Does prehabilitation before esophagectomy improve postoperative outcomes? A systematic review and meta-analysis.

Esophagectomy for esophageal cancer is associated with high morbidity. It remains unclear whether prehabilitation, a strategy aimed at optimizing patients' physical and mental functioning prior to surgery, improves postoperative outcomes. A systematic review and meta-analysis was conducted to evaluate the effect of prehabilitation on post-operative outcomes after esophagectomy. Data sources included Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and PEDro, with information from 1 January 2000 to 5 August 2023. The analysis included randomized controlled trials and observational studies that compared prehabilitation interventions to standard care prior to esophagectomy. A random effects model was used to generate a pooled estimate for pairwise meta-analysis, meta-analysis of proportions, and meta-analysis of means. A total of 1803 patients were included with 584 in randomized controlled trials (RCTs) and 1219 in observational studies. In the randomized evidence, there were no significant differences between prehabilitation and control in the odds of postoperative pneumonia (15.0 vs. 18.9%, odds ratio (OR) 1.06 [95% confidence interval (CI): 0.66;1.72]) or pulmonary complications (14 vs. 25.6%, OR 0.68 [95% CI: 0.32;1.45]). In the observational data, there was a reduction in both postoperative pneumonia (22.5 vs. 32.9%, OR 0.48 [95% CI: 0.28;0.83]) and pulmonary complications (26.1 vs. 52.3%, OR 0.35 [95% CI: 0.17;0.75]) with prehabilitation. Hospital and intensive care unit length of stay (days), operative mortality, and severe complications (Clavien-Dindo ≥ 3) did not differ between groups in both the randomized data and observational data. Prehabilitation demonstrated reductions in postoperative pneumonia and pulmonary complications in observational studies, but not RCTs. The overall certainty of these findings is limited by the low quality of the available evidence.

Ten-Year Survival and Recurrence Patterns After Three-Field Lymph Node Dissection for Squamous Cell and Adenocarcinoma of the Esophagus.

OBJECTIVE: The aim was to determine the prevalence of metastases to the cervical and recurrent laryngeal cervicothoracic (CT) nodes as well as survival and recurrence patterns after esophagectomy with three-field lymph node dissection (TFD) in patients with predominately adenocarcinoma (AC) of the esophagus. BACKGROUND: Although esophagectomy with TFD is commonly practiced in Japan and Southeast Asia for squamous cell cancer (SCC) of the esophagus, there are only a handful of reports about its' utilization and survival benefit in North American patients. METHODS: This is a retrospective case series of patients who had an esophagectomy with TFD. The primary outcomes of interest were the prevalence of nodal metastases to the CT nodes as well as overall survival (OS) and disease-free survival. Secondary outcomes included time to recurrence, recurrence patterns, operative morbidity as well as 30 and 90-day mortality. RESULTS: Two hundred forty-two patients with esophageal cancer (AC: 67%) underwent esophagectomy with TFD. Metastases to the CT nodes were present in 56 patients (23%: AC 20% and SCC 30%). Positive CT nodes were present in 14% of pT1/T2 tumors and 30% of pT3 tumors. For the 56 patients with CT positive nodes, 5-year OS was 25% (AC:16%; SCC:39%). Fifteen of 56 (26.7%) patients with metastases to the CT nodes were alive and disease-free at a minimum of 5 years postoperatively. Ten-year OS was 43% for all patients with SCC and 28% for patients with AC. CONCLUSIONS: Metastases to the CT nodes are common in both SCC and AC of the esophagus and may be present in at least 14% of early lesions. Five-year survival is encouraging particularly for patients with esophageal SCC cancer.

Surgical Treatment at an Academic Medical Center is Associated with Statistically Insignificant Lung Cancer Survival Outcome Differences Related to ZIP Code.

