bluuebunny/crossref_metadata_2025 huggingface dataset:
Trophectoderm biopsy is associated with adverse obstetric outcomes rather than neonatal outcomes
Authors: Ji Hui , Zhang Mian-Qiu , Zhou Qiao , Zhang Song , Dong Li , Li Xiu-Ling , Zhao Chun , Ding Hui , Ling Xiu-Feng
Published: March 2023

Background

With the wide application of preimplantation genetic testing (PGT) with trophectoderm (TE) biopsy, the safety of PGT has always been a concern. Since TE subsequently forms the placenta, it is speculated that the removal of these cells was associated with adverse obstetrical or neonatal outcomes after single frozen-thawed blastocyst transfer (FBT). Previous studies report contradictory findings with respect to TE biopsy and obstetric and neonatal outcomes.

Methods

We conducted a retrospective cohort study including 720 patients with singleton pregnancies from single FBT cycles who delivered at the same university-affiliated hospital between January 2019 and March 2022. The cohorts were divided into two groups: the PGT group (blastocysts with TE biopsy, n = 223) and the control group (blastocysts without biopsy, n = 497). The PGT group was matched with the control group by propensity score matching (PSM) analysis at a ratio of 1:2. The enrolled sample sizes in the two groups were 215 and 385, respectively.

Results

Patient demographic characteristics were comparable between the groups after PSM except for the proportion of recurrent pregnancy loss, which was significantly higher in the PGT cohort (31.2 vs. 4.2%, P < 0.001). Patients in the PGT group had significantly higher rates of gestational hypertension (6.0 vs. 2.6%, adjusted odds ratio (aOR) 2.91, 95% confidence interval (CI) 1.18–7.18, P = 0.020) and abnormal umbilical cord (13.0 vs. 7.8%, aOR 1.94, 95% CI 1.08–3.48, P = 0.026). However, the occurrence of premature rupture of membranes (PROM) (12.1 vs. 19.7%, aOR 0.59, 95% CI 0.35–0.99, P = 0.047) was significantly lower in biopsied blastocysts than in unbiopsied embryos. There were no significant differences in regard to other obstetric and neonatal outcomes between the two groups.

Conclusions

Trophectoderm biopsy is a safe approach, as the neonatal outcomes from biopsied and unbiopsied embryos were comparable. Furthermore, PGT is associated with higher risks of gestational hypertension and abnormal umbilical cord but may have a protective effect on PROM.
Advanced tubal pregnancy at 34 weeks with eclampsia and HELLP syndrome: a case report and literature re
Authors: Liu Yang , Xu Xiaoping , Liu Qian , Luo Xiaolan , Cai Bin , He Jingyuan , Liu Ruiqian
Published: March 2023

Background

Tubal ectopic pregnancies in the late stages of pregnancy are uncommon, and reports on their complications are scarce. We present the case of a woman who had a tubal ectopic pregnancy at around 34 weeks and developed severe pre-eclampsia complications.

Case

A 27-year-old woman presented to our hospital several times with vomiting and convulsions. A physical exam revealed hypertension, scattered ecchymosis, and a large abdominal mass. A computed tomography (CT) scan performed in an emergency revealed an empty uterus, a stillbirth baby in the abdominal cavity, and a crescent-shaped placenta. Blood tests revealed that the patient had a low platelet count and clotting dysfunction. Laparotomy confirmed advanced right fallopian tube pregnancy without rupture, and salpingectomy was performed. Pathological examination revealed a significantly thickened tubal wall, adhesion of the placenta, and poor placental perfusion.

Conclusion

The unusually thickened muscular layer of the tube may be one of the reasons for tubal pregnancy progressing to an advanced stage. Placenta adhesion and the special site to which it is attached reduce the risk of rupture. The detection of a crescent-shaped placenta on imaging may aid in the accurate diagnosis, distinguishing between abdominal and tubal pregnancy. Women with advanced ectopic pregnancy are more likely to develop pre-eclampsia and have poorer maternal-fetal outcomes. These negative outcomes may be influenced by abnormal artery remodeling, villous dysplasia, and placental infarction.
Efficacy, safety and biomarker analysis of durvalumab in patients with mismatch-repair deficient or microsatellite instability-high solid tumours
Authors: Geurts Birgit S. , Battaglia Thomas W. , van Berge Henegouwen J. Maxime , Zeverijn Laurien J. , de Wit Gijs F. , Hoes Louisa R. , van der Wijngaart Hanneke , van der Noort Vincent , Roepman Paul , de Leng Wendy W. J. , Jansen Anne M. L. , Opdam Frans L. , de Jonge Maja J. A. , Cirkel Geert A. , Labots Mariette , Hoeben Ann , Kerver Emile D. , Bins Adriaan D. , Erdkamp Frans G.L. , van Rooijen Johan M. , Houtsma Danny , Hendriks Mathijs P. , de Groot Jan-Willem B. , Verheul Henk M. W. , Gelderblom Hans , Voest Emile E.
Published: March 2023

