Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis.

BACKGROUND: The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy. METHODS: We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis. RESULTS: The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors. DISCUSSION: At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment.

Evolution of Initial Treatment for Desmoid Tumors.

INTRODUCTION: Desmoid tumors (DTs) are rare, fibroblastic cell proliferations that can exhibit locally aggressive behavior but lack metastatic potential. Initial management has traditionally involved upfront resection; however, contemporary guidelines and expert panels have increasingly advocated for prioritizing active surveillance strategies. METHODS: A single-institution, retrospective chart review identified all patients diagnosed with a primary DT at any site from 2007 to 2020. The primary outcome was the initial management strategy over time. Secondary outcomes included treatment-free survival (TFS) and time to treatment (TTT) for those undergoing active surveillance, as well as recurrence-free survival (RFS) and time to recurrence for those undergoing resection. RESULTS: Overall, 103 patients were included, with 68% female and a median follow-up of 44 months [24-74]. The most common tumor locations included the abdominal wall (27%), intra-abdominal/mesenteric (25%), chest wall (19%), and extremity (10%). Initial management included resection (60%), systemic therapy (20%), active surveillance (18%), and cryoablation (2%). Rates of surgical resection significantly decreased (p < 0.001) over time, from 69.6% prior to 2018 to 29.2% after 2018. For those treated with upfront resection, 5-year RFS was 41.2%, and for patients undergoing initial active surveillance, TFS was 66.7% at 2 years, with a median TTT of 4 months [4-10]. CONCLUSIONS: This single-institution cohort at a tertiary medical center spanning over a decade demonstrates the transition to active surveillance for initial management of DTs, and highlights salient metrics in the era of surveillance. This trend mirrors recommended treatment strategies by expert panels and consensus guidelines.

Changes in the trends of initial treatment for newly diagnosed prostate cancer in Japan: a nationwide multi-institutional study.

BACKGROUND: In previous large-scale studies conducted through 2010, androgen deprivation therapy (ADT) was the most common initial treatment for prostate cancer patients in Japan. However, recent advancements in treatment technologies have significantly affected the management of prostate cancer in Japan. This study analyzed the trends in initial treatments for prostate cancer based on two nationwide surveys. METHODS: Two Japan-wide multi-institutional surveys, J-CaP2010 and J-CaP2016, were conducted to enroll patients newly histologically diagnosed with prostate cancer in 2010 and 2016-18, respectively. Both surveys included age at diagnosis, initial PSA level, ISUP Grade Group, TNM classification, and initial treatment for prostate cancer. RESULTS: J-CaP2010 included data from 8192 patients across 140 institutions, whereas J-CaP2016 included data from 21 841 patients across 186 institutions. In J-CaP2016, the proportion of radical prostatectomy (RP) and radiation therapy (RT) in the initial treatment increased (from 32% to 36% and 21% to 26%, respectively), whereas the proportion of ADT decreased (from 40% to 29%) compared with those in J-CaP2010. The increase in RP or RT was noticeable in patients aged 75 years and older (from 20% to 38%) and those with high-risk localized cancer (from 58% to 74%) or locally advanced cancer (from 38% to 56%). The proportion of active surveillance or watchful waiting increased in patients with low-risk localized cancer (from 21% to 41%). The proportion of robot-assisted RP within all RPs and the proportion of intensity-modulated RT within all RTs increased remarkably (from 2.3% to 78% and 20% to 50%, respectively). CONCLUSIONS: In Japan, RP and RT have increased as initial treatments for prostate cancer, whereas ADT has decreased. Consequently, RP has emerged as the most commonly selected initial treatment, replacing ADT.

Comparative prospective cohort study of efficacy and safety according to dosage and administration of ceftriaxone for community-acquired pneumonia.

