bluuebunny/crossref_metadata_2025_split huggingface dataset:
High blood lead levels of children in a gold mining community in Osun State, Nigeria: an urgent call for action
Authors: Akinwumi Ifeoluwa A , Adegoke Samuel A , Oyelami Oyeku A , Akinwumi Abiodun E , Adedeji Tewogbade A 
Published: June 2023

ABSTRACT

Background
Environmental exposure from artisanal gold mining activities is a major risk for high blood lead levels (BLLs) in children. Over the last decade, artisanal gold mining activities have been on a sharp increase in some parts of Nigeria. This study compared BLLs of children in the mining community of Itagunmodi and a 50-km distant non-mining community of Imesi-Ile, Osun State, Nigeria.

Methods
This community-based study investigated 234 apparently healthy children, with 117 each from Itagunmodi and Imesi-Ile. Relevant history, examination and laboratory findings including BLLs were recorded and analysed.

Results
All participants had BLLs above the cut-off value of 5 µg/dl. However, the mean BLL of subjects living in the gold-mining community (24.2±5.3 µg/dl) was significantly higher than for children in the non-mining area of Imesi-Ile (19.5±6.4 µg/dl; p&lt;0.001). Children in the gold mining community were 3.07 times more likely to have a BLL ≥20 µg/dl than those in the non-mining environment (odds ratio [OR] 3.07 [95% confidence interval {CI} 1.79 to 5.2], p&lt;0.001). Similarly, the odds of having a BLL ≥30 µg/dl was 7.84 times more likely among children living in gold mining Itagunmodi than in Imesi-Ile (OR 7.84 [95% CI 2.32 to 26.46], p&lt;0.0001). BLL was not associated with socio-economic and nutritional status of the participants.

Conclusions
In addition to introduction and enforcement of safe mining practices, regular screening for lead toxicity is advocated for children in these communities.
Systemic Nonsteroidal Anti-Inflammatories for Analgesia in Postoperative Critical Care Patients: A Systematic Review and Meta-Analysis of Randomized Control Trials
Authors: Ma Chen Hsiang , Tworek Kimberly B. , Kung Janice Y. , Kilcommons Sebastian , Wheeler Kathleen , Parker Arabesque , Senaratne Janek , Macintyre Erika , Sligl Wendy , Karvellas Constantine J. , Zampieri Fernando G. , Kutsogiannis Demetrios Jim , Basmaji John , Lewis Kimberley , Chaudhuri Dipayan , Sharif Sameer , Rewa Oleksa G. , Rochwerg Bram , Bagshaw Sean M. , Lau Vincent I. 
Published: June 2023

OBJECTIVES:
While opioids are part of usual care for analgesia in the ICU, there are concerns regarding excess use. This is a systematic review of nonsteroidal anti-inflammatory drugs (NSAIDs) use in postoperative critical care adult patients.

DATA SOURCES:
We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, trial registries, Google Scholar, and relevant systematic reviews through March 2023.

STUDY SELECTION:
Titles, abstracts, and full texts were reviewed independently and induplicate by two investigators to identify eligible studies. We included randomized control trials (RCTs) that compared NSAIDs alone or as an adjunct to opioids for systemic analgesia. The primary outcome was opioid utilization.

DATA EXTRACTION:
In duplicate, investigators independently extracted study characteristics, patient demographics, intervention details, and outcomes of interest using predefined abstraction forms. Statistical analyses were conducted using Review Manager software Version 5.4. (The Cochrane Collaboration, Copenhagen, Denmark).

DATA SYNTHESIS:
We included 15 RCTs (n = 1,621 patients) for admission to the ICU for postoperative management after elective procedures. Adjunctive NSAID therapy to opioids reduced 24-hour oral morphine equivalent consumption by 21.4 mg (95% CI, 11.8–31.0 mg reduction; high certainty) and probably reduced pain scores (measured by Visual Analog Scale) by 6.1 mm (95% CI, 12.2 decrease to 0.1 increase; moderate certainty). Adjunctive NSAID therapy probably had no impact on the duration of mechanical ventilation (1.6 hr reduction; 95% CI, 0.4 hr to 2.7 reduction; moderate certainty) and may have no impact on ICU length of stay (2.1 hr reduction; 95% CI, 6.1 hr reduction to 2.0 hr increase; low certainty). Variability in reporting adverse outcomes (e.g., gastrointestinal bleeding, acute kidney injury) precluded their meta-analysis.

