Comparison of traditional growth rods and magnetically controlled growing rods in early-onset scoliosis: a case-matched mid term follow-up study.

PURPOSE: Early-onset scoliosis (EOS) has always been a challenging situation for spine surgeons. The aim of treatment is to control the direction of curve progression to allow for the complete development of lungs. Among all the growth constructs available, traditional growth rods (TGR) and magnetically controlled growth rods (MCGR) are most widely used. The MCGR has been introduced a few years back and there is a dearth of long-term follow-up studies. The purpose of this study is to compare the effectiveness of TGR and MCGR for the treatment of EOS. METHODS: All patients of EOS managed with either TGR or MCGR were included in the study. The patients managed with other methods or having follow-up < 2-years were excluded from the study. A total of 20 patients were recruited in the MCGR group and 28 patients were recruited in the TGR group. Both groups were matched by etiology, gender, pre-operative radiological parameters, and complications including unplanned surgeries. RESULTS: The mean age in our study was 7.90 years in the MCGR group and 7.46 years in the TGR group. The mean duration of follow-up in the MCGR group was 50.89 months and in the TGR group 94.2 months. Pre-operative cobb's angle in the coronal plane and T1-S1 were comparable in both groups with a mean cobb's angle of 65.4 in MCGR and 70.5 in TGR. The mean T1-S1 length in the MCGR group was 36.1cms and in the TGR group was 35.2 cms (p = 0.18). The average increase in T1-S1 length was 1.3 cm/year in the TGR group and 1.1 cm/year in the MCGR group (p > 0.05). The TGR patients underwent 186 open lengthening surgeries and 11 unplanned surgeries for various complications. The MCGR group has 180 non-invasive lengthening with only 4 unplanned returns to OT for various causes. CONCLUSION: The curve correction was similar in both TGR and MCGR groups. The average T1-S1 length achieved on final follow-up was similar in both groups. The MCGR patients have attained similar correction with fewer invasive procedures and lesser complications compared to the TGR group.

Breast lymphomas: Clinical and pathological insights from a tertiary cancer care center in India.

BACKGROUND: Breast lymphomas are a rare group of malignancies that are further subdivided into primary and secondary. AIMS: To study the pathological and clinical course of breast lymphomas. MATERIALS AND METHODS: This is a retrospective analysis of patients treated at our institute over a period of 4.5 years from September 2018 to February 2023. The details of all the patients diagnosed with breast lymphoma were reviewed and analysed for the histomorphological, immunohistochemical, clinical, and treatment details. Appropriate statistical analysis including Kaplan-Meier methods was used. RESULTS: Out of 11 cases of breast lymphoma, five were primary and six were secondary. It was seen predominantly in females (82%) and the age range was 31 to 73 years. Diffuse large B cell lymphoma (DLBCL) was the predominant morphology (73%), along with single rare cases of ALK-negative anaplastic large cell lymphoma, Burkitt lymphoma, and small lymphocytic lymphoma. The treatment details were analyzed for 7 patients. The median follow-up was 28 months. Rituximab along with CHOP regimen or its variants was commonly used as first-line treatment with initial response rates of 71%. The median progression-free survival was 5 months. The median overall survival was 15 months. CONCLUSION: Lymphomas of the breast are rare but it is crucial to differentiate them from the commoner breast carcinomas as the treatment and prognosis vary vastly.

A rare case of spontaneous giant pneumorrachis presenting with cauda equina syndrome: a case report.

INTRODUCTION: Pneumorrachis is presence of air in the epidural space. It could be the result of trauma, barotrauma, iatrogenic or spontaneous. The pneumorrachis per se is an underdiagnosed entity as most of the patients are asymptomatic or have subclinical symptoms. The spontaneous occurrence of pneumorrachis has been reported in literature but giant spontaneous occurrence causing cauda equina syndrome has not been reported so far. CASE PRESENTATION: We report a case of 56-year-old male patient who came to our OPD on wheelchair with complains of difficulty in walking for 6 months with dribbling of urine for 2 months with on and off back pain. His perianal sensation was reduced with absent voluntary anal contraction. Imaging revealed giant air pockets in the spinal canal of L5-S1 extending upto L4-L5. It was managed surgically wherein laminectomy without fusion was done. The patient responded well to the treatment. DISCUSSION: There are many causes of pneumorrachis described in literature. Most of the cases of pneumorrachis are asymptomatic and incidentally diagnosed. With the improvement in radio-diagnostic modalities, the diagnosis of pneumorrachis can be easily established. When symptomatic, they can be managed conservatively. Those presenting with neurological deficit may require surgical intervention or other invasive intervention.

