Divergent Cellular Expression Patterns of PD-L1 and PD-L2 Proteins in Breast Cancer.

PD-L1 immunohistochemistry (IHC) has become an established method for predicting cancer response to targeted anti-PD1 immunotherapies, including breast cancer (BC). The alternative PD-1 ligand, PD-L2, remains understudied but may be a complementary predictive marker. Prospective analysis of 32 breast cancers revealed divergent expression patterns of PD-L1 and PD-L2. PD-L1-positivity was higher in immune cells than in cancer cells (median = 5.0% vs. 0.0%; p = 0.001), whereas PD-L2-positivity was higher in cancer cells than immune cells (median = 30% vs. 5.0%; p = 0.001). Percent positivity of PD-L1 and PD-L2 were not correlated, neither in cancer cells nor immune cells. Based on a cut-point of ≥1% positivity, ER+ tumors (n = 23) were frequently PD-L2-positive (73.9%), whereas only 40.9% were PD-L1-positive. These data suggest differential control of cellular PD-L1 and PD-L2 expression in BC and a potential role for PD-L2 IHC as a complementary marker to PD-L1 to improve selection of aggressive ER+ BC that may benefit from anti-PD-1 therapy.

The Role of Demographic and Clinical Factors in Germline Mutation Testing for Patients with Primary Hyperparathyroidism.

INTRODUCTION: Guidelines recommending genetic counseling in primary hyperparathyroidism (PHPT) vary. To further delineate current recommendations, this study examined genetic counseling referral patterns and rates of mutations in surgical patients with PHPT. PATIENTS AND METHODS: A single-institution review was performed of adult patients who underwent parathyroidectomy for presumed sporadic PHPT. Genetic testing indications of hypercalcemia onset ≤ 40 years, multigland disease (MGD), family history (FHx) of PHPT, or other clinical indications suspicious for a PHPT-related endocrinopathy were examined by demographics and mutation detection rates. RESULTS: Genetic counseling was performed in 237 (37.9%) of 625 patients. Counseling was discussed but not performed in 121 (19.4%) patients. No evidence was noted of genetic referral discussion in the remaining 267 (42.7%). Of these groups, patients who received genetic counseling were youngest, p < 0.001 [median age 55.3 (IQR 43.2, 66.7) years]. The majority of patients with indications of age ≤ 40 years (65.7%), FHx (78.0%), and other clinical indications (70.7%) underwent genetic counseling, while most with MGD (57.0%) did not. Eight mutations were detected in 227 patients (3.5%). Mutations included: MEN1 (n = 2), CDC-73 (n = 4), and CASR (n = 2). Detection was most common in patients with FHx (4/71, 5.6%), then age ≤ 40 years (3/66, 4.5%), and other clinical indications (3/80, 3.8%). No mutations were identified in 48 patients tested solely for MGD. CONCLUSIONS: Most patients with onset of hypercalcemia age ≤ 40 years, positive FHx, or other clinical concerns underwent genetic counseling, while most with MGD did not. As no germline mutations were identified in patients with MGD alone, further investigation of MGD as a sole indication for genetic counseling may be warranted.

Older Patients With Asymptomatic Primary Hyperparathyroidism: Should Criteria for Surgery Be Expanded?

