[Clinical analysis of 18 children with aggressive mature B-cell lymphoma after liver transplantation].

Objective: To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation. Methods: This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis. Results: Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions: The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.

[Association between abnormal oral glucose tolerance test patterns in the second trimester and large for gestational age newborns].

Objective: To investigate the impact of abnormal patterns of 75 g oral glucose tolerance test (OGTT) in the second trimester on the risk of large for gestational age (LGA) newborn deliveries. Methods: General clinical data and OGTT results of 66 290 pregnant women who received regular prenatal care and delivered in Guangdong Maternal and Child Health Hospital from December 24, 2016 to July 26, 2022 were collected. According to the results of OGTT, the pregnant women were divided into 8 groups: normal blood glucose group (normal fasting blood glucose, 1-hour and 2-hour after oral glucose, 54 518 cases), gestational diabetes mellitus (GDM) 0 group (only abnormal fasting blood glucose, 1 430 cases), GDM 1 group (only abnormal blood glucose at 1-hour after oral glucose, 2 150 cases), GDM 2 group (only abnormal blood glucose at 2-hour after oral glucose, 3 736 cases), GDM 0+1 group (both fasting blood glucose and 1-hour after oral glucose were abnormal, 371 cases), GDM 0+2 group (both fasting blood glucose and 2-hour after oral glucose were abnormal, 280 cases), GDM 1+2 group (abnormal blood glucose at 1-hour and 2-hour after oral glucose, 2 981 cases) and GDM 0+1+2 group (abnormal fasting blood glucose, 1-hour and 2-hour after oral glucose, 824 cases). Multivariate logistic regression was used to analyze the effects of different abnormal OGTT patterns on LGA. In addition, the blood glucose measurements at the three time points of OGTT were combined and used as continuous variables in the receiver operating characteristic (ROC) curve to evaluate the predictive value of each blood glucose measurement mode for LGA and the area under the curve (AUC) was compared. Results: (1) Multivariate logistic regression analysis showed that the risks of LGA were significantly increased in GDM 0 group (OR=1.76, 95%CI: 1.50-2.08; P<0.001), GDM 0+1 group (OR=2.29, 95%CI: 1.72-3.04; P<0.001), and GDM 0+1+2 group (OR=1.98, 95%CI: 1.61-2.43; P<0.001). (2) ROC curve analysis showed that fasting blood glucose, 1-hour after oral glucose, 2-hour after oral glucose, fasting+1-hour after oral glucose, fasting+2-hour after oral glucose, 1-hour+2-hour after oral glucose, and fasting+1-hour+2-hour after oral glucose had certain predictive value for LGA (all P<0.001). The AUC of fasting blood glucose measurement was higher than that of 2-hour blood glucose measurement in predicting LGA, and the difference was statistically significant (P<0.05). There was no significant difference in the AUC between fasting blood glucose and other blood glucose measurement modes for predicting LGA (all P>0.05). Conclusions: In the abnormal OGTT patterns, pregnant women with abnormal fasting blood glucose, abnormal fasting+1-hour after oral glucose, and abnormal fasting+1-hour+2-hour after oral glucose have an increased risk of LGA. Fasting blood glucose measurement is of great significance for the prediction of LGA, and could be used as an optimal indicator to evaluate the risk of LGA in clinical practice.

[Intraoperative optical coherence tomography guided precise corneal suture in the treatment of acute keratoconus].

