bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance to anti-PD1 therapies in patients with advanced melanoma: systematic literature review and application of the Society for Immunotherapy of Cancer Immunotherapy Resistance Taskforce anti-PD1 resistance definitions
Authors: Shui Irene M. , Scherrer Emilie , Frederickson Andrew , Li Joyce W. , Mynzhassarova Anel , Druyts Eric , Tawbi Hussein
Published: October 2022

Nearly half of advanced melanoma patients do not achieve a clinical response with anti-programmed cell death 1 protein (PD1) therapy (i.e. primary resistance) or initially achieve a clinical response but eventually progress during or following further treatment (i.e. secondary resistance). A consensus definition for tumor resistance to anti-PD1 monotherapy was published by Society for Immunotherapy of Cancer Immunotherapy Resistance Taskforce (SITC) in 2020. A systematic literature review (SLR) of clinical trials and observational studies was conducted to characterize the proportions of advanced melanoma patients who have progressed on anti-PD1 therapies. The SLR included 55 unique studies and the SITC definition of primary resistance was applied to 37 studies that specified disease progression by best overall response. Median and range of patients with primary resistance in studies that specified first-line and second-line or higher anti-PD1 monotherapy was 35.50% (21.19–39.13%; n = 4 studies) and 41.54% (30.00–56.41%, n = 3 studies); median and range of patients with primary resistance in studies that specified first-line and second-line or higher combination therapy was 30.23% (15.79–33.33%; n = 6 studies), and 70.00% (61.10–73.33%; n = 3 studies). Primary resistance to anti-PD1 monotherapies and when in combination with ipilimumab are higher in patients receiving second-line or higher therapies, in patients with acral, mucosal, and uveal melanoma, and in patients with active brain metastases. The percentage of patients with primary resistance was generally consistent across clinical trials, with variability in resistance noted for observational studies. Limitations include applying the SITC definitions to combination therapies, where consensus definitions are not yet available. Future studies should highly consider utilizing the SITC definitions to harmonize how resistance is classified and facilitate meaningful context for clinical activity.
Exercise Leg Blood Flow Is Preserved in Long-term Breast Cancer Survivors Previously Treated With Anthracycline Chemotherapy
Authors: Beaudry Rhys I. , Akins John D. , Richey Rauchelle E. , Brothers R. Matthew , Nelson Michael D. , Sarma Satyam , Tucker Wesley J. , Haykowsky Mark J.
Published: October 2022

Purpose:

The objective of this investigation was to compare the acute hemodynamic responses during single-leg knee extension (SLKE) exercise between female breast cancer (BC) survivors previously treated with anthracycline chemotherapy and age- and sex-matched control (CON) subjects.

Methods:

Fourteen BC survivors (age: 61 ± 7 yr; time post-anthracycline therapy: 12 ± 6 yr) and nine CON subjects (age: 59 ± 7 yr) performed SLKE exercise at 25%, 50%, and 75% of peak power output during which heart rate, blood pressure (BP), leg blood flow (Doppler ultrasonography), and vascular conductance (leg blood flow/mean BP) were measured. Quadriceps mass was estimated from thigh volume and skinfold measures.

Results:

Breast cancer survivors had lower quadriceps mass compared with CON subjects (1803 ± 607 vs 2601 ± 1102 g, P = .04). No difference was found between groups for maximal SLKE power output (28 ± 11 vs 34 ± 17 W, P = .35), heart rate (109 ± 14 vs 103 ± 13 bpm, P = .36), or mean arterial BP (122 ± 18 vs 119 ± 26 mm Hg, P = .33). Rest and submaximal exercise mean arterial BP, leg blood flow (indexed to quadriceps muscle mass), and leg vascular conductance were not significantly different between BC survivors and CON subjects.

Conclusion:

Leg blood flow during submaximal SLKE exercise is preserved in long-term BC survivors previously treated with anthracycline chemotherapy.
Chronic Obstructive Pulmonary Disease Patients With High Peripheral Blood Eosinophil Counts Have Better Predicted Improvement in 6MWD After Rehabilitation
Authors: Shui Li-Li , Cai Ji-Jun , Zhong Xiao-Qing , Li You-Lun , He Mao-Rui , Chen Ya-Juan
Published: October 2022

Purpose:

The objective of this investigation was to determine whether chronic obstructive pulmonary disease (COPD) patients with high blood eosinophil (EOS) counts had better improvement in 6-min walk test (6MWT) after pulmonary rehabilitation (PR).

Methods:

Fifty COPD patients were randomly assigned to either the rehabilitation group (RG) or the control group (CG). Patients in the RG (8 wk PR + routine medication) and the CG (routine medication) were followed for 32 wk. According to the blood EOS level, the RG was divided into an EOS ≥ 200 cells/μL group and EOS < 200 cells/μL group. The 6MWT distance, Borg Scale, and COPD Assessment Test (CAT) were evaluated before intervention and 8 wk and 32 wk later.

Results:

After the 8-wk intervention, 37 patients (19 RG/18 CG) completed the study. At 8-wk and 32-wk follow-up from baseline, a statistically significant difference was found between these two groups in the 6MWT, Borg Scale, and CAT. Compared with baseline, the 6MWT in the RG increased 49.1 ± 40.2 m (95% CI, 29.7-68.5, P < .001) at 8 wk and 60.8 ± 42.1 m (95% CI, 40.5-81.6, P < .001) at 32 wk. In addition, the improvement of 6MWT in the EOS ≥ 200 cells/μL RG group was higher than that in the EOS < 200 cells/μL group (40.1 ± 17.6 m, 95% CI, 36.8-43.4; P = .036) at 32-wk follow-up from baseline.

