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The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.

Introduction Anti-PD-(L)1 immune checkpoint inhibitors (ICI) improve survival in patients with advanced non-small cell lung cancer (aNSCLC). The clinical features, survival, and burden of toxicities of patients with aNSCLC alive >1 year from ICI initiation are poorly understood. Materials and Methods We defined ICI survivors as patients alive >1 year after ICI start and retrospectively reviewed demographics, treatment, and immune-related adverse events (irAEs). Long-term irAEs were defined as ongoing irAEs lasting >1 year; burden of toxicity measures were based on percentage of days a patient experienced toxicity. Using linear and logistic regression, we evaluated association between demographics and disease characteristics with burden of toxicity. Results We identified 114 ICI survivors from 317 patients with aNSCLC. Half (52%) experienced an irAE of any grade, and 23.7% developed long-term irAEs. More ICI survivors with irAES in the first year had never smoked (P = .018) or received ICIs as frontline therapy (P = .015). The burden of toxicity in the first year significantly correlated with the burden of toxicity afterward (ρ = 0.72; P < .001). No patients with progressive disease had a high burden of toxicity, and they experienced 30.6% fewer days with toxicity than those with stable disease. Increased duration of therapy was associated with higher odds of experiencing toxicity. Half of ICI survivors with irAEs were still receiving treatment for unresolved irAEs at time of death or last follow-up. Conclusion Significant proportions of ICI survivors have unresolved long-term toxicities. These data support a growing need to understand long-term toxicity to optimize management of those treated with ICIs.

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

OBJECTIVE Non–small cell lung cancer (NSCLC) is the most common primary tumor to develop brain metastasis. Prognostic markers are needed to better determine survival after neurosurgical resection of intracranial disease. Given the importance of mutation subtyping in determining systemic therapy and overall prognosis of NSCLC, the authors examined the prognostic value of mutation status for postresection survival of patients with NSCLC brain metastasis. METHODS The authors retrospectively analyzed all cases of NSCLC brain metastasis with available molecular testing data that were resected by a single surgeon at a single academic center from January 2009 to February 2019. Mutation status, demographic characteristics, clinical factors, and treatments were analyzed. Association between predictive variables and overall survival after neurosurgery was determined with Cox regression. RESULTS Of the included patients (n = 84), 40% were male, 76% were smokers, the mean ± SD Karnofsky Performance Status was 85 ± 14, and the mean ± SD age at surgery was 63 ± 11 years. In total, 23%, 26%, and 4% of patients had EGFR, KRAS, and ALK/ROS1 alterations, respectively. On multivariate analysis, survival of patients with EGFR (HR 0.495, p = 0.0672) and KRAS (HR 1.380, p = 0.3617) mutations were not significantly different from survival of patients with wild-type (WT) tumor. However, the subgroup of patients with EGFR mutation who also received tyrosine kinase inhibitor (TKI) therapy had significantly prolonged survival (HR 0.421, p = 0.0471). In addition, postoperative stereotactic radiosurgery (HR 0.409, p = 0.0177) and resected tumor diameter < 3 cm (HR 0.431, p = 0.0146) were also significantly associated with prolonged survival, but Graded Prognostic Assessment score ≤ 1.0 (HR 2.269, p = 0.0364) was significantly associated with shortened survival. CONCLUSIONS Patients with EGFR mutation who receive TKI therapy may have better survival after resection of brain metastasis than patients with WT tumor. These results may inform counseling and decision-making regarding the appropriateness of resection of NSCLC brain metastasis.

