Surveillance Group Research Articles

Cost-Effectiveness of Prophylactic Cranial Irradiation vs. MRI Surveillance for Extensive Stage Small Cell Lung Cancer

Due to conflicting prospective data, controversy exists regarding prophylactic cranial irradiation (PCI) in extensive stage small cell lung cancer (ES-SCLC). We sought to evaluate the cost-effectiveness of PCI versus MRI surveillance alone in the context of modern radiotherapy treatment modalities using available evidence and the CMS alternative payment model (APM).A Markov state transition model was constructed using software to perform a cost-effectiveness analysis comparing MRI surveillance alone with PCI for ES-SCLC. PCI in the base case analysis was assumed to be 25 Gy in 10 fractions delivered with a 3D conformal radiotherapy technique (3D-CRT) without daily image guidance. In the MRI surveillance alone arm, MRI surveillance was assumed to be performed at baseline then every 3 months for the first year and every 6 months for year 2, consistent with the surveillance plan currently being implemented in the SWOG MAVERICK cooperative group trial (NCT04155034). Clinical parameters were obtained from clinical trial data, and cost data were based on 2019 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness to pay threshold of $100,000 per QALY gained. One-way and probabilistic sensitivity analyses were performed to consider model uncertainty.In the base case scenario, PCI was not cost-effective with an ICER of $168,456 per QALY gained compared to MRI surveillance alone, assuming that overall survival was 10 months and 12.5 months for MRI surveillance alone and PCI, respectively. One-way sensitivity analysis showed that results were most sensitive to the variation of overall survival and cognitive decline rates between the two groups. In a scenario analysis, when all patients receive hippocampal-avoidance PCI (HA-PCI), the model results become near cost effective with PCI due to presumed lower rate of cognitive decline (ICER $129,307 per QALY gained). If HA-IMRT with memantine was also utilized for salvage treatment in all patients in the MRI surveillance group with the assumption above, PCI was found to be cost effective ($88,096 per QALY gained). In addition, the total radiation therapy reimbursement per episode suggested by APM for radiation therapy for brain metastases ($10,783) is almost identical to the current Medicare reimbursement rate for 10 fractions with HA-IMRT ($10,445). Thus, this scenario analysis also reflected the use of the APM.PCI was not cost effective compared to MRI surveillance alone due to the neurocognition decline impact of PCI based on available evidence. HA-PCI may be a potential cost-effective strategy for ES-SCLC, with expected confirmation following the ongoing SWOG MAVERICK trial, which includes assessments of cognitive function.

Intervention versus surveillance in patients with common bile duct stones detected by intraoperative cholangiography: a population-based registry study.

Each year 13 000 patients undergo cholecystectomy in Sweden, and routine intraoperative cholangiography (IOC) is recommended to minimize bile duct injuries. The risk of requiring endoscopic retrograde cholangiopancreatography (ERCP) following cholecystectomy for common bile duct (CBD) stones where IOC is omitted and in patients with CBD stones left in situ is not well known. Data were retrieved from the population-based Swedish Registry of Gallstone Surgery and ERCP between 1 January 2009 and 10 December 2019. Primary outcome was risk for postoperative ERCP for retained CBD stones. A total of 134 419 patients that underwent cholecystectomy were included and 2691 (2.0 per cent) subsequently underwent ERCP for retained CBD stones. When adjusting for emergency or planned cholecystectomy, preoperative symptoms suggestive of CBD stones, sex and age, there was an increased risk for ERCP when IOC was not performed (hazard ratio (HR) 1.4, 95 per cent c.i. 1.3 to 1.6). The adjusted risk for ERCP was also increased if CBD stones identified by IOC were managed with surveillance (HR 5.5, 95 per cent c.i. 4.8 to 6.4). Even for asymptomatic small stones (less than 4 mm), the adjusted risk for ERCP was increased in the surveillance group compared with the intervention group (HR 3.5, 95 per cent c.i. 2.4 to 5.1). IOC plus an intervention to remove CBD stones identified during cholecystectomy was associated with reduced risk for retained stones and unplanned ERCP, even for the smallest asymptomatic CBD stones.