Objective: This study aimed to observe the clinical efficacy of precise suturing of posterior elastic layer fissures guided by intraoperative optical coherence tomography (OCT) in conjunction with anterior chamber puncture and drainage, and corneal thermokeratoplasty for the treatment of severe acute edematous keratoconus. Methods: Non-randomized controlled trial. Data were collected for a study involving 31 cases of acute edematous keratoconus patients who underwent surgical treatment at the Shandong Eye Hospital between June 2017 and July 2021. Among them, there were 30 male and 1 female patients, with an age range of 11 to 32 years and a mean age of (19.80±5.80) years. Eighteen patients in the study group underwent precise suturing of posterior elastic layer fissures guided by intraoperative OCT, in combination with anterior chamber puncture and drainage, and corneal thermokeratoplasty. Thirteen patients in the control group did not undergo suturing. Preoperative visual acuity, corneal edema diameter, corneal thickness, and posterior elastic layer fissure length were collected. Evaluation was performed using slit lamp microscopy, anterior segment OCT, and other methods to assess the time of initial postoperative corneal edema resolution and closure of the posterior elastic layer fissure. Deep lamellar keratoplasty was performed 2 to 4 weeks after edema resolution, and the corneal bed scar repair and visual acuity of the two groups were compared. Results: In the suturing group, the corneas of all 18 patients were accurately sutured to the deep stromal layer near the posterior elastic layer. The time for corneal edema resolution was 2.50 (1.00, 6.25) days in the suturing group and 7.00 (6.00, 10.50) days in the control group. The fissure healing time was 7.50 (7.00, 12.00) days in the suturing group and 14.00 (9.00, 14.00) days in the control group. The differences were statistically significant (all P<0.05). After 2 weeks, the central corneal thickness decreased to (529.80±174.50) µm in the suturing group and (612.00±205.12) µm in the control group. The suturing group showed accurate corneal suturing to the deep stromal layer near the posterior elastic layer, resulting in central corneal flattening, closure of voids in the stroma, and a significant decrease in corneal thickness. All 18 patients in the suturing group successfully completed deep lamellar keratoplasty, with 6 cases (6/18) experiencing mild graft bed leakage during surgery but without affecting the deep lamellar keratoplasty. One year postoperatively, the visual acuity (logarithm of the minimum resolution angle) was 0.23±0.12 in the suturing group and 0.33±0.11 in the control group, with a statistically significant difference (P<0.05). Conclusions: In the treatment of severe acute edematous keratoconus, precise suturing of posterior elastic layer fissures guided by intraoperative OCT, in conjunction with anterior chamber puncture and drainage, and corneal thermokeratoplasty, can rapidly alleviate corneal edema and promote the healing of posterior elastic layer fissures. This approach achieves better visual outcomes for subsequent lamellar keratoplasty surgeries. The use of intraoperative OCT guidance allows accurate positioning of the posterior elastic layer fissure in terms of location, direction, and depth of corneal stromal voids, thereby assisting surgeons in precise suturing.

[Application of intraoperative optical coherence tomography in deep lamellar keratoplasty].

Objective: To evaluate the clinical application value of intraoperative optical coherence tomography (iOCT) in deep anterior lamellar keratoplasty (DALK) using the big-bubble technique to bare Descemet's membrane. Methods: Retrospective case series. Clinical data of 92 patients (92 eyes) with monocular stromal corneal diseases who underwent big-bubble DALK in the Eye Hospital of Shandong First Medical University from January 2020 to August 2021 were collected. There were 53 males and 39 females. The average age was (53.2±16.0) years old. All patients underwent iOCT scanning to determine the location and depth of the injection needle after initial removal of the corneal lesion, to observe the integrity of the recipient bed, Descemet's membrane, after complete lesion removal, and to observe the adhesion between the corneal graft and the recipient bed and check folds on the recipient bed after suturing of the corneal graft. The intraoperative perforation of Descemet's membrane, postoperative thickness of the cornea and the recipient bed, visual acuity, and corneal astigmatism were recorded. Results: By iOCT, the thickness of the recipient bed was found to be about 1/2 of the corneal thickness and relatively uniform in all directions in 62 eyes (67.4%), so the sterile air was injected from the center of the recipient bed to separate it from the stromal layer. In 30 eyes (32.6%) with an uneven thickness of the recipient bed, the sterile air was injected from the paracentral area of the recipient bed. Under the guidance of iOCT scanning, 89 eyes (96.7%) did not experience any perforation of Descemet's membrane during surgery. The Descemet's membrane folds in the central 5-mm area of the recipient bed was observed and flattened in 20 eyes with the assistance of iOCT scanning. The postoperative corneal thickness was (578.95±108.26) µm, and the recipient bed thickness was (36.06±23.11) µm. The best corrected visual acuity of all patients at 6 months after surgery was 0.57±0.25 logMAR, which was significantly better than that before surgery (1.61±1.27 logMAR; P<0.001). The average corneal astigmatism at 6 months after surgery was (2.72±2.44) diopters. Conclusions: The application of iOCT scanning in DALK surgery assisted by the big-bubble method can provide safe guidance for surgeons to adopt correct surgical procedures, decrease the risk of Descemet's membrane perforation, reduce the recipient bed folds, and facilitate corneal interlayer adhesion, thereby improving the visual prognosis.

