bluuebunny/crossref_metadata_2025 huggingface dataset:
Bebtelovimab-Induced Bradycardia Leading to Cardiac Arrest
Authors: Gearges Christina , Haider Hibah , Rana Vishal , Asghar Zahra , Kewalramani Anjali , Kuschner Zachary
Published: August 2022

BACKGROUND:

Bebtelovimab is a monoclonal antibody used to prevent progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Complications of SARS-CoV-2 infection can include cardiac effects including sinus bradycardia.

CASE SUMMARY:

We describe the case of an 86-year-old male infected with SARS-CoV-2 who experienced bradycardia with cardiac arrest immediately following infusion of Bebtelovimab with return of spontaneous circulation obtained following 1 minute of chest compressions and administration of atropine. His bradycardia resolved, and he was extubated on hospital day 1, found to be neurologically intact, and discharged on hospital day 9.

CONCLUSIONS:

Due to the time course of the patient’s symptomatology, we attribute the bradycardic arrest to the Bebtelovimab infusion. This case illustrates the need for further research into the etiology of bradycardia due to SARS-CoV-2 infection and to examine potential links to monoclonal antibody infusion. It also serves as important caution to maintain close cardiac monitoring while administering monoclonal antibodies for SARS-CoV-2.
Melanoma risk during immunomodulating treatment
Authors: Zheng Yixuan James , Ho Wilson , Sanlorenzo Martina , Vujic Igor , Daud Adil , Algazi Alain , Rappersberger Klemens , Ortiz-Urda Susana
Published: August 2022

Immunosuppressive therapy is standard for the treatment of inflammatory diseases and for minimizing rejection in transplant patients. However, immunosuppressant drugs are associated with an increased risk of certain cancers. In particular, melanoma is an immunogenic tumor and as such, is strongly influenced by the immune system. We performed this literature review to summarize the effects of commonly used immunomodulating agents on melanoma development, recurrence and progression. We outline the mechanism of action of each drug and discuss the available evidence on its influence on melanoma. Based on existing literature, we recommend avoiding the following agents in patients with a history of invasive melanoma: cyclosporine, sirolimus, natalizumab, IL-6 inhibitors, cyclophosphamide, methotrexate and the tumor necrosis factor-alpha inhibitors infliximab and etanercept. If there are no viable alternative agents, we recommend for these patients to see a dermatologist every 6 months for a thorough skin examination.
No Reduction in Revision Risk Associated With Highly Cross-linked Polyethylene With or Without Antioxidants Over Conventional Polyetheylene in TKA: An Analysis From the American Joint Replacement Registry
Authors: Kendall Jamil , Pelt Christopher E. , Imlay Benjamin , Yep Patrick , Mullen Kyle , Kagan Ryland
Published: August 2022

Background

Highly cross-linked polyethylene (HXLPE) can improve wear properties in TKA, but it can also lead to decreased mechanical properties. Antioxidants were added to HXLPE to improve its mechanical properties while retaining the improved wear characteristics. However, it remains unclear whether these modifications to conventional polytheylene used in TKA have resulted in a change in the revision risk.

Questions/purposes

We used American Joint Replacement Registry data to ask: (1) Is there a difference in all-cause revision in patients who underwent TKA using HXLPE with or without an antioxidant doping compared with conventional polyethylene? (2) Is there a difference in revision for aseptic failure in patients who underwent TKA using HXLPE with or without an antioxidant doping compared with conventional polyethylene?

Methods

We analyzed American Joint Replacement Registry data from 2012 to 2019. We identified 339,366 primary TKAs over the study period in patients older than 65 years and linked procedures to supplemental Centers for Medicare & Medicaid data where available. Patient total number of reported comorbidities, gender, age, region, polyethylene characteristics, procedure dates, and indication for revision were recorded. Median follow-up was 34 months. We compared HXLPE with or without antioxidants to conventional polyethylene. Event-free percent survival curves and Cox proportional hazard regression modeling was used for all-cause revision and revision for aseptic failure.

Results

Compared with conventional polyethylene, there was no difference in all-cause revision with HXLPE with an antioxidant (HR 1.06 [95% CI 0.98 to 1.14]; p = 0.13) or HXLPE without an antioxidant (HR 1.04 [95% CI 0.97 to 1.11]; p = 0.28). Compared with conventional polyethylene, there was no difference in revision for aseptic failure with HXLPE with an antioxidant (HR 1.07 [95% CI 0.99 to 1.14]; p = 0.08) or HXLPE without an antioxidant (HR 1.03 [95% CI 0.97 to 1.01]; p = 0.30).

Conclusion

We found no difference in revision risk between HXLPE with or without an antioxidant and conventional polyethylene during this time frame. HXLPE polyethylene, with or without an antioxidant, should not be widely adopted until or unless it is shown to be superior to conventional polyethylene in TKA.

Level of Evidence

Level III, therapeutic study.
Differences in rates of pelvic lymph node dissection in National Comprehensive Cancer Network favorable, unfavorable intermediate and high-risk prostate cancer across United States SEER registries
Authors: Flammia Rocco Simone , Hoeh Benedikt , Chierigo Francesco , Hohenhorst Lukas , Sorce Gabriele , Tian Zhen , Leonardo Costantino , Graefen Markus , Terrone Carlo , Saad Fred , Shariat Shahrokh F. , Briganti Alberto , Montorsi Francesco , Chun Felix K. H. , Gallucci Michele , Karakiewicz Pierre I.
Published: August 2022

Background

The National Comprehensive Cancer Network (NCCN) guidelines recommend pelvic lymph node dissection (PLND) in NCCN high- and intermediate-risk prostate cancer patients. We tested for PLND nonadherence (no-PLND) rates within the Surveillance Epidemiology and End Results (2010–2015).

