Omentin-1 ameliorates pulmonary arterial hypertension by inhibiting endoplasmic reticulum stress through AMPKα signaling.

BACKGROUND: Endothelial dysfunction of the pulmonary artery contributes to hypoxia-induced pulmonary arterial hypertension (PAH). Omentin-1, as a novel adipocytokine, plays an important protective role against cardiovascular diseases. However, the effect and underlying mechanisms of omentin-1 against PAH remain unclear. METHODS: PAH was induced in SD (Sprague & Dawley) rats via a low-oxygen chamber for 4 weeks. Hemodynamic evaluation was undertaken using a PowerLab data acquisition system, and histopathological analysis was stained with hematoxylin and eosin (H&E). Endothelial function of pulmonary artery was assessed using wire myography. RESULTS: We found that omentin-1 significantly improved pulmonary endothelial function in rats exposed to hypoxia and attenuated PAH. Mechanistically, we found that omentin-1 increased phosphorylated 5'­adenosine monophosphate­activated protein kinase (p­AMPK) level and reduced endoplasmic reticulum (ER) stress and increased NO production in pulmonary artery from rats exposed to hypoxia. However, the effect of omentin-1 was abolished by treatment with AMPK inhibitor (Compound C). CONCLUSIONS: Our results reveal a protective effect of omentin-1 in PAH via inhibiting ER stress through AMPKα signaling and provide an agent with translational potential for the treatment of PAH.

The occurrence of asthma in an extensive-stage small-cell lung cancer patient after combination therapy with atezolizumab and anlotinib: a case report.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, with early metastasis and high recurrence. Since therapeutic options are limited, ES-SCLC has a characteristically short survival period and extremely poor prognosis. A combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic drugs can achieve promising efficacy and safety in patients with ES-SCLC as a second-line or subsequent treatment, extending survival to some extent. However, the clinical outcomes remain mostly unsatisfactory and are sometimes affected by treatment-related adverse events. Case presentation: A 57-year-old woman with ES-SCLC was administered a combination therapy of atezolizumab (a PD-L1 inhibitor) and anlotinib [an oral multi-targeted tyrosine kinase inhibitor (TKI)]. She survived for 22 months, with no disease progression during the 28 courses of therapy. Unexpectedly, despite having no history of asthma, the patient developed asthma while receiving this regimen. This is possibly related to T-cell activation and the tumor immune microenvironment, which induce allergic inflammation after PD-L1 blockade. Conclusions: This is the first report of an asthma-negative ES-SCLC patient who developed asthma after receiving atezolizumab plus anlotinib. Although this combination therapy may effectively extend survival in SCLC patients, asthmatic symptoms should be closely monitored.

Case report: The first account of undifferentiated sarcoma with epithelioid features originating in the pleura.

Undifferentiated epithelioid sarcoma (USEF) is a rare subtype of undifferentiated soft tissue sarcoma that presents unique challenges in clinical diagnosis and treatment. Here, we report a case of USEF occurring in the pleura of a 51-year-old man for the first time. Thoracoscopic examination revealed widespread nodular changes, and pathological analysis confirmed the presence of numerous epithelioid atypical cells. Immunohistochemical (IHC) analysis demonstrated an undifferentiated phenotype with distinct characteristics: epithelial membrane antigen (foci +), vimentin (+), Ki-67 (+70% +), TTF-1 (+), P53 (mutant type +90%), INI-1 (+), and CK5/6 (small foci +). Immunohistochemical examination of the tumor showed that the tumor was an undifferentiated epithelioid sarcoma. High-throughput DNA sequencing revealed pivotal mutations, including a nonsense mutation in the NF1 gene (c.641A > G(p.H214R)). and critical TP53 missense mutation (c.641A > G(p.H214R)). This TP53 mutation, with a tumor mutation burden of 16.5 Muts/Mb, signifies a high level of genomic instability, likely contributing to the rapid progression and aggressiveness of the disease. Detection of the TP53 mutation provides essential insights, indicating the disease's rapid progression and highlighting the potential for targeted therapies. Although the patient's disease progressed extremely rapidly and he tragically died within a week, we discussed the results of IHC and DNA sequencing in detail and discussed his possible treatment options. Insights gained from this case will be critical in shaping future diagnostic and therapeutic paradigms for USEF, particularly in the context of TP53 mutations.