Non-cell-autonomous cancer progression from chromosomal instability.

Chromosomal instability (CIN) is a driver of cancer metastasis1-4, yet the extent to which this effect depends on the immune system remains unknown. Using ContactTracing-a newly developed, validated and benchmarked tool to infer the nature and conditional dependence of cell-cell interactions from single-cell transcriptomic data-we show that CIN-induced chronic activation of the cGAS-STING pathway promotes downstream signal re-wiring in cancer cells, leading to a pro-metastatic tumour microenvironment. This re-wiring is manifested by type I interferon tachyphylaxis selectively downstream of STING and a corresponding increase in cancer cell-derived endoplasmic reticulum (ER) stress response. Reversal of CIN, depletion of cancer cell STING or inhibition of ER stress response signalling abrogates CIN-dependent effects on the tumour microenvironment and suppresses metastasis in immune competent, but not severely immune compromised, settings. Treatment with STING inhibitors reduces CIN-driven metastasis in melanoma, breast and colorectal cancers in a manner dependent on tumour cell-intrinsic STING. Finally, we show that CIN and pervasive cGAS activation in micronuclei are associated with ER stress signalling, immune suppression and metastasis in human triple-negative breast cancer, highlighting a viable strategy to identify and therapeutically intervene in tumours spurred by CIN-induced inflammation.

Breast lymphoma: General review.

BACKGROUND: Lymphoma of the breast can be classified as either primary breast lymphoma (PBL) or secondary to systemic lymphoma (SBL). PBL is a rare disease with Diffuse Large B cell Lymphomas (DLBCL) being the most common subtype. OBJECTIVES: In the current study, we represented eleven cases diagnosed with breast lymphoma in our trust; two of them had PBL and nine had SBL. We focused mainly on the clinical presentation, diagnosis, management and outcomes. METHODS: We did this retrospective review for all breast lymphoma patients who were diagnosed in our trust during the periods from 2011-2022. Patients' data were obtained from the hospital recording system. We followed up these patients thus far to identify the outcome of treatment in each patient. RESULTS: Eleven patients were included in our review. All patients were females. Average age of diagnosis was 66.1 ± 13 years of age. Eight patients were diagnosed with DLBCL, two patients were diagnosed with follicular lymphomas, and the last one had lymphoplasmacytic lymphoma. Chemotherapy +∕- radiotherapy was the standard treatment regimen in all patients. Four patients passed away within one year of chemotherapy, five patients achieved complete remission, one patient had two relapses and is still under treatment, while the last patient was diagnosed recently and still awaiting treatment. CONCLUSION: Primary breast lymphoma is an aggressive disease. The treatment for PBL is mainly systemic with chemoradiotherapy. The role of surgery is now limited to the diagnosis of the disease. Early diagnosis and proper treatment are crucial for the management of such cases.

A Case Report of Native Coronary Artery Thrombosis With Heparin-Induced Thrombocytopenia.

Heparin is an anticoagulant which has been widely used in various clinical settings, from thromboprophylaxis to the treatment of thromboembolism. Heparin-induced thrombocytopenia (HIT) is a rare medical condition with severe complications if unrecognised, and it carries significant risks of co-morbidities and mortality. The incidence of HIT is relatively less common in low molecular weight heparin. HIT is more common in the venous system than the arterial circulatory system, and it is rare to see multi-vessel coronary artery thrombosis due to HIT. We hereby report a case of multi-vessel coronary thrombosis secondary to low molecular weight HIT, presenting as a case of ST-segment elevation myocardial infarction. We learned from the case that low molecular weight heparin can cause thrombosis secondary to HIT and HIT could be one of the differential diagnoses in those presenting with ST-elevation myocardial infarct and recent exposure to low molecular weight heparin.