Conclusion:

An 8-wk PR can improve the exercise capacity of COPD patients, and the benefits persistent for 24 wk. The improvement in the 6MWT was more significant in COPD patients with a high blood EOS count.
Effects of Low-dose Splenic Irradiation on T lymphocyte Immune Function
Authors: Li Yanzi , Lv Hongying , Liang Donghai , Jiang Tao , Zhao Wei , Zhou Fei , Jiao Chenchen , Zhou Yuyuan , Yu Hongsheng
Published: October 2022

Relevant studies have confirmed that the stimulation of spleen function caused by low-dose splenic irradiation can have positive effects on tumors and other diseases. This study aimed to determine radiation-induced changes in spleen index, lymphocyte subsets, spleen cell apoptosis, and pathological features of the spleen in mice. The mouse model was established by irradiating the spleen at different doses. The mice were divided into the following groups: blank control, low-dose, low-dose fractionated irradiation, and challenge dose irradiation. The mice were sacrificed under humanitarian conditions, and spleen tissue and peripheral blood were collected. The spleen index was calculated, and flow cytometry was used to analyze spleen T lymphocyte subsets and spleen apoptosis. The pathological changes in the spleen were determined by hematoxylin and eosin (H&E) staining. The spleen index of mice in the low-dose fractionated irradiation group was significantly increased compared with that in the blank control group. The spleen indexes of the low-dose irradiation and low-dose fractionated irradiation groups were much higher than that of the challenge dose irradiation group. Compared with the blank control group, the percentage of CD3+ and CD4+ T lymphocytes in the peripheral blood and spleen tissues in the low-dose irradiation and low-dose fractionated irradiation groups was significantly increased, whereas that from the challenge dose irradiation group was obviously decreased. CD8+ T lymphocytes in the peripheral blood and spleen tissues in the low-dose irradiation, low-dose fractionated irradiation, and challenge dose irradiation groups were significantly lower than those in the blank control group. The apoptosis rate of the spleen in the challenge dose irradiation group was significantly higher than that in the blank control, low-dose irradiation, and low-dose fractionated irradiation groups. H&E staining analysis of the spleen showed pathological changes in the different irradiation groups compared with the blank control group. Low-dose irradiation and low-dose fractionated irradiation can change the T lymphocyte subsets in the peripheral blood and spleen of mice, which can promote immune excitation and improve immune effects.
PROGRESSION OF MYOPIC MACULOPATHY IN PATIENTS WITH MYOPIC TRACTION MACULOPATHY AFTER VITRECTOMY
Authors: Park Hyo Song , Lee Christopher Seungkyu , Koh Hyoung Jun
Published: October 2022

Purpose:

To compare the progression of myopic maculopathy with or without vitrectomy in patients with myopic traction maculopathy (MTM).

Methods:

Seventy-seven eyes with MTM were classified into either the observation group (n = 38) or the vitrectomy group (n = 39). Progression of myopic maculopathy was assessed with fundus photography using infrared images. Progression within stage was evaluated as an increase in the area of atrophic lesions on infrared images using ImageJ software. The rate of progression was compared using the paired t-test.

Results:

The mean follow-up period was 60.0 ± 47.5 months. The initial mean stage of myopic maculopathy for the observation group was 1.86 ± 0.86, and it progressed to 2.00 ± 0.83 (P = 0.023) at the last visit. For the vitrectomy group, the stage progressed from 1.82 ± 0.96 to 2.05 ± 1.09 (P = 0.011). Four eyes (10.5%) in the observation group showed progression at 87.3 months, and seven eyes (17.9%) in the vitrectomy group showed progression at 31.3 months.

Conclusion:

Surgery in patients with MTM may accelerate the progression of myopic maculopathy. Therefore, care should be taken when considering surgery for patients with MTM.
CHOROIDAL VASCULAR DENSITY IN DIABETIC RETINOPATHY ASSESSED WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY
Authors: Nakano Hideyuki , Hasebe Hiruma , Murakami Kenji , Nakamura Yusuke , Fukuchi Takeo
Published: October 2022

Purpose:

We aimed to assess choroidal vascularity by diabetic retinopathy (DR) stage using the choroidal vascular density (CVD) obtained from swept-source optical coherence tomography en-face images.

Methods:

This prospective, cross-sectional, multicenter study included patients from Niigata City General Hospital and Saiseikai Niigata Hospital between October 2016 and October 2017. Choroidal vascular density was obtained by binarizing swept-source optical coherence tomography en-face images of patients with diabetes and those with DR, patients without DR, and healthy age-matched volunteers.

Results:

Patients were allocated to the healthy control (n = 28), no DR (n = 23), nonproliferative DR (NPDR) without diabetic macular edema (DME) (n = 50), NPDR + DME (n = 38), and proliferative DR (PDR) or any previous treatment with panretinal photocoagulation (n = 26) groups. Investigation of the choriocapillaris slab level indicated that the no DR group had significantly high CVD values (P < 0.05), and the PDR groups had significantly low CVD values (P < 0.01). Investigation of the large choroidal vessel level indicated that the NPDR + DME and PDR groups had significantly lower CVD values than the control group (P < 0.05 and P < 0.01, respectively).