BACKGROUND: Low socioeconomic status is a well-characterized adverse prognostic factor in large lung cancer databases. However, such characterizations may be confounded as patients of lower socioeconomic status are more often treated at low-volume, non-academic centers. We evaluated whether socioeconomic status, as defined by ZIP code median income, was associated with differences in lung cancer resection outcomes within a high-volume academic medical center. METHODS: Consecutive patients undergoing resection for non-small cell lung cancer were identified from a prospectively maintained database (2011-18). Patients were assigned an income value based on the median income of their ZIP code as determined by census-based geographic data. We stratified the population into income quintiles representative of SES and compared demographics (chi-square), surgical outcomes, and survival (Kaplan-Meier). RESULTS: We identified 1,693 patients, representing 516 ZIP codes. Income quintiles were Q1: $24,421-53,151; Q2:$53,152-73,982; Q3:$73,983-99,063; Q4:$99,064-123,842; and Q5:$123,843-250,001. Compared to Q5 patients, Q1 patients were younger (median 69 vs. 73, p < 0.001), more likely male (44 vs. 36%, p = 0.035), and more likely Asian, Black, or self-identified as other than white, Asian, or Black. (67 vs. 11%, p = < 0.001). We found minor differences in surgical outcomes and no significant difference in 5-year survival between Q1 and Q5 patients (5-year: 86 vs. 85%, p = 0.886). CONCLUSIONS: Surgical care patterns at a high-volume academic medical center are similar among patients from varying ZIP codes. Surgical treatment at such a center is associated with no survival differences based upon socioeconomic status as determined by ZIP code. Centralization of lung cancer surgical care to high-volume centers may reduce socioeconomic outcome disparities.

Systematic Review - Neuroprotection of ketosis in acute injury of the mammalian central nervous system: A meta-analysis.

To evaluate the neuroprotection exerted by ketosis against acute damage of the mammalian central nervous system (CNS). Search engines were interrogated to identify experimental studies comparing the mitigating effect of ketosis (intervention) versus non-ketosis (control) on acute CNS damage. Primary endpoint was a reduction in mortality. Secondary endpoints were a reduction in neuronal damage and dysfunction, and an 'aggregated advantage' (composite of all primary and secondary endpoints). Hedges' g was the effect measure. Subgroup analyses evaluated the modulatory effect of age, insult type, and injury site. Meta-regression evaluated timing, type, and magnitude of intervention as predictors of neuroprotection. The selected publications were 49 experimental murine studies (period 1979-2020). The intervention reduced mortality (g 2.45, SE 0.48, p < .01), neuronal damage (g 1.96, SE 0.23, p < .01) and dysfunction (g 0.99, SE 0.10, p < .01). Reduction of mortality was particularly pronounced in the adult subgroup (g 2.71, SE 0.57, p < .01). The aggregated advantage of ketosis was stronger in the pediatric (g 3.98, SE 0.71, p < .01), brain (g 1.96, SE 0.18, p < .01), and ischemic insult (g 2.20, SE 0.23, p < .01) subgroups. Only the magnitude of intervention was a predictor of neuroprotection (g 0.07, SE 0.03, p 0.01 per every mmol/L increase in ketone levels). Ketosis exerts a potent neuroprotection against acute damage to the mammalian CNS in terms of reduction of mortality, of neuronal damage and dysfunction. Hematic levels of ketones are directly proportional to the effect size of neuroprotection.

Percutaneous and Open Tracheostomy in Patients with COVID-19: Comparison and Outcomes of an Institutional Series in New York City.