Context: Patients with primary hyperparathyroidism (PHPT) can present with variable signs, symptoms, and end-organ effects. Clinical practice guidelines influence referral for consideration of parathyroidectomy. Objective: This study compared the demographic, biochemical, and symptom profile and examine indications for surgery in patients older than 50 years who underwent parathyroidectomy to determine how changes to current guidelines may affect recommendations for parathyroidectomy. Methods: A retrospective review was conducted of patients age 50 years or older who underwent initial parathyroidectomy for sporadic PHPT from 2012 to 2020. Patients were classified by indications for surgery per guideline criteria (classic, asymptomatic, and no criteria met) and age group (AG): 50 to 59 years; 60 to 69 years; 70 years or older. Patients were treated at a high-volume tertiary medical center by endocrine surgeons. Results: Of 1182 patients, 367 (31%) classic and 660 (56%) asymptomatic patients met the criteria for surgery. The most common indications for surgery were extent of hypercalcemia (51%), osteoporosis (28%), and nephrolithiasis (27%). Of the 155 (13%) patients who did not meet the criteria, neurocognitive symptoms (AG1: 88% vs AG2: 81% vs AG3: 70%; P = .14) and osteopenia (AG1: 53% vs AG2: 68% vs AG3: 68%; P = .43) were frequently observed regardless of patient age. If the age threshold of younger than 50 years was expanded to 60, 65, or 70 years, an additional 61 (5%), 99 (8%), and 124 (10%) patients in the entire cohort would have met the guideline criteria for surgery, respectively. Conclusion: Expanding current guidelines for PHPT to include a broader age range, osteopenia, and neurocognitive symptoms may allow for earlier surgical referral and evaluation for definitive treatment.

Impact of state telehealth policies on telehealth use among patients with newly diagnosed cancer.

BACKGROUND: Telehealth restrictions were relaxed under the COVID-19 public health emergency. We examined telehealth use before and during the pandemic among patients with newly diagnosed cancers and the association between state policies and telehealth use. METHODS: The study cohort was constructed from Optum's deidentified Clinformatics Data Mart and included patients with lymphoma, female breast cancer, colorectal cancer, prostate cancer, and lung cancer diagnosed between March 1, 2019, and March 31, 2021. We performed an interrupted time series analysis to examine the trend of cancer-related telehealth use within 1 month of diagnosis relative to the timing of the COVID-19 public health emergency and multivariable logistic regressions to examine factors-specifically, state parity laws and regulations on cross-state practice-associated with telehealth. RESULTS: Of 110 461 patients, the rate of telehealth use peaked at 33.4% in April 2020, then decreased to 12% to 15% between September 2020 and March 2021. Among the 53 982 patients diagnosed since March 2020, telehealth use was statistically significantly lower for privately insured patients residing in states with coverage-only parity or no or unspecified parity than those in states with coverage and payment parity (adjusted rate = 20.2%, 19.1%, and 23.3%, respectively). The adjusted rate was lower for patients in states with cross-state telehealth policy limitations than for those in states without restrictions (14.9% vs 17.8%). CONCLUSIONS: Telehealth use by patients diagnosed with cancer during the pandemic was higher among those living in states with more generous parity and less restrictive rules for cross-state practice. Policy makers contemplating whether to permanently relax certain telehealth policies must consider the impact on vulnerable patient populations who can benefit from telehealth.

Isolation and survival: The impact of local and MSA isolation on survival among non-Hispanic Black women diagnosed with breast cancer in the United States using a SEER-Medicare cohort.

BACKGROUND: Residential segregation is an important factor that negatively impacts cancer disparities, yet studies yield mixed results and complicate clear recommendations for policy change and public health intervention. In this study, we examined the relationship between local and Metropolitan Statistical Area (MSA) measures of Black isolation (segregation) and survival among older non-Hispanic (NH) Black women with breast cancer (BC) in the United States. We hypothesized that the influence of local isolation on mortality varies based on MSA isolation-specifically, that high local isolation may be protective in the context of highly segregated MSAs, as ethnic density may offer opportunities for social support and buffer racialized groups from the harmful influences of racism. METHODS: Local and MSA measures of isolation were linked by Census Tract (CT) with a SEER-Medicare cohort of 5,231 NH Black women aged 66-90 years with an initial diagnosis of stage I-IV BC in 2007-2013 with follow-up through 2018. Proportional and cause-specific hazards models and estimated marginal means were used to examine the relationship between local and MSA isolation and all-cause and BC-specific mortality, accounting for covariates (age, comorbidities, tumor stage, and hormone receptor status). FINDINGS: Of 2,599 NH Black women who died, 40.0% died from BC. Women experienced increased risk for all-cause mortality when living in either high local (HR = 1.20; CI = 1.08-1.33; p < 0.001) or high MSA isolation (HR = 1.40; CI = 1.17-1.67; p < 0.001). A similar trend existed for BC-specific mortality. Pairwise comparisons for all-cause mortality models showed that high local isolation was hazardous in less isolated MSAs but was not significant in more isolated MSAs. INTERPRETATION: Both local and MSA isolation are independently associated with poorer overall and BC-specific survival for older NH Black women. However, the impact of local isolation on survival appears to depend on the metropolitan area's level of segregation. Specifically, in highly segregated MSAs, living in an area with high local isolation is not significantly associated with poorer survival. While the reasons for this are not ascertained in this study, it is possible that the protective qualities of ethnic density (e.g., social support and buffering from experiences of racism) may have a greater role in more segregated MSAs, serving as a counterpart to the hazardous qualities of local isolation. More research is needed to fully understand these complex relationships. FUNDING: National Cancer Institute.

