bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive treatment of Cronkhite-Canada syndrome: A case report and literature review
Authors: Hu Hailong , Wu Yating , Zhang Yaqin , Zhang Li , Zhang Jianfa , Zhang Rui
Published: February 2023

Introduction:

Cronkhite-Canada syndrome (CCS) is currently considered to be a non-hereditary disease, which is relatively rare clinically. It is also known as polyposis hyperpigmentation alopecia nail dystrophy syndrome, it is a syndrome characterized by gastrointestinal polyposis and ectodermal changes, the main manifestations are gastrointestinal symptoms, skin pigmentation, alopecia, and hypothyroidism.

Case presentation:

In this paper, the clinical characteristics, diagnosis and treatment of a case of CCS admitted to Huanghe Sanmenxia Hospital were analyzed. In the course of treatment, traditional Chinese medicine was used, but no hormone, and the patient’s clinical symptoms were greatly relieved.

Conclusions:

CCS is rare, there is no specific treatment, and traditional Chinese medicine may can greatly relieve the clinical symptoms of patients. However, it’s still having to be verified by a large sample, multi-center, long-term treatment follow-up studies.
Brown tumor of the cervical spine with primary hyperparathyroidism: A case report and literature review
Authors: Liu Zirui , Yang Hao , Tan Hongyu , Song Ruipeng , Zhang Yang , Zhao Liang
Published: February 2023

Rationale:

Brown tumor (BT), an uncommon focal lytic bone tumor, is a non-neoplastic and reactive process caused by increased osteoclastic activity and fibroblastic proliferation in primary or secondary hyperparathyroidism. Vertebral tumor causing neural compression is relatively rare, especially in the cervical spine.

Patient concerns:

A 29-year-old man developed neck pain and arm radicular pain 4 months ago, with the level of serum calcium significantly higher than normal. Computed tomography scan of the cervical spine revealed an expansile lytic lesion occupying the C6 body, left pedicle, and left lamina of C5–6.

Diagnoses:

Osteoclastoma according to imaging and histopathological results.

Interventions:

A laminectomy of C5–6 was performed.

Outcomes:

One month later, he was re-hospitalized due to nausea and vomiting and the serum calcium, was still, kept at a high level. Additionally, the parathormone (PTH) was greatly higher than normal. BT with primary hyperparathyroidism due to the parathyroid tumor was considered. After the surgery of the right parathyroid gland was performed, serum calcium and PTH both decreased, and computed tomography showed good recovery.

Lessons:

BTs might be misdiagnosed as other giant cell tumors, thus when giant cell tumors are considered, serum calcium and PTH examination may be needed to exclude BTs.
Better survival and prognosis in SCLC survivors after combined second primary malignancies: A SEER database-based study
Authors: Wang Silin , Hu Sheng , Huang Shengfei , Su Lang , Guo Qiang , Wu Bo , Ye Jiayue , Zhang Deyuan , Zhang Yang , Zhang Wenxiong , Wei Yiping
Published: February 2023

With recent advances in treatment modalities, the survival time for patients with small cell lung cancer (SCLC) has increased, along with the likelihood of recurrence of a second primary tumor. However, patient treatment options and prognosis remain uncertain. This research evaluated the survival rates of patients with SCLC with a second malignancy, aiming to provide new insights and statistics on whether to proceed with more active therapy. SCLC patients were selected based on the Surveillance, Epidemiology, and End Results (SEER) database, updated on April 15, 2021. We defined those with SCLC followed by other cancers (1st of 2 or more primaries) in the sequence number as S-second primary malignant cancer (S-SPM). Those who had other cancers followed by SCLC (2nd of 2 or more primaries) were defined as OC-SCLC. We performed Kaplan–Meier survival analysis, life table analysis, univariate analysis, stratified analysis, and multiple regression analysis of patient data. We considered the difference statistically meaningful at P < .05. After selection, data for 88,448 participants from the SEER database was included in our analysis. The mean survival time for patients with S-SPM was 69.349 months (95% confidence interval [CI]: 65.939, 72.759), and the medium duration of survival was 34 months (95% CI: 29.900, 38.100). Univariate analysis showed that for overall survival, the hazard ratio (HR) of S-SPM was 0.367 (95% CI: 0.351, 0.383), which was 0.633 lower than that of patients with solitary SCLC and 0.606 lower than that of patients with OC-SCLC. For cancer-specific survival (CSS), the HR of S-SPM was 0.285 (95% CI: 0.271, 0.301), which was 0.715 lower than for patients with solitary SCLC and 0.608 lower than that for patients with OC-SCLC. Multiple regression analysis showed that the HR values of S-SPM were lower than those of patients with single SCLC and those with OC-SCLC, before and after adjustment for variables. Kaplan–Meier survival curves showed that patients with S-SPM had significantly better survival times than the other groups. The survival time and prognosis of patients with S-SPM were clearly superior to those with single SCLC and OC-SCLC.
SARS-CoV-2 seroprevalence among children in Latvia: A cross-sectional study
Authors: Sapronova Krista , Kaķe Rūta , Pavāre Jana , Grāvele Dagne , Šēla Ivita , Ērgle Estere , Isarova Dana , Grīnberga Zanda , Zavadska Dace
Published: February 2023