Background

In this study we aimed to evaluate the efficacy and safety of the PD-L1 inhibitor durvalumab across various mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) tumours in the Drug Rediscovery Protocol (DRUP). This is a clinical study in which patients are treated with drugs outside their labeled indication, based on their tumour molecular profile.

Patients and methods

Patients with dMMR/MSI-H solid tumours who had exhausted all standard of care options were eligible. Patients were treated with durvalumab. The primary endpoints were clinical benefit ((CB): objective response (OR) or stable disease ≥16 weeks) and safety. Patients were enrolled using a Simon like 2-stage model, with 8 patients in stage 1, up to 24 patients in stage 2 if at least 1/8 patients had CB in stage 1. At baseline, fresh frozen biopsies were obtained for biomarker analyses.

Results

Twenty-six patients with 10 different cancer types were included. Two patients (2/26, 8%) were considered as non-evaluable for the primary endpoint. CB was observed in 13 patients (13/26, 50%) with an OR in 7 patients (7/26, 27%). The remaining 11 patients (11/26, 42%) had progressive disease. Median progression-free survival and median overall survival were 5 months (95% CI, 2-not reached) and 14 months (95% CI, 5-not reached), respectively. No unexpected toxicity was observed. We found a significantly higher structural variant (SV) burden in patients without CB. Additionally, we observed a significant enrichment of JAK1 frameshift mutations and a significantly lower IFN-γ expression in patients without CB.

Conclusion

Durvalumab was generally well-tolerated and provided durable responses in pre-treated patients with dMMR/MSI-H solid tumours. High SV burden, JAK1 frameshift mutations and low IFN-γ expression were associated with a lack of CB; this provides a rationale for larger studies to validate these findings.

Trial registration

Clinical trial registration: NCT02925234. First registration date: 05/10/2016.
Intracranial efficacy and safety of furmonertinib 160 mg with or without anti-angiogenic agent in advanced NSCLC patients with BM/LM as salvage therapy
Authors: Xu Ziyi , Hao Xuezhi , Wang Qi , Yang Ke , Li Junling , Xing Puyuan
Published: March 2023

Objectives

Central nervous system (CNS) metastases including brain metastases (BM) and leptomeningeal metastases (LM) are frequent in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), and are correlated with poor outcomes. In this study, we evaluated the efficacy of single-agent furmonertinib 160 mg or combining with anti-angiogenic agent in NSCLC patients who had developed BM/LM progression from previous tyrosine kinase inhibior (TKI) treatment.

Methods

EGFR-mutated NSCLC patients who developed BM (the BM cohort) or LM progression (the LM cohort) were included, having received furmonertinib 160 mg daily as second-line or later treatment, with or without anti-angiogenic agents. The intracranial efficacy was evaluated by intracranial progression-free survival (iPFS).

Results

Totally 12 patients in the BM cohort and 16 patients in the LM cohort were included. Almost one half of patients in the BM cohort and a majority in the LM cohort had a poor physical status, with a Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥2. The administration of single-agent furmonertinib or combination treatment achieved a median iPFS of 3.6 months (95%CI 1.435–5.705) in the BM cohort, and 4.3 months (95%CI 2.094–6.486) in the LM cohort. Subgroup and univariate analysis has shown that a good ECOG-PS correlated with a favorable efficacy of furmonertinib in the BM cohort (median iPFS = 2.1 with ECOG-PS ≥ 2 vs. 14.6 months with ECOG-PS < 2, P < 0.05). Overall, any grade of adverse events (AEs) occured in 46.4% of patients (13/28). Among them, 14.3% of patients (4 of 28) had grade 3 or higher AEs, and were all under control, led to no dose reductions or suspension.