Deep learning classification of deep ultraviolet fluorescence images toward intra-operative margin assessment in breast cancer.

Background: Breast-conserving surgery is aimed at removing all cancerous cells while minimizing the loss of healthy tissue. To ensure a balance between complete resection of cancer and preservation of healthy tissue, it is necessary to assess themargins of the removed specimen during the operation. Deep ultraviolet (DUV) fluorescence scanning microscopy provides rapid whole-surface imaging (WSI) of resected tissues with significant contrast between malignant and normal/benign tissue. Intra-operative margin assessment with DUV images would benefit from an automated breast cancer classification method. Methods: Deep learning has shown promising results in breast cancer classification, but the limited DUV image dataset presents the challenge of overfitting to train a robust network. To overcome this challenge, the DUV-WSI images are split into small patches, and features are extracted using a pre-trained convolutional neural network-afterward, a gradient-boosting tree trains on these features for patch-level classification. An ensemble learning approach merges patch-level classification results and regional importance to determine the margin status. An explainable artificial intelligence method calculates the regional importance values. Results: The proposed method's ability to determine the DUV WSI was high with 95% accuracy. The 100% sensitivity shows that the method can detect malignant cases efficiently. The method could also accurately localize areas that contain malignant or normal/benign tissue. Conclusion: The proposed method outperforms the standard deep learning classification methods on the DUV breast surgical samples. The results suggest that it can be used to improve classification performance and identify cancerous regions more effectively.

Severity of Prior Coronavirus Disease 2019 is Associated With Postoperative Outcomes After Major Inpatient Surgery.

OBJECTIVE: To determine how the severity of prior history (Hx) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection influences postoperative outcomes after major elective inpatient surgery. BACKGROUND: Surgical guidelines instituted early in the coronavirus disease 2019 (COVID-19) pandemic recommended a delay in surgery of up to 8 weeks after an acute SARS-CoV-2 infection. This was based on the observation of elevated surgical risk after recovery from COVID-19 early in the pandemic. As the pandemic shifts to an endemic phase, it is unclear whether this association remains, especially for those recovering from asymptomatic or mildly symptomatic COVID-19. METHODS: Utilizing the National COVID Cohort Collaborative, we assessed postoperative outcomes for adults with and without a Hx of COVID-19 who underwent major elective inpatient surgery between January 2020 and February 2023. COVID-19 severity and time from infection to surgery were each used as independent variables in multivariable logistic regression models. RESULTS: This study included 387,030 patients, of whom 37,354 (9.7%) were diagnosed with preoperative COVID-19. Hx of COVID-19 was found to be an independent risk factor for adverse postoperative outcomes even after a 12-week delay for patients with moderate and severe SARS-CoV-2 infection. Patients with mild COVID-19 did not have an increased risk of adverse postoperative outcomes at any time point. Vaccination decreased the odds of respiratory failure. CONCLUSIONS: Impact of COVID-19 on postoperative outcomes is dependent on the severity of illness, with only moderate and severe disease leading to a higher risk of adverse outcomes. Existing perioperative policies should be updated to include consideration of COVID-19 disease severity and vaccination status.

Frequent upregulation of HER2 protein in hormone-receptor-positive HER2-negative breast cancer after short-term neoadjuvant endocrine therapy.

