Michael M Awad

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Researchers measured levels of specific circular RNA molecules, microRNAs, and inflammatory proteins in the blood of diabetic kidney disease patients at different stages of severity. As kidney disease worsened, circular RNA and its associated receptor were progressively reduced, while the microRNA and inflammatory markers rose. These molecular changes track kidney disease stage and could serve as a new panel of biomarkers for monitoring disease progression.

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A graph neural network was applied to spatial maps of immune and tumor cells in lung cancer tissue from 506 patients to capture complex neighborhood relationships that simple cell count methods miss. The model predicted patient survival with a concordance index of 0.82, and analysis revealed that CD8 T cells near tumor cells predicted better outcomes, while the same cells near immunosuppressive regulatory T cells were less beneficial. This approach provides a new framework for spatially resolved immune biomarker development in lung cancer.

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Researchers analyzed the evolutionary history of gene amplification — a common way cancers boost cancer-driving genes — across 86,000 cancer cells from nearly 100 patients and experimental systems. Two distinct amplification types were found to evolve very differently: chromosomal amplifications were dynamic and clone-specific, while circular DNA outside chromosomes (ecDNA) showed structural complexity and tissue-specific prevalence. These findings have direct implications for predicting which tumors might respond to therapies targeting gene amplification.

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This large multicenter study found that lung adenocarcinomas lacking the protein TTF-1 (about 15-20% of cases) respond significantly worse to immunotherapy, chemoimmunotherapy, and KRAS inhibitors compared to TTF-1-positive tumors. TTF-1-negative tumors were enriched for aggressive mutations like STK11 and KEAP1 and showed lower PD-L1 expression. Routine TTF-1 testing could help identify patients unlikely to benefit from current standard treatments and who may need different approaches.

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Lung cancers driven by KRAS G12C and G12D mutations were compared in mouse models and patient data, finding G12C tumors grow more slowly and attract more immune cell infiltration. G12D tumors relapsed faster after targeted drug treatment, but combining a KRAS G12D inhibitor with immune checkpoint blockade produced durable immune responses in some models. These differences between mutation types have direct clinical implications for sequencing and combining targeted and immune therapies.

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In a multicenter study of stage III lung cancer patients treated with chemoradiation followed by durvalumab immunotherapy, those with KRAS mutations had significantly worse progression-free survival (16 vs. 28 months) and more brain metastases. The worst outcomes were in tumors with KRAS co-mutated with CDKN2A or STK11. These findings identify a high-risk group where adding KRAS inhibitors to standard treatment may be warranted in future trials.

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A bacterium isolated from local sources was found to produce an antibacterial compound (a putative lipopeptide) using waste cooking oil as its carbon source, with strong activity against both E. coli and Staphylococcus aureus. Molecular docking simulations suggested the active component binds key bacterial enzymes to disrupt cell function. This proof-of-concept shows that low-cost, renewable feedstocks can support production of effective natural antibacterials.

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An exploratory analysis of the CheckMate 77T clinical trial examined outcomes specifically in stage III lung cancer patients with N2 (mediastinal lymph node) disease treated with perioperative nivolumab plus chemotherapy. In N2 patients, nivolumab improved event-free survival at 1 year (70% vs. 45%) and pathological complete response rate (22% vs. 5.6%), with high rates of surgical resection and lymph node downstaging. These findings support perioperative immunotherapy as effective even in patients with the most advanced nodal involvement.

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MTAP gene deletions, which occur alongside CDKN2A deletions in about 10% of NSCLCs, were found to frequently co-occur with EGFR and other driver mutations and were associated with shorter time to treatment discontinuation on osimertinib. One patient with EGFR-mutant, MTAP-deleted NSCLC responded to a PRMT5 inhibitor, pointing toward a synthetic lethal targeting strategy. These results set the stage for clinical trials of PRMT5 inhibitors in driver-positive, MTAP-deleted NSCLC.