AI-Assisted Treatment Planning for Dental Implant Placement: Clinical vs AI-Generated Plans.

Background: Dental implant placement is a critical procedure in modern dentistry, requiring precise treatment planning to ensure successful outcomes. Traditionally, treatment planning has relied on the expertise of clinicians, but recent advancements in artificial intelligence (AI) have opened up the possibility of AI-assisted treatment planning. Materials and Methods: Twenty patients requiring dental implant placement were included in this comparative study. For each patient, a clinical treatment plan was created by an experienced dentist, while an AI algorithm, trained on a dataset of implant placement cases, generated an alternative plan. Various parameters, including implant position, angulation, and depth, were compared between the two plans. Surgical templates were fabricated based on both plans to guide implant placement accurately. Results: The results of this study indicate that AI-generated treatment plans closely align with clinical plans in terms of implant positioning, angulation, and depth. Mean discrepancies of less than 1 mm and 2 degrees were observed for implant position and angulation, respectively, between the two planning methods. The AI-generated plans also showed a reduction in planning time, averaging 10 min compared to the clinical planning, which averaged 30 min per case. Additionally, the surgical templates based on AI-generated plans exhibited similar accuracy in implant placement as those based on clinical plans. Conclusion: AI-assisted treatment planning for dental implant placement demonstrates promising results in terms of accuracy and efficiency.

Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells. Transfer learning using transcriptional data from patient-derived organoid and CAF cocultures provided in silico validation of CAF induction of inflammatory and EMT epithelial cell states. Further experimental validation in cocultures demonstrated integrin beta 1 (ITGB1) and vascular endothelial factor A (VEGFA) interactions with neuropilin-1 mediating CAF-epithelial cell cross-talk. Together, this study introduces transfer learning from human single-cell data to organoid coculture analyses for experimental validation of discoveries of cell-cell cross-talk and identifies fibroblast-mediated regulation of EMT and inflammation. SIGNIFICANCE: Adaptation of transfer learning to relate human single-cell RNA sequencing data to organoid-CAF cocultures facilitates discovery of human pancreatic cancer intercellular interactions and uncovers cross-talk between CAFs and tumor cells through VEGFA and ITGB1.

Lumbar Transforaminal Injection of Steroids versus Platelet-Rich Plasma for Prolapse Lumbar Intervertebral Disc with Radiculopathy: A Randomized Double-Blind Controlled Pilot Study.

STUDY DESIGN: Double-blind randomized controlled pilot study. PURPOSE: The purpose of this study was to compare outcomes of steroids with autologous platelet-rich plasma (PRP) administered by lumbar transforaminal injection (LTI) in patients with lumbar radiculopathy. OVERVIEW OF LITERATURE: Degenerative disc disease of the lumbar spine is one of the most common conditions managed by spine surgeons in routine practice. Once conservative management fails, LTI is diagnostic and often therapeutic. Steroids are the gold standard drug used for LTI but have limitations and side effects. METHODS: In this single-center double-blind randomized controlled pilot study, 46 patients were recruited and randomized by the lottery method. The Visual Analog Scale (VAS) for leg pain, modified Oswestry Disability Index (mODI), and Short-Form 12 (SF-12) were assessed at 1 week, 3 weeks, 6 weeks, 6 months, and 1 year. RESULTS: Both groups were comparable in terms of demographics, preprocedure VAS scores, mODI, and SF-12 scores (p=0.52). At the 1-week follow-up, the steroid group had significantly better improvement than the PRP group (p=0.0001). At the 3-week follow-up, both groups showed comparable outcomes; however, the PRP group had better symptom improvement. At 6 weeks and 6 months, the PRP group had better outcomes (VAS, p<0.0001; ODI, p=0.02; SF-12, p=0.002). Moreover, 17 and 16 patients in the steroid and PRP groups underwent repeat LTI with steroids or surgery because of pain recurrence during follow-up. At 1 year, no difference in outcomes was observed. CONCLUSIONS: PRP may be a useful alternative to steroids for LTI in lumbar radiculopathy. Although improvement was delayed and 1-year outcomes were comparable, the 6-week and 6-month outcomes were better with PRP than with LTI. Multiple PRP injections may be beneficial because of its autologous nature. However, further studies with a larger number of participants, longer follow-up, and repeat LTIs are warranted to draw definite conclusions.