BACKGROUND: Endocrine resistant metastatic disease develops in ~ 20-25% of hormone-receptor-positive (HR+) breast cancer (BC) patients despite endocrine therapy (ET) use. Upregulation of HER family receptor tyrosine kinases (RTKs) represent escape mechanisms in response to ET in some HR+ tumors. Short-term neoadjuvant ET (NET) offers the opportunity to identify early endocrine escape mechanisms initiated in individual tumors. METHODS: This was a single arm, interventional phase II clinical trial evaluating 4 weeks (± 1 week) of NET in patients with early-stage HR+/HER2-negative (HER2-) BC. The primary objective was to assess NET-induced changes in HER1-4 proteins by immunohistochemistry (IHC) score. Protein upregulation was defined as an increase of ≥ 1 in IHC score following NET. RESULTS: Thirty-seven patients with cT1-T3, cN0, HR+/HER2- BC were enrolled. In 35 patients with evaluable tumor HER protein after NET, HER2 was upregulated in 48.6% (17/35; p = 0.025), with HER2-positive status (IHC 3+ or FISH-amplified) detected in three patients at surgery, who were recommended adjuvant trastuzumab-based therapy. Downregulation of HER3 and/or HER4 protein was detected in 54.2% of tumors, whereas HER1 protein remained low and unchanged in all cases. While no significant volumetric reduction was detected radiographically after short-term NET, significant reduction in tumor proliferation rates were observed. No significant associations were identified between any clinicopathologic covariates and changes in HER1-4 protein expression on multivariable analysis. CONCLUSION: Short-term NET frequently and preferentially upregulates HER2 over other HER family RTKs in early-stage HR+/HER2- BC and may be a promising strategy to identify tumors that utilize HER2 as an early endocrine escape pathway. CLINICAL TRIAL REGISTRY: Trial registration number: NCT03219476.

Analysis of Deep Ultraviolet Fluorescence Images for Intraoperative Breast Tumor Margin Assessment.

Positive margin status after breast-conserving surgery (BCS) is a predictor of higher rates of local recurrence. Intraoperative margin assessment aims to achieve negative surgical margin status at the first operation, thus reducing the re-excision rates that are usually associated with potential surgical complications, increased medical costs, and mental pressure on patients. Microscopy with ultraviolet surface excitation (MUSE) can rapidly image tissue surfaces with subcellular resolution and sharp contrasts by utilizing the nature of the thin optical sectioning thickness of deep ultraviolet light. We have previously imaged 66 fresh human breast specimens that were topically stained with propidium iodide and eosin Y using a customized MUSE system. To achieve objective and automated assessment of MUSE images, a machine learning model is developed for binary (tumor vs. normal) classification of obtained MUSE images. Features extracted by texture analysis and pre-trained convolutional neural networks (CNN) have been investigated for sample descriptions. A sensitivity, specificity, and accuracy better than 90% have been achieved for detecting tumorous specimens. The result suggests the potential of MUSE with machine learning being utilized for intraoperative margin assessment during BCS.

Severity of Prior COVID-19 Infection is Associated with Postoperative Outcomes Following Major Inpatient Surgery.

Objective: To determine the association between severity of prior history of SARS-CoV-2 infection and postoperative outcomes following major elective inpatient surgery. Summary Background Data: Surgical guidelines instituted early in the COVID-19 pandemic recommended delay in surgery up to 8 weeks following an acute SARS-CoV-2 infection. Given that surgical delay can lead to worse medical outcomes, it is unclear if continuation of such stringent policies is necessary and beneficial for all patients, especially those recovering from asymptomatic or mildly symptomatic COVID-19. Methods: Utilizing the National Covid Cohort Collaborative (N3C), we assessed postoperative outcomes for adults with and without a history of COVID-19 who underwent major elective inpatient surgery between January 2020 and February 2023. COVID-19 severity and time from SARS-CoV-2 infection to surgery were each used as independent variables in multivariable logistic regression models. Results: This study included 387,030 patients, of which 37,354 (9.7%) had a diagnosis of preoperative COVID-19. History of COVID-19 was found to be an independent risk factor for adverse postoperative outcomes even after a 12-week delay for patients with moderate and severe SARS-CoV-2 infection. Patients with mild COVID-19 did not have an increased risk of adverse postoperative outcomes at any time point. Vaccination decreased the odds of mortality and other complications. Conclusions: Impact of COVID-19 on postoperative outcomes is dependent on severity of illness, with only moderate and severe disease leading to higher risk of adverse outcomes. Existing wait time policies should be updated to include consideration of COVID-19 disease severity and vaccination status.

