Radiotherapy with targeted and immunotherapy improved overall survival and progression-free survival for hepatocellular carcinoma with portal vein tumor thrombosis.

BACKGROUND: The efficacy of radiotherapy (RT) combined with targeted therapy and immunotherapy in treating hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) is still unclear. This study investigated the efficacy and safety of RT combined with targeted therapy and immunotherapy in HCC with PVTT. MATERIALS AND METHODS: Seventy-two patients with HCC with PVTT treated with tyrosine kinase inhibitor (TKI) plus programmed cell death protein-1 (PD-1) inhibitor with or without RT from December 2019 to December 2023 were included. After propensity score matching (PSM) for adjusting baseline differences, 32 pairs were identified in RT + TKI + PD-1 group (n = 32) and TKI + PD-1 group (n = 32). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: Median OS (mOS) in RT + TKI + PD-1 group was significantly longer than TKI + PD-1 group (15.6 vs. 8.2 months, P = .008). Median PFS (mPFS) in RT + TKI + PD-1 group was dramatically longer than TKI + PD-1 group (8.1 vs. 5.2 months, P = .011). Patients in TKI + PD-1 + RT group showed favorable ORR and DCR compared with TKI + PD-1 group (78.1% vs. 56.3%, P = .055; 93.8% vs. 81.3%, P = .128). Subgroup analysis demonstrated a remarkable OS and PFS benefit with TKI + PD-1 + RT for patients with main PVTT (type III/IV) and those of Child-Pugh class A. Multivariate analysis confirmed RT + TKI + PD-1 as an independent prognostic factor for longer OS (HR 0.391, P = .024) and longer PFS (HR 0.487, P = .013), with no mortality or severe TRAEs. CONCLUSION: RT combined with TKI and PD-1 inhibitor could significantly improve mOS and mPFS without inducing severe TRAEs or mortality.

A comparison between robotic-assisted and open approaches for large ventral hernia repair-a multicenter analysis of 30 days outcomes using the ACHQC database.

INTRODUCTION: Over the last few decades, there has been an increase in the use of a minimally invasive (MIS) approach for complex hernias involving component separation. A robotic platform provides better visualization and mobilization of tissues for component separation. We aim to assess the outcomes of open and robotic-assisted approaches for large VHR utilizing the ACHQC national database. METHODS: A retrospective review of prospectively collected data from the Abdominal Core Health Quality Collaborative (ACHQC) was performed to include all adult patients who had primary and incisional midline ventral hernias larger than 10 cm and underwent elective open and robotic hernia repairs with mesh from January 2013 to March 2023. Univariate and multivariate analyses were performed comparing Open and Robotic approaches. RESULTS: The ACHQC database identified 5,516 patients with midline hernias larger than 10 cm who underwent VHR. The open group (OG) had 4,978 patients, and the robotic group (RG) had 538. The RG had a higher median BMI (33.3 kg/m2 (IQR 29.8-38.1) vs 32.7 (IQR 28.7-36.6) (p < 0.001). Median hernia width was 15 cm (IQR 12-18) in the OG and 12 cm in the RG (10-14) (p < 0.001). Sublay positioning of the mesh was the most common. The fascial closure was higher in the RG (524; 97% versus 4,708; 95%-p = 0.005). Median Length of Stay (LOS) was 5 days (IQR 4-7) in the OG and 2 days (IQR 1-3) in the RG (p < 0.001). The readmission rate was higher in the OG (n = 374; 7.5% vs n = 16; 3%; p < 0.001). 30-day SSI were higher in the OG (343; 6.9%% vs 14; 2.6%; p < 0.001). Logistic regression analysis identified diabetes (OR 1.6; CI 1.1-2.1; p = 0.006) and BMI (OR 1.04, CI 1.02-1.06; p < 0.001) as predictors of SSIs, while the robotic approach was protective (OR 0.35, CI 0.17-0.64; p = 0.002). For SSO, logistic regression showed BMI (OR 1.04, CI 1.03-1.06; p < 0.001) and smoking (OR 1.8, CI 1.3-2.4; p < 0.001) as predictors Robotic approach was associated with lower readmission rates (OR .04, CI 0.2-0.6; p < 0.001). CONCLUSION: A robotic approach improves early 30-day outcomes compared to an open technique for large VHR. There was no difference in SSO at 30 days.