During 2018-2019, the Rhode Island Department of Health (RIDOH) and the Missouri Department of Health and Senior Services (DHSS) investigated cases of metal poisonings associated with commercially and home-prepared cakes decorated with products referred to as luster dust. Several types of glitters and dusts, broadly known as luster dust,* for use on prepared foods can be purchased online and in craft and bakery supply stores (1). Decorating foods with luster dust and similar products is a current trend, popularized on television programs, instructional videos, blogs, and in magazine articles.† Some luster dusts are specifically produced with edible ingredients that can be safely consumed. Companies that make edible luster dust are required by law to include a list of ingredients on the label (2). Luster dusts that are safe for consumption are typically marked "edible" on the label. Some luster dusts used as cake decorations are not edible or food grade; labeled as "nontoxic" or "for decorative purposes only," these luster dusts are intended to be removed before consumption (3). RIDOH (2018) and Missouri DHSS (2019), investigated heavy metal poisonings associated with commercially and home-prepared cakes decorated with luster dust after receiving reports of children (aged 1-11 years) who became ill after consuming birthday cake. Cases in Rhode Island were associated with copper ingestion, and the case in Missouri was associated with a child's elevated blood lead level. In Rhode Island, luster dust products that had been used in cake frosting were found to contain high levels of multiple metals.§ These events indicate that increased vigilance by public health departments and further guidance to consumers and bakeries are needed to prevent unintentional poisonings. Labeling indicating that a product is nontoxic does not imply that the product is safe for consumption. Explicit labeling indicating that nonedible products are not safe for human consumption is needed to prevent illness from inappropriate use of inedible products on foods. Educating consumers, commercial bakers, and public health professionals about potential hazards of items used in food preparation is essential to preventing illness and unintentional poisoning from toxic metals and other nonedible ingredients.

Facial trauma can have long-lasting physical and mental consequences. Trauma to the nose is commonly seen in the emergency department. Nasal lacerations account for 7% of all facial lacerations. Thorough examination and documentation including photographs is important for documentation and creating a reconstruction plan. Underlying damage to cartilage or bone must be reconstructed initially or in a delayed fashion to recreate the pretrauma anatomy and function. There are several options for soft tissue nasal reconstruction, including local flaps, skin grafts, pedicle flaps, and free flaps. At present there is no standard of care for postoperative facial trauma wound care.

Background: Prognostic risk factors for completely resected stage IA non-small-cell lung cancers (NSCLCs) have advanced minimally over recent decades. Although several biomarkers have been found to be associated with cancer recurrence, their added value to TNM staging and tumor grade are unclear. Methods: Features of preoperative low-dose CT image and histologic findings of hematoxylin- and eosin-stained tissue sections of resected lung tumor specimens were extracted from 182 stage IA NSCLC patients in the National Lung Screening Trial. These features were combined to predict the risk of tumor recurrence or progression through integrated deep learning evaluation (IDLE). Added values of IDLE to TNM staging and tumor grade in progression risk prediction and risk stratification were evaluated. Results: The 5-year AUC of IDLE was 0.817 ± 0.037 as compared to the AUC = 0.561 ± 0.042 and 0.573 ± 0.044 from the TNM stage and tumor grade, respectively. The IDLE score was significantly associated with cancer recurrence (p < 0.0001) even after adjusting for TNM staging and tumor grade. Synergy between chest CT image markers and histological markers was the driving force of the deep learning algorithm to produce a stronger prognostic predictor. Conclusions: Integrating markers from preoperative CT images and pathologist’s readings of resected lung specimens through deep learning can improve risk stratification of stage 1A NSCLC patients over TNM staging and tumor grade alone. Our study suggests that combining markers from nonoverlapping platforms can increase the cancer risk prediction accuracy.

Dietary factors are known to influence urinary fluoride (UF) levels in nonpregnant people. Maternal UF is used as a biomarker of fluoride exposure; however, dietary influences on UF during pregnancy are unknown. We compared UF levels and assessed the associations between UF and five select dietary influences in pregnancy vs. one-year postpartum: dietary fluoride (F), calcium intake from diet (Ca-diet), calcium intake from supplements (Ca-sup), dietary acid load (AL), and table salt use (TS) in 421 women exposed to fluoridated salt in the Mexican diet. Spot UF (mg/L) was measured by microdiffusion/fluoride-specific electrode and dilution-corrected with specific gravity (SG). Dietary variables were estimated from a validated Food Frequency Questionnaire. Comparisons among UF in pregnancy vs. one-year postpartum were performed with non-parametric tests. Associations between dietary variables and UF were assessed using random effect models (for pregnancy) and linear regression (for one-year postpartum). SG-corrected UF (median, range) during pregnancy (0.77, 0.01–4.73 mg/L) did not significantly differ from one-year postpartum (0.75, 0.15–2.62 mg/L) but did increase every 10 gestational weeks, β = 0.05 (CI: 0.00–0.10). Different dietary influences on UF were identified at each state. Although Ca-diet and AL were not associated with UF in either state, Ca-sup decreased UF only during pregnancy, β = − 0.012 mg/L (CI: − 0.023–0.00). Reporting TS use was associated with 12% increase in UF only at one-year postpartum (p = 0.026). These results suggest different dietary influences on UF in the pregnant state, which need consideration when using UF as a biomarker of fluoride exposure.

ImportancePathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS).ObjectiveWe sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630.Design, Setting, and ParticipantsRTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes.InterventionPatients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone.Main Outcomes and MeasuresOverall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017.ResultsOverall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45).Conclusions and RelevanceThis ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies.Trial RegistrationClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

Zusammenfassung Beim SPECT-CT erfolgt die Fusionierung der Bilder der funktionellen Bildgebung der Szintigraphie mit der strukturellen Darstellung des CT. Hierdurch lassen sich hohe Ortsauflosungen erzielen. Die erhobenen Befunde korrelieren gut mit der tatsachlichen Schmerzgenese. Insbesondere am Fus kann diese Technik bei komplexen Fragestellungen einen Mehrwert liefern.

Objective:To estimate dietary fluoride intake (F) over the course of pregnancy and the overall adjusted difference in dietary F intake by pregnancy stages and levels of compliance with dietary recommendations.Design:Secondary data analysis from a longitudinal pregnancy cohort study in a population exposed to fluoridated salt. Women were followed during the early, middle and late stages of their pregnancy (n 568). The dietary intake of recommended prenatal nutrients according to Mexican dietary guidelines and F intake (mg/d) was estimated with a validated FFQ. Data were summarised with descriptive statistics. Levels of F intake were compared with the USA’s Institute of Medicine adequate intake (AI) of 3 mg/d for pregnancy. Adjusted differences in F intake by pregnancy stages and levels of compliance with recommendations were estimated using random effects models.Setting:Mexico City.Participants:Women participating in the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) project, from 2001 to 2003.Results:Median dietary F intake throughout pregnancy ranged from 0·64 (interquartile range (IQR) 0·38) in the early to 0·70 (IQR 0·42) in the middle, and 0·72 (IQR 0·44) mg/d in the late stage (0·01 mg F/kg per d). Corresponding adjusted intakes of F were 0·72 (95 % CI 0·70, 0·74), 0·76 (95 % CI 0·74, 0·77) and 0·80 (95 % CI 0·78, 0·82) mg/d. Women who were moderately and highly compliant with Mexican dietary recommendations ingested, on average, 0·04 and 0·14 mg F/d more than non-compliant women (P < 0·005).Conclusions:Dietary F intake was below current AI, was greater with the progression of pregnancy and in women who were moderately and highly compliant with dietary recommendations.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

Mini-Implantate in der Fus- und Sprunggelenkchirurgie werden zunehmend eingesetzt. Ziel der Implantate ist der Erhalt der Funktion der Gelenke, unter Berucksichtigung der Biologie und der Ruckzugsmoglichkeiten. Fruhe Versuche mit Mini-Implantaten im Sinne von silastischen Implantaten oder Teilprothesen brachten nicht den erhofften Erfolg. Mit Einfuhrung eines modernen metallischen Mini-Implantats konnten die ersten Erfolge am MTP‑I sowie dem oberen Sprunggelenk (OSG) erzielt werden. Seit wenigen Jahren steht ein Implantat aus Polyvinylalkohol zur Versorgung des arthrotischen MTP‑I zur Verfugung. Implantate aus Polylactid konnen als Interpositionsarthroplastiken bei Arthrosen der Lisfranc-Gelenkreihe oder des MTP‑I zum Einsatz kommen. Eine neue Technik ohne Langzeiterfahrung bei therapierefraktaren Defekten des Talus stellt die Versorgung mittels Hemiprothese dar. Dieser Artikel gibt einen Uberblick uber die momentan verfugbaren Mini-Implantate. Der Einsatz als mogliche Alternative zur Vollprothese oder Versteifung wird vor dem Hintergrund der aktuell verfugbaren Literatur kritisch beleuchtet.