Frequent Upregulation Of HER2 Protein In Hormone Receptor-Positive HER2-Negative Breast Cancer After Short-Term Neoadjuvant Endocrine Therapy.

Background. Endocrine resistant metastatic disease develops in ~20-25% of hormone-receptor positive (HR+) breast cancer (BC) patients despite endocrine therapy (ET) use. Upregulation of HER family receptor tyrosine kinases (RTKs) represent escape mechanisms in response to ET in some HR+ tumors. Short-term neoadjuvant ET (NET) offers the opportunity to identify early endocrine escape mechanisms initiated in individual tumors. Methods. This was a single arm, interventional phase II clinical trial evaluating 4 weeks (+/-1 week) of NET in patients with early-stage HR+/HER2-negative (HER2-) BC. The primary objective was to assess NET-induced changes in HER1-4 proteins by immunohistochemistry (IHC) score. Protein upregulation was defined as an increase of ≥1 in IHC score following NET. Results. Thirty-seven patients with cT1-T3, cN0, HR+/HER2- BC were enrolled. In 35 patients with evaluable tumor HER protein after NET, HER2 was upregulated in 48.6% (17/35; p=0.025), with HER2-positive status (IHC 3+ or FISH-amplified) detected in three patients at surgery, who were recommended adjuvant trastuzumab-based therapy. Downregulation of HER3 and/or HER4 protein was detected in 54.2% of tumors, whereas HER1 protein remained low and unchanged in all cases. While no significant volumetric reduction was detected radiographically after short-term NET, significant reduction in tumor proliferation rates were observed. No significant associations were identified between any clinicopathologic covariates and changes in HER1-4 protein expression on multivariable analysis. Conclusion . Short-term NET frequently and preferentially upregulates HER2 over other HER-family RTKs in early-stage HR+/HER2- BC and may be a promising strategy to identify tumors that utilize HER2 as an early endocrine escape pathway. Trial registration number: NCT03219476 Date of registration for prospectively registered trials: July 17, 2017.

Current Trends in the Utilization of Preoperative Breast Magnetic Resonance Imaging Among Women With Newly Diagnosed Breast Cancer.

PURPOSE: The clinical benefit of preoperative breast magnetic resonance imaging (MRI) for early-stage breast cancer (BC) remains controversial. We examined trends and the associated factors of preoperative breast MRI use. METHODS: This study cohort, constructed from Optum Clinformatics database, included women with early-stage BC who had a cancer surgery between March 1, 2008, and December 31, 2020. Preoperative breast MRI was performed between the date of BC diagnosis and index surgery. Multivariable logistic regressions, one for elderly (65 years and older) and the other for non-elderly patients (younger than 65 years), were performed to examine factors associated with the use of preoperative MRI. RESULTS: Among 92,077 women with early-stage BC, the crude rate of preoperative breast MRI increased from 48% in 2008 to 60% in 2020 for nonelderly and from 27% to 34% for elderly women. For both age groups, non-Hispanic Blacks were less likely (odds ratio [OR]; 95% CI, younger than 65 years: 0.75, 0.70 to 0.81; 65 years and older: 0.77, 0.72 to 0.83) to receive preoperative MRI than non-Hispanic White patients. Across Census divisions, the highest adjusted rate was observed in Mountain division (OR compared with New England; 95% CI, younger than 65 years: 1.45, 1.27 to 1.65; 65 years and older: 2.42, 2.16 to 2.72). Other factors included younger age, fewer comorbidities, family history of BC, axillary node involvement, and neoadjuvant chemotherapy for both age groups. CONCLUSION: The use of preoperative breast MRI has steadily increased. Aside from clinical factors, age, race/ethnicity, and geographic location were associated with preoperative MRI use. This information is important for future implementation or deimplementation strategies of preoperative MRI.

