[Comparison of the population covered by the 2024 version of the WHO's hepatitis B prevention and treatment guidelines and the Chinese antiviral treatment guidelines].

Objective: This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB). Methods: The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications. Results: A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines. Conclusion: The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

Physical health-related quality of life trajectories over two years following breast cancer diagnosis in older women: a secondary analysis.

PURPOSE: To identify distinct trajectories of physical health-related quality of life (HRQoL) in older women over the first two years following breast cancer diagnosis, and to examine characteristics associated with trajectory group membership. METHODS: A secondary analysis of a longitudinal study of women diagnosed with stage I-III breast cancer who completed surveys within eight months of diagnosis and six, twelve, and eighteen months later that focuses on a subset of women aged ≥ 65 years (N = 145).Physical HRQoL was assessed using the Physical Component Score (PCS) of the SF-36 Health Survey. Finite mixture modeling identified distinct PCS trajectories. Multivariable logistic regression identified variables predictive of low PCS group membership. RESULTS: Two distinct patterns of PCS trajectories were identified. The majority (58%) of women had PCS above the age-based SF-36 population norms and improved slightly over time. However, 42% of women had low PCS that remained low over time. In multivariable analyses, older age, difficulty paying for basics, greater number of medical comorbidities, and higher body mass index were associated with low PCS group membership. Cancer treatment and psychosocial variables were not significantly associated. CONCLUSION: A large subgroup of older women reported very low PCS that did not improve over time. Older age, obesity, multiple comorbidities, and lower socioeconomic status may be risk factors for poorer PCS in women with breast cancer. Incorporating routine comprehensive geriatric assessments that screen for these factors may help providers identify older women at risk for poorer physical HRQoL post breast cancer treatment.

Patient-reported esthetic outcomes following lower extremity free flap reconstruction: A cross-sectional multicenter study.

INTRODUCTION: The goal of lower-extremity reconstructions is primarily to salvage the leg; however, esthetic outcomes are also important. This study aimed to assess the impact of a lower extremity free tissue transfer regarding social functioning, patient-reported esthetic outcomes, and possible differences between fasciocutaneous vs. muscle flaps. MATERIAL AND METHODS: For this cross-sectional multicenter study, patients operated between 2003 and 2021, with a minimum follow-up of 12 months, were identified. Outcomes were obtained from 89 patients. Patient-reported outcomes were assessed using a questionnaire containing 5-point Likert scale questions grouped in three groups: aspect of the reconstructed leg, the aspect of the donor site, and the negative impact on social functioning. Physical functioning and mental health were assessed with the Short-Form-36. RESULTS: The overall score for negative impact on social functioning was 22.2. This was 46.7 for the esthetic satisfaction of the reconstructed leg and 57.1 for the donor site. No significant differences were seen between patients who underwent a reconstruction with a fasciocutaneous flap compared to a muscle flap. Secondary surgical procedures for improving the esthetic aspect were performed in 12% of the patients in the fasciocutaneous group and 0% in the muscle group. CONCLUSION: Our results show that the most optimal esthetic outcome is not defined by the type of flap. We found a strong correlation between physical functioning and the negative impact on social functioning that a reconstructed lower extremity may have. The result of this study can be taken into consideration during the shared decision-making process of choosing the most optimal reconstruction.

[Marked improvement in rheumatoid lung nodules after treatment with tocilizumab combined with glucocorticoids and leflunomide: a case report and literature review].

Rheumatoid arthritis (RA), a chronic autoimmune disorder, is characterized by erosive inflammation of bone and cartilage, leading to progressive joint destruction. Pulmonary involvement occurs in approximately 60% of RA patients, manifests most commonly as interstitial lung disease and, less commonly, as rheumatoid lung nodules. Here, we report a 50-year-old woman, non-smoker, with recurrent cough and sputum of 7 years' duration, accompanied by a chest CT showing multiple cavitary nodules in both lungs. She had been treated empirically at several medical centers and was finally diagnosed with rheumatoid lung nodules. Marked improvement in rheumatoid lung nodules was observed after treatment with tocilizumab in combination with glucocorticoids and leflunomide. The aim of this study was to improve clinicians' understanding of rheumatoid lung nodules by analyzing the clinical features, diagnosis, and treatment of this case, and reviewing the relevant medical literature.