Materials and methods

We identified all radical prostatectomy patients who fulfilled the NCCN PLND guideline criteria (N = 23,495). No-PLND rates were tabulated and further stratified according to NCCN risk subgroups, race/ethnicity, geographic distribution, and year of diagnosis.

Results

Overall, the no-PLND rate was 26%; it was 41%, 25%, and 11% in the NCCN intermediate favorable, intermediate unfavorable, and high-risk prostate cancer patients, respectively (p < 0.001). Over time, the no-PLND rates declined in the overall cohort and within each NCCN risk subgroup. Georgia exhibited the highest no-PLND rate (49%), whereas New Jersey exhibited the lowest (15%). Finally, no-PLND race/ethnicity differences were recorded only in the NCCN intermediate unfavorable subgroup, where Asians exhibited the lowest no-PLND rate (20%) versus African Americans (27%) versus Whites (26%) versus Hispanic-Latinos (25%).

Conclusions

The lowest no-PLND rates were recorded in the NCCN high-risk patients followed by NCCN intermediate unfavorable and favorable risk in that order. Our findings suggest that unexpectedly elevated differences in no-PLND rates warrant further examination. In all the NCCN risk subgroups, the no-PLND rates decreased over time.
Clearance of Piperacillin–Tazobactam and Vancomycin During Continuous Renal Replacement With Regional Citrate Anticoagulation
Authors: Sharrock Lucy , Ankravs Melissa J. , Deane Adam M. , Rechnitzer Thomas , Wallis Steven C. , Roberts Jason A. , Bellomo Rinaldo
Published: August 2022

Background:

The use of regional citrate anticoagulation during continuous venovenous hemodiafiltration (CVVHDF) has increased worldwide. However, data on its effect on the pharmacokinetics of antibiotics are limited. In this study, the authors aimed to measure the clearance of piperacillin–tazobactam and vancomycin in patients receiving CVVHDF with regional citrate anticoagulation.

Methods:

This study measured piperacillin–tazobactam and vancomycin concentrations in patients receiving CVVHDF with regional citrate anticoagulation. Dosing regimens were independently selected by intensivists. Arterial blood and effluent fluid samples were obtained over a single dosing interval and analyzed using ultra-high-performance liquid chromatography with tandem mass spectrometry.

Results:

Seventeen sampling intervals in 15 patients (9 receiving piperacillin–tazobactam only, 4 receiving vancomycin only, and 2 receiving both) were used. The median overall clearance for piperacillin was 35.2 mL/min [interquartile range (IQR): 32.2–38.6], 70 mL/min (IQR: 62.7–76.2) for tazobactam, and 29.5 mL/min (IQR: 26.2–32) for vancomycin.

Conclusions:

This is the first study to quantify the pharmacokinetics of vancomycin and piperacillin–tazobactam in patients receiving CVVHDF with regional citrate anticoagulation. These results indicate high clearance and provide key information to guide optimal dosing.
A Novel Orderset Driven Emergency Department Atrial Fibrillation Algorithm to Increase Discharge and Risk-appropriate Anticoagulation
Authors: Roumpf Steven K. , Kline Jeffrey A. , Dandamudi Gopi , Schaffer Jason T. , Flack Tara , Gallaher Wesley , Weaver Allison M. , Hunt Ina , Thinnes Erynn , Strachan Christian C. , Hall Cassandra , Pafford Carl , Hunter Benton R.
Published: August 2022

Introduction:

Patients with atrial fibrillation (AF) are frequently admitted from the emergency department (ED), and when discharged, are not reliably prescribed indicated anticoagulation. We report the impact of a novel computerized ED AF pathway orderset on discharge rate and risk-appropriate anticoagulation in patients with primary AF.

Methods:

The orderset included options for rate and rhythm control of primary AF, structured risk assessment for thrombotic complications, recommendations for anticoagulation as appropriate, and follow up with an electrophysiologist. All patients discharged from the ED in whom the AF orderset was utilized over an 18-month period comprised the primary study population. The primary outcome was the rate of appropriate anticoagulation or not according to confirmed CHADS-VASC and HASBLED scores. Additionally, the percentage of primary AF patients discharged directly from the ED was compared in the 18-month periods before and after introduction of the orderset.

Results:

A total of 56 patients, average age 57.8 years and average initial heart rate 126 beats/minute, were included in the primary analysis. All 56 (100%; 95% confidence interval, 94-100) received guideline-concordant anticoagulation. The discharge rates in the pre- and postorderset implementation periods were 29% and 41%, respectively (95% confidence interval for 12% difference, 5-18).

Conclusions:

Our novel AF pathway orderset was associated with 100% guideline-concordant anticoagulation in patients discharged from the ED. Availability of the orderset was associated with a significant increase in the proportion of ED AF patients discharged.
A CONSENSUS ON RISK MITIGATION FOR BROLUCIZUMAB IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Holz Frank G. , Iida Tomohiro , Maruko Ichiro , Sadda SriniVas R.
Published: August 2022

Purpose:

Brolucizumab has high efficacy in retinal fluid resolution and provides the possibility for longer dosing intervals in the treatment of neovascular age-related macular degeneration. However, brolucizumab has been associated with events of retinal vasculitis and retinal vascular occlusion typically in the presence of other signs of intraocular inflammation (IOI). The purpose of this report is to provide guidance on the use of brolucizumab for neovascular age-related macular degeneration to a global audience.