Bei der Pathogenese des Pes planovalgus kommt der medialen Saule des Fuses eine besondere Rolle zu. Die relevanten Strukturen umfassen den tibiokalkaneonavikularen Bandapparat, die navikulokuneiformen Gelenke inklusive der Ossa cuneiformia selbst und auch das erste tarsometatarsale Gelenk. Daher ist eine Kombination knocherner und weichteiliger Korrekturen bei der Korrektur des Pes planovalgus zu berucksichtigen. Die hier vorliegende Arbeit beschreibt stabilisierende und korrigierende Eingriffe an der medialen Saule des Fuses mitsamt der zugrundeliegenden Anatomie und Biomechanik.

Chondral and osteochondral lesions of the talus (OLTs) remain a challenging issue with numerous operative treatments proposed to date. The aim of this study was to evaluate 1-year follow-up data in the German Cartilage Registry (KnorpelRegister DGOU). Among 401 patients in the database, 114 patients with a complete 1-year Foot and Ankle Outcome (FAOS) score for subscale Pain as the primary variable were included. A total of 12 different surgical treatments were performed. However, 8 techniques were carried out in negligible numbers of patients (n = 1–3), leaving 89 patients treated with the following techniques: arthroscopic antegrade bone marrow stimulation (group A; n = 32), autologous chondrocyte implantation with autologous cancellous bone grafting (group B; n = 9), matrix-augmented bone marrow stimulation (group C; n = 22), and matrix-augmented bone marrow stimulation with autologous cancellous bone grafting (group D; n = 26). Group differences and possible influencing variables such as age and sex were evaluated. Level of significance was set at p

Severe complications and morbidity after orthognathic surgery are infrequently encountered and even more infrequently reported considering the extent to which this procedure is performed by surgeons within the specialty of maxillofacial surgery. Avascular necrosis of the maxilla after Le Fort I osteotomy is perhaps the most dreaded outcome of orthognathic surgery. However, it accounts for an extremely small subset of overall surgical complications. The reported risk factors associated with avascular maxillary necrosis include segmental osteotomies, vertical posterior impactions, large transverse expansions, anterior advancements exceeding 9 to 10 mm, an improper surgical technique, excessive soft tissue degloving of the maxilla, intraoperative hemorrhage, perforation or laceration of the palatal soft tissue pedicle, previous maxillary or palatal surgery, and other medical comorbidities. Although anecdotal cases of total maxillary necrosis after orthognathic surgery have been alluded to within the specialty as a whole, to the best of our knowledge, no previous studies have reported total maxillary necrosis occurring after routine orthognathic surgery. We have presented a truly unique case of total maxillary avascular necrosis that occurred after standard 1-piece Le Fort I osteotomy in a patient without medical or surgical risk factors for the complication either known preoperatively or identified postoperatively. The resultant maxillary defect from total avascular necrosis was comprehensively treated with surgical debridement of the nonviable maxilla, osteocutaneous fibular free flap reconstruction, staged endosseous implant reconstruction of the neomaxilla, and comprehensive prosthodontic rehabilitation.

Background Here, we investigated radiological responses following chemotherapy alone as compared to both radiation/chemotherapy (chemoRT) in patients with thymic epithelial tumors (TETs) who did not receive upfront surgery. Methods TETs treated at a tertiary academic cancer center between January 2007 and July 2018 were identified. Patients received chemotherapy or chemoRT as initial therapy and pre‐ and post‐treatment scans were available. Student's t‐test, Wilcoxon rank‐sum tests, and Cox proportional hazards method were used to compare clinical details and survival between groups. The primary outcome was change in tumor size, which was compared between groups using linear mixed‐effects regression models, adjusting for baseline tumor size, age, and histology. Results A total of 24 of 114 patients with TETs identified met the inclusion criteria. The majority of patients had 67% thymoma (67%, n = 16) and AJCC8 III–IVA disease (58%, n = 14). Median age was 58.5 years (range: 33–76), median initial tumor volume was 187.1 cc (range: 28.7–653.6) and diameter was 8.5 cm (range: 4.5–14.3). Half of the patients received upfront chemotherapy (n = 12: 83% cisplatin/adriamycin/cyclophosphamide) or chemoRT (n = 12: 58% carboplatin/paclitaxel; median RT dose: 63 Gy [range: 60–70 Gy]). At a median imaging follow‐up of 15 months (range: 0–86): ChemoRT was associated with increased average radiological response compared to chemotherapy alone (volume: −47.0 cc more, P, ChemoRT was associated with a greater radiologic response than chemotherapy alone in patients with upfront unresectable TET