Historical redlining and breast cancer treatment and survival among older women in the United States.

BACKGROUND: Breast cancer (BC) is the most common cancer among US women, and institutional racism is a critical cause of health disparities. We investigated impacts of historical redlining on BC treatment receipt and survival in the United States. METHODS: Home Owners' Loan Corporation (HOLC) boundaries were used to measure historical redlining. Eligible women in the 2010-2017 Surveillance, Epidemiology, and End Results-Medicare BC cohort were assigned a HOLC grade. The independent variable was a dichotomized HOLC grade: A and B (nonredlined) and C and D (redlined). Outcomes of receipt of various cancer treatments, all-cause mortality (ACM), and BC-specific mortality (BCSM) were analyzed using logistic or Cox models. Indirect effects by comorbidity were examined. RESULTS: Among 18 119 women, 65.7% resided in historically redlined areas (HRAs), and 32.6% were deceased at a median follow-up of 58 months. A larger proportion of deceased women resided in HRAs (34.5% vs 30.0%). Of all deceased women, 41.6% died of BC; a larger proportion resided in HRAs (43.4% vs 37.8%). Historical redlining is a statistically significant predictor of poorer survival after BC diagnosis (hazard ratio = 1.09, 95% confidence interval [CI] = 1.03 to 1.15 for ACM, and hazard ratio = 1.26, 95% CI = 1.13 to 1.41 for BCSM). Indirect effects via comorbidity were identified. Historical redlining was associated with a lower likelihood of receiving surgery (odds ratio = 0.74, 95% CI = 0.66 to 0.83, and a higher likelihood of receiving palliative care odds ratio = 1.41, 95% CI = 1.04 to 1.91). CONCLUSION: Historical redlining is associated with differential treatment receipt and poorer survival for ACM and BCSM. Relevant stakeholders should consider historical contexts when designing and implementing equity-focused interventions to reduce BC disparities. Clinicians should advocate for healthier neighborhoods while providing care.

Limited disease progression in endocrine surgery patients with treatment delays due to COVID-19.

BACKGROUND: The COVID-19 pandemic profoundly impacted the delivery of care and timing of elective surgical procedures. Most endocrine-related operations were considered elective and safe to postpone, providing a unique opportunity to assess clinical outcomes under protracted treatment plans. METHODS: American Association of Endocrine Surgeon members were surveyed for participation. A Research Electronic Data Capture survey was developed and distributed to 27 institutions to assess the impact of COVID-19-related delays. The information collected included patient demographics, primary diagnosis, resumption of care, and assessment of disease progression by the surgeon. RESULTS: Twelve out of 27 institutions completed the survey (44.4%). Of 850 patients, 74.8% (636) were female; median age was 56 (interquartile range, 44-66) years. Forty percent (34) of patients had not been seen since their original surgical appointment was delayed; 86.2% (733) of patients had a delay in care with women more likely to have a delay (87.6% vs 82.2% of men, χ2 = 3.84, P = .05). Median duration of delay was 70 (interquartile range, 42-118) days. Among patients with a delay in care, primary disease site included thyroid (54.2%), parathyroid (37.2%), adrenal (6.5%), and pancreatic/gastrointestinal neuroendocrine tumors (1.3%). In addition, 4.0% (26) of patients experienced disease progression and 4.1% (24) had a change from the initial operative plan. The duration of delay was not associated with disease progression (P = .96) or a change in operative plan (P = .66). CONCLUSION: Although some patients experienced disease progression during COVID-19 delays to endocrine disease-related care, most patients with follow-up did not. Our analysis indicated that temporary delay may be an acceptable course of action in extreme circumstances for most endocrine-related surgical disease.

Automated assessment of breast margins in deep ultraviolet fluorescence images using texture analysis.

