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PURPOSE The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. MATERIALS AND METHODS Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,542 patients with complete information on potentially relevant variables. The results were validated in an independent data set. RESULTS Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided ( https://www.eortc.org/IGCCCG-Update ). CONCLUSION The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.

Contains fulltext : 248305.pdf (Publisher’s version ) (Closed access) CONTEXT: Treatment of metastatic urothelial carcinoma is currently undergoing a rapid evolution. OBJECTIVE: This overview presents the updated European Association of Urology (EAU) guidelines for metastatic urothelial carcinoma. EVIDENCE ACQUISITION: A comprehensive scoping exercise covering the topic of metastatic urothelial carcinoma is performed annually by the Guidelines Panel. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. EVIDENCE SYNTHESIS: Platinum-based chemotherapy is the recommended first-line standard therapy for all patients fit to receive either cisplatin or carboplatin. Patients positive for programmed death ligand 1 (PD-L1) and ineligible for cisplatin may receive immunotherapy (atezolizumab or pembrolizumab). In case of nonprogressive disease on platinum-based chemotherapy, subsequent maintenance immunotherapy (avelumab) is recommended. For patients without maintenance therapy, the recommended second-line regimen is immunotherapy (pembrolizumab). Later-line treatment has undergone recent advances: the antibody-drug conjugate enfortumab vedotin demonstrated improved overall survival and the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib appears active in case of FGFR3 alterations. CONCLUSIONS: This 2021 update of the EAU guideline provides detailed and contemporary information on the treatment of metastatic urothelial carcinoma for incorporation into clinical practice. PATIENT SUMMARY: In recent years, several new treatment options have been introduced for patients with metastatic urothelial cancer (including bladder cancer and cancer of the upper urinary tract and urethra). These include immunotherapy and targeted treatments. This updated guideline informs clinicians and patients about optimal tailoring of treatment of affected patients.

Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. Setting: Online Delphi survey and consensus conference. Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), 7–9 (agree). A priori (level 1) consensus was defined as 70% agreement and 15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach, The authors would like to thank Peter E. Clark from Atrium Health, Levine Cancer Institute, Charlotte, NC, USA, for his contribution to the Delphi survey. Angela Corstorphine of Kstorfin Medical Communications Ltd provided medical writing support with the preparation of this manuscript; this support was funded jointly by EAU and ESMO.

Purpose Understanding trends and patterns in the use of minimally invasive glaucoma surgery (MIGS) and patient profiles undergoing each procedure is important given their relative expense and unknown long-term safety and effectiveness. Design Retrospective analysis. Participants Minimally invasive glaucoma surgeries and standard glaucoma surgeries recorded in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry. Methods We used the data from IRIS® Registry between 2013 and 2018 (inclusive) to measure the annual number of MIGS and standard surgical techniques (trabeculectomy or glaucoma drainage device [GDD] placement) performed in the United States, stratified by demographic characteristics. Secondary analyses of concurrent surgeries and of subsequent surgeries for MIGS and standard surgical technique also were conducted. Main Outcome Measures Trends and sociodemographic characteristics of MIGS use in the United States. Results Two hundred three thousand three hundred thirty-two eyes and 232 537 unique procedures had associated, documented International Statistical Classification of Diseases and Related Health Problems (ICD), Ninth or Tenth Revision, codes for glaucoma and were included in final analyses. Among eyes with documented glaucoma diagnoses, a substantial increase in annual MIGS procedures occurred over the study period (from 7586 in 2013 to 39 677) and a smaller decrease in standard glaucoma procedures (from 16 215 to 13 701). The proportion of iStent procedures almost tripled during the study period (from 14% to 40%), and by 2017 accounted for almost half (43.7%) of all glaucoma surgeries in the United States. Twenty-one thousand twenty-five of all eyes (10.3%) underwent multiple procedures: 7638 (36.3%) on the same day and 13 387 (63.7%) on subsequent days. Endocyclophotocoagulation and iStent placement were the most common concurrent procedures (55.4% of all concurrent procedures). Trabeculectomy and GDD placement were most commonly followed by another standard glaucoma surgery, but when followed by sequential MIGS, endocyclophotocoagulation and goniotomy were the most common procedures performed (33.0% and 21.9%, respectively). Conclusions A significant increase in MIGS use occurred over the recent 6-year period, despite limited evidence of their long-term safety or effectiveness, highlighting the need for trials comparing safety and outcomes of novel MIGS versus traditional surgical treatments for glaucoma.

Purpose The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients. Methods Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR). Results The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH p = 0.012) and 32% vs. 59% (p ≤ 0.001), respectively. Conclusions LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification.

Aim Cardiopulmonary resuscitation (CPR) in hospitalized infants is a relatively uncommon but high-risk event associated with mortality. The study objective was to identify factors associated with mortality and survival among infants who receive CPR in the neonatal intensive care unit (NICU) or pediatric intensive care unit (PICU). Methods Retrospective observational study of infants with an index CPR event in the NICU or PICU between 1/1/06 and 12/31/18 in the American Heart Association’s Get With The Guidelines-Resuscitation registry. Associations between patient, event, unit, and hospital factors and the primary outcome, mortality prior to discharge, were examined using multivariable logistic regression. Results Among 3521 infants who received CPR, 2080 (59%) died before discharge, with 25% mortality during CPR and 40% within 24 h. Mortality prior to discharge occurred in 65% and 47% of cases in the NICU and PICU, respectively. Factors most strongly independently associated with pre-discharge mortality were vasoactive agent before CPR (adjusted odds ratio (aOR): 2.77, 95% confidence interval (CI) 2.15–3.58), initial pulseless condition (aOR: 2.38, 95% CI 1.46–3.86) or development of pulselessness (aOR: 2.36, 95% CI 1.78–3.12), and NICU location compared with PICU (aOR: 3.85, 95% CI 2.86–5.19). Endotracheal intubation during CPR was associated with decreased odds of pre-discharge mortality (aOR: 0.40, 95% CI 0.33−0.49). Conclusion Infants who receive CPR in the intensive care unit experience high mortality rates; identifiable patient, event, and unit factors increase the odds of mortality. Further investigation should explore the association between unit type, resuscitation processes, and mortality.