Background This study demonstrates the anatomy of the pedicled temporal artery posterior auricular skin (TAPAS) flap, its variable arc of rotation based on stepwise dissection, and case reports demonstrating clinical use. This flap provides excellent color match and ultrathin tissue for targeted reconstruction of small- to medium-sized facial subunit defects. Methods Twenty-six cadaver dissections were performed. The authors measured the reach and rotation limits of the flap in a pedicled fashion depending on a stepwise approach for vascular pedicle dissection. Two clinical cases demonstrating maximum arc of rotation are seen. Results The pedicled TAPAS flap maximal rotation limits allow for reconstruction of facial subunits encompassing nearly the entire ipsilateral face. No venous congestion, wound complications, or partial/total flap loss were encountered with extreme clinical applications. Conclusion The pedicled TAPAS flap has extensive versatility for reconstruction of a variety of facial subunit defects. The flap also has, in theory, multiple applications for intraoral reconstruction.

Despite progress in immunotherapy, identifying patients that respond has remained a challenge. Through analysis of whole-exome and targeted sequence data from 5,449 tumors, we found a significant correlation between tumor mutation burden (TMB) and tumor purity, suggesting that low tumor purity tumors are likely to have inaccurate TMB estimates. We developed a new method to estimate a corrected TMB (cTMB) that was adjusted for tumor purity and more accurately predicted outcome to immune checkpoint blockade (ICB). To identify improved predictive markers together with cTMB, we performed whole-exome sequencing for 104 lung tumors treated with ICB. Through comprehensive analyses of sequence and structural alterations, we discovered a significant enrichment in activating mutations in receptor tyrosine kinase (RTK) genes in nonresponding tumors in three immunotherapy treated cohorts. An integrated multivariable model incorporating cTMB, RTK mutations, smoking-related mutational signature and human leukocyte antigen status provided an improved predictor of response to immunotherapy that was independently validated.

Virtual surgical planning (VSP), computer aided design/computer aided modeling, and 3-dimensional printing technology have been shown to improve surgical accuracy and efficiency in head and neck reconstruction. However, persisting criticism of the technology is that it does not adequately address the soft tissue-related aspects of reconstructive surgery. Prior publication on the computed tomographic angiography (CTA) perforator localization technique has demonstrated how soft tissue planning can be incorporated directly into existing VSP workflows.The aim of this study is to prospectively assess the accuracy, precision, negative predictive value (NPV), and positive predictive value (PPV) of the CTA perforator localization technique for VSP of osteocutaneous fibular free flaps.A prospective observational study in a consecutive cohort of subjects undergoing VSP of osteocutaneous fibular free flaps at Mayo Clinic between 2018 and 2020 was completed. All cutaneous perforators from the peroneal system of the selected donor leg were identified preoperatively through a previously reported CTA tracing method and registered into the VSP. Perforators were classified as primary or secondary based on whether the perforators were targeted for use in the final reconstructive plan. Perforator measurements obtained from the VSP were cross-referenced with intraoperatively obtained measurements of actual perforator locations to calculate accuracy, precision, NPV, PPV, sensitivity, and specificity of the CTA localization technique.Sixty consecutive subjects were enrolled in the study. A total of 141 perforators were identified preoperatively on CTA and 145 perforators were identified on operative exposure. One perforator identified on preoperative CTA was not identified on surgical exposure (false positive perforator). Six perforators were identified on operative exposure alone without recognition on preoperative CTA (false negative perforators). The accuracy of CTA perforator identification was 96.52%. Median precision of perforator localization was 0.3 cm (standard deviation 0.40) between CTA and operatively identified locations. PPV of the technique was 99.29% and NPV was 90.00%.The CTA localization technique for identifying and incorporating cutaneous perforator locations into VSP of osteocutaneous fibular free flaps is a reliable, accurate, and precise technique to employ in the modern paradigm of guided surgery for head and neck reconstruction.

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as “preferred interventions,” whereas others are categorized as either “other recommended interventions” or “useful under certain circumstances.”