Methods:

A literature review was conducted on adverse events related to IOI after administration of brolucizumab in eyes with neovascular age-related macular degeneration.

Results:

Possible risk factors for IOI and retinal vascular occlusion after brolucizumab should be considered before administering brolucizumab. Patients who receive brolucizumab should be educated on the symptoms, signs, and time course of IOI after brolucizumab. Before each injection of brolucizumab, physicians should assess the eye for any signs of inflammation and not treat with brolucizumab if inflammation is detected. Treatment of IOI should be prompt and provided with particular attention to the posterior segment.

Conclusion:

Careful patient selection, patient education, assessment for inflammation, and intensive treatment of possible inflammation are important when using brolucizumab in patients with neovascular age-related macular degeneration.
Stimulation of alpha-1 adrenoceptors may intensify cutaneous inflammation in complex regional pain syndrome
Authors: Wijaya Linda K. , Morici Michael V. , Stumbles Philip A. , Finch Philip M. , Drummond Peter D.
Published: August 2022

Alpha-1 adrenoceptors are overexpressed in the epidermis of a subgroup of patients with complex regional pain syndrome (CRPS). Activating α1-adrenoceptors in epidermal cells increases production of the proinflammatory cytokine interleukin-6 (IL-6), a mediator of inflammation. To investigate whether this might exacerbate inflammation in CRPS, primary keratinocytes or dermal fibroblasts were cultured from skin biopsies obtained from the affected limb of 25 patients and a similar site in 28 controls. The fundamental proinflammatory cytokine, tumor necrosis factor alpha, was administered for 24 hours to initiate inflammation. After this, cells were incubated for 6 hours with the α1-adrenoceptor agonist phenylephrine. Exposure to tumor necrosis factor alpha induced proinflammatory cytokine mRNA production and protein secretion in keratinocytes and fibroblasts and enhanced α1B-adrenoceptor mRNA expression in keratinocytes. Additional stimulation of α1 adrenoceptors with phenylephrine increased the production of IL-6 mRNA and protein secretion in both cell types. Under all conditions, gene and protein α1-adrenoceptor levels and cytokine gene expression and protein secretion were similar, overall, in patients and controls, except for abnormally high α1-adrenoceptor protein levels in the keratinocytes of 3 of 17 patients. These findings suggest that persistent inflammation in CRPS is not due to dysfunction of skin cells but is a normal response to extrinsic signals. After α1-adrenoceptor stimulation of keratinocytes, increases in IL-6 mRNA but not protein were proportional to basal α1-adrenoceptor protein levels. Skin cells play an important role in persistent inflammation in CRPS. Potentially, a positive feedback loop between α1-adrenoceptors and IL-6 production in skin cells contributes to this inflammatory state.
Effects of the Collective Gratitude on Work Engagement
Authors: Komase Yu , Akiyama Hiroto , Kawakami Norito
Published: August 2022

Objective

Work engagement is a key concept because of its positive association with physical/mental health, job performance, and well-being. This study aims to examine the relationship between organizational-level gratitude (collective gratitude) as a work climate and work engagement.

Methods

Utrecht Work Engagement Scale measured work engagement. Gratitude at Work Scale measured individual-level gratitude, and collective gratitude was calculated by aggregating individual-level gratitude after confirming within-group agreement and the intraclass correlations. Multilevel analysis was conducted.

Results

A total of 1187 workers from 72 organizations were analyzed. The multilevel analysis showed a significant positive association between collective gratitude and work engagement while controlling for individual-level confounders.

Conclusions

The findings indicated developing collective gratitude would improve work engagement in the workplace. It would be useful for managers and occupational health staff to consider collective gratitude initiatives.
Association between acute care collaborations and health care utilization as compared to stand-alone facilities in the Netherlands: a quasi-experimental study
Authors: Wackers Erik M.E. , Stadhouders Niek W. , Maessen Martijn F.H. , Tanke Marit A.C. , Gaakeer Menno I. , van Dulmen Simone A. , Jeurissen Patrick P.T.
Published: August 2022

Health systems invest in coordination and collaboration between emergency departments (ED) and after-hours primary care providers (AHPCs) to alleviate pressure on the acute care chain. There are substantial gaps in the existing evidence, limited in sample size, follow-up care, and costs. We assess whether acute care collaborations (ACCs) are associated with decreased ED utilization, hospital admission rates, and lower costs per patient journey, compared with stand-alone facilities. The design is a quasi-experimental study using claims data. The study included 610 845 patients in the Netherlands (2017). Patient visits in ACCs were compared to stand-alone EDs and AHPCs. The number of comorbidities was similar in both groups. Multiple logistic and gamma regressions were used to determine whether patient visits to ACCs were negatively associated with ED utilization, hospital admission rates, and costs. Logistic regression analysis did not find an association between patients visiting ACCs and ED utilization compared to patients visiting stand-alone facilities [odds ratio (OR), 1.01; 95% confidence interval (CI), 1.00–1.03]. However, patients in ACCs were associated with an increase in hospital admissions (OR, 1.07; 95% CI, 1.04–1.09). ACCs were associated with higher total costs incurred during the patient journey (OR, 1.02; 95% CI, 1.01–1.03). Collaboration between EDs and AHPCs was not associated with ED utilization, but was associated with increased hospital admission rates, and higher costs. These collaborations do not seem to improve health systems’ financial sustainability.
Mifepristone: A Safe Method of Medical Abortion and Self-Managed Medical Abortion in the Post-Roe Era
Authors: Schmidt Elizabeth O. , Katz Adi , Stein Richard A.
Published: August 2022

Background:

The U.S. Supreme Court's Dobbs v. Jackson Women's Health Organization decision on June 24, 2022 effectively overturned federal constitutional protections for abortion that have existed since 1973 and returned jurisdiction to the states. Several states implemented abortion bans, some of which banned abortion after 6 weeks and others that permit abortion under limited exceptions, such as if the health or the life of the woman is in danger. Other states introduced bills that define life as beginning at fertilization. As a result of these new and proposed laws, the future availability of mifepristone, one of two drugs used for medical abortion in the United States, has become the topic of intense debate and speculation.