Innovations in the Treatment of Dystrophic Epidermolysis Bullosa (DEB): Current Landscape and Prospects.

Dystrophic epidermolysis bullosa (DEB) is one of the major types of EB, a rare hereditary group of trauma-induced blistering skin disorders. DEB is caused by inherited pathogenic variants in the COL7A1 gene, which encodes type VII collagen, the major component of anchoring fibrils which maintain adhesion between the outer epidermis and underlying dermis. DEB can be subclassified into dominant (DDEB) and recessive (RDEB) forms. Generally, DDEB has a milder phenotype, while RDEB patients often have more extensive blistering, chronic inflammation, skin fibrosis, and a propensity for squamous cell carcinoma development, collectively impacting on daily activities and life expectancy. At present, best practice treatments are mostly supportive, and thus there is a considerable burden of disease with unmet therapeutic need. Over the last 20 years, considerable translational research efforts have focused on either trying to cure DEB by direct correction of the COL7A1 gene pathology, or by modifying secondary inflammation to lessen phenotypic severity and improve patient symptoms such as poor wound healing, itch, and pain. In this review, we provide an overview and update on various therapeutic innovations for DEB, including gene therapy, cell-based therapy, protein therapy, and disease-modifying and symptomatic control agents. We outline the progress and challenges for each treatment modality and identify likely prospects for future clinical impact.

[Analysis of the clinical features and the risk factors of severe human metapneu movirus-associated community acquired pneumonia in children].

Objective: To investigate the clinical characteristics and the risk factors of severe human metapneumovirus (hMPV)-associated community acquired pneumonia (CAP) in children. Methods: A retrospective case summary was conducted. From December 2020 to March 2022, 721 children who were diagnosed with CAP and tested positive for hMPV nucleic acid by PCR-capillary electrophoresis fragment analysis of nasopharyngeal secretions at the Yuying Children's Hospital, the Second Affiliated Hospital of Wenzhou Medical University were selected as the research objects. The clinical characteristics, epidemiological characteristics and mixed pathogens of the two groups were analyzed. According to CAP diagnostic criteria, the children were divided into the severe group and the mild group. Chi-square test or Mann-Whitney rank and contrast analysis was used for comparison between groups, while multivariate Logistic regression was applied to analyze the risk factors of the severe hMPV-associated CAP. Results: A total of 721 children who were diagnosed with hMPV-associated CAP were included in this study, with 397 males and 324 females. There were 154 cases in the severe group. The age of onset was 1.0 (0.9, 3.0) years, <3 years old 104 cases (67.5%), and the length of hospital stay was 7 (6, 9) days. In the severe group, 67 children (43.5%) were complicated with underlying diseases. In the severe group, 154 cases (100.0%) had cough, 148 cases (96.1%) had shortness of breath and pulmonary moist rales, and 132 cases (85.7%) had fever, 23 cases (14.9%) were complicated with respiratory failure. C-reactive protein (CRP) was elevated in 86 children (55.8%), including CRP≥50 mg/L in 33 children (21.4%). Co-infection was detected in 77 cases (50.0%) and 102 strains of pathogen were detected, 25 strains of rhinovirus, 17 strains of Mycoplasma pneumoniae, 15 strains of Streptococcus pneumoniae, 12 strains of Haemophilus influenzae and 10 strains of respiratory syncytial virus were detected. Six cases (3.9%) received heated and humidified high flow nasal cannula oxygen therapy, 15 cases (9.7%) were admitted to intensive care unit, and 2 cases (1.3%) received mechanical ventilation. In the severe group, 108 children were cured, 42 children were improved, 4 chlidren were discharged automatically without recovery and no death occurred. There were 567 cases in the mild group. The age of onset was 2.7 (1.0, 4.0) years, and the length of hospital stay was 4 (4, 6) days.Compared with the mild group, the proportion of children who age of disease onset <6 months, CRP≥50 mg/L, the proportions of preterm birth, congenital heart disease, malnutrition, congenital airway malformation, neuromuscular disease, mixed respiratory syncytial viruses infection were higher (20 cases (13.0%) vs. 31 cases (5.5%), 32 cases (20.8%) vs. 64 cases (11.3%), 23 cases (14.9%) vs. 44 cases (7.8%), 11 cases (7.1%) vs. 18 cases (3.2%), 9 cases (5.8%) vs. 6 cases (1.1%), 11 cases (7.1%) vs. 12 cases (2.1%), 8 cases (5.2%) vs. 4 cases (0.7%), 10 cases (6.5%) vs. 13 cases (2.3%), χ2=0.42, 9.45, 7.40, 4.94, 11.40, 8.35, 3.52, 6.92, all P<0.05). Multivariate Logistic regression analysis showed that age<6 months (OR=2.51, 95%CI 1.29-4.89), CRP≥50 mg/L (OR=2.20, 95%CI 1.36-3.57), prematurity (OR=2.19, 95%CI 1.26-3.81), malnutrition (OR=6.05, 95%CI 1.89-19.39) were the independent risk factors for severe hMPV-associated CAP. Conclusions: Severe hMPV-associated CAP is most likely to occur in infants under 3 years old and has a higher proportion of underlying diseases and co-infection. The main clinical manifestations are cough, shortness of breath and pulmonary moist rales, fever. The overall prognosis is good. Age<6 months, CRP≥50 mg/L, preterm birth, malnutrition are the independent risk factors for severe hMPV-associated CAP.