Spatial analysis of areas at risk for schistosomiasis in the Alto Tietê Basin, São Paulo, Brazil

The present study identified locations with the presence of Biomphalaria and the areas at risk for Schistosoma mansoni, the etiological agent of schistosomiasis, in the Metropolitan Region of São Paulo (MRSP), located in the Alto Tietê Basin (ATB), São Paulo, Brazil. The study area comprises floodplains of the Tietê River from its source, in Salesópolis, to Rasgão Dam, in Pirapora do Bom Jesus, covering 39 municipalities. Data from the planorbidic chart of the malacology laboratory of the Endemic Control Superintendence for 2008–2016 were used, as well as data from the notification forms of cases of human schistosomiasis in 2006–2015 made available by the Epidemiological Surveillance Groups of Mogi das Cruzes and Osasco, and by the Health and Surveillance Coordination of São Paulo. These data were used to generate maps of the distribution of Biomphalaria, of the scanning analysis, of the Gi statistics of the autochthonous and imported schistosomiasis cases, and of the flow of cases imported from other Brazilian states and municipalities in the state of São Paulo to the study area. A total of 21,618 specimens of the genus Biomphalaria were captured and six species were identified. Biomphalaria tenagophila was the predominant species in the region and of greatest epidemiological importance as it is the main responsible for the transmission of the disease in the state of São Paulo. A total of 3,623 cases of schistosomiasis were reported in the study area, and São Paulo and Guarulhos were the municipalities with the highest number of autochthonous and imported cases during the study period. The imported cases originated from 21 Brazilian states plus the Federal District and from 51 municipalities in São Paulo state located outside the study area. Autochthonous clusters with high risk for the occurrence of schistosomiasis were identified in the municipalities of São Paulo, Guarulhos, Santa Isabel/Mogi das Cruzes/Arujá, and Cotia/Itapevi. Clusters of imported cases were also identified in Itaquaquecetuba, at the border of Cotia/Itapevi and Suzano/São Paulo/Mogi das Cruzes. The presence of B. tenagophila in the ATB and in the clusters of autochthonous cases herein identified, although not carrying schistosome larvae, represents a risk for the transmission of infectious agents. The human population in the MRSP mainly occupies the lowlands of the Tietê River, which are locations with poor coverage of basic sanitation. Therefore, measures for the control and surveillance of schistosomiasis such as educational actions, improvements in basic sanitation, and the malacological and epidemiological monitoring of these areas are extremely important.

Surveillance of indeterminate pulmonary nodules detected with CT in a Swedish population-based study (SCAPIS): psychosocial consequences and impact on health-related quality of life—a multicentre prospective cross-sectional study

ObjectivesTo investigate whether surveillance of pulmonary nodules detected with low-dose CT (LDCT) impacted health-related quality of life and psychosocial consequences in the Swedish population-based study, Swedish CArdioPulmonary bioImage Study (SCAPIS).DesignA...

Any Postoperative Surveillance Improves Survival After Endovascular Repair of Ruptured Abdominal Aortic Aneurysms

Endovascular aortic repair (EVAR) has become first-line therapy for ruptured abdominal aortic aneurysms (rAAA). Rigorous surveillance imaging after EVAR is recommended due to the high risk of endograft complications in this population. Follow-up compliance is known to be poor after elective EVAR but has not been studied in patients after EVAR for rAAA (rEVAR). Our objective is to investigate patient factors that predict incomplete surveillance and examine how compliance impacts outcomes after rEVAR. This was a retrospective observational study of patients undergoing rEVAR at a multiple hospital single health care center (2003-2020). Patients were excluded if they underwent open conversion during their index hospitalization or died within 60 days of surgery. Follow-up surveillance was broadly categorized as complete surveillance (1-month postoperative visit and annually thereafter) or incomplete surveillance, which comprised both patients completely lost to follow-up (LTF) and those with less than recommended postoperative surveillance (minimal compliance; MC). We investigated predictors of complete vs incomplete surveillance by multivariate logistic regression. Kaplan-Meier curves were generated for surveillance groups and compared using the log-rank test. Multivariate Cox regression was used to explore the effect of surveillance compliance on survival. One-hundred sixty patients (mean age: 74 ± 10.1 years, 81.2% male) out of 673 total rAAA met study inclusion criteria. The majority were white (96.5%) with a history of tobacco use (69.7%), hypertension (59.6%), and coronary artery disease (56.0%). Complete surveillance was seen in 41.3% of our cohort. The remainder had either MC (29.4%) or were LTF (29.4%). On multivariable regression, longer driving distance from home to treating hospital, male sex, and lack of a primary care provider (PCP) were associated with incomplete surveillance. Death occurred in 65 (40.6%) and reintervention in 25 (15.6%) patients during the study period. Survival was not different between complete and incomplete surveillance groups (P = .24). Subgroup analysis revealed a similar survival for patients with complete surveillance and those with minimal compliance. On multivariate Cox analysis, any follow-up conferred improved survival over LTF (hazard ratio, 0.57; 95% confidence interval, 0.331-0.997; P = .049) (Fig). Incomplete follow-up surveillance was observed in over 50% of patients who underwent rEVAR and was associated with longer driving distance, male sex, and lack of listed PCP. Any follow-up after rEVAR conferred a survival advantage. Thus, identification of patient level risk factors for poor follow-up before discharge will guide the design of mitigation strategies to prevent LTF.