Areas of Uncertainty:

Although its safety and effectiveness has been confirmed by many studies, the use of mifepristone has been politicized regularly since its approval. Areas of future study include mifepristone for induction termination and fetal demise in the third trimester and the management of leiomyoma.

Data Sources:

PubMed, Society of Family Planning, American College of Obstetricians and Gynecologists, the World Health Organization.

Therapeutic Advances:

The use of no-touch medical abortion, which entails providing a medical abortion via a telehealth platform without a screening ultrasound or bloodwork, expanded during the COVID-19 pandemic, and studies have confirmed its safety. With the Dobbs decision, legal abortion will be less accessible and, consequently, self-managed abortion with mifepristone and misoprostol will become more prevalent.

Conclusions:

Mifepristone and misoprostol are extremely safe medications with many applications. In the current changing political climate, physicians and pregnancy-capable individuals must have access to these medications.
Racial/Ethnic Disparities in the Management of Pediatric Acute Pancreatitis Across Children’s Hospitals
Authors: Dike Chinenye R. , Lyden Elizabeth , Quirós‐Tejeira Ruben E. , Ma Jihyun , McCulloh Russell
Published: August 2022

Objectives:

Racial or ethnic disparities in health care delivery and resource utilization have been reported in a variety of pediatric diseases. In acute pancreatitis (AP), there is an association between Black race and increased inpatient mortality. Data on the association of race and ethnicity and resource use for managing pediatric AP are lacking. The aim of this study is to investigate this potential association in pediatric AP.

Methods:

Retrospective study of children 0–18 years diagnosed with AP in the Pediatric Health Information System (PHIS) database from 2012 to 2018. Descriptive statistics were used to summarize cohort characteristics. Race/ethnicity classifications included non‐Hispanic Black (NHB), non‐Hispanic White (NHW, used as reference), Hispanic, and “Other.” Associations between patient characteristics and race/ethnicity were determined using χ2 tests. Generalized linear mixed regression model was used to determine the association of race/ethnicity with odds of resource utilization, costs, and length of hospital stay after adjusting for covariates with a random intercept for site.

Results:

Five thousand nine hundred sixty‐three patients from 50 hospitals were included. Adjusted analysis showed that NHB children hospitalized with AP were at lower odds of receiving opioids in the first 24 hours [adjusted odds ratio (aOR) = 0.82, 95% confidence interval (CI) = 0.70–0.98] and receiving intravenous fluids during the hospitalization (aOR = 0.64, 95% CI = 0.43–0.96) when compared with NHW children. Additionally, NHB and Hispanic children had a prolonged adjusted mean length of hospital stay and higher hospital costs when compared with NHW children. Although there was no significant association between race/ethnicity and diagnosis of pancreatic necrosis or sepsis, Hispanic and “Other” children were at higher odds of receiving antibiotics during hospitalization for AP (aOR = 1.33, 95% CI = 1.13–1.57 and aOR = 1.37, 95% CI = 1.09–1.73, respectively) than NHW children.

Conclusions:

Disparities exist in utilization of health care interventions for pediatric AP patients by race/ethnicity. Future studies should investigate why these disparities exist and if these disparities affect outcomes.
Nurse Practitioner Leadership Essential
Authors: Kapu April
Published: August 2022

This month's column highlights the importance of a comprehensive employee onboarding program for newly hired nurse practitioners and 6 essential components for a successful program.
An Effective Model for Unit-Based Advanced Practice Provider/Physician Collaboration on a Complex Medicine Hospital Unit
Authors: Millwee Sara , Hall Mary Ann Kirkconnell
Published: August 2022

Advanced practice provider care effectively improves outcomes and reduces costs. During COVID-19 challenges and staffing shortages, a team developed and piloted a collaborative advanced practice provider/physician hospital medicine model that resulted in improved outcomes, costs, and quality metrics, including increased productivity and revenue, decreased length of stay, and decreased medical emergency team/rapid response calls.
Impressions of Conventional Bedside Discharge Teaching Among Readmitted Heart Failure Patients
Authors: Gatto Dawn , Newcomb Patricia
Published: August 2022

OBJECTIVE

The purpose of this project was to report patient impressions of discharge teaching delivered by nurses among a population of heart failure (HF) inpatients.

BACKGROUND

Heart failure readmissions are frequently attributed to the quality of discharge teaching delivered by nurses.

METHODS

Thematic analysis, an atheoretical approach to the identification, organization, and analysis of themes in texts, was used to explore the data collected from patient interviews.

RESULTS

Sixteen interviews were conducted with patients readmitted for HF on dedicated cardiac units. Six major themes were identified including: 1) recall of instructions; 2) comprehension; 3) teaching media; 4) follow-up; 5) role of caregivers; 6) mismatch between nurse and patient concerns; and 7) readmission stories.