[Characteristics of serum autoantibodies in patients with lupus nephritis and tubulointerstitial damage].

OBJECTIVE: To observe the tubulointerstitial damage (TID) in lupus nephritis (LN) and investigate the relationship between autoantibodies and TID in lupus nephritis. METHODS: This cross-sectional study was conducted in a comprehensive tertiary hospital in Peking University Shenzhen Hospital. From March 2012 to July 2021, LN patients who performed renal biopsy were enrolled in the study. Clinical, laboratory and pathology data were collected. We classified the patients into none-or-mild group and moderate-to-severe groups according to the severity of interstitial fibrosis (IF) /tubular atrophy (TA) or tubulointerstitial inflammation (TII). The t test, U test and Chi-square test were used for statistical analysis as appropriate. RESULTS: A total of 226 patients were included, of who 190 (84%) were female with a median age of 32 (26, 39) years. 89% (201/226) of the patients who pathologically proved to be proliferative LN by renal biopsy. The frequency of moderate-to-severe TII and moderate-to-severe IF/TA was 30% (67/226) and 34% (76/226) respectively. For autoantibodies, the patients with moderate-to-severe TII had a lower rate of positive serum anti-ribonucleoprotein (anti-RNP) antibodies than the patients with none-or-mild TII (34% vs. 51%), and moderate-to-severe IF/TA had a lower rate of positive anti-ribosomal P protein (anti-P) antibodies than patients with none-or-mild IF/TA (19% vs. 33%). For other clinical indicators, the patients with moderate-to-severe TII and moderate-to-severe IF/TA were more often combined with proliferative LN, hypertension and anemia than the patients with none-or-mild TII and none-or-mild IF/TA, respectively. The patients with moderate-to-severe TII had higher serum creatinine values and lower glomerular filtration rates than the patients with none-or-mild TII. The patients with moderate-to-severe IF/TA had higher serum creatinine values, and lower glomerular filtration rates than the patients with none-or-mild IF/TA. CONCLUSION: In patients with LN in Southern China, anti-RNP antibodies and anti-P antibodies may be potential protective factors for TII and IF/TA, respectively. More studies are needed to identify the risk factors of lupus patients with TID and investigate the correlation between autoantibodies and TID, which are critical for developing better preventive and therapeutic strategies to improve the survival rate of LN.

