bluuebunny/crossref_metadata_2025 huggingface dataset:
Midterm results after arthroscopic femoral neck osteoplasty combined with labral debridement for cam type femoroacetabular impingement in active adults
Authors: Migliorini Filippo , Maffulli Nicola , Bell Andreas , Cuozzo Francesco , Hildebrand Frank , Weber Christian David
Published: January 2023

Introduction

Arthroscopic labral procedures are frequently undertaken in patients with femoroacetabular impingement (FAI). The role of arthroscopic femoral neck osteoplasty is well established, but less is known about labral procedures. This study evaluates the midterm efficacy and feasibility of arthroscopic osteoplasty with concomitant labral debridement for cam impingement in active adults.

Methods

The present study was conducted according to the STROBE Statement. All 108 patients who underwent primary hip arthroscopy for cam type FAI combined with labral debridement were considered. Axial and anteroposterior plain radiographs of the pelvis were obtained preoperatively to identify the cam deformity and assess the presence of osteoarthritis, the lateral centre-edge angle, and the alpha angle. The ROM (flexion, extension, abduction, adduction, and intra/extra rotation) was evaluated. The following PROMs were administered: visual analogic scale (VAS), Tegner Activity Scale, non-arthritic hip score (NAHS), the international Hip Outcome Tool (iHOT-33) overall score, and related subscales: symptoms and functional limitations, sports and recreational activities, job-related concerns, and social, emotional, and lifestyle concerns.

Results

At a mean of 2.0 ± 1.1 months, all 108 patients returned to their daily activities with no limitation. At a mean of 2.6 ± 1.4 months, all 108 patients were able to return to sport with no limitation. At 11.9 ± 2.1-month follow-up, no differences were reported in the range of motion compared to baseline: flexion (P = 0.3), extension (P = 0.09), abduction (P = 0.1), adduction (P = 0.3), internal rotation (P = 0.4), and external rotation (P = 0.6). At 72.8 ± 21.7-month follow-up, the mean VAS score was 1.7 ± 3.0, Tegner Activity Scale 3.5 ± 1.4, NAHS 92.1 ± 21.5, iHOT33 83.3 ± 27.2. At a mean of 21.7 ± 15.5 months following the index procedure, 14 of 108 patients had undergone total hip arthroplasty. No further revisions or complications were reported.

Conclusion

Arthroscopic femoral neck osteoplasty with concomitant labral debridement for cam type of FAI in active adults yields the reliable results, with a rate of progression to total hip arthroplasty of 13% (14 of 108) at 3-year follow-up. All patients returned to their daily activities with no limitation 2 months postoperatively. Within 3 months, all patients returned to sport with no limitations. No complication related to the index procedure was reported, and no further arthroscopic procedures were necessary.
Intra- and interobserver reliability analysis of pediatric lower limb parameters on digital long leg radiographs
Authors: Braun Sebastian , Brenneis Marco , Holder Jana , Meurer Andrea , Stief Felix
Published: January 2023

Background

Malalignments of the lower extremity are common reasons for orthopedic consultation because it may lead to osteoarthritis in adulthood. An accurate and reliable radiological assessment of lower limb alignment in children and adolescents is essential for clinical decision-making on treatment of limb deformities and for regular control after a surgical intervention.

Objective

First, does the analysis of full-length standing anteroposterior radiographs show a good intra- and interobserver reliability? Second, which parameter is most susceptible to observer-dependent errors? Third, what is the Standard Error of Measurement (SEM95%) of the absolute femoral and tibial length?

Methods

Two observers evaluated digital radiographs of 144 legs from 36 children and adolescents with pathological valgus alignment before a temporary hemiepiphysiodesis and before implant removal. Parameters included Mechanical Femorotibial Angle (MFA), Mechanical Axis Deviation (MAD), mechanical Lateral Distal Femoral Angle (mLDFA), mechanical Medial Proximal Tibial Angle (mMPTA), mechanical Lateral Proximal Femoral Angle (mLPFA), mechanical Lateral Distal Tibial Angle (mLDTA), Joint Line Convergence Angle (JLCA), femur length, tibial length. Intra- and interobserver reliability (ICC2,1), SEM95% and proportional errors were calculated.

Results

The intra- and interobserver reliability for almost all measurements was found to be good to excellent (Intra-ICC2,1: 0.849–0.999; Inter-ICC2,1: 0.864–0.996). The SEM95% of both observers was found to be ± 1.39° (MFA), ± 3.31 mm (MAD), ± 1.06° (mLDFA) and ± 1.29° (mMPTA). The proportional error of MAD and MFA is comparable (47.29% vs. 46.33%). The relevant knee joint surface angles show a lower proportional error for mLDFA (42.40%) than for mMPTA (51.60%). JLCA has a proportional error of 138%. Furthermore, the SEM95% for the absolute values of the femoral and tibial length was 4.53 mm for the femur and 3.12 mm for the tibia.

Conclusions

In conclusion, a precise malalignment measurement and the knowledge about SEM95% of the respective parameters are crucial for correct surgical or nonsurgical treatment. The susceptibility to error must be considered when interpreting malalignment analysis and must be considered when planning a surgical intervention. The results of the present study elucidate that MAD and MFA are equally susceptible to observer-dependent errors. This study shows good to excellent intra- and interobserver ICCs for all leg alignment parameters and joint surface angles, except for JLCA.

