Complete Response to Pembrolizumab in Stage IV Alveolar Soft Part Sarcoma After Failure of Four Lines of Treatment: A Case Report and Literature Review.

Alveolar soft part sarcoma (ASPS) is a rare malignant tumor that manifests as a slow-growing soft tissue mass and frequently presents with distant metastasis. The prognosis is variable, and complete remission of metastatic disease has rarely been reported. Our patient was diagnosed with metastatic ASPS at the age of 17, with a primary forearm lesion and metastasis to the lungs. She underwent surgical resection of her forearm mass, followed by adjuvant chemotherapy and radiation to target the lung metastasis. Over the next decade, she had a complicated course of treatment. Her disease continued to slowly progress despite treatment with sunitinib, pazopanib, and a combination of docetaxel and gemcitabine. We eventually treated her with immune checkpoint inhibitors (ICIs). Pembrolizumab, initially in combination with bevacizumab and later as monotherapy, resulted in significant tumor shrinkage, especially in the pulmonary lesions, within the first three months. Subsequent imaging reported complete remission within 15 months and no disease recurrence at her three-year follow-up. Our case highlights one of the very few reported cases of complete remission achieved in metastatic ASPS after treatment with ICIs. ICIs could offer hope for disease remission in advanced ASPS, a rare malignancy that has proven difficult to treat successfully in the past. More studies need to be conducted to further evaluate the efficacy and any associated predictors of successful treatment.

A comparative analysis of RNA-Seq and NanoString technologies in deciphering viral infection response in upper airway lung organoids.

In this study, we delved into the comparative analysis of gene expression data across RNA-Seq and NanoString platforms. While RNA-Seq covered 19,671 genes and NanoString targeted 773 genes associated with immune responses to viruses, our primary focus was on the 754 genes found in both platforms. Our experiment involved 16 different infection conditions, with samples derived from 3D airway organ-tissue equivalents subjected to three virus types, influenza A virus (IAV), human metapneumovirus (MPV), and parainfluenza virus 3 (PIV3). Post-infection measurements, after UV (inactive virus) and Non-UV (active virus) treatments, were recorded at 24-h and 72-h intervals. Including untreated and Mock-infected OTEs as control groups enabled differentiating changes induced by the virus from those arising due to procedural elements. Through a series of methodological approaches (including Spearman correlation, Distance correlation, Bland-Altman analysis, Generalized Linear Models Huber regression, the Magnitude-Altitude Score (MAS) algorithm and Gene Ontology analysis) the study meticulously contrasted RNA-Seq and NanoString datasets. The Magnitude-Altitude Score algorithm, which integrates both the amplitude of gene expression changes (magnitude) and their statistical relevance (altitude), offers a comprehensive tool for prioritizing genes based on their differential expression profiles in specific viral infection conditions. We observed a strong congruence between the platforms, especially in identifying key antiviral defense genes. Both platforms consistently highlighted genes including ISG15, MX1, RSAD2, and members of the OAS family (OAS1, OAS2, OAS3). The IFIT proteins (IFIT1, IFIT2, IFIT3) were emphasized for their crucial role in counteracting viral replication by both platforms. Additionally, CXCL10 and CXCL11 were pinpointed, shedding light on the organ tissue equivalent's innate immune response to viral infections. While both platforms provided invaluable insights into the genetic landscape of organoids under viral infection, the NanoString platform often presented a more detailed picture in situations where RNA-Seq signals were more subtle. The combined data from both platforms emphasize their joint value in advancing our understanding of viral impacts on lung organoids.

Systemic oncological therapy in breast cancer patients on dialysis.

The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease (ESRD) over time. However, this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer. Breast cancer treatment typically involves surgery, radiation, and systemic therapies, with approaches tailored to cancer type, stage, and patient preferences. However, renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions. This review emphasizes the need for optimized dosing and administration strategies for systemic breast cancer treatments in dialysis patients, aiming to ensure both efficacy and safety. Additionally, challenges in breast cancer screening and diagnosis in this population, including soft-tissue calcifications, are highlighted.