XTX301, a Tumor-Activated Interleukin-12 Has the Potential to Widen the Therapeutic Index of IL12 Treatment for Solid Tumors as Evidenced by Preclinical Studies.

IL12 is a proinflammatory cytokine, that has shown promising antitumor activity in humans by promoting the recruitment and activation of immune cells in tumors. However, the systemic administration of IL12 has been accompanied by considerable toxicity, prompting interest in researching alternatives to drive preferential IL12 bioactivity in the tumor. Here, we have generated XTX301, a tumor-activated IL12 linked to the human Fc protein via a protease cleavable linker that is pharmacologically inactivated by an IL12 receptor subunit beta 2 masking domain. In vitro characterization demonstrates multiple matrix metalloproteases, as well as human primary tumors cultured as cell suspensions, can effectively activate XTX301. Intravenous administration of a mouse surrogate mXTX301 demonstrated significant tumor growth inhibition (TGI) in inflamed and non-inflamed mouse models without causing systemic toxicities. The superiority of mXTX301 in mediating TGI compared with non-activatable control molecules and the greater percentage of active mXTX301 in tumors versus other organs further confirms activation by the tumor microenvironment-associated proteases in vivo. Pharmacodynamic characterization shows tumor selective increases in inflammation and upregulation of immune-related genes involved in IFNγ cell signaling, antigen processing, presentation, and adaptive immune response. XTX301 was tolerated following four repeat doses up to 2.0 mg/kg in a nonhuman primate study; XTX301 exposures were substantially higher than those at the minimally efficacious dose in mice. Thus, XTX301 has the potential to achieve potent antitumor activity while widening the therapeutic index of IL12 treatment and is currently being evaluated in a phase I clinical trial.

Gender bias in colorectal surgery fellowship letters of recommendation.

BACKGROUND: As leaders strive to create equitable surgical pipelines, one process under scrutiny is letters of recommendation (LORs). We sought to review the Colon and Rectal Surgery (CRS) Resident Candidate Assessment questionnaire and LORs for gendered differences. METHODS: This retrospective observational study of letters of recommendation to CRS fellowship during the 2018-2019 application cycle utilized linguistic Inquiry and Word Count (LIWC2015) software to assess letter length and themes comparing differences by applicant and referee gender. RESULTS: 103 applicants (35 â€‹% women) with 363 LORs (16 â€‹% written by women) were included. Short answer responses were longer for women applicants, while LORs were longer for men applicants (368 vs 325 words p â€‹= â€‹0.03). Men applicants' strengths had more technical skill descriptors, while women applicants' strengths had more emotional language and cognitive and perceptual words. CONCLUSIONS: This study found significant differences between LORs written for CRS fellowship applicants based on gender.

[Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study].

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

Advancing full-field metrology: rapid 3D imaging with geometric phase ferroelectric liquid crystal technology in full-field optical coherence microscopy.

Optical coherence microscopy (OCM) is a variant of OCT in which a high-numerical aperture lens is used. Full-field OCM (FF-OCM) is an emerging non-invasive, label-free, interferometric technique for imaging of surface structures or semi-transparent biomedical subjects with micron-scale resolutions. Different approaches to three dimensional full-field optical metrology are reviewed. The usual method for the phase-shifting technique in FF-OCM involves mechanically moving a mirror to change the optical path difference for obtaining en-face OCM images. However, with the use of a broadband source in FF-OCM, the phase shifts of different spectral components are not the same, resulting in the ambiguities in 3D image reconstruction. In this study, we demonstrate, by imaging tissues and cells, a unique geometric phase-shifter based on ferroelectric liquid crystal technology, to realize achromatic phase-shifting for rapid three-dimensional imaging in a FF-OCM system.

Comparison of higher-order aberrations between implantable collamer lens V4c implantation and simulated spectacle correction in patients with high myopia.