Microscopy with ultraviolet surface excitation (MUSE) is increasingly studied for intraoperative assessment of tumor margins during breast-conserving surgery to reduce the re-excision rate. Here we report a two-step classification approach using texture analysis of MUSE images to automate the margin detection. A study dataset consisting of MUSE images from 66 human breast tissues was constructed for model training and validation. Features extracted using six texture analysis methods were investigated for tissue characterization, and a support vector machine was trained for binary classification of image patches within a full image based on selected feature subsets. A weighted majority voting strategy classified a sample as tumor or normal. Using the eight most predictive features ranked by the maximum relevance minimum redundancy and Laplacian scores methods has achieved a sample classification accuracy of 92.4% and 93.0%, respectively. Local binary pattern alone has achieved an accuracy of 90.3%.

Long-term Quality of Life After Parathyroidectomy for Primary Hyperparathyroidism: A Systematic Review.

Importance: Definitive treatment of primary hyperparathyroidism (pHPT) with curative parathyroidectomy has been shown to improve nonspecific neurocognitive symptoms and may improve long-term quality of life (QOL). However, QOL is not currently routinely assessed preoperatively, and as a result, diminished QOL may be overlooked as an indication for surgery. Objective: To examine results for measures of long-term QOL after parathyroidectomy in patients with pHPT. Evidence Review: A systematic, English-language literature review was performed to assess the long-term association of parathyroidectomy, defined as a minimum of 1-year postoperative follow-up, with QOL in patients with pHPT. We conducted a search of PubMed and Scopus using Medical Subject Heading (MeSH) terms for hyperparathyroidism, parathyroid hormone, parathyroidectomy, hypercalcemia, and quality of life. All relevant literature published between June 1998 and February 15, 2021, was included. Study selection was guided by the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) strategy. Findings: Thirty-one studies conducted in 14 countries with a minimum of 1 year of follow-up were included, comprising 3298 patients with pHPT (2975 underwent parathyroidectomy; 323 were observed), 5445 age- and sex-matched control participants, and 386 control patients with benign thyroid disease. To assess QOL, 21 studies (68%) used a general tool, the 36-item Short Form Survey (SF-36), and 8 (26%) used the disease-specific tool Parathyroidectomy Assessment of Symptoms (PAS). The remaining studies used a combination of 10 additional QOL tools. The median follow-up period was 1 year (range, 1-10 years). Of the 31 studies, 27 (87%) demonstrated significant score improvement in long-term QOL after parathyroidectomy, including 1 study that showed continued improvement in QOL 10 years after parathyroidectomy. The remaining 4 studies (13%) reported mixed results. Conclusions and Relevance: This systematic review suggests that parathyroidectomy is associated with improved and sustained QOL in patients with pHPT. Patients with pHPT should be screened with a validated QOL tool such as the SF-36 or PAS at the time of diagnosis to guide discussion of these symptoms in the preoperative setting and the potential for long-term improvement after curative parathyroidectomy.

A phase 2 trial of a topical antiseptic bundle in head and neck cancer surgery: Effects on surgical site infection and the oral microbiome.

BACKGROUND: Head and neck cancer (HNC) surgery remains an important component of management but is associated with a high rate of surgical site infection (SSI). We aimed to assess the safety and efficacy of a topical mucosal antiseptic bundle in preventing SSI and evaluate microbial predictors of infection through a genomic sequencing approach. METHODS: This study was an open-label, single-arm, single-center, phase 2 trial of a topical mucosal antiseptic bundle in patients with HNC undergoing aerodigestive tract resection and reconstruction. Patients underwent topical preparation of the oral mucosa with povidone-iodine (PI) and chlorhexidine gluconate (CHG) pre- and intra-operatively followed by oral tetracycline ointment every 6 hours for 2 days post-operatively. The primary outcome was change in bacterial bioburden at the oral surgical site. Secondary outcomes included safety, SSI, and microbial predictors of infection. FINDINGS: Of 27 patients screened between January 8, 2021, and May 14, 2021, 26 were enrolled and 25 completed the study. There were no antiseptic-related adverse events. The topical mucosal antiseptic bundle significantly decreased oral bacterial colony-forming units from pre-operative levels (log10 mean difference 4·03, 95%CI 3·13-4·;92). There were three SSI (12%) within 30 days. In correlative genomic studies, a distinct set of amplicon sequence variants in the post-operative microbiome was associated with SSI. Further, despite no instance of post-operative orocervical fistula, metagenomic sequence mapping revealed the oral cavity as the origin of the infectious organism in two of the three SSI. INTERPRETATION: The bacterial strains which subsequently caused SSI were frequently identified in the pre-operative oral cavity. Accordingly, a topical antiseptic bundle decreased oral bacterial bioburden throughout the peri-operative period and was associated with a low rate of SSI, supporting further study of topical antisepsis in HNC surgery. FUNDING: Alliance Oncology.