Context Several cross-sectional studies have assessed the association of lead exposure with type 2 diabetes and cardiometabolic risk factors in adults; however, studies of such associations in childhood are rare. Objective We assessed the prospective associations of prenatal exposure to lead with type 2 diabetes and cardiometabolic risk factors in children. Design The Early Life Exposure in Mexico to Environmental Toxicants is a birth cohort study of pregnant women and their offspring. Setting Public hospitals in Mexico City. Patients or Other Participants Women were recruited during pregnancy; their offspring were recruited for a follow-up visit at age 10 to 18 years (n = 369). Main Outcome Measures We measured fasting serum markers of type 2 diabetes and cardiometabolic risk factors in children, including fasting glucose, insulin, and lipids. The index of insulin resistance was calculated. Results The geometric mean of maternal blood lead levels (BLLs) during pregnancy was 4.3 µg/dL (95% confidence interval [CI]): 4.0-4.6 µg/dL) in the entire sample. In boys, those with maternal BLLs ≥ 5 µg/dL (compared with those with BLLs < 5 µg/dL) had significantly lower z scores for total cholesterol (β = -0.41, 95% CI: -0.71, -0.12), high-density lipoprotein cholesterol (β = -0.32, 95% CI: -0.59, -0.05), and low-density lipoprotein cholesterol (β = -0.52, 95% CI: -0.81, -0.22), adjusting for covariates. No associations were detected in girls. Conclusions In our study, we found that higher prenatal exposure to lead was associated with lower levels of cholesterol in children following a sex-specific pattern. Further studies with a larger sample size that examine whether sex is a potential modifier are needed to confirm our findings.

Background A previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak. Methods In order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Results Of the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (n = 8) or were actually on-label (n = 5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate=43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available. Conclusion Off-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies.

Zusammenfassung Hintergrund Zehenamputationen und Strahlresektionen zahlen zu den Minor-Amputationen am Fus, Obwohl Zehenamputationen und Strahlresektionen zur Therapie von vielen Pathologien eignet, ist das Diabetische Fussyndrom der haufigste Grund fur diese Amputationen. In den letzten Jahren ist es zu einem Anstieg von Minor-Amputationen im Vergleich zu den Major-Amputationen gekommen. Durch die Vermeidung bzw. Abkehr von den Major-Amputationen rucken die Minor-Amputationen des Fuses und deren Durchfuhrungen in den chirurgischen Blickpunkt. Material und Methode Ziel der hier vorliegenden Arbeit ist die Vorstellung der operativen Technik von Zehenamputation und Strahlresektion und deren Bedeutung in der aktuellen der Literatur. Schlussfolgerungen Zehenamputationen und Strahlresektionen sind sichere Minor-Amputationsverfahren fur viele Indikationen und bieten eine schnelle postoperative Aufbelastung. Trotz guten primaren Heilungsraten ist eine interdisziplinare perioperative Behandlung bei Diabetespatienten substanziell um die Re-Amputationsrate und Mortalitatsrate gering zu halten.

Zusammenfassung Der Hallux rigidus ist eines der haufigsten Beschwerdebilder des Fuses. Besonders Sportler sind gefahrdet, einen fruhzeitigen Verschleis im Metatarsophalangealgelenk I (MTP-I) zu entwickeln. Je nach gewahlter Sportart kann es hierbei zu Einschrankungen und Folgeproblemen kommen. Dieser Artikel liefert eine Ubersicht uber mogliche konservative und operative Therapieoptionen insbesondere in Hinblick auf die Wiederaufnahme der sportlichen Aktivitat. Unter Berucksichtigung der aktuellen Literatur sind neben Einlagenversorgung und manueller Therapie operativ besonders die Cheilektomie und MTP-I-Arthrodese zu empfehlen. Zuletzt haben Hydrogel-Implantate eine zunehmende Verbreitung erfahren. Diese konnen eine gute operative Alternative darstellen. Eine abschliesende Bewertung diesbezuglich ist aktuell aber noch nicht moglich.