Docosahexaenoic Acid Reverses Epithelial-Mesenchymal Transition and Drug Resistance by Impairing the PI3K/AKT/ Nrf2/GPX4 Signalling Pathway in Docetaxel-Resistant PC3 Prostate Cancer Cells.

Drug resistance is a serious problem in cancer therapy. Growing evidence has shown that docosahexaenoic acid has anti-inflammatory and chemopreventive abilities. Studies have shown that autophagy inhibition and ferroptosis are promising therapeutic strategies for overcoming multidrug resistance. This study was aimed to examine whether docosahexaenoic acid (DHA) could reverse docetaxel resistance in prostate cancer cells. Cell survival was examined by MTT and colony formation. Protein expression was determined by Western blot. Reactive oxygen species (ROS) production was measured by flow cytometry. DHA displayed anti-cancer effects on proliferation, colony formation, migration, apoptosis, autophagy and epithelial mesenchymal transition. Glutathione-S-transferase π is an enzyme that plays an important role in drug resistance. DHA inhibited GSTπ protein expression and induced cytoprotective autophagy by regulating the PI3K/AKT signalling pathway in PC3R cells. DHA combined with PI3K inhibitor (LY294002) enhanced apoptosis by alleviating the expression of LC3B, (pro-) caspase- 3 and (uncleaved) PARP. DHA induced ferroptosis by attenuating the expression of glutathione peroxidase 4 (GPX4) and nuclear erythroid 2-related factor 2 (Nrf2). DHA-treated PC3R cells produced ROS. The ROS and cytotoxicity were reversed by treatment with ferrostatin-1. DHA combined with docetaxel inhibited EMT by regulating the expression of E-cadhein and N-cadherin. In summary, DHA reversed drug resistance and induced cytoprotective autophagy and ferroptosis by regulating the PI3K/AKT/Nrf2/GPX4 signalling pathway in PC3R cells. We propose that DHA could be developed as a chemosensitizer and that the PI3K/AKT /Nrf2/GPX4 signalling pathway might be a promising therapeutic target for overcoming cancer drug resistance.

[Analysis of 42 cases of childhood superior vena cava syndrome associated with mediastinal malignancy].

Objective: To summarize the clinical features, management and outcome of superior vena cava syndrome (SVCS) associated with mediastinal malignancy in children. Methods: Clinical data of 42 children of SVSC associated with mediastinal malignancy in Shanghai Children's Medical Center from January 2015 to December 2021 were collected and analyzed retrospectively. The clinical manifestations, pathological diagnosis, disease diagnosis process, and prognosis were summarized. Results: Among 42 children of SVCS associated with mediastinal malignancy, there were 31 males and 11 females. The age at diagnosis was 8.5 (1.9, 14.9) years. Cough and wheezing (33 cases, 79%), orthopnea (19 cases, 45%) and facial edema (18 cases, 43%) occurred most commonly. T-cell lymphoblastic lymphoma (T-LBL) was the most frequent pathological diagnosis (25 cases, 60%), followed by T-cell acute lymphoblastic leukemia (T-ALL) (7 cases, 17%), anaplastic large cell lymphoma (4 cases, 10%) and diffuse large B-cell lymphoma (2 cases, 5%), peripheral T-lymphoma, Hodgkin lymphoma, Ewing's sarcoma and germ cell tumor (1 case each). Pathological diagnosis was confirmed by bone marrow aspiration or thoracentesis in 14 cases, peripheral lymph node biopsy in 6 cases, and mediastinal biopsy in 22 cases. Twenty-seven cases (64%) had local anesthesia. Respiratory complications due to mediastinal mass developed in 3 of 15 cases who received general anesthesia. Of the 42 cases, 27 cases had sustained remission, 1 case survived with second-line therapy after recurrence, and 14 cases died (2 cases died of perioperative complications and 12 cases died of recurrence or progression of primary disease). The follow-up time was 36.7 (1.2, 76.1) months for 27 cases in continuous complete remission. The 3-year overall survival (OS) and events free survival (EFS) rates of 42 children were 59% (95%CI 44%-79%) and 58% (95%CI 44%-77%) respectively. Conclusions: SVCS associated with mediastinal malignancy in children is a life-threatening tumor emergency with high mortality. The most common primary disease is T-LBL. The most common clinical symptoms and signs are cough, wheezing, orthopnea and facial edema. Clinical management should be based on the premise of stable critical condition and confirm the pathological diagnosis through minimal invasive operation.