Primary Renal Lymphoma: A Rare Cause of Bilateral Renal Enlargement and Acute Renal Failure in a Patient With Rheumatoid Arthritis.

Primary renal lymphoma (PRL) is a rare non-Hodgkin's lymphoma (NHL) involving the kidneys without evidence of extra-renal involvement. We describe a 66-year-old female who presented with bilateral pleural effusions, and acute renal failure and was diagnosed with primary renal diffuse large B-cell lymphoma (DLBCL). She presented with shortness of breath due to bilateral pleural effusions and acute renal failure. Computed tomography (CT) of the chest reported bilateral pleural effusions. Thoracocentesis and subsequent fluid analysis reported non-malignant effusion. Her kidney function worsened during her hospital stay, requiring dialysis. Nonspecific findings such as bilateral renal enlargement on imaging prompted a renal biopsy. Histopathology reported mixed tubulointerstitial atypical lymphocytic CD 20 and BCL-6 positive cell infiltrates, confirming non-Hodgkin diffuse large B-cell lymphoma. Whole-body positron emission tomography/CT (PET/CT) and brain magnetic resonance imaging (MRI) ruled out the involvement of any other organs or lymph nodes, confirming our diagnosis of PRL. She was treated with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Her kidney function recovered fully and remained normal at the one-year follow-up. We highlight the importance of recognizing PRL as an underlying cause of renal failure and its association with autoimmune diseases. Prompt investigation with timely diagnosis and treatment can result in improved morbidity and mortality in these patients.

Metastatic Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans With Lung Metastasis: A Case Report.

Dermatofibrosarcoma protuberans (DFSP) is a low- to intermediate-grade dermal soft tissue malignant tumor (sarcoma) with a high local recurrence rate but low metastatic potential. DFSP is characterized by uniform spindle cell fascicles arranged classically in a storiform pattern and by CD34 immunoreactivity. On gross examination, DFSP usually manifests as a white or yellow soft tissue mass with a smooth outer surface and poor circumscription. In this study, we report a case of DFSP with fibrosarcomatous transformation, a rare but well-known phenomenon encountered in DFSP that is correlated with an increased risk of adverse outcomes in patients with DFSP. A 45-year-old male presented with a progressively enlarging lump on his left shoulder, initially suspected of being a lipoma but diagnosed as a fibrosarcomatous transformation of DFSP. Surgical resection was performed, with the subsequent identification of metastatic sarcoma in pulmonary nodules. Robotic-assisted thoracoscopy excised the nodules, confirming metastatic sarcoma with aggressive behavior. Despite negative adjuvant treatment plans, the patient remains under surveillance with imaging, showing no recurrence in recent scans. Continued follow-up with medical and surgical oncology is planned. DFSP is a rare soft tissue sarcoma characterized by indolent growth and low metastatic potential, except in fibrosarcomatous transformation cases. Molecularly, DFSP is defined by a COL1A1-PDGFB fusion transcript that is targetable with imatinib therapy. Treatment involves wide surgical resection, with adjuvant radiation therapy in select cases. Radiation therapy may be employed in cases with close or positive margins, while conventional chemotherapy has limited utility. Multidisciplinary collaboration is crucial for optimal management. Overall, this case underscores the challenges in diagnosing and managing aggressive sarcomas like fibrosarcomatous DFSP, emphasizing the importance of vigilant surveillance and multidisciplinary collaboration in optimizing patient outcomes. Further research is needed to understand the mechanisms underlying fibrosarcomatous transformation and to explore novel therapeutic avenues for this challenging malignancy.

B cells in perivascular and peribronchiolar granuloma-associated lymphoid tissue and B-cell signatures identify asymptomatic Mycobacterium tuberculosis lung infection in Diversity Outbred mice.