Evaluating the Use of ChatGPT to Accurately Simplify Patient-centered Information about Breast Cancer Prevention and Screening.

Purpose To evaluate the use of ChatGPT as a tool to simplify answers to common questions about breast cancer prevention and screening. Materials and Methods In this retrospective, exploratory study, ChatGPT was requested to simplify responses to 25 questions about breast cancer to a sixth-grade reading level in March and August 2023. Simplified responses were evaluated for clinical appropriateness. All original and simplified responses were assessed for reading ease on the Flesch Reading Ease Index and for readability on five scales: Flesch-Kincaid Grade Level, Gunning Fog Index, Coleman-Liau Index, Automated Readability Index, and the Simple Measure of Gobbledygook (ie, SMOG) Index. Mean reading ease, readability, and word count were compared between original and simplified responses using paired t tests. McNemar test was used to compare the proportion of responses with adequate reading ease (score of 60 or greater) and readability (sixth-grade level). Results ChatGPT improved mean reading ease (original responses, 46 vs simplified responses, 70; P < .001) and readability (original, grade 13 vs simplified, grade 8.9; P < .001) and decreased word count (original, 193 vs simplified, 173; P < .001). Ninety-two percent (23 of 25) of simplified responses were considered clinically appropriate. All 25 (100%) simplified responses met criteria for adequate reading ease, compared with only two of 25 original responses (P < .001). Two of the 25 simplified responses (8%) met criteria for adequate readability. Conclusion ChatGPT simplified answers to common breast cancer screening and prevention questions by improving the readability by four grade levels, though the potential to produce incorrect information necessitates physician oversight when using this tool. Keywords: Mammography, Screening, Informatics, Breast, Education, Health Policy and Practice, Oncology, Technology Assessment Supplemental material is available for this article. © RSNA, 2023.

A Three-year Retrospective Study Looking at Preventing Hospital Acquired Thrombosis.