Conclusion

Single-agent furmonertinib 160 mg or in combination of anti-angiogenic agent is an optional salvage therapy for advanced NSCLC patients who developed BM/LM progression from prior EGFR-TKI treatment, with a promising efficacy and an acceptable safety profile, and is worth of further exploration.
Phase II clinical trial of sequential treatment with systemic chemotherapy and intraperitoneal paclitaxel for gastric and gastroesophageal junction peritoneal carcinomatosis - STOPGAP trial
Authors: Senthil Maheswari , Dayyani Farshid
Published: March 2023

Background

Studies from Asia indicate that normothermic intraperitoneal chemotherapy (NIPEC) may confer survival benefit in patients with gastric peritoneal carcinomatosis (PC). However, data regarding this approach is lacking in western population. The current STOPGAP trial is intended to assess 1-year progression-free survival benefit of sequential systemic chemotherapy and paclitaxel NIPEC in patients with gastric/ gastroesophageal junction (GEJ) adenocarcinoma PC.

Methods

This is a prospective, single center, single arm, phase II investigator-initiated clinical trial. Patients with histologically proven gastric/GEJ (Siewert 3) adenocarcinoma with positive peritoneal cytology or PC will be eligible to participate after three months of standard of care systemic chemotherapy and with no evidence of visceral metastasis on restaging scans. The primary treatment is iterative paclitaxel NIPEC with systemic paclitaxel and 5-fluorouracil, which will be administered on days1 and 8 and repeated every three weeks for 4 cycles. Patients will undergo diagnostic laparoscopy both before and after NIPEC to assess peritoneal cancer index (PCI). Patients with PCI less than or equal to 10 in whom complete cytoreduction (CRS) is feasible may opt to undergo CRS with heated intraperitoneal chemotherapy (HIPEC). The primary endpoint is 1-year progression free survival and secondary endpoints are overall survival and patient reported quality of life outcomes measured by EuroQol- 5 dimensions-5 level (EuroQol-5D-5L) questionnaire.

Discussion

If the sequential approach of systemic chemotherapy followed by paclitaxel NIPEC proves beneficial, then this approach could be used in larger, muti-institutional randomized clinical trial of gastric PC.

Trial Registration

The trial was registered on 21/02/2021, under clinical trials.gov; Identifier: NCT04762953.
Raltitrexed enhanced antitumor effect of anlotinib in human esophageal squamous carcinoma cells on proliferation, invasiveness, and apoptosis
Authors: Zhen Hongchao , Tian Jizheng , Li Guangxin , Zhao Pengfei , Zhang Ying , Che Juanjuan , Cao Bangwei
Published: March 2023

Background

Anlotinib is a multi-targeted receptor tyrosine kinase inhibitor (TKI) which has exhibited encouraging clinical activity in advanced non-small cell lung cancer (NSCLC) and soft tissue sarcoma. Raltitrexed is well known to be effective in the treatment of colorectal cancer in China. The present study aims to investigate the combinatory antitumor effect of anlotinib and raltitrexed on human esophageal squamous carcinoma cells and further explore the molecular mechanisms in vitro.

Methods

Human esophageal squamous cell lines KYSE-30 and TE-1 were treated with anlotinib or raltitrexed, or both, then cell proliferation was measured by MTS and colony formation assay; cell migration and invasion were detected by wound-healing and transwell assays; cell apoptosis rate was studied by flow cytometry and the transcription of apoptosis-associated proteins were monitored by quantitative polymerase chain reaction (qPCR) analysis. Finally, western blot was performed to check phosphorylation of apoptotic proteins after treatment.

Results

Treatment with raltitrexed and anlotinib showed enhanced inhibitory effects on cell proliferation, migration and invasiveness compared with raltitrexed or anlotinib monotherapy. Meanwhile, raltitrexed combined with anlotinib strongly increased cell apoptosis percentage. Moreover, the combined treatment down-regulated mRNA level of the anti-apoptotic protein Bcl-2 and invasiveness-associated protein matrix metalloproteinases-9 (MMP-9), while up-regulated pro-apoptotic Bax and caspase-3 transcription. Western blotting showed that the combination of raltitrexed and anlotinib could inhibit the expression of phosphorylated Akt (p-Akt), Erk (p-Erk) and MMP-9.

