture results, optimizing treatment duration (antibiotic time out), pharmacy-based interventions, and education.

Results

We recruited 617 patients: 249 in the baseline period (BP) and 588 in the implementation period (IP). The patients in the IP group were younger, weighed less, had higher critical care requirements, and had higher ALRI.

With implementation, we observed an increase in antibiotic days of therapy (1051 vs. 831; RR: 1.23 (1.14;1.33); p<0.001). After adjusting for age and place of hospitalization, the differences were significant. This increase was at the expense of a higher use of Access group antibiotics (382 vs. 310; RR: 1.23 (1.14;1.33); p<0.001) and lower use of the Watch group according to the WHO classification (552 vs. 623; RR: 0.89 (0.84; 0.94); p<0.001).

We observed a decrease in antibiotic resistance in the IP group (5% vs. 13%; p<0.001) at the expense of extended-spectrum β-lactamase.

We found no differences in mortality rates between the two periods.

Conclusion

Through a QI initiative, the use of antibiotic stewardship programs in pediatric hospitals was shown to be feasible and may improve antibiotic use. We observed a decrease in antibiotic resistance, which may be due to an increase in antibiotic Access group use.
Mucin 5AC is a sensitive surface marker for sessile serrated lesions: results from a systematic review and meta-analysis
Authors: Liu Kevin , Sachar Moniyka , Popov Violeta , Pei Ziheng , Quarta Giulio
Published: February 2024

Sessile serrated lesions (SSLs) are a class of colon polyps which are challenging to detect through current screening methods but are highly associated with colon cancer. We reasoned that a biomarker sensitive for SSLs would be clinically useful to improve detection. Recent endoscopic and histopathologic studies suggest that SSLs are associated with alterations in intestinal mucin expression but the frequency with which this occurs is not known. We performed a meta-analysis of available pathologic studies comparing mucin expression on SSLs to normal colonic mucosa, tubular adenomas (TAs), villous adenomas (VAs), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). We searched Medline, Pubmed, and Embase and found 440 publications in this topic, and 18 total studies met inclusion. We found that MUC5AC expression was more common in SSLs compared to normal colonic mucosa (OR=82.9, p<0.01), TAs (OR=11, p<0.01), and TSAs (OR=3.6, p=0.04). We found no difference in MUC5AC expression between SSLs versus HPs (OR=2.1, p=0.09) and no difference in MUC5AC expression between left colon and right colon HPs, with an OR=1.8, p=0.23. We found that MUC5AC expression was found commonly on VAs, SSLs, and TSAs while the frequency on colon cancers declined. MUC5AC is also upregulated in inflammatory bowel disease and in response to intestinal infections. MUC5AC expression highlights the potential of mucins as sensitive biomarkers, though not specific to SSLs. Further research into the clinical utilization of MUC5AC could enhance SSL detection.