Exploring the therapeutic role of early heparin administration in ARDS management: a MIMIC-IV database analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe respiratory condition characterized by a high mortality rate, the management of which relies on supportive care and a profound understanding of its pathophysiology. Heparin, with its anticoagulant and potential anti-inflammatory properties, offers a new therapeutic opportunity for the treatment of ARDS. METHODS: In this retrospective cohort study, we examined the MIMIC-IV database for ARDS patients who received prophylactic heparin within the first 72 h of ICU admission. Employing propensity score matching and inverse probability weighting (IPW) analysis, we evaluated the impact of early heparin use on patient outcomes, focusing on mortality rates. RESULTS: Patients who received prophylactic heparin had a significantly lower in-hospital mortality rate compared to those who did not (13.55% vs 17.93%, HR = 0.71, 95% CI: 0.54-0.93, P = 0.012). This result remained significant after propensity score matching (12.75% vs 17.93%, HR = 0.65, 95% CI 0.47-0.90, P = 0.010). Analysis using five different statistical models indicated that early use of heparin significantly reduced the in-hospital mortality rate, with HR = 0.669 (95% CI 0.487-0.919, P = 0.013) in the doubly robust model without balanced covariates; HR = 0.705 (95% CI 0.515-0.965, P = 0.029) with all covariates considered; HR = 0.660 (95% CI 0.491-0.888, P = 0.006) in the propensity score (IPW) model; HR = 0.650 (95% CI 0.470-0.900, P = 0.010) in the propensity score matching model; and HR = 0.706 (95% CI 0.536-0.930, P = 0.013) in the multivariate Cox regression model. Secondary outcomes indicated that heparin use was also associated with reduced mortality rates at 60 days, and 90 days. CONCLUSION: This research highlights that early prophylactic administration of heparin may substantially lower mortality in ARDS patients. These findings underscore the potential of heparin as a key component in the management of ARDS, offering a new perspective and novel strategies for clinical treatment.

Variety of femoral anteversion and its measurement in cementless total hip arthroplasty: Does robotic technology improve accuracy?

BACKGROUND: High-performance total hip arthroplasty (THA) depends on the accurate position of components. However, femoral anteversion is variable, and current studies only used traditional instruments to evaluate it, such as protractor and spirit level with limited cases. This study aimed to identify the variability in the measured femoral native anteversion and intraoperative stem anteversion under different measurement methods, including intraoperative robotic method. We hypothesized that robotic technology was more accurate than traditional instruments for femoral anteversion evaluation. METHODS: This study included 117 hips of patients who underwent robotic-assisted THA between November 2019 and March 2021. Preoperative native femoral anteversion was measured using a robotic system. Intraoperative femoral stem anteversion was evaluated visually, and then measured with a goniometer and a robotic system, respectively. Variability in the measured femoral native anteversion and intraoperative femoral stem anteversion was calculated and compared. Intraclass correlation coefficient (ICC) and Pearson correlation analysis were used to assess the consistency and correlation of anteversion of different measurements and postoperative CT-measured stem anteversion, respectively. RESULTS: The result of measurement for preoperative native femoral anteversion was more variable than the intraoperative robotic-measured stem anteversion. Intraoperative robotic-measured stem version showed the highest correlation with postoperative CT measurement of stem version (r = 0.806, P < 0.001), while intraoperative surgeon estimation had the lowest correlation coefficient (r = 0.281, P = 0.025). As for the consistency with postoperative CT measurement of femoral stem anteversion, the intraoperative robotic-measured femoral stem version also had the highest value (ICC = 0.892, P < 0.001). CONCLUSION: Native femoral anteversion was variable preoperatively. Using cementless stems, anteversion was also highly variable. Robotic assessment for stem anteversion during surgery was more consistent with the final position than the preoperative assessment and conventional intraoperative estimation.

Two highly conjugated ergosterols from the fungus Psathyrella rogueiana and their anti-inflammatory activity.

Two previously undescribed ergosterols containing a highly conjugated ring system, psathrosterols A and B (1 and 2), have been isolated from the fungus Psathyrella rogueiana. Their structures with absolute configurations were established by extensive spectroscopic methods, as well as single crystal X-ray diffraction. Compounds 1 and 2 showed inhibitory activity against NO production with IC50 values of 22.3 and 16.4 µM, respectively.

Morphology and Molecular Phylogeny Reveal Five New Species of Laccaria (Hydnangiaceae, Agaricales) from Southern China.