Conclusions

This study indicated that raltitrexed enhanced the antitumor effects of anlotinib on human ESCC cells by down-regulating phosphorylation of Akt and Erk, providing a novel treatment option for patients with esophageal squamous cell carcinoma (ESCC).
Diagnosis and management of ADHD: a pediatric perspective on practice and challenges in Switzerland
Authors: Zysset A. , Robin D. , Albermann K. , Dratva J. , Hotz S. , Wieber F. , von Rhein M.
Published: March 2023

Background

Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in childhood. In Switzerland, the complex diagnosis and treatment are being carried out by adolescent−/child psychiatrists, and pediatricians. Guidelines recommend a multimodal therapy for patients with ADHD. However, it has been questioned whether health professionals follow this approach or favor drug therapy. This study aims to provide insights into the practice of pediatricians in Switzerland regarding diagnosis and treatment of ADHD and their perceptions of these processes.

Method

An online survey (self-report) about current practices of diagnosis and management as well as challenges regarding ADHD was distributed to office-based pediatricians in Switzerland. One hundred fifty-one pediatricians participated. Results show that therapy options were almost always discussed with parents and older children. Exchange with parents (81%) and level of child’s suffering (97%) were central when selecting therapy options.

Results

Therapies about which pediatricians informed most often were: pharmacological therapy, psychotherapy, and multimodal therapy. Challenges voiced were the subjectivity of diagnostic criteria and dependence on third parties, low availability of psychotherapy, and a rather negative public attitude towards ADHD. Needs that were expressed were further education for all professionals, support for coordination with specialists and schools as well as improvement of information on ADHD.

Conclusions

Pediatricians do consider a multimodal approach when treating ADHD and take the families` and children’s opinions into account. Improvements of the availability of child and youth psychotherapy, the strengthening of the interprofessional cooperation with therapists and schools, and efforts to increase public knowledge about ADHD are proposed.
Probable enterotoxin-associated toxic shock syndrome caused by Staphylococcus epidermidis
Authors: Pomputius William F. , Kilgore Samuel H. , Schlievert Patrick M.
Published: March 2023

Background

We describe a case of a toxic shock-like syndrome in a child, which was associated with Staphylococcus epidermidis instead of Staphylococcus aureus or Streptococcus pyogenes, the usual causes of toxic shock syndrome.

Case presentation

The patient was an 8-year-old boy who developed a toxic shock syndrome-like illness, including fever, hypotension, and rash. The Staphylococcus epidermidis isolate was cultured from urine, but this organism was unavailable for toxin testing. Multiple blood cultures were negative. Instead, a highly novel assay was used on acute plasma from the patient which demonstrated the presence of the genes for superantigens, staphylococcal enterotoxins A, C, D, and E. Superantigens are the known causes of toxic shock syndrome.

Conclusions

Our study suggests strongly that Staphylococcus epidermidis was causing the TSS symptoms through the known Staphylococcus aureus superantigens. It is unknown how many other such patients exist; this should be explored. Of great importance is that PCR performed directly on blood plasma in the absence of microbial isolation could be used to demonstrate superantigen genes.
(Cost-)effectiveness of a personalized multidisciplinary eHealth intervention for knee arthroplasty patients to enhance return to activities of daily life, work and sports – rationale and protocol of the multicentre ACTIVE randomized controlled trial
Authors: Straat A. Carlien , Maarleveld Jantine M. , Smit Denise J. M. , Visch Lara , Hulsegge Gerben , Huirne Judith A. F. , van Dongen J. M. , van Geenen Rutger C. , Kerkhoffs Gino M. M. J. , Anema Johannes R. , Coenen Pieter , Kuijer P. Paul F. M.
Published: March 2023

Background

With the worldwide rising obesity epidemic and the aging population, it is essential to deliver (cost-)effective care that results in enhanced societal participation among knee arthroplasty patients. The purpose of this study is to describe the development, content, and protocol of our (cost-)effectiveness study that assesses a perioperative integrated care program, including a personalized eHealth app, for knee arthroplasty patients aimed to enhance societal participation post-surgery compared to care as usual.