Impact of social vulnerability index on patients with alcohol-related liver disease.

INTRODUCTION: Alcohol related liver disease (ALD) affects diverse communities with individual and social characteristics that can impact outcomes. The social vulnerability index (SVI) assigns a score between 0 and 1, where higher scores represent an increased risk of social vulnerability. We sought to assess the impact of SVI on outcomes of patients hospitalized with ALD with access to social support services. METHODS AND MATERIALS: Hospitalizations for ALD at our institution between March and August 2019 were reviewed. All patients were assigned an SVI score based on their residential census tract. Per our standard practice, patients were screened by care coordinators to identify needs for rehabilitation counseling, and care coordination after discharge. Demographics, hepatic decompensation, critical care needs, readmission, and mortality were compared. RESULTS: Among 73 patients admitted for alcoholic hepatitis, 32 had a low SVI and 42 had a high SVI. African American patients were more likely to have a higher SVI (35% vs 0%, p=<0.001). No significant difference in outcomes based on SVI was noted. There were 393 patients admitted for alcoholic cirrhosis including 166 with a low SVI and 227 with a high SVI. Patients that were African American (23.6% vs 5.5%, p=<0.001) or disabled (41.4% vs 29.5%, p = 0.008) had a higher SVI. No significant difference in outcomes based on SVI was noted. CONCLUSION: Most patients admitted for ALD had a high SVI; however, SVI did not impact hospitalization outcomes.

Microbial etiology of vertebral osteomyelitis/discitis amid the opioid epidemic.

OBJECTIVE: The primary goal of this study was to establish the current microbial trends in vertebral osteomyelitis/discitis (VOD) amid the opioid epidemic and to determine if intravenous drug use (IVDU) predisposes one to a unique microbial profile of infection. METHODS: The authors performed a retrospective cohort study consisting of 1175 adult patients diagnosed with VOD between 2011 and 2022 at a single quaternary center. Data were acquired through retrospective chart review, with pertinent demographic and clinical information collected. RESULTS: Staphylococcus aureus was the most cultured organism in both the IVDU and non-IVDU groups at 56.1% and 40.7%, respectively. In the IVDU cohort, Serratia marcescens was the next most prevalently cultured organism at 13.9%. CONCLUSIONS: The present study demonstrates that in the IVDU population S. marcescens is an organism of high concern. The potential for Serratia spp. infection should be accounted for when selecting empirical antimicrobial therapy in VOD patients.

Control of Fusarium Head Blight of Wheat with Bacillus velezensis E2 and Potential Mechanisms of Action.

Wheat plants are impacted by Fusarium head blight (FHB) infection, which poses a huge threat to wheat growth, development, storage and food safety. In this study, a fungal strain was isolated from diseased wheat plants and identified as Fusarium asiaticum F1, known to be a member of the Fusarium graminearum species complex, agents causally responsible for FHB. In order to control this disease, new alternatives need to be developed for the use of antagonistic bacteria. Bacillus velezensis E2 (B. velezensis E2), isolated from a previous investigation in our laboratory, showed a notable inhibitory effect on F. asiaticum F1 growth and deoxynivalenol (DON) synthesis in grains. The spore germination of F. asiaticum F1 was significantly reduced and the spores showed vesicular structures when treated with B. velezensis E2. Observations using scanning electron microscopy (SEM) showed that the hyphae of F. asiaticum F1 were shrunken and broken when treated with B. velezensis E2. The RNA-seq results of F1 hyphae treated with B. velezensis E2 showed that differentially expressed genes (DEGs), which were involved in multiple metabolic pathways such as toxin synthesis, autophagy process and glycan synthesis, especially the genes associated with DON synthesis, were significantly downregulated. In summary, those results showed that B. velezensis E2 could inhibit F. asiaticum F1 growth and reduce the gene expression of DON synthesis caused by F1. This study provides new insights and antagonistic mechanisms for the biological control of FHB during wheat growth, development and storage.

The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity.

The Orthopoxvirus (OPXV) genus of the Poxviridae includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the P2L gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.