INTRODUCTION: Limited prospective evidence has been accumulated regarding the efficacy and safety of ceftriaxone (CTRX) based on differences in dosage and administration of the drug as empiric therapy for community-acquired pneumonia (CAP). This study aimed to compare initial treatment failure, 30-day mortality, and side effects between two groups of hospitalized adult CAP patients: one receiving intravenous CTRX at 1g twice daily (1gq12hr) and the other receiving 2g once daily (2gq24hr). METHODS: We prospectively included patients with CAP admitted to our hospital between October 2010 and December 2018. We analyzed patients initially treated solely with CTRX as either 1gq12hr or 2gq24hr. The primary outcome was initial treatment failure, while secondary outcomes were 30-day mortality and side effects. Inverse probability of treatment weighting (IPTW) analysis was used to minimize biases. RESULTS: Among the 457 CAP patients, 186 patients were in the 1gq12hr group and 271 patients were in the 2gq24hr group. After IPTW analysis, no significant differences in initial treatment failure rate (2.43 % vs 4.46 %, p = 0.27) or 30-day mortality rate (2.95 % vs 6.43 %, p = 0.13) were seen between groups. A small but noteworthy tendency was noted in the frequency of side effects between the two groups (1.04 % vs 4.20 %, p = 0.08) following IPTW analysis, even though the difference was not significant. CONCLUSIONS: This study did not find any significant difference between ceftriaxone 1gq12hr and 2gq24hr regarding efficacy or safety in adult patients with CAP. However, CTRX 1gq12hr may represent a safer option in terms of side effects.

Factors affecting the readiness for hospital discharge of initially treated pulmonary tuberculosis patients in China: a phenomenological study.

BACKGROUND: Despite readiness for hospital discharge widespread popularity since readiness for hospital discharge introduction in 1979 and extensive study, readiness for hospital discharge among pulmonary tuberculosis (PTB) patients has not yet been investigated. Moreover, the factors influencing this process remain unclear. OBJECTIVE: The objective of this study was to investigate the factors influencing readiness for hospital discharge in initially treated PTB patients using the capability, opportunity, motivation-behavior (COM-B) model. METHODS: This phenomenological study was conducted from December 2023 to March 2024. Face-to-face individual interviews were conducted with 18 initially treated patients with PTB according to a semistructured interview guide developed on the basis of the COM-B model. The interview data were subjected to analysis using NVivo 14 software and Colaizzi's method. RESULTS: As a result, 6 themes and 14 subthemes were identified. Physical capability for readiness for hospital discharge (subthemes included poor health status, early acquisition of adequate knowledge about PTB, inadequate knowledge about readiness for hospital discharge), psychological capability for readiness for hospital discharge(subthemes included false perceptions about readiness for hospital discharge, high treatment adherence), physical opportunity for readiness for hospital discharge (subthemes included high continuity of transition healthcare, insufficient financial support, insufficient informational support), social opportunity for readiness for hospital discharge (subthemes included stigmatization, inadequate emotional support), reflective motivation for readiness for hospital discharge (subthemes included lack of reflection on coping with difficulties, intention to develop a readiness for hospital discharge plan), and automatic motivation for readiness for hospital discharge (subthemes included strong desire to be cured, negative emotions). CONCLUSION: We established factors related to readiness for hospital discharge in initially treated PTB patients in terms of capability, opportunity and motivation, which can inform the future development of readiness for hospital discharge plans. To improve patients' readiness for hospital discharge, patients need to be motivated to plan and desire readiness for hospital discharge, patients' knowledge and treatment adherence should be improved, and patients' transition healthcare continuity and emotional support should be focused on. Moreover, the quality of readiness for hospital discharge and discharge education should be assessed in a timely manner to identify impeding factors and provide interventions.

Emergency treatment of pelvic ring injuries: state of the art.

High energy pelvic injuries sustain significant mortality rates, due to acute exsanguination and severe associated injuries. Managing the hemodynamically unstable trauma patient with a bleeding pelvic fracture still forms a major challenge in acute trauma care. Various approaches have been applied through the last decades. At present the concept of Damage Control Resuscitation (DCR) is universally accepted and applied in major trauma centers internationally. DCR combines hemostatic blood transfusions to restore blood volume and physiologic stability, reduced crystalloid fluid administration, permissive hypotension, and immediate hemorrhage control by operative or angiographic means. Different detailed algorithms and orders of hemostatic procedures exist, without clear consensus or guidelines, depending on local traditions and institutional setups. Fracture reduction and immediate stabilization with a binder constitute the basis for angiography and embolization (AE) or pelvic packing (PP) in the hemodynamically unstable patient. AE is time consuming and may not be available 24/7, whereas PP offers a quick and technically easy procedure well suited for the patient in extremis. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has also been described as a valuable adjunct in hemostatic non-responders, but merely constitute a bridge to surgical or angiographic hemostasis and its definitive role in DCR is not yet clearly established. A swift algorithmic approach to the hemodynamically unstable pelvic injury patient is required to achieve optimum results. The present paper summarizes the available literature on the acute management of the bleeding pelvic trauma patient, with emphasis on initial assessment and damage control resuscitation including surgical and angiographic hemostatic procedures. Furthermore, initial treatment of open fractures and associated injuries to the nervous and genitourinary system is outlined.