In patients with non–small-cell lung cancer treated with anti–PD-1/PD-L1 agents, no specific radiation parameter was significantly associated with immune-related (IR) pneumonitis. We identify on subset analysis of patients who developed IR pneumonitis and received chest radiation, patients were numerically more likely to have received chest radiation with curative intent than with palliative intent (89% vs. 11 that approached statistical significance. PURPOSE: To investigate the relationship between radiotherapy (RT), in particular chest RT, and development of immune-related (IR) pneumonitis in non–small-cell lung cancer (NSCLC) patients treated with anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-LI). PATIENTS AND METHODS: Between June 2011 and July 2017, NSCLC patients treated with anti–PD-1/PD-L1 at a tertiary-care academic cancer center were identified. Patient, treatment, prior RT (intent, technique, timing, courses), and IR pneumonitis details were collected. Treating investigators diagnosed IR pneumonitis clinically. Diagnostic IR pneumonitis scans were overlaid with available chest RT plans to describe IR pneumonitis in relation to prior chest RT. We evaluated associations between patient, treatment, RT details, and development of IR pneumonitis by Fisher exact and Wilcoxon rank-sum tests. RESULTS: Of the 188 NSCLC patients we identified, median follow-up was 6.78 (range, 0.30–79.3) months and median age 66 (range, 39–91) years; 54% (n = 102) were male; and 42% (n = 79) had stage I-III NSCLC at initial diagnosis. Patients received anti–PD-1/PD-L1 monotherapy (n = 127, 68%) or PD-I/PD-LI -based combinations (n = 61, 32%). In the entire cohort, 70% (132/188) received any RT, 53% (100/188) chest RT, and 37% (70/188) curative-intent chest RT. Any grade IR pneumonitis occurred in 19% (36/188; 95% confidence interval, 13.8–25.6). Of those who developed IR pneumonitis and received chest RT (n = 19), patients were more likely to have received curative-intent versus palliative-intent chest RT (17/19, 89%, vs. 2/19, 11%; P = .051). Predominant IR pneumonitis appearances were ground-glass opacities outside high-dose chest RT regions. CONCLUSION: No RT parameter was significantly associated with IR pneumonitis. On subset analysis of patients who developed IR pneumonitis and who had received prior chest RT, IR pneumonitis was more common in patients who received curative-intent chest RT. Attention should be paid to NSCLC patients receiving curative-intent RT followed by anti –PD-I/PD-LI agents.

Genetic and environmental interactions predispose certain groups to lung cancer, including families. Families or caregiving units experience the disease interdependently. We have previously evaluated the concerns and preferences of patients in addressing the lung cancer experience and cancer risks in their families. This qualitative study evaluates the concerns and preferences of family members and caregivers of patients with lung cancer in the lung cancer experience and familial cancer risks. We held focus groups to discuss the format and timing of addressing these preferences and concerns. Qualitative data generated was analyzed using a grounded theory approach. Five focus groups totaling 19 participants were conducted. Seven themes were identified: (1) journey to lung cancer diagnosis has core dimensions for patient and family, (2) importance of communication between patients, families, and providers, (3) challenges for caregivers and family, (4) mixed perceptions of lung cancer causation among relatives, (5) discussion of cancer risk with relatives has complex dynamics, (6) impact of diagnosis on family health behaviors and screening, (7) role of genetic counseling. Family members of patients with lung cancer are interested in discussing risk factors, prevention, and diagnoses and also would like access to other supportive services do learn about and cope with some of the stresses and barriers they experience in the family lung cancer journey. The diagnosis represents a potential teachable moment with the opportunity to reduce the risk of LC development or improve early detection in LC patient’s family members.

Zusammenfassung Der Hallux rigidus ist eine der am haufigsten auftretenden Beschwerdebilder der Fuschirurgie. Ungeachtet der klinischen Relevanz ist die Studienlage hinsichtlich der konservativen Therapie uberschaubar. Die hier dargestellten Studien liefern eine Ubersicht und Einordnung der konservativen Therapieoptionen zu diesem Themengebiet. Unter Berucksichtigung der aktuellen Literatur sind eine Einlagenversorgung und Schuhzurichtung sowie die Manuelle Therapie for hallux rigidus grade I-II empfehlenswert.