Sarcoid-like reactions to immune checkpoint inhibitors: Incidence, treatment course, and impact on cancer progression and survival.

INTRODUCTION: Sarcoid-like reactions (SLRs) to immune checkpoint inhibitors (ICIs) are a rare but increasingly recognized immune-related adverse event of which the clinical significance is unclear. METHODS: We conducted a retrospective cohort study at a tertiary academic center of consecutive patients who received at least one dose of ICI from 2013 to 2020. Patient characteristics, risk factors, and outcomes were compared between patients with and without SLR following ICI treatment. RESULTS: A total of 2963 cancer patients received at least 1 dose of ICI between 2013 and 2020, and 7 patients (0.24 %) developed SLR. There were no significant demographic differences between patients with and without SLR following ICI. SLRs occurred in 5 of 451 (1.07 %) melanoma patients and 2 of 840 (0.24 %) non-small cell lung cancer patients. Two of the 7 patients had multi-organ SLR, and both were symptomatic requiring systemic corticosteroids and permanent ICI discontinuation, while single organ SLR patients did not require immune suppression. Development of SLR did not appear to have negative impact on cancer progression or overall survival; in fact, a trend towards improved progression-free and overall survival was observed (median time: 1363 days vs 127 days, p = 0.091; 1387 days vs 428.5 days, p = 0.19, respectively). CONCLUSIONS: SLRs are a known but understudied complication associated with ICI therapy. Multisystem SLR patients were more symptomatic and required ICI discontinuation and immune suppression. Larger studies are needed to fully evaluate the impact of SLR on cancer outcomes.

Isolation and Characterization of Paenibacillus polymyxa B7 and Inhibition of Aspergillus tubingensis A1 by Its Antifungal Substances.

Screening of Bacillus with antagonistic effects on paddy mold pathogens to provide strain resources for biological control of mold in Oryza sativa L. screening of Bacillus isolates antagonistic towards Aspergillus tubingensis from rhizosphere soil of healthy paddy; classification and identification of antagonistic strains by biological characteristics and 16S rDNA sequence analysis; transcriptome sequencing after RNA extraction from Bacillus-treated Aspergillus tubingensis; and extraction of inhibitory crude proteins of Bacillus by ammonium sulfate precipitation; inhibitory crude protein and Bacillus spp. were treated separately for A. tubingensis and observed by scanning electron microscopy (SEM). An antagonistic strain of Bacillus, named B7, was identified as Paenibacillus polymyxa by 16S rDNA identification and phylogenetic evolutionary tree comparison analysis. Analysis of the transcriptome results showed that genes related to secondary metabolite biosynthesis such as antifungal protein were significantly downregulated. SEM results showed that the mycelium of A. tubingensis underwent severe rupture after treatment with P. polymyxa and antifungal proteins, respectively. In addition, the sporocarp changed less after treatment with P. polymyxa, and the sporangium stalks had obvious folds. P. polymyxa B7 has a good antagonistic effect against A. tubingensis and has potential for biocontrol applications of paddy mold pathogens.

Reliability and validity of the cancer-related dysfunctional beliefs and attitudes about sleep scale in cancer patients.

BACKGROUND: Insomnia is a common health problem among cancer patients, which is not only a physical problem but also a psychological problem. Sleep plays an important role in the mental and somatic rehabilitation of cancer patients, and the sleep beliefs and attitudes of cancer patients are key factors in improving their sleep situation and quality of life. The aim of this study was to translate the Cancer-Related Dysfunctional Beliefs and Attitudes about Sleep (C-DBAS-14) scale into Chinese and to validate its reliability and validity in cancer patients. METHOD: The C-DBAS-14 scale was translated into Chinese using the backward and forward translation procedure. The reliability of the scale was measured by internal consistency, split-half reliability and retest reliability. The validity of the scale was assessed through the content validity indicators, exploratory factor analysis and validation factor analysis. RESULT: The Cronbach's ɑ coefficient of the Chinese version of the C-DBAS-14 was 0.932 while the McDonald's omega coefficient (ω t) was 0.934. The split-half reliability coefficient was 0.908, and the test-retest reliability was 0.857. The four-factor model was obtained using exploratory factor analysis, explaining 72.7% of the variance, with each item loading greater than 0.4 on the common factor. The results of the confirmatory factor analysis revealed that all indicators of model fit were within an acceptable range, indicating a well-fitting model. CONCLUSION: The Chinese version of the C-DBAS-14 has good reliability and validity among cancer patients. It can be used to measure the sleep beliefs and attitudes of Chinese cancer patients.