Antifungal use via outpatient parenteral antimicrobial therapy.

BACKGROUND: Antifungal administration via outpatient parenteral antimicrobial therapy (OPAT) is infrequent. As patients with invasive fungal infections (IFIs) receiving OPAT are at high risk of readmissions, careful, risk-based patient selection and monitoring is important. OBJECTIVES: To describe our experience managing IFIs via OPAT, including assessment of risk factors associated with unplanned readmissions. PATIENTS AND METHODS: A retrospective cohort study of outpatients from two tertiary hospitals in Western Australia managed with parenteral antifungals for the treatment of IFIs from 2012 to 2020. Outcomes assessed were unplanned OPAT-related readmissions; adverse events and achievement of treatment aim at the completion of OPAT. RESULTS: Forty-six patients were included, encompassing 696 OPAT days. Twenty-three (50%) patients received intravenous (IV) liposomal amphotericin B (L-AmB), 23 (50%) received IV echinocandins and one (2%) patient received IV fluconazole. One patient received both IV L-AmB and an echinocandin. Unplanned OPAT-related readmissions occurred in 13 (28%) patients and any adverse event occurred in 19 (41%), most commonly nephrotoxicity amongst patients receiving L-AmB. On univariate analysis, unplanned OPAT-related readmissions were more common in Mucorales infection, L-AmB doses of ≥5 mg/kg and otorhinolaryngologic (ENT) infections. At the completion of OPAT, attainment of treatment aims occurred in 28 (61%) patients. CONCLUSIONS: Patients receiving parenteral antifungals via OPAT experience high rates of unplanned readmissions and adverse events. Risk factor identification may facilitate optimal patient selection and establishment of treatment aims.

Effects of regional anaesthesia on mortality in patients undergoing lower extremity amputation: A retrospective pooled analysis.

Background and Aims: Lower extremity amputation (LEA) is a commonly performed surgery and is associated with significant mortality and morbidity. This review compares the impact of anaesthetic technique on 30-day mortality and other perioperative outcomes in patients undergoing LEA. Methods: A systematic search of databases including PubMed, Embase, Scopus and Cochrane Central Register of Controlled Trials, from January 2010 to March 2021, was performed. Studies were eligible if they compared 30-day mortality following either general anaesthesia (GA) or regional anaesthesia (RA), in adult patients undergoing LEA. Results: Ten retrospective observational studies were identified. Four of these studies utilised a propensity-score matching technique. Based on these four studies, RA when compared to GA, is not associated with a reduction in the 30-day mortality (Odds ratio 0.83, 95% confidence interval (CI): 0.65, 1.05, I2 20%, P = 0.12). Also there is a very low level of evidence that RA may result in a decrease in the hospital length-of-stay and intensive care unit admissions of patients undergoing LEA. Conclusion: RA does not decrease the 30-day postoperative mortality in patients undergoing LEA when compared to GA.

Restoring type VII collagen in skin.

New therapeutic hope is emerging for people with the rare inherited blistering skin disease recessive dystrophic epidermolysis bullosa (RDEB). Gurevich et al.1 have reported early-phase clinical trial data evaluating a topical herpes simplex virus 1 vector to restore missing type VII collagen in RDEB skin and heal wounds.

Exploring beyond the limit: How comparative stochastic performance affects retesting outcomes in six commercial SARS CoV-2 nucleic acid amplification tests.