Coronavirus disease 2019 (COVID-19) is a major global health concern. In contrast to adults, the course of the disease has been observed to be mild or even asymptomatic in children. It is therefore both clinically and epidemiologically important to measure the seroprevalence in children and adolescents to discern the overall morbidity of the disease and to compare these findings with similar data collected globally. We conducted a cross-sectional study between March and July of 2022 at the Children Clinical University Hospital in Riga, Latvia, to evaluate the seroprevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Participants aged 0 to 18 years were enrolled during hospitalization for reasons other than COVID-19. The levels of SARS-CoV-2 spike protein and nucleocapsid antibodies were measured in blood samples. The possibility of transplacental antibody transport was evaluated by directly interviewing the mothers of participants aged 18 months and younger. Various demographic and epidemiological risk factors and their association with seroprevalence were analyzed. Positive SARS-CoV-2 nucleocapsid antibodies were designated the main criterion for seropositivity. Of 200 enrolled children, 173 were found to be seropositive, resulting in an overall seroprevalence of 86.5%. The highest seroprevalence was detected in children and adolescents aged 12 to 18 years. With the progression of the COVID-19 pandemic, the seroprevalence in children has increased significantly. We found that almost 1-third of seropositive children in our study population were unaware of being previously infected with SARS-CoV-2 due to an asymptomatic course of the disease. Our study findings pertaining to high seropositivity among children and adolescents might be beneficial for public authorities to adapt epidemiological strategies and prevention measures. The high seroprevalence rate reported here and in many other populations around the world suggests that COVID-19 will likely become one of the many seasonal viral infections.
Personalized downstaging treatment with ADT, chemotherapy and add-on zimberelimab for very-high-risk clinically localized prostate cancer: A case report
Authors: Li Jie , Gu Tengfei , Hu Shengping , Wang Liang , Chen Ting
Published: February 2023

Rationale:

Very-high-risk prostate cancer (PCa) is associated with poor prognosis. Radical prostatectomy (RP) is an option for selected high-risk PCa cases, especially in younger, healthier patients. However, a high Gleason score and high T stage can increase the risk of RP. Neoadjuvant therapy has been reported in high- or very-high-risk PCa, but its clinical use remains controversial.

Diagnoses and patient concerns:

A 53-year-old male patient diagnosed with PCa was referred to our hospital. The patient’s Gleason score was 4 + 5, and the clinical stage was T4N0M0, with an abnormally enlarged prostate adhering to the rectum and leading to decreased mobility of the rectum, suggesting a very-high-risk PCa inappropriate for RP. However, instead of external beam radiation therapy, which is the standard treatment for inoperable PCa, the patient insisted on RP.

Interventions:

Androgen deprivation therapy plus docetaxel was chosen as the first downstaging treatment; however, the tumor was too slightly downsized to undergo RP. Therefore, zimberelimab was added after confirmation of a genomic feature of high microsatellite instability and high tumor mutational burden status.

Outcomes:

After 4 doses of zimberelimab, the prostate shrank significantly. The patient successfully completed RP after another dose of zimberelimab, and achieved a pathological complete response (pCR).

Lessons:

Our case represents a successful attempt at personalized treatment and provides preliminary evidence for the clinical use of downstaging therapy of androgen deprivation therapy, chemotherapy, and add-on zimberelimab for very-high-risk clinically localized PCa.
Primary acinic cell carcinoma of the trachea: A case report and literature review
Authors: Yang Mai-Qing , Wang Zhi-Qiang , Li Xiu-Feng , Chen Li-Qian , Zhang Hai-Ning , Zhang Ke-Xin , Xu Hong-Tao
Published: February 2023

Rationale:

Salivary gland-type acinic cell carcinoma (ACC) is a low-grade malignancy. Primary ACC of the trachea and lungs is rare; here, we describe 1 such case. The histological morphology of tracheal ACC was similar to that of its salivary gland-associated equivalent. Because of its rarity, it is easily misdiagnosed as another type of tracheal or lung tumor. Microscopic analysis of pathological features and immunohistochemistry help diagnose primary ACC of the trachea and lungs.

Patient concerns:

A 33-year-old female complained of shortness of breath and hemoptysis for 2 years, and reported the symptoms to have aggravated over the last 4 months. The patient was admitted to our hospital for further treatment. Enhanced computed tomography revealed a soft tissue density nodule shadow in the trachea, which was approximately 1.3 × 1.2 cm in size.

Diagnoses:

Based on the clinical information, morphological features, and immunohistochemistry, the pathological diagnosis was primary ACC of the trachea.

Intervention:

The tracheal lesion was resected with an electric snare, electrotomy, freezing, and an argon knife using a rigid bronchoscope.

Outcomes:

The patient’s postoperative course was uneventful.