A CRISPR/Cas9-based visual toolkit enabling multiplex integration at specific genomic loci in Aspergillus niger.

Aspergillus niger is a highly versatile fungal strain utilized in industrial production. The expression levels of recombinant genes in A. niger can be enhanced by increasing the copy number. Nevertheless, given the prolonged gene editing cycle of A. niger, a "one-step" strategy facilitating the simultaneous integration of recombinant genes into multiple genomic loci would provide a definitive advantage. In our previous study, a visual multigene editing system (VMS) was designed to knock out five genes, employing a tRNA-sgRNA array that includes the pigment gene albA and the target genes. Building upon this system, hybrid donor DNAs (dDNAs) were introduced to establish a clustered regularly interspaced short palindromic repeats (CRISPR)-based multiplex integration toolkit. Firstly, a CRISPR-Cas9 homology-directed repair (CRISPR-HDR) system was constructed in A. niger by co-transforming the CRISPR-Cas9 plasmid (with a highly efficient sgRNA) and the dDNA, resulting in precise integration of recombinant xylanase gene xynA into the target loci (the ß-glucosidase gene bgl, the amylase gene amyA, and the acid amylase gene ammA). Subsequently, the length of homology arms in the dDNA was optimized to achieve 100% editing efficiency at each of the three gene loci. To achieve efficient multiplex integration in A. niger, the CRISPR plasmid pLM2 carrying a sgRNA-tRNA array was employed for concurrent double-strand breaks at multiple loci (bgl, amyA, ammA, and albA). Hybrid dDNAs were then employed for repair, including dDNA1-3 (containing xynA expression cassettes without selection markers) and dDNAalbA (for albA knockout). Among the obtained white colonies (RLM2'), 23.5% exhibited concurrent replacement of the bgl, amyA, and ammA genes with xynA (three copies). Notably, the xynA activity obtained by simultaneous insertion into three loci was 48.6% higher compared to that obtained by insertion into only the bgl locus. Furthermore, this multiple integration toolkit successfully enhanced the expression of endogenous pectinase pelA and Candida antarctica lipase CALB. Hence, the combined application of VMS and the CRISPR-HDR system enabled the simultaneous application of multiple selection markers, facilitating the rapid generation in the A. niger cell factories.

Tandem T:Slim X2 Insulin Pump Use in Clinical Practice Among Pregnant Individuals With Type 1 Diabetes: A Retrospective Observational Cohort Study.

BACKGROUND: Insulin pump use is increasing in frequency among pregnant individuals with type 1 diabetes (T1D). Automated insulin delivery (AID) technologies have not been studied extensively in pregnancy. METHOD: We present a retrospective case series of eight individuals with T1D who used the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, Inc., CA, USA) during pregnancy. Weekly continuous glucose monitor and insulin pump data were analyzed from electronic medical records and data-sharing portals. Safety, glycemic control, and pregnancy outcomes were examined with both the control IQ (CIQ) and basal IQ (BIQ) algorithms. RESULTS: Six CIQ and two BIQ users were studied. The mean glycated hemoglobin (A1C) during pregnancy was 6.1%, and the average time in pregnancy-recommended glycemic range (TIR; 63-140mg/dL) was 67.9%. There were no instances of diabetic ketoacidosis or severe hypoglycemia. CIQ users had a higher mean sensor glucose (127.6 mg/dL) compared to BIQ participants (118.4 mg/dL). However, the average time below range (<63 mg/dL) was 6.1% in BIQ participants compared to 1.5% in CIQ participants. CIQ participants used several strategies to achieve glycemic targets, including daytime use of sleep activity. An increased basal-to-bolus insulin ratio was negatively correlated with TIR (r=-0.415). CONCLUSIONS: Tandem t:slim X2 insulin pumps were safely used during pregnancy in eight individuals with T1D, with variable success in achieving recommended glycemic targets. Further research is needed to understand differences in CIQ and BIQ use in pregnancy. AID device manufacturers must additionally develop further methods to target lower glucose for pregnant users.