Because most humans resist Mycobacterium tuberculosis infection, there is a paucity of lung samples to study. To address this gap, we infected Diversity Outbred mice with M. tuberculosis and studied the lungs of mice in different disease states. After a low-dose aerosol infection, progressors succumbed to acute, inflammatory lung disease within 60 days, while controllers maintained asymptomatic infection for at least 60 days, and then developed chronic pulmonary tuberculosis (TB) lasting months to more than 1 year. Here, we identified features of asymptomatic M. tuberculosis infection by applying computational and statistical approaches to multimodal data sets. Cytokines and anti-M. tuberculosis cell wall antibodies discriminated progressors vs controllers with chronic pulmonary TB but could not classify mice with asymptomatic infection. However, a novel deep-learning neural network trained on lung granuloma images was able to accurately classify asymptomatically infected lungs vs acute pulmonary TB in progressors vs chronic pulmonary TB in controllers, and discrimination was based on perivascular and peribronchiolar lymphocytes. Because the discriminatory lesion was rich in lymphocytes and CD4 T cell-mediated immunity is required for resistance, we expected CD4 T-cell genes would be elevated in asymptomatic infection. However, the significantly different, highly expressed genes were from B-cell pathways (e.g., Bank1, Cd19, Cd79, Fcmr, Ms4a1, Pax5, and H2-Ob), and CD20+ B cells were enriched in the perivascular and peribronchiolar regions of mice with asymptomatic M. tuberculosis infection. Together, these results indicate that genetically controlled B-cell responses are important for establishing asymptomatic M. tuberculosis lung infection.

Clinical Presentation, Tumor Characteristics, and Management of Intradiverticular Transitional Cell Carcinoma of the Urinary Bladder: A Systematic Review.

Intradiverticular transitional cell carcinoma (TCC) of the bladder poses unique challenges due to its presentation within the bladder diverticula. This review synthesizes current knowledge on the diagnosis and management of this condition, emphasizing the need for early detection to optimize patient outcomes. The literature underscores the importance of tailored treatment strategies, ranging from radical surgeries to adjuvant chemotherapy, to combat the aggressive nature of intradiverticular TCC. Additionally, stringent post-treatment surveillance protocols are vital in addressing high recurrence rates. Future research directions include biomarker identification, comparative efficacy studies of treatment modalities, and the exploration of innovative therapeutic approaches such as immunotherapy. Longitudinal studies analyzing patient outcomes will provide valuable insights into survival rates and quality of life post-treatment, informing future clinical guidelines. This comprehensive review aims to enhance understanding and management strategies for intradiverticular TCC, paving the way for improved patient care and outcomes in this challenging form of bladder cancer.

Beyond Midostaurin: Role of Avapritinib in Managing Systemic Mastocytosis.

We present a case of an adult male who presented with pancytopenia accompanied by symptomatic anemia, necessitating chronic transfusions. He was diagnosed with systemic mastocytosis with an associated hematologic neoplasm. Following an inadequate response to midostaurin therapy, the patient was initiated on the newly approved avapritinib. The patient showed significant improvements in all three blood cell lines; however, he developed leg edema, blepharedema, and gum bleeding on this medication. This case underscores the intricacies of managing a patient with advanced systemic mastocytosis, the emerging role of highly selective KIT inhibition in its treatment, and the practical management of adverse medication effects.

Hypercalcemia and Bone Metastasis in a Case of Large Cell Neuroendocrine Carcinoma With Unknown Primary.

Large cell neuroendocrine carcinoma (LCNEC) constitutes a rare subset of highly undifferentiated malignancies known for their aggressive nature. Although these tumors commonly originate in the lungs and gastrointestinal tract, their potential occurrence is not restricted to specific anatomical sites, giving rise to a variety of symptoms. Notably, cases of neuroendocrine tumors (NETs) with an unidentified primary source exhibit a graver prognosis and shorter survival periods compared to those with clearly identified origins. NETs frequently demonstrate a propensity to metastasize, spreading to diverse anatomical regions such as the liver, lungs, lymph nodes, and bones, illustrating their aggressive nature and the complexity of their management. In this context, we present the case of a 59-year-old male who sought medical attention in the emergency department due to right upper quadrant (RUQ) abdominal pain. Initial diagnostic assessments revealed significantly elevated liver function tests and severe hypercalcemia. A right upper quadrant ultrasound (RUQ US) was subsequently performed, which revealed heterogeneous hepatic echotexture with innumerable echogenic masses, suggesting a metastatic process. A computed tomography (CT) scan was then ordered to evaluate further the RUQ US findings, which showed numerous hypovascular liver masses, raising concerns of malignancy. A liver biopsy confirmed a diagnosis of LCNEC with an unidentified primary source.