Summary Background PD-1 and PD-L1 inhibitors are active in metastatic urothelial carcinoma, but positive randomised data supporting their use as a first-line treatment are lacking. In this study we assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urothelial carcinoma. Methods KEYNOTE-361 is a randomised, open-label, phase 3 trial of patients aged at least 18 years, with untreated, locally advanced, unresectable, or metastatic urothelial carcinoma, with an Eastern Cooperative Oncology Group performance status of up to 2. Eligible patients were enrolled from 201 medical centres in 21 countries and randomly allocated (1:1:1) via an interactive voice-web response system to intravenous pembrolizumab 200 mg every 3 weeks for a maximum of 35 cycles plus intravenous chemotherapy (gemcitabine [1000 mg/m2] on days 1 and 8 and investigator's choice of cisplatin [70 mg/m2] or carboplatin [area under the curve 5] on day 1 of every 3-week cycle) for a maximum of six cycles, pembrolizumab alone, or chemotherapy alone, stratified by choice of platinum therapy and PD-L1 combined positive score (CPS). Neither patients nor investigators were masked to the treatment assignment or CPS. At protocol-specified final analysis, sequential hypothesis testing began with superiority of pembrolizumab plus chemotherapy versus chemotherapy alone in the total population (all patients randomly allocated to a treatment) for the dual primary endpoints of progression-free survival (p value boundary 0·0019), assessed by masked, independent central review, and overall survival (p value boundary 0·0142), followed by non-inferiority and superiority of overall survival for pembrolizumab versus chemotherapy in the patient population with CPS of at least 10 and in the total population (also a primary endpoint). Safety was assessed in the as-treated population (all patients who received at least one dose of study treatment). This study is completed and is no longer enrolling patients, and is registered at ClinicalTrials.gov , number NCT02853305 . Findings Between Oct 19, 2016 and June 29, 2018, 1010 patients were enrolled and allocated to receive pembrolizumab plus chemotherapy (n=351), pembrolizumab monotherapy (n=307), or chemotherapy alone (n=352). Median follow-up was 31·7 months (IQR 27·7–36·0). Pembrolizumab plus chemotherapy versus chemotherapy did not significantly improve progression-free survival, with a median progression-free survival of 8·3 months (95% CI 7·5–8·5) in the pembrolizumab plus chemotherapy group versus 7·1 months (6·4–7·9) in the chemotherapy group (hazard ratio [HR] 0·78, 95% CI 0·65–0·93; p=0·0033), or overall survival, with a median overall survival of 17·0 months (14·5–19·5) in the pembrolizumab plus chemotherapy group versus 14·3 months (12·3–16·7) in the chemotherapy group (0·86, 0·72–1·02; p=0·0407). No further formal statistical hypothesis testing was done. In analyses of overall survival with pembrolizumab versus chemotherapy (now exploratory based on hierarchical statistical testing), overall survival was similar between these treatment groups, both in the total population (15·6 months [95% CI 12·1–17·9] with pembrolizumab vs 14·3 months [12·3–16·7] with chemotherapy; HR 0·92, 95% CI 0·77–1·11) and the population with CPS of at least 10 (16·1 months [13·6–19·9] with pembrolizumab vs 15·2 months [11·6–23·3] with chemotherapy; 1·01, 0·77–1·32). The most common grade 3 or 4 adverse event attributed to study treatment was anaemia with pembrolizumab plus chemotherapy (104 [30%] of 349 patients) or chemotherapy alone (112 [33%] of 342 patients), and diarrhoea, fatigue, and hyponatraemia (each affecting four [1%] of 302 patients) with pembrolizumab alone. Six (1%) of 1010 patients died due to an adverse event attributed to study treatment; two patients in each treatment group. One each occurred due to cardiac arrest and device-related sepsis in the pembrolizumab plus chemotherapy group, one each due to cardiac failure and malignant neoplasm progression in the pembrolizumab group, and one each due to myocardial infarction and ischaemic colitis in the chemotherapy group. Interpretation The addition of pembrolizumab to first-line platinum-based chemotherapy did not significantly improve efficacy and should not be widely adopted for treatment of advanced urothelial carcinoma. Funding Merck Sharp and Dohme, a subsidiary of Merck, Kenilworth, NJ, USA.

Purpose: The extent to which routine genomic sequencing can identify relevant secondary genomic alterations among BRAFV600E-mutant papillary thyroid carcinoma (PTC) is unknown. Such markers would prove highly valuable for prognostic purposes. Experimental Design: We reviewed clinicopathologic data of 225 patients with BRAFV600E-mutant PTC and integrated them with genomic data derived from targeted next-generation sequencing (NGS) on tumor specimens. We defined patient subgroups based on bona fide secondary oncogenic events (separate from BRAFV600E) and compared their clinical features and outcomes with those without additional oncogenic alterations. Results: Additional oncogenic alterations were identified in 16% of tumors. Patients in the “BRAF+additional mutations” group were more likely to be at high American Thyroid Association (ATA) risk of recurrence (48.6% vs. 17.6%; P = 0.0009), had larger baseline tumor (2.7 vs. 1.9 cm; P = 0.0005) and more advanced stage at presentation (14.3% vs. 1.1% stage 4; P < 0.0001). Importantly, over a 65-month follow-up, disease-specific mortality (DSM) was increased when additional mutations were identified (13.8% vs. 1.4% in the BRAF-only group; P = 0.005). Separately, we identified a subcluster of patients harboring oncogenic mutations in key effectors of the PI3K/AKT/mTOR pathway, which were independently associated with DSM (OR = 47.9; 95% confidence interval, 3.5–1,246.5; P = 0.0043). Conclusions: Identification of additional PIK3/AKT/mTOR alterations in patients with BRAFV600E-mutant PTC provides important and actionable prognostic risk stratification. These data support genomic profiling of PTC tumors to inform prognosis and clinical strategy.

COVID-19 became a pandemic with a worldwide impact leading to stay-at-home orders, death, economic difficulties, and a significant influence on daily lives. Dental services became limited at this time, causing increased concerns for patients requiring urgent dental care. We report the case of a 5-year-old previously healthy male who presented to our hospital’s emergency department (ED) with facial swelling secondary to infected maxillary left molars. Extractions were performed in the ED with moderate sedation. He was later found to be COVID-19 positive before admission for intravenous antibiotics. The use of universal precautions during the pandemic in treating patients with possible COVID-19 symptoms and in aerosol-generating procedures is recommended. Evaluating and providing treatment to our patients with urgent dental care should not be delayed to prevent further complications and decrease the burden placed on the ED, which may be limited in its ability to provide definitive care.

To evaluate the association between chronic diuretic exposures and enteral electrolyte use in infants developing severe bronchopulmonary dysplasia (sBPD). Retrospective longitudinal cohort study in infants admitted to United States children’s hospitals. We identified diuretic exposures and measured enteral NaCl and KCl use during pre-defined exposure risk-interval days. We used mixed-effects logistic regression to model the association between diuretic exposures and electrolyte use. We identified 442,341 subject-days in 3252 infants. All common diuretic classes and class combinations were associated with increased NaCl and KCl use. Thiazide monotherapy was associated with greater electrolyte use than loop monotherapy. The addition of potassium-sparing diuretics was associated with a limited reduction in KCl use compared to thiazide monotherapy. Chronic diuretic exposures are associated with increased NaCl and KCl use. Presumptions about the relative impact of different diuretic classes on electrolyte derangements may be inaccurate and require further study.