Ultrasound Features and Performance of Afirma Gene Sequencing Classifier in Cytologically Indeterminate Thyroid Nodules.

Background: Cytologically indeterminate thyroid nodules (ITN) pose a management challenge. Here we analyze if adding ultrasound characteristics to Afirma Genome Sequence Classifier (GSC) results increases GSC diagnostic performance. Methods: We retrospectively analyzed 237 GSC-tested Bethesda III/IV ITNs between July 2017 and December 2019 and classified them by American Thyroid Association (ATA) and the Thyroid Imaging Reporting and Data System (TIRADS) of the American College of Radiology. Results: The benign call rate was higher in Bethesda III ITNs with TIRADS <5 vs TIRADS 5 (89% vs 68%. P = .015). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of GSC in ATA high-risk Bethesda III ITNs vs lower were 100% vs 80% (P = 1), 89.5% vs 91.5% (P = .67), 66.7% vs 25% (P = .13), and 100% vs 99.2% (P = 1), respectively, and for TIRADS 5 vs <5 were 100% vs 80% (P = 1), 88.2% vs 91.4% (P = .65), 71.4% vs 23.5% (P = .06), and 100% vs 99.3% (P = 1). The sensitivity, specificity, PPV, and NPV of GSC in high-risk ATA Bethesda IV ITNs vs lower were 66.7% vs 100% (P = .42), 83.3% vs 85.7% (P = 1), 66.7% vs 64.3% (P = 1), and 83.3% vs 100% (P = .3), respectively, and for TIRADS 5 vs <5 were 66.7% vs 90% (P = .42), 88.9% vs 83.8% (P = 1), 66.7% vs 60% (P = 1), and 88.9% vs 96.9% (P = .39). Conclusion: Sensitivity, specificity, NPV, and PPV of GSC were not significantly different in ATA high-risk and TIRADS 5 ITNs compared to ATA < high-risk and TIRADS 1-4 ITNs.

A retrospective analysis of anticoagulant safety among heart transplant recipients undergoing endomyocardial biopsy.

BACKGROUND: Transvenous endomyocardial biopsy is an invasive procedure which is used to diagnose rejection following an orthotopic heart transplant. Endomyocardial biopsy is widely regarded as low risk with all-cause complication rates below 5% in most safety studies. Following transplant, some patients require therapeutic anticoagulation. It is unknown whether anticoagulation increases endomyocardial biopsy bleeding risk. METHODS: Records from 2061 endomyocardial biopsies performed for post-transplant rejection surveillance at our institution between November 2016 and August 2022 were reviewed. Bleeding complications were defined as vascular access-related hematoma or bleeding, procedure-related red blood cell transfusion, and new pericardial effusion. Relative risk and small sample-adjusted 95% confidence interval was calculated to investigate the association between bleeding complications and anticoagulation. RESULTS AND CONCLUSIONS: The overall risk of bleeding was 1.2% (25/2061 cases). There was a statistically significant increase in bleeding among patients on intravenous (RR 4.46, CI 1.09-18.32) but not oral anticoagulants (RR .62, CI .15-2.63) compared to patients without anticoagulant exposure. There was a trend toward increased bleeding among patients taking warfarin with INR ≥ 1.8 (RR 3.74, CI .90-15.43). Importantly, no bleeding events occurred in patients taking direct oral anticoagulants such as apixaban. Based on these results, intravenous rather than oral anticoagulation was associated with a significantly higher risk of bleeding complications following endomyocardial biopsy.

Tipping the scale in abdominal wall reconstruction: An analysis of short- and long-term outcomes by body mass index.