Trial registration: This study was registered with DRKS (German Clinical Trials Register) under the number DRKS00015053.

Level of evidence

I, Diagnostic Study.
High-risk human papillomavirus genotype distribution among women with gynecology complaints in northwest Ethiopia
Authors: Derbie Awoke , Maier Melanie , Amare Bereket , Misgan Eyaya , Nibret Endalkachew , Liebert Uwe G. , Woldeamanuel Yimtubezinash , Abebe Tamrat
Published: January 2023

Background

Human papillomavirus (HPV) genotypes differ by geographic location. With the advent of HPV vaccination and HPV-based cervical screening tests in Ethiopia, a nationwide dataset on the genotype distribution of HPV among women has paramount importance in the fight against cervical cancer. However, there is limited data in this regard in the northwest part of the country. Therefore, this study aimed to identify the genotype distribution of high-risk HPVs among women presenting with cervical abnormalities.

Methods

A health facility-based cross-sectional study was conducted at Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Bahir Dar–Ethiopia. Women aged ≥ 30 years who visited the hospital gynecology unit from 01 March 2019 to 30 October 2021 were included. Following general and pelvic examinations, a senior gynecologist collected cervical punch biopsies for histopathological examinations and cervical swabs for HR-HPV detection using the Abbott Alinity m system (Abbott Molecular, Des Plaines, IL, USA). Extended genotyping was carried out with the INNO-LiPA HPV Genotyping Extra II assay (INNO-LiPA; Fujirebio Europe, Ghent, Belgium) as per the manufacturer protocols at the Institute of Virology, Leipzig University Hospital, Germany.

Results

We included 355 women with a mean age of 46.4 ± 11.4 years. The majority of the participants, 277 (79.4%) were sexually active before the age of 18 years and 180 (51.6%) had multiple sexual partners. Forty-eight (13.5%) of the participants were HIV positive. The proportion of HR-HPV was 53.0% (n = 188; 95%CI: 47.8–58.1%). From these samples, 13 different HR-HPV types with a total of 258 sequences were identified. The detection of HR-HPV increased significantly with an increase in the age of the participants. The predominant identified HR-HPV was HPV16, 50.4% followed by HPV31 (9.7%), HPV33 (8.5%), HPV39, and HPV68 each (5.8%) and HPV18 (4.7%). Of the total HR-HPV-positive women, 23.9% (45/188) were infected with multiple HR-HPV types. All HPV16, HPV18, HPV35, and HPV45 genotypes (as a single or in coinfections) were found to be associated with either high-grade lesions or cervical cancer.

Conclusions

HR-HPV infection was reportedly higher among women in the present study area. Based on our findings, we strongly recommend the nonavalent HPV vaccine for immunization and any HPV-based screening method to take into consideration the predominant genotypes circulating in the country. The role of multiple HPV infections in high-grade cervical lesions entails further study in Ethiopia.
How to dose follitropin delta for the first insemination cycle according to the ESHRE and ASRM guidelines; a retrospective cohort study
Authors: Arab Suha , Frank Russell , Ruiter Jacob , Dahan Michael H.
Published: January 2023

Background

Follitropin Delta (FD) is indicated exclusively for in-vitro fertilization however, being a gonadotropin it could be used for other purposes. A dosing algorithm exists for FD and IVF but is needed for intrauterine insemination (IUI) cycles. The objective of this study is to determine dosing for FD for the first controlled ovarian hyperstimulation (COH) cycle according to current stimulation guidelines.

Results

A retrospective study of 157 subjects from a single university fertility center from January 2017 to March 2020, was performed. All patients stimulated with FD for IUI were included. The number of failed, normal, or overstimulation cycles was determined based on stimulating not more than 2 mature follicles. We then stratified the group based on the AFC, AMH, and body weight. Of 157 subjects, 49% stimulated correctly, 5.6% failed and 45.4% overstimulated. An analysis of the COH IUI cycles based on stratification and over or lack of stimulation per published guidelines found that women with a bodyweight < 80 kg or AMH ≥ 1.5 ng/ml or AFC ≥ 10 initially stimulate with FD 2.0 to 3.0mcg daily. For women with an AFC of 6–9 stimulate with Follitropin Delta 3.0mcg daily. For women with an AFC < 6 or serum AMH < 1.5 ng/ml stimulate with FD 3.0–4.0mcg daily. For women with body weight > 80 kg stimulate initially with daily with 4.0–6.0mcg FD.