ObjectiveDetermine risk of death or neurodevelopmental impairment (NDI) in infants with late-onset sepsis (LOS) versus late-onset, antibiotic-treated, blood culture-negative conditions (LOCNC).DesignRetrospective cohort study.Setting24 neonatal centres.PatientsInfants born 1/1/2006–31/12/2014, at 22–26 weeks gestation, with birth weight 401–1000 g and surviving >7 days were included. Infants with early-onset sepsis, necrotising enterocolitis, intestinal perforation or both LOS and LOCNC were excluded.ExposuresLOS and LOCNC were defined as antibiotic administration for ≥5 days with and without a positive blood/cerebrospinal fluid culture, respectively. Infants with these diagnoses were also compared with infants with neither condition.OutcomesDeath or NDI was assessed at 18–26 months corrected age follow-up. Modified Poisson regression models were used to estimate relative risks adjusting for covariates occurring ≤7 days of age.ResultsOf 7354 eligible infants, 3940 met inclusion criteria: 786 (20%) with LOS, 1601 (41%) with LOCNC and 1553 (39%) with neither. Infants with LOS had higher adjusted relative risk (95% CI) for death/NDI (1.14 (1.05 to 1.25)) and death before follow-up (1.71 (1.44 to 2.03)) than those with LOCNC. Among survivors, risk for NDI did not differ between the two groups (0.99 (0.86 to 1.13)) but was higher for LOCNC infants (1.17 (1.04 to 1.31)) compared with unaffected infants.ConclusionsInfants with LOS had higher risk of death, but not NDI, compared with infants with LOCNC. Surviving infants with LOCNC had higher risk of NDI compared with unaffected infants. Improving outcomes for infants with LOCNC requires study of the underlying conditions and the potential impact of antibiotic exposure.

Purpose: During the COVID-19 pandemic, there is growing concern that patients are forgoing necessary care. Emergency departments (ED) represent an important site of eye care. We analyzed patterns of ED visits at an eye-specific ED since the declaration of the public health crisis. Materials and Methods: In this retrospective, cross-sectional single center study, medical records of 6744 patients who presented to the Massachusetts Eye and Ear ED between March 1st and April 30th in 2018, 2019, and 2020 were studied. The primary outcome measures were total volume of ED visits, proportion of urgent ED visits, and proportion of surgical visits. Results: Overall, the median number of daily visits to the ED decreased by 18 visits per day since the declaration of public health guidelines (interquartile range, 9-24, p < 0.001). This accounted for a 32% decrease in the total volume of ED visits in 2020 compared to prior years during the study period (p < 0.001). There was a 9% increase in the proportion of primary diagnoses considered urgent (p = 0.002). The proportion of visits requiring urgent surgery increased by 39% (p = 0.004). Conclusion: The total number of eye-specific ED visits dropped compared to prior years while the proportion of urgent visits increased. Patients were likely more reluctant to seek eye care, deferring less urgent evaluation.

Thoracic growing teratoma syndrome (TGTS) is a rare disease in patients with germ cell tumors. Other than a few case reports and a limited number of case series, studies of this topic are not available. We retrospectively analyzed the data from our patients who received surgery for TGTS between 1999 and 2016. Descriptive statistical analyses were performed to analyze the characteristics of the patients, tumors, and short-term outcomes. Furthermore, the long-term outcomes and survival curves were analyzed using the Kaplan–Meier method. Twenty-nine patients underwent surgery for TGTS. The median age was 32 years (range: 19–50 years). All patients received cisplatin-based chemotherapy. Many of the patients had multilocalized TGTS (n = 10). The median tumor size was 64.5 mm (range 10-210 mm). In all cases, R0 resection was achieved. The minor morbidity, major morbidity, and mortality rates were 3.4%, 6.9%, and 0%, respectively. Altogether, 28 patients were included in the long-term follow-up analysis, with a median follow-up time of 94 months (13–237 months). The 5-, 10-, and 15-year survival rates were 93%, 93%, and 84%, respectively. TGTS may occur in multiple localizations and grow to a large tumor size. The resection of TGTS can be performed with low morbidity and mortality rates and is associated with good overall survival after complete resection. Important are an early detection and knowledge of the systemic treatment options by the oncologist and urologist, as well as a thoracic surgeon with a large experience in extended thoracic resections.

Background Circulating tumors cells (CTCs) are considered an early step towards metastasis and have been linked to poor prognosis in several types of cancer. CTCs in squamous cell carcinoma of the head and neck (SCCHN) have an unclear role. Methods In this prospective study, patients with locally advanced or metastatic SCCHN had CTC counts assessed before starting systemic treatment using the CellSearch System. Select cases also had sequential CTC evaluation. Presence of CTCs was correlated with patient characteristics and outcomes. Results Forty‐eight patients enrolled, and 36 had evaluable clinical data and baseline CTC counts. Twenty‐five patients had locally advanced disease (LAD) and 11 had metastatic disease. ≥1 CTCs were detected in six patients with LAD (24%) and four with metastatic disease (36%). On univariate analysis, smoking was associated with CTCs. Conclusion CTCs are not associated with prognosis in patients with LAD and metastatic disease; however, they are present in this patient population, and ≥1 CTCs is associated with a history of smoking. Level of evidence 1b; individual prospective cohort study., Circulating tumors cells (CTCs) were detected in 6/25 patients with locoregionally advanced disease (24%) and 4/11 with metastatic squamous cell carcinoma of the head and neck (36%). On univariate analysis, smoking was associated with CTCs.

Purpose To compare the average intraocular pressure (IOP) among smokers, past smokers, and never smokers using the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry. Design Retrospective database study of the IRIS® Registry data. Participants Intelligent Research in Sight Registry patients who were seen by an eye care provider during 2017. Methods Patients were divided into current smoker, past smoker, and never smoker categories. The IOP was based on an average measurement, and separate analyses were performed in patients with and without a glaucoma diagnosis based on International Classification of Diseases (Ninth Edition and Tenth Edition) codes. Stratified, descriptive statistics by glaucoma status were determined, and the relationship between smoking and IOP was assessed with a multivariate linear regression model. Main Outcome Measures Mean IOP. Results A total of 12 535 013 patients were included. Compared with never smokers, current and past smokers showed a statistically significantly higher IOP by 0.92 mmHg (95% confidence interval [CI], 0.88–0.95 mmHg) and 0.77 mmHg (95% CI, 0.75–0.79 mmHg), respectively, after adjusting for age, gender, glaucoma, age-related macular degeneration, diabetic retinopathy, cataract, glaucoma surgery, cataract surgery, and first-order interactions. In addition, the difference in IOP between current and never smokers was the highest in the fourth decade, regardless of the glaucoma status (glaucoma group, 1.14 mmHg [95% CI, 1.00–1.29 mmHg]; without glaucoma group, 0.68 mmHg [95% CI, 0.65–0.71 mmHg]). Conclusions Current smokers and past smokers have higher IOP than patients who never smoked. This difference is higher in patients with an underlying glaucoma diagnosis.