Relationship between CD4+ T-cell counts at baseline and initial periodontal treatment efficacy in patients undergoing treatment for HIV infection: A retrospective observational study.

AIM: To retrospectively investigate the relationship between the CD4+ T-cell counts at baseline and the efficacy of the initial periodontal treatment of patients undergoing treatment for human immunodeficiency virus (HIV) infection using the periodontal inflamed surface area (PISA). MATERIALS AND METHODS: Thirty-three patients with chronic periodontitis who had undergone periodontal examination at baseline and after the initial periodontal treatment were enrolled. PISA was calculated from the periodontal probing depth and bleeding on probing, and the ratio of PISA after treatment to that at baseline (PISA response ratio) was calculated. Groups with a response ratio of <1 and ≥1 were defined as the improvement and the non-improvement groups, respectively. RESULTS: PISA after the initial periodontal treatment significantly decreased compared with that at baseline (p < .05). A weak negative correlation was found between the PISA response ratio and CD4+ T-cell counts at baseline (p < .05). The CD4+ T-cell counts at baseline were significantly higher in the improvement group than in the non-improvement group (p < .05). Multivariate analysis revealed that the CD4+ T-cell counts at baseline was an independent factor that affects the PISA (p < .05). CONCLUSIONS: The higher the CD4+ T-cell counts at baseline in patients undergoing treatment for HIV infection, the more effective the initial periodontal treatment.

Intravenous immunoglobulin for interstitial lung diseases of anti-melanoma differentiation-associated gene 5-positive dermatomyositis.

OBJECTIVE: Rapidly progressive interstitial lung disease (RP-ILD) in DM patients positive for anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibody (MDA5-DM) often have a poor prognosis, frequently fatal. As there is a scarcity of data regarding the effect of intravenous immunoglobulin (IVIG) on RP-ILD in MDA5-DM patients (MDA5-RPILD), we conducted this study to determine the efficacy of a IVIG add-on initial treatment. METHODS: Patients with newly-onset MDA5-RPILD from September 2018 to June 2020 were retrospectively reviewed for 6 months in the First Affiliated Hospital of Zhengzhou University. They were divided into two groups: IVIG and non-IVIG groups. The major measurement of treatment outcome was the difference in the mortality in 3-month and 6-month between two group patients. Other relevant indicators were also recorded, including the incidence of infection, the dosages of GCs, the remission rate and the variables in laboratory data. RESULTS: The IVIG group (n = 31) showed significantly lower 6-month mortality rate than the non-IVIG group (n = 17) (22.6% vs 52.9%; P =0.033). The IVIG group patients had a higher remission rate at 3 months (71.0% vs 41.2%; P =0.044). Gradual reduction was observed in the first 3 months with regard to the titre of anti-MDA5 autoantibody, the serum level of ferritin and the ground glass opacification GGO scores. CONCLUSION: IVIG adjunct therapy is a very effective first-line treatment for patients with MDA5-RPILD. IVIG may increase the survival and remission rate by lowering ferritin concentration, anti-MDA5 titre and GGO score.

Sociodemographic factors associated with the first administration of anti-seizure medication in patients with focal epilepsy in Western China.