Conclusions

Follitropin Delta can be used safely for controlled ovarian stimulation and insemination at doses easily dispensed by the current methods of delivery, within the current published guidelines for follicle development.
Toward nutrition improving outcome of critically ill patients: How to interpret recent feeding RCTs?
Authors: Gunst Jan , Casaer Michael P. , Preiser Jean-Charles , Reignier Jean , Van den Berghe Greet
Published: January 2023

Although numerous observational studies associated underfeeding with poor outcome, recent randomized controlled trials (RCTs) have shown that early full nutritional support does not benefit critically ill patients and may induce dose-dependent harm. Some researchers have suggested that the absence of benefit in RCTs may be attributed to overrepresentation of patients deemed at low nutritional risk, or to a too low amino acid versus non-protein energy dose in the nutritional formula. However, these hypotheses have not been confirmed by strong evidence. RCTs have not revealed any subgroup benefiting from early full nutritional support, nor benefit from increased amino acid doses or from indirect calorimetry-based energy dosing targeted at 100% of energy expenditure. Mechanistic studies attributed the absence of benefit of early feeding to anabolic resistance and futile catabolism of extra provided amino acids, and to feeding-induced suppression of recovery-enhancing pathways such as autophagy and ketogenesis, which opened perspectives for fasting-mimicking diets and ketone supplementation. Yet, the presence or absence of an anabolic response to feeding cannot be predicted or monitored and likely differs over time and among patients. In the absence of such monitor, the value of indirect calorimetry seems obscure, especially in the acute phase of illness. Until now, large feeding RCTs have focused on interventions that were initiated in the first week of critical illness. There are no large RCTs that investigated the impact of different feeding strategies initiated after the acute phase and continued after discharge from the intensive care unit in patients recovering from critical illness.
Transcriptomic alterations underlying metaplasia into specific metaplastic components in metaplastic breast carcinoma
Authors: Lien Huang-Chun , Hsu Chia-Lang , Lu Yen-Shen , Chen Tom Wei-Wu , Chen I.-Chun , Li Yu-Chia , Huang Chiun-Sheng , Cheng Ann-Lii , Lin Ching-Hung
Published: January 2023

Background

Metaplastic breast carcinoma (MpBC) typically consists of carcinoma of no special type (NST) with various metaplastic components. Although previous transcriptomic and proteomic studies have reported subtype-related heterogeneity, the intracase transcriptomic alterations between metaplastic components and paired NST components, which are critical for understanding the pathogenesis underlying the metaplastic processes, remain unclear.

Methods

Fifty-nine NST components and paired metaplastic components (spindle carcinomatous [SPS], matrix-producing, rhabdoid [RHA], and squamous carcinomatous [SQC] components) were microdissected from specimens obtained from 27 patients with MpBC for gene expression profiling using the NanoString Breast Cancer 360 Panel on a NanoString nCounter FLEX platform. BC360-defined signatures were scored using nSolver software.

Results

Hierarchical clustering and principal component analysis revealed a heterogeneous gene expression profile (GEP) corresponding to the NST components, but the GEP of metaplastic components exhibited subtype dependence. Compared with the paired NST components, the SPS components demonstrated the upregulation of genes related to stem cells and epithelial–mesenchymal transition and displayed enrichment in claudin-low and macrophage signatures. Despite certain overlaps in the enriched functions and signatures between the RHA and SPS components, the specific differentially expressed genes differed. We observed the RHA-specific upregulation of genes associated with vascular endothelial growth factor signaling. The chondroid matrix-producing components demonstrated the upregulation of hypoxia-related genes and the downregulation of the immune-related MHC2 signature and the TIGIT gene. In the SQC components, TGF-β and genes associated with cell adhesion were upregulated. The differentially expressed genes among metaplastic components in the 22 MpBC cases with one or predominantly one metaplastic component clustered paired NST samples into clusters with correlation with their associated metaplastic types. These genes could be used to separate the 31 metaplastic components according to respective metaplastic types with an accuracy of 74.2%, suggesting that intrinsic signatures of NST may determine paired metaplastic type. Finally, the EMT activity and stem cell traits in the NST components were correlated with specimens displaying lymph node metastasis.

Conclusions

We presented the distinct transcriptomic alterations underlying metaplasia into specific metaplastic components in MpBCs, which contributes to the understanding of the pathogenesis underlying morphologically distinct metaplasia in MpBCs.
Proteomic aptamer analysis reveals serum markers that characterize preclinical systemic sclerosis (SSc) patients at risk for progression toward definite SSc
Authors: Bellocchi Chiara , Assassi Shervin , Lyons Marka , Marchini Maurizio , Mohan Chandra , Santaniello Alessandro , Beretta Lorenzo
Published: January 2023

Background

The study of molecular mechanisms characterizing disease progression may be relevant to get insights into systemic sclerosis (SSc) pathogenesis and to intercept patients at very early stage. We aimed at investigating the proteomic profile of preclinical systemic sclerosis (PreSSc) via a discovery/validation two-step approach.

Methods

SOMAcan aptamer-based analysis was performed on a serum sample of 13 PreSSc (discovery cohort) according to 2001 LeRoy and Medsger criteria (characterized solely by Raynaud phenomenon plus a positive nailfold capillaroscopy and SSc-specific antibodies without any other sign of definite disease) and 8 healthy controls (HCs) age, gender, and ethnicity matched. Prospective data were available up to 4±0.6 years to determine the progression to definite SSc according to the EULAR/ACR 2013 classification criteria. In proteins with relative fluorescence units (RFU) > |1.5|-fold vs HCs values, univariate analysis was conducted via bootstrap aggregating models to determine the predicting accuracy (progression vs non-progression) of categorized baseline protein values. Gene Ontologies (GO terms) and Reactome terms of significant proteins at the adjusted 0.05 threshold were explored. Significant proteins from the discovery cohort were finally validated via ELISAs in an independent validation cohort of 50 PreSSc with clinical prospective data up to 5 years. Time-to-event analysis for interval-censored data was used to evaluate disease progression.