The 2015 American Thyroid Association (ATA) guidelines recommended that low-risk, differentiated thyroid cancers (DTC) between 1 and 4 cm may be treated with thyroid lobectomy alone. We sought to determine the effect of these guideline changes on the rate of completion thyroidectomy (CT) for low-risk DTC and factors influencing surgical decision-making. All patients from 2014 to 2018 who received an initial thyroid lobectomy at our institution with final pathology demonstrating DTC were included. Patients were divided into “pre” and “post” guideline cohorts (2014–2015 and 2016–2018, respectively). The rate of CT was compared between the two cohorts. Patient demographics and tumor characteristics were examined for association with CT. A total of 163 patients met study criteria: 63 patients in the 2014–2015 (“pre”) and 100 in the 2016–2018 (“post”) group. In the “pre” period, 41 (65.1%) patients received CT compared with 43 (43.0%) in the “post” period (p

Although prior studies have reported that patients with anaplastic thyroid carcinoma (ATC) with a focal anaplastic component may have a prolonged survival compared to other ATC patients, the outcome data are limited. We evaluated a cohort of ATC resected between 2003 and 2018. Tumor slides were reviewed to confirm the diagnosis and to identify cases with a minor ATC component (defined as comprising < 10% of the tumor). We evaluated the clinical outcome of these patients compared to that of all other cohort patients (characterized as having conventional ATC). Our cohort was composed of 24 cases of ATC that underwent resection, including 8 (33%) with a minor ATC component. Tumors with a minor ATC component were predominantly associated with papillary thyroid carcinoma. For patients with tumors with a minor ATC component, the 1-year and 2-year survival rates and median survival for patients who died of disease were 88%, 43%, and 17 months (range 6-73 months), respectively. In comparison, for patients with conventional ATC, the 1-year and 2-year survival rates and median survival for patients who died of disease were 56%, 44%, and 7 months (range 2-26 months), respectively. There was no difference in 1- and 2-year survival or overall survival by Kaplan-Meier analysis for patients with tumors with a minor ATC component and those with conventional ATC. In conclusion, the difference in overall survival between ATC groups in our cohort was not significant; however, this could be due to the small cohort size or due to characteristics of our group with a minor ATC component; that is, no tumors in this group were limited to the thyroid (stage IVA), resectability with negative margins was infrequent, and 38% of this group had distant metastases at diagnosis (stage IVC).

AIM: Flow Disruptions (FDs) are deviations from the progression of care that compromise safety and efficiency of a specific process. The study aim was to identify the impact of FDs during neonatal resuscitation and determine their association with key process and outcome measures. METHODS: Prospective observational study of video recorded delivery room resuscitations of neonates

Background: Florida's Healthy Start Program is a statewide prenatal screening program that aims to identify pregnant women at risk of adverse birth outcomes. However, the effectiveness of this legislatively mandated prenatal risk screening tool in predicting poor birth outcomes is unknown. This study aimed to evaluate associations between risk factors self-reported on this screening tool and adverse birth outcomes. Materials and Methods: A 1-year retrospective birth cohort at a large academic referral center was created. Risk factors reported on the tool by mothers who had a preterm or low-birthweight (LBW) infant were compared with those reported by mothers who delivered full-term non-LBW infants in bivariate and multivariate analyses. All data were extracted from maternal or infant electronic health records. Results: The Mother/Infant Dyad Screening cohort consisted of 528 dyads. We identified two items on the screening tool that significantly associated with adverse birth outcomes, but which do not currently contribute to the total risk score used to identify women for referral to preventive social services. These items were feeling alone and thinking it was not a good time to be pregnant. Conclusions: Comprehensive prenatal risk screening is an underutilized strategy in medicine. Florida's mandatory self-reported, prenatal survey can identify women at risk for poor neonatal outcomes. A more nuanced understanding how women are interpreting survey items and a re-evaluation of scoring practices may allow the tool to better serve as a model for other programs seeking to identify pregnant women at risk of poor birth outcomes.

Background Although high-grade salivary gland cancers (SGCs) often express androgen receptor (AR) and/or HER-2/neu, therapeutically targeting these receptors in SGC remains investigational. We investigated the prevalence of receptor expression and the benefit of adjuvant HER-2 directed therapy in the high-risk postoperative setting and explored the clinical utility of sequentially targeting these receptors in the setting of advanced disease. Materials and Methods We clinically annotated 95 patients with SGC (excluding adenoid cystic carcinoma) treated at our institution from 2002 to 2019 and recorded AR, HER-2/neu status, and tumor genomic profiling results when available. Clinicopathologic information was then integrated with outcomes. Results Of 95 patients, most had high-risk histologies, with salivary duct carcinoma (SDC) as the most frequent diagnosis (43, 45%). Thirty-five (37%) experienced recurrence (51% SDC). HER-2/neu was positive (1–3+) by immunostaining in 34 of 52 (65%) evaluable cases. There was no difference in survival based on HER-2/neu or AR expression. Nine of 17 (53%) patients with HER-2+ SDC received adjuvant chemoradiation with trastuzumab. Median disease-free survival (DFS) and overall survival (OS) were longer among patients with HER-2/neu 3+ staining tumors who received adjuvant trastuzumab versus those who did not (DFS, 117 vs. 9 months; p = .02; OS, 74 vs. 43 months; p = .02), with no difference among other HER-2/neu subgroups (0–2+). Two of nine (22%) patients treated with adjuvant trastuzumab demonstrated recurrence, both with low HER-2/neu staining intensity (1+). Longer time to recurrence (hazard ratio, 0.94; p = .01) predicted improved outcomes. Both androgen deprivation and HER-2-directed therapies had clinical benefit beyond the first-line metastatic setting, with partial response observed beyond second-line use. Conclusion Although prospective data are lacking, the use of adjuvant trastuzumab in high-risk patients with SGC appears beneficial, particularly among patients with tumors exhibiting HER-2/neu 3+ immunostaining. Implications for Practice Results of this study showed an improved disease-free and overall survival in patients treated with adjuvant trastuzumab for high-risk salivary gland cancers with strong HER-2/neu staining intensity. Following recurrence or metastatic spread, sequential HER-2, and androgen-directed therapies may benefit certain patients with salivary gland cancer.