BACKGROUND: Morbid obesity, with a body mass index 35 kg/m2, is a commonly used cutoff for denying elective transversus abdominis release. Although obesity is linked to short-term wound morbidity, its effect on long-term outcomes remains unknown, calling into question if a cutoff is justified. We sought to compare 1-year recurrence rates after transversus abdominis release based on body mass index and to evaluate short- and long-term outcomes. METHODS: Patients undergoing open, clean transversus abdominis release from August 2014 to January 2022 at our institution with 1-year follow-up completed were identified. Univariate and multivariable analyses were performed to determine the association of body mass index with 90-day wound events, 1-year hernia recurrence, and hernia-specific quality of life. Covariates included body mass index, diabetes, recurrent hernia, hernia width, fascial closure, surgical site occurrence requiring procedural intervention, previous abdominal wall surgical site infection, inflammatory bowel disease, mesh weight, and mesh-to-hernia size ratio. RESULTS: A total of 1,089 patients were included. Increasing body mass index was associated with surgical site infection (adjusted odds ratio = 1.59; 95% confidence interval, 1.14-1.77; P < .01) and surgical site occurrence (adjusted odds ratio = 1.42; 95% confidence interval, 1.13-1.74; P < .01) but was not associated with surgical site occurrence requiring procedural intervention. Hernia width was associated with surgical site occurrence (adjusted odds ratio = 1.4; 95% confidence interval, 1.08-1.82; P < .01) and surgical site occurrence requiring procedural intervention (adjusted odds ratio = 1.4; 95% confidence interval, 1.08-1.82; P = .01). Hernia recurrence rate at 1 year was lower for the body mass index ≥35 kg/m2 group (7% vs 12%; P = .02). Hernia width (odds ratio = 1.33; 95% confidence interval, 1.02-1.74; P = .04) was associated with recurrence; body mass index was not (P = .11). Both groups experienced significant improvement in hernia-specific quality of life at 1 year. CONCLUSION: Morbid obesity is associated with 90-day wound morbidity; however, short-term complications did not translate to higher reoperation or long-term recurrence rates. The impact of body mass index on hernia recurrence is likely overstated. An arbitrary body mass index cutoff of 35 kg/m2 should not be used to deny symptomatic patients abdominal wall reconstruction.

Comparison of outcomes in vaccinated versus unvaccinated COVID-19 kidney transplant recipients, a single center retrospective study-Is the taboo justified?

INTRODUCTION: We assessed differences in the post-transplant outcomes between COVID-19 vaccinated and unvaccinated Kidney transplant (KTx) recipients. METHODS: We conducted a retrospective, single-center study of 400 KTx from 2/1/2021 to 4/30/2022 with 6-21 months follow-up. Primary outcomes included differences in the incidence of post-transplant COVID-19, ICU admission for COVID-19, death, and graft failure between the two groups. Secondary outcomes were inpatient floor admission, outpatient-management, length of hospital stay during COVID-19 admission. We also reported rejection, DGF, CMV needing treatment, and BK PCR >10 000 in baseline characteristics. RESULT: 70.5% (282/400) were fully vaccinated, and 29.5% (118/400) were unvaccinated. 33% (92/282) of vaccinated and 39% (46/118) of unvaccinated patients developed COVID-19 (p-value .03). In both groups, 16% received outpatient treatments for COVID-19. 3% (12/282) of the vaccinated and 8% (11/118) unvaccinated were admitted to the general floors (p-value .06), and 1% (3/282) of the vaccinated and 3.3% (4/118) of the unvaccinated patients needed admission to the ICU (p-value .2). The length of stay was 12 days in both groups. 13/282 (4.6%) vaccinated patients and 7/118 (5.93%) unvaccinated patients died during the follow-up period (p-value = .3). COVID-19 was deemed the etiology of death in 5/13 cases in the vaccinated and 3/7 in the unvaccinated. DGF, rejection, CMV requiring treatment, and BK PCR >10 000 were comparable between groups. CONCLUSION: The incidence of COVID-19 was higher in unvaccinated than in vaccinated KTx. The two groups were not statistically different for other primary outcomes, including the need for hospital admissions (outpatient, general floor, ICU), length of hospital stay, death, and graft failure.

Roles of cGAS-STING Pathway in Radiotherapy Combined with Immunotherapy for Hepatocellular Carcinoma.