BACKGROUND: Hospital-acquired venous thromboembolism (HA-VTE) is defined as cases of venous thromboembolism (VTE) that occur in a hospital and within ninety days of a hospital admission. Deep vein thromboses (DVTs) most commonly occur within the deep veins of the pelvis and legs. If the thrombus dislodges and travels to the lungs, it can result in a pulmonary embolus (PE). VTE is associated with significant morbidity and mortality, accounting for almost 10% of all hospital deaths. If risk factors are correctly identified and VTE prophylaxis is prescribed, VTE can be a preventable condition. In 2010, NHS England launched The National Venous Thromboembolism Prevention Programme. This included NICE guidance, and a VTE risk assessment tool, which must be completed for at least 95% of patients on admission. The National Thrombosis Survey, published by Thrombosis UK, studied how this program was implemented locally, and audited HA-VTE prevention strategies nationally. OBJECTIVES: Using the Thrombosis Survey and NICE guidance as an aide, this study collects data about hospital-acquired DVT (HA-DVT) at the Queen Elizabeth Hospital in Gateshead (QEH) and aims to: 1. Identify cases of HA-DVT and understand the clinical circumstances surrounding these cases 2. Assess the quality of VTE preventative measures at QEH 3. Outline potential improvement in reducing the incidence of HA-VTE at this hospital Methods: This retrospective cohort study used electronic records to identify all cases of DVT between April 2019 and April 2022 at QEH. Cases of HA-DVT were defined as: a positive ultrasound doppler report and either the case occurring in the 90 days following an inpatient stay, or beyond two days into an admission. For these cases of HA-DVT, we recorded the: reason for admission; admitting specialty; presence of an underlying active cancer and deaths occurring within 90 days of diagnosis. We assessed the quality of VTE preventative measures, by recording the: completion of VTE risk assessments; prescription of weight-adjusted pharmacological VTE prophylaxis and provision of VTE prophylaxis on discharge. For HA-DVT cases occurring within 90 days of an inpatient stay, the preventative measures were assessed on the original admission. Electronic records were used to record the completion rate of the National VTE risk assessment tool for all inpatients during this time frame. RESULTS: The VTE risk assessment tool was completed for 98.5% of all admissions. One hundred and thirty-five cases of HA-DVT were identified between April 2019 and April 2022. Sixteen patients with HA-DVT did not have VTE prophylaxis prescribed on admission. Eleven of these patients had a clearly documented reason why anticoagulation was avoided. In HA-DVT cases where pharmacological VTE prophylaxis was prescribed, 23% were prescribed an inappropriate dose for their weight. If anticoagulation was required on discharge, this was prescribed appropriately in 94% of cases. About 31% of the patients with HA-DVT had an underlying active malignancy. Thirty-nine patients died within 90 days of the DVT being diagnosed; in only 1 case was VTE thought to be a contributing factor to death. CONCLUSION: The hospital exceeded the national standard of VTE risk assessment completion on admission (greater than 95%). For almost a quarter of patients with HA-DVT, the dose of thromboprophylaxis prescribed was not appropriate for weight. In five cases of HA-DVT, thromboprophylaxis was omitted with no clear justification. HA-DVT often affects the most clinically vulnerable patients and is associated with a high mortality.

Is FAST FORWARD the Way Forward in Radiotherapy for Locally Advanced Breast Cancer - Learnings From the COVID Pandemic.

INTRODUCTION: Low middle-income countries (LMICs), including India, have paucity of external beam radiotherapy (RT) machines leading to prolonged wait times for RT. Delay in delivery of RT has been shown to adversely affect outcomes in locally advanced breast cancer (LABC). With the availability of results of multiple randomized controlled trials, hypofractionated RT delivered over 3 to 4 weeks became the standard of care in breast cancer RT. METHODS: We conducted a retrospective audit of 172 LABC patients treated with ultrahypofractionated adjuvant RT (radiotherapy completed in 1 week) during the COVID pandemic. Log rank and Cox-regression model used for univariate and multi-variate analyses. RESULTS: No patient developed grade 3 esophagitis. Grade 2 esophagitis requiring short term narcotic analgesics was seen in 12 (6.9%) patients. Grade 2 or higher toxicity peaked between 2 and 3 weeks after RT. The estimated 2 and 3- year recurrence free survival (RFS) for the cohort is 87.1 % and 81.4 %, respectively. The estimated 2 and 3-year overall survival for the cohort is 95% and 91.3%. On multivariate analysis, presence of extra-nodal extension was found to be an independent factor associated with worse RFS (P = .028). CONCLUSIONS: FAST FORWARD protocol RT in LABC appears well tolerated.

Pattern of Care and Outcomes of Gallbladder Cancer Patients: Retrospective Study from a High Incidence Region in India.

Lakhan KasyapIntroduction Gallbladder cancer (GBC) is the 20th most common cancer in India with a crude incidence rate of 2.3 per 100,000 persons. Of note, it is relatively common in states which fall in the Gangetic plains. Patients often present in the advanced stage and have an unfavorable prognosis. Materials and Methods From January to June 2021, 170 treatment-naive GBC (adenocarcinoma) patients who were registered at a tertiary care cancer center in North India, were included. Data were extracted from electronic medical records and was analyzed with SPSS. Results Median age was 56 years (range 32-77 years) and 65.5% ( n = 112) were female. Incidental GBC was found in 20% patient ( n = 34). Majority of patients (79.4%, n = 135) had preserved performance status. Advanced GBC was present in 85.8% ( n = 146) patients (locally advanced = 37.0% and metastatic = 48.8%). Biliary drainage procedure was performed in 24% of patients (68% of patients with obstructive jaundice). More than half of patients (53.5%) were lost to follow-up without any treatment. There were 33 patients (19.4%) who underwent surgery and 20 of them received neoadjuvant chemotherapy. Adjuvant chemotherapy and adjuvant radiotherapy were received by 13 and 2 patients, respectively. Palliative chemotherapy was administered to 46 patients. The most common chemotherapy regimen was gemcitabine-cisplatin. At a median follow-up of 1.7 months (95% confidence interval, 1-2.4 months), 42 patients (24%) progressed and 24 patients (14%) died, with 6 months estimated progression-free survival and overall survival being 60.2 and 79%, respectively. Conclusion GBC is an aggressive and lethal malignancy predominantly affecting females in the fifth decade with dismal outcomes. Improved access to health care, an aggressive approach in operable cases, and optimization of systemic and adjuvant therapy are the need of the hour.