CONCLUSIONS:
In postoperative critical care adult patients, systemic NSAIDs reduced opioid use and probably reduced pain scores. However, the evidence is uncertain for the duration of mechanical ventilation or ICU length of stay. Further research is required to characterize the prevalence of NSAID-related adverse outcomes.
Angiotensin II for the Treatment of Refractory Shock: A Matched Analysis*
Authors: Smith Lane M. , Mentz Graciela B. , Engoren Milo C. 
Published: June 2023

OBJECTIVES:
To determine if angiotensin II is associated with improved outcomes as measured by 30- and 90-day mortality as well as other secondary outcomes such as organ dysfunction and adverse events.

DESIGN:
Retrospective, matched analysis of patients receiving angiotensin II compared with both historical and concurrent controls receiving equivalent doses of nonangiotensin II vasopressors.

SETTING:
Multiple ICUs in a large, university-based hospital.

PATIENTS:
Eight hundred thirteen adult patients with shock admitted to an ICU and requiring vasopressor support.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Angiotensin II use had no association with the primary outcome of 30-day mortality (60% vs 56%; p = 0.292). The secondary outcome of 90-day mortality was also similar (65% vs 63%; p = 0.440) as were changes in Sequential Organ Failure Assessment scores over a 5-day monitoring period after enrollment. Angiotensin II was not associated with increased rates of kidney replacement therapy (odds ratio [OR], 1.39; 95% CI, 0.88–2.19; p = 0.158) or receipt of mechanical ventilation (OR, 1.50; 95% CI, 0.41–5.51; p = 0.539) after enrollment, and the rate of thrombotic events was similar between angiotensin II and control patients (OR, 1.02; 95% CI, 0.71–1.48; p = 0.912).

CONCLUSIONS:
In patients with severe shock, angiotensin II was not associated with improved mortality or organ dysfunction and was not associated with an increased rate of adverse events.
Analysis of Protein Biomarkers From Hospitalized COVID-19 Patients Reveals Severity-Specific Signatures and Two Distinct Latent Profiles With Differential Responses to Corticosteroids*
Authors: Verhoef Philip A. , Spicer Alexandra B. , Lopez-Espina Carlos , Bhargava Akhil , Schmalz Lee , Sims Matthew D. , Palagiri Ashok V. , Iyer Karthik V. , Crisp Matthew J. , Halalau Alexandra , Maddens Nicholas , Gosai Falgun , Syed Anwaruddin , Azad Saleem , Espinosa Aimee , Davila Francisco , Davila Hugo , Evans Neil R. , Smith Scott , Reddy Bobby , Sinha Pratik , Churpek Matthew M. 
Published: June 2023

OBJECTIVES:
To identify and validate novel COVID-19 subphenotypes with potential heterogenous treatment effects (HTEs) using electronic health record (EHR) data and 33 unique biomarkers.

DESIGN:
Retrospective cohort study of adults presenting for acute care, with analysis of biomarkers from residual blood collected during routine clinical care. Latent profile analysis (LPA) of biomarker and EHR data identified subphenotypes of COVID-19 inpatients, which were validated using a separate cohort of patients. HTE for glucocorticoid use among subphenotypes was evaluated using both an adjusted logistic regression model and propensity matching analysis for in-hospital mortality.

SETTING:
Emergency departments from four medical centers.

PATIENTS:
Patients diagnosed with COVID-19 based on International Classification of Diseases, 10th Revision codes and laboratory test results.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Biomarker levels generally paralleled illness severity, with higher levels among more severely ill patients. LPA of 522 COVID-19 inpatients from three sites identified two profiles: profile 1 (n = 332), with higher levels of albumin and bicarbonate, and profile 2 (n = 190), with higher inflammatory markers. Profile 2 patients had higher median length of stay (7.4 vs 4.1 d; p < 0.001) and in-hospital mortality compared with profile 1 patients (25.8% vs 4.8%; p < 0.001). These were validated in a separate, single-site cohort (n = 192), which demonstrated similar outcome differences. HTE was observed (p = 0.03), with glucocorticoid treatment associated with increased mortality for profile 1 patients (odds ratio = 4.54).