Results

In the discovery cohort, 286 out of 1306 proteins analyzed via SomaScan, were differentially expressed versus HCs. Ten proteins were significantly associated with disease progression; analysis through GO and Reactome showed differentially enriched pathways involving angiogenesis, endothelial cell chemotaxis, and endothelial cell chemotaxis to fibroblast growth factor (FGF). In the validation cohort, endostatin (HR=10.23, CI95=2.2–47.59,p=0.003) was strongly associated with disease progression, as well as bFGF (HR=0.84, CI95=0.709-0.996,p=0.045) and PAF-AHβ (HR=0.372, CI95=0.171–0.809,p=0.013)

Conclusions

A distinct protein profile characterized PreSSc from HCs and proteins associated with hypoxia, vasculopathy, and fibrosis regulation are linked with the progression from preclinical to definite SSc. These proteins, in particular endostatin, can be regarded both as markers of severity and molecules with pathogenetic significance as well as therapeutic targets.
A case of doxorubicin and cyclophosphamide therapy-induced type 1 diabetes: a case report
Authors: Miyabayashi Makoto , Onishi Shunichiro , Yoshida Tomohiko , Takemoto Minoru
Published: January 2023

Background

Patients receiving immune checkpoint inhibitors have been reported to develop autoimmune endocrine diseases, including type 1 diabetes, although few drugs have been shown to induce type 1 diabetes. Additionally, it is important to note that drugs other than immune checkpoint inhibitors could lead to the development of type 1 diabetes.

Case presentation

A 54-year-old Filipino female patient underwent surgery for left-sided breast cancer. Postoperative chemotherapy was initiated, including doxorubicin (Adriamycin) and cyclophosphamide therapy. The patient was brought to our hospital by ambulance after consciousness disturbance following three courses of doxorubicin and cyclophosphamide therapy and was hospitalized. Her blood glucose and hemoglobin A1c levels were 1661 mg/dL and 11.9%, respectively. The patient was diagnosed with diabetic ketoacidosis after arterial blood gas analysis indicated a blood pH of 7.120. Her insulin secretion was impaired, and her anti-glutamic acid decarboxylase antibody test result was significantly positive.

Conclusions

The present case shows that doxorubicin and cyclophosphamide therapy may cause unexpected adverse responses, such as type 1 diabetes, though rarely, and highlights the importance of careful patient follow-up. This report is the first to present a case of type 1 diabetes that suddenly developed after doxorubicin and cyclophosphamide treatment.
Effect of logging residue removal and mechanical site preparation on productivity of the subsequent Scots pine (Pinus sylvestris L.) stands
Authors: Węgiel Andrzej , Jakubowski Jakub , Molińska-Glura Marta , Polowy Krzysztof , Węgiel Jolanta , Gornowicz Roman
Published: January 2023

Key message

Removal of logging residue negatively affected tree diameter and height, but had no significant effect on the basal area of the subsequent stand (in the mid-term). On the other hand, different methods of mechanical site preparation (bedding, plowing furrows, and trenching) had no effect on tree growth 1 year after planting, but had a significant effect on tree diameter, tree height, and basal area in the mid-term. Bedding treatments could have a significant positive impact on the productivity of the subsequent Scots pine stands, even when planted on sandy, free-draining soils.

Context

Increased use of logging residues in forests may address the growing demand for renewable energy. However, concerns have arisen regarding the depletion of the forest soil, resulting in a decrease in the productivity of the next forest generation. Identifying the drivers of forest growth may be the key to understanding the relationship between logging residue removal and stand productivity.

Aims

Quantifying the effect of three mechanical site preparation methods (bedding, plowing furrows, and trenching) combined with five methods of logging residue management (complete removal, comminution, incineration, leaving whole, comminution with, and without mixing with topsoil) on growth of subsequent Scots pine stands, 1 year and 12 years after planting.

Methods

The experiment was set up as a randomized complete block design of 45 plots with three replications of combinations of three mechanical site preparation methods and five logging residue treatment methods.

Results

The effects of the different methods of mechanical site preparation were not significant 1 year after planting but bedding treatment caused increase in DBH, tree height, and basal area after 12 years. Various methods of logging residue management did not cause any differences in the survival rate nor the basal area of the next-generation stands; however, there was a significant influence on tree sizes. Moreover, the effects changed with time; in plots with a complete removal of logging residues, the trees were the highest 1 year after planting, but after 12 years, their height and DBH were the lowest.