BACKGROUND: Epilepsy is a severe chronic neurologic disease with a prevalence of 0.7% worldwide; anti-seizure medications (ASMs) are the mainstay of epilepsy treatment. The effects of sociodemographic factors on the characteristics of initial treatment in patients with newly diagnosed focal epilepsy in Western China are unknown. This study was conducted to explore sociodemographic factors associated with initial treatment characteristics. METHODS: Patients with focal epilepsy on continuous ASM treatment who visited to our epilepsy center at Sichuan Provincial People's Hospital between January 2018 and December 2019 were recruited. Data on initial treatment status and sociodemographic variables were obtained from the patients with a questionnaire designed by our researchers. We examined whether sociodemographic factors were associated with epileptic patients' access to neurologists and prescriptions of individual ASMs. RESULTS: A total of 569 patients completed this study. We found that patients with a higher education level, aged < 16 years, and with a higher household disposable income were more likely to receive treatment from a neurologist than their counterparts. Patients with a lower personal income level and who were treated at a junior hospital were more likely to receive prescriptions for carbamazepine, and those who were younger than 16 years were less likely to receive prescriptions for carbamazepine and oxcarbazepine. Patients with a higher education level, with a higher household disposable income level, who were younger than 16 years, and who were treated at a senior hospital were more likely to receive prescriptions for levetiracetam than their counterparts. Adult, female patients with focal epilepsy treated at a senior hospital were more likely to receive prescriptions for lamotrigine. CONCLUSIONS: This observation suggests that sociodemographic characteristics are associated with access to neurologists and prescriptions of individual antiepileptic drugs. These data may help public health officials establish guidelines for doctors and distribute resources according to the needs of different patient groups.

Comparison of three different dose regimens of methylprednisolone as initial therapy for pemphigus vulgaris of moderate severity: A single-center retrospective study from Turkey.

BACKGROUND: Currently, no consensus exists on the dosing regimen of corticosteroids in relation to disease severity in pemphigus vulgaris. OBJECTIVE: To evaluate the efficacy of three initial dose regimens of methylprednisolone in the treatment of moderate pemphigus. METHODS: We retrospectively analysed the data of 46 patients with moderate pemphigus vulgaris, who initially received either low (0.60-0.80 mg/kg/day), moderate (0.81-1.20 mg/kg/day) or high (1.21-2.0 mg/kg/day) doses of methylprednisolone. RESULTS: The median time to disease control and hospital stay was shortest in the high-dose group (8.5 days and 27.5 days, respectively). The low-dose group had the highest rate of adjuvant therapy (88.8%, P = 0.035). Cumulative methylprednisolone doses and corticosteroid-related adverse events were similar in the moderate- and high-dose groups. The initial methylprednisolone dose showed a significant inverse correlation with time to disease control (r = -0.319, P = 0.031) and a weak inverse correlation with length of hospital stay (r = -0.282, P = 0.058). LIMITATIONS: Retrospective design and small patient size are major limitations. CONCLUSION: In the treatment of moderate pemphigus vulgaris, high initial doses of corticosteroid seem to provide early disease control and shortened hospital stay without notable increases in cumulative corticosteroid doses. This treatment strategy may lower the risk for nosocomial infections and reduce the economic burden of pemphigus.

The initial treatment of complex proximal humerus fracture affects the outcome of revision with reverse shoulder arthroplasty.

PURPOSE: The purpose of the study is to report the results of reverse shoulder arthroplasty (RSA) after three types of initial treatment performed for complex proximal humeral fracture (PHF): conservative, reduction and internal fixation (RIF), or hemiarthroplasty. METHODS: This is a retrospective study of 63 patients separated into three groups with a minimum follow-up of two years. Group I included 25 patients with an initial conservative fracture treatment, group II included 25 patients treated by RIF, and group III included 13 patients initially treated by hemiarthroplasty. Patients were assessed using the absolute Constant-Murley score, functional parameters, complications rate, and radiological follow-up. RESULTS: One patient died and five were lost to follow-up. All functional outcomes improved significantly post-operatively for the three groups (p < 0.005). The mean Constant-Murley score increased from 13.7 to 54.1 (group I); 16.6 to 48.5 (group II); and 22.6 to 48.2 (group III) (p < 0.001). The gain of Constant-Murley and SST scores was better for group I (p = 0.049 and 0.028, respectively), while post-operative pain was better in group III (p = 0.033). The complication rate was 38% in group III, 30% in group II, and 14.3% in group I. CONCLUSIONS: Reverse shoulder arthroplasty represents a good surgical option in complex proximal humeral fracture sequelae. Whatever the initial treatment, function and motion of the shoulder are improved. The final result is better if the initial treatment was conservative. The group initially treated with hemiarthroplasty had the most complications.