Epigastric Pain and Dysphagia in a 36-Year-Old Man Due to Primary Esophageal Small Cell Carcinoma.

BACKGROUND Small cell carcinoma is an aggressive malignant neuroendocrine tumor that most commonly occurs in the lung. Primary small cell carcinoma of the esophagus (PSCCE) is rare and is an aggressive malignancy with poor prognosis and no clear management guidelines. This report describes the case of a 36-year-old man presenting with epigastric pain, dysphagia, and melena due to a primary esophageal small cell carcinoma. CASE REPORT A 36-year-old presented to the Emergency Department (ED) with epigastric pain associated with food intake. Initial workup was unremarkable, and a presumed clinical diagnosis of reflux esophagitis and peptic strictures was made, prompting empiric treatment with anti-secretory therapies. Despite these therapies, he presented to the emergency room with progressively worsening dysphagia. Endoscopic examination (EGD) revealed a large necrotic mass, and computed tomography (CT) imaging revealed liver metastasis. Biopsies from both the liver and esophageal masses confirmed small cell carcinoma. His clinical course was complicated by a broncho-esophageal fistula, leading to massive hemoptysis, necessitating intubation. Unfortunately, his condition deteriorated rapidly, and he chose to pursue hospice care. He died 3 months after his initial presentation. CONCLUSIONS This report has presented a rare case of primary esophageal small cell carcinoma and our approach to management. We highlight the importance of early diagnosis, supported by histopathology, and the need for management guidelines.

Acute cardiovascular complications of disseminated intravascular coagulation in acute myeloid leukemia.

BACKGROUND: Disseminated intravascular coagulation (DIC) is a common complication of all leukemia subtypes, but it is an especially prominent feature of Acute Myeloid Leukemias (AML). DIC complicating AML can lead to a variety of complications, however, its association with acute cardiovascular complications has not been reported before. METHODS: National Inpatient Sample Database was used to procure individuals with AML, and baseline demographics and comorbidities were collected using ICD-10-DM codes. Patients were stratified into those with and without DIC. Greedy propensity matching using R was performed to match the two cohorts in 1:1 ratio on age, gender, and fifteen other baseline comorbidities. Univariate analysis pre and post-match along with binary logistic regression analysis post-match were used to analyze outcomes. RESULTS: Out of a total of 37,344 patients with AML, 996 had DIC. DIC patients were younger, predominantly males, and had lower prevalence of baseline cardiovascular comorbidities. DIC patients had statistically significant higher mortality (30.2 % vs 7.8 %), acute myocardial infarction (5.1 % vs 1.8 %), acute pulmonary edema (2.3 % vs 0.7 %), cardiac arrest (6.4 % vs 0.9 %), and acute DVT/PE (6.6 % vs 2.7 %). Logistic regression model after matching showed similar outcomes along with significantly higher rates of acute heart failure in DIC patients. CONCLUSION: These findings highlight the importance of close cardiovascular monitoring and prompt recognition of complications in AML patients with DIC. The underlying mechanisms involve a complex interplay of procoagulant factors, cytokine release, and endothelial dysfunction. Further studies are needed to develop targeted interventions for prevention and management of these complications.

Predicting response to neoadjuvant chemotherapy for colorectal liver metastasis using deep learning on prechemotherapy cross-sectional imaging.