CONCLUSIONS:
In this multicenter study combining EHR data with research biomarker analysis of patients with COVID-19, we identified novel profiles with divergent clinical outcomes and differential treatment responses.
Design and Implementation of a Leadership Development Program for Early-Stage Investigators: Initial Results
Authors: Bredella Miriam A. , Patel Karan A. , Leyne Maire , Levy Anne S. , Tannous Bakhos A. , Bouxsein Mary L. 
Published: June 2023

Abstract:
Leadership skills are essential for a successful career in medical research but are often not formally taught. To address these gaps, we designed a leadership development program for early-stage investigators.
A 9-month virtual program with monthly 2-hour interactive sessions was designed, covering topics such as Leadership in Research, Mentoring, Building Diverse and Inclusive Teams, Managing Conflict, Influencing without Authority, Grant Administration, and Management. An anonymized survey was sent to participants before and after completion of the program, and the results were compared using the chi-squared test.
Over a 2-year period, we selected two cohorts of 41 and 46 participants, respectively. After completion of the program, 92% of survey respondents indicated that the program met their expectations and 74% had made use of skills they learned. Participants enjoyed meeting new people and discussing common challenges. There was an increase in participants' perceived understanding of personal leadership qualities, mentoring, communication, conflict resolution, grant management, and collaboration with industry (P < .05).
A leadership development program for early-stage investigators led to a significant increase in participants' perceived understanding of personal leadership qualities and competencies. It also offered participants the opportunity to meet other researchers in the institution and discuss common challenges.
Cutaneous Lesions of Mastocytosis: Mast Cell Count, Morphology, and Immunomolecular Phenotype
Authors: Damman Jeffrey , Diercks Gilles F.H. , van Doorn Martijn B. , Pasmans Suzanne GMA , Hermans Maud A.W. 
Published: June 2023

Abstract:
Mastocytosis is a condition characterized by accumulation of clonal mast cells (MCs) that often involves the skin. Pathologists are often challenged with skin biopsies with a question of cutaneous lesions of mastocytosis (CLM) including cutaneous mastocytosis, mastocytosis in the skin, or systemic mastocytosis. The histopathological criteria for CLM remain poorly defined due to heterogeneity of the published literature and the lack of comparative prospective studies. MC count is greatly influenced by detection and counting techniques, criteria for viable MCs used, anatomical location biopsied, and the dermal level that is analyzed. Although MC numbers in CLM can be significantly higher compared with healthy controls and a patient with other inflammatory skin diseases, in some instances, considerable overlap exists. Based on the largest studies published, it is suggested that a number of MCs between 75 and 250 MCs/mm2 are a range in which CLM should be considered and, above 250 MC/mm2, a diagnosis of CLM can be made. A recent study showed a high specificity of >95% of a MC count >139 MC/mm2 compared with patients with other inflammatory skin diseases. Noteworthy, the total number and percentage of MCs is significantly higher in children compared with adults, particularly in polymorphic maculopapular cutaneous mastocytosis. In difficult cases, ancillary techniques such as D816V mutation analysis on formalin-fixed paraffin-embedded tissue have a high sensitivity and specificity. There is no enough evidence that immunohistochemistry of CD25, CD2, or CD30 has any additional value in the diagnosis, subtyping, or clinical course of mastocytosis.
Merkel Cell Carcinoma In Situ Arising in Association With an Infundibular Cyst With Unusual Reticulated Infundibulocystic Proliferation
Authors: Peralta Isairis , Dacey Elizabeth B. , King Roy 
Published: June 2023

Abstract:
Merkel cell carcinoma (MCC) is an uncommon aggressive primary cutaneous neuroendocrine tumor usually arising on sun exposed skin of older patients. Most Merkel cell carcinomas are diagnosed as invasive tumors with only rare cases of MCC in situ (MCCIS) reported. MCCs are often associated with other cutaneous neoplasms and more recently have been described in association with cystic lesions, albeit rarely. We present a unique case of an 80-year-old male with a slow growing nodular lesion on the right buttock that on excision demonstrated MCCIS arising within an infundibular cyst with unusual reticulated infundibulocystic proliferation. The MCCIS was intimately associated with the infundibulocystic proliferation and demonstrated immunopositivity for CK20, CD56, AE1/AE3, synaptophysin, and Merkel cell polyoma virus. The confinement of the MCC to the epithelium together with the Merkel cell polyoma virus positivity further supports the assumption that viral positive MCC may derive from epithelial linage.
Cured HCV patients with suboptimal hepatitis B vaccine response exhibit high self-reactive immune signatures
Authors: Zhou Ming-Ju , Zhang Chao , Fu Yuan-Jie , Wang Haiyan , Ji Yingjie , Huang Xia , Li Lin , Wang Ye , Qing Song , Shi Yanze , Shen Lili , Wang You-Yuan , Li Xiao-Yu , Li Yuan-Yuan , Chen Si-Yuan , Zhen Cheng , Xu Ruonan , Shi Ming , Wang Fu-Sheng , Cheng Yongqian 
Published: June 2023

Background and Rationale:
Chronic HCV infection induces lasting effects on the immune system despite viral clearance. It is unclear whether certain immune alterations are associated with vaccine responses in cured HCV patients.