Assessing evidence-based medicine and opioid/barbiturate as first-line acute treatment of pediatric migraine and primary headache: A retrospective observational study of health systems data.

OBJECTIVES: To evaluate providers' use and predictors of evidence-based medicine or opioid/barbiturate as first-line acute treatment for children's initial presentation of acute migraine or primary headache. METHODS: This retrospective, observational study utilized patient (children ages 6-17) and provider/encounter characteristics extracted from the patient's Electronic Health Record from 2008-2014 during an initial encounter for migraine or primary headache. The primary outcome was provider evidence-based medicine utilization; overall prescriptions and opioid/barbiturate prescriptions were also evaluated. Hierarchical linear modeling examined whether Level 1 (patient: Demographic, insurance type) and Level 2 (provider/encounter: Treatment setting/location, encounter diagnoses) characteristics influenced outcomes. RESULTS: In all, 38,926 patients (56.7% female, mean age = 12.1) and 1617 providers were evaluated. Only 17.7% of patients were diagnosed with migraine; 16.1% received evidence-based medicine. Older children (OR = 1.07, p < 0.001), females (OR = 1.14, p < 0.001), and those diagnosed with migraine (OR = 4.71, p < 0.001) were more likely to receive evidence-based medicine. Among prescriptions, 15.8% were for opioids/barbiturates. Older children (OR = 1.14, p < 0.001) and those cared for in the emergency department/urgent care (OR = 2.02, p < 0.001) were at increased risk. CONCLUSIONS: Demographics and migraine diagnosis are associated with evidence-based medicine and opioid/barbiturates. Primary care provides an opportunity to target provider interventions to enhance effective pediatric headache treatment.

Predicting responsiveness to a sustained reading and spelling intervention in children with dyslexia.

The present study aimed to predict responsiveness to a sustained two-phase reading and spelling intervention with a focus on declarative and procedural learning respectively in 122 second-grade Dutch children with dyslexia. We related their responsiveness to intervention to precursor measures (phonological awareness, rapid automatized naming ability, letter knowledge, and verbal working memory) and related word and pseudoword reading and spelling outcomes of the sustained intervention to initial reading and spelling abilities, and first-phase, initial treatment success. Results showed that children with dyslexia improved in reading accuracy and efficiency and in spelling skills during the two phases of the intervention although the gap with typical readers increased. In reading efficiency, rapid automatized naming, and in reading and spelling accuracy phoneme deletion predicted children's responsiveness to intervention. Additionally, children's initial reading abilities at the start of the intervention directly (and indirectly, via initial treatment success, in reading efficiency) predicted posttest outcomes. Responsiveness to intervention in spelling was predicted by phoneme deletion, and spelling at posttest was indirectly, via initial treatment success, predicted by children's initial spelling abilities. Finally, children's initial treatment success directly predicted reading efficiency and spelling outcomes at posttest.

Initial antibiotic treatment of serious bacterial infections.

The article summarizes the known facts regarding the selection of antibiotics for the treatment of sepsis and similar serious infections, their mechanism of action, dosage and mode of administration. Particular attention is paid to early antibiotic therapy: a delay of several hours in the onset of antibiotic therapy can be tolerated if it helps to clarify the aethiology and to refine the treatment. However, in case of the very acute infections it is necessary to start antibiotic treatment immediately; diagnostic procedures are mentioned that can be used for the selection of the appropriate drug.

[A cross-sectional study on application of glucocorticoid in systemic lupus erythematosus patients].