BACKGROUND AND OBJECTIVES: Deep learning models (DLMs) are applied across domains of health sciences to generate meaningful predictions. DLMs make use of neural networks to generate predictions from discrete data inputs. This study employs DLM on prechemotherapy cross-sectional imaging to predict patients' response to neoadjuvant chemotherapy. METHODS: Adult patients with colorectal liver metastasis who underwent surgery after neoadjuvant chemotherapy were included. A DLM was trained on computed tomography images using attention-based multiple-instance learning. A logistic regression model incorporating clinical parameters of the Fong clinical risk score was used for comparison. Both model performances were benchmarked against the Response Evaluation Criteria in Solid Tumors criteria. A receiver operating curve was created and resulting area under the curve (AUC) was determined. RESULTS: Ninety-five patients were included, with 33,619 images available for study inclusion. Ninety-five percent of patients underwent 5-fluorouracil-based chemotherapy with oxaliplatin and/or irinotecan. Sixty percent of the patients were categorized as chemotherapy responders (30% reduction in tumor diameter). The DLM had an AUC of 0.77. The AUC for the clinical model was 0.41. CONCLUSIONS: Image-based DLM for prediction of response to neoadjuvant chemotherapy in patients with colorectal cancer liver metastases was superior to a clinical-based model. These results demonstrate potential to identify nonresponders to chemotherapy and guide select patients toward earlier curative resection.

COVID-Induced Thrombotic Thrombocytopenic Purpura: A Case Report and Treatment-Focused Review.

Thrombotic thrombocytopenic purpura (TTP) is a rare disease that is part of a vast spectrum of thrombotic microangiopathies (TMAs). Despite the rarity of TTP, clinicians must maintain a high suspicion of this disease. The condition is characterized by fever, low platelets, hemolytic anemia, renal abnormalities, and neurological dysfunction. However, all these symptoms are not necessarily present in all the patients. In this review, we describe a case of a 51-year-old female who presented to the emergency department (ED) with chief complaints of dizziness and lightheadedness, subsequently leading to a diagnosis of TTP, caused as a result of COVID-19. This review raises awareness so that there is early recognition of any hematological manifestations associated with COVID-19, reducing the morbidity and mortality associated with the disease. Due to the unpredictability of COVID-19 and its complications, robust research is needed to understand the mechanism and determine which patients are more at risk for adverse outcomes.

Association of CT-Derived Skeletal Muscle and Adipose Tissue Metrics with Frailty in Older Adults.

RATIONALE AND OBJECTIVES: Tools are needed for frailty screening of older adults. Opportunistic analysis of body composition could play a role. We aim to determine whether computed tomography (CT)-derived measurements of muscle and adipose tissue are associated with frailty. MATERIALS AND METHODS: Outpatients aged ≥ 55 years consecutively imaged with contrast-enhanced abdominopelvic CT over a 3-month interval were included. Frailty was determined from the electronic health record using a previously validated electronic frailty index (eFI). CT images at the level of the L3 vertebra were automatically segmented to derive muscle metrics (skeletal muscle area [SMA], skeletal muscle density [SMD], intermuscular adipose tissue [IMAT]) and adipose tissue metrics (visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT]). Distributions of demographic and CT-derived variables were compared between sexes. Sex-specific associations of muscle and adipose tissue metrics with eFI were characterized by linear regressions adjusted for age, race, ethnicity, duration between imaging and eFI measurements, and imaging parameters. RESULTS: The cohort comprised 886 patients (449 women, 437 men, mean age 67.9 years), of whom 382 (43%) met the criteria for pre-frailty (ie, 0.10 < eFI ≤ 0.21) and 138 (16%) for frailty (eFI > 0.21). In men, 1 standard deviation changes in SMD (ß = -0.01, 95% confidence interval [CI], -0.02 to -0.001, P = .02) and VAT area (ß = 0.008, 95% CI, 0.0005-0.02, P = .04), but not SMA, IMAT, or SAT, were associated with higher frailty. In women, none of the CT-derived muscle or adipose tissue metrics were associated with frailty. CONCLUSION: We observed a positive association between frailty and CT-derived biomarkers of myosteatosis and visceral adiposity in a sex-dependent manner.

Straw incorporation into microplastic-contaminated soil can reduce greenhouse gas emissions by enhancing soil enzyme activities and microbial community structure.