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Lung cancers in patients with the autoimmune disease systemic sclerosis (SSc) showed a striking lack of common targetable driver mutations (EGFR, fusions) but were enriched for TP53 mutations and APOBEC mutational signatures — even in patients who never smoked heavily. This distinct genomic profile, also seen in other inflammatory lung diseases, suggests a unique disease mechanism driven by chronic inflammation rather than tobacco exposure. These findings have practical implications: patients with SSc-related lung cancer may not benefit from standard targeted therapies.

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This study showed that having two separate primary lung cancers both carrying MET exon 14 mutations can be definitively identified only through DNA-based sequencing, since RNA-based tests simply report the same mutation type without distinguishing the specific DNA change. Eight patients were identified with multiple distinct primary METex14-mutant lung cancers, confirmed by genomic evidence of separate clonal origins. This has important staging implications — what looks like metastatic disease may actually be multiple independent primary cancers.

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A multicenter analysis of 4,157 advanced NSCLC patients found that detailed smoking history — including current vs. former status and cumulative pack-years — strongly and independently predicted who would benefit from immunotherapy alone, while the same patterns were less pronounced for chemoimmunotherapy. Never-smokers with PD-L1 high tumors actually derived greater benefit from adding chemotherapy to immunotherapy. Molecular analysis revealed that smoking-associated differences in tumor mutation burden, immune infiltration, and blood proteins explain these outcome differences.

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This narrative review evaluated 99 studies on 3D-printed resin composite materials for permanent dental fillings and crowns, finding they currently fall short of conventionally milled materials in mechanical strength and color stability. However, 3D-printed restorations showed comparable or better fit at the margins compared to milled alternatives. The authors conclude 3D-printed composites are not yet a direct substitute for milled restorations in demanding situations but may be suitable for less mechanically stressed applications.

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A national survey of fellowship program directors in surgical subspecialties found that nearly half were unaware of an ABS policy allowing general surgery residents to take flexible subspecialty rotations (FIST) during training. Among the small number who had trained fellows who participated in FIST, most reported those fellows performed comparably or better than peers. This highlights a major awareness gap in graduate medical education that, if addressed, could improve surgical residency training pathways.

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Researchers used long-term imaging in zebrafish and spatial transcriptomics to identify specific pockets within melanoma tumors — called CRATERs — where CD8 T cells form prolonged killing interactions with cancer cells during immunotherapy. After immune stimulation, CRATERs expanded and became the primary sites of tumor destruction. In humans, higher CRATER density after immune checkpoint blockade correlated with clinical response, positioning CRATERs as a potential tissue-based biomarker of immunotherapy success.

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This study used a clinical digital pathology platform to prospectively measure four immune markers (CD8, FOXP3, PD-1, PD-L1) in over 2,000 cancer biopsies across 14 cancer types. Patients with high numbers of intratumoral CD8 or PD-1 cells had significantly better survival across all cancer types, independent of stage and treatment. This large-scale validation supports routine immunoprofiling as a clinically meaningful tool across multiple cancer types.

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A one-year pilot program tested case-log requirements for a new hernia and abdominal wall surgery fellowship designation, finding that all fellows met goals for inguinal hernia volume but none fully met ventral hernia targets due to mid-year rule changes and variation in hospital volume. The experience highlighted the need for standardized case-log definitions and revealed differences in hernia case availability across fellowship programs. This data will inform refinement of the fellowship requirements before wider rollout.

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A meta-analysis of six phase 3 trials found that adding CTLA-4 inhibitors to PD-1/PD-L1 immunotherapy did not improve overall survival in the broad NSCLC population, but did benefit two specific subgroups: patients with PD-L1-negative tumors and those with STK11 mutations. The 5-year overall survival benefit in these groups was clinically meaningful. These findings support a biomarker-selected approach to using dual immune checkpoint blockade rather than applying it broadly.

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A multicenter retrospective study of patients with BRAF V600E-mutant metastatic lung cancer found that first-line immunotherapy (with or without chemotherapy) was associated with longer overall survival than BRAF/MEK inhibitors (41 vs. 25 months), particularly in smokers, patients with high PD-L1, and those with TP53 co-mutations. BRAF/MEK inhibitor toxicity rates were similar whether given first-line or after immunotherapy. These hypothesis-generating data suggest immunotherapy may be preferable upfront in certain subgroups.