OBJECTIVE: The aim of this study was to report the safety, efficacy, and early results of tracheostomy in patients with COVID-19 and determine whether differences exist between percutaneous and open methods. SUMMARY BACKGROUND DATA: Prolonged respiratory failure is common in symptomatic patients with COVID-19, the disease process caused by infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Tracheostomy, although posing potential risk to the operative team and other healthcare workers, may be beneficial for safe weaning of sedation and ventilator support. However, short- and long-term outcomes remain largely unknown. METHODS: A prospectively collected database of patients with COVID-19 undergoing tracheostomy at a major medical center in New York City between April 4 and April 30, 2020 was reviewed. The primary endpoint was need for continued mechanical ventilation. Secondary outcomes included complication rates, sedation weaning, and need for intensive care unit (ICU) level of care. Patient characteristics, perioperative conditions, and outcomes between percutaneous and open groups were analyzed. RESULTS: During the study period, 67 consecutive patients underwent tracheostomy, including 48 males and 19 females with a median age of 66 years [interquartile range (IQR) 52-72]. Two surgeons alternated techniques, with 35 tracheostomies performed percutaneously and 32 via an open approach. The median time from intubation to tracheostomy was 23 days (IQR 20-26). At a median follow-up of 26 days, 52 patients (78%) no longer required mechanical ventilation and 58 patients (87%) were off continuous sedation. Five patients (7.5%) died of systemic causes. There were 11 total complications (16%) in 10 patients, most of which involved minor bleeding. There were no significant differences in outcomes between percutaneous and open methods. CONCLUSIONS: Tracheostomy under apneic conditions by either percutaneous or open technique can be safely performed in patients with respiratory failure due to COVID-19. Tracheostomy facilitated weaning from continuous intravenous sedation and mechanical ventilation. Continued follow-up of these patients to ascertain long-term outcome data is ongoing.

Amyloid Aggregation of Streptococcus mutans Cnm Influences Its Collagen-Binding Activity.

The cnm gene, coding for the glycosylated collagen- and laminin-binding surface adhesin Cnm, is found in the genomes of approximately 20% of Streptococcus mutans clinical isolates and is associated with systemic infections and increased caries risk. Other surface-associated collagen-binding proteins of S. mutans, such as P1 and WapA, have been demonstrated to form an amyloid quaternary structure with functional implications within biofilms. In silico analysis predicted that the ß-sheet-rich N-terminal collagen-binding domain (CBD) of Cnm has a propensity for amyloid aggregation, whereas the threonine-rich C-terminal domain was predicted to be disorganized. In this study, thioflavin-T fluorescence and electron microscopy were used to show that Cnm forms amyloids in either its native glycosylated or recombinant nonglycosylated form and that the CBD of Cnm is the main amyloidogenic unit of Cnm. We then performed a series of in vitro, ex vivo, and in vivo assays to characterize the amylogenic properties of Cnm. In addition, Congo red birefringence indicated that Cnm is a major amyloidogenic protein of S. mutans biofilms. Competitive binding assays using collagen-coated microtiter plates and dental roots, a substrate rich in collagen, revealed that Cnm monomers inhibit S. mutans binding to collagenous substrates, whereas Cnm amyloid aggregates lose this property. Thus, while Cnm contributes to recognition and initial binding of S. mutans to collagen-rich surfaces, amyloid formation by Cnm might act as a negative regulatory mechanism to modulate collagen-binding activity within S. mutans biofilms and warrants further investigation. IMPORTANCE Streptococcus mutans is a keystone pathogen that promotes caries by acidifying the dental biofilm milieu. The collagen- and laminin-binding glycoprotein Cnm is a virulence factor of S. mutans. Expression of Cnm by S. mutans is hypothesized to contribute to niche expansion, allowing colonization of multiple sites in the body, including collagen-rich surfaces such as dentin and heart valves. Here, we suggest that Cnm function might be modulated by its aggregation status. As a monomer, its primary function is to promote attachment to collagenous substrates via its collagen-binding domain (CBD). However, in later stages of biofilm maturation, the same CBD of Cnm could self-assemble into amyloid fibrils, losing the ability to bind to collagen and likely becoming a component of the biofilm matrix. Our findings shed light on the role of functional amyloids in S. mutans pathobiology and ecology.

Tumoral CD10 expression correlates with aggressive histology and prognosis in patients with malignant pleural mesothelioma.