AIMS Hobnail variant of papillary thyroid carcinoma (PTC) is an aggressive PTC subtype characterised by a hobnail cytomorphology. However, some classic PTC have a 'hobnail-like' cytomorphology associated with thick, hyalinised, variably oedematous fibrovascular cores that appears to be a form of ischaemic/degenerative atypia. METHODS AND RESULTS We studied three cohorts to compare the histopathological characteristics and clinical outcome of 'hobnail-like' classic PTC and true hobnail variant of PTC: cohort 1, PTC consecutively resected between 2016 and 2017 (to assess frequency of 'hobnail-like' cytomorphology); cohort 2, 20 'hobnail-like' classic PTC resected between 2005 and 2007 (to assess clinical outcome); and cohort 3, seven true hobnail variant of PTC. A 'hobnail-like' cytomorphology was identified in 16% of consecutively resected PTC. Compared with true hobnail variant, 'hobnail-like' classic PTC occurred in younger patients (mean age 40 years versus 68 years, P

Background Following birth, women may access preventive care in adult settings or, with their infants, in pediatric settings. Preventive care can improve future birth outcomes and long-term health, particularly for women with health risks. Methods This cohort study linked mother-infant Medicaid claims from 12 states for 2007-2011 births. Pregnancy claims identified health risk categories: maternal cardiovascular (diabetes, hypertension, pre-eclampsia, obesity), maternal mental health (depression, anxiety), and premature birth. Claims for 1 year following birth identified adult and pediatric preventive visits. Logistic regression assessed the relationship between visits and risks, adjusting for maternal demographics, perinatal health care utilization, year, and state. Results Of 594,888 mother-infant dyads with Medicaid eligibility for 1 year following birth, 36% had health risks. In total, 38% of all dyads, and 33% with health risks, had no adult preventive visits. Dyads had a median of 1 (IQR, 0-2) adult and 3 (IQR, 2-5) pediatric preventive visits. A total of 72% of dyads had more preventive visits in pediatric than adult settings. In regression, preterm birth was associated with lower odds of any adult preventive visits [odds ratio (OR), 0.97; 95% confidence interval (CI), 0.95-0.99], and maternal health risks with higher odds (cardiovascular OR, 1.19; 95% CI, 1.18-1.21; mental health OR, 1.87; 95% CI, 1.84-1.91), compared with dyads without risk. Conclusions Maternal health risks were associated with increased adult preventive visits, but 38% of dyads had no adult preventive visits in the year following birth. Most dyads had more opportunities for preventive care in pediatric settings than adult settings.

PURPOSE The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium. MATERIALS AND METHODS Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients. RESULTS Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH. CONCLUSION PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.

OBJECTIVES To determine if birth hospitalization length of stay (LOS) and infant rehospitalization changed during the coronavirus disease 2019 (COVID-19) era among healthy, term infants. METHODS Retrospective cohort study using Epic’s Cosmos data from 35 health systems of term infants discharged ≤5 days of birth. Short birth hospitalization LOS (vaginal birth RESULTS Among 202 385 infants (57 110 from the COVID-19 era), short birth hospitalization LOS increased from 28.5% to 43.0% for all births (vaginal: 25.6% to 39.3%, cesarean: 40.1% to 61.0%) during the pandemic and persisted after multivariable adjustment (all: aOR 2.30, 95% confidence interval [CI] 2.25–2.36; vaginal: aOR 2.12, 95% CI 2.06–2.18; cesarean: aOR 3.01, 95% CI 2.87–3.15). Despite shorter LOS, infant rehospitalizations decreased slightly during the pandemic (1.2% to 1.1%); results were similar in adjusted analysis (all: aOR 0.83, 95% CI 0.76–0.92; vaginal: aOR 0.82, 95% CI 0.74–0.91; cesarean: aOR 0.87, 95% CI 0.69–1.10). There was no change in the proportion of rehospitalization diagnoses between eras. CONCLUSIONS Short infant LOS was 51% more common in the COVID-19 era, yet infant rehospitalization within a week did not increase. This natural experiment suggests shorter birth hospitalization LOS among family- and clinician-selected, healthy term infants may be safe with respect to infant rehospitalization, although examination of additional outcomes is needed.

International audience; Context: This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). Objective: To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted. Evidence synthesis: Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non–muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in “fit” patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1–negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/. Conclusions: This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. Patient summary: The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease. Radical cystectomy with urinary diversion remains the mainstay of managing muscle-invasive bladder cancer (MIBC). The use of neoadjuvant chemotherapy (NAC) has improved overall survival rates, but selection of patients who will benefit most from NAC remains challenging. In case bladder-preserving strategies are considered, patient stratification according to their risk profile is imperative and management should be discussed in a multidisciplinary team. As yet, there are no validated prognostic molecular markers to guide the clinical management of MIBC. In a metastatic setting, cisplatin-based chemotherapy remains the first choice in fit patients. In unfit patients, based on interim results from two on-going clinical trials, first-line treatment with pembrolizumab or atezolizumab for urothelial cancer is restricted to Programmed Death Ligand 1-positive patients only.

Background Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. Purpose The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study. Methods Patients had left ventricular ejection fraction between ≥30% and 125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each. Results CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed median 23.3% NT-proBNP reduction, vs. 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and positive trends for cardiac fibrosis biomarkers. Conclusions This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. The indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Cardior Pharmaceuticals GmbH

Background Leukodystrophies are a rare class of disorders characterized by severe neuromotor disability. There is a strong need for research regarding the functional status of people with leukodystrophy which is limited by the need for in-person assessments of mobility. The purpose of this study is to assess the reliability of the Gross Motor Function Measure-88 (GMFM-88) using telemedicine compared with standard in-person assessments in patients with leukodystrophy. Methods A total of 21 subjects with a diagnosis of leukodystrophy (age range = 1.79-52.82 years) were evaluated by in-person and by telemedicine evaluations with the GMFM-88 by physical therapists. Inter-rater reliability was assessed through evaluation of the same subject by two independent raters within a three-week period (n = 10 encounters), and intrarater reliability was assessed through blinded rescoring of video-recorded assessments after a one-week time interval (n = 6 encounters). Results Remote assessments were performed by caregivers in all 21 subjects using resources found in the home with remote guidance. There was agreement between all paired in-person and remote measurements (Lin's concordance correlation ≥0.995). The Bland-Altman analysis indicated that the paired differences were within ±5%. Intrarater and inter-rater reliability demonstrated an intraclass correlation coefficient of >0.90. Conclusions These results support that remote application of the GMFM-88 is a feasible and reliable approach to assess individuals with leukodystrophy. Telemedicine application of outcome measures may be of particular value in rare diseases and those with severe neurologic disability that impacts the ability to travel.