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Two cell surface proteins found preferentially on neuroendocrine cancers — DLL3 and SEZ6 — were surveyed across 124 tumor samples from eight different primary sites. Both were positive in roughly 78-81% of cases, frequently co-expressed, and maintained their expression in transformed and brain-metastatic tumors. This landscape characterization identifies the population of patients most likely to benefit from therapies targeting these proteins currently in clinical development.

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This narrative review synthesizes data from over 40 studies on patients with gastroparesis whose symptoms failed to improve after pyloric drainage procedures (laparoscopic pyloroplasty or endoscopic myotomy). It identifies predictors of failure and proposes a structured management algorithm that escalates through diagnostic tests, medication optimization, and tailored salvage procedures based on patient physiology. The review highlights important gaps in definitions and comparative data that future prospective studies need to fill.

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The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) pilot-tested an online competency-based surgical education curriculum (the Master's Program) with 27 surgeons through usability testing and surveys. Participants rated the content highly and found it easy to navigate, particularly early-career surgeons, but experienced practitioners wanted more advanced material. The findings support broader adoption of the program with targeted improvements in navigation and content depth for senior surgeons.

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In a real-world analysis of 115 patients with resectable NSCLC who received neoadjuvant chemoimmunotherapy outside clinical trials, 78% proceeded to surgery and 17% achieved a pathological complete response. High PD-L1 expression and KRAS mutations were associated with complete response, while age over 72 was the main barrier to surgery. These results confirm the effectiveness and feasibility of this regimen in routine clinical practice, with similar outcomes to pivotal trials.

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An institutional clinical workflow called ImmunoProfile was developed and applied prospectively to tumor biopsies from 2,023 patients across 14 cancer types, using automated multiplex immunofluorescence to quantify immune cells. Patients with high intratumoral CD8 or PD-1 cells had significantly lower risk of death, independent of cancer type and stage. This pan-cancer validation demonstrates the clinical utility of standardized spatial immune profiling as a routine diagnostic tool.

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A five-center study compared first-line MET tyrosine kinase inhibitors vs. immunotherapy (with or without chemotherapy) in 158 patients with MET exon 14-mutant metastatic NSCLC, finding no overall survival difference between strategies. However, MET TKIs were better in patients with low PD-L1 or brain/bone metastases, while immunotherapy was better in patients with very high PD-L1. These findings support individualized treatment selection based on PD-L1 level and pattern of metastases.

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Semi-structured interviews with 19 general surgery residents found they view medical student teaching as a meaningful professional responsibility, though their confidence and engagement vary with clinical workload and their own skill level. Residents primarily see themselves as mentors and cultural guides rather than purely technical teachers. The study proposes a framework for better supporting residents in their teaching roles and suggests institutions formalize recognition of this work.

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Researchers used advanced electron microscopy to characterize the microscopic structure of the calcium salt layer formed by a dental adhesive molecule (10-MDP) at the tooth surface, finding it is not crystalline as previously thought, but rather an amorphous layered structure. The layers trap adhesive resin components through a nanomechanical interlocking mechanism rather than chemical bonding. This new structural model explains the long-term durability of 10-MDP-based dental adhesives.

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Pulmonary sarcomatoid carcinoma (PSC), a rare and aggressive subtype of lung cancer, was found to respond better to immunotherapy than to chemotherapy across multiple institutional cohorts and a national database. Response rates to immunotherapy ranged from 37-43% in PSC, higher than in lung adenocarcinoma, and were driven by very high PD-L1 expression in the majority of PSC tumors. Genomic analysis showed PSC has a distinct mutation profile compared to other lung cancer subtypes, including enrichment for NF1 and NF2 mutations.

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A survey of 66 general surgery residents across four institutions found that degree of introversion or extraversion influenced preferred learning approaches in lectures and simulation settings. Introverted residents preferred anonymous feedback polls, while extraverted residents found competitive skills challenges more motivating. These findings support tailoring surgical education environments to personality traits, particularly in lecture and simulation-based training.