Microplastic (MP) contamination poses a substantial threat to agroecosystems, disrupting soil properties, nutrient cycles, and microbial communities and ultimately affecting plant growth and ecosystem resilience. The effects of straw addition on the storage of soil organic carbon (SOC) and greenhouse gas emissions have been extensively explored, but these effects have not been examined in the context of MP contamination. To assess the impacts of legume straw and polyethylene microplastics on SOC fractions and carbon dioxide (CO2) and nitrous oxide (N2O) emissions, 7-month soil incubation experiments were performed. The results revealed that the inclusion of legume straw in soil considerably increased microbial SOC compared to the control. However, straw addition to MP-contaminated soil reduced microbial SOC compared to that in soil containing only straw. In contrast, the addition of straw to MP-contaminated soil elevated (+44%) the SOC mineral relative to the sole application of straw. Intriguingly, straw incorporation into MP-contaminated soil reduced microbial biomass carbon and nitrogen relative to soil containing only straw. Straw addition to MP-contaminated soil enhanced the nitrification activity and reduced the relative expression of AOBamoABC gene compared to sole straw-incorporated soil and the control. Greenhouse gas emissions were also modulated; for instance, straw incorporation into MP-contaminated soil reduced CO2 and N2O emissions by -11% and -46%, compared to straw incorporation alone. The urease and phosphatase activities were decreased (-58% and -12%) in the MP-polluted soil with straw incorporation compared with those in the soil in which only straw was applied. However, invertase and catalase activities were upregulated in the straw-incorporated soil contaminated with MPs. Straw addition in the MP-polluted soil considerably enhanced (+2%) the microbial community structure (indicated by PLFA) compared to the sole straw application. These results provide a comprehensive perspective on the role of legume straw incorporation in addressing MP pollution, showcasing its potential for sustainable agricultural practices in the face of evolving environmental challenges.

A multifunctional vanillin-infused chitosan-PVA hydrogel reinforced by nanocellulose and CuO-Ag nanoparticles as antibacterial wound dressing.

Wound healing is an intricate and ever-evolving phenomenon that involves a series of biological processes and multiple stages. Despite the growing utilization of nanoparticles to enhance wound healing, these approaches often overlook properties like mechanical stability, toxicity, and efficacy. Hence, a multifunctional wound dressing is fabricated using Chitosan-PVA membrane crosslinked with vanillin and reinforced with nano-cellulose and CuO-Ag nanoparticles in this study. FTIR, SEM, and XRD were employed to study the morphology and structural properties of the membrane. Biomedical tests including biodegradability, antimicrobial study, cytotoxicity, and animal models were conducted to evaluate the membrane's performance as a wound healing material. The membrane displayed impressive mechanical strength, measuring as high as 49.985 ± 2.31 MPa, and had a hydrophilic nature, with moisture retention values up to 98.84 % and swelling percentages as high as 191.67 %. It also demonstrated biodegradable properties and high cell viability of up to 92.30 %. Additionally, the fabricated membranes exhibited excellent antimicrobial activity against both gram-positive and gram-negative bacteria, with maximum zone of inhibition measuring 16.8 ± 0.7 mm and 9.2 ± 0.1 mm, respectively. Moreover, the membranes also demonstrated superior wound healing properties. These results suggested great potential of fabricated membranes as an effective wound dressing material.

Regional and National Trends in Consumption of Antimicrobials in Pakistan; Pre and Post-COVID (2019-2021).