Objective: To explore the status of glucocorticoid application in patients with systemic lupus erythematosus (SLE) in China. Methods: Epidemiological survey was used. The SLE patients who met the 1997 classification criteria of American College of Rheumatology were enrolled. The usage of glucocorticoid and related adverse reactions were recorded and analyzed. Results: A total of 400 SLE patients were enrolled, including 35 men and 365 women. The average age was (37.4±14.0) years old, and the average duration of disease was (6.7±5.8) years. There were 310 patients using glucocorticoid as maintenance. Sixty-one percent (n=244) patients started using medium dose (prednisone 30-<60 mg/d) as the initial treatment of glucocorticoid, which lasted for(37±11)days.The time of drug duration in patients with low dose prednisone (7.5-<30 mg/d)and high dose (60-100 mg/d) was(92±20)and(17±3)days respectively (P<0.05 between 3 groups). However, patients receiving different initial dosage were of no discrepancy in the maintenance therapy. During maintenance, even though 51.0% (n=158) patients were on prednisone 2.5-5 mg/d, the duration of drug use in >5-10 mg/d groupwas longer[(29.9±3.3) months]. Patients with involvement of internal organs had a higher tendency to use 60-100 mg/d prednisone or pulse-dose therapy in the initial treatment, nevertheless these two groups had no difference of maintenance dosage. Among all 400 patients, 62 patients withdrew glucocorticoid, including 17 patients with disease remission (4.3%), 44 by self-withdrawal and one with adverse reaction. Conclusion: In China, the medium dosage of glucocorticoid is the most common initial treatment in patients with SLE.Prednisone 2.5-5 mg/d was the most common choicefor maintenance therapy. Currently, the proportion of glucocorticoid withdrawal remains low in SLE patients achieving remission.

Smoking's impact on pocket closure after nonsurgical periodontal treatment in relation to bleeding on probing.

OBJECTIVES: Our aim was to investigate the impact of smoking on pocket closure at six months after treatment of severe periodontitis, in relation to residual clinical inflammation. METHOD AND MATERIALS: The clinical records of deep pockets (probing depth≥6 mm, n=984) in 46 individuals with periodontitis were analyzed. Following baseline clinical assessments (plaque index, probing depth, clinical attachment level, and bleeding on probing), non-surgical periodontal treatment was performed. Clinical assessments were repeated at 2 and 24 weeks after periodontal therapy. A logistic regression model using generalised estimation equations (GEE) adapting the cluster robust standard errors was performed to investigate potential associations between bleeding on probing and pocket closure at post-treatment 24 weeks. RESULTS: Absence of bleeding at two weeks after non-surgical treatment related to pocket closure after six-months. Pockets that do not bleed neither at baseline nor two weeks (OR=2.7; P <.005) and pockets of non-smokers (OR=6.32; P <.001) and females (OR=1.79; P =.022) associated with pocket closure at six months. CONCLUSION: Pocket closure is associated with being a non-smoker and the absence of inflammation after non-surgical periodontal treatment, which indicates the importance of smoking cessation and inflammation control in achieving optimal clinical outcomes.

Comparative efficacy and safety of tenofovir amibufenamide vs tenofovir alafenamide in the initial 48-week treatment of high viral load chronic hepatitis B: A single-centre retrospective study.

BACKGROUND/AIM: Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB). METHODS: We retrospectively collected clinical data from March 1 2022 to June 30 2022 for highly viremic CHB patients who received either TMF (n = 58) or TAF (n = 32) as their initial monotherapy at Beijing YouAn Hospital. To understand the efficacy and safety of TMF over 48 weeks, we compared the virological response rates and HBeAg/HBsAg serological clearance rates between TMF and TAF groups. Also, the changes in serum creatinine, eGFR and serum lipid levels were assessed. RESULTS: Baseline median HBV DNA levels were 7.85 (6.89, 8.36) IgIU/ml for TMF and 7.44 (6.89, 8.03) IgIU/ml for TAF. Median ALT levels were 102.0 (56.0, 210.0) U/L for TMF and 195.0 (73.5, 371.0) U/L for TAF, with HBeAg positivity rates of 70.7% and 75.0%, respectively. At 48 weeks, virological response rates (HBV DNA <10 IU/ml) were 43.5% (20/46) for TMF and 42.9% (12/28) for TAF (p = 1.000). ALT normalization rates were 87.9% for TMF and 90.6% for TAF (p = .969), and HBeAg serological clearance rates were 21.1% and 18.2%, respectively (p = 1.000). No patients achieved HBsAg clearance. Compared with the baseline, LDL-C levels increased, while eGFR decreased, with no significant differences in serum creatinine, triglycerides and total cholesterol levels noted at week 48 for both TMF and TAF groups. CONCLUSION: TMF demonstrates comparable antiviral efficacy to TAF when used as initial therapy in highly viremic CHB patients, with similar impacts on renal function and lipid profiles.

Characteristics of primary Sjogren's syndrome with articular manifestations at initial treatment.