Lessons:

It is important to prevent misdiagnosis of this type of tumor as another type of lung tumor. Morphological and immunohistochemical features can be useful in diagnosing primary ACC of the trachea and lungs.
Two-stage revision of infected hip prosthesis after post-operative antibiotic therapy: An observational study
Authors: Taheriazam Afshin , Saeidinia Amin
Published: February 2023

Infection is a major threatening side effect after total hip arthroplasty (THA) that its management is so difficult and is accompanied by different complications. The aim of this study was to determine the outcomes of patients underwent 2-staged THA after a course of antibiotic therapy. It was an observational prospective study performed during 2009 and 2019. We managed 51 patients with infected THA using a method in which antibiotic prophylaxis was performed after THA. We followed the same protocol for treatment of patients included 2-staged revision: in first stage, removal of infected instruments were performed and insertion of a hand-made antibiotic-cement spacer was done until erythrocyte sedimentation rate and CRP were normalized. In second stage, an un-cemented prosthesis was re-implanted in femoral side and post-operative IV antibiotic were administered for a week. Patients were monitored for about 15 months. Data were analyzed. There were 3 patients developed recurrent infection required girdlestone due to the aging. One of them needed to remove implant and 2 other with 3 times of re-infection were treated by antibiotic therapy. Other 10 cases were treated first by re-changing the cement. The rate of successful treatment was 78.4% (40 of 51) after the primary surgery and antibiotic therapy. This rose to 92.1% (47 of 51) following more debridement and antibiotic therapy. The merging of staged surgical debridement, using spacer of cement-antibiotic and re-implant beside 1-week intravenous antibiotic therapy, leaded to appropriate early outcomes in this series.
Meta-analysis of the occurrence of hepatocellular carcinoma after the treatment of entecavir and tenofovir for chronic hepatitis B
Authors: Tang Kaiyue , Cheng Huizhen , Wang Haiyan , Guo Yueping
Published: February 2023

Background:

Tenofovir and Entecavir are recommended as the first-line medicine of treatment for chronic hepatitis B. The occurrence of hepatocellular carcinoma after the treatment of chronic hepatitis B is a major problem. For the time being it is still unclear whether there remains a difference in risk correlation of hepatocellular carcinoma after the treatment of Tenofovir and Entecavir for chronic hepatitis B. Since previous studies have raised different ideas, this article aims to come to a conclusion targeting such a topic through analyzing the latest data.

Methods:

We searched some databases, such as PubMed, Web of Science, and Cochrane Library, for related studies on patients with chronic hepatitis B receiving the treatment of Tenofovir and Entecavir and then developing hepatocellular carcinoma. The search time was set to begin from the establishment time of the above-mentioned databases to May 2022. Two researchers were designated to screen the literature independently according to the inclusion and exclusion criteria set in this study; they then evaluated the quality of the literature included and extracted the data. Revman 5.3 software was used for meta-analysis.

Results:

After screening the literature, a total of 20 pieces of cohort study literature conformed to the inclusion criteria. Among which were 62,860 cases of patients receiving Entecavir, and 27,544 cases of patients receiving Tenofovir; there were 3669 cases with the occurrence of hepatocellular carcinoma in the Entecavir group and 1089 cases with the occurrence of hepatocellular carcinoma in Tenofovir group. The result of Meta analysis of these 20 pieces of literature shows that compared with the Tenofovir group, the Entecavir group has a lower occurrence rate of hepatocellular carcinoma, and the difference is statistically significant. The results are expressed as odd ratio (OR) and 95% confident interval (95%CI), (OR = 1.66, 95%CI: 1.35–2.05, P < .05). The result of Meta analysis of 10 studies related to Korea shows that the occurrence rate of hepatocellular carcinoma in the Tenofovir group is lower than that of the Entecavir group, and the difference is statistically significant (OR = 1.59, 95%CI: 1.29–1.95, P < .05). The result of meta-analysis of 5 studies related to China shows that the occurrence rate of hepatocellular carcinoma of Tenofovir group is lower than that of Entecavir group, and the difference is statistically significant (OR = 2.35, 95%CI: 1.15–4.81, P < .05).

Conclusion:

The occurrence rate of hepatocellular carcinoma after the treatment of tenofovir for chronic hepatitis B is lower than that of the treatment of entecavir.
Diffusion tensor tractography of the corticobulbar tract in a dysphagic patient with progressive supranuclear palsy: A case report
Authors: Han In Jun , Kwon Hyeok Gyu , Lee Woong-Woo , Yoon Ra Gyoung , Choi Hyoseon , Kim Hyun Jung
Published: February 2023

Rationale:

This paper reports the changes over time in the corticobulbar tract (CBT) analyzed using diffusion tensor tractography (DTT) in a dysphagic patient with progressive supranuclear palsy (PSP).

Patient concerns:

A 53-year-old man initially presented with dysarthria, gait disturbance, and bradykinesia, and approximately 1-year later, downward gaze paralysis appeared. Initially, there was no dysphagia; however, approximately 2 years after visiting the hospital, symptoms of dysphagia, including difficulty swallowing pills, aspiration, and oral movement impairments appeared. The symptoms gradually progressed, and finally, mouth opening was severely damaged to the extent that it was difficult to orally feed.

Interventions:

We performed diffusion tensor imaging 3 times; at 3-month, 20-month, and 41-month from onset.

Outcomes:

On 3-month DTT, the left CBT was well reconstructed, whereas the right CBT showed partial tearing. In the 20-month DTT, both CBTs became thinner compared to the 3-month DTT. On 41-month DTT, both CBTs became much thinner than after 3-month and 20-month DTT.