Approach:
Thirteen cured HCV patients received the standard 3-dose hepatitis B vaccine and were followed up at the 0, 1st, 6th, and 7th months (M0, M1, M6, and M7) after the first dose of vaccination. Thirty-three-color and 26-color spectral flow cytometry panels were used for high-dimensional immunophenotyping of the T-cell and B-cell subsets, respectively.

Results:
Compared to the healthy controls (HC), 17 of 43 (39.5%) immune cell subsets showed abnormal frequencies in cured HCV patients. Patients with cured HCV were further divided into high responders (HR, n = 6) and nonresponders (NR1, n = 7) based on the levels of hepatitis B surface antibodies at M1. Alterations in cell populations were more significant in NR1. Moreover, we found that high levels of self-reactive immune signatures, including Tregs, TD/CD8, IgD-only memory B, and autoantibodies, were associated with suboptimal hepatitis B vaccine responses.

Conclusions:
Our data suggest that cured HCV patients exhibit persistent perturbations in the adaptive immune system, among which highly self-reactive immune signatures may contribute to a suboptimal hepatitis B vaccine response.
A System for Rapidly Yet Rigorously Evaluating the Quality of Randomized Controlled Trials
Authors: Smith Eric G. , Grigorian Hannah L. 
Published: June 2023

AbstractThis tutorial describes a system for rapidly yet rigorously assessing the quality of randomized controlled trials (RCTs). The system has 7 criteria, represented by the acronym “BIS FOES.” The BIS FOES system directs readers to assess RCTs based on the following 7 criteria: the RCT's use (or not) of effective (1) Blinding; the RCT's use (or not) of (2) Intent-to-Treat Analysis; the RCT's (3) Size and other information reflecting the effectiveness of randomization; the amount of sample lost during (4) Follow-up; the (5) Outcomes examined by the RCT (specifically, the outcomemeasuresused by the RCT), the (6) Effects reported (ie, the statistical and clinical significance of the RCT's primary, secondary, and safety findings), and any (7) Special Considerations (ie, additional strengths, limitations, or notable features of the RCT). The first 6 criteria are of basic importance to the assessment of every RCT, whereas the Special Considerations criteria allows the system to be expanded to include virtually any other important aspect of the RCT. This tutorial explains the importance of these criteria and how to assess them. This tutorial also describes how many BIS FOES criteria can be initially assessed from the RCT Abstract while also directing readers to specific locations in the RCT article where additional important information can be found. We hope that the BIS FOES system will help healthcare trainees, but also potentially clinicians, researchers, and the general public, rapidly and thoroughly assess RCTs.
The Association Between Female Genital Schistosomiasis and Other Infections of the Lower Genital Tract in Adolescent Girls and Young Women: A Cross-Sectional Study in South Africa
Authors: Shukla Jilna Dilip , Kleppa Elisabeth , Holmen Sigve , Ndhlovu Patricia D. , Mtshali Andile , Sebitloane Motshedisi , Vennervald Birgitte Jyding , Gundersen Svein Gunnar , Taylor Myra , Kjetland Eyrun Floerecke 
Published: June 2023

Objectives/Purposes of the Study
This study aimed to explore the relationship between female genital schistosomiasis (FGS), sexually transmitted infections, bacterial vaginosis, and yeast among young women living in Schistosoma haematobium-endemic areas.

Methods
In a cross-sectional study of young women, sexually active, aged 16 to 22 years in rural KwaZulu-Natal, South Africa, in 32 randomly selected rural schools in schistosomiasis-endemic areas, the authors performed gynecological and laboratory investigations, diagnosed FGS and other infections, and did face-to-face interviews.

Results
Female genital schistosomiasis was the second most prevalent current genital infection (23%), significantly more common in those who had urinary schistosomiasis (35%), compared with those without (19%, p < .001). In the FGS-positive group, 35% had human papillomavirus compared with 24% in the FGS-negative group (p = .010). In the FGS-positive group, 37% were seropositive for herpes simplex virus infection, compared with 30% in the FGS-negative group (p = .079). There were significantly fewer chlamydia infections among women with FGS (20%, p = .018) compared with those who did not have FGS (28%).