Conclusion:

We found that at the choriocapillaris slab level, the no DR group had a higher CVD and the NPDR with DME and PDR groups had a lower CVD than the control group. At the level of the large choroidal vessels, the NPDR with DME and PDR groups had a lower CVD than the control group. There were significant differences in choroidal vasculature found using CVD obtained from swept-source optical coherence tomography en-face images of patients with diabetes and DR.
Glaucoma Detection in Myopic Eyes: Structural and Vascular Assessment by Optic Coherence Tomography Methods
Authors: Cakir Ihsan , Altan Cigdem , Yalcinkaya Gulay , Yayla Gizem , Alagoz Nese , Basgil Pasaoglu Isil , Yasar Tekin
Published: October 2022

Précis:

Retinal nerve fiber layer (RNFL) thickness is helpful in the diagnosis of glaucoma in myopic eyes but neuroretinal rim (NRR) thickness is the most valuable measure. However, changes in optical coherence tomography angiography (OCT-A) parameters are insufficient for the diagnosis of mild to moderate glaucoma in myopia.

Purpose:

To detect how a multimodal evaluation, which includes RNFL, NRR thickness, and optic nerve head (ONH) OCT-A, affects glaucoma diagnosis in myopic patients.

Materials and Methods:

Parameters of healthy myopic and myopic glaucoma eyes with an axial length of ≥24 mm were compared. The ONH structural features and peripapillary RNFL thickness were determined with Cirrus 5000 HD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA). The Cirrus 5000 HD-OCT with AngioPlex was utilized to perform OCT-A imaging. The sensitivity and specificity levels were calculated by the best cut-off values with area under curve (AUC).

Results:

One hundred healthy myopic and 54 myopic glaucoma eyes were evaluated. In all areas, myopic glaucoma patients exhibited lower RNFL and NRR thickness than healthy myopic individuals (P<0.05), with the exception of nasal quadrant RNFL thickness (P=0.152). The mean entire and 4 quadrants of global radial peripapillary capillary (RPC)-perfusion and global RPC flux index (FI) were significantly lower in the group of myopic glaucoma patients except for the nasal quadrant mean RPC perfusion (P=0.224). The average RNFL and NRR thickness had a significant difference in AUC for the diagnosis of glaucoma in myopic individuals (P=0.001, for each). The average NRR showed excellent diagnostic performance, whereas the average RNFL showed good diagnostic performance. Average RPC perfusion and average RPC FI showed poor diagnostic ability. The average NRR AUC was more significant than average RPC perfusion and average RPC FI AUC (P<0.001).

Conclusions:

Although RNFL thickness was helpful to diagnose glaucoma in patients with myopia, the diagnostic power of NRR thickness performed best. OCT-A parameters showed poor diagnostic accuracy for glaucoma and the observed perfusion decrease in myopic glaucoma eyes was not sufficiently discriminative compared with NRR and RNFL thickness measurements.
Clinical Application of CLSM, Dermoscope, and Wood’s Lamp in Diagnosis and Differential Diagnosis of Five Hypopigmentation Disorders: A Cross-Sectional Study
Authors: Lu Yu , Wan Xiao , Lu Quan-Sheng , Sun Chao , Lyu Shan-Rong , Li Yi-Zhi , Jiang Guan
Published: October 2022

Objective:

Noninvasive instruments including confocal laser scanning microscope (CLSM), dermoscope, and Wood’s lamp afford the advantage of obtaining skin microanatomical images quickly, in real-time, and dynamically. However, further understanding is needed regarding the differences between various techniques for diagnosis on hypopigmentation diseases. This study was aimed to observe the characteristics of hypopigmentation diseases by using CLSM, dermoscope, and Wood’s lamp, in order to provide evidence for clinician to choose appropriate instruments for assistant diagnosis.

Methods:

In total, data from 397 patients with vitiligo, nevus anemicus, achromic nevus, pityriasis alba, and senile leukoderma were collected from January 2019 to January 2021 in affiliated hospital of Xuzhou Medical University. CLSM, dermoscope, and Wood’s lamp were used to analyze the characteristics of lesions and the differences between the diseases. Enumeration data were presented as frequencies and percentages.

Results:

CLSM showed that the pigment ring of vitiligo was absent (126/126, 100.0%), senile leukoderma had hypopigmentation, skin atrophy and thinning, and flat epidermis mutation (79/79, 100.0%). In dermoscope, vitiligo showed a milky white hypopigmented area (113/126, 89.8%), nevus anemicus showed a clear but irregular (38/45, 84.4%) white hypopigmentation area (41/45, 91.1%), pityriasis alba showed a clear and light white hypopigmented area, with a grayish-white chaff-like scaly appearance (98/107, 91.6%), senile leukoderma showed a white radially hypopigmentation area with a small amount of pigmentation (79/79, 100.0%). Under Wood’s lamp, bright blue-white patches with clear boundaries can be observed in vitiligo, nevus anemicus, pityriasis alba (93/107, 86.9%) and senile leukoderma appeared clear bluish-white patches, achromic nevus appeared unclear bluish-white patches, respectively.

Conclusion:

Vitiligo, nevus anemicus, achromic nevus, pityriasis alba, and senile leukoderma all belong to hypopigmentation diseases, however, they have own imaging characteristics under CLSM, dermoscope, and Woods lamp techniques, which may be used to help the diagnosis and differential diagnosis of these diseases.
Anagen effluvium due to azathioprine in a patient with normal thiopurine S-methyltransferase levels: A videodermoscopic analysis
Authors: Shah Swapnil , Ankad Balachandra S , Rajagopal Tanuja
Published: October 2022

Introduction:

Anagen effluvium (AE) is caused by impaired mitotic activity of matrix cells in the hair follicles. It presents with sudden loss of hair and myelosuppression. The diagnosis is based on the clinical history, trichoscopy, and trichogram.

We herein report a case in which videodermoscopy revealed new trichoscopic features of AE caused by azathioprine in a patient with normal thiopurine S-methyltransferase levels.