Microbiological Surveillance of Biogas Plants: Targeting Acetogenic Community.

Acetogens play a very important role in anaerobic digestion and are essential in ensuring process stability. Despite this, targeted studies of the acetogenic community in biogas processes remain limited. Some efforts have been made to identify and understand this community, but the lack of a reliable molecular analysis strategy makes the detection of acetogenic bacteria tedious. Recent studies suggest that screening of bacterial genetic material for formyltetrahydrofolate synthetase (FTHFS), a key marker enzyme in the Wood-Ljungdahl pathway, can give a strong indication of the presence of putative acetogens in biogas environments. In this study, we applied an acetogen-targeted analyses strategy developed previously by our research group for microbiological surveillance of commercial biogas plants. The surveillance comprised high-throughput sequencing of FTHFS gene amplicons and unsupervised data analysis with the AcetoScan pipeline. The results showed differences in the acetogenic community structure related to feed substrate and operating parameters. They also indicated that our surveillance method can be helpful in the detection of community changes before observed changes in physico-chemical profiles, and that frequent high-throughput surveillance can assist in management towards stable process operation, thus improving the economic viability of biogas plants. To our knowledge, this is the first study to apply a high-throughput microbiological surveillance approach to visualise the potential acetogenic population in commercial biogas digesters.

Annual and lifetime economic productivity loss due to adult out-of-hospital cardiac arrest in the United States: A study for the CARES Surveillance Group

ObjectiveTo estimate the annual and lifetime economic productivity loss due to adult out-of-hospital cardiac arrest (OHCA) in the United States (U.S.). MethodsAll adult (age ≥ 18 years) non-traumatic EMS-treated OHCA with complete data for age, sex, race, and survival outcomes from the CARES database for 2013–2018 were included. Annual and lifetime labor productivity values, based on age and gender, were obtained from previously published national economic data. Productivity losses for OHCA events were calculated by year in U.S. dollars. Productivity losses for survivors were assigned by cerebral performance category score (CPC): CPC 1 and 2 = 0% productivity loss; CPC 3–5 = 100% productivity loss. Sensitivity analyses were performed assigning CPC 2 varying productivity losses (0–100%) based on CPC score and discharge location. Lifetime productivity values assumed 1% annual growth and 3% discount rate and were adjusted for inflation based on 2016 values. Results were extrapolated to annual U.S. population estimates for the study period. ResultsA total of 338,492 (96.5%) cases met inclusion criteria. The mean annual and lifetime productivity losses per OHCA in 2018 were $48,224 and $638,947 respectively. The total annual economic productivity loss due to OHCA in the U.S. increased from $7.4B in 2013 to $11.3B in 2018. Lifetime economic productivity loss increased from $95.2B in 2013 to $150.2B in 2018. Sensitivity analyses yielded similar findings. Per annual death, OHCA ranked third ($10.2B) in annual economic productivity loss in the U.S. behind cancer ($22.9B) and heart disease ($20.3B) in 2018. ConclusionAdult non-traumatic OHCA events are associated with significant annual and lifetime economic productivity losses and should be the focus of public health resources to improve preventative measures and survival outcomes.

Early detection of duodenal cancer by upper gastrointestinal-endoscopy in Lynch syndrome.