Conclusions

It can be concluded that bedding treatments could have a significant positive impact on the productivity of the subsequent Scots pine stands. No effect found of different logging residue treatments on the productivity of Scots pine stands further confirms that the increased removal of biomass from the forest environment does not necessarily result in its rapid degradation. Observations at longer term are however needed to obtain the full spectrum of responses to logging residue removal.
Screening for opioid use disorder and co-occurring depression and post-traumatic stress disorder in primary care in New Mexico
Authors: Murray-Krezan Cristina , Dopp Alex , Tarhuni Lina , Carmody Mary D. , Becker Kirsten , Anderson Jessica , Komaromy Miriam , Meredith Lisa S. , Watkins Katherine E. , Wagner Katherine , Page Kimberly ,   the CLARO Study Group
Published: January 2023

Background

Identifying patients in primary care services with opioid use disorder and co-occurring mental health disorders is critical to providing treatment. Objectives of this study were to (1) assess the feasibility of recruiting people to screen in-person for opioid use disorder and co-occurring mental health disorders (depression and/or post-traumatic stress disorder) in primary care clinic waiting rooms in preparation for a randomized controlled trial, and (2) compare results of detecting these disorders by universal in-person screening compared to electronic health record (EHR) diagnoses.

Methods

This cross-sectional feasibility and pilot study recruited participants from four primary care clinics, two rural and two urban, from three health care organizations in New Mexico. Inclusion criteria were adults (≥ 18 years), attending one of the four clinics as a patient, and who spoke English or Spanish. Exclusion criteria were people attending the clinic for a non-primary care visit (e.g., dental, prescription pick up, social support). The main outcomes and measures were (1) recruitment feasibility which was assessed by frequencies and proportions of people approached and consented for in-person screening, and (2) relative differences of detecting opioid use disorder and co-occurring mental health disorders in waiting rooms relative to aggregate EHR data from each clinic, measured by prevalence and prevalence ratios.

Results

Over two-weeks, 1478 potential participants were approached and 1145 were consented and screened (77.5% of patients approached). Probable opioid use disorder and co-occurring mental health disorders were identified in 2.4% of those screened compared to 0.8% in EHR. Similarly, universal screening relative to EHR identified higher proportions of probable opioid use disorder (4.5% vs. 3.4%), depression (17.5% vs. 12.7%) and post-traumatic stress disorder (19.0% vs. 3.6%).

Conclusions

Universal screening for opioid use disorder, depression, and post-traumatic stress disorder was feasible, and identified three times as many patients with these co-occurring disorders compared to EHR. Higher proportions of each condition were also identified, especially post-traumatic stress disorder. Results support that there are likely gaps in identification of these disorders in primary care services and demonstrate the need to better address the persistent public health problem of these co-occurring disorders.
Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome
Authors: Lv Juan , Xue Guozhong , Zhang Yunxia , Wang Xinbin , Dai Enlai
Published: January 2023

Background

Glomerular damage is a common clinical indicator of nephrotic syndrome. High-dose hormone treatment often leads to hormone resistance in patients. How to avoid resistance and improve the efficiency of hormone therapy draws much attention to clinicians.

Methods

Adriamycin (ADR) was used to induce nephropathy model in SD rats. The rats were treated with dexamethasone (DEX), icariin (ICA), and DEX + ICA combination therapy. The changes in urinary protein (UP), urea nitrogen (BUN), and serum creatinine (SCR) contents in rats were detected by enzyme-linked immunosorbent assay (ELISA), and the degree of pathological injury and the expression level of podocin were detected by HE staining and immunohistochemistry, to test the success of the model and the therapeutic effects of three different ways. The effect of treatments on podocytes autophagy was evaluated via transfection of mRFP-GFP-LC3 tandem adenovirus in vitro.

Results

The contents of UP, SCR, and BUN were significantly increased, the glomerulus was seriously damaged, and the expression of Nephrosis2 (NPHS2) was significantly decreased in the ADR-induced nephrotic syndrome rat model compared to that of the control group. DEX, ICA, and the DEX + ICA combined treatment significantly alleviated these above changes induced by ADR. The combined treatment of DEX + ICA exhibited better outcome than single treatment. The combined treatment also restored the podocyte autophagy, increased the expression of microtubule-associated protein light-chain 3II (LC3II), and reduced the expression of p62 in vitro. The combined treatment protects podocytes by mediating the PI3K/AKT/mTOR (rapamycin complex) signaling pathway.

Conclusion

ICA enhances the therapeutic effect of DEX on the nephrotic syndrome.
Integrated investigation of the clinical implications and targeted landscape for RNA methylation modifications in hepatocellular carcinoma
Authors: Zhang Jianping , Gao Jie , Hu Mingchao , Xu Shiyu , Cheng Chun , Zheng Wenjie , Zhang Jie
Published: January 2023

Background

RNA methylation (RM) is a crucial post-translational modification (PTM) that directs epigenetic regulation. It mostly consists of N1-methyladenosine (m1A), 5-methylcytosine (m5C), N3-methylcytidine (m3C), N6-methyladenosine (m6A), and 2′-O-methylation (Nm). The “writers” mainly act as intermediaries between these modifications and associated biological processes. However, little is known about the interactions and potential functions of these RM writers in hepatocellular carcinoma (HCC).

