2 Chicago firefighters, teenager injured in Lincoln Park apartment fire
Firefighters responded to a fire on the third floor of a four-story apartment building in the 2300 block of South Ashland Avenue, Chicago Fire Department officials said.
Two firefighters who were injured were taken to the hospital in good condition. A teenage boy was taken to Lurie Children's Hospital for treatment to be checked for smoke inhalation.
No other injuries were reported, and no further information was immediately available Saturday afternoon.
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Medscape
30 minutes ago
- Medscape
Q&A: Cervical Cancer
Maurie Markman, MD Dr Maurie Markman, an internationally recognized medical oncologist and president of medicine and science at City of Hope, specializes in gynecologic malignancies. In this interview, he discusses the transformative role of immunotherapy in advanced and recurrent cervical cancer treatment. He also addresses practical management considerations for special populations, immunotherapy toxicity profiles, surveillance strategies, resistance mechanisms, and the field's future directions. How has immunotherapy transformed the landscape for recurrent and metastatic cervical cancer, and what defines the current standard of care? The transformation has been nothing short of remarkable. Before immunotherapy, we were essentially offering patients with cervical cancer single-agent cisplatin with awful toxicity and minimal response rates; it was a pretty dismal situation. The introduction of pembrolizumab in the first-line setting has been a true game-changer. Based on the KEYNOTE-826 trial results, pembrolizumab — combined with platinum-based chemotherapy, with or without bevacizumab — significantly prolonged both progression-free and overall survival compared to chemotherapy alone.[1,2] This has become our standard approach for PD-L1-positive disease.[3] In practice, this means that patients who previously had almost no effective therapy options now have a regimen that produces meaningful tumor responses and substantial survival gains. We're talking about dramatically improved outcomes where none existed before. The current standard involves simultaneous administration of all agents from cycle 1. For patients who are candidates for triple therapy, we give pembrolizumab on day 1 with cisplatin or carboplatin plus paclitaxel and add bevacizumab at its usual dose and schedule if there are no contraindications.[3] The beauty is that pembrolizumab toxicities don't meaningfully interact with chemotherapy or bevacizumab; the immune-related adverse events occur independently of vascular toxicities. We only withhold bevacizumab for patient-specific reasons like recent major surgery or active fistula, not because of immunotherapy concerns. Walk us through PD-L1 testing and biomarker strategies. What should oncologists know about patient selection? Every patient with recurrent or metastatic cervical cancer should undergo PD-L1 testing using an FDA-approved assay; this is nonnegotiable.[3] The score is reported as a combined positive score (CPS), which is the number of PD-L1-staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100. A CPS of 1 or more is considered PD-L1-positive based on FDA definition and KEYNOTE-826 data. Essentially, if at least 1% of cells are PD-L1-positive based on this formula, the tumor qualifies for pembrolizumab-based therapy.[1,2] But we don't stop there. While PD-L1 remains the primary biomarker, we routinely obtain comprehensive genomic testing because other features can influence the treatment strategy. NCCN (National Comprehensive Cancer Network) recommends testing for MSI/MMR in recurrent disease.[3] Although MSI-H is uncommon in cervical cancer, any patient with MSI-H or high tumor mutational burden would be eligible for pembrolizumab on a tumor-agnostic basis. We also recommend comprehensive panel testing, including HER2 amplification/overexpression and NTRK fusions.[3] These markers may not predict pembrolizumab response per se, but they identify other targeted therapies if immunotherapy fails. For example, HER2 overexpression opens the door to trastuzumab deruxtecan later in the treatment course. How do targeted therapies like trastuzumab deruxtecan and tisotumab vedotin fit into the treatment paradigm? This is where things get exciting for the small subset of patients with specific molecular targets. HER2 overexpression occurs in roughly 2%-6% of cervical cancers, but it's clinically significant when these are present. The DESTINY-PanTumor02 trial included a cervical cancer cohort and showed impressive activity; the confirmed objective response rate was about 50% overall, and in the subset with IHC 3+ tumors, it reached 75%.