Case presentation:

A 20-year-old woman presented with sudden loss of hair following treatment with oral azathioprine. Evaluation of the thiopurine S-methyltransferase (TPMT) were within normal limits both in genotype and phenotype levels. Hair pull test was positive. Trichoscopy revealed yellow dots and multiple black dots, empty yellow dots, dark lines, upright regrowing hairs, and circle hairs. Azathioprine was stopped, and minoxidil 5% and oral multivitamin were started. Post-treatment trichoscopic analysis revealed terminal hairs and upright regrowing hairs

Discussion:

AE is characterized by abrupt loss of anagen hairs due to impaired metabolic activity. Trichoscopy in AE shows coudability hairs, black dots, exclamation mark hairs, multiple broken shafts, and regrowing hairs. Empty yellow dots, yellow dots with black dots, pigtail hairs, and dark lines were additional features in this study.

Conclusion:

Trichoscopy assists in the accurate diagnosis of AE. Adverse effects of azathioprine can be observed even with normal TPMT levels. Weekly monitoring is therefore of prime importance.
Secukinumab efficacy in the treatment of pediatricpsoriasis in China: a case series
Authors: Ma Yi-Ping , Jia Hong
Published: October 2022

Introduction:

There is a lack of data on the use of biologic therapy inrefractory pediatric psoriasis in China. This study presents pediatric psoriasis cases treated with Secukinumab in our center.

Case presentation:

In this retrospective case series,we collected the data of moderate to severe psoriasis patients under 18 years old treated with secukinumab in our hospital from 2019 to 2020. The demographic data, previous treatments, efficacy and side effects were recorded and analyzed.

Discussion:

These five patients had a median age of 10 years (8-17) with a median history of plaque psoriasis of 2 years.At Week 4, 3 out of 5 cases have achieved PASI 75, and at Week 16, 100% of the patients have achieved PASI 100.No adverse events occurred.

Conclusion:

It is safe and effective to treat recalcitrant pediatric psoriasis with secukinumab. Larger series are needed to confirm our observation.
Treatment of Basal Cell Carcinoma Involving the Medial Canthus by Multiple Local Flaps: A Case Report
Authors: Fei Yang-Honghong , Jin Jian , Sun Hua-Feng , Fan Hao , Hong Xu-Dong , Chen Ai-Fen , Lu Hai-Shan , Wu Jin-Fang
Published: October 2022

Introduction:

Basal cell carcinoma (BCC) is a skin malignancy that commonly appears on the face. Although surgical resection remains the therapeutic gold standard, it always produces a skin defect. Fine aesthetic reconstruction is a persisting challenge for all dermatologists. We herein present a case of BCC affecting the patient’s medial canthus.

Case presentation:

A 61-year-old woman presented with BCC of her right medial canthus. After lesion excision, a 2.5- × 3.5-cm skin defect remained in her canthal area. We used three local flaps to cover the defect according to aesthetic subunits. The defect over the nasal dorsum was covered by a glabellar flap, the upper eyelid defect was covered by a rotation advancement flap, and the lower eyelid defect was covered by a subcutaneous island pedicle flap. The result remained both functionally and aesthetically satisfactory throughout 2 months of follow-up.

Discussion:

Skin malignancies can occur in areas that require special treatment. The medial canthus is a fundamental element of the “facial triangle.” Restoration of color, texture, and thickness of the soft tissue is essential in this area. Full-thickness skin grafts and single flaps seem unsuitable for large defects in this region. Instead, a combination of local flaps according to aesthetic subunits can give desirable results.

Conclusion:

Defects in the medial canthus are difficult to reconstruct. This case provides a novel technique for the treatment of BCC in the medial canthus. Multiple local flaps were used to cover the defect with low tension, giving both a good cosmetic appearance and effective structural reconstruction.
Affective Depression Mediates PTSD to Suicide in a Sample of Treatment-Seeking First Responders
Authors: Whitworth James , Galusha Jeanine , Carbajal Jose , Ponder Warren N. , Schuman Donna L.
Published: October 2022

Objective

The aim of this study was to examine the associations of comorbid posttraumatic stress disorder (PTSD), affective or somatic depression, and suicide among first responders (FRs).

Method

We used baseline data from FRs (N = 232) who sought services at a nonprofit mental health agency specializing in treating trauma exposed FRs. We conducted two PROCESS simple mediation models with PTSD as the predictor, affective depression and somatic depression as the mediators, and suicidality as the dependent variable.

Results

Affective depression significantly mediated the relationship between PTSD and suicidality, whereas somatic depression did not. The direct effect of PTSD on suicidality was not significant.

Limitations

These data are cross-sectional and should be followed up with longitudinal analyses across the course of treatment.

Conclusions

To reduce suicide risk, it is recommended that clinicians target affective depression instead of PTSD symptoms.
Postmenopausal Vaginal and Cervical Cancer Risk Related to In Utero Diethylstilbestrol Exposure
Authors: Wamakima Bridgette W. , McKinney Sara , Bookman Laura , Gompers Annika , Hacker Michele R. , Farid Huma
Published: October 2022

Objectives

Women exposed to diethylstilbestrol (DES) in utero have an increased risk of clear cell adenocarcinoma of the lower genital tract, requiring lifelong cervical and vaginal cancer screening. We examined the incidence of DES-related cancers in postmenopausal women 50 years and older.

Materials and Methods

We conducted a retrospective chart review of patients 50 years and older exposed to DES in utero who received care at our institution. Patients were identified using billing codes and/or searching through the electronic record for the word DES. With this 2-pronged approach, we reviewed a total of 503 charts with confirmed DES exposure to identify gynecologic cancer occurrence.