PURPOSE: To investigate the differences in higher-order aberrations between non-toric or toric implantable collamer lens (ICL or TICL) V4c implantation and simulated spectacle correction. METHODS: Patients with high myopia who underwent ICL/TICL V4c implantation were enrolled. The "total no defocus" pattern of iTrace aberrometry to simulate the condition of spectacle correction was measured before ICL/TICL implantation, and higher-order aberrations in this condition were compared to those 3 months after surgery. Related factors with changes in coma were comprehensively analyzed. RESULTS: A total of 89 right eyes of 89 patients were included. Compared to simulated spectacle correction, total-eye coma (P<0.0001 ICL, P<0.0001 TICL) and internal coma (P<0.0001 ICL, P<0.001 TICL) decreased in the ICL- and TICL-treated groups after surgery. Total-eye secondary astigmatism (P<0.0001 ICL, P=0.007 TICL) and internal secondary astigmatism (P<0.0001 ICL, P=0.009 TICL) were also decreased in both groups postoperatively. Spherical error showed positive correlations with variation in total-eye coma (r=0.37, P=0.004 ICL; r=0.56, P=0.001 TICL) and internal coma (r=0.30, P=0.02 ICL and r=0.45, P=0.01 TICL). Axial length revealed negative correlations with changes in total-eye coma (r=-0.45, P<0.001 ICL; r=-0.39, P=0.03 TICL) and internal coma (r=-0.28, P=0.03 ICL and r=-0.42, P=0.02 TICL). CONCLUSIONS: Both ICL- and TICL-treated groups demonstrated a decrease in coma and secondary astigmatism after 3 months, postoperatively. ICL/TICL may confer a compensatory effect on coma aberration and secondary astigmatism. Patients with a higher myopia achieved a greater improvement in coma and may benefit more from ICL/TICL implantation than from spectacle correction implantation than from spectacle correction.

Research highlight: surgical outcomes of gluteal VY plasty after extensive abdominoperineal resection or total pelvic exenteration.

OBJECTIVE: To describe a suitable alternative technique for reconstruction of the pelvic floor after extensive resection. To review our outcomes of gluteal VY plasty in the reconstruction of the pelvic floor after extensive abdominoperineal resection (conventional or extralevator abdominoperineal resection, total pelvic exenteration, or salvage surgery). DESIGN: Retrospective cohort study. SETTING: An academic hospital and tertiary referral centre for the treatment of locally advanced or locally recurrent rectal cancer, and salvage surgery in The Netherlands. PATIENTS: Forty-one consecutive patients who underwent a pelvic floor reconstruction with gluteal VY plasty at Maastricht University Medical Centre between January 2017 and February 2021 were included. The minimum duration of follow-up was 2 years. MAIN OUTCOME MEASURES: Perineal herniation is the primary outcome measure. Furthermore, the occurrence of minor and major postoperative complications and long-term outcomes were retrospectively assessed. RESULTS: Thirty-five patients (85.4%) developed one or more complications of whom twenty-one patients experienced minor complications and fourteen patients developed major complications. Fifty-seven percent of complications was not related to the VY reconstruction. Six patients (14.6%) recovered without any postoperative complications during follow-up. Three patients developed a perineal hernia. CONCLUSIONS: A gluteal VY plasty is a suitable technique for reconstruction of the pelvic floor after extensive perineal resections resulting in a low perineal hernia rate, albeit the complication rate remains high in this challenging group of patients.

First-in-Human Integrated Use of a Dedicated Microsurgical Robot with a 4K 3D Exoscope: The Future of Microsurgery.

Innovative techniques can help overcome the limitations of the human body. Operating on very small structures requires adequate vision of the surgical field and precise movements of sophisticated instruments. Both the human eye and hand are limited when performing microsurgery. Conventional microsurgery uses operation microscopes to enhance the visualization of very small structures. Evolving technology of high-definition 3D cameras provides the opportunity to replace conventional operation microscopes, thereby improving ergonomics for surgeons. This leaves the human hand as a limiting factor in microsurgery. A dedicated robot for microsurgery has been developed to overcome this limitation and enhance the precision and stability of the surgeons' hands. We present the first-in-human case in reconstructive microsurgery where both technologies are integrated using a dedicated microsurgical robot in combination with a 4K 3D exoscope.