BACKGROUND: Currently, tumor-node-metastasis stage and histologic type are the established prognostic factors for malignant pleural mesothelioma, whereas no prognostic markers have been established for clinical practice. We investigated the prognostic value of CD10, a metalloproteinase that can promote cancer aggressiveness through enzymatic degradation and intracellular signaling crosstalk, in malignant pleural mesothelioma. METHODS: CD10 immunostaining was performed for 176 cases of malignant pleural mesothelioma (epithelioid, 148; biphasic, 14; sarcomatoid, 14), and its expression was dichotomized as negative (no staining) or positive (any staining). Epithelioid tumors were classified as pleomorphic subtype when cytologic pleomorphism was ≥10 % of the tumor. Overall survival (OS) was analyzed by log-rank tests and Cox proportional hazard models. RESULTS: Tumoral CD10 expression was identified in 42 % of epithelioid non-pleomorphic tumors, 57 % of epithelioid pleomorphic tumors, 79 % of biphasic tumors, and 93 % of sarcomatoid tumors (p < 0.001). Positive CD10 expression was correlated with higher mitotic count (p = 0.002). Overall survival for patients with positive CD10 expression was significantly shorter than that for patients with negative CD10 expression in all patients (p = 0.001) and in patients with epithelioid tumor (p = 0.04). On multivariate analysis, CD10 expression was an independent prognostic factor for all patients (hazard ratio 1.48; p = 0.019). CONCLUSIONS: Tumoral CD10 expression correlated with aggressive histologic types and higher mitotic activity and is an independent prognostic factor for patients with malignant pleural mesothelioma.

Wedge resection, segmentectomy, and lobectomy: oncologic outcomes based on extent of surgical resection for ≤2 cm stage IA non-small cell lung cancer.

Background: Long-standing controversy has existed over whether sublobar resection is an adequate oncological procedure for clinical stage IA non-small cell lung cancer (NSCLC) ≤2 cm, despite the recent randomized trial reports of Japanese Clinical Oncology Group (JCOG) 0802 and Cancer and Leukemia Group B (CALGB) 140503 demonstrating non-inferior outcomes with sublobar resection compared to lobectomy. As practice patterns shift, we sought to compare oncologic outcomes in patients with these early-stage tumors after wedge resection, segmentectomy, or lobectomy in a contemporary, real-world, cohort. Methods: A retrospective review of a prospectively maintained database from a single institution was conducted from 2011 to 2020 to identify all patients with clinically staged IA1 or IA2 NSCLC (tumors ≤2 cm with no nodal involvement). The primary outcomes of interest were overall survival (OS) and disease-free survival (DFS), with secondary outcomes of lung cancer-specific survival (LCSS), recurrence patterns, and perioperative morbidity and mortality. Results: A total of 480 patients were identified; 93 (19.4%) patients underwent wedge resection, 90 (18.7%) received segmentectomy, and 297 (61.9%) underwent lobectomy. Patients who underwent wedge resection had worse Eastern Cooperative Oncology Group (ECOG) performance status (23.7% ECOG 1 or 2 vs. 5.6% among segmentectomy and 5.4% among lobectomy, P<0.05). Both wedge resection and segmentectomy patients had lower preoperative mean percentage of predicted forced expiratory volume in one second (%FEV1) compared to the lobectomy group (81.8% and 82.6% vs. 89.6%, P=0.002), a higher proportion of patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), and a higher Charlson Comorbidity Index. There were no statistically significant differences in 5-year OS, DFS, or LCSS between groups: 90%, 61%, 78% for wedge resections compared with 85%, 75%, 86% for segmentectomy, and 87%, 77%, 87% for lobectomy, respectively. Recurrence was observed in 17 patients who underwent wedge resection (18.3%, 8 local, 9 distant), 12 patients who received segmentectomy (13.4%, 6 local, 6 distant), and 38 patients who underwent lobectomy (12.8%, 11 local, 27 distant), which was not significantly different (P=0.36). Conclusions: Patients with inferior performance status or lower baseline pulmonary function are more likely to receive wedge resection for clinical stage IA NSCLC ≤2 cm in size. For these small tumors, lobectomy, segmentectomy, and wedge resection provide comparable oncologic outcomes.

Survival difference among adult and pediatric mediastinal yolk sac tumors cases: A meta-analysis of case reports.