Conclusions
Female genital schistosomiasis was the second most common genital infection after herpes simplex virus. Human papillomavirus infection was significantly associated with FGS, but Chlamydia was negatively associated with FGS. Women with FGS may have had more frequent contact with the health system for genital discharge. The results show the importance of the inclusion of FGS in the national management protocols for genital infections in areas endemic for S. haematobium and highlight a more comprehensive approach to diagnosis and genital disease management.
Can Concurrent Chemoradiotherapy Add Meaningful Benefit in Addition to Induction Chemotherapy in the Management of Borderline Resectable and Locally Advanced Pancreatic Cancer?
Authors: Saha Animesh , Wadsley Jonathan , Sirohi Bhawna , Goody Rebecca , Anthony Alan , Perumal Karthikeyan , Ulahanan Danny , Collinson Fiona 
Published: June 2023

ObjectivesThe role of concomitant chemoradiotherapy or radiotherapy (RT) after induction chemotherapy (IC) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma is debatable. This systematic review aimed to explore this.MethodsWe searched PubMed, MEDLINE, EMBASE, and Cochrane database. Studies were selected reporting outcomes on resection rate, R0 resection, pathological response, radiological response, progression-free survival, overall survival, local control, morbidity, and mortality.ResultsThe search resulted in 6635 articles. After 2 rounds of screening, 34 publications were selected. We found 3 randomized controlled studies and 1 prospective cohort study, and the rest were retrospective studies. There is consistent evidence that addition of concomitant chemoradiotherapy or RT after IC improves pathological response and local control. There are conflicting results in terms of other outcomes.ConclusionsConcomitant chemoradiotherapy or RT after IC improves local control and pathological response in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. The role of modern RT in improving other outcome requires further research.
Outcomes of Distal Pancreatectomy With Celiac Axis Resection for Pancreatic Cancer
Authors: Shin Dakyum , Hong Sarang , Park Yejong , Kwak Bong Jun , Lee Woohyung , Song Ki Byung , Lee Jae Hoon , Kim Song Cheol , Hwang Dae Wook 
Published: June 2023

Objectives
This study aimed to show the clinical and oncologic outcomes of distal pancreatectomy with celiac axis resection (DP-CAR) from a high-volume single center and analyze them from diverse perspectives.

Methods
Forty-eight patients with pancreatic body and tail cancer with celiac axis involvement who underwent DP-CAR were included in the study. The primary outcome was morbidity and 90-day mortality, and the secondary outcome was overall survival and disease-free survival.

Results
Morbidity (Clavien-Dindo classification grade ≥3) occurred in 12 patients (25.0%). Thirteen patients (27.1%) had pancreatic fistula grade B and 3 patients (6.3%) had delayed gastric emptying. The 90-day mortality was 2.1% (n = 1). The median overall survival was 25.5 months (interquartile range, 12.3–37.5 months) and median disease-free survival was 7.5 months (interquartile range, 4.0–17.0 months). During the follow-up period, 29.2% of participants survived for up to 3 years and 6.3% survived for up to 5 years.

Conclusions
Despite its associated morbidity and mortality, DP-CAR should be considered as the only therapeutic option for pancreatic body and tail cancer with celiac axis involvement when carried out on carefully selected patients performed by a highly experienced group.
Breakthrough Symptoms Remain an Unmet Need in Symptomatic Patients With Neuroendocrine Tumors and Carcinoid Syndrome
Authors: Liu Eric , Hoffman Kathleen D. , Murfin Gary , Eccard Hannah 
Published: June 2023

Objectives
The aims of the study were to assess the effects of breakthrough carcinoid syndrome symptoms on well-being in neuroendocrine tumor (NET) patients insufficiently controlled on long-acting somatostatin analog (SSA) and to assess patient experience with treatment options, physician communication, and disease information sources.

Methods
This study surveyed US NET patients from 2 online communities, experiencing at least one symptom, by utilizing a 64-item questionnaire.

Results
One hundred patients participated: 73% female, 75% age 56 to 75 years, and 93% White. Primary tumor distribution was as follows: gastrointestinal NET (n = 55), pancreatic NET (n = 33), lung NET (n = 11), and other NET (n = 13). All patients were actively treated with one long-acting SSA and experiencing breakthrough symptoms: diarrhea, flushing, or other (13% experienced one, 30% two, 57% greater than two). More than one third of treated patients experienced carcinoid-related symptoms daily. Sixty percent of respondents reported not having short-acting “rescue” treatment available, impacting well-being though anxiety or depression (45%), trouble exercising (65%), sleeping (57%), employment (54%), and maintaining friendships (43%).

Conclusions
Breakthrough symptoms remain an unmet need, even in treated patients with NETs. Though still relying on physicians, NET patients are now also using the Internet. Improved awareness of optimal SSA use may improve syndrome control.