Importance Telemedicine has been shown to have had reduced uptake among historically marginalized populations within multiple medical specialties during the COVID-19 pandemic. An evaluation of health disparities among patients receiving ophthalmic telemedical care during the pandemic is needed. Objective To evaluate disparities in the delivery of ophthalmic telemedicine at Massachusetts Eye and Ear (MEE) during the COVID-19 pandemic. Design, setting, and participants This retrospective, cross-sectional study analyzed clinical visits at a single tertiary eye care center (MEE) from January 1 to December 31, 2020. Patients who had ophthalmology and optometry clinical visits at the MEE during the study period were included. Exposures Telemedicine vs in-person clinical encounters. Main outcomes and measures Variables associated with use of ophthalmic telemedicine during the study period. Results A total of 2262 telemedicine ophthalmic encounters for 1911 patients were included in the analysis. The median age of the patients was 61 (interquartile range, 43-72) years, and 1179 (61.70%) were women. With regard to race and ethnicity, 87 patients (4.55%) identified as Asian; 128 (6.70%), as Black or African American; 23 (1.20%), as Hispanic or Latino; and 1455 (76.14%), as White. On multivariate analysis, factors associated with decreased receipt of telemedical care included male sex (odds ratio [OR], 0.86; 95% CI, 0.77-0.96), Black race (OR, 0.69; 95% CI, 0.56-0.86), not speaking English (OR, 0.63; 95% CI, 0.48-0.81), educational level of high school or less (OR, 0.83; 95% CI, 0.71-0.97), and age (OR per year of age, 0.99; 95% CI, 0.989-0.998). When comparing telephone- and video-based telemedicine visits, decreased participation in video-based visits was associated with age (OR per year of age, 0.96; 95% CI, 0.94-0.98), educational level of high school or less (OR, 0.54; 95% CI, 0.29-0.99), being unemployed (OR, 0.28; 95% CI, 0.12-0.68), being retired (OR, 0.22; 95% CI, 0.10-0.42), or having a disability (OR, 0.09; 95% CI, 0.04-0.23). Conclusions and relevance The findings of this cross-sectional study, though limited to retrospective data from a single university-based practice, suggest that historically marginalized populations were less likely to receive ophthalmic telemedical care compared with in-person care during the first year of the COVID-19 pandemic in the US. Understanding the causes of these disparities might help those who need access to virtual care.

Aims This first‐in‐human clinical trial of P218, a novel dihydrofolate reductase inhibitor antimalarial candidate, assessed safety, tolerability, pharmacokinetics and food effects in healthy subjects. Methods The study consisted of two parts. Part A was a double‐blind, randomized, placebo‐controlled, parallel group, ascending dose study comprising seven fasted cohorts. Eight subjects/cohort were randomized (3:1) to receive either a single oral dose of P218 (10, 30, 100, 250, 500, 750 and 1000 mg) or placebo. Part B was an open‐label, cross‐over, fed/fasted cohort (eight subjects) that received a 250 mg single dose of P218 in two treatment periods. Results P218 was generally well tolerated across all doses; 21 treatment‐emergent adverse events occurred in 15/64 subjects. Nine adverse events in five subjects, all of mild intensity, were judged drug related. No clinically relevant abnormalities in ECG, vital signs or laboratory tests changes were observed. P218 was rapidly absorbed, with C max achieved between 0.5 and 2 hours post dose. Plasma concentrations declined bi‐exponentially with half‐life values ranging from 3.1 to 6.7 hours (10 and 30 mg), increasing up to 8.9 to 19.6 hours (doses up to 1000 mg). Exposure values increased dose‐proportionally between 100 and 1000 mg for P218 (parent) and three primary metabolites (P218 β‐acyl glucuronide, P218‐OH and P218‐OH β‐acyl glucuronide). Co‐administration of P218 with food reduced C max by 35% and delayed absorption by 1 hour, with no significant impact on AUC. Conclusion P218 displayed favourable safety, tolerability and pharmacokinetics. In view of its short half‐life, a long‐acting formulation will be needed for malaria chemoprotection.

Acute abdominal emergencies in calves due to abomasal disorders, gastrointestinal ileus, or peritonitis are characterized by a rapid disease progression and usually require immediate surgical intervention. Those conditions are associated with a guarded prognosis, and the aim of the present study was to assess the prognostic relevance of preoperatively measured plasma l-lactate concentrations (l-LAC) in a large study population of calves with a broad spectrum of acute abdominal emergencies. For the purpose of this study, the medical records of 587 calves admitted to a veterinary teaching hospital over a 10-yr period were analyzed retrospectively. Plasma l-LAC was measured as part of a routinely performed biochemistry panel before initiation of surgical intervention. Hyper-l-lactatemia (plasma l-LAC >2.2 mmol/L) was evident in 75% of calves, and the overall survival rate until hospital discharge was 31%. Calves with a negative outcome were younger (median: 3.4 vs. 6 wk) and had higher plasma l-LAC (median: 4.96 vs. 3.09 mmol/L) than calves with a positive outcome. At the individual diagnosis level, l-LAC was associated with mortality in calves with a diagnosis of mesenteric torsion, right-sided dilated abomasum, small intestinal volvulus, or paralytic ileus, but not in calves suffering from peritonitis, malformations, abomasal volvulus, bloat, or small intestinal intussusceptions. Considering the whole study population, the area under the receiver operating characteristic (ROC) curve for plasma l-LAC was 0.66 [95% confidence interval (CI): 0.61-0.70]. A classification tree analysis indicated that l-LAC >8.84 mmol/L and age categories of

Patients with end-stage renal disease treated with dialysis are often prescribed complex medication regimens, placing them at risk for drug-drug interactions and other medication-related problems. Particularly in the context of a broader interest in more patient-centered value-based care, improving medication management is an increasingly important focus area. However, current medication management metrics, designed for the broader patient population, may not be well suited to the specific needs of patients with kidney disease, especially given the complexity of medication regimens used by dialysis patients. We propose a kidney pharmacy-focused quality pyramid that is intended to provide a framework to guide dialysis organizations, health care providers, and/or clinicians with respect to an optimal medication management approach for dialysis patients. Incorporation of core programs in medication management, including medication reconciliation, safety programs, and medication therapy management for patients at high risk for medication-related problems, may result in improved outcomes. Although a growing body of evidence supports the concept that active medication management can improve medication adherence and reduce medication-related problems, these strategies are viewed as costly and are not widely deployed. However, if done effectively, pharmacy-led medication management has the potential to be one of the more cost-effective disease management strategies and may greatly improve outcomes for these complex patients. Index Words: end-stage renal disease, medication management, pharmacy

Background Australian Aboriginal and Torres Strait Islander (Indigenous) peoples face major health disadvantage across many conditions. Recording of patients’ Indigenous status in general practice records supports equitable delivery of effective clinical services. National policy and accreditation standards mandate recording of Indigenous status in patient records, however for a large proportion of general practice patient records it remains incomplete. We assessed the completeness of Indigenous status in general practice patient records, and compared the patient self-reported Indigenous status to general practice medical records. Methods A cross sectional analysis of Indigenous status recorded at 95 Australian general practices, participating in the Australian Chlamydia Control Effectiveness Pilot (ACCEPt) in 2011. Demographic data were collected from medical records and patient surveys from 16 to 29 year old patients at general practices, and population composition from the 2011 Australian census. General practitioners (GPs) at the same practices were also surveyed. Completeness of Indigenous status in general practice patient records was measured with a 75% benchmark used in accreditation standards. Indigenous population composition from a patient self-reported survey was compared to Indigenous population composition in general practice records, and Australian census data. Results Indigenous status was complete in 56% (median 60%, IQR 7–81%) of general practice records for 109,970 patients aged 16–29 years, and Indigenous status was complete for 92.5% of the 3355 patients aged 16–29 years who completed the survey at the same clinics. The median proportion per clinic of patients identified as Indigenous was 0.9%, lower than the 1.8% from the patient surveys and the 1.7% in clinic postcodes (ABS). Correlations between the proportion of Indigenous people self-reporting in the patient survey (5.2%) compared to status recorded in all patient records (2.1%) showed a fair association (r = 0.6468; p