Impaired Dynamic Sarcoplasmic Reticulum Ca Buffering in Autosomal Dominant CPVT2.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal cardiac arrhythmia syndrome triggered by catecholamines released during exercise, stress, or sudden emotion. Variants in the calsequestrin-2 gene (CASQ2), encoding the major calcium (Ca) binding protein in the sarcoplasmic reticulum (SR), are the second most common cause of CPVT. Recently, several CASQ2 gene variants, such as CASQ2-K180R, have been linked to an autosomal dominant form of Casq2-linked CPVT (CPVT2), but the underlying mechanism is not known. METHODS: A K180R mouse model was generated using CRIPSR/Cas9. Heterozygous and homozygous K180R mice were studied using telemetry ECG recordings in vivo. Ventricular cardiomyocytes were isolated and studied using fluorescent Ca indicators and patch clamp. Expression levels and localization of SR Ca-handling proteins were evaluated using Western blotting and immunostaining. Intra-SR Ca kinetics were quantified using low-affinity Ca indicators. RESULTS: K180R mice exhibit an autosomal dominant CPVT phenotype following exercise or catecholamine stress. Upon catecholamine stress, K180R ventricular cardiomyocytes exhibit increased spontaneous SR Ca release events, triggering delayed afterdepolarizations and spontaneous beats. K180R had no effect on levels of Casq2, Casq2 polymers, or other SR Ca-handling proteins. Intra-SR Ca measurements revealed that K180R impaired dynamic intra-SR Ca buffering, resulting in a more rapid rise of free Ca in the SR during diastole. Steady-state SR Ca buffering and total SR Ca content were not changed. Consistent with the reduced dynamic intra-SR buffering, K180R causes reduced SR Ca release refractoriness. CONCLUSIONS: CASQ2-K180R causes CPVT2 via a heretofore unknown mechanism that differs from CASQ2 variants associated with autosomal recessive CPVT2. Unlike autosomal recessive CASQ2 variants, K180R impairs the dynamic buffering of Ca within the SR without affecting total SR Ca content or Casq2 protein levels. Our data provide insight into the molecular mechanism underlying autosomal dominant CPVT2.

[The relationship between adenovirus infection and severe acute hepatitis of unknown etiology].

Adenovirus infection can occur in all regions or countries of the world, with no obvious seasonality, but pandemics mostly occur in winter or early spring. Adenovirus infection is self-limited among immunocompetent host with supportive care, however fatal infection can occur among immunocompromised patients, mainly affecting respiratory, gastrointestinal tract and adjunctiva and very rarely causing hepatitis, cholecystitis, pancreatitis, hemorrhagic cystitis, myocarditis, meningitis or encephalitis. Adenovirus hepatitis mainly occur in malignant tumors or organ transplantation patients, but acute severe hepatitis can occur even in immunocompetent children or adults. On 5 April 2022, WHO was notified of 10 cases of severe acute hepatitis of unknown etiology in children. As of 21 April 2022, at least 169 cases of acute hepatitis of unknown origin have been reported from 12 countries (including 11 WHO European Region countries and the United States). Adenovirus has been detected in at least 74 cases; SARS-CoV-2 was identified in 20 cases of those that were tested. Furthermore, 19 were detected with a SARS-CoV-2 and adenovirus co-infection. At present, the etiology has not been fully elucidated. The leading hypotheses center around adenovirus, and the relationship with SARS-CoV-2 needs to be further ruled out.

Spotlighting Research During COVID-19: Introduction of an International Online Multi-Round Research Competition for Trainees.

PROBLEM: The coronavirus pandemic led to the cancellation of many academic events. While some transitioned to virtual formats, others disappeared, offering fewer opportunities for trainees to share research. Facing this challenge, the Association of Women Surgeons developed a novel approach. Designed to promote greater global inclusion, increase audience engagement and opportunities for networking and feedback from practicing surgeons, they restructured their annual trainee research symposium as a virtual, multi-round competition. APPROACH: Submission to the research competition was open to trainees at any level. The competition comprised four rounds: (1) visual abstracts (all welcomed), (2) three-minute "Quickshot" presentation (32 advance), (3) eight-minute oral presentations (16 advance), and (4) final question-and-answer style defense (final 4 compete). Progression through the first three rounds was determined by public voting. Winners were determined by live voting during the final session. OUTCOMES: A total of 73 visual abstracts were accepted for presentation. Fifty-six percent (n = 41) of first authors were medical students, 36% residents (n = 26), and 7% fellows (n = 6). Five were from international first authors (7%). Abstracts represented research topics including basic science (n = 6, 8%)), clinical outcomes (n = 38, 52%), and education (n = 29, 40%). Social media impressions exceeded a total of 30,000 views. NEXT STEPS: This virtual, multi-round research competition served as a blueprint for a novel approach to research dissemination. The format enabled expanded US national and international engagement with trainees in all stages of their career. Future research symposia should consider the impact of popularity bias, timing, and voting strategies during the event planning period to optimize success.