BACKGROUND: Mediastinal Yolk sac tumors (YST) are rare and highly malignant extragonadal germ cell tumors with rapid growth and early metastases. We sought to conduct a meta-analysis of published case reports/case series to compare differences in survival, demographics, and treatment modalities between adult and pediatric patients with YST. METHODS: Ovid Embase, Cochrane, and Ovid Medline databases were searched for primary mediastinal pure YST cases. The primary outcome was overall survival (OS). Log-rank and Cox regression were used. This study is registered on PROSPERO (CRD42022367586). RESULTS: Among 846 studies, 87 met our inclusion criteria including 130 patients (Adults: 90 and Pediatrics: 40). About 41.5% of the patients were from the United States. The median age was 23.0 (Q1-Q3: 17.0-30.0), 88.5% were males, and (32.3%) were Asian. Stage II represented almost 40%. AFP was elevated in 96.9%. Respiratory distress was the presenting symptom in 65.4%. Chemotherapy, radiotherapy, and surgery were utilized in 84.6, 23.1, and 64.7% respectively. Median OS was 24 months (Adults: 23 months, Pediatrics: 25 months, P = 0.89). 3- and 5-year OS were 34.4% and 22.9% in adults and 41.5% and 41.5% in pediatrics, respectively. On multivariate analysis, anterior location of tumors, receipt of chemotherapy, and undergoing surgery were associated with better OS. CONCLUSION: Primary mediastinal YSTs are rare, but lethal neoplasms. Our meta-analysis showed that mediastinal YSTs mimic other non-seminomatous mediastinal GCTs in terms of clinical characteristics and available treatment options. Early diagnosis, neoadjuvant chemotherapy, and surgical resection are the key points for effective management and improved outcomes.

Postinfarction Ventricular Septal Ruptures During the COVID-19 Pandemic: Two Case Series.

This case series highlights the occurrence of hemodynamically significant ventricular septal defects (VSDs) in two patients presenting with ST-elevation myocardial infarction (STEMI) during the COVID-19 pandemic. This paper aims to emphasize the delayed presentation of cardiac emergencies, such as STEMI, due to concerns about contracting COVID-19. This delay has led to an increased risk of rare complications, including VSD, associated with STEMI. The first case involves a 92-year-old male with a history of hypertension, hyperlipidemia, chronic kidney disease, and coronary artery disease. He presented with acute chest pain, and diagnostic tests revealed ST elevations and a VSD. Despite intervention efforts, including hemodynamic support, the patient's condition deteriorated, and he passed away due to advanced age and high surgical risk. The second case involves a 62-year-old female with a medical history of diabetes, hypertension, and hyperlipidemia. She presented with left-sided chest pain, and an angiogram revealed a mid-right coronary artery stenosis and a thrombus. During the procedure, the patient experienced hypotension, requiring hemodynamic support. Subsequent evaluations identified a large VSD with right ventricular dysfunction. The patient underwent a series of interventions, including a ventricular assist device and VSD closure, but experienced multi-organ failure and ultimately passed away. VSDs following acute myocardial infarction (MI) are rare but life-threatening complications. Early revascularization is crucial in preventing the development of VSDs. These cases demonstrate the importance of prompt diagnosis and intervention, as delayed presentation increases the risk of mechanical complications. Surgical closure remains the definitive treatment for postinfarction VSDs.

Agranulocytosis Secondary to Cancer Chemotherapy Associated With Higher In-Hospital Mortality in Patients With Central Line Insertion During a Hospital Stay.

Background Agranulocytosis secondary to cancer chemotherapy (ASCC) remains a leading cause of morbidity and mortality. Central line-associated bloodstream infections (CLABSI) are also particularly prevalent in these populations and may portend a poorer outcome. Our study serves to investigate the relationship between patients with agranulocytosis secondary to cancer chemotherapy and the insertion of a central venous catheter (CVC) with respect to in-hospital mortality. Methods and results We utilized the National Inpatient Survey 2019 database. We utilized the International Classification of Diseases (ICD)-10 CM codes to identify ASCC and other medical comorbidities. We utilized ICD-10 PCS codes to identify CVC insertions. Multivariate logistic regression was utilized to study the effect of CVC insertion on in-hospital mortality. In patients with ASCC, CVC insertion was associated with a higher in-hospital mortality (unadjusted: 11.9% vs. 1%, p<0.001, adjusted OR 19.27, 95% CI 5.84 - 65.6, p<0.001) adjusted for baseline characteristics and other comorbidities. Patients in the study cohort who were older than 70 years of age also had a higher in-hospital mortality relative to younger age groups (adjusted OR 2.31, 95% CI 1.04-5.13, p<0.039). Conclusion In patients with ASCC, CVC insertion during hospitalization is associated with higher in-hospital mortality.