Aims The activity that the immune checkpoint inhibitor (ICI) cemiplimab has recently demonstrated has led to a paradigm shift in the management of patients with advanced cutaneous squamous cell carcinoma (cSCC). To identify predictive biomarkers of response to ICIs in advanced cSCC, we studied 33 patients who received ICI therapy at the Dana-Farber/Harvard Cancer Center (DF/HCC) and analysed sequencing data for a subset of these patients. Methods We collected clinical data using electronic health records and genomic data using the institutional OncoPanel platform of the DF/HCC. We compared tumour genomics with data from previously sequenced cSCC cohorts. Results We observed high tumour mutational burden regardless of smoking status and response to ICI and longer median overall survival among those patients who achieved an ICI response. We compared the genetic data from our cohort with data from other cohorts that included fewer patients with distant metastatic disease. Although our cohort had a similar genetic landscape to those of comparator cohorts, mutations in PIK3C2B were more common in our study. In our cohort, copy number alterations (CNAs) in the 3q chromosomal arm appeared to predict response to ICI therapy. Conclusion CNAs in the 21–27 bands of chromosome arm 3q, a region that includes PIK3CA, ETV5 and BCL6, may represent predictors of response to ICI and may be candidates for drug targeting in combination or sequence with ICI agents.

Context The impact of Hashimoto thyroiditis (HT) on the risk of thyroid cancer and its accurate detection remains unclear. The presence of a chronic lymphocytic infiltration imparts a logical mechanism potentially altering neoplastic transformation, while also influencing the accuracy of diagnostic evaluation. Methods We performed a prospective, cohort analysis of 9851 consecutive patients with 21,397 nodules ≥1 cm who underwent nodule evaluation between 1995 and 2017. The definition of HT included (i) elevated thyroid peroxidase antibody (TPOAb) level and/or (ii) findings of diffuse heterogeneity on ultrasound, and/or (iii) the finding of diffuse lymphocytic thyroiditis on histopathology. The impact of HT on the distribution of cytology and, ultimately, on malignancy risk was determined. Results A total of 2651 patients (27%) were diagnosed with HT, and 3895 HT nodules and 10,168 non-HT nodules were biopsied. The prevalence of indeterminate and malignant cytology was higher in the HT vs non-HT group (indeterminate: 26.3% vs 21.8%, respectively, P < 0.001; malignant: 10.0% vs 6.4%, respectively, P < 0.001). Ultimately, the risk of any nodule proving malignant was significantly elevated in the setting of HT (relative risk, 1.6; 95% CI, 1.44 to 1.79; P < 0.001), and was maintained when patients with solitary or multiple nodules were analyzed separately (HT vs non-HT: 24.5% vs 16.3% solitary; 22.1% vs 15.4% multinodular; P < 0.01). Conclusion HT increases the risk of thyroid malignancy in any patient presenting for nodule evaluation. Diffuse sonographic heterogeneity and/or TPOAb positivity should be used for risk assessment at time of evaluation.

Approximately 420 men are diagnosed with germ-cell cancer (GCC) in Switzerland each year. Recent international guidelines outline management issues, but many aspects remain controversial in an area of highly individualised treatments. Even more than in other tumour types, in GCC the challenge is to choose exactly the correct treatment for an individual patient. Overtreatment in patients likely to be cured must be avoided to reduce long-term toxicities. On the other hand, treatment intensification is required in patients presenting with adverse prognostic factors. Therefore, referral to expert centres or consultations with an expert for a second opinion is strongly recommended. In 2020, Swiss experts discussed their strategies in a consensus meeting during the virtual Swiss Oncology and Haematology Congress (SOHC) in order to harmonise their concepts and to suggest optimal strategies for the management of GCC patients in Switzerland. Votes on controversial issues were obtained and are presented in this review wherever applicable.

Purpose: To examine patterns of standard (trabeculectomy or glaucoma drainage devices, GDDs) vs novel (minimally invasive glaucoma surgery, MIGS) surgical techniques in the US.Methods: We used the American Academy of Ophthalmology (AAO) IRIS® Registry (Intelligent Research in Sight) queried between 2013 and 2018 (inclusive) to calculate the cumulative proportion of stand-alone, concurrent (same day) or sequential (subsequent day) glaucoma surgical techniques performed in each glaucoma diagnosis type. Secondary analyses of adjusted proportions of concurrent and sequential surgeries stratified by glaucoma diagnosis were also performed.Results: Of 203,146 eyes receiving glaucoma surgeries, open angle glaucoma (OAG) was most likely to undergo all types of intervention. The iStent was the most commonly performed MIGS, primarily for those with normal tension glaucoma (NTG) or OAG (p < .001). Conversely, GDD was the most commonly performed procedure in secondary glaucoma or other (specified) glaucoma (p < .001). ECP and iStent were the most common concurrent procedures performed; most often for OAG and NTG (p < .001). After an initial standard surgery, most eyes underwent recurrent standard interventions (90.3%). ECP was the most common MIGS performed after an initial standard surgery; particularly in primary angle-closure (PACG) and secondary glaucoma eyes (p < .001).Conclusion: Glaucoma type may influence the choice of glaucoma procedures and the decision to perform concurrent as well sequential surgical procedures. Given the poorly understood long term safety and effectiveness of MIGS, and with substantially increasing use of MIGS procedures in recent years, future studies comparing their safety and effectiveness vs standard interventions, for a variety of glaucoma types, is needed.

Purpose: Surgery often represents the best chance for disease control in locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN). We investigated dual immune-checkpoint inhibition [anti–PD-1, nivolumab (N), and anti-KIR, lirilumab (L)] before and after salvage surgery to improve disease-free survival (DFS). Patients and Methods: In this phase II study, patients received N (240 mg) + L (240 mg) 7 to 21 days before surgery, followed by six cycles of adjuvant N + L. Primary endpoint was 1-year DFS; secondary endpoints were safety, pre-op radiologic response, and overall survival (OS). Correlatives included tumor sequencing, PD-L1 scoring, and immunoprofiling. Results: Among 28 patients, the median age was 66, 86% were smokers; primary site: 9 oral cavity, 9 oropharynx, and 10 larynx/hypopharynx; 96% had prior radiation. There were no delays to surgery. Grade 3+ adverse events: 11%. At the time of surgery, 96% had stable disease radiologically, one had progression. Pathologic response to N + L was observed in 43% (12/28): 4/28 (14%) major (tumor viability, TV ≤ 10%) and 8/28 (29%) partial (TV ≤ 50%). PD-L1 combined positive score (CPS) at surgery was similar regardless of pathologic response (P = 0.71). Thirteen (46%) recurred (loco-regional = 10, distant = 3). Five of 28 (18%) had positive margins, 4 later recurred. At median follow-up of 22.8 months, 1-year DFS was 55.2% (95% CI, 34.8–71.7) and 1-year OS was 85.7% (95% CI, 66.3–94.4). Two-year DFS and OS were 64% and 80% among pathologic responders. Conclusions: (Neo)adjuvant N + L was well tolerated, with a 43% pathologic response rate. We observed favorable DFS and excellent 2-year OS among high-risk, previously treated patients exhibiting a pathologic response. Further evaluation of this strategy is warranted.