Gestational Trophoblastic Neoplasia-A Retrospective Analysis of Patients Treated at a Tertiary Care Oncology Center in North India.

Anuj GuptaObjectives The aim of this study was to do a retrospective analysis of patients of gestational trophoblastic neoplasia (GTN) treated at our center concerning their clinical features and treatment outcomes. Materials and Methods Patients diagnosed and treated from May 2018 to December 2021 were included. All relevant information pertaining to eligible patients was retrieved from the electronic medical records. Patients were risk-stratified based on the World Health Organization (WHO) risk scoring system with a score of seven and above being classified into the high-risk category. Patients were monitored for response by measuring ß-human chorionic gonadotrophin (ß-HCG) levels before each consecutive cycle. Statistical Analysis Appropriate statistical analysis was performed using SPSS version 26. Results Records of 39 eligible patients were analyzed for clinical features out of which 38 were eligible for response assessment. The median age of presentation was 28 years with the majority of patients (79.4%) diagnosed based on ß-HCG levels and clinical history alone. The most common symptom was bleeding per vagina (64%), while the majority of antecedent pregnancies were abortions (59%). Of the 14 low-risk category patients, 12 received single-agent methotrexate/actinomycin D, while 2 received etoposide, methotrexate actinomycin D (EMACO) regimen. Overall response rates were 85.7% with the others responding to the second-line EMACO regimen. Five patients in this group had a WHO score of 5 or 6 and all of them responded to single-agent treatment. Among the 25 high-risk category patients, all received the EMACO regimen with high-dose methotrexate added to those with brain metastasis. The response rate was 87.5% with all the nonresponders having features of ultra-high risk of liver/brain metastasis and/or a WHO score of more than 12. While one nonresponder had expired despite treatment, the other two responded to the etoposide methotrexate and actinomycin D/ etoposide and cisplatin regimen. Conclusion Our results are in consonance with other reported studies. The subcategories of low-risk GTN with a WHO score of 5 and 6 and high-risk GTN with ultra-high-risk features deserve further research in the form of multicenter prospective studies.

MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression.

Increased mitochondrial function may render some cancers vulnerable to mitochondrial inhibitors. Since mitochondrial function is regulated partly by mitochondrial DNA copy number (mtDNAcn), accurate measurements of mtDNAcn could help reveal which cancers are driven by increased mitochondrial function and may be candidates for mitochondrial inhibition. However, prior studies have employed bulk macrodissections that fail to account for cell type-specific or tumor cell heterogeneity in mtDNAcn. These studies have often produced unclear results, particularly in prostate cancer. Herein, we developed a multiplex in situ method to spatially quantify cell type-specific mtDNAcn. We show that mtDNAcn is increased in luminal cells of high-grade prostatic intraepithelial neoplasia (HGPIN), is increased in prostatic adenocarcinomas (PCa), and is further elevated in metastatic castration-resistant prostate cancer. Increased PCa mtDNAcn was validated by 2 orthogonal methods and is accompanied by increases in mtRNAs and enzymatic activity. Mechanistically, MYC inhibition in prostate cancer cells decreases mtDNA replication and expression of several mtDNA replication genes, and MYC activation in the mouse prostate leads to increased mtDNA levels in the neoplastic prostate cells. Our in situ approach also revealed elevated mtDNAcn in precancerous lesions of the pancreas and colon/rectum, demonstrating generalization across cancer types using clinical tissue samples.