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A small retrospective series found that SMARCA4 mutations can be acquired late in the course of lung adenocarcinoma progression, emerging in about 2% of patients who underwent multiple genomic tests. These acquired mutations appeared under therapy pressure and were associated with increased tumor mutation burden and, in some cases, a shift to a more undifferentiated tumor appearance. This identifies SMARCA4 as a rare but clinically significant resistance mechanism in lung cancer.

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Mutations in the DNA methylation enzyme DNMT3A were found in 4.7% of NSCLCs and associated with significantly improved responses to PD-(L)1 immunotherapy (41.7% vs. 21.5% response rate) independent of other known biomarkers. The mutations reduce DNMT3A protein levels, and cell line analysis linked low DNMT3A expression to an immune-active tumor phenotype. DNMT3A mutation may represent a new biomarker to identify NSCLC patients most likely to respond to immunotherapy.

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This review covers single-atom catalysts (SACs) — materials where individual metal atoms are isolated on a support surface — and their performance in converting CO2 into useful products like fuels or chemicals. SACs achieve high efficiency due to unique electronic properties, and machine learning is emerging as a tool to predict which SAC configurations will work best. The review identifies remaining challenges in synthesis scalability and stability that must be overcome for practical carbon capture applications.

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The final overall survival analysis of the CheckMate 816 trial confirmed that adding nivolumab to pre-surgery chemotherapy for resectable NSCLC significantly improves 5-year survival compared to chemotherapy alone (65.4% vs. 55.0%, hazard ratio 0.72). Patients who achieved a pathological complete response had a 95.3% 5-year survival rate. This definitive survival benefit cements neoadjuvant nivolumab plus chemotherapy as a standard of care for resectable NSCLC.

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A multicenter study examined neoadjuvant chemoimmunotherapy in patients with stage III NSCLC involving the most advanced tumor extent (T4) or multiple lymph node stations (N2/N3). Despite technically borderline or unresectable disease, 75% underwent surgical resection and 29% achieved a pathological complete response. Those who achieved complete response had dramatically better event-free survival, supporting this approach as a strategy to convert initially unresectable disease to curative surgery.

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Analysis of national residency case logs showed that while general surgery residents are performing more cholecystectomies overall, the number performed with intraoperative cholangiography (IOC) has declined significantly from 2012 to 2023. University-affiliated programs had the lowest IOC rates, and more IOCs are now being done by senior residents rather than distributed across training years. This trend risks producing a generation of surgeons inadequately trained in a safety-critical technique for preventing bile duct injuries.

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A randomized trial compared two techniques for placing dental implants in the challenging low-density bone of the upper jaw — a new reverse drilling method versus the standard bone-condensing (osteotome) technique. Both methods produced comparable implant stability and success rates, but patients in the reverse drilling group reported less pain and swelling. The reverse drilling technique appears to be a viable, less invasive alternative to osteotome techniques in soft posterior maxillary bone.

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Among 271 advanced NSCLC patients who stopped immunotherapy specifically because of immune-related side effects, outcomes varied strongly based on how long they had been on treatment before stopping. Those who received more than 6 months of treatment before toxicity had a median post-discontinuation survival of nearly 7 years, versus 21 months for those who stopped within 3 months. Longer treatment duration, good initial response, and PD-L1 positivity all predicted continued disease control after stopping treatment for toxicity.

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A pan-cancer genomic analysis identified MET gene rearrangements (fusions) in about 0.04% of 46,000+ solid tumors, and preliminary results from a phase II trial of the MET inhibitor vebreltinib showed a 50% objective response rate across diverse cancer types. Resistance emerged through kinase domain mutations similar to those seen in other MET-altered cancers. These data establish MET fusions as actionable targets across tumor types and support continued clinical development of targeted MET therapy.

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This study found that activating mutations in the MET kinase domain can emerge as a resistance mechanism in NSCLC driven by other oncogenes (EGFR, KRAS, etc.), occurring in about 0.15% of cases overall and acquired under therapy pressure in 88% of sequenced cases. Cell line experiments confirmed these mutations confer resistance to the primary targeted therapy, and combining that therapy with a MET inhibitor overcame the resistance. This identifies MET kinase domain mutation as a specific acquired resistance mechanism requiring co-targeting strategies.