We aim to study kinetics of anti-SARS-CoV-2 IgG antibody levels in subjects with COVID-19 for up to 11 months and the potential influential factors. The study was a prospective longitudinal study. The analyses were based on 77 serum/plasma samples with a mean of 4 samples per participant (range 1 – 18) in 20 participants with at least one positive Polymerase Chain Reaction testing result from 19 March 2020 up to 10 February 2021. Among the subjects (median age 34.5 years, 65% male), IgG level declined with the follow-up time (per month; geometric mean ratio [GMR] 0.73; 95% CI, 0.72 – 0.74). In a small sample of subjects from the general population with COVID-19, IgG levels declined non-linearly from month 2 to 11 with individual heterogeneity in quantity and changing speed and may be associated with gender, race and the loss of smell and taste.

Purpose To compare the rate of postoperative endophthalmitis after immediately sequential bilateral cataract surgery (ISBCS) versus delayed sequential bilateral cataract surgery (DSBCS) using the American Academy of Ophthalmology Intelligent Research in Sight (IRIS) Registry database. Design Retrospective cohort study. Participants Patients in the IRIS Registry who underwent cataract surgery from 2013 through 2018. Methods Patients who underwent cataract surgery were divided into 2 groups: (1) ISBCS and (2) DSBCS (second-eye surgery ≥1 day after the first-eye surgery) or unilateral surgery. Postoperative endophthalmitis was defined as endophthalmitis occurring within 4 weeks of surgery by International Classification of Diseases (ICD) code and ICD code with additional clinical criteria. Main Outcome Measures Rate of postoperative endophthalmitis. Results Of 5 573 639 IRIS Registry patients who underwent cataract extraction, 165 609 underwent ISBCS, and 5 408 030 underwent DSBCS or unilateral surgery (3 695 440 DSBCS, 1 712 590 unilateral surgery only). A total of 3102 participants (0.056%) met study criteria of postoperative endophthalmitis with supporting clinical findings. The rates of endophthalmitis in either surgery eye between the 2 surgery groups were similar (0.059% in the ISBCS group vs. 0.056% in the DSBCS or unilateral group; P = 0.53). Although the incidence of endophthalmitis was slightly higher in the ISBCS group compared with the DSBCS or unilateral group, the odds ratio did not reach statistical significance (1.08; 95% confidence interval, 0.87–1.31; P = 0.47) after adjusting for age, sex, race, insurance status, and comorbid eye disease. Seven cases of bilateral endophthalmitis with supporting clinical data in the DSBCS group and no cases in the ISBCS group were identified. Conclusions Risk of postoperative endophthalmitis was not statistically significantly different between patients who underwent ISBCS and DSBCS or unilateral cataract surgery.

BACKGROUND AND OBJECTIVES We measured within-hospital concordance of mothers with opioid use disorder (OUD) and newborns with neonatal abstinence syndrome (NAS) or opioid exposure (OE). Secondarily, we described the demographics of mothers and newborns with and without opioid-related diagnoses. METHODS We used hospital discharge abstracts from California, Florida, New Jersey, and Pennsylvania in 2016. Descriptive statistics were used to compare newborns and mothers with and without opioid-related diagnoses. Within-hospital frequencies of mothers with OUD and newborns with NAS and OE were compared. Pearson’s correlation coefficients were calculated. RESULTS In 474 hospitals, we found 896 702 mothers (0.6% with OUD) and 910 867 newborns (0.47% with NAS, 0.85% with OE, and 0.07% with both). Although the frequency of mothers and newborns with opioid-related diagnoses in a hospital was strongly correlated (r = 0.81), more infants were identified than mothers in most hospitals (68.3%). Mothers with OUD were more likely to be white (79% vs 40.9%), on Medicaid (75.4% vs 44.0%), and receive care in rural hospitals (20.6% vs 17.6%), compared with mothers without OUD. Newborns with NAS had demographics similar to women with OUD. Newborns with OE were disproportionately Black (22% vs 7%) or Hispanic (22% vs 9%). CONCLUSIONS More newborns are diagnosed with opioid-related disorders than mothers are. Although infants diagnosed with NAS had demographics similar to mothers with OUD, infants with OE were more likely to be Black or Hispanic. The lack of diagnostic coding of maternal OUD and the racial differences in diagnoses warrant attention.

Background The goal of regionalized perinatal care, specifically levels of maternal care, is to improve maternal outcomes through risk-appropriate obstetric care. Studies of levels of maternal care are limited by current approaches to identify a hospital’s level of care, often relying on hospital self-reported data, which is expensive and challenging to collect and validate. The study objective was to develop an empiric approach to determine a hospital’s level of maternal care using administrative data reflective of the patient care provided and apply this approach to describe the levels of maternal care available over time. Methods Retrospective cohort study of mother-infant dyads who delivered in California, Missouri, and Pennsylvania hospitals from 2000 to 2009. Linked mother-infant administrative records with an infant born at 24–44 weeks’ gestation and a birth weight of 400–8000 g were included. Using the American College of Obstetricians and Gynecologists and the Society for Maternal Fetal Medicine descriptions of levels of maternal care, four levels were classified based on the appropriate location of care for patients with specific medical or pregnancy conditions. Individual hospitals were assigned a level of maternal care annually based on the volume of patients who delivered reflective of the four classified levels as determined by International Classification of Diseases and Current Procedural Terminology. Results Based on the included 6,895,000 mother-infant dyads, the obstetric hospital levels of maternal care I, II, III and IV were identified. High-risk patients more frequently delivered in hospitals with higher level maternal care, accounting for 8.9, 10.9, 13.8, and 16.9% of deliveries in level I, II, III and IV hospitals, respectively. The total number of obstetric hospitals decreased over the study period, while the proportion of hospitals with high-level (level III or IV) maternal care increased. High-level hospitals were located in more densely populated areas. Conclusion Identification of the level of maternal care, independent of hospital self-reported variables, is feasible using administrative data. This empiric approach, which accounts for changes in hospitals over time, is a valuable framework for perinatal researchers and other stakeholders to inexpensively identify measurable benefits of levels of maternal care and characterize where specific patient populations receive care.