BACKGROUND: Efforts to combat antimicrobial resistance, a growing public health problem in Pakistan, have been hampered by the lack of high-quality national and provincial-level antimicrobial consumption data. The singular objective of this retrospective study was to measure antimicrobial consumption over 3 years between 2019 and 2021. METHODS: The study was designed to estimate antimicrobial consumption at National and Regional levels. Antimicrobial consumption data was collected by IQVIA covering 110 districts of Pakistan in which 88% of sales are census (accurate sales collected directly from distributors), whereas 12% of sales (sales of 300 pharmacies) are projected on the national level. To determine the usage for 3 consecutive years, the consumption of antibiotics was calculated as defined daily doses (DDD) of antibiotics per 1000 inhabitants per day (DID). RESULTS: The results of our study demonstrated a steep increase in the consumption of antimicrobials from 2019 to 2021. An increase in consumption of most classes of antibiotics was observed both nationally and Regionally. Quinolones, penicillins (co-amoxiclav), macrolides, and third-generation cephalosporins remained the most frequently used antibiotics nationally. A 40% increase in intravenous use of antimicrobials was observed between 2019 and 2021 at the national level. Moxifloxacin, Levofloxacin, Ciprofloxacin, and linezolid were the most commonly used intravenous antibiotics. Region 7 (Peshawar) demonstrated the highest consumption, followed by Region 1 (Karachi) and Region 6 (Faisalabad). Among the most commonly used antibiotics, the use of third-generation cephalosporin (cefixime), quinolones, penicillins (amoxicillin + clavulanic acid), and macrolides (azithromycin) was most noticeable in all regions, particularly in those with the higher consumption of antibiotics. CONCLUSIONS: Although the increase in consumption of all antibiotics is concerning, the steep increase in the use of watch and reserve category antibiotics during the study period calls for immediate actions to limit and regulate their usage.

A Meta-Analysis of Randomized Clinical Trials Assessing the Efficacy of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer.

Prostate cancer ranks as the second most common malignancy in males. Prostate cancer progressing on androgen deprivation therapy (ADT) is castration-resistant prostate cancer (CRPC). Poly-ADP ribose polymerase (PARP) inhibitors (PARPis) have been at the forefront of the treatment of CRPC. We aim to better characterize the progression-free survival (PFS) and overall survival (OS) in metastatic CRPC patients treated with PARPis. A systemic review search was conducted using National Clinical Trial (NCT), PubMed, Embase, Scopus, and Central Cochrane Registry. The improvement in overall survival was statistically significant, favoring PARPis (hazard ratio (HR) 0.855; 95% confidence interval (CI) 0.752-0.974; p = 0.018). The improvement in progression-free survival was also statistically significant, with results favoring PARPis (HR 0.626; 95%CI 0.566-0.692; p = 0.000). In a subgroup analysis, similar results were observed where the efficacy of PARPis was evaluated in a subgroup of patients without homologous recombination repair (HRR) gene mutation, which showed improvement in PFS favoring PARPis (HR 0.747; 95%CI 0.0.637-0.877; p = 0.000). Our meta-analysis of seven RCTs showed that PARPis significantly increased PFS and OS when used with or without antihormonal agents like abiraterone or enzalutamide.

Attention2Minority: A salient instance inference-based multiple instance learning for classifying small lesions in whole slide images.

Multiple instance learning (MIL) models have achieved remarkable success in analyzing whole slide images (WSIs) for disease classification problems. However, with regard to giga-pixel WSI classification problems, current MIL models are often incapable of differentiating a WSI with extremely small tumor lesions. This minute tumor-to-normal area ratio in a MIL bag inhibits the attention mechanism from properly weighting the areas corresponding to minor tumor lesions. To overcome this challenge, we propose salient instance inference MIL (SiiMIL), a weakly-supervised MIL model for WSI classification. We introduce a novel representation learning for histopathology images to identify representative normal keys. These keys facilitate the selection of salient instances within WSIs, forming bags with high tumor-to-normal ratios. Finally, an attention mechanism is employed for slide-level classification based on formed bags. Our results show that salient instance inference can improve the tumor-to-normal area ratio in the tumor WSIs. As a result, SiiMIL achieves 0.9225 AUC and 0.7551 recall on the Camelyon16 dataset, which outperforms the existing MIL models. In addition, SiiMIL can generate tumor-sensitive attention heatmaps that is more interpretable to pathologists than the widely used attention-based MIL method. Our experiments imply that SiiMIL can accurately identify tumor instances, which could only take up less than 1% of a WSI, so that the ratio of tumor to normal instances within a bag can increase by two to four times.