[4] Based on these results, NCCN now recommends routine HER2 testing (IHC with FISH reflex) in recurrent/metastatic disease and lists trastuzumab deruxtecan as a category 2A, second-line option for HER2-positive tumors (IHC 3+ or 2+).[3] So, while only a minority of patients have HER2-positive disease, those who do have access to an active ADC (antibody-drug conjugate) therapy after first-line treatment. Tisotumab vedotin represents another significant advance. This tissue factor-directed ADC received full FDA approval in April 2024 for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, and it's now the only NCCN category 1 preferred option for second-line therapy.[3,5] What's particularly interesting is the ongoing innovaTV 205 (GOG-3024) trial combining tisotumab vedotin with pembrolizumab in the first-line setting; the NCCN guidelines already note this combination as an option for PD-L1-positive patients based on encouraging phase 2 activity.[3] The rationale behind these ADCs is compelling: They can target tumor cells independent of the PD-1 pathway, potentially overcoming immunotherapy resistance mechanisms. How do you approach treatment in special populations such as elderly patients, those with poor performance status, and PD-L1-negative disease? This requires individualized decision-making and honest conversations about goals of care. Age alone is never a contraindication; we don't refuse immunotherapy solely because of chronological age. However, older patients often have more comorbidities that can amplify even low-grade toxicities. Before treating such patients, we carefully assess overall health, lab values, and organ function.[6] For truly frail patients or those with poor performance status (ECOG [Eastern Cooperative Oncology Group] ≥ 2) due to disease burden, we discuss goals of care candidly. Sometimes we choose single-agent chemotherapy or best supportive care instead of full triple therapy. For moderately impaired patients who seem reasonably functional, we may proceed with chemo-immunotherapy but with closer monitoring and potentially modified dosing. The key is vigilant follow-up; these patients need frequent labs and clinic visits to catch toxicity early. We personalize the approach: full regimen if they can tolerate it, otherwise a modified strategy. For PD-L1-negative disease, pembrolizumab isn't indicated, so we revert to traditional approaches: platinum-based chemotherapy plus bevacizumab when feasible, followed by second-line agents like topotecan or irinotecan.[3] We still ensure broad molecular profiling since targets like NTRK fusions or microsatellite instability could open second-line options, but immunotherapy is reserved for PD-L1-positive cases per label. What are the key principles for managing immunotherapy-related toxicities, and are there cervical cancer-specific considerations? Toxicity management for pembrolizumab in cervical cancer follows the same principles as other tumors. There are no cervical cancer-specific immune toxicities. We monitor for the usual immune-related adverse events (thyroid function tests, skin checks, GI symptoms) and treat according to standard guidelines like steroids for grade ≥ 2 colitis and hormone replacement for hypothyroidism. The main caveat is that many patients with cervical cancer have had extensive prior therapy (eg, radiation, cisplatin) and may have compromised organ function or poor performance status at baseline. This means that even the same immune side effect could be more clinically challenging. For example, a patient with heavy tumor burden and GI involvement might not tolerate low-grade colitis as well as someone with good performance status.[6] We apply common sense; patients with multiple comorbidities or moderate ECOG 2-3 status require very close monitoring since any grade 3-4 immune-related adverse event could tip the balance. In practice, we treat most patients with PD-L1-positive disease regardless of age or mild frailty, but we have a lower threshold to hold therapy and manage side effects aggressively in vulnerable populations. What does surveillance look like during and after immunotherapy, and what emerging resistance mechanisms concern you? Unlike some other cancers, we don't have reliable tumor markers to follow in cervical cancer. There's no CA-125 equivalent. We rely entirely on imaging, typically CT scans every 3 months or as clinically indicated by symptoms. For patients with visceral disease, we image the chest, abdomen, and pelvis together.