With increasing use of immune checkpoint inhibitors (ICIs) for advanced NSCLC, there is increasing recognition of immune-related adverse events associated with ICI use. We recently reported increased incidence of checkpoint inhibitor pneumonitis (CIP) in ICI-treated NSCLC patients. Since development of immune-related adverse events in other organ systems has been associated with either no change or even improvement in tumor response/cancer outcomes, we sought to better understand the impact of CIP development on overall survival in ICI-treated NSCLC patients. Using baseline and follow-up data collected on a cohort of 205 ICI-treated NSCLC patients, we used a multi-state modeling approach to understand the effect of developing CIP on the risk of death. We observed time-dependent changes in risk of developing and recovery from CIP, with an increased risk of both developing and recovering from CIP in the first year after initiating ICI. We found that developing CIP independently increased the risk of transitioning to death in both adjusted and unadjusted models. In the multivariate model, we found that the increase in mortality associated with CIP was only seen in patients with adenocarcinoma tumor histology. Collectively, these findings suggest that in NSCLC, development of CIP worsens survival in patients receiving immunotherapy.

Dietary factors are known to influence urinary fluoride (UF) levels in nonpregnant people. Maternal UF is used as a biomarker of fluoride exposure; however, dietary influences on UF during pregnancy are unknown. We compared UF levels and assessed the associations between UF and five select dietary influences in pregnancy vs. one-year postpartum: dietary fluoride (F), calcium intake from diet (Ca-diet), calcium intake from supplements (Ca-sup), dietary acid load (AL), and table salt use (TS) in 421 women exposed to fluoridated salt in the Mexican diet. Spot UF (mg/L) was measured by microdiffusion/fluoride-specific electrode and dilution-corrected with specific gravity (SG). Dietary variables were estimated from a validated Food Frequency Questionnaire. Comparisons among UF in pregnancy vs. one-year postpartum were performed with non-parametric tests. Associations between dietary variables and UF were assessed using random effect models (for pregnancy) and linear regression (for one-year postpartum). SG-corrected UF (median, range) during pregnancy (0.77, 0.01-4.73 mg/L) did not significantly differ from one-year postpartum (0.75, 0.15-2.62 mg/L) but did increase every 10 gestational weeks, β = 0.05 (CI: 0.00-0.10). Different dietary influences on UF were identified at each state. Although Ca-diet and AL were not associated with UF in either state, Ca-sup decreased UF only during pregnancy, β = - 0.012 mg/L (CI: - 0.023-0.00). Reporting TS use was associated with 12% increase in UF only at one-year postpartum (p = 0.026). These results suggest different dietary influences on UF in the pregnant state, which need consideration when using UF as a biomarker of fluoride exposure.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

Background: Lead can adversely affect child health across a wide range of exposure levels. We describe the distribution of blood lead levels (BLLs) in U.S. children ages 1–11 y by selected sociodemographic and housing characteristics over a 40-y period. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) II (1976–1980), NHANES III (Phase 1: 1988–1991 and Phase II: 1991–1994), and Continuous NHANES (1999–2016) were used to describe the distribution of BLLs (in micrograms per deciliter; 1μg/dL=0.0483μmol/L) in U.S. children ages 1–11 y from 1976 to 2016. For all children with valid BLLs (n=27,122), geometric mean (GM) BLLs [95% confidence intervals (CI)] and estimated prevalence ≥5μg/dL (95% CI) were calculated overall and by selected characteristics, stratified by age group (1–5 y and 6–11 y). Results: The GM BLL in U.S. children ages 1–5 y declined from 15.2μg/dL (95% CI: 14.3, 16.1) in 1976–1980 to 0.83μg/dL (95% CI: 0.78, 0.88) in 2011–2016, representing a 94.5% decrease over time. For children ages 6–11 y, GM BLL declined from 12.7μg/dL (95% CI: 11.9, 13.4) in 1976–1980 to 0.60μg/dL (95% CI: 0.58, 0.63) in 2011–2016, representing a 95.3% decrease over time. Even so, for the most recent period (2011–2016), estimates indicate that approximately 385,775 children ages 1–11 y had BLLs greater than or equal to the CDC blood lead reference value of 5μg/dL. Higher GM BLLs were associated with non-Hispanic Black race/ethnicity, lower family income-to-poverty-ratio, and older housing age. Discussion: Overall, BLLs in U.S. children ages 1–11 y have decreased substantially over the past 40 y. Despite these notable declines in population exposures to lead over time, higher GM BLLs are consistently associated with risk factors such as race/ethnicity, poverty, and housing age that can be used to target blood lead screening efforts. https://doi.org/10.1289/EHP7932