Results

Within the 503 selected charts, 28 cases of gynecologic cancer occurrence were identified. Ten patients had cervical cancer and one patient had vaginal cancer. Only 1 woman of 503 developed a DES-related cervical or vaginal malignancy after age 50 years. No patients were diagnosed with cervical or vaginal cancer after age 65 years.

Conclusions

Diethylstilbestrol-related malignancies are rare in those older than 50 years. Current cervical cancer screening guidelines recommend cessation of screening in an average risk, adequately screened patient at age 65 years, but patients exposed to DES have historically received lifelong screening. However, we found no cases of cervical or vaginal cancer related to DES after age 65 years, suggesting that screening recommendations could be changed for these patients to align with current screening guidelines.
Immunotherapy Provides Electrophysiological Recovery and Excellent Clinical Response in Sjogren’s Syndrome–Linked Quite Severe Autonomic Neuropathy
Authors: Sokmen Okan , Temucin Cagri Mesut , Ayhan Seker Cansu , Tan Ersin
Published: October 2022

Introduction:

The autonomic system is frequently affected in Sjogren’s syndrome (SS), but presentation with severe autonomic neuropathy is infrequent. Herein, we present a patient with primary SS-linked autonomic neuropathy, which is significantly clinic and electrophysiological responsive to immunotherapy.

Case Report:

A 29-year-old female patient was admitted to our neurology department with recurrent syncope, postural light-headedness, and weight loss. Neurological examination revealed tonic pupils. The baseline composite autonomic symptom score-31 was 51 (0 to 75), and baseline functional ability score was 10 (0 to 100%). In the follow-up, syncope episodes that frequently develop during the day required the patient to lie in the supine position in bed all day and were triggered even by coming to a slightly sitting position. Neurophysiologic testing showed evidence of cardiovagal and sudomotor impairment. The patient was diagnosed with SS after detailed investigations. A 5-day course of intravenous immunoglobulin (IVIg) was given, and she continued IVIg once a month. After 6 months, she could walk long distances without support, and gastrointestinal complaints and syncopes had significantly decreased. After ~1.5 years, she had a composite autonomic symptom score-31 score of 11 and a functional ability score of 80%. Control heart rate variability analysis showed a significant improvement in the values of SD of the RR interval and root mean square of successive RR interval differences.

Conclusions:

In SS-linked severe autonomic neuropathy, immunotherapy can provide electrophysiological recovery in addition to excellent clinical response.
Immune-Checkpoint-Inhibitor Therapy—Principles and Relevance of Biomarkers for Pathologists and Oncologists
Authors: Darr Christopher , Hilser Thomas , Kesch Claudia , Isgandarov Aykhan , Reis Henning , Wahl Milan , Kasper-Virchow Isabel , Hadaschik Boris A. , Grünwald Viktor
Published: October 2022

Immune-checkpoint-inhibitor (ICI) therapy has been one of the major advances in the treatment of a variety of advanced or metastatic tumors in recent years. Therefore, ICI-therapy is already approved in first-line therapy for multiple tumors, either as monotherapy or as combination therapy. However, there are relevant differences in approval among different tumor entities, especially with respect to PD-L1 testing. Different response to ICI-therapy has been observed in the pivotal trials, so PD-L1 diagnostic testing is used for patient selection. In addition to PD-L1 testing of tumor tissue, liquid biopsy provides a noninvasive way to monitor disease in cancer patients and identify those who would benefit most from ICI-therapy. This overview focuses on the use of ICI-therapy and how it relates to common and potential future biomarkers for patient-directed treatment planning.
Clonal-pattern Seborrheic Keratosis
Authors: Goldsmith Joshua F. , Montaser Kouhsari Laleh , Tahan Steven R.
Published: October 2022

Seborrheic keratosis is a benign epidermal tumor. Seborrheic keratosis with clonal pattern (CPSK) displays histologic features distinct from other subtypes of SK (non-CPSK). We sought to quantitatively assess the risk of recurrence and progression to squamous cell carcinoma (SCC), either in situ or invasive, of incompletely excised CPSKs. We studied all 244 cases from 238 patients of “seborrheic keratosis, clonal pattern” diagnosed in our institution over a 10-year period (2008-2018). Demographic, clinical, pathologic, and follow-up data were gleaned from electronic health records. Following glass slide review, CPSK lesions were divided into 2 groups: CPSK with cytologic atypia and CPSK without cytologic atypia. For comparison, 107 non-CPSKs were studied as controls. The minimum follow-up period was 2 years (median=4 y). All lesions were incompletely excised. Eighteen of 244 CPSKs (7.4%) recurred at or adjacent to the site of initial partial removal compared with 1.9% of non-CPSKs. Five of the 18 (28%) recurrent CPSKs recurred as CPSK, 11 (61%) as SCC in situ, and 3 (17%) as invasive SCC. The mean time to recurrence was 3.1 years. Two non-CPSKs recurred as non-CPSKs. Overall CPSKs were more likely to recur than non-CPSKs (P=0.04). CPSKs with atypia were more likely to recur than CPSKs without atypia (P=0.03). The upgrade rate to SCC at least in situ of all recurrent CPSK lesions with atypia was 78%. Our results suggest that pathologists should report the presence of clonal pattern when observed in seborrheic keratoses, indicate the presence of atypia, and provide lesional margin assessment.
Microcribriform Adenocarcinoma of Salivary Glands
Authors: Weinreb Ilan , Hahn Elan , Dickson Brendan C. , Rooper Lisa M. , Rupp Niels J. , Freiberger Sandra N. , Lubin Daniel , Gagan Jeffrey , Bishop Justin A.
Published: October 2022