[3] We continue therapy as long as patients derive benefit (response or stable disease) without prohibitive toxicity. The surveillance schedule is similar to other metastatic cancers: every 2-3 cycles (6-8 weeks) for the first 6 months and then every 3 months if stable. Regarding resistance mechanisms, this is an active area of research that keeps me up at night. We know from other cancers that tumors can evade immunotherapy through several routes: downregulating antigen presentation machinery, upregulating alternative checkpoints like LAG-3 or TIM-3, or creating an immunosuppressive microenvironment. In cervical cancer specifically, these mechanisms haven't been fully elucidated. What's clear is our need for effective second-line strategies. This is where ADCs become particularly attractive; they target tumor cells independent of the PD-1 pathway.[4,5] Beyond HER2-targeted and tissue factor-directed ADCs, new conjugates targeting novel antigens are in development. The field is also exploring combination strategies adding other checkpoint inhibitors or stimulatory agents and novel approaches like therapeutic vaccines. What developments in earlier-stage disease and emerging trials should we be watching? Immunotherapy is rapidly moving upstream, and this trend will likely accelerate. Pembrolizumab was recently approved in combination with definitive chemoradiation for high-risk locally advanced cervical cancer (FIGO 2014 stage III–IVA) based on the ENGOT-cx11/GOG-3047 (KEYNOTE-A18) trial.[7] This trial showed that adding pembrolizumab after chemo-RT improves outcomes, and NCCN guidelines now include this as a category 1 recommendation.[3] Whether to extend immunotherapy to even earlier stages remains to be proven. For bulky stage IB or IIA disease, we'd need to weigh benefits against long-term toxicity and cost. The current priority is optimizing use in high-risk settings where relapse rates are significant, rather than treating early-stage patients we already cure with surgery or chemoradiation. Several trials deserve attention. The innovaTV 205 (GOG-3024) study combining tisotumab vedotin with pembrolizumab in first-line treatment is particularly intriguing; the rationale is that tisotumab vedotin may provide synergy with PD-1 blockade.[3] Other ongoing trials are testing combinations of PD-1 inhibitors with CTLA-4 inhibitors or novel immunomodulators.[8,9,10] Looking ahead, ADC combinations and additional checkpoint combinations represent the major themes. We're also seeing movement toward incorporating immunotherapy into adjuvant settings for high-risk patients. The goal is to build on our success in metastatic disease and prevent recurrences before they occur. Of course, while we're making these therapeutic advances, we can't forget that prevention through HPV vaccination and screening remains our best strategy for reducing cervical cancer incidence overall.
Medscape
30 minutes ago
- Medscape
Diagnosis of Renal Cell Carcinoma: 5 Things to Know
Renal cell carcinoma (RCC), the most common form of kidney cancer, accounts for approximately 90%-95% of all primary renal malignancies. When diagnosed at an early, localized stage, RCC carries a favorable prognosis with a 5-year relative survival rate of 93%. However, survival drops significantly with disease progression, falling to approximately 75% for regional disease and just 18% for metastatic disease, underscoring the importance of early diagnosis. Because RCC often remains asymptomatic in its early stages, it is frequently discovered incidentally or goes undetected until progression occurs. Routine CT screening for RCC is neither practical nor cost-effective, prompting interest in more efficient, targeted diagnostic strategies. Advances in imaging and the integration of artificial intelligence (AI) are helping clinicians detect RCC earlier and with greater accuracy. Here are five things to know about the diagnosis of RCC and the evolution of diagnostic technologies. 1. Imaging is the cornerstone of RCC diagnosis. Up to 60% of RCCs are discovered incidentally, most often during abdominal imaging — particularly CT scans — performed for unrelated indications. Patients with incidentally discovered RCC tend to have better outcomes than those diagnosed after symptom onset, as incidental detection is more likely to identify tumors at a surgically resectable and nonmetastatic stage. Cross-sectional imaging, particularly contrast-enhanced CT, remains the primary modality for evaluating suspected RCC and is used routinely for both diagnosis and post-treatment surveillance. CT provides high-resolution assessments of tumor morphology, enhancement patterns, size, location, and venous invasion — information that is critical for accurate staging and surgical planning. MRI is an important alternative when CT is contraindicated, such as in patients with renal insufficiency or iodine allergy, or when CT findings are inconclusive. MRI offers excellent soft-tissue contrast and is particularly useful for delineating tumor extension into the renal vein or inferior vena cava. Multiparametric