Small bowel cancer (SBC) is the malignancy with the highest standardized incidence ratio in Lynch syndrome (LS) patients. Of all SBCs, about 50% are duodenal cancers (DCs), therefore being accessible by esophago-gastro-duodenoscopy (EGD) for surveillance. We asked whether early detection of DC is possible for LS patients undergoing surveillance by EGD and if surveillance should be limited to specific subgroups. Data for LS patients with DC were retrieved from the registry of the German Consortium for Familial Intestinal Cancer. Patients undergoing active surveillance by EGDs (surveillance group) were compared to those who did not (nonsurveillance group) regarding tumor stage at diagnosis. Union for International Cancer Control stages I-IIA were defined as early stage disease and IIB-IV as advanced stage disease. Statistical analysis was performed using Fisher's exact test. Among 2015 patients with pathogenic variants in any mismatch-repair-gene, 47 patients with 49 DCs were identified. In 10% of cases, patients were under 35 years at diagnosis; family and personal tumor history did not correlate with DC diagnosis. Pathogenic germline variants in MSH6, PMS2 or EPCAM were present in 10% of patients. Statistical analysis could be performed on 13 DC patients in the surveillance group and 14 in the nonsurveillance group. Early detection was possible for 71% of patients in the surveillance group and 29% of patients in the nonsurveillance group (P=.021). Early detection of DC by EGD in LS patients is feasible regardless of family history, mutational status and should start no later than 25 years of age.

Bilateral Prophylactic Nipple-Sparing Mastectomy: Analysis of the Risk-Reducing Effect in BRCA1/2 Mutation Carriers.

Mutations in the BRCA1 or BRCA2 genes increase the lifetime risk of developing breast cancer to 68-72% by the age of 80. One of the modalities to manage the risk is a prophylactic mastectomy. Bilateral nipple-sparing mastectomy specifically offers the most favorable esthetic outcomes but the evidence for its oncological safety remains limited. Thus, we aimed to compare the occurrence of breast cancer between nipple-sparing mastectomy and surveillance groups of BRCA1 or BRCA 2 mutations carriers. BRCA1 or BRCA2-positive patients undergoing bilateral prophylactic nipple-sparing mastectomy at our department were identified. Only those unaffected by breast cancer were eligible. Each patient was pair-matched with a BRCA1 or BRCA2-positive patient of equal age from the surveillance group. Breast cancer incidence in both groups was recorded and the results were compared. None of 105 patients who underwent NSM between 2009 and 2019 at a single institution with a mean follow-up time of 50months developed breast cancer over this time period. One patient in this group died of an unrelated cause. Nine patients from 105 in the match-paired surveillance group were diagnosed with breast cancer during a mean follow-up time of 58.3months, however, none of them died. To the best of our knowledge, this is the largest single-center study of risk-reducing bilateral NSM in healthy BRCA1 or BRCA2 mutation carriers. Based on our results and those of other series, we conclude that NSM in its current form appears to be at least equally as safe as other types of mastectomy for preventing breast cancer in BRCA1 or BRCA2 mutation carriers. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Presentation of ovarian cancer in women with BRCA mutations

<h3>Objectives:</h3> Investigate the clinical presentation and diagnosis of ovarian cancer in women with <i>BRCA</i> mutations. <h3>Methods:</h3> Retrospective cohort study of all women in an integrated healthcare system with pathogenic mutations identified between 1/1/2003-12/31/2018 who were diagnosed with ovarian cancer (OC). Primary outcome was stage of OC; secondary outcomes included method of diagnosis in women with genetic testing before OC diagnosis, interval to diagnosis, and age at genetic testing and ovarian cancer diagnosis. <h3>Results:</h3> Of the 299 women with OC and a <i>BRCA</i> mutation, 41 women were diagnosed with OC after <i>BRCA</i> testing, with 26 (63%) diagnosed on risk-reducing salpingo-oophorectomy (RRSO), 4 (10%) diagnosed by abnormal surveillance testing, and 11 (27%) diagnosed with symptoms. Median age at OC diagnosis was 55, 54, and 58 years for the RRSO, surveillance and symptom groups respectively. Women with a known <i>BRCA</i> mutation status at the time of their OC diagnosis were more likely to have earlier stage OC compared to those who underwent genetic testing after their OC diagnosis (54% vs 15%, <i>p</i><0.001). <h3>Conclusions:</h3> In women with a known <i>BRCA</i> mutation, most OC is diagnosed in older women and at the time of RRSO. Women with a known <i>BRCA</i> mutation at the time of their OC diagnosis were more likely to have earlier stage disease compared to those who underwent genetic testing after their OC diagnosis. The late age at genetic testing of these patients, as well as the earlier stage disease seen in those with a known <i>BRCA</i> mutation, highlights the need for earlier genetic testing and RRSO. Cancers diagnosed on RRSO are more likely to be early stage. Few cancers are detected by surveillance.