CONCLUSION

Discharge teaching could be improved by diminishing the volume of print materials distributed to HF patients, providing simple summaries of the most relevant advice, focusing on patient concerns more than the hospital agenda, and directly including home caregivers in teaching.
Epithelioid Vascular Lesions: The Differential Diagnosis and Approach in Cytology and Small Biopsies
Authors: Tabish Nabil , Monaco Sara E.
Published: August 2022

Vascular neoplasms are rare tumors with a multitude of clinical presentations and behavior, which make accurate identification and subclassification challenging on limited small biopsies. Within the spectrum of these lesions, the ones with epithelioid morphology, such as epithelioid hemangioendothelioma and epithelioid angiosarcoma, are particularly challenging given the morphologic overlap with nonvascular lesions and the limited cells due to hemodilution on sampling. Herein, we review the differential diagnosis of epithelioid vascular neoplasms, with a focus on the cytomorphology, differential diagnoses, and ancillary studies that pathologists should be aware of when evaluating small biopsies and aspirates, including novel translocations, and associated monoclonal immunohistochemistry antibodies, that can help in the diagnosis of some of these tumors. Awareness of these morphologic and ancillary study findings in these rare tumors will hopefully allow pathologists to recognize and render-specific diagnoses on limited samples of these challenging lesions.
Desmoplastic Adamantinoma-like Thymic Carcinoma
Authors: Suster David I. , Mejbel Haider , Mackinnon Alexander C. , Suster Saul
Published: August 2022

Five cases of a heretofore unreported rare variant of thymic carcinoma characterized by a striking resemblance to adamantinoma of the mandible are described. The tumors occurred in 4 women and 1 man aged 58 to 76 years (mean: 67.8 y); they arose in the anterior mediastinum and measured from 5.3 to 12.0 cm in greatest diameter (mean: 8.9 cm). Presenting symptoms included chest pain, shortness of breath, and in 2 patients, pleural effusion. One tumor was asymptomatic and discovered incidentally. Histologically, the tumors were extensively desmoplastic, and the cellular proliferation was characterized by multiple islands of squamous epithelium with striking peripheral palisading of nuclei and central areas containing clear cells resembling a stellate reticulum. Areas of preexisting spindle cell thymoma were identified in 2 cases; these areas gradually merged with the higher-grade component of the lesion. Cystic changes were noted in 3 cases. Immunohistochemical studies in 3 cases showed the tumor cells were positive for cytokeratins, p40 and p63, and all showed a high proliferation rate (>50% nuclear positivity) with Ki-67. Next-generation sequencing was performed in 2 cases that showed amplification of the AKT1 gene (copy numbers 6 and 13). Clinical follow-up in 3 patients showed recurrence and metastasis after 1 and 2 years; 1 patient passed away 2 years after diagnosis due to the tumor. Desmoplastic adamantinoma-like thymic carcinoma represents an unusual histologic variant of thymic carcinoma that needs to be distinguished from metastases from similar tumors to the mediastinum.
CD163 Immunohistochemical “Circle Sign” Staining Pattern Differentiates Sinonasal Papillomas From Morphologically Similar Non-neoplastic Lesions
Authors: Sterling Brent C. , Mehrad Mitra , Ely Kim A. , Lewis James S.
Published: August 2022

Sinonasal papillomas are a diverse group of benign epithelial neoplasms of the sinonasal tract. Inverted papilloma, in particular, must be distinguished from other lesions with no malignant potential. The aim of this study was to distinguish sinonasal papillomas from morphologically similar lesions using CD163 immunostaining. Cases from a 19-year period were identified. These included 49 inverted, 10 exophytic, and 12 oncocytic papillomas, 21 chronic sinusitides with squamous metaplasia, 27 inflammatory polyps, 5 verrucae vulgares, 5 respiratory epithelial adenomatoid hamartomas, and 6 DEK::AFF2 carcinomas of the sinonasal tract. A subset of biopsy cases (8 inverted papillomas, 5 inflammatory polyps) was separately analyzed. CD163 immunohistochemistry (IHC) was performed. A unique “circle” staining pattern was identified in the surface epithelium. After locating a hotspot, circles were quantified in 10 consecutive high-power fields. Circles were present in 66/71 (93%) cases of sinonasal papilloma, with a mean of 35 circles/10 HPF (range: 0 to 160/10 HPF) and a median of 19 circles/10 HPF. Circles were present in 20/58 (34%) non-neoplastic cases, with a mean of 2 circles/10 HPF (range: 0 to 27/10 HPF) and a median of 0. Considering all resection and biopsy cases, performance for distinguishing papillomas from non-neoplastic lesions was best at a cutoff of 10 circles/10 HPF (2-tailed P<0.0001) with sensitivity, specificity, positive predictive value, and negative predictive value of 66.2%, 93.1%, 92.1%, and 69.2%, respectively. The results were similar in the biopsy subset. One other neoplastic entity, the DEK::AFF2 carcinomas, also showed prominent CD163 circle staining. In summary, sinonasal papillomas demonstrate extensive CD163 “circle” staining in the epithelium compared with the non-neoplastic lesions studied. As such, the “circle sign” on CD163 IHC may be helpful in distinguishing between diagnoses, particularly on small biopsies or equivocal specimens.
Digital rehabilitation for hand and wrist pain: a single-arm prospective longitudinal cohort study
Authors: Costa Fabíola , Janela Dora , Molinos Maria , Moulder Robert G. , Lains Jorge , Francisco Gerard E. , Bento Virgílio , Yanamadala Vijay , Cohen Steven P. , Correia Fernando Dias
Published: August 2022

Introduction:

Wrist and hand represent the third most common body part in work-related injuries, being associated with long-term absenteeism. Telerehabilitation can promote access to treatment, patient adherence, and engagement, while reducing health care–related costs.