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In 178 NSCLC patients with brain metastases treated with immunotherapy plus brain radiation, higher PD-L1 expression predicted longer survival and better control of both brain and body disease, but also correlated with higher rates of symptomatic radiation necrosis. Local recurrence after radiation was rare (1-4%) regardless of PD-L1. These findings help clinicians counsel patients on the trade-offs between improved tumor control and increased risk of radiation brain injury in high PD-L1 patients.

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Patients aged 80 or older with PD-L1-high NSCLC receiving first-line pembrolizumab had similar response rates and progression-free survival as younger patients, but shorter overall survival, largely because they were less likely to receive second-line therapy after progression. Tumor immune profiling showed a distinct immunophenotype in older patients, with higher regulatory T cells and closer immune-tumor cell proximity. These findings support not excluding elderly patients from immunotherapy on age grounds alone, while highlighting the need for better second-line treatment strategies.

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Using automated deep learning to measure skeletal muscle on CT scans, researchers found that sarcopenia (low muscle mass) was present in 36% of NSCLC patients and was independently associated with roughly double the risk of severe chemotherapy toxicity across two different treatment cohorts. Sarcopenia also predicted worse overall survival in patients treated with chemotherapy and surgery. This automated assessment could be integrated into routine staging CT scans to identify patients needing dose modification or nutritional support.

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This review traces the evolution of simulation-based training for robotic surgery over 25 years, from basic skill curricula to the integration of AI, augmented reality, and objective performance tracking built into modern robotic systems. While frameworks like Fundamentals of Robotic Surgery exist, standardized advanced curricula and validated assessment tools for complex robotic procedures lag behind clinical practice. The authors argue that surgical training must accelerate development of comprehensive, validated educational frameworks as robotic platforms rapidly advance.

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A series of 8 patients with lateral knee osteoarthritis, valgus deformity, and patellar instability were treated with combined femoral osteotomy and tibial tubercle transposition to simultaneously correct all three problems in one operation. One additional patient received tibial tubercle transposition alone. The article describes the surgical technique and early outcomes of this combined approach for a complex orthopedic condition.

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This case report describes the surgical treatment of a patient with both a valgus-deformed knee and a low-sitting (baja) patella causing chronic instability. The patient underwent a medial closing-wedge femoral osteotomy combined with relocation of the tibial tuberosity. The case illustrates the importance of addressing all contributing anatomical abnormalities simultaneously in patellar instability surgery.

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Gene deletions — not just mutations — of STK11, KEAP1, and SMARCA4 were found in roughly 13-15% each of non-squamous NSCLC cases and were associated with the same poor outcomes to chemoimmunotherapy as mutations in these genes (lower response rates, shorter survival). These deletions were also linked to lower PD-L1 expression and higher aneuploidy. Standard genomic profiling should capture these deletions to fully characterize patients' likelihood of immunotherapy benefit.

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The randomized SQUINT trial tested nivolumab plus ipilimumab versus chemotherapy plus nivolumab in metastatic squamous cell lung cancer and found that tumors with activating MAPK pathway changes responded better to immunotherapy overall. These MAPK-altered tumors had higher CD8 T cell infiltration and a more favorable immune ratio. This identifies MAPK pathway status as a potential predictive biomarker for immunotherapy benefit in squamous lung cancer.

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This systematic review of 12 animal studies and 5 clinical trials found that curcumin, the active compound in turmeric, improved multiple features of polycystic ovary syndrome (PCOS) including hormone levels, follicle development, and metabolic markers like lipids and insulin. The effects appear driven mainly by curcumin's anti-inflammatory and antioxidant properties rather than weight loss. The authors call for more human trials to confirm and build on these findings.

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This review summarizes the emerging uses of EndoFLIP — a probe that measures the stretchability of the stomach and intestinal connections — in bariatric surgery and endoscopy. It describes how the device helps assess sleeve stomach pouch size, detect narrowing after weight loss procedures, and predict reflux risk. The review concludes that EndoFLIP has real utility in bariatric settings though its full role is still being defined.