The genus Laccaria is a type of cosmopolitan and ecologically important fungal group. Members can form ectomycorrhizal associations with numerous trees, and some species are common edible fungi in local markets. Although some new species from China are recently published, the species diversity of Laccaria is still unclear in China. In this study, some samples of Laccaria were collected from southern China, and morphological characteristics and phylogenetic analyses based on the multilocus dataset of ITS-LSU-tef1-rpb2 confirmed five new species. Laccaria miniata, L. nanlingensis and L. neovinaceoavellanea were collected from subtropical broad-leaved forests, and L. rufobrunnea and L. umbilicata were collected from subtropical mixed forests of southwest China. Full descriptions, illustrations, comparisons with similar species and phylogenetic analysis are provided.

Prone versus lateral position in acute hypoxemic respiratory failure patients with HFNO therapy: study protocol for a multicentre randomised controlled open-label trial.

BACKGROUND: High-flow nasal oxygen (HFNO) therapy is a leading treatment technique for acute hypoxemic respiratory failure (AHRF), but its treatment failure rate remains high. The awake prone position (APP) has been proven to increase oxygenation and reduce the endotracheal intubation rate in patients with COVID-19-induced AHRF. However, the APP is poorly tolerated in patients, and its performance in improving prognoses is controversial. The lateral position has a similar mechanism and effect to the prone position, but it is more tolerable than the prone position. Therefore, it is worth exploring whether the lateral position is better for awake patients with AHRF. METHODS: This is a protocol for a three-arm parallel-group multicentre randomised controlled open-label exploratory trial. A total of 583 patients from two hospitals in Chongqing, China, will be randomised to take the semi-recumbent position, lateral position, or prone position at a ratio of 1:1:1. Patients are all diagnosed with AHRF secondary to non-COVID-19 pneumonia or lung infection and receiving HFNO therapy. The primary outcome is ventilator-free days in 28 days. The secondary outcomes are the 28-day intubation rate, 28-day all-cause mortality, total position change time, the incidence of adverse events, number of hours using HFNO therapy, length of hospital and intensive care unit (ICU) stay, and others. We will conduct subgroup analyses on the arterial partial pressure of oxygen to the fraction of inspiration oxygen (PaO2/FiO2) ratio (> 200 mmHg or ≤ 200 mmHg), time from admission to intervention implementation (< 24 h or ≥ 24 h), position changing time, and different diagnoses. DISCUSSION: This trial will explore the prognostic effects of the APP with that of the lateral position in awake patients with non-COVID-19AHRF and compare the differences between them. To provide evidence for clinical decision-making and further research on position management. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry. The registration number is ChiCTR2200055822 . Registered on January 20, 2022.

Using novel porous metal pillars for tibial bone defects in primary total knee arthroplasty.

BACKGROUND: The optimal method to treat tibial bone defects during primary total knee arthroplasty (TKA) is still unclear. A novel technique of porous metal pillar augmentation has been applied recently. This study aimed to assess the short-term outcomes of primary TKA with the use of novel porous metal pillars for tibial bone defects. METHODS: A total of 24 cases (22 patients) of primary TKA between January 2019 and December 2020 using porous metal pillars for tibial bone defects were reviewed. Clinical results were evaluated using the Knee Society knee score (KSKS) and function score (KSFS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and range of motion (ROM). Hip-knee-ankle angle (HKAA), femorotibial angle (FTA), and radiolucent lines were assessed radiologically. RESULTS: The median follow-up period was 36.0 months (interquartile range: 31-37 months). The KSKS, KSFS, WOMAC score, and ROM improved significantly at the final follow-up assessment compared with the preoperative evaluation. Both of the HKAA and FTA were corrected after surgery. Only one knee had a nonprogressive radiolucent line at the bone-cement interface. No radiolucent lines were detected around the pillar in any of the cases. There were no cases of prosthesis loosening and revision. CONCLUSIONS: The use of novel porous metal pillars yielded satisfactory clinical outcomes and reliable radiological evidence of fixation in this study with a minimum 2-year follow-up. Porous metal pillar augmentation can be considered as a valuable and easy-to-use method for the management of tibial bone defects in primary TKA.

The association between early fluid strategy and prognosis of acute respiratory distress syndrome: A post hoc study of CHARDS.