Prehospital Tibial Intraosseous Drug Administration is Associated with Reduced Survival Following Out of Hospital Cardiac Arrest: A study for the CARES Surveillance Group

BackgroundRecent reports have questioned the efficacy of intraosseous (IO) drug administration for out-of-hospital cardiac arrest (OHCA) resuscitation. Our aim was to determine whether prehospital administration of resuscitative medications via the IO route was associated with lower rates of return of spontaneous circulation (ROSC) and survival to hospital discharge than peripheral intravenous (IV) infusion in the setting of OHCA. MethodsWe obtained data on all OHCA patients receiving prehospital IV or IO drug administration from the three most populous counties in Michigan over three years. Data was from the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) database. The association between route of drug administration and outcomes was tested using a matched propensity score analysis. ResultsFrom a total of 10,626 OHCA patients, 6869 received parenteral drugs during their prehospital resuscitation (37.8% by IO) and were included in analysis. Unadjusted outcomes were lower in patients with IO vs. IV access: 18.3% vs. 23.8% for ROSC (p < 0.001), 3.2% vs. 7.6% for survival to hospital discharge (p < 0.001), and 2.0% vs. 5.8% for favorable neurological function (p < 0.001). After adjustment, IO route remained associated with lower odds of sustained ROSC (OR 0.72, 95% CI 0.63–0.81, p < 0.001), hospital survival (OR 0.48, 95% CI 0.37–0.62, p < 0.001), and favorable neurological outcomes (OR 0.42, 95% CI 0.30–0.57, p < 0.001). ConclusionIn this cohort of OHCA patients, the use of prehospital IO drug administration was associated with unfavorable clinical outcomes.

Health-Related Quality of Life Among Patients With HR+/HER2– Early Breast Cancer

The goal of this study was to characterize health-related quality of life (HRQOL) among patients diagnosed with early-stage, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. A multinational (United States, Japan, France, Germany, Italy, Spain, and United Kingdom) study of patients diagnosed with stage I to III HR+/HER2- breast cancer, either receiving adjuvant treatment or under postadjuvant surveillance, was conducted between June and October 2019. Patients were identified by their consulting physician and invited to complete the Functional Assessment of Cancer Therapy-Breast (FACT-B) and the EQ-5D-5L pen and paper questionnaires. EQ-5D-5L index scores were derived by using available country-specific health state value sets, where available, and numerically compared with general population scores derived from published normative and population data. Descriptive summary statistics were reported for FACT-B, Functional Assessment of Cancer Therapy-General (FACT-G) (total and specific subscales), the EQ-5D index scores, and the EQ-VAS scores for each country. Results were stratified according to disease-free treatment status (active adjuvant treatment or postadjuvant surveillance), age (25-44, 45-54, 55-64, or ≥65 years), stage (I, II, or III), and menopausal status at the time of questionnaire completion (pre-/peri-menopausal or postmenopausal). Overall, 1110 patients completed the HRQOL questionnaires (mean age, 59 years; 79% active adjuvant treatment, and 21% under surveillance postadjuvant treatment at time of questionnaire administration; 31% stage I, 48% stage II, and 20% stage III at diagnosis). Of these, 1102 completed the FACT-B and 1083 completed the EQ-5D-5L questionnaires. The mean (SD) FACT-B total score was 99.0 (21.9). The mean FACT-G total score was 72.5 (17.8), which was comparable to the published normative score. The mean EQ-5D index and EQ-VAS scores for each country were similar to corresponding population means; EQ-5D index scores ranged from 0.842 (0.098) in Japan to 0.916 (0.109) in France, and EQ-VAS scores from 68.0 (18.4) in Germany to 78.6 (16.4) in the United States. In addition, mean scores were comparable between the active adjuvant treatment and postadjuvant surveillance groups for the FACT-B total (99.4 [22.5] and 97.7 [19.7], respectively), FACT-G total (72.8 [18.3] and 71.3 [16.0]), EQ-5D index score (0.868 [0.135] and 0.869 [0.142]), and EQ-VAS (74.9 [17.2] and 74.4 [16.1]). Patient-reported HRQOL among patients with HR+/HER2- early breast cancer who were disease-free was high, with reported scores comparable to normative scores. These results improve our understanding of HRQOL among patients with early disease and may facilitate future studies examining the potential impact of adjuvant treatment and disease recurrence, including metastasis.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

Risk factors associated with surveillance loss after endoscopic submucosal dissection in patients with gastric neoplasm.