Convergent alterations in the tumor microenvironment of MYC-driven human and murine prostate cancer.

The tissue microenvironment in prostate cancer is profoundly altered. While such alterations have been implicated in driving prostate cancer initiation and progression to aggressive disease, how prostate cancer cells and their precursors mediate those changes is unclear, in part due to the inability to longitudinally study the disease evolution in human tissues. To overcome this limitation, we performed extensive single-cell RNA-sequencing (scRNA-seq) and rigorous molecular pathology of the comparative biology between human prostate cancer and key time points in the disease evolution of a genetically engineered mouse model (GEMM) of prostate cancer. Our studies of human tissues, with validation in a large external data set, revealed that cancer cell-intrinsic activation of MYC signaling was the top up-regulated pathway in human cancers, representing a common denominator across the well-known molecular and pathological heterogeneity of human prostate cancer. Likewise, numerous non-malignant cell states in the tumor microenvironment (TME), including non-cancerous epithelial, immune, and fibroblast cell compartments, were conserved across individuals, raising the possibility that these cell types may be a sequelae of the convergent MYC activation in the cancer cells. To test this hypothesis, we employed a GEMM of prostate epithelial cell-specific MYC activation in two mouse strains. Cell communication network and pathway analyses suggested that MYC oncogene-expressing neoplastic cells, directly and indirectly, reprogrammed the TME during carcinogenesis, leading to the emergence of cascading cell state alterations in neighboring epithelial, immune, and fibroblast cell types that paralleled key findings in human prostate cancer. Importantly, among these changes, the progression from a precursor-enriched to invasive-cancer-enriched state was accompanied by a cell-intrinsic switch from pro-immunogenic to immunosuppressive transcriptional programs with coinciding enrichment of immunosuppressive myeloid and Treg cells in the immune microenvironment. These findings implicate activation of MYC signaling in reshaping convergent aspects of the TME of prostate cancer as a common denominator across the otherwise well-documented molecular heterogeneity of human prostate cancer.

Somatic mutations reveal hyperactive Notch signaling and racial disparities in prurigo nodularis.

Prurigo nodularis (PN) is a chronic inflammatory skin disease that disproportionately affects African Americans and is characterized by pruritic skin nodules of unknown etiology. Little is known about genetic alterations in PN pathogenesis, especially relating to somatic events which are often implicated in inflammatory conditions. We thus performed whole-exome sequencing on 54 lesional and nonlesional skin biopsies from 17 PN patients and 10 atopic dermatitis (AD) patients for comparison. Somatic mutational analysis revealed that PN lesional skin harbors pervasive somatic mutations in fibrotic, neurotropic, and cancer-associated genes. Nonsynonymous mutations were most frequent in NOTCH1 and the Notch signaling pathway, a regulator of cellular proliferation and tissue fibrosis, and NOTCH1 mutations were absent in AD. Somatic copy-number analysis, combined with expression data, showed that recurrently deleted and downregulated genes in PN lesional skin are associated with axonal guidance and extension. Follow-up immunofluorescence validation demonstrated increased NOTCH1 expression in PN lesional skin fibroblasts and increased Notch signaling in PN lesional dermis. Finally, multi-center data revealed a significantly increased risk of NOTCH1-associated diseases in PN patients. In characterizing the somatic landscape of PN, we uncover novel insights into its pathophysiology and identify a role for dysregulated Notch signaling in PN.

Incurable advanced salivary gland tumours: a retrospective analysis and peek into the perplexing clinical and molecular intricacies from a tertiary care centre in India.