Objective:

Report the results of a fully remote digital care program (DCP) for wrist and hand pain (WP).

Methods:

A single-arm interventional study was conducted on individuals with WP applying for a DCP. Primary outcome was the mean change in the Numerical Pain Rating Scale after 8 weeks (considering a minimum clinically important change of 30%). Secondary outcomes were: disability (Quick Disabilities of the Arm, Shoulder, and Hand questionnaire), analgesic intake, surgery intention, mental health (patient health questionnaire [PHQ-9] and generalized anxiety disorder [GAD-7]), fear-avoidance beliefs (FABQ-PA), work productivity and activity impairment, and engagement.

Results:

From 189 individuals starting the DCP, 149 (78.8%) completed the intervention. A significant pain improvement was observed (51.3% reduction (2.26, 95% CI 1.73; 2.78)) and 70.4% of participants surpassing minimum clinically important change. This change correlated with improvements in disability (52.1%), FABQ-PA (32.2%), and activities impairment recovery (65.4%). Improvements were also observed in other domains: surgery intent (76.1%), mental health (67.0% in anxiety and 72.7% in depression), and overall productivity losses (68.2%). Analgesic intake decreased from 22.5% to 7.1%. Mean patient satisfaction score was 8.5/10.0 (SD 1.8).

Conclusions:

These findings support the feasibility and utility of a fully remote DCP for patients with WP. Clinically significant improvements were observed in all health-related and productivity-related outcomes, alongside very high patient adherence rates and satisfaction. This study strengthens that management of WP is possible through a remote DCP, decreasing access barriers and potentially easing health care expenditure.
The clinical relevance of sensory nerve coaptation in DIEP flap breast reconstruction evaluated using the BREAST-Q
Authors: Bijkerk Ennie , Beugels Jop , van Kuijk Sander M.J. , Lataster Arno , van der Hulst René R.W.J. , Tuinder Stefania M.H.
Published: August 2022

Introduction:

Sensory nerve coaptation in autologous breast reconstruction positively affects the sensory recovery in the reconstructed breast. However, patient-reported outcomes are currently lacking and no conclusions on the clinical relevance of nerve coaptation could be drawn. The aim of this study was to evaluate the clinical relevance of nerve coaptation in deep inferior epigastric perforator (DIEP) flap breast reconstruction.

Methods:

A prospective cohort study was conducted with patients with innervated or noninnervated DIEP flap breast reconstruction between August 2016 and August 2018, and completed a BREAST-Q questionnaire at a minimum of 12 months postoperative, in combination with a preoperative questionnaire or at 6 months postoperative. The domain “Physical well-being of the chest” was the primary outcome and patients answered additional sensation-specific questions. Sensation was measured using Semmes-Weinstein monofilaments.

Results:

In total, 120 patients were included (65 innervated and 55 noninnervated reconstructions). A clinically relevant difference was found in BREAST-Q scores in favor of patients with innervated reconstructions in general, and for delayed reconstructions in specific. Patients with sensate breast reconstruction more often experienced better and pleasant sensation.

Conclusions:

This study demonstrated that nerve coaptation in DIEP flap breast reconstruction, specifically in delayed reconstructions, resulted in clinically relevant higher patient-reported outcomes for the BREAST-Q domain “Physical well-being of the chest” and that better sensation was perceived pleasantly. However, the BREAST-Q does not adequately address sensation, and the introduction and validation of new scales is required to fill in these gaps to confirm the clinical relevance of nerve coaptation reliably.
Efficacy and Safety of Botulinum Toxin Type A in the Treatment of Benign Parotid Hypertrophy: a Prospective, Single-arm Clinical Trial
Authors: Chen Zong , Chen Zhiyou , Liu Wenhui , Wei Zhiru , Pang Ran , Cheng Xu , Wang Shuqi , Chen Shengjun , Liu Linbo , Li Guangshuai
Published: August 2022

Background:

Benign parotid hypertrophy (BePH) makes the earlobe area appear “swollen”, and weakens the lateral facial contour and esthetics. Efficacious treatment for BePH is not available. We evaluated the efficacy and safety of botulinum toxin type A (BTX-A) for BePH treatment.

Methods:

Thirty-six participants with BePH were enrolled and treated with BTX-A injection. After 6 months of follow-up, changes in the thickness and length of the superficial lobe of the parotid gland (SLPG) were assessed. Analyses of patient subgroups and image analyses were also undertaken to assess improvement.

Results:

Thirty-three participants completed this study. The SLPG thickness was reduced significantly after BTX-A injection, but the longitudinal diameter of the PG was not changed significantly (p < 0.001 and p = 0.146, respectively). Subgroup analyses showed that the degree of PG hypertrophy affected treatment efficacy and degree of improvement, but age and sex did not (p < 0.001, p = 0.137, and p = 0.138, respectively). Image analyses showed improvement in the facial contour (p < 0.05). Serious adverse reactions or complications were not observed.