Myocarditis as a Complication of Campylobacter jejuni-Associated Enterocolitis: A Report of Two Cases.

Myocarditis refers to inflammation of the heart muscle and may occur individually or together with pericarditis, which refers to inflammation of the saclike tissue layer that surrounds the heart. They may have infectious or non-infectious etiologies. Campylobacter jejuni, a major cause of gastroenteritis worldwide, may also cause myocarditis in rare situations. We present two cases highlighting this rare complication of diarrheal disease caused by Campylobacter jejuni infection and subsequent development of myocarditis. Both patients presented with chest pain and multiple episodes of watery diarrhea, with initial EKGs showing ST segment changes, as well as elevated inflammatory markers and elevated troponins. GI panels for both patients were positive for Campylobacter jejuni. Based on their presentations and investigative findings, they were diagnosed with myocarditis secondary to Campylobacter infection, and their symptoms subsided with appropriate management. It is unclear if the myocardial damage, in this case, is a direct effect of the toxin on cardiac myocytes or secondary to an immunologic phenomenon. Regardless, Campylobacter jejuni-associated myocarditis remains a rare phenomenon and needs to be considered in the differential of patients presenting with concurrent chest pain and diarrheal symptoms.

A Gut-Wrenching Feeling: Overcoming Cognitive Biases in an Atypical Presentation of Chronic Mesenteric Ischemia.

Chronic mesenteric ischemia is a rare but serious condition that can present with a variety of symptoms, including abdominal pain, diarrhea, and weight loss. Our case report presents a 63-year-old male with a past medical history of generalized anxiety disorder, Barrett's esophagus, hypertension, hyperlipidemia, chronic obstructive pulmonary disease (COPD) with active smoking who initially presented with severe diffuse abdominal pain, nausea, vomiting, and chronic diarrhea resulting in malnutrition and 40-pound weight loss over a six-month span. The patient underwent extensive diagnostic evaluation and was diagnosed with Yersinia gastroenteritis via gastroenteritis panel (GI Panel), explaining all of the patient's symptoms. The patient underwent treatment for said gastroenteritis but did not experience remission of symptoms, leading to further diagnostic evaluations; a definitive diagnosis was not found, yet the patient's symptoms persisted. The patient then underwent extensive serologic and endoscopic evaluation, after extensive imaging and diagnostic work-up, the patient was finally diagnosed with chronic mesenteric ischemia (CMI) of the superior mesenteric artery (SMA) with severe celiac and inferior mesenteric artery (IMA) stenosis. The patient initially underwent stenting (7 mm by 26 mm Balloon Mounted LifestreamTM Covered Stent; Becton Dickson (BD); Franklin Lakes, NJ, USA), which provided temporary relief to his symptoms, however, the relief did not last long. Upon reimaging, the patient was found to have stenosis of the stent, leading to the eventual placement of a bare-metal stent (ExpressTM LD 7 x 27 mm balloon mounted bare-metal stent; Boston Scientific; Boston, MA, USA) across the celiac artery as well as the placement of an IMA stent (InnovaTM Self-expanding 5 x 20 mm bare-metal stent; Boston Scientific). This eventually resulted in the resolution of the patient's symptoms, eventual weight gain, and improvement in quality of life.

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non-small cell lung cancer: Results from a randomized trial.