Lessons:

We observed the degree of CBT injury over time in a dysphagic patient with PSP. These results suggest that the analysis of CBT using DTT is helpful in predicting the degree of dysphagia and prognosis in patients with PSP.
Femoral head cartilage reconstruction using autologous osteochondral mosaicplasty: A case report
Authors: Lee Hyeonjoon , Kim Hyoung Tae , Jo Suenghwan
Published: February 2023

Rationale:

Cartilage injuries of the femoral head may occur following hip dislocation. As a rare injury, controversy persists regarding ideal treatment of damaged femoral head cartilage. Here we report the case of a patient who developed a large cartilage injury to the femoral head following anterior hip dislocation for which autologous osteochondral mosaicplasty with a graft harvested from the ipsilateral femoral head achieved a satisfactory outcome.

Patient concerns:

A 62-year-old man developed a right hip dislocation after a fall from a 5-m height and was referred to our institution.

Diagnoses:

The initial diagnosis was anterior hip dislocation. Upon hip joint reduction, a simple radiograph and computed tomography scan showed a large cartilage defect in the superolateral region of the femoral head. Multiple bony fragments were visible within the joint.

Interventions:

The hip joint was surgically dislocated. The large cartilage defect of the femoral head was treated with autologous mosaicplasty using an osteochondral autograft transfer system using multiple osteochondral plugs retrieved from a non-weight-bearing portion of the ipsilateral femoral head.

Outcomes:

Diagnostic hip arthroscopy performed at 8 months postoperative confirmed full incorporation of the osteochondral graft into the native femoral head. At the 2-year follow-up, the patient was pain-free, had a normal range of motion and displayed no evidence of osteoarthritis.

Lessons:

Isolated femoral head cartilage injuries may occur as a consequence of anterior hip dislocation. A femoral head with a large irregular cartilage defect can be treated with mosaicplasty using an osteochondral autograft from a non-weight-bearing portion of the ipsilateral femoral head.
The potential role of vitamin E in patients with glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis
Authors: Abdelwahab Omar Ahmed , Akil Khaled , Seif Ali , Allam Mahmoud , Sherif Mohamed El-Sebaey , Al-Alfy Mohamed N.
Published: February 2023

Background:

As an antioxidant, vitamin E (VitE) may benefit the erythrocytes by protecting glutathione from oxidation by free radicals and peroxide-generating processes.

Methods:

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines when reporting this systematic review. We searched 6 electronic databases (PubMed, Scopus, Web of Science, and Cochrane Library) until May 8, 2022. We included all relevant studies. According to the study design, the Cochrane assessment tool (Risk of Bias 2), Risk Of Bias In Non-randomized Studies - of Interventions checklists, and National Institutes of Health tools were used to assess the risk of bias.

Continuous data were pooled as a mean difference (MD) with a relative 95% confidence interval. The protocol was registered on PROSPERO (CRD42022333848).

Results:

Six studies were included in the meta-analysis with a total of 181 patients. Compared with the control group, VitE significantly improved the hemoglobin level for chronic hemolysis (MD = 2.72 g/dL, P < .0001) and for acute hemolysis (MD = 1.18 g/dL, P < .0001). It also decreased the reticulocyte level for chronic hemolysis (MD = −1.39 P < .0001) and for acute hemolysis (MD = −1.42%, P < .0001). For before and after studies, the use of VitE significantly improved the level of packed cell volume (MD = 0.56%, P < .00001), red blood cell half-life (MD = 2.19 days, P < .0001), and decreased the reticulocytes level (MD = −1.41%, P < .00001).

Conclusion:

Among patients with glucose-6-phosphate dehydrogenase deficiency, VitE might provide benefits such as increasing the hemoglobin, packed cell volume levels, red blood cell half-life, and decreasing the reticulocyte level, so reducing hemolysis. Further high-quality, well-designed randomized controlled trials are recommended.
Bone cemented K-wire fixation versus elastic stable intramedullary nailing fixation of paediatric proximal humerus fractures: A prospective cohort study
Authors: Liu Shibo , Zhang Yanlong , Cao Jinchao , Fu Shijie , Peng Aqin
Published: February 2023

Background:

The objective of this study is to compare the treatments of pediatric displaced proximal humerus fractures with external-fixation technique using the combination of K-wires and bone-cement versus close reduction and internal fixation technique using elastic stable intramedullary nail.

Methods:

From April 2016 to March 2020, 72 children with proximal humeral fractures were allocated to group A and 44 children with proximal humeral fractures were allocated to group B. Patients in group A were treated with bone-cemented K-wire fixation, and patients in group B were treated with elastic stable intramedullary nailing. The function of the upper limb was assessed using the Shortened Version of the Disabilities of the Arm, Shoulder and Hand questionnaire and Neer score. Patient satisfaction was assessed using the 10-cm visual analogue scale.

Results:

Bone healing was achieved in group A and B after a mean time of 6.1 ± 1.2 and 6.4 ± 1.1 weeks, respectively. The mean surgical time of groups was 33 ± 9 and 54 ± 12 minutes, respectively. The mean Quick Disabilities of the Arm, Shoulder and Hand questionnaire score of groups were 0.5 ± 1.4 and 0.7 ± 1.5, respectively. Based on Neer score, we obtained 69 excellent and 3 good results in group A, and 41 excellent and 3 good results in group B. There were significant differences regarding duration of operation, cost of treatment, and postoperative angle at bone healing (P < .05).