BackgroundAfter endoscopic submucosal dissection of gastric neoplasms, surveillance endoscopy is required for patients with synchronous or metachronous neoplasms. We aimed to evaluate the risk factors associated with surveillance loss in patients who underwent endoscopic submucosal dissection.MethodsNinety-five patients treated with endoscopic submucosal dissection for gastric neoplasms between May 2015 and June 2016 were retrospectively reviewed. Clinicopathologic factors, sociodemographic factors, psychiatric measures, and associated risk factors for surveillance loss were evaluated. The chi-square or Fisher exact test, t-test, and logistic regression analysis were used in data analysis.ResultsTwenty-five (26.3%) patients were identified as having surveillance loss. Compared to the surveillance group, the surveillance loss group was old and had dysplasia, and a healthy American Society of Anesthesiologists physical status. Similarly, surveillance loss was related to low symptom perception, low incidence of alexithymia, mindful awareness, and high trait forgiveness. Logistic regression analysis showed that dysplasia (odds ratio, 15.23; 95% CI, 1.56–149.09, P=0.019), old age (odds ratio, 7.14; 95% CI, 1.90–26.88, P=0.004), and American Society of Anesthesiologists physical status 1 (odds ratio, 3.99; 95% CI, 1.09–14.60, P=0.037) were associated with surveillance loss.ConclusionsDysplasia, old age, and the American Society of Anesthesiologists physical status 1 were associated with surveillance loss in patients who underwent gastric endoscopic submucosal dissection. It could be helpful to proactively monitor patients with such conditions after gastric endoscopic submucosal dissection.

Hospital length of stay, do not resuscitate orders, and survival for post-cardiac arrest patients in Michigan: A study for the CARES Surveillance Group

ObjectiveCurrent guidelines recommend deferring prognostic decisions for at least 72 h following admission after Out of Hospital cardiac arrest (OHCA). Most non-survivors experience withdrawal of life sustaining therapy (WLST), and early WLST may adversely impact survival. We sought to characterize the hospital length of stay (LOS) and timing of Do Not Resuscitate (DNR) orders (as surrogates for WLST), to assess their relationship to survival following cardiac arrest. DesignWe performed a retrospective cohort study of probabilistically linked cardiac arrest registries (Cardiac Arrest Registry to Enhance Survival (CARES) and Michigan Inpatient Database (MIDB) from 2014 to 2017. PatientsAdult (≥18 years) patients admitted following OHCA were included. We considered LOS ≤ 3 days (short LOS) and written DNR order with LOS ≤ 3 days (Early DNR) as indicators of early WLST. Our primary outcome was survival to hospital discharge. We utilized multilevel logistic regression clustered by hospital to examine associations of these variables, patient characteristics and survival to hospital discharge. Measurement and Main ResultsWe included 3644 patients from 38 hospitals with >30 patients. Patients mean age was 62.4 years and were predominately male (59.3%). LOS ≤ 3 days (ORadj = 0.11) and early DNR (ORadj = 0.02) were inversely associated with survival to discharge. There was a non-significant inverse association between hospital rates of LOS ≤ 3 days and survival (p = 0.11), and Early DNR and survival (p = 0.83). In the multilevel model, using median odd ratios to assess variation in LOS ≤ 3 days and survival, patient characteristics contributed more to variability in surviival than between-hospital variation. However, between-hospital variation contributed more to variability than patient characteristics in the provision of early DNR orders. ConclusionsWe observed that LOS ≤ 3 days for post-arrest patients was negatively-associated with survival, with both patient characteristics and between-hospital variation associated with outcomes. However, between-hospital variation appears to be more highly-associated with provision of early DNR orders than patient characteristics. Further work is needed to assess variation in early DNR orders and their impact on patient survival.

Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer.