Methods

The expression properties and genetic alterations of 38 RM writers were assessed in HCC samples from five bioinformatic datasets. Two patterns associated with RM writers were identified using consensus clustering. Then, utilizing differentially expressed genes (DEGs) from different RM subtypes, we built a risk model called RM_Score. Additionally, we investigated the correlation of RM_Score with clinical characteristics, tumor microenvironment (TME) infiltration, molecular subtypes, therapeutic response, immunotherapy effectiveness, and competing endogenous RNA (ceRNA) network.

Results

RM writers were correlated with TME cell infiltration and prognosis. Cluster_1/2 and gene.cluster_A/B were shown to be capable of distinguishing the HCC patients with poor prognosis after consensus and unsupervised clustering of RNA methylation writers. Additionally, we constructed RNA modification pattern-specific risk model and subdivided the cases into RM_Score high and RM_Score low subgroups. In individual cohorts or merged datasets, the high RM_Score was related to a worse overall survival of HCC patients. RM_Score also exhibited correlations with immune and proliferation related pathways. In response to anti-cancer treatments, the RM_Score had a negative correlation (drug sensitive) with drugs that focused on the MAPK/ERK and metabolism signaling, and a positive correlation (drug resistant) with compounds targeting RKT and PI3K/mTOR signaling pathway. Notably, the RM_Score was connected to the therapeutic effectiveness of PD-L1 blockage, implying that RM writers may be the target of immunotherapy to optimize clinical outcomes. Additionally, a ceRNA network was generated including 2 lncRNAs, 4 miRNAs, and 7 mRNAs that was connected to RM writers.

Conclusions

We thoroughly investigated the potential functions of RNA methylation writers and established an RM_patterns-based risk model for HCC patients. This study emphasized the critical functions of RM modification in TME infiltration, targeted therapy, and immunotherapy, providing potential targets for HCC.
Reflective practice and psychotherapy case experience of Specialty Doctors and Associate Specialists (SAS) working in psychiatry: UK-wide survey
Authors: Vaida Alina , Awal Masud
Published: January 2023

Aims and method

To survey nationwide opportunities for Balint-type and reflective support group participation and psychotherapy training among doctors classified as Specialty Doctors and Associate Specialists in psychiatry (‘SAS psychiatrists’) and the professional benefits and barriers to access.

Results

Approximately 9% of SAS psychiatrists responded, from all UK regions. A minority reported participating in a Balint-type group (27.3%) or reflective practice/support group (30.9%), and only 6.5% were not interested in participating. Although 44.8% planned to see a psychotherapy case, most reported barriers, particularly time constraints, job plans and lack of support. The 22.1% who reported already gaining psychotherapy case experience reported many benefits, including becoming a better listener (84.8%), more empathetic (81.2%), enjoying work more (78.8%) and overall becoming a better psychiatrist (90.9%).

Clinical implications

The reported interest in Balint group and psychotherapy training opportunities exceeded existing provision; psychotherapy case experience benefited professional development and self-reported clinical capabilities. Healthcare trusts and boards need to consider more actively supporting SAS psychotherapy training and reflective practice.
Social interactions within the Sudanese healthcare system: traditional healers and psychiatrists
Authors: Altamih Randa Ahmed Abdalrheem , Elmahi Osman Kamal Osman
Published: January 2023

From a cultural perspective, traditional healing has had a substantial impact on psychiatric management in rural African communities, but the services provided by traditional healers are not integrated with the mental health services provided by primary healthcare. In Sudan, modern psychiatry has seen minimal development beyond the capital city of Khartoum. In rural communities, traditional health practitioners (THPs) are the first point of entry to mental health services. Effective collaboration between THPs and consultant psychiatrists should be encouraged by the introduction of health education that targets THPs, especially in rural communities. This would facilitate the integration of mental health services into primary healthcare and help achieve universal health coverage for psychiatric disorders in Sudan.
National Cancer Grid Virtual Tumor Boards of Head and Neck Cancers: An Innovative Approach to Multidisciplinary Care
Authors: Thiagarajan Shivakumar , Poojari Vinisha , Tuljapurkar Vidisha , Ghosh-Laskar Sarbani , Fatehi Khuzema , Babu Sajith , Penumadu Prashant , Patil Asawari , Joshi Amit , Kumar Suman , Chaukar Devendra , Kannan Ravi , Pramesh C.S.
Published: January 2023

PURPOSE

Virtual tumor board (VTB) via videoconference facility involving multiple specialists in the decision making for various tumors is well accepted, especially in high-income countries. Information on virtual tumor boards for head and neck cancers especially from low- and middle-income countries is sparse. In this study, we have audited the findings of the National Cancer Grid VTBs performed for head and neck cancers.

METHODS

All patients discussed in the head and neck VTBs at our center between December 2016 and February 2022 were included in the study. Details such as the type of institute sending patients for discussion, its location, subsites within the head and neck region, histopathology, treatment setting or question for the VTB, and availability of guidelines for such patient scenarios were assessed. Also, a survey was sent to assess the usefulness of the VTBs.