Conclusions:

The external cemented K-wire fixation is a useful and reliable alternative technique for the treatment of severely displaced proximal humerus fractures in children. The technique is a minimally invasive procedure with minimal complications.
Distal femur nonunion: Risk factors and validation of RUST scores
Authors: Graf Ryan M. , Shaw Jordan T. , Simske Natasha M. , Siy Patricia N. , Siy Alexander B. , Kliethermes Stephanie A. , Whiting Paul S.
Published: February 2023

Objectives:

(1) The purpose of this study was to investigate immediate postoperative weight-bearing status and other potential risk factors for nonunion after locked plating of distal femur fractures and (2) to compare clinical and radiographic union using the previously validated Radiographic Union Scale for Tibia (RUST) and modified RUST scores.

Design:

This is a retrospective cohort analysis.

Setting:

Academic Level-1 trauma center.

Patients/Participants:

Ninety patients with distal femur fractures (OTA/AO 33-A, including periprosthetic) treated with lateral locked plating over a 10-year period.

Intervention:

Distal femur fracture fixation with lateral locked plating; surgical intervention to facilitate bone healing in cases of nonunion.

Main Outcome Measurements:

Nonunion rate, construct rigidity scores, RUST, and modified RUST scores.

Results:

Seventy-eight of 90 patients (87%) achieved clinical union (13% nonunion rate). Rigidity score was significantly associated with risk of nonunion (P = 0.003). No significant association was detected between nonunion and postoperative weight-bearing status (P = 0.77) or other previously identified risk factors. Patients who achieved fracture union had significantly higher mean (SD) RUST (10.67 [1.37] vs. 6.53 [1.48], P < 0.001) and modified RUST (13.47 [2.20] vs. 6.94 [1.79], P < 0.001) scores than patients who developed nonunion. Sensitivity (Sn) analyses identified a RUST score threshold of 9 for diagnosing clinical union (Sn 93.6% and specificity [Sp] 91.7%) and a modified RUST score threshold of 8 (Sn 93.6%, Sp 91.7%).

Conclusions:

Immediate postoperative weight-bearing status does not seem to affect nonunion rates. We observed a statistically significant association between rigidity score and nonunion. This study supports the utility of the RUST and modified RUST scores in distal femur metaphyseal fractures.

Level of Evidence:

Therapeutic Level IV.
ACTH-Secreting Renal Neuroendocrine Tumor on 68Ga-DOTATATE PET/CT
Authors: Xu Si , Liu Yang , Zhou Jinxin , Zhang Yifan
Published: February 2023

Adrenocorticotropic hormone (ACTH)–secreting renal neuroendocrine tumor (NET) is extremely rare. A left renal mass was detected on ultrasound in a 26-year-old patient with ACTH-dependent Cushing syndrome. The lesion demonstrated slightly high density and moderate uptake of radiotracer on 68Ga-DOTATATE PET/CT, suspected to be a NET. Renal vein sampling revealed excessive ACTH secretion from the left kidney. Histopathological examination after surgery finally confirmed the diagnosis of a functioning renal NET.
Proposed MIBG Scan–Based Tumor Response Criteria of High-Specific-Activity 131I-MIBG Therapy in Metastatic Pheochromocytoma/Paraganglioma
Authors: Lu Yang , Xu Guofan , Jimenez Camilo
Published: February 2023

High-specific-activity 131I-MIBG (Azedra) is the only Food and Drug Administration–approved therapy for metastatic pheochromocytomas and paragangliomas, which are rare neuroendocrine tumors with limited treatment options. Based on our experience, we proposed here functional imaging-based tumor response criteria for these patient cohorts. Each response category was illustrated with typical sample cases, and clinical correlation was provided.
Caregiving and Friendship
Authors: Madden Elizabeth B. , Therrien Michelle , Bislick Lauren , Wallace Sarah E. , Goff-Albritton Rachel , Vilfort-Garces Ana , Constantino Christopher , Graven Lucinda
Published: February 2023

Friendship is an essential component of quality of life. The ongoing lifestyle changes and strain typically experienced by care partners of people with aphasia (PWA) can impact their social network, with friendships being particularly vulnerable to change. This study aimed to understand the impact of caregiving on care partners' friendships over time from the perspective of care partners of PWA. An online survey addressing care partners' demographics, care recipients' demographics, and care partners' perceptions of their friendships over time (before caregiving and during the acute and chronic stages of caregiving) was codesigned with three care partner stakeholders and then distributed to other individuals who care for a person with aphasia. Survey responses from 35 care partners of PWA who completed the survey were analyzed using quantitative and qualitative methods. Most participants reported their friendships were different in both the acute and chronic stages of caregiving compared with before caregiving. Overall, perceived friendship satisfaction and support decreased over time. Qualitative analysis revealed five main factors that could either facilitate or hinder care partner friendships, including role changes, personal characteristics, friendship initiation, friendship interactions, and outside influences. This work highlights that caring for a loved one with aphasia negatively impacts friendships for many care partners, and these friendship changes are often long-lasting. More resources for managing the impact of aphasia on care partners' social lives are needed, which, in turn, might improve the friendships and well-being of both the care partner and their loved one with aphasia.
Stakeholder-Engaged Research
Authors: Strong Katie A. , Douglas Natalie F. , Johnson Rebecca , Silverman Maura , Azios Jamie H. , Archer Brent
Published: February 2023