OBJECTIVE: Several trials have recently reported the safety of pulmonary resection after neoadjuvant immunotherapy with encouraging major pathological response rates. We report the detailed adverse events profile from a recently conducted randomized phase II trial in patients with resectable non-small cell lung cancer treated with neoadjuvant durvalumab alone or with sub-ablative radiation. METHODS: We conducted a randomized phase II trial in patients with non-small cell lung cancer clinical stages I to IIIA who were randomly assigned to receive neoadjuvant durvalumab alone or with sub-ablative radiation (8Gyx3). Secondary end points included the safety of 2 cycles of preoperative durvalumab with and without radiation followed by pulmonary resection. Postoperative adverse events within 30 days were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: Sixty patients were enrolled and randomly assigned, with planned resection performed in 26 patients in each arm. Baseline demographics and clinical variables were balanced between groups. The median operative time was similar between arms: 128 minutes (97-201) versus 146 minutes (109-214) (P = .314). There was no 30- or 90-day mortality. Grade 3/4 adverse events occurred in 10 of 26 patients (38%) after monotherapy and in 10 of 26 patients (38%) after dual therapy. Anemia requiring transfusion and hypotension were the 2 most common adverse events. The median length of stay was similar between arms (5 days vs 4 days, P = .172). CONCLUSIONS: In this randomized trial, the addition of sub-ablative focal radiation to durvalumab in the neoadjuvant setting was not associated with increased mortality or morbidity compared with neoadjuvant durvalumab alone.

Should sampling of three N2 stations be a quality metric for curative resection of stage I lung cancer?

OBJECTIVE: In 2022, the American College of Surgeons Commission on Cancer issued standard 5.8 quality metric for curative lung cancer resections requiring nodal resection from 3 N2 stations. In this report, we compare oncologic outcomes after resection of 3 N2 stations versus 2 N2 stations in stage I non-small cell lung cancer. METHODS: A retrospective review from a single institution database was conducted from 2011 to 2020 to identify patients with clinical stage I non-small cell lung cancer. Patients with a history of lung cancer, carcinoid tumors, and ground-glass lesions less than 50% solid component were excluded. The primary outcome was overall survival. Secondary outcomes included disease-free survival, recurrence patterns, and nodal upstaging. RESULTS: A total of 581 patients were identified and divided into 2 groups based on the number of N2 stations examined: Group A had 2 N2 stations examined (364 patients), and group B had 3 or more N2 stations examined (217 patients). Baseline demographic and clinical characteristics were similar between groups. In group A, N1 and N2 positive nodal stations were present in 8.2% (30/364) and 5.2% (19/364) of patients versus 7.4% (16/217) and 5.5% (12/217), respectively, in group B. Five-year overall survival and disease-free survival were 89% and 74% in group A versus 88% and 78% in group B, respectively. Recurrence occurred in 56 patients (15.4%) in group A (6.6% local and 8.8% distant) and 29 patients (13.4%) in group B (5.1% local and 8.3% distant; P = .73). CONCLUSIONS: There was no significant difference in oncological outcomes in stage I non-small cell lung cancer resections that included 2 N2 stations compared with at least 3 N2 stations examined.

Tumor-Targeted Nonablative Radiation Promotes Solid Tumor CAR T-cell Therapy Efficacy.

Infiltration of tumor by T cells is a prerequisite for successful immunotherapy of solid tumors. In this study, we investigate the influence of tumor-targeted radiation on chimeric antigen receptor (CAR) T-cell therapy tumor infiltration, accumulation, and efficacy in clinically relevant models of pleural mesothelioma and non-small cell lung cancers. We use a nonablative dose of tumor-targeted radiation prior to systemic administration of mesothelin-targeted CAR T cells to assess infiltration, proliferation, antitumor efficacy, and functional persistence of CAR T cells at primary and distant sites of tumor. A tumor-targeted, nonablative dose of radiation promotes early and high infiltration, proliferation, and functional persistence of CAR T cells. Tumor-targeted radiation promotes tumor-chemokine expression and chemokine-receptor expression in infiltrating T cells and results in a subpopulation of higher-intensity CAR-expressing T cells with high coexpression of chemokine receptors that further infiltrate distant sites of disease, enhancing CAR T-cell antitumor efficacy. Enhanced CAR T-cell efficacy is evident in models of both high-mesothelin-expressing mesothelioma and mixed-mesothelin-expressing lung cancer-two thoracic cancers for which radiotherapy is part of the standard of care. Our results strongly suggest that the use of tumor-targeted radiation prior to systemic administration of CAR T cells may substantially improve CAR T-cell therapy efficacy for solid tumors. Building on our observations, we describe a translational strategy of "sandwich" cell therapy for solid tumors that combines sequential metastatic site-targeted radiation and CAR T cells-a regional solution to overcome barriers to systemic delivery of CAR T cells.