Conclusions:

BTX-A can be used to treat BePH, reduce PG volume, and improve the facial contour.
DAAM (Dermal Auto-Augmentation Mastopexy) – maintaining maximal volume in primary breast lift surgery and when combined with breast implant removal.
Authors: Rand Richard P.
Published: August 2022

Mastopexy is performed to lift, reshape and restore tone to the ptotic breast. Dermal Auto-Augmentation Mastopexy (DAAM) maintains the maximal existing tissue volume because an average of only 11.3 grams is removed per side. This potentially avoids the need for prosthetic implants in patients concerned about breast implant issues. The procedure utilizes flexible freehand shaping and is also an ideal mastopexy when prosthetic implants are removed because it requires minimal undermining and preserves blood flow to the tissues. Long-term results are extremely stable without revision even in cases of dramatic laxity.
Finding the Balance Between Reduced Opioid Prescribing and Patient-reported Pain Management Among General Surgery Patients
Authors: Gudmundsdottir Hallbera , Ubl Daniel S. , Yost Kathleen J. , Gazelka Halena M. , Habermann Elizabeth B. , Thiels Cornelius A.
Published: August 2022

Objective:

To compare patient-reported outcomes before and after implementation of evidence-based, procedure-specific opioid prescribing guidelines.

Background:

The opioid epidemic remains a significant public health issue. Many institutions have responded by reducing opioid prescribing after surgery. However, the impact of this on patient-reported outcomes remains poorly understood.

Methods:

Opioid-naïve adults undergoing 12 elective general surgery procedures at a single institution prospectively completed telephone surveys at median 26 days from discharge. Patients were compared before (March 2017–January 2018) and after (May 2019–November 2019) implementation of evidence-based, procedure-specific opioid prescribing guidelines.

Results:

A total of 603 preguideline and 138 postguideline patients met inclusion criteria and completed surveys. Overall, 60.5% of preguideline and 92.5% of postguideline prescriptions fell within recommendations (P<0.001), while refill rates were similar (4.5% vs 5.8%, P=0.50). A statistically significant drop in median morphine milligram equivalent prescribed was observed for 9 of 12 procedures (75%). No opioids were prescribed for 16.7% of patients in both cohorts (P=0.98). While 93.3% of preguideline and 87.7% of postguideline patients were very/somewhat satisfied with their pain control, the proportion of patients who were very/somewhat dissatisfied increased from 4.2% to 9.4% (P=0.039).

Conclusions:

Prescribing guidelines successfully reduced opioid prescribing without increased refill rates. Despite decreased prescribing overall, there was a continued reluctance to prescribe no opioids after surgery. Although most patients experienced good pain control, there remains a subset of patients whose pain is not optimally managed in the era of reduced opioid prescribing.
Autoimmune neuromyotonia
Authors: Comperat Louis , Pegat Antoine , Honnorat Jérôme , Joubert Bastien
Published: August 2022

Purpose of review

Autoimmune neuromyotonia encompasses a group of rare immune-mediated neurological disorders frequently associated with anti-contactin-associated protein-like 2 (CASPR2) antibodies and featuring clinical and electrical signs of peripheral nerve hyperexcitability (PNH). We aim to summarize the current knowledge on immune-mediated neuromyotonia, focusing on clinical presentations, pathophysiology, and management.

Recent findings

Neuromyotonia is a major feature of several autoimmune neurological syndromes characterized by PNH with or without central neurological system involvement. Experimental and clinical evidence suggest that anti-CASPR2 antibodies are directly pathogenic in autoimmune neuromyotonia patients.

Neuromyotonia, a form of PNH, is a major feature in several syndromes associated with anti-CASPR2 antibodies, including cramp-fasciculation syndrome, Isaacs syndrome, Morvan syndrome, and autoimmune limbic encephalitis. Diagnosis relies on the identification of motor, sensory, and autonomic signs of PNH along with other neurological symptoms, anti-CASPR2 antibody-positivity, and of characteristic electroneuromyographic abnormalities. Paraneoplastic associations with thymoma are possible, especially in Morvan syndrome. Patients usually respond to immune-active treatments, including steroids, intravenous immunoglobulins, plasma exchanges, and rituximab.
Autoimmune nodopathies, an emerging diagnostic category
Authors: Martín-Aguilar Lorena , Lleixà Cinta , Pascual-Goñi Elba
Published: August 2022

Purpose of review

In the last decade, antibodies targeting cell adhesion molecules of the node of Ranvier were described in patients with autoimmune neuropathies. These nodal/paranodal antibodies associate with specific clinicopathological features that are different from classical chronic inflammatory demyelinating polyneuropathy (CIDP). In this review, we will summarize recent findings establishing autoimmune nodopathies (AN) as a new category of autoimmune neuropathies.

Recent findings

AN include anti-contactin 1, anti-contactin-associated protein 1, anti-neurofascin 155 and anti-pan-neurofascin antibody-mediated neuropathies. Their clinical spectrum includes acute, subacute or chronic onset sensory-motor neuropathies mimicking Guillain-Barré syndrome (GBS) and CIDP, although they differ in their response to standard therapy with intravenous immunoglobulin (IVIG). Neurophysiologically they overlap with acquired demyelinating neuropathies, but ultrastructural studies and animal models demonstrated antibody-mediated pathology restricted to the node of Ranvier. Anti-contactin1 and anti-pan-neurofascin also associate with nephrotic syndrome. Nodal/paranodal antibodies are predominantly of the immunoglobulin (IgG)4 subclass during the chronic phase of the disease, but complement-fixing IgG3 antibodies are detected during the early phase and associate with aggressive onset and IVIG response. Nodal/paranodal antibodies testing is key in the diagnosis of AN.