There is a need for intervention to support friendship for people living with aphasia. The purpose of this article is to describe a stakeholder engagement process that involved researchers, clinicians, people living with aphasia, and care partners to inform such intervention. Through reflection and firsthand accounts of non–university-based researchers, people not typically represented in the research process, we share details of two main lessons learned throughout the stakeholder engagement journey: (1) accessible engagement and (2) team correspondence. Finally, we describe experiences with use of the Social Convoy Model to support discussion and engagement about friendship and aphasia. We argue that this tool be a consideration in future intervention research in this area to support people with aphasia communicating their friendship priorities and goals. Although the richness of multistakeholder research teams has been documented, we hope that this article provides detail that is not commonly shared thus illuminating the process. We also hope to provide a transparent account of the cost and time required to ensure equity across stakeholder groups.
Posttraumatic Growth in People Living With Aphasia
Authors: Brancamp Tami U.
Published: February 2023

The purpose of this original essay is to describe the process of developing a stakeholder-engaged research (SER) team with people who have aphasia. The SER process is described through the lens of posttraumatic growth and depreciation in aphasia. This article describes the process of modifying the Posttraumatic Growth and Depreciation Inventory (PTGI-42; Baker et al., 2008
;
Cann et al., 2010) with a multistakeholder research team so that individuals with aphasia may have a greater opportunity to be included in posttraumatic growth stroke outcome research. Posttraumatic growth is the positive psychological change that can be experienced as a result of the struggle with highly challenging life situations (Calhoun & Tedeschi, 2001) whereas posttraumatic depreciation is the inverse of growth, the negative aspects. To understand posttraumatic growth and depreciation in people living with aphasia, it is important that they be included in the research. To do so, we need to include people with aphasia in the research process and provide measurement tools that are aphasia friendly and accessible so that people with aphasia can participate in research and have their voices heard. This article describes the process, benefits, and challenges of stakeholder-engaged research.
New-onset refractory status epilepticus and febrile infection-related epilepsy syndrome
Authors: Sculier Claudine , Gaspard Nicolas
Published: February 2023

Purpose of review

The concept and understanding of new-onset refractory status epilepticus (NORSE), and its subtype with prior fever known as febrile infection-related epilepsy syndrome (FIRES) have evolved in the recent past. This review aims to summarize the recent developments in the pathophysiology, diagnosis and management of these challenging conditions.

Recent findings

NORSE and FIRES can have many different causes. Although the list of possible causes is still growing, they mostly fall in the categories of autoimmune encephalitis and genetic disorders. However, despite extensive investigations, most cases of NORSE and FIRES remain cryptogenic. Recent studies have pointed towards the key role of autoinflammation as a unifying pathophysiological mechanism in these cases. These findings also support the use of immunomodulatory treatment in this setting. Consensus recommendations on the management of NORSE and FIRES have recently been published.

NORSE and FIRES remain challenging conditions to diagnose and treat. Recent findings from clinical and basic research and new recommendations, reviewed in this article, contribute to an emerging framework for management and future research.
Urbanicity and alcohol use epidemiology in the 21st century
Authors: Castaldelli-Maia João Mauricio
Published: February 2023

Purpose of review

This review aimed to gather recent studies that could identify the specificities in the relationship between urbanization and alcohol use epidemiology in the current century.

Recent findings

Although we find lower rates of alcohol use among adolescents in urban environments than in rural ones, this difference tends to diminish until it disappears by the time they reach adulthood. In addition to excessive marketing and increased accessibility, several urban environment characteristics have been related to alcohol use. First, problematic alcohol use is linked to stress and mental health problems like depression and anxiety, which are common in metropolitan areas. Second, alcohol use behaviors are influenced by homelessness, loneliness, and deprivation in megacities, where female and male individuals have presented more similar alcohol use behaviors (i.e. gender convergence). Third, treatment levels for alcohol use disorders are very low.

There is a new epidemiological wave of alcohol consumption in large urban centers, largely influenced by advertisement and marketing. Social and psychological risk factors and subpopulations of interest were identified for preventive interventions in large urban centers (i.e. advertisement regulation). In addition, increasing the availability of treatment, including specific medications for alcohol use disorder, should be strongly encouraged.
Mucormycosis-causing fungi in humans: a meta-analysis establishing the phylogenetic relationships using internal transcribed spacer (ITS) sequences
Authors: Gunathilaka M. G. R. S. S. , Senevirathna R. M. I. S. K. , Illappereruma S. C. , Keragala K. A. R. K. , Hathagoda K. L. W. , Bandara H. M. H. N.
Published: February 2023

Introduction. Mucormycosis is a severe angio-invasive fungal infection caused by mucormycetes, a group of fungi that are ubiquitous in the environment. The incidence of mucormycosis has been surging rapidly due to the global corona virus disease 2019 (COVID-19) pandemic.

Gap Statement. The complete picture of the causative fungi associated with mucormycosis and their phylogenetic relationships are not well defined.