We aimed to assess general fluid management in China and evaluate the association between fluid balance and survival outcomes in acute respiratory distress syndrome (ARDS) patients. A retrospective, multicenter study including ARDS patients was conducted. We described the fluid management of ARDS patients in China. Furthermore, clinical characteristics and outcomes of patients subdivided by cumulative fluid balance were also analyzed. Multivariable logistic regression analysis was performed with hospital mortality as the outcome. From June 2016 to February 2018, 527 ARDS patients were included in our study. The mean cumulative fluid balance was 1669 (-1101 to 4351) mL in the first 7 day after intensive care unit (ICU) admission. Patients were divided into four groups based on cumulative fluid balance of the first 7 day after ICU admission: Group I (≤0 L), Group II (>0 L, ≤3 L), Group III (>3 L, ≤5 L), and Group IV (>5 L). Significantly lower hospital mortality was observed in patients with a lower cumulative fluid balance on day 7 of ICU admission (20.5% in Group I vs. 32.8% in Group II, 38.5% in Group III, and 50% in Group IV, p < 0.001). A lower fluid balance is associated with lower hospital mortality in patients with ARDS. However, a large-scale and well-designed randomized controlled trial is needed in the future.

Clinical and biomarker analyses of sintilimab plus gemcitabine and cisplatin as first-line treatment for patients with advanced biliary tract cancer.

The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification.

Successful treatment with osimertinib for nonmucinous bronchioloalveolar carcinoma with massive bronchorrhea and respiratory failure: a case report and literature review.

Background: Correct diagnosis of bronchioloalveolar carcinoma (BAC) is often delayed due to the lack of familiarity with the condition among clinicians as its sporadic nature and its symptoms are similar to other respiratory issues. Among these, acute respiratory failure (ARF) caused by massive bronchorrhea is rarely associated with BAC. Here we first reported osimertinib in the treatment of BAC with bronchorrhea and ARF. Case Description: A 38-year-old woman presented with massive bronchorrhea and progressive dyspnea. A chest computed tomography (CT) scan showed consolidation with air bronchograms and multiple nodules in both lungs. The patient had no history of chronic pulmonary disease, diabetes mellitus, hypertension or smoke. The patient was initially diagnosed with pneumonia, but ARF developed despite the antibiotic therapy provided. Lung biopsy results revealed nonmucinous BAC. Osimertinib (80 mg daily) was prescribed and proved effective for the first time with an improved ARF and a decreased multiple nodules or consolidation in the lungs during the follow-up period. Conclusions: It is important for physicians to recognize the typical symptoms and radiological manifestations of BAC to avoid misdiagnosis or late diagnosis. This is especially important since early diagnosis allows for immediate epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, which is a potentially beneficial treatment for patients with BAC.

Medial wall reconstruction using metal disc augments in revision total hip arthroplasty.

PURPOSE: Medial acetabular bone defects are frequently encountered in revision total hip arthroplasty (THA), but few studies have focused on their reconstruction. This study aimed to report the radiographic and clinical results after medial acetabular wall reconstruction using metal disc augments in revision THA. METHODS: Forty consecutive revision THA cases using metal disc augments for medial acetabular wall reconstruction were identified. Post-operative cup orientation, the centre of rotation (COR), stability of acetabular components and peri-augments osseointegration were measured. The pre-operative and post-operative Harris Hip Score (HHS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were compared. RESULTS: The mean post-operative inclination and anteversion were 41.88 ± 6.70° and 16.73 ± 5.35°, respectively. The median vertical and lateral distance between the reconstructed CORs and the anatomic CORs were -3.45 mm (interquartile range [IQR]: -11.30 mm, -0.02 mm) and 3.18 mm (IQR: -0.03 mm, 6.99 mm). Thirty-eight cases completed the minimum two year clinical follow-up, whereas 31 had a minimum two year radiographic follow-up. Acetabular components were radiographically stable with bone ingrowth in 30 cases (30/31, 96.8%) while one case was classified as radiographic failure. Osseointegration around disc augments was observed in 25 of 31 cases (80.6%). The median HHS improved from 33.50 (IQR: 27.50-40.25) pre-operatively to 90.00 (IQR: 86.50-96.25) (p < 0.001), whereas the median WOMAC significantly improved from 38.02 (IQR: 29.17-46.09) to 85.94 (IQR: 79.43-93.75) (p < 0.001). CONCLUSION: In revision THA with severe medial acetabular bone defect, disc augments could provide favorable cup position and stability, peri-augments osseointegration, with satisfactory clinical scores.