Patients with cancer experience a higher burden of SARS-CoV-2 infection, disease severity, complications, and mortality, than the general population. SARS-CoV-2 mRNA vaccines are highly effective in the general population; however, few data are available on their efficacy in patients with cancer. Using a prospective cohort, we assessed the seroconversion rates and anti-SARS-CoV-2 spike protein antibody titers following the first and second dose of BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in patients with cancer in US and Europe from January to April 2021. Among 131 patients, most (94%) achieved seroconversion after receipt of two vaccine doses. Seroconversion rates and antibody titers in patients with hematological malignancy were significantly lower than those with solid tumors. None of the patients with history of anti-CD-20 antibody in the 6 months before vaccination developed antibody response. Antibody titers were highest for clinical surveillance or endocrine therapy groups and lowest for cytotoxic chemotherapy or monoclonal antibody groups.

Clinical management of atypical ductal hyperplasia on vacuum-assisted biopsy of microcalcifications: External validation study of a decision tree selecting patients eligible for surveillance

BackgroundAtypical lesions found on percutaneous breast biopsy raise specific management issues. The aim of this study was to validate the previous performance of a decision tree defined by Forgeard et al to select a subset of patients at low-risk of surgical diagnostic upgrade that would be eligible for surveillance. MethodsA consecutive series of 211 patients diagnosed with ADH on vacuum-assisted biopsy (VAB) of clustered microcalcifications alone, then operated in our institution, was reviewed. Histological findings on percutaneous cores were compared with definitive diagnoses on surgical specimens. The rate of cancer underestimation on VAB was analyzed in the four arms and two management attitudes defined in the scheme, using size and quality of microcalcification removal and the number of ADH foci. ResultsNinety-eight women with ADH met the inclusion criteria. Overall, 20 cancers were diagnosed at surgery, showing a malignancy rate of 44% (17/39 patients) in the surgery group and of 5% (3/59 patients) in the surveillance group, which was not significantly different from the 2% rate in the monitored reference group (p > 0.64). The malignancy rate increased significantly with the size of clustered microcalcifications (0% when < 6mm, 17% when between 6mm and 21 mm, 48% when > 21 mm, p < 0001) and the number of ADH foci on VAB (14% when ≤ 2, 45% when > 2, p < 0.005). ConclusionOur results corroborate – within the limits of large confidence intervals – those obtained with the reference decision tree. Due to statistical uncertainty, however, they need to be prospectively validated in a broader series.

Prevalence of Iodine Deficiency Disorders (IDD) among School Going Children in Rural Areas of Bangalore

Spectrum of IDD includes simple goitre to debilitating problems like mental retardation, psychomotor defect and still birth. School-age children of 6 to 12 years are considered as an important target group for surveillance of IDD because they are highly vulnerable, easy to access, and also their applicability in a variety of surveillance activities. The objective of the study was to estimate prevalence of goitre among school children of rural areas of Bangalore urban district and to estimate the urine iodine excretion and the salt iodine content in a sub sample. A cross sectional descriptive study was conducted among school going children of rural areas of Bangalore Urban district. Cluster sampling method was used to select in 30 villages. A sample of 90 children was selected from each village. All 2703 children were examined for goiter, 540 salt samples and 270 urine samples were collected for iodine estimation. Goitre prevalence in the study population was 33%. Maximum prevalence of goitre was observed in ≥10 years age group followed by 8-9 years and 6-7 years age group and equally distributed among boys and girls. The Median Urine Iodine (MUI) levels detected were 12.5 mg/l and median salt iodine detected was 27.5 ppm. The total goitre rate is above 5% in the children surveyed between 6-12 years age group indicating the district is endemic for goitre. The goitre grade 1+2 prevalence is ≥30% indicating a severe public health problem with current adequate nutritional iodine intake.

Clinicopathologic Characteristics of Thyroid Nodules Positive for PTEN Mutations on Preoperative Molecular Testing