Aim. This meta-analysis aimed to collate all confirmed fungal pathogens that cause mucormycosis, and assess their taxonomic relationships.

Methodology. All types of articles in the PubMed database that report fungi as a cause of mucormycosis were reviewed. We summarized the fungal morphological characteristic up to the genus level. The internal transcribed spacer (ITS) nucleotide sequences of these fungi were retrieved from the National Center for Biotechnology Information (NCBI) and UNITE databases whenever available, and multiple sequence analysis was conducted using Clustal W. The phylogenetic tree was constructed using mega version 7.

Results. Forty-seven fungal species were identified as pathogens causing mucormycosis in humans. Thirty-two fungal species were phylogenetically grouped into three clades, and it was evident that the ITS sequences have well-conserved regions in all clades, especially from the 400th to 500th base pairs.

Conclusion. The findings of this work contribute to the descriptive data for fungi that cause mucormycosis, emphasizing the need for robust phylogenetic approaches when identifying clinical isolates from infected patients.
Sertraline has in vitro activity against both mature and forming biofilms of different Candida species
Authors: Rodrigues Daniel Sampaio , Cabral Vitória Pessoa de Farias , Barbosa Amanda Dias , Sá Lívia Gurgel do Amaral Valente , Moreira Lara Elloyse Almeida , de Andrade Neto João Batista , da Silva Cecília Rocha , de Moraes Manoel Odorico , Silva Jacilene , Marinho Emmanuel Silva , dos Santos Helcio Silva , da Costa Érica Rayanne Mota , Silveira Maria Janielly Castelo Branco , e Silva Larissa Holanda , Nobre Júnior Hélio Vitoriano
Published: February 2023

Candida spp. infections are a serious health problem, especially in patients with risk factors. The acquisition of resistance, often associated with biofilm production, makes treatment more difficult due to the reduced effectiveness of available antifungals. Drug repurposing is a good alternative for the treatment of infections by Candida spp. biofilms. The present study evaluated the in vitro antibiofilm activity of sertraline in reducing the cell viability of forming and matured biofilms, in addition to elucidating whether effective concentrations are safe. Sertraline reduced biofilm cell viability by more than 80 % for all Candida species tested, acting at low and safe concentrations, both on mature biofilm and in preventing its formation, even the one with highest virulence. Its preventive mechanism seemed to be related to binding with ALS3. These data indicate that sertraline is a promising drug with anticandidal biofilm potential in safe doses. However, further studies are needed to elucidate the antibiofilm mechanism and possible application of pharmaceutical forms.
Interpreting discordant SARS-CoV-2 diagnostic test results
Authors: Egbelowo Oluwaseun F. , Fox Spencer J. , Gibson Graham C. , Meyers Lauren Ancel
Published: February 2023

We introduce a model to interpret discordant SARS-CoV-2 test results and estimate that an individual receiving a positive rapid antigen test followed by a negative Nucleic Acid Amplification Test had only a 12-24% chance of being infected in the United States from March 2020 to May 2022.
Time warping between main epidemic time series in epidemiological surveillance
Authors: Morel Jean-David , Morel Jean-Michel , Alvarez Luis
Published: February 2023

The most common reported epidemic time series in epidemiological surveillance are the daily or weekly incidence of new cases, the hospital admission count, the ICU admission count, and the death toll, which played such a prominent role in the struggle to monitor the Covid-19 pandemic. We show that pairs of such curves are related to each other by a generalized renewal equation depending on a smooth time varying delay and a smooth ratio generalizing the reproduction number. Such a functional relation is also explored for pairs of simultaneous curves measuring the same indicator in two neighboring countries. Given two such simultaneous time series, we develop, based on a signal processing approach, an efficient numerical method for computing their time varying delay and ratio curves, and we verify that its results are consistent. Indeed, they experimentally verify symmetry and transitivity requirements and we also show, using realistic simulated data, that the method faithfully recovers time delays and ratios. We discuss several real examples where the method seems to display interpretable time delays and ratios. The proposed method generalizes and unifies many recent related attempts to take advantage of the plurality of these health data across regions or countries and time, providing a better understanding of the relationship between them. An implementation of the method is publicly available at theEpiInvertCRAN package.

Author summary

To monitor an epidemic, it is crucial to understand the relationship between the incidence of new cases, the hospital admission count, the ICU admission count, and the death toll time series. The relationship between any pair of such indicators can be formulated in terms of temporal delays and ratios which evolve across time. Given two such time series, we develop, based on a signal processing approach, an efficient numerical method for computing their time varying delay and ratio curves. Using realistic simulated data, we show that the method faithfully recovers time delays and ratios. In addition, we discuss several applications to real epidemic data where the method seems to output interpretable time delays and ratios. The obtained relationship between these epidemic time series is a key issue in epidemiological surveillance. The proposed technique provides a new tool to visualize, compare, and understand the evolution of key epidemiological time series. An implementation of the method is publicly available at theEpiInvertCRAN package.
A cell-level discriminative neural network model for diagnosis of blood cancers
Authors: Robles Edgar E. , Jin Ye , Smyth Padhraic , Scheuermann Richard H. , Bui Jack D. , Wang Huan-You , Oak Jean , Qian Yu
Published: February 2023

Motivation

Precise identification of cancer cells in patient samples is essential for accurate diagnosis and clinical monitoring but has been a significant challenge in machine learning approaches for cancer precision medicine. In most scenarios, training data are only available with disease annotation at the subject or sample level. Traditional approaches separate the classification process into multiple steps that are optimized independently. Recent methods either focus on predicting sample-level diagnosis without identifying individual pathologic cells or are less effective for identifying heterogeneous cancer cell phenotypes.