MRI enhances evaluation by generating high-resolution images that help differentiate benign from malignant masses and reveal tumor-specific characteristics, such as vascularity or cellular density, that may aid in subtype classification. Ultrasonography is a useful first-line tool in the evaluation of renal masses, particularly for distinguishing cystic from solid renal lesions. While it lacks the sensitivity and spatial resolution of CT or MRI — especially for small or isoechoic tumors — it is noninvasive, cost-effective, and widely available, making it a practical choice for routine imaging. It is particularly effective in the initial characterization of simple renal cysts and monitoring Bosniak category I and II lesions. Advanced CT technologies are enhancing the characterization of renal lesions while reducing radiation exposure and contrast-agent requirements. In centers where available, dual-energy CT allows quantification of iodine content, which can help differentiate enhancing solid masses from cystic or nonenhancing lesions. It also enables virtual unenhanced imaging, potentially eliminating the need for noncontrast scans. Photon-counting CT improves spatial resolution and material decomposition, which may aid in detecting subtle renal lesions. Early clinical studies show it offers image quality and lesion conspicuity comparable to, or exceeding, conventional CT and MRI. PET/CT with tracers such as 18F-FDG, 124I-girentuximab, and PSMA-targeted agents (eg, 68Ga-PSMA) are under investigation for both diagnosis and treatment monitoring in RCC. These molecular imaging tools have shown promise for detecting primary tumors and metastatic disease. The phase 3 ZIRCON trial showed that 89Zr-girentuximab PET/CT achieved 85% sensitivity and 87% specificity for identifying clear-cell RCC. Bone scans are typically reserved for patients with bone pain or elevated alkaline phosphatase levels suggestive of skeletal metastases. PET/CT with 18F-FDG may aid in staging and treatment response assessment, particularly in aggressive or metabolically active RCC subtypes, although their utility varies depending on RCC subtype and metabolic activity. 2. AI is enhancing imaging interpretation. AI is becoming increasingly integrated into RCC diagnosis, particularly in the analysis of CT and MRI scans. AI algorithms can help radiologists identify and characterize renal masses with high accuracy, helping to distinguish benign from malignant lesions and potentially reducing unnecessary biopsies. Radiomics, a subfield of AI, extracts and analyzes high-dimensional imaging features not visible to the human eye. Radiomics-based models have been used to classify RCC subtypes, predict tumor behavior, and support prognostic and treatment decisions, especially in complex or ambiguous cases. AI can also automate nephrometry scoring systems, which quantify renal tumor complexity based on parameters such as size, location, and proximity to critical structures. These scores guide surgical decision-making, including the feasibility of partial nephrectomy. Automated systems may help reduce inter-reader variability and streamline preoperative planning. 3. Laboratory testing aids the initial evaluation. While imaging is essential, laboratory studies play a critical role in the initial evaluation and ongoing management of patients with RCC. In patients presenting with hematuria, flank pain, unexplained weight loss, or systemic findings, recommended laboratory tests typically include: Urinalysis, with urine cytology if a centrally located lesion suggests possible urothelial carcinoma Complete blood cell count with differential Serum electrolytes and renal function tests (eg, creatinine, blood urea nitrogen) Liver function tests (aspartate aminotransferase, alanine aminotransferase), which may be abnormal in the presence of paraneoplastic Stauffer syndrome Serum calcium to assess for hypercalcemia, a common paraneoplastic finding RCC is associated with several paraneoplastic syndromes, including: Hypercalcemia (due to ectopic parathyroid hormone-related protein production) Erythrocytosis (from ectopic erythropoietin secretion) Stauffer syndrome, a reversible nonmetastatic hepatic dysfunction Identifying these laboratory abnormalities can support a diagnosis of RCC, guide further testing, and influence management decisions, especially in advanced or atypical presentations. 