Although great strides have been made in the management and treatment of hepatocellular carcinoma (HCC), its prognosis is still poor yielding a high mortality. Immunotherapy is recommended for treating advanced HCC, but its efficiency is hampered because of hepatic immunosuppression. Stimulator of interferon genes (STING) pathway, serving as a critical cytoplasmic DNA-sensing process, is reported to initiate the antitumor immune response, and link the innate immunity to the adaptive immune system. Radiotherapy has been well acknowledged to induce destruction and release of tumor-derived DNA into the cytoplasm, which then activates the cGAS-STING pathway. On this basis, radiotherapy can be used as a sensitizer for immunotherapy, and its combination with immunotherapy may bring in changes to the suboptimal efficacy of immune checkpoint inhibitor monotherapy. In this review, we summarized the roles of cGAS-STING pathway in regulation of radiotherapy combined with immunotherapy for treating HCC.

Historical Obesity and Early-Onset Cancers: A Propensity-Weighted Analysis of the National Health and Nutrition Examination Survey.

BACKGROUND: The incidence of early-onset obesity-related cancers (diagnosed < 50 years) is increasing in the U.S. We examined the reported historical body mass index (BMI) of adults with early and later-onset cancers to explore relation to obesity. METHODS: We queried the 1999-2018 NHANES database for adults diagnosed with obesity-related cancers (colorectal, non-colorectal gastrointestinal, uterine, breast). We classified early and late-onset cancer based on a diagnosis age of < 50 and ≥ 50 years, respectively. Propensity-weighted analysis was used to compare prior historical BMIs between the matched groups. RESULTS: After weighing, we included 2,966,528 patients with obesity-related cancers, 846,211 (28%) of which were < 50 years. In the matched analysis, 69.1% of early-onset CRC cases were diagnosed as obese (BMI ≥ 30 kg/m2) before cancer diagnosis, compared to 47.2% of late-onset cases (p < 0.03). Similarly, a higher percentage of adults with other early-onset gastrointestinal cancers had prior obesity as compared to the late-onset cohort (70.3% vs. 40.5%, p = 0.0002). BMI showed a trend toward higher values at ages 20-24 for early-onset CRC and 30-34 for other gastrointestinal cancers. In contrast, later-onset CRC and other gastrointestinal cancers exhibited higher BMI values at later ages (30-34 and 35-39, respectively). Early-onset uterine cancer was linked to a higher BMI compared to later-onset cancer (34.0 vs. 31.1 kg/m2, p < 0.0001), with a trend towards a higher BMI before 19 years old. CONCLUSIONS: Our nationally representative data reveal that higher and earlier body fatness in adulthood associates with early-onset gastrointestinal and uterine cancers. These findings underscore the importance of intensifying efforts to combat early-life obesity.

Exome sequencing in the pediatric neuromuscular clinic leads to more frequent diagnosis of both neuromuscular and neurodevelopmental conditions.

INTRODUCTION/AIMS: Exome sequencing (ES) has proven to be a valuable diagnostic tool for neuromuscular disorders, which often pose a diagnostic challenge. The aims of this study were to investigate the clinical outcomes associated with utilization of ES in the pediatric neuromuscular clinic and to determine if specific phenotypic features or abnormal neurodiagnostic tests were predictive of a diagnostic result. METHODS: This was a retrospective medical record review of 76 pediatric neuromuscular clinic patients who underwent ES. Based upon clinical assessment prior to ES, patients were divided into two groups: affected by neuromuscular (n = 53) or non-neuromuscular (n = 23) syndromes. RESULTS: A diagnosis was made in 28/76 (36.8%), with 29 unique disorders identified. In the neuromuscular group, a neuromuscular condition was confirmed in 78% of those receiving a genetic diagnosis. Early age of symptom onset was associated with a significantly higher diagnostic yield. The most common reason neuromuscular diagnoses were not detected on prior testing was due to causative genes not being present on disease-specific panels. Changes to medical care were made in 57% of individuals receiving a diagnosis on ES. DISCUSSION: These data further support ES as a powerful diagnostic tool in the pediatric neuromuscular clinic and highlight the advantages of ES over gene panels, including the ability to identify diagnoses regardless of etiology, identify genes newly associated with disease, and identify multiple confounding diagnoses. Rapid and accurate diagnosis by ES can not only end the patient's diagnostic odyssey, but often impacts patients' medical management and genetic counseling of families.

Mediating effect of successful aging on the relationship between psychological resilience and death anxiety among middle-aged and older adults with hypertension.