Methods

The intervention will be tested in a multicentre randomized controlled trial with eleven participating Dutch medical centers (i.e., hospitals and clinics). Working patients on the waiting-list for a total- or unicompartmental knee arthroplasty with the intention to return to work after surgery will be included. After pre-stratification on medical centre with or without eHealth as usual care, operation procedure (total- or unicompartmental knee arthroplasty) and recovery expectations regarding return to work, randomization will take place at the patient-level. A minimum of 138 patients will be included in both the intervention and control group, 276 in total. The control group will receive usual care. On top of care as usual, patients in the intervention group will receive an intervention consisting of three components: 1) a personalized eHealth intervention called ikHerstel (‘I Recover’) including an activity tracker, 2) goal setting using goal attainment scaling to improve rehabilitation and 3) a referral to a case-manager. Our main outcome is quality of life, based on patient-reported physical functioning (using PROMIS-PF). (Cost-)effectiveness will be assessed from a healthcare and societal perspective. Data collection has been started in 2020 and is expected to finish in 2024.

Discussion

Improving societal participation for knee arthroplasty is relevant for patients, health care providers, employers and society. This multicentre randomized controlled trial will evaluate the (cost-)effectiveness of a personalized integrated care program for knee arthroplasty patients, consisting of effective intervention components based on previous studies, compared to care as usual.

Trial registration

Trialsearch.who.int; reference no. NL8525, reference date version 1: 14–04-2020.
Comparison between primary repair and augmented repair with gastrocnemius turn-down flap for acute Achilles tendon rupture: a retrospective study with minimum 2-year follow-up
Authors: Yang Shuai , Shi Weili , Yan Wenqiang , Ao Yingfang , Guo Qinwei , Yang Yuping
Published: March 2023

Background

To explore and compare the clinical outcomes in patients undergoing primary repair versus augmented repair with a gastrocnemius turn-down flap for acute Achilles tendon rupture.

Methods

From 2012 to 2018, the clinical data of 113 patients with acute Achilles tendon rupture who were treated with primary repair or augmented repair with a gastrocnemius turn-down flap by the same surgeon were retrospectively reviewed. The patients’ preoperative and postoperative scores on the visual analog scale (VAS), American Orthopaedic Foot and Ankle Society Ankle⁃Hindfoot (AOFAS) score, the Victorian Institute of Sport Assessment⁃Achilles (VISA-A), the Achilles tendon total rupture score (ATRS), and the Tegner Activity Scale were examined and compared. The postoperative calf circumference was measured. A Biodex isokinetic dynamometer was used to evaluate the plantarflexion strength on both sides. The time to return to life and exercise as well as the strength deficits in both groups were recorded. Finally, the correlation analyses between patient characteristics and treatment details with clinical outcomes were conducted.

Results

In total, 68 patients were included and completed the follow-up. The 42 and 26 patients who were treated with primary repair and augmented repair were assigned to group A and B, respectively. No serious postoperative complications were reported. No significant between-group differences in any outcomes were observed. It was found that female sex was correlated with poorer VISA-A score (P = 0.009), complete seal of paratenon was correlated with higher AOFAS score (P = 0.031), and short leg cast was correlated with higher ATRS score (P = 0.006).

Conclusions

Augmented repair with a gastrocnemius turn-down flap provided no advantage over primary repair for the treatment of acute Achilles tendon rupture. After surgical treatment, females tended to had poorer outcomes, while complete seal of paratenon and short leg cast contributed to better results.

Level of evidence

Cohort study; Level of evidence, 3.
Characteristics and outcomes of patients who did not respond to a national spine surgery registry
Authors: Kaur Simran , Alhaug Ole Kristian , Dolatowski Filip C. , Solberg Tore K. , Lønne Greger
Published: March 2023

Background

Loss to follow-up may bias outcome assessments in medical registries. This cohort study aimed to analyze and compare patients who failed to respond with those that responded to the Norwegian Registry for Spine Surgery (NORspine).

Methods

We analyzed a cohort of 474 consecutive patients operated for lumbar spinal stenosis at four public hospitals in Norway during a two-year period. These patients reported sociodemographic data, preoperative symptoms, and Oswestry Disability Index (ODI), numerical rating scales (NRS) for back and leg pain to NORspine at baseline and 12 months postoperatively. We contacted all patients who did not respond to NORspine after 12 months. Those who responded were termed responsive non-respondents and compared to 12 months respondents.