4. Biopsy may be needed in select cases. Although RCC is often diagnosed based on imaging findings, biopsy remains an important tool in select cases, particularly when imaging findings are inconclusive, histologic confirmation is required prior to treatment, or active surveillance is being considered. The choice of biopsy technique depends on tumor size, tumor location, patient comorbidities, and the specific clinical context. Common approaches include: Percutaneous core needle biopsy: This is typically performed under CT or ultrasound guidance. It is the most frequently used method for renal biopsy, provides tissue for histopathologic and immunohistochemical analysis, and carries a low complication rate. Fine-needle aspiration (FNA): FNA may be used to obtain cytologic material. FNA is often used as an adjunct to core biopsy; it is less definitive when used alone. Laparoscopic or surgical biopsy: This may be necessary when percutaneous biopsy is not feasible, such as with deep or anatomically challenging tumors or when larger tissue samples are needed for molecular profiling. Liquid biopsy approaches — including analysis of circulating tumor DNA, circulating tumor cells, or other biomarkers — are currently investigational but may offer future utility in RCC diagnosis, prognosis, and treatment monitoring, particularly for identifying minimal residual disease or recurrence. Histologic analysis can confirm the diagnosis of RCC, distinguish between subtypes (eg, clear cell, papillary, chromophobe), and help determine the prognosis and treatment strategy. 5. Accurate staging and grading inform the diagnosis and prognosis. Staging and grading are essential components of the RCC diagnostic process. Together, they inform prognosis, guide treatment selection, and determine eligibility for surgical or systemic therapy. Staging follows the TNM system and assesses: Tumor size and local extent (T) Regional lymph node involvement (N) Presence of distant metastases (M) Grading evaluates the tumor's cellular features to estimate its aggressiveness. While the older Fuhrman grading system may still appear in some contexts, most institutions now use the ISUP/WHO grading system, which assesses nuclear characteristics in clear-cell and papillary RCC. Final stage and grade are based on the integration of imaging findings and histologic evaluation from biopsy or surgical specimens. These metrics are critical for risk stratification and treatment planning, including decisions regarding active surveillance, nephrectomy, or systemic therapy.
Wall Street Journal
31 minutes ago
- Wall Street Journal
A Wedding Season Skincare Essential
Living in New York City (and attending all those aforementioned weddings), I'm tough on my feet. I walk just about everywhere, often in shoes that aren't necessarily made for trekking long distances. I can put up with a little soreness here and there, and I try to avoid blisters at all costs with strategically placed bandages, but my less-than-gentle treatment of my feet has led to dry skin and cracked heels. And whether I'm wearing strappy sandals at a wedding or going barefoot in a yoga class, it can be both uncomfortable and a little embarrassing. Luckily, the Pedestrian Project balm works quickly. I first tried it out a few days ahead of traveling to Arizona for a wedding. I was impressed with how soft my previously dry heels felt after two days of applying the balm morning and night. My skin stayed smooth and resisted cracking even in dry, unseasonably-warm-for-April 100-degree heat. Since then, it's become a permanent fixture in my nighttime routine. How does it work? The balm is made with a blend of mango butter and candelilla wax to lock in moisture, as well as African shea butter to soften skin. It glides effortlessly onto heels, toes or anywhere you could use a little extra hydration—the texture feels thick and butter-like. The formula also includes black currant seed oil, which is anti-inflammatory, and vitamin E to soothe inflamed or itchy skin. The scent is lovely, somewhere between lightly citrusy and herbal, but not overpowering. I still get calluses and dry patches occasionally, but when I do, the balm swiftly comes to the rescue. And while it works well on its own, I find it's even more effective after I exfoliate with Soft Services' Buffing Bar, or for extra-tough calluses, a foot file, like this one from Dr. Scholl's. The balm also solves my main issue with other footcare products that come in tubes or tubs—it's not messy. All I have to do is apply the balm with its handy stick applicator and slip on a pair of socks. I don't even have to touch my feet (not that I would mind, since the product isn't greasy in the slightest). In the morning, I wake up with smoother skin than I thought was possible. Ideally, I'd love to get a fresh pedicure ahead of every formal event I attend, but if time doesn't allow for an appointment and I'm left to DIY at home, Pedestrian Project's balm comes in handy every time. It may not help soothe sore feet after dancing all night (I'm still on the hunt for that miracle product), but at least my skin is smooth, soft and comfortable as ever.