Objective: The aging trend of China's population is severe and successful aging (SA) is imminent. Aging can lead to various chronic diseases, with hypertension being the most common. Due to this lifelong disease, patients suffer from many anxieties, as death anxiety (DA) can be the most prevalent. Studies have exhibited that middle-aged adults approaching the transition to an older state show more pronounced DA than the more senior. It has been suggested that psychological resilience (PR) can reduce DA. Therefore, this study aimed to analyze the mediating effect of SA between PR and DA in middle-aged and older adults with hypertension. Methods: A cross-sectional survey was designed. From August to December 2021, 298 middle-aged and older adults with hypertension were selected by multistage cluster random sampling in three districts (Ling he District, Gu ta District, and Tai He District) of Jinzhou City, Liaoning Province. They were surveyed using the demographic questionnaires, the Conner-Davidson Resilience Scale, the Successful Aging Inventory, and the Chinese version of a Likert-type Templer-Death Anxiety Scale. Descriptive analyses, independent sample T-test, and one-way analysis of variance (ANOVA) were used to describe demographic characteristics among hypertensive patients with different characteristics, respectively. Statistics were considered significant when P < 0.05. Pearson correlation coefficients describe the relationship between PR, SA, and DA. The research model was shaped through Structural Equation Modeling (SEM). SPSS PROCESS macro was used to verify the mediation model. A binary logistic regression model was used with DA as the dependent variable. Results: The scores for PR, SA, and DA in hypertensive patients are (49.52 ± 14.38) points, (51.22 ± 7.63) points, and (46.67 ± 9.03) points. PR was negatively correlated with DA (r = -0.307, P < 0.01). Moreover, incorporating SA as a mediating variable in PR and DA, SA was positively correlated with PR (r = 0.335, P < 0.01) and DA (r = 0.085, P > 0.05). The direct effect is opposite to the sign of the indirect effect. There is a suppression between PR and DA with a percentage of 20.7%. Good self-assessed health status [0.057 (0.018, 0.183)] may be a protective factor for DA. Conclusion: Healthcare providers should improve the PR of middle-aged and older adults with hypertension through interventions that reduce DA and increase the likelihood of SA.

Early wound morbidity and clinical outcomes associated with P4HB mesh compared to permanent synthetic mesh in umbilical and small to medium, routine ventral hernia repairs.

Background: Permanent synthetic meshes such as polypropylene (PP) have been utilized for hernia repair for decades, but concerns remain regarding potential long-term, mesh-related complications. A resorbable polymer such as poly-4-hydroxybutyrate (P4HB) represents an alternative with high initial strength, that gradually resorbs, leaving an abdominal wall that is at least as strong as it would be in its native state. We aimed to compare early wound morbidity and clinical outcomes associated with P4HB to traditional, permanent PP in umbilical and small to medium, routine ventral hernias using data from the Abdominal Core Health Quality Collaborative (ACHQC). Methods: Inclusion criteria for the umbilical cohort included: all Centers for Disease Control and Prevention (CDC) wound classes, all Ventral Hernia Working Group (VHWG) hernia grades, and hernia defects <3 cm. The small to medium, routine ventral hernia cohort was limited to CDC class I wounds, VHWG hernia grades I and II, and hernia defects <5 cm. The study group was comprised of P4HB meshes; the comparator group was an aggregate of PP meshes. Clinical outcomes were assessed at 30 days. Results: There was no significant difference in early wound morbidity, readmission, or reoperation between the P4HB and PP cohorts. A small number of patients experienced SSO, with ≤4% requiring procedural intervention. None of the patients (0% in all cases) experienced skin/soft tissue necrosis, infected seroma, infected hematoma, exposed/contaminated/infected mesh, enterocutaneous fistula, graft failure, or pain requiring intervention at 30-days. However, P4HB was associated with significantly greater operative time, length of stay, and use of myofascial release compared to PP (p < 0.05 in all cases). Conclusions: Short-term clinical outcomes associated with resorbable P4HB mesh are comparable to permanent synthetic PP mesh in umbilical and small to medium, routine ventral hernia repairs, despite significant differences in operative time and length of stay. Longer-term follow-up is needed to expand on the clinical relevance of these short-term findings.