[Hepatic manifestations of hematological diseases].

Liver involvement is often observed in hematological disorders, resulting in liver abnormality, including unconjugated hyperbilirubinemia, monoclonal hyperglobulinemia, portal vein, or hepatic vein thrombosis or portal hypertension, hepatosplenomegaly, or iron accumulation in the liver. Here we summarize the major hematological diseases that often affect the liver: hemolytic anemia, defect in coagulation or anti-coagulation factors, myeloproliferative neoplasm, hemophagocytic lymphohistiocytosis, multiple myeloma, leukemia, and lymphoma. We hope this review will help clinicians diagnose and manage the patients with liver involvement by hematological disorders.

Partially intraosseous schwannoma of the distal humerus with increased enhancement after biopsy: Radiologic-pathologic correlation.

Intraosseous schwannomas are rare benign tumors that most often occur at the mandible or sacrum. We present an unusual case of a bilobed schwannoma of the distal humerus with both intraosseous and extraosseous components. The extraosseous component was non-enhancing on initial MRI and enhanced on a subsequent MRI obtained after biopsy. We hypothesize that this change was attributable to decreased intra-tumoral pressure secondary to biopsy-related disruption of the tumor capsule.

[Evaluation of the efficacy of a new variable frequency stimulation sacral neuromodulation in the treatment of detrusor hyperactivity with impaired contractility].

A total of 16 detrusor hyperactivity with impaired contractility (DHIC) patients who received 12 weeks remote variable frequency stimulation (VFS) were enrolled at the First Affiliated Hospital of Zhengzhou University from September 2020 to February 2021. The voiding diary, symptom score scales and incidence of complications were completed and recorded at baseline, constant frequency stimulation (CFS) and VFS phases. Compared with the CFS phase, voiding times, urge incontinence times and daily catheterization volume were reduced; average voiding amount and functional bladder capacity increased; and the quality of life score and mental health questionnaire assessment were improved in the VFS phase(all P<0.05). In the end, among all 16 patients, there were 14 whose symptoms had improved, and there were no new complications such as pain or infection at the implantation site, electrode displacement, and electric shock sensation in the stimulation area. VFS-SNM can not only improve the DHIC patients' lower urinary tract symptoms during storage and urination period, but also improve the patients' quality of life and satisfaction of the therapy.

Rural hospitals are not associated with worse postoperative outcomes for colon cancer surgery.

PURPOSE: We sought to determine whether colorectal cancer surgery can be done safely at rural hospitals. The current study compared outcomes among rural patients who underwent colon resection at rural and nonrural hospitals. METHODS: Medicare beneficiaries who underwent colon resection for cancer between 2013 and 2017 were identified using the Medicare Inpatient Standard Analytic Files. Patients and hospitals were designated as rural based on rural-urban continuum codes. Risk-adjusted postoperative outcomes and hospitalization spending were compared among patients undergoing resection at rural versus nonrural hospitals. RESULTS: Among 3,937 patients who resided in a rural county and underwent colon resection for cancer, mean age was 76.3 (SD: 7.1) years and 1,432 (36.4%) patients underwent operative procedure at a rural hospital. On multivariable analyses, no differences in postoperative outcomes were noted among Medicare beneficiaries undergoing colon resection for cancer at nonrural versus rural hospitals. Specifically, the risk-adjusted probability of experiencing a postoperative complication at a nonrural hospital was 15.4% (95% CI: 14.1%-16.8%) versus 16.3% (95% CI: 14.2%-18.3%) at a rural hospital (OR 1.08, 95% CI: 0.85-1.38); 30-day mortality (nonrural: 2.9%, 95% CI: 2.2-3.6 vs rural: 3.5%, 95% CI: 2.4-4.5) was also comparable. In addition, price standardized, risk-adjusted expenditures were similar at nonrural ($18,610, 95% CI: $18,037-$19,183) and rural ($19,010, 95% CI: $18,630-$19,390) hospitals. CONCLUSION: Among rural Medicare beneficiaries who underwent a colon resection for cancer, there were no differences in postoperative outcomes among nonrural versus rural hospitals. These findings serve to highlight the importance of policies and practice guidelines that secure safe, local surgical care, allowing rural clinicians to accommodate strong patient preferences while delivering high-quality surgical care.