Objectives: To examine the comparative stochasticity profile of six commercial SARS-CoV-2 nucleic acid amplification tests (NAATs) and how this may affect retesting paradigms. Methods: Commercial quality control (QC) material was serially diluted in viral transport media to create a panel covering 10-10,000 copies/ml. The panel was tested across six commercial NAATs. A subset of high cycle threshold results was retested on a rapid PCR assay to simulate retesting protocols commonly used to discriminate false positives. Results: Performance beyond the LOD differed among assays, with three types of stochasticity profiles observed. The ability of the rapid PCR assay to reproduce a true weak positive specimen was restricted to its own stochastic performance at the corresponding viral concentration. Conclusion: Stochastic performance of various NAATs overlap across low viral concentrations and affect retesting outcomes. Relying on retesting alone to discriminate false positives risk missing true positives even when a more sensitive assay is deployed for confirmatory testing.

Dynamic cervical flexion/extension atlantodental interval and functional outcome of the Harms technique for posterior C1/2 fixation: A retrospective analysis of 16 atlantoaxial subluxation cases in a tertiary medical center.

BACKGROUND: The aim of this study was to assess the relationship between the atlantodental interval (ADI) on dynamic flexion/extension cervical radiographs and functional outcomes of posterior spinal fixation by the Harms technique for atlantoaxial subluxation (AAS). Dynamic flexion/extension on cervical radiographs is a standard assessment for evaluation of C1/2 instability in AAS patients. Most studies focused on postoperative ADI and functional outcome, including pain and fusion rate; only few studies compared dynamic ADI change pre- to post-operatively. MATERIAL AND METHODS: Retrospectively, we reviewed the medical records of 16 patients who underwent posterior spinal fixation in our center from 2018 to 2019. We used dynamic cervical flexion/extension radiographs to assess the pre- to postoperative change at 12 months in ADI of flexion (ADIf), ADI of extension (ADIe), ADI between flexion/extension (ADIΔ), C1/2 fusion rate and functional outcomes measured by the modified Japanese Orthopaedic Association scale (mJOA scale). Postoperative CT at 3∼12 months assessed screw positioning on the Gertzbein and Robbins classification. RESULTS: In the 16 patients included in this study, ADIf, ADIe and ADIΔ were significantly reduced, from respectively 8.0mm, 5.0mm and 3.0mm preoperatively to 4.6mm, 3.8mm and 0.8mm at 12 months' follow-up. The fusion rate was 81% and the mJOA score recovery rate was 34.9±14.7%. Although the screw malposition rate was higher than in other studies in C1(10%) and C2(20%), there were no new neurologic deficits or worsening of symptoms at follow-up. CONCLUSIONS: The ADIΔ showed significant reduction, showing that the Harms technique of posterior spinal fixation can effective in maintaining the stability of the atlantoaxial joint and improving functional outcome.

[Development and evaluation of a machine learning prediction model for large for gestational age].

Objective: To develop and validate a useful predictive model for large gestational age (LGA) in pregnancy using a machine learning (ML) algorithm and compare its performance with the traditional logistic regression model. Methods: Data were obtained from the National Free Preconception Health Examination Project in China, carried out in 220 counties of 31 provinces from 2010 to 2012, covering all rural couples with a planned pregnancy. This study included all teams of childbearing age who delivered newborns within 24-42 weeks of gestational age and their newborns. Ten different ML algorithms were used to establish LGA prediction models, and the prediction performance of these models was evaluated. Results: A total of 104 936 newborns were included, including 54 856 boys (52.3%) and 50 080 girls (47.7%). The incidence of LGA was 11.7% (12 279). The imbalance between the two groups was addressed by the under- sampling technique, after which the overall performance of the ML models was significantly improved. The CatBoost model achieved the highest area under the receiver-operating-characteristic curve (AUC) value of 0.932. The logistic regression model had the worst performance, with an AUC of 0.555. Conclusions: In predicting the risk for LGA in pregnancy, the ML algorithms outperform the traditional logistic regression method. Compared to other ML algorithms, CatBoost could improve the performance, and it deserves further investigation.