AN have emerged as a new diagnostic category pathologically different from acquired demyelinating neuropathies. Clinically they overlap with GBS and CIDP although they associate with specific clinical features that should lead to clinical suspicion. Nodal/paranodal antibodies are key effector mechanisms of disease and good diagnostic and disease-monitoring biomarkers in AN.
Deep clustering of bacterial tree images
Authors: Hayati Maryam , Chindelevitch Leonid , Aanensen David , Colijn Caroline
Published: August 2022

The field of genomic epidemiology is rapidly growing as many jurisdictions begin to deploy whole-genome sequencing (WGS) in their national or regional pathogen surveillance programmes. WGS data offer a rich view of the shared ancestry of a set of taxa, typically visualized with phylogenetic trees illustrating the clusters or subtypes present in a group of taxa, their relatedness and the extent of diversification within and between them. When methicillin-resistant
Staphylococcus aureus
(MRSA) arose and disseminated widely, phylogenetic trees of MRSA-containing types of
S. aureus
had a distinctive ‘comet’ shape, with a ‘comet head’ of recently adapted drug-resistant isolates in the context of a ‘comet tail’ that was predominantly drug-sensitive. Placing an
S. aureus
isolate in the context of such a ‘comet’ helped public health laboratories interpret local data within the broader setting of
S. aureus
evolution. In this work, we ask what other tree shapes, analogous to the MRSA comet, are present in bacterial WGS datasets. We extract trees from large bacterial genomic datasets, visualize them as images and cluster the images. We find nine major groups of tree images, including the ‘comets’, star-like phylogenies, ‘barbell’ phylogenies and other shapes, and comment on the evolutionary and epidemiological stories these shapes might illustrate.

This article is part of a discussion meeting issue ‘Genomic population structures of microbial pathogens’.
Selfish, promiscuous and sometimes useful: how mobile genetic elements drive horizontal gene transfer in microbial populations
Authors: Haudiquet Matthieu , de Sousa Jorge Moura , Touchon Marie , Rocha Eduardo P. C.
Published: August 2022

Horizontal gene transfer (HGT) drives microbial adaptation but is often under the control of mobile genetic elements (MGEs) whose interests are not necessarily aligned with those of their hosts. In general, transfer is costly to the donor cell while potentially beneficial to the recipients. The diversity and plasticity of cell–MGEs interactions, and those among MGEs, result in complex evolutionary processes where the source, or even the existence of selection for maintaining a function in the genome, is often unclear. For example, MGE-driven HGT depends on cell envelope structures and defense systems, but many of these are transferred by MGEs themselves. MGEs can spur periods of intense gene transfer by increasing their own rates of horizontal transmission upon communicating, eavesdropping, or sensing the environment and the host physiology. This may result in high-frequency transfer of host genes unrelated to the MGE. Here, we review how MGEs drive HGT and how their transfer mechanisms, selective pressures and genomic traits affect gene flow, and therefore adaptation, in microbial populations. The encoding of many adaptive niche-defining microbial traits in MGEs means that intragenomic conflicts and alliances between cells and their MGEs are key to microbial functional diversification.

This article is part of a discussion meeting issue ‘Genomic population structures of microbial pathogens’.
Genome-scale metabolic network reconstructions of diverse
Escherichia
strains reveal strain-specific adaptations
Authors: Monk Jonathan M.
Published: August 2022

Bottom-up approaches to systems biology rely on constructing a mechanistic basis for the biochemical and genetic processes that underlie cellular functions. Genome-scale network reconstructions of metabolism are built from all known metabolic reactions and metabolic genes in a target organism. A network reconstruction can be converted into a mathematical format and thus lend itself to mathematical analysis. Genome-scale models (GEMs) of metabolism enable a systems approach to characterize the pan and core metabolic capabilities of the
Escherichia
genus. In this work, GEMs were constructed for 222 representative strains of
Escherichia
across HC1100 levels spanning the known
Escherichia
phylogeny. The models were used to study
Escherichia
metabolic diversity and speciation on a large scale. The results show that unique strain-specific metabolic capabilities correspond to different species and nutrient niches. This work is a first step towards a curated reconstruction of pan-
Escherichia
metabolism.

This article is part of a discussion meeting issue ‘Genomic population structures of microbial pathogens’.
The effect of sequencing and assembly on the inference of horizontal gene transfer on chromosomal and plasmid phylogenies
Authors: Huisman Jana S. , Vaughan Timothy G. , Egli Adrian , Tschudin-Sutter Sarah , Stadler Tanja , Bonhoeffer Sebastian
Published: August 2022

The spread of antibiotic resistance genes on plasmids is a threat to human and animal health. Phylogenies of bacteria and their plasmids contain clues regarding the frequency of plasmid transfer events, as well as the co-evolution of plasmids and their hosts. However, whole genome sequencing data from diverse ecological or clinical bacterial samples are rarely used to study plasmid phylogenies and resistance gene transfer. This is partially due to the difficulty of extracting plasmids from short-read sequencing data. Here, we use both short- and long-read sequencing data of 24 clinical extended-spectrumβ-lactamase (ESBL)-producingEscherichia colito estimate chromosomal and plasmid phylogenies. We compare the impact of different sequencing and assembly methodologies on these phylogenies and on the inference of horizontal gene transfer. We find that chromosomal phylogenies can be estimated robustly with all methods, whereas plasmid phylogenies have more variable topology and branch lengths across the methods used. Specifically, hybrid methods that use long reads to resolve short-read assemblies (HybridSPAdes and Unicycler) perform better than those that started from long reads during assembly graph generation (Canu). By contrast, the inference of plasmid and antibiotic resistance gene transfer using a parsimony-based criterion is mostly robust to the choice of sequencing and assembly method.

This article is part of a discussion meeting issue ‘Genomic population structures of microbial pathogens’.