The landscape of salivary gland carcinomas is ever-changing, with a growing list of new tumors and newly elucidated variants of well-known tumor entities. The routine use of next-generation sequencing has been instrumental in identifying novel fusions and tumor entities, which has helped bring the classification to a more objective and evidenced-based model. However, morphology remains critical in assessing the validity of these novel molecular findings, and most importantly, in assessing which of these findings will have an impact on the prognosis and treatment decisions for patients. The recognition of microsecretory adenocarcinoma (MSA) as a distinct low-grade malignancy of salivary glands, underpinned by MEF2C::SS18, and a single possibly related case of SS18::ZBTB7A, recently expanded this growing list of distinctive tumors. It was not until now, however, that the morphology of the latter case was known to be unique and reproducible. The authors have now seen 4 of these distinctive tumors that show a combination of distinctive oncocytic cells forming compact glandular growth as well as amphophilic cells forming tubular growth, and suggest the appellation “microcribriform adenocarcinoma” (MCA). So far, these tumors appear to preferentially occur in nonoral sites (2 parotid, 1 submandibular gland, and 1 bronchial seromucous glands). By immunohistochemistry, they express S100 and SOX-10 with focal outer myoepithelial cells marked by circumferential p63, p40, and smooth muscle actin staining around some of the nests and tubules. The tumors show infiltrative growth within a hyalinized and myxoid stroma. Cytologically, they appear generally low grade, similar to MSA. The morphologic and molecular uniformity of these 4 microcribriform adenocarcinoma cases warrants their recognition, and while related to MSA, they are sufficiently different to be classified as a distinct tumor. So far, in limited follow-up, these tumors appear to be relatively indolent.
Recovery and Resiliency in 29 Big Cities: Results From the 2021 Public Health Workforce Interests and Needs Survey
Authors: Juliano Chrissie , Schaffer Kay , Gambatese Melissa
Published: October 2022

Context:

Big Cities Health Coalition member health departments (BCHC HDs) serve more than 61 million people across their jurisdictions, nearly 20% of the US population. As such, they have particular challenges and opportunities in how they do their work. This article focuses on BCHC HDs that participated in the 2021 Public Health Workforce Interests and Needs Survey (PH WINS) and describes workplace perceptions, training needs, COVID-19 efforts, and well-being.

Objective:

To describe key characteristics of the governmental public health workforce among BCHC HDs, including demographics, perceptions, and needs.

Design:

Using a subsample of data from the 2021 PH WINS that included 29 BCHC HDs, descriptive statistics on many of the topics covered by the 2021 PH WINS were analyzed and compared with the 2017 PH WINS.

Setting:

Twenty-nine BCHC HDs in cities across the United States.

Participants:

In total, 7922 of 29 661 staff members (response rate of 27%) from participating BCHC HDs.

Results:

Most BCHC HD respondents self-identified as a woman (76%, 95% confidence interval [CI]: 75%-77%), and as Black, Indigenous, and people of color (69%, 95% CI: 68%-70%), similar to findings from the 2017 PH WINS (75%, 95% CI: 74%-76%; 67%, 95% CI: 66%-69%, respectively). Most respondents believe that their organization prioritizes diversity, equity, and inclusion (70%, 95% CI: 69%-72%). Thirty percent (95% CI: 29%-32%) intend to leave their organizations within 1 year, and 18% (95% CI: 17%-19%) plan to retire within 5 years. Staff connect their work with agency goals and priorities (86%, 95% CI: 85%-87%) and are determined to give their best effort every day (91%, 95% CI: 90%-91%).

Conclusion:

As the need for an all-encompassing focus on COVID-19 lessons, BCHC HDs should continue to focus on prioritizing staff retention, enhancing communication between senior staff and employees, and fostering an environment where innovation and creativity are rewarded.
Subchorionic Hematoma Volume Measured by Virtual Organ Computer-Aided Analysis in the Prediction of First-Trimester Pregnancy Outcome
Authors: Xu Chaoli , Wang Wenrong , Yang Bin , Zhu Minmin
Published: October 2022

This study aimed to assess the association of subchorionic hematoma (SCH) size measured by virtual organ computer-aided analysis (VOCAL) with the first-trimester pregnancy outcome. A total of 139 first-trimester pregnancies from 6 to 12 weeks of gestational age with SCH were included. The circumference, area, and volume of the SCH (Cs, As, and 3DVs) and gestational sac (Cg, Ag, and 3DVg) were automatically calculated by VOCAL. Interobserver agreement was assessed with the intraclass correlation coefficient and Bland-Altman plot. Odds ratios for the clinical and ultrasound characteristics of adverse pregnancy outcomes were estimated by univariate or multivariable logistic regression. There was high interobserver agreement in VOCAL measurements of the SCH and gestational sac (intraclass correlation coefficients, >0.900). By univariate regression analysis, women with adverse pregnancy outcomes were more likely to have vaginal bleeding, a larger As and 3DVs, and higher Cs/Cg, As/Ag, and 3DVs/3DVg ratios (all P < 0.05). In the multivariable regression analysis, a higher 3DVs/3DVg ratio of SCH (odds ratio, 1.034; 95% confidence interval [CI], 1.015–1.053; P = 0.000) and vaginal heavy bleeding had a significant positive relationship with the risk of adverse pregnancy outcomes (odds ratio, 7.846; 95% CI, 1.104–55.737; P = 0.039) remained associated with an increased risk of adverse pregnancy outcomes. With 11.87% as the cutoff, the receiver operating characteristic curve yielded a good predictive performance (area under the curve, 0.713) and high sensitivity (91.18%). The measurements of SCH by VOCAL provide high reliability for estimating the total hematoma burden in first-trimester pregnant patients. A greater volume proportion (3DVs/3DVg) of SCH worsens the pregnancy outcome, and a greater risk of adverse pregnancy outcome also associated with the severity of vaginal bleeding.
Short-Term Outcomes of Fiberoptic Bronchoscopy-guided Resection and Anastomosis Control in Thoracic Surgery
Authors: Geyik Fatih Dogu , Dogruyol Talha , Kahraman Selime , Arslan Gulten , Saracoglu Kemal Tolga , Demirhan Recep
Published: October 2022