The Current Distribution of Oncomelania hupensis Snails in the People's Republic of China Based on a Nationwide Survey.

Schistosomiasis is a helminth infection caused by the genus Schistosoma, which is still a threat in tropical and sub-tropical areas. In the China, schistosomiasis caused by Schistosoma japonicum is mainly endemic to the Yangtze River valley. The amphibious snail Oncomelania hupensis (O. hupensis) is the unique intermediate host of S. japonicum; hence, snail control is a crucial approach in the process of schistosomiasis transmission control and elimination. In 2016, a nationwide snail survey was conducted involving all snail habitats recorded since 1950 in all endemic counties of 12 provinces. A total of 53,254 existing snail habitats (ESHs) were identified, presenting three clusters in Sichuan Basin, Dongting Lake, and Poyang Lake. The overall habitat area was 5.24 billion m2, of which 3.58 billion m2 were inhabited by O. hupensis. The area inhabited by snails (AIS) in Dongting and Poyang Lakes accounted for 76.53% of the population in the country. Three typical landscape types (marshland and lakes, mountains and hills, and plain water networks) existed in endemic areas, and marshland and lakes had a predominant share (3.38 billion m2) of the AIS. Among the 12 endemic provinces, Hunan had a share of nearly 50% of AIS, whereas Guangdong had no ESH. Ditches, dryland, paddy fields, marshland, and ponds are common habitat types of the ESH. Although the AIS of the marshland type accounted for 87.22% of the population in the whole country, ditches were the most common type (35,025 or 65.77%) of habitat. Six categories of vegetation for ESHs were identified. A total of 39,139 habitats were covered with weeds, accounting for 55.26% of the coverage of the area. Multiple vegetation types of snail habitats appeared in the 11 provinces, but one or two of these were mainly dominant. Systematic sampling showed that the presence of living snails was 17.88% among the 13.5 million sampling frames. The occurrence varied significantly by landscape, environment, and vegetation type. The median density of living snails in habitats was 0.50 per frame (0.33 m × 0.33 m), and the highest density was 40.01 per frame. Furthermore, two main clusters with high snail densities and spatial correlations indicated by hotspot analysis were identified: one in Hunan and Hubei, the other in Sichuan. This national survey is the first full-scale census on the distribution of O. hupensis, which is significant, as transmission interruption and elimination are truly becoming the immediate goal of schistosomiasis control in China. The study discerns the detailed geographic distribution of O. hupensis with the hotspots of snail density in China. It is beneficial to understand the status of the snail population in order to finally formulate further national control planning.

Omadacycline for the treatment of severe pneumonia caused by Chlamydia psittaci complicated with acute respiratory distress syndrome during the COVID-19 pandemic.

Introduction: Chlamydia psittaci infection in humans is a rare cause that mainly present as community-acquired pneumonia. Severe Chlamydia psittaci pneumonia can lead to acute respiratory distress syndrome (ARDS), septic shock, or multiple organ dysfunction with a mortality rate of 15%-20% before accurate diagnosis and targeted treatment. Metagenomic next-generation sequencing (mNGS) has an advantage in achieving early diagnosis. In the study, omadacycline implementation was described to provide a better understanding of effectiveness in severe psittacosis pneumonia with ARDS. Methods: Sixteen patients with severe psittacosis pneumonia with ARDS were selected between September 2021 and October 2022. They were diagnosed using mNGS and treated with omadacycline. Retrospective analysis of clinical manifestations, laboratory data, disease progression, diagnostic tool, treatment, and prognosis was summarized. Results: Common symptoms included fever, dyspnea, and cough. All patients developed ARDS, accompanied by septic shock (43.7%) and pulmonary embolism (43.7%). Laboratory data showed normal leucocytes, increased creatine kinase isoenzyme, and decreased albumin with liver dysfunction in most patients. All patients had increased neutrophils, C-reactive protein, procalcitonin, and D-dimer with decreased lymphocytes. Airspace consolidation, ground glass opacity, and pleural effusion were found on chest CT. mNGS results were obtained in 24-48 h to identify the diagnosis of Chlamydia psittacosis. All patients received mechanical ventilation with omadacycline treatment. Fourteen patients experienced complete recovery, while the other two patients died from multidrug-resistant bacterial infection and renal failure. Conclusion: mNGS has a significant value in the diagnosis of Chlamydia psittaci infection. Timely treatment of omadacycline can improve prognosis and provide a promising new option for the treatment of severe Chlamydia psittaci pneumonia with ARDS.