RESULTS

A total of 208 patients were discussed in 54 VTB sessions. The most common head and neck sites discussed in the VTBs were the oral cavity (n = 64, 30.7%) followed by skull base/nose and paranasal sinuses/eyelid-orbit tumors (n = 49, 23.5%). Nonsquamous cell carcinoma was the most common histopathology discussed; recurrent cancers/residual diseases were the most common treatment settings (n = 134, 64.4%) for which there were no existing guidelines. Survey results showed that most VTB decisions were implementable, and respondents felt that VTBs were a useful educational tool as well.

CONCLUSION

Our study affirms the feasibility of VTBs in low- and middle-income countries' health care systems for managing uncommon malignancies and clinical situations, which act as an important educational platform.
Phase I Study of Single-Agent Anti–Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates
Authors: Brahmer Julie R. , Drake Charles G. , Wollner Ira , Powderly John D. , Picus Joel , Sharfman William H. , Stankevich Elizabeth , Pons Alice , Salay Theresa M. , McMiller Tracee L. , Gilson Marta M. , Wang Changyu , Selby Mark , Taube Janis M. , Anders Robert , Chen Lieping , Korman Alan J. , Pardoll Drew M. , Lowy Israel , Topalian Suzanne L.
Published: January 2023

Purpose

Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti–PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates.

Patients and Methods

Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non–small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti–PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy.

Results

Anti–PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti–PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells ≥ 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment.

Conclusion

Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.
Ertugliflozin Delays Insulin Initiation and Reduces Insulin Dose Requirements in Patients With Type 2 Diabetes: Analyses From VERTIS CV
Authors: Dagogo-Jack Samuel , Frederich Robert , Liu Jie , Cannon Christopher P , Shi Harry , Cherney David Z I , Cosentino Francesco , Masiukiewicz Urszula , Gantz Ira , Pratley Richard E
Published: January 2023

Context

VERTIS CV evaluated the cardiovascular safety of ertugliflozin in patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD).

Objective

The aim of these analyses was to assess the insulin requirements of VERTIS CV patients over the trial duration.

Methods

Patients received ertugliflozin 5 mg, 15 mg, or placebo once daily; mean follow-up was 3.5 years. Time to insulin initiation in patients who were insulin naïve at baseline, change in insulin dose in patients receiving baseline insulin, and hypoglycemia incidence in both patient groups were assessed.

Results

In VERTIS CV, mean duration of type 2 diabetes was 13.0 years; glycated hemoglobin was 8.2%. Among 4348 (53%) insulin-naïve patients, the likelihood of insulin initiation was significantly reduced with ertugliflozin vs placebo (ertugliflozin 5 mg: hazard ratio [HR] 0.70, 95% CI 0.58-0.84; ertugliflozin 15 mg: HR 0.64, 95% CI 0.53-0.78). Time to insulin initiation was delayed with ertugliflozin; the estimated delay in reaching a 10% cumulative incidence of new insulin initiations vs placebo was 399 days with ertugliflozin 5 mg and 669 days with ertugliflozin 15 mg. Among 3898 (47%) patients receiving baseline insulin, the likelihood of requiring a ≥20% increase in insulin dose was significantly reduced with ertugliflozin vs placebo (ertugliflozin 5 mg: HR 0.62, 95% CI 0.52-0.75; ertugliflozin 15 mg: HR 0.51, 95% CI 0.41-0.62). The incidence of hypoglycemia events was not increased with ertugliflozin treatment.

Conclusion

In VERTIS CV patients, ertugliflozin reduced the likelihood of insulin initiation, delayed the time to insulin initiation by up to ∼1.8 years, and reduced insulin dose requirements vs placebo, without increasing hypoglycemia events.
The Effect of Early Time-Restricted Eating vs Later Time-Restricted Eating on Weight Loss and Metabolic Health
Authors: Liu Juanhong , Yi Pan , Liu Feng
Published: January 2023

Context

It remains controversial whether the choice of the daily eating window early or later in time-restricted eating (TRE) intervention (early or later TRE) has different effects on weight loss and metabolic health.

Objective

A network meta-analysis was performed to evaluate the efficacy between early and later TRE in adults with obesity or overweight.

Methods

We searched PubMed, Embase, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) published until October 16, 2022. We conducted a network meta-analysis to evaluate the efficacy of early and later TRE on body weight and metabolic parameters, including glycemic metabolism, blood pressure, and lipid profiles.

Results

Twelve RCTs with 730 obese or overweight adults were included in this meta-analysis. Early TRE and later TRE both elicited moderate reductions in body weight and insulin resistance (IR) (homeostasis model assessment of IR) when compared to non-TRE. Interestingly, early TRE showed more effectiveness than later TRE in improving IR (early vs later TRE: −0.44; 95% CI, −0.86 to −0.02; P < .05), whereas no statistically significant difference was detected in weight loss (early vs later TRE: −0.31 kg; 95% CI, −1.15 to 0.53 kg; P >.05). In addition, early TRE rather than later TRE showed significant benefits in glycemic metabolism and blood pressure when compared to non-TRE. No significant differences between early and later TRE were observed for fasting blood glucose, blood pressure, and lipid profiles.