A Rare Initial Presentation of Aortic Intramural Hematoma: A Case Report and Literature Review.

Aortic intramural hematoma (AIH) is a life-threatening emergency that involves aortic wall integrity and is characterized by either a direct rupture of the vasa vasorum or spontaneous bleeding of an arterial plaque located in the tunica media of the aortic wall. A notable difference between AIH and acute aortic dissection is the absence of an intimal flap, a finding discernable on computed tomography angiography (CTA). Follow-up imaging allows for the monitoring of disease progression or early findings of impending complications. While some patients may require surgical intervention, medical management with blood pressure control remains the mainstay in treatment. Our case describes a patient who was found to be in cardiac arrest secondary to ventricular fibrillation and was then found to have presumed Stanford Type A aortic dissection on CTA. After reviewing the scans, the diagnosis was reclassified to AIH due to the absence of an intimal flap, the patient was then managed medically for AIH with antihypertensive medications.

Hemophagocytic Lymphohistiocytosis in a Patient With Post-acute COVID-19 Infection.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation with extensive inflammation and tissue destruction due to abnormal immune activation. Post-COVID-19 patients who have recovered with negative serologic tests may also present with secondary HLH, an unusual finding that our case demonstrates. A 73-year-old male with a notable past medical history of fall COVID-19 infection approximately 11 months prior presented initially to emergency services with a chief complaint of high fevers, lethargy, and progressive changes in mentation gradually progressive over the last 5 months' duration. This presentation was concerning for HLH in view of the patient's high H score and clinical suspicion for HLH, and he was initiated on dexamethasone 20 mg daily. intravenous immune globulin (IVIG) protocol was also trialed, despite which the patient continued to deteriorate before expiring during the course of the hospitalization. sHLH following COVID-19 infection remains a poorly understood phenomenon. The severity of the COVID-19 infection does not appear to be related to one's predisposition to develop sHLH. The mortality of HLH remains high even with appropriate therapy.

Extent of Resection Influences Survival in Early-Stage Lung Cancer With Occult Nodal Disease.

BACKGROUND: Minimal literature exists evaluating the impact of the extent of resection on survival in patients with small, early-stage non-small cell lung cancer (NSCLC) found to have occult nodal disease. We hypothesized that sublobar resection has comparable overall survival to patients undergoing lobectomy for clinical stage IA NSCLC that harbors occult nodal disease. METHODS: The National Cancer Database was reviewed for identification of patients with clinical stage IA NSCLC who underwent wedge resection, segmentectomy, or lobectomy and were found to have occult nodal disease. Overall survival was compared between groups, and a multivariate Cox regression model identified factors associated with worse survival. RESULTS: Occult nodal disease occurred in 6.1% of all patients with clinical stage IA disease undergoing resection. Patients undergoing wedge resection and segmentectomy found to have occult nodal disease were older (67.6 ± 9.6 years of age vs 66.1 ± 9.3 years of age vs 65.6 ± 9.5 years of age; P = .004) and had more advanced pathologic stage (pStage III: 68.7% vs 50.5% vs 41.5%; P < .001) than those receiving lobectomy. There was no difference in the median overall survival between segmentectomy and lobectomy (68.5 months vs 57.6 months; P = .200). However, wedge resection was independently associated with worse overall survival when controlling for other preoperative variables (hazard ratio, 1.23; 95% confidence interval, 1.01-1.51; P = .042). CONCLUSIONS: Review of the National Cancer Database suggests that there is no improvement in overall survival in patients undergoing lobectomy vs segmentectomy in carefully selected patients with clinical stage IA NSCLC harboring occult nodal disease. However, those undergoing wedge resection may have worse overall survival than those undergoing both lobectomy and segmentectomy.