Variation in parathyroid adenoma size in patients with sporadic, primary hyperparathyroidism: small gland size does not preclude single gland disease.

PURPOSE: Small, abnormal parathyroid glands are usually associated with multigland hyperplasia in patients with primary hyperparathyroidism (pHPT). The purpose of this study was to determine the association between parathyroid adenoma size and biochemical cure rates in patients undergoing single gland parathyroidectomy. METHODS: The study included patients with sporadic pHPT who underwent initial parathyroidectomy and met intraoperative PTH criteria for cure after resection of a single adenoma (SGD). Patients were divided into quartiles (Q1 = smallest) based on gland weight and maximum dimension; cure rates were compared across groups. RESULTS: A single parathyroid adenoma was removed in 517 patients, with a median gland weight of 500 mg (range 50-11890). Median maximum gland dimension was 15 mm (range 5-55). With median follow-up of 28 months (range 6-81), the biochemical cure rate was 97.1%. There was no difference in cure rate by gland weight (Q1 94.6%, Q2 96.9%, Q3 98.4%, Q4 98.5%, p = 0.217) or maximum gland dimension (Q1 95.6%, Q2 97.6%, Q3 97.1%, Q4 98.2%, p = 0.641). When Q1 patients (by gland weight) were divided by quartile, there was no difference in cure rates (93.1% [50-140 mg]; 95.2% [150-190 mg]; 97.1% [200-230 mg]; 93.3% [240-280 mg]; p = 0.665). CONCLUSION: For patients with pHPT who underwent single gland parathyroidectomy, there was no difference in cure rates by gland weight or maximum dimension. These data suggest that the removal of parathyroid adenomas as small as 50 mg with an appropriate decline in ioPTH likely represent single gland disease and additional exploration may not be necessary.

Underdiagnosis of primary hyperparathyroidism in patients with osteoarthritis undergoing arthroplasty.

BACKGROUND: Primary hyperparathyroidism (HPT) is commonly underdiagnosed and undertreated. Joint pain is a nonspecific symptom associated with osteoarthritis or primary HPT. We hypothesize that patients treated for osteoarthritis are underdiagnosed with primary HPT. METHODS: Adult patients diagnosed with hip/knee osteoarthritis at the Medical College of Wisconsin from January 2000 to October 2020 were queried. Patients with a calcium level drawn within 1 year of diagnosis of osteoarthritis were included. Patients who had undergone prior parathyroidectomy were excluded. Patients were stratified by serum calcium level, HPT diagnosis, and PTH level. Arthroplasty rates were compared between groups. RESULTS: Of 54,788 patients, 9,967 patients (18.2%) had a high serum calcium level, of whom 1,089 (10.9%) had a diagnosis of HPT. Only 76 (7.0%) patients with HPT underwent parathyroidectomy, 208 (19.1%) underwent knee/hip arthroplasty, and 14 (1.3%) underwent both. Arthroplasty was performed in 1,793 patients without evaluation and/or definitive treatment for HPT. There were higher rates of arthroplasty performed in patients with a high serum calcium level compared with those without (21.2% vs 17.4%, P < .001). CONCLUSION: Patients with high serum calcium levels were more likely to undergo arthroplasty than those with normocalcemia. Hypercalcemia in the setting of hip or knee osteoarthritis should prompt a full evaluation for primary HPT.