Somatic and germline mutations of PTEN tumor suppressor gene are associated with follicular-pattern thyroid tumors and PTEN Hamartoma Tumor Syndrome (PHTS). The incidence of cancer in thyroid nodules positive for PTEN mutations on fine-needle aspiration (FNA) is not well defined. The aim of this study was to characterize diagnostic and phenotypic features of thyroid nodules with preoperatively detected PTEN mutations and their impact on management. Thyroid nodules with PTEN mutations on ThyroSeq v3 GC testing of FNA and core needle biopsy specimens from November 2017 to July 2020 were identified from the ThyroSeq Molecular Database. Demographic and clinicopathologic data were obtained through retrospective chart review. We identified 49 PTEN mutation-positive nodules from 48 patients. Patients were 57 years old on average (range 14-88) and 80% female. Cytology was predominantly indeterminate (73% atypia of undermined significance, 18% follicular neoplasm). There were 18 (29%) frameshift, 6 (10%) splice site, and 39 (62%) single nucleotide variant PTEN mutations. Fourteen (29%) nodules had two PTEN mutations, 5 (10%) had copy number alterations, and single cases had concurrent BRAF K601N, EZH1, and NRAS mutations. Surveillance was pursued for 27 (56%) and surgery for 21 (44%) patients (16 lobectomies, 5 total thyroidectomies). There were 14 follicular adenomas (FA), 4 oncocytic FA’s, 1 oncocytic hyperplastic nodule, and 1 encapsulated follicular variant papillary thyroid carcinoma (EFVPTC). The EFVPTC had two low-frequency PTEN mutations, PTEN locus loss, an NRAS mutation, and was a low-risk tumor with capsular but no angiolymphatic invasion. Four (8.3%) patients had confirmed or suspected PHTS, all with multiple nodules. Two had surgery finding no malignancies (2 FA). One PHTS patient had a prior thyroidectomy for a MET mutation-positive nodule that was follicular carcinoma. On US, the mean nodule size of patients who had surgery was larger than the surveillance group (3.2 cm vs. 2.3 cm, p=0.02) but there was no difference in TI-RADS level (p=0.54). There was no difference in mean nodule size (3.5 cm vs. 2.6 cm, p=0.35) or TI-RADS level (p=0.81) between PHTS and non-PHTS patients. Among surveillance patients, follow-up US was done at 1 year in 13/19 (68%) and 2 years in 3/6 (50%) of eligible cases. Only 1/19 (5%) underwent repeat FNA for increased nodule size. No thyroid malignancy was found with a mean of 1.75 years of follow-up (range 1.00-2.78). The EFVPTC patient had no recurrence after 1.05 years of follow-up. In summary, thyroid nodules with isolated somatic PTEN mutations are primarily benign and can be safely followed with serial imaging. Nodules with multiple PTEN mutations were only associated with malignancy when accompanied by an additional NRAS mutation. About 8% of patients with PTEN mutations may be PHTS patients who may be at greater risk for malignancy.

Calf Vein Thrombosis Outcomes Comparing Anticoagulation and Serial Ultrasound Imaging Management Strategies

ObjectiveTo compare outcomes among patients with calf deep vein thrombosis (DVT) stratified by management strategy because distal or calf DVT is said to have low rates of propagation, embolization, and recurrence and, as such, guideline recommendations include provisions for serial imaging without treatment. Patients and MethodsConsecutive patients with ultrasound-confirmed acute DVT involving the calf veins (January 1, 2016, to August 1, 2018) were identified by scrutinizing the Gonda Vascular Center Ultrasound database. Patients were segregated into 2 categories depending on management strategy; anticoagulation vs serial surveillance ultrasound without anticoagulation. Outcomes including venous thromboembolism (VTE) recurrence, bleeding, death, and net clinical benefit were compared by treatment strategy. ResultsThere were 483 patients with calf DVT identified; 399 were treated with anticoagulation therapy and 84 were managed with surveillance ultrasound. Patients in the surveillance group were older (70.0±13.9 vs 63.0±14.9 years; P<.001) and more likely to have had a recent hospitalization (76.2% [64/84] vs 45.4% [181/399]; P<.001). Common reasons for choosing ultrasound surveillance included guideline prescriptive (58.3% [49/84]), active bleeding (21.4% [18/84]), and recent surgery (17.9% [15/84]). The VTE recurrence composite was lower for patients treated with anticoagulants (7.3% [29/399]) compared with surveillance (14.3% [12/84]; P=.04). The DVT propagation was less frequent in the treated group (2.8% [11/399] vs 8.3% [7/84]; P=.01). There was no difference in bleeding or mortality outcomes by management strategy. Net clinical benefit (VTE recurrence plus major bleeding) favored anticoagulant therapy (9.8% [39/399] vs 20.2% [17/84]; P<.01). ConclusionPatients with calf DVT treated with anticoagulants had significantly better outcomes compared with those managed by a strategy of serial ultrasound surveillance without increasing bleeding outcomes.