Objectives: Articular manifestations have been reported in 19.3%-53.5% of patients with primary Sjogren's syndrome. Our aim was to profile the clinical characteristics of Chinese patients with primary Sjogren's syndrome who presented with articular manifestations at the time of initial treatment. Methods: We conducted a retrospective study of 129 primary Sjogren's syndrome patients admitted to the second Affiliated Hospital of Dalian Medical University between April 2016 and December 2021 for initial treatment. Clinical and serological features, extra-articular involvement, and initial treatment were compared between primary Sjogren's syndrome patients with and without articular manifestations. Results: Fifty-seven (44.2%) primary Sjogren's syndrome patients had articular manifestations (mean age at diagnosis: 53.4 years), of which 42 (73.7%) presented with symmetrical distribution, 21 (36.8%) patients had rheumatoid factor positivity, and 11 (20.0%) patients had anti-cyclic citrullinated peptide antibodies positivity (mean 6.8 RU/mL); imaging examinations showed no signs of structural damage in these patients. The presence of articular manifestations showed positive correlation with anti-cyclic citrullinated peptide antibody level (odds ratio (OR) 1.01, 95% confidence interval (CI): 1.00-1.02; p = 0.049), C-reactive protein level (OR 1.15, 95% CI: 1.10-1.20; p = 0.000), and European League Against Rheumatism Sjogren syndrome disease activity index scores (OR 1.18, 95% CI: 1.11-1.25; p = 0.000). Ninety (69.8%) primary Sjogren's syndrome patients received hydroxychloroquine therapy. Hydroxychloroquine treatment was significantly less frequently used in articular manifestation patients (35 (70.0%) vs 55 (85.9%); p = 0.038). Conclusions: Symmetrical polyarthritis was the most common clinical manifestation of primary Sjogren's syndrome patients with articular manifestations in this cohort. Articular manifestations were associated with higher prevalence of C-reactive protein level, and European League Against Rheumatism Sjogren syndrome disease activity index score.

The potential positive effect of periodontal treatment on brain function activity using functional magnetic resonance imaging analysis.

Background/purpose: There are reports on the relationship between periodontal treatment and the whole body. The purpose of the present study was to investigate the effect of periodontal initial treatment on brain function activity by improving periodontal tissue and the occlusal status of subjects with periodontitis. Materials and methods: The subjects were 13 patients with periodontitis. Following the patient's informed written consent, the periodontal initial treatment provided to the patient included tooth brushing instruction, scaling and root planning, however, occlusal adjustment was not performed at this stage. Periodontal examination, occlusal force examination and fMRI results were also evaluated at the initial and the reevaluation examinations. Results: After the periodontal initial treatment had been performed, periodontal tissue had significantly improved. In addition, cerebral blood flow in the insula and primary motor cortex was also improved, as confirmed by fMRI. Conclusion: This result suggests that the periodontal ligament has recovered and the periodontal ligament neuron have been further subjected to clenching in the insula.

Optimal surgical population for cervical lymph node dissection in PTC.

Objective: There is still controversy about whether cervical lymph node dissection should be performed in surgical treatment of PTC. Based on the data of thyroid cancer patients from Liaocheng People's Hospital from 2015 to 2018, this study focused on appropriate indications for cervical lymph node dissection surgery. Methods: The clinical and pathological data of patients with initial treatment of PTC in thyroid surgery department from 2015 to 2018 were collected. In all cases, 1001 patients underwent total thyroidectomy + central lymph node dissection, and 1107 patients underwent total thyroidectomy + central + cervical lymph node dissection. Results: The average metastasis rate of all cases was 57.23%, and even the metastasis rate of PTMC was as high as 48.97%. The total metastasis rate of central and lateral cervical lymph nodes was 74.44%, and the cervical lymph nodes were present in 49.32% of the metastatic cases. In 55.56% of the cases, the tumor diameter was more than 1 cm, and the metastasis rate of cervical lateral area was 56%. With the increase of tumor diameter, the cervical metastasis rate increased from 22.54% to 73.33%. Conclusion: The metastasis rate of PTC is more than 50%, and nearly half of them have cervical metastasis, especially in patients with high risk factors. We observed that PTC 1 cm or greater has significant rates of metastasis.