Background: Salivary gland tumours are rare cancers with variable course and prognosis. There is a paucity of data, especially for the advanced stages. Materials and methods: This is a retrospective analysis carried out in our institute. All patients seeking treatment for incurable advanced salivary gland tumours from October 2018 to September 2022 were included. Relevant clinical data were collected and appropriate statistical analysis was applied. Results: 30 patients were included in the analysis. The parotid gland was the most common site of origin (73%). Adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC) were equally (37%) the most common pathological subtypes. The majority of patients were males (73%) and lungs (57%) were the most common site of metastases. On molecular analysis, SDC had high rates of androgen receptor (AR) (90%) and human epidermal growth factor receptor 2 (HER2) (55%) positivity. Mucoepidermoid carcinoma (MEC) had AR and HER2 positivity rates of 17% and 20%, respectively, while for ACC it was even lower. A variety of treatment regimens including hormonal therapy, anti-HER2 targeted therapy and chemotherapy were used in first-line treatment. With an overall response rate (ORR) of 10/21 (48%), only 9/21 (43%) went on to receive second-line treatment with an ORR of 4/9 (44%). The progression-free survival (PFS) with first-line treatment (PFS1) was a median of 5 months. The median PFS1 was worst for MEC. The median overall survival (OS) was 10 months. Median OS for ACC, SDC and MEC were 11, 10 and 7 months, respectively. At 24 months, ACC had much higher survival (50%) than others (10%) indicating a proportion of ACC with an indolent course. Conclusion: Our analysis highlights the variable disease biology of advanced salivary gland tumours and throws light on the various possible treatment targets and strategies. Molecular profiling and advancement in targeted therapies are expected to increase survival in this group of rare cancers.

Intravenous BCG vaccination reduces SARS-CoV-2 severity and promotes extensive reprogramming of lung immune cells.

Bacillus Calmette-Guérin (BCG) confers heterologous immune protection against viral infections and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here, we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model. BCG vaccination conferred a modest reduction on lung SCV2 viral load, bronchopneumonia scores, and weight loss, accompanied by a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. BCG uniquely recruited immunoglobulin-producing plasma cells to the lung suggesting accelerated local antibody production. BCG vaccination also recruited elevated levels of Th1, Th17, Treg, CTLs, and Tmem cells, with a transcriptional shift away from exhaustion markers and toward antigen presentation and repair. Similarly, BCG enhanced recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, that show reduced IFN-associated gene expression. Our observations indicate that BCG vaccination protects against SCV2 immunopathology by promoting early lung immunoglobulin production and immunotolerizing transcriptional patterns among key myeloid and lymphoid populations.

Retrotransposon LINE-1 bodies in the cytoplasm of piRNA-deficient mouse spermatocytes: Ribonucleoproteins overcoming the integrated stress response.

Transposable elements (TE) are mobile DNA sequences whose excessive proliferation endangers the host. Although animals have evolved robust TE-targeting defenses, including Piwi-interacting (pi)RNAs, retrotransposon LINE-1 (L1) still thrives in humans and mice. To gain insights into L1 endurance, we characterized L1 Bodies (LBs) and ORF1p complexes in germ cells of piRNA-deficient Maelstrom null mice. We report that ORF1p interacts with TE RNAs, genic mRNAs, and stress granule proteins, consistent with earlier studies. We also show that ORF1p associates with the CCR4-NOT deadenylation complex and PRKRA, a Protein Kinase R factor. Despite ORF1p interactions with these negative regulators of RNA expression, the stability and translation of LB-localized mRNAs remain unchanged. To scrutinize these findings, we studied the effects of PRKRA on L1 in cultured cells and showed that it elevates ORF1p levels and L1 retrotransposition. These results suggest that ORF1p-driven condensates promote L1 propagation, without affecting the metabolism of endogenous RNAs.

Cardiac Catheterization via Direct Access of Venoarterial Extracorporeal Membrane Oxygenation Circuit.

Obtaining arterial access for cardiac catheterization can be both challenging and morbid in patients supported by venoarterial extracorporeal membrane oxygenation (VA-ECMO). While catheterization performed by obtaining endovascular access through the ECMO circuit itself has been described, all previous cases utilized a Y-connector and accessory tubing limb. We report a novel technique whereby arterial access was obtained directly via standard VA-ECMO arterial return tubing, through which coronary angiography was successfully performed in a 67-year-old woman. This technique may reduce the incidence of morbidity attendant with obtaining vascular accesses in patients on ECMO without requiring insertion of new circuit components.

Corrigendum: Convergent antibody responses are associated with broad neutralization of hepatitis C virus.

[This corrects the article DOI: 10.3389/fimmu.2023.1135841.].