Results

We developed a generalized end-to-end differentiable model, the Cell Scoring Neural Network (CSNN), which takes the available sample-level training data and predicts both the diagnosis of the testing samples and the identity of the diagnostic cells in the sample, simultaneously. The cell-level density differences between samples are linked to the sample diagnosis, which allows the probabilities of individual cells being diagnostic to be calculated using backpropagation. We applied CSNN to two independent clinical flow cytometry datasets for leukemia diagnosis. In both qualitative and quantitative assessments, CSNN outperformed preexisting neural network modeling approaches for both cancer diagnosis and cell-level classification. Post hoc decision trees and 2D dot plots were generated for interpretation of the identified cancer cells, showing that the identified cell phenotypes match the cancer endotypes observed clinically in patient cohorts. Independent data clustering analysis confirmed the identified cancer cell populations.

Availability

The source code of CSNN and datasets used in the experiments are publicly available on GitHub and FlowRepository.

Contact

Edgar E. Robles:roblesee@uci.eduand Yu Qian:mqian@jcvi.org

Supplementary information

Supplementary data are available on GitHub and atBioinformaticsonline.
Computer Vision Identifies Recurrent and Non-Recurrent Ductal Carcinoma in situ Lesions with Special Emphasis on African American Women
Authors: Saatchi Yunus , Schanen Parker , Cheung Richard A. , Petty Howard R.
Published: February 2023

Although the existence of non-recurrent and recurrent forms of ductal carcinoma in situ (DCIS) of the breast are observed, no evidence-based test can make this distinction. This retrospective case-control study used archival DCIS samples stained with anti-phospho-Ser226-GLUT1 (glucose transporter type 1) and anti-phosphofructokinase type L (PFKL) antibodies. Immunofluorescence micrographs were used to create machine learning (ML) models of recurrent and non-recurrent biomarker patterns, which were evaluated in cross-validation studies. Clinical performance was assessed by holdout studies using patients’ whose data were not used in training. Micrographs were stratified by the recurrence probability of each image. Recurrent patients were defined by at least one image with a probability of recurrence>98% whereas non-recurrent patients had none. These studies demonstrated no false negatives, identified true positives, and uniquely identified true negatives. Roughly 20% of the microscope fields of recurrent lesions were computationally recurrent. Strong prognostic results were obtained for both Caucasian and African American women. Our machine tool provides the first means to accurately predict recurrent and non-recurrent patient outcomes. We suggest that at least some false positives were true positives that benefitted from surgical intervention. The intracellular locations of phospho-Ser226-GLUT1 and phosphofructokinase type L likely participate in cancer recurrences by accelerating glucose flux, a key feature of the Warburg Effect.
Benefits of near-universal vaccination and treatment access to manage COVID-19 burden in the United States
Authors: Yang Fuhan , Tran Thu Nguyen-Anh , Howerton Emily , Boni Maciej F , Servadio Joseph L
Published: February 2023

Background

As we enter the fourth year of the COVID-19 pandemic, SARS-CoV-2 infections still cause high morbidity and mortality in the United States. During 2020-2022, COVID-19 was one of the leading causes of death in the United States and by far the leading cause among infectious diseases. Vaccination uptake remains low despite this being an effective burden reducing intervention. The development of COVID-19 therapeutics provides hope for mitigating severe clinical outcomes. This modeling study examines combined strategies of vaccination and treatment to reduce the burden of COVID-19 epidemics over the next decade.

Methods

We use a validated mathematical model to evaluate the reduction of incident cases, hospitalized cases, and deaths in the United States through 2033 under various levels of vaccination and treatment coverage. We assume that future seasonal transmission patterns for COVID-19 will be similar to those of influenza virus. We account for the waning of infection-induced immunity and vaccine-induced immunity in a future with stable COVID-19 dynamics. Due to uncertainty in the duration of immunity following vaccination or infection, we consider two exponentially-distributed waning rates, with means of 365 days (one year) and 548 days (1.5 years). We also consider treatment failure, including rebound frequency, as a possible treatment outcome.

Results

As expected, universal vaccination is projected to eliminate transmission and mortality. Under current treatment coverage (13.7%) and vaccination coverage (49%), averages of 89,000 annual deaths (548-day waning) and 120,000 annual deaths (365-day waning) are expected by the end of this decade. Annual mortality in the United States can be reduced below 50,000 per year with >81% annual vaccination coverage, and below 10,000 annual deaths with >84% annual vaccination coverage. Universal treatment reduces hospitalizations by 88% and deaths by 93% under current vaccination coverage. A reduction in vaccination coverage requires a comparatively larger increase in treatment coverage in order for hospitalization and mortality levels to remain unchanged.

Conclusions

Adopting universal vaccination and universal treatment goals in the United States will likely lead to a COVID-19 mortality burden below 50,000 deaths per year, a burden comparable to that of influenza virus.