Conclusion

This meta-analysis suggests that people may choose early TRE for more effective weight management and metabolic benefits. Nevertheless, further large-scale RCTs are warranted to verify our findings.
Mortality as a Function of Survival
Authors: Alvarez Jesús-Adrián , Vaupel James W.
Published: January 2023

Everyone has a chronological age. Because survivorship declines relentlessly in populations with age-specific death rates greater than zero, everyone also has a survivorship age (“s-age”), the age at which a proportion s of the population is still alive. S-ages can be estimated for both periods and cohorts. While trajectories of mortality over chronological ages differ (e.g., across populations, over time, by sex, or by any subpopulation), mortality trajectories over s-ages are similar, a sign that populations experience similar mortality dynamics at specific levels of survivorship. We show that this important demographic regularity holds for 23 sex-specific populations analyzed during a period comprising more than 100 years.
The Role of Suburbanization in Metropolitan Segregation After 1940
Authors: Logan John R. , Kye Samuel , Carlson H. Jacob , Minca Elisabeta , Schleith Daniel
Published: January 2023

The three decades from 1940 through 1970 mark a turning point in the spatial scale of Black–White residential segregation in the United States compared with earlier years. We decompose metropolitan segregation into three components: segregation within the city, within the suburbs, and between the city and its suburbs. We then show that extreme levels of segregation were well established in most cities by 1940, and they changed only modestly by 1970. In this period, changes in segregation were greater at the metropolitan scale, driven by racially selective population growth in the suburbs. We also examine major sources of rising segregation, including region, metropolitan total, and Black population sizes, and indicators of redlining in the central cities based on risk maps prepared by the Home Owners Loan Corporation (HOLC) in the late 1930s. In addition to overall regional differences, segregation between the city and suburbs and within suburbia increased more in metropolitan areas with larger Black populations, but this relationship was found only in the North. In contrast to some recent theorizing, there is no association between preparation of an HOLC risk map or the share of city neighborhoods that were redlined and subsequent change in any component of segregation.
Geographic Trends in the Neurosurgery Match During the COVID-19 Pandemic
Authors: Moya Addi N. , Whisonant Cees T. , Shahriari Shawhin R. K. , McDonald Casey D. , Ederle Amanda C. , Laarakker Avra S. , Borah Gregory L.
Published: January 2023

In the present article, the impact of the COVID-19 pandemic on geographical trends in the neurosurgery match in successfully matched applicants was analyzed. A cross-sectional analysis for the years from 2017 to 2021 was performed. Successful applicants' region, state, and medical school were compared with the location of their matched residency program. The number of applicants matching at a residency program within the same region or state as their home medical school or their own medical school was then evaluated. One hundred fifteen neurosurgery residency programs and 1066 successfully matched applicants were included in the analysis. When comparing 2021 with previous years, no significant change in the percentage of applicants matching at their home region (43.1% vs 49.7%,P= .09), home state (25.1% vs 26.3%,P= .69), or home program (19.9% vs 18.7%,P= .70) was found. The COVID-19 pandemic did not significantly affect geographic trends during the neurosurgery match in 2021. This is of note as the COVID-19 pandemic significantly affected the match in other competitive specialties, including plastic surgery, dermatology, and otolaryngology. Despite limited away rotations, it is possible that neurosurgery programs did not change their applicant selection criteria and implemented systems to virtually interact with applicants outside of their local region.
Investigation of mutational spectrum in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma
Authors: Zahid Tazeen , Khan Dr. Muhammad Umer , Zulfiqar Aymn , Jawad Fatima , Saleem Anosh , Khan Ahmad Raza
Published: January 2023

Objective: To identify the genetic variants in the CYP1B1 gene associated with Primary Congenital Glaucoma (PCG) and to predict its pathological effect.

Method: A descriptive study was conducted in the time period of nine months (September 2021-May 2022) after the ethical approval was taken from The Children Hospital and Institute of Child Health (CH & ICH). Two milliliters of the blood sample from PCG-affected individuals were collected in EDTA vacutainers and genomic DNA was extracted by a phenol-chloroform method. The semi-quantification of extracted DNA was done by agarose gel electrophoresis. PCR amplification was performed by specific primers of CYP1B1 gene then termination sequencing (di-deoxy) was done to detect the genetic variants. Different bioinformatics tools such as BLAST, Ensembl, Clustal Omega, Polyphen and SIFT were used for the further analysis of mutation causing the disease.

Results: A total of 85% of patients were bilaterally affected, while 15% were unilaterally affected. Mutation analysis identified five non related known variants. Two missense mutations (c.355 G/T p.A119S and c.685G/A p.E229K) occurred in 94% patients and intragenic SNP occurred in 29% patients along with the 1% somatic (c.693C/A p.F231L) and stop gained mutation (c.840C/A p.C280*).

Conclusion: Genetic analysis in the current study showed that 85% of PCG affected patients were due to the CYP1B1 mutation, and disease heterogeneity might be reduced through genetic counseling.

doi: https://doi.org/10.12669/pjms.39.2.7081

How to cite this: Zahid T, Khan MU, Zulfiqar A, Jawad F, Saleem A, Khan AR. Investigation of mutational spectrum in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma. Pak J Med Sci. 2023;39(2):---------. doi: https://doi.org/10.12669/pjms.39.2.7081

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.