Background:

In thoracic surgery practice, bronchial closure and anastomosis are relatively easy in technical terms; however, it is also the procedure that is most open to the development of complications with high morbidity. This study aimed to investigate the effect of simultaneous evaluation of bronchial closure under fiberoptic bronchoscopy guidance during lung resection on the development of complications.

Materials and Methods:

Patients aged over 18 years who underwent elective lung resection in our clinic between 2017 and 2021 were included in the study. Postoperative complications were recorded and statistically analyzed.

Results:

The mean age of the patients was 61.4±10.4 years, and 267 patients were male (75.4%) and 87 (24.6%) were female. Thoracotomy was performed in 258 (72.9%) patients and lung resection with the video-assisted thoracoscopic surgery technique in 96 (27.1%) patients. During the follow-up, complications were observed during the first 30 days in 78 (22.0%) of the patients and later in 9 (2.5%). Surgical mortality occurred in 11 patients (3.1%), and the rate of readmission to the intensive care unit was 5.6% (n=20).

Conclusion:

We consider that the control of the resection line with the active use of fiberoptic bronchoscopy during surgery is important for the prevention of the development of bronchial morbidity. Complications in the early period can be reduced by ensuring that the remaining bronchus is not narrowed, there are no residual stump structures that may disrupt the bronchial line, such as cartilage, and bronchial washing is frequently undertaken.
Interischial Spine Distance Is a Simple Index of the Narrow Pelvis That Can Predict Difficulty During Laparoscopic Low Anterior Resection
Authors: Ichikawa Nobuki , Homma Shigenori , Yoshida Tadashi , Emoto Shin , Imaizumi Ken , Matsui Hiroki , Tani Michio , Miyaoka Yoichi , Taketomi Akinobu
Published: October 2022

Background:

A narrow pelvis makes laparoscopic rectal resection difficult. This study aimed to evaluate whether a simple measurement on computed tomography can predict procedural difficulty.

Methods:

A total of 62 patients with low rectal cancer underwent conventional laparoscopic low anterior resection. The interischial spine (IS) distance (ie, the distance between the ischial spines) was measured on an axial computed tomography slice. The operative time, blood loss, and time from the insertion of linear staplers to completion of clamping on the distal end of the rectum (clamp time) were compared between patients with narrow or wide pelvises.

Results:

Overall, 42 men and 20 women with low rectal cancer were assessed. The mean tumor size was 34.5 mm. Total or tumor-specific mesorectal excisions were performed in all cases; high ligation and resection of the inferior mesenteric arteries were carried out in 92% of patients. The mean operative time and blood loss were 206 minutes and 15 mL, respectively. Four patients (6.5%) experienced postoperative complications, including 2 anastomotic leaks (3.2%). The mean IS distance was 93.3 mm. In simple linear regression analysis, a shorter IS distance correlated with a longer operative time (R
2=0.08, P=0.030) and the clamp time (R
2=0.07, P=0.046). Using a receiver operating characteristic curve, a narrow pelvis was defined as an IS distance <94.7 mm. Multivariate regression analysis revealed that an IS distance <94.7 mm (odds ratio: 3.51; P=0.04) was independently associated with a longer clamp time.

Conclusions:

The IS distance is a simple and useful measurement for predicting the difficulty of laparoscopic low anterior resection.
Compliance with education on evidence-based oral hygiene principles among dental students and staff: a best practice implementation project
Authors: Alizadeh Mahasti , Nastarin Parastou , Talebpour Amin
Published: October 2022

Objectives:

This study aims to assess compliance with evidence-based criteria regarding oral hygiene principle education provided for children and adolescents in the Tabriz Faculty of Dentistry.

Introduction:

Oral health problems might lead to lowering the quality of life amongst children and adolescents; so, providing education regarding oral health principles is of great importance.

Methods:

Eight audit criteria were assessed using the JBI Practical Application of Clinical Evidence System and Getting Research into Practice audit and feedback tool. Barriers were identified and dental students and staff were instructed by the team members and asked to educate children and adolescents referred to orthodontic department about oral hygiene practices. Changes in audit criteria were collected by direct observation and interview and reported using descriptive statistics.

Results:

In the follow-up phase, the percentage of patients who were advised to brush their teeth with fluoride toothpaste twice a day, floss daily, and seek regular dental check-ups increased, as compared with the baseline audit (37, 43 and 33%, respectively). Professional fluoride application, fissure sealant and individualized intervention and/or prevention treatment plans increased by 30, 35 and 15%, respectively in the follow-up phase; while advice on diet and risks of alcohol, tobacco and smoking increased by 93%.

Conclusion:

The use of standard clinical audit tools in dentistry wards causes improvement in the compliance with providing oral hygiene principle instructions among dental students and staff. Standard tools can increase the effectiveness of corrective interventions by identifying weaknesses in the patient care process correctly.
Compliance with best practice recommendations for colonoscopy bowel preparation among hospitalized patients at a tertiary adult hospital
Authors: Ullah Hamid , Chima Charles C.
Published: October 2022

Introduction:

Proper bowel preparation is essential to successful colonoscopies. The quality of bowel preparation is often poorer in the inpatient settings compared with outpatient settings. This can result in repeat procedures and increased hospital length of stay.