Effect of blood lipids and lipid-lowering therapies on osteoarthritis risk: A Mendelian randomization study.

Background: We aimed to investigate the effects of blood lipids and lipid-lowering agents on osteoarthritis (OA) risk. Materials and methods: We performed Mendelian randomization (MR) analyses to estimate the causal effect of blood low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels on knee and hip OA. Single nucleotide polymorphisms (SNPs) were selected from large genome-wide association studies (GWASs) of individuals of European ancestry as genetic instruments for blood lipid levels. The associations of selected genetic instruments with knee and hip OA were estimated in a recent GWAS of the UK Biobank and arcOGEN datasets. Univariate and multivariate MR analyses were performed to detect and adjust for potential pleiotropy. Furthermore, genetic instruments in HMGCR, NPC1L1, and PCSK9 regions were used to mimic LDL-C-lowering effects of statin, ezetimibe, and evolocumab, respectively. Results: Genetically determined LDL-C increments led to reduced risks of both knee OA (OR = 0.91 per 1-SD increment, 95% CI: 0.86-0.95, P = 6.3 × 10-5) and hip OA (OR = 0.92, 95% CI: 0.85-0.99, P = 0.027). Multivariate MR analysis proved that the effect was independent of HDL-C, TG, and body mass index. TG increment was associated with reduced risks of hip OA in the univariate MR analysis; however, this was not supported by the multivariate MR analysis. Genetically proxied LDL-C-lowering effects of statins are related to increased risks of knee OA but not hip OA. Conclusions: The findings suggested that LDL-C increments have independent protective effects on both knee and hip OA. LDL-C-lowering effects of statins may increase the risk of knee OA.

[Short-term effectiveness of medial unicompartmental knee arthroplasty in patients younger than 60 years of age].

Objective: To compare the short-term effectiveness of medial unicompartmental knee arthroplasty (UKA) between patients younger or older than 60 years of age, and to investigate the impact of age on the effectiveness. Methods: The clinical data of 182 patients (182 knees) who underwent medial UKA between July 2016 and June 2018 were retrospectively analyzed, of which 72 patients were less than 60 years old (group A) and 110 patients were more than 60 years old (group B). There was a significant difference in age between groups (t=-20.198, P<0.001). No significant difference was found in gender, body mass index, surgical sides, Kellgren-Lawrence grading, disease duration, and preoperative Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score between groups (P>0.05). The postoperative hospital stay and complications were recorded, and the WOMAC score, satisfaction score, and prosthesis revision were compared between groups. Results: The length of postoperative hospital stay was (4.50±1.09) days in group A, and (4.46±1.29) days in group B, with no significant difference between groups (t=0.198, P=0.844). All incisions healed by first intention. The incidences of early postoperative complications in groups A and B were 5.6% and 3.6%, respectively, and the difference was not significant (χ2=0.061, P=0.804). All patients were followed up. The follow-up time were 28-50 months (mean, 36 months) in group A and 28-50 months (mean, 35 months) in group B. At last follow-up, the WOMAC scores of both groups significantly improved when compared with those before operation (P<0.05), and there was no significant difference between groups (P>0.05) in the difference before and after operation. The satisfaction scores were 6.6±1.7 in group A and 6.9±1.6 in group B, with no significant difference between groups (t=-1.326, P=0.186). There was no revision surgery in both groups during follow-up period. Conclusion: Age has no significant effect on the prognosis of medial UKA, and patients younger than 60 years of age can also obtain good short-term effectiveness.

Symptom duration is associated with failure of periprosthetic joint infection treated with debridement, antibiotics and implant retention.

Background: Debridement, antibiotics, and implant retention (DAIR) is an alternative treatment strategy for periprosthetic joint infection (PJI). However, no consensus exists regarding which patient population(s) may be most suitable for DAIR. This study aims to investigate the overall infection control rate and explore the prognostic factors associated with acute, hematogenous, and chronic PJIs treated with DAIR. Methods: We retrospectively reviewed the included patients who were diagnosed with PJI and underwent DAIR at two institutions from 2009 to 2018 (n = 104). We collected the clinical data, including demographics, preoperative laboratory tests, Charlson Comorbidity Index, surgical information, and culture organism results. Treatment success was defined according to the criteria reported by Diaz-Ledezma. All patients were followed for at least one year unless failure preceded that time point. A multivariable analysis was utilized to identify prognostic factors associated with treatment, and a Kaplan-Meier survival analysis was used to depict the infection control rate. Results: The overall treatment success rate in the current cohort of patients was 67.3% at a median 38.6 (interquartile range: 23.5, 90.7) months follow-up. Patients with a duration of infectious symptoms of more than ten days were more likely to fail (P = 0.035, hazard ratio 8.492, 95% confidence interval 1.159-62.212). There was no difference among acute, hematogenous, and chronic infections in terms of failure rate (P = 0.161). Conclusions: DAIR is a reasonable treatment option for PJI, and its use in the setting of chronic infection does not appear to be a contraindication. Performing DAIR within ten days of the presentation of symptoms had a higher rate of treatment success.

New insights into the genus Gyroporus (Gyroporaceae, Boletales), with establishment of four new sections and description of five new species from China.

Species of Gyroporus from southern China were studied in this study. Based on morphology and molecular phylogenetic analyses of DNA sequences from the nuclear ribosomal internal transcribed spacer (ITS), the nuclear ribosomal large subunit (nrLSU), and the mitochondrial adenosine triphosphate ATP synthase subunit 6 (atp6), Gyroporus was divided into four main branches in the phylogenetic tree, and four sections were firstly proposed i.e. Gyroporus sect. Castaneus, G. sect. Cyanescens, G. sect. Longicystidiatus and G. sect. Pallidus. Five new species, i.e. G. alboluteus, G. atrocyanescens, G. pseudolongicystidiatus, G. pallidus and G. subcaerulescens, were revealed from China, and their phylogenetic positions were also analysed. Among them, G. alboluteus and G. pallidus were nested into the sect. Pallidus, although morphologically similar to G. castaneus; G. atrocyanescens and G. subcaerulescens, with obvious cyanescent oxidation reactions, were nested into the sect. Cyanescens; and G. pseudolongicystidiatus characterised by its long cystidia and was nested into the sect. Longicystidiatus. The new species were formally described and illustrated in the present study, and a key to the sections and species of Gyroporus in China was provided.

NOTCH1 mutation associates with impaired immune response and decreased relapse-free survival in patients with resected T1-2N0 laryngeal cancer.

Background: Patients with early-stage laryngeal cancer, even stage T1-2N0, are at considerable risk of recurrence and death. The genetic and immunologic characteristics of recurrent laryngeal cancer remain unclear. Methods: A total of 52 T1-2N0 laryngeal cancer patients were enrolled. Of these, 42 tissue samples were performed by targeted DNA sequencing, and 21 cases were performed by NanoString immuno-oncology targeted RNA sequencing to identify the distinct molecular bases and immunologic features associated with relapse in patients with early laryngeal cancer, respectively. Results: To the best to our knowledge, we present for the first time an overview of the genomic mutation spectrum of early-stage laryngeal cancers. A total of 469 genomic alterations were detected in 211 distinct cancer-relevant genes, and the genes found to be mutated in more than five patients (>10%) included tumor protein p53 (TP53, 78.5%), FAT atypical cadherin 1 (FAT1, 26%), LDL receptor related protein 1B (LRP1B, 19%), cyclin dependent kinase inhibitor 2A (CDKN2A, 17%), tet methylcytosine dioxygenase 2 (TET2, 17%), notch receptor 1 (NOTCH1, 12%) and neuregulin 1 (NRG1, 12%). Recurrent laryngeal cancer demonstrated a higher tumor mutation burden (TMB), as well as higher LRP1B mutation and NOTCH1 mutation rates. Univariate and multivariate analyses revealed that high TMB (TMB-H) and NOTCH1 mutation are independent genetic factors that are significantly associated with shorter relapse-free survival (RFS). Simultaneously, the results of the transcriptome analysis presented recurrent tumors with NOTCH1 mutation displayed upregulation of the cell cycle pathway, along with decreased B cells score, T cells score, immune signature score and tumor-infiltrating lymphocytes (TILs) score. The Cancer Genome Atlas (TCGA)-laryngeal cancer dataset also revealed weakened immune response and impaired adhesion functions in NOTCH1-mutant patients. Conclusions: Genomic instability and impaired immune response are key features of the immunosurveillance escape and recurrence of early laryngeal cancer after surgery. These findings revealed immunophenotypic attenuation in recurrent tumors and provided valuable information for improving the management of these high-risk patients. Due to the small number of patients in this study, these differences need to be further validated in a larger cohort.