Objective:

The aim of this evidence implementation project was to assess and improve compliance with best practice recommendations for bowel preparation prior to colonoscopy.

Methods:

The project was done in three phases for patients hospitalized at a tertiary adult hospital: the initial audit; clinical practice change that included providing patients with both oral and written education about bowel preparation; and a follow-up audit.

Results:

The baseline audit showed that the hospital was already fully compliant with two out of four best practice criteria. For two criteria with poor compliance rates at baseline, we improved compliance for criterion 1 (giving patients both oral and written education about bowel preparation) from 8 to 40%, while compliance rate for criterion 4 [using 2 l polyethylene glycol – (PEG) or adding ascorbic acid to 4 l PEG] remained at 0% at the end of the intervention.

Conclusion:

The JBI evidence implementation program provided a structured approach to analyze colonoscopy bowel preparation practices and develop strategies to align policies with the best practice recommendation of providing written education about bowel preparation. However, there is need for more conclusive evidence to identify the most ideal inpatient bowel preparation formulation.
Engaging in word recognition elicits highly specific modulations in visual cortex
Authors: White Alex L. , Kay Kendrick , Tang Kenny , Yeatman Jason D.
Published: October 2022

A person’s cognitive state determines how their brain responds to visual stimuli. The most common such effect is a response enhancement when stimuli are task-relevant and attended rather than ignored. In this fMRI study, we report a surprising twist on such attention effects in the visual word form area (VWFA), a region that plays a key role in reading. We presented participants with strings of letters and visually similar shapes which were either relevant for a specific task (lexical decision or gap localization) or ignored (during a fixation dot color task). In the VWFA, the enhancement of responses to attended stimuli occurred only for letter strings, whereas the shapes evokedsmallerresponses when attended than when ignored. The enhancement of VWFA activity was accompanied by strengthened functional connectivity with higher-level language regions. These task-dependent modulations of response magnitude and functional connectivity were specific to the VWFA and absent in the rest of visual cortex. We suggest that language regions send targeted excitatory feedback into the VWFA only when the observer is trying to read. This feedback enables the discrimination of familiar and nonsense words, and is distinct from generic effects of visual attention.
Coupled functional physiological phenotyping and simulation model to estimate dynamic water use efficiency and infer transpiration sensitivity traits
Authors: Sun Ting , Cheng Rui , Sun Yudong , Jiang Rujia , Wang Zhuoyi , Fang Pingping , Wu Xinyang , Ning Kang , Xu Pei
Published: October 2022

As agricultural drought becomes more frequent worldwide, it is essential to improve crop productivity whilst reducing the water consumption to achieve a sustainable production. Plant transpiration rate and water use efficiency (WUE) collectively determine the yield performance, yet it is challenging to balance the two in breeding programs due to still insufficient mechanistic understanding of the traits. Here we demonstrate the feasibility and effectiveness of calculating dynamic and momentary WUE by coupling WUE model and the state-of-the-art functional physiological phenotyping (FPP). We also present the method of quantifying genotype-specific traits reflecting sensitivity of transpiration to radiation (STr-Rad) and vapor pressure deficit (STr-VPD), under evolving developmental stage and water availability. Using these methods, we revealed the genotypic difference of STr-Radand STr-VPDin three watermelon accessions, the dramatic change in each of them across the drought treatment phases, and the quantitative impacts of them on dynamic WUE patterns. Based on our results and computational simulations, a general principle for transpiration ideotype design is proposed, which highlights the benefits of lowering STr-VPDto increase WUE and increasing STr-Radto offset the decline of Tr. FPP-enabled phenomic selection will help screen for elite crops lines with desired transpiration sensitivities.
Structural surfaceomics reveals an AML-specific conformation of Integrin-β2 as a CAR-T therapy target
Authors: Mandal Kamal , Wicaksono Gianina , Yu Clinton , Adams Jarrett J. , Hoopmann Michael R. , Temple William C. , Escobar Bonell Patiño , Gorelik Maryna , Ihling Christian H. , Nix Matthew A. , Naik Akul , Ramos Emilio , Kasap Corynn , Steri Veronica , Serrano Juan Antonio Camara , Salangsang Fernando , Phojanakong Paul , McMillan Melanie , Gavallos Victor , Leavitt Andrew D. , Sinz Andrea , Huang Benjamin J. , Stieglitz Elliot , Smith Catherine C. , Moritz Robert L. , Sidhu Sachdeva S. , Huang Lan , Wiita Arun P.
Published: October 2022

Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here, we explore the hypothesis that tumor cells express cancer-specific surface protein conformations, invisible to standard target discovery pipelines evaluating gene or protein expression, that can be identified and immunotherapeutically targeted. We term this strategy, integrating cross-linking mass spectrometry (XL-MS) with glycoprotein surface capture, “structural surfaceomics”. As a proof of principle, we apply this technology to acute myeloid leukemia, a hematologic malignancy with dismal outcomes and no known optimal immunotherapy target. We identify the activated conformation of integrin-β2 as a structurally-defined, widely-expressed, AML-specific target. We develop and characterize recombinant antibodies to this protein conformation, and show that chimeric antigen receptor (CAR) T-cells eliminate AML cells and patient-derived xenografts without notable toxicity versus normal hematopoietic cells. Our findings validate an AML conformation-specific target antigen while demonstrating a toolkit for applying these strategies more broadly.