Results

One hundred forty (30%) did not respond to NORspine 12 months after surgery and 123 were available for additional follow-up. Sixty-four of the 123 non-respondents (52%) responded to a cross-sectional survey done at a median of 50 (36–64) months after surgery. At baseline, non-respondents were younger 63 (SD 11.7) vs. 68 (SD 9.9) years (mean difference (95% CI) 4.7 years (2.6 to 6.7); p =  < 0.001) and more frequently smokers 41 (30%) vs. 70 (21%) RR (95%CI) = 1.40 (1.01 to 1.95); p = 0.044. There were no other relevant differences in other sociodemographic variables or preoperative symptoms. We found no differences in the effect of surgery on non-respondents vs. respondents (ODI (SD) = 28.2 (19.9) vs. 25.2 (18.9), MD (95%CI) = 3.0 ( -2.1 to 8.1); p = 0.250).

Conclusion

We found that 30% of patients did not respond to NORspine at 12 months after spine surgery. Non-respondents were somewhat younger and smoked more frequently than respondents; however, there were no differences in patient-reported outcome measures. Our findings suggest that attrition bias in NORspine was random and due to non-modifiable factors.
Locked intramedullary nailing of open fractures in resource-poor settings: a prospective observational study of challenges and functional outcomes in 101 fractures at Ogbomoso, Nigeria
Authors: Adesope Adesina Stephen , Olusayo Amole Isaac , Owolabi James Idowu , Oyewusi Oluwafemi Oyewole , Goodness Adefokun Imri , Uwale Eyesan Samuel
Published: March 2023

Background

Trauma is now one of the fastest growing epidemics globally but low and middle-income countries (LMICs) are more severely affected in terms of cost, disability and death. The high-energy trauma of road traffic accidents and violence often produces open fractures which can be difficult to manage in resource-poor settings. Adequate stabilization, such as provided by locked nails, has been found to ensure better outcome for open fractures. There is dearth of published studies on the use of locked intramedullary nail in the treatment of open fractures in Nigeria.

Methods

This is a prospective observational study of all the 101 open fractures of the humerus, femur and tibia treated over a period of 92 months with Surgical Implant Generation Network (SIGN) nail. Fracture severity was classified according to the modified Gustilo-Anderson system. The intervals between fracture and antibiotics administration, débridement and definitive fixation, as well as surgery duration and method of fracture reduction were noted. Outcomes measured at follow-up included infection, ongoing radiographic healing, knee flexion/shoulder abduction beyond ninety degrees (KF/SA > 900), full weight bearing (FWB), painless squatting (PS&S)/shoulder abduction-external rotation (SAER).

Results

Most of the patients fall between ages 20 and 49 years; 75.5% of them were males. There were more Gustilo-Anderson type IIIA fractures than other types but nine type IIIB tibia fractures were also nailed. The overall infection rate was 15%, contributed mostly by the type IIIB fractures. By the 12th post-operative week, at least 79% had ongoing radiographic healing and had achieved all of KF/SA > 900, FWB, and PS&S/SAER.

Conclusion

The SIGN nail’s solid construct reduces the risk of infection and allows earlier use of the limb, making it particularly suitable in LIMCs where socioeconomic functioning often requires an unhindered use of the limbs.
Case report of avascular necrosis of the glans penis after PAE embolization
Authors: Liu Jun , Gong Yang-Yang , Ran Can , Liu Hong-Jian , Zeng Ding-Sheng , Feng You-Gang
Published: March 2023

Background

Prostate artery embolization (PAE) is a relatively safe and effective alternative method for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. The adverse events caused by PAE are primarily mild, including urinary tract infection, acute urinary retention, dysuria, fever, etc. Severe complications, such as nontarget organ embolism syndrome or penile glans ischemic necrosis, are rare. Here, we report a case of severe ischemic necrosis of the glans penis after PAE and review the literature.

Case presentation

An 86-year-old male patient was admitted to the hospital due to progressive dysuria with gross hematuria. The patient underwent placement of a three-way urinary catheter to facilitate continuous bladder flushing, hemostasis, and rehydration. After admission, his hemoglobin decreased to 89 g/L. After an examination, the diagnosis was benign prostatic hyperplasia with bleeding. During communication with the patient regarding treatment, he requested prostate artery embolization due to his advanced age and concomitant disease status. He underwent bilateral prostate artery embolization under local anesthesia. His urine gradually turned clear. However, on the 6th day after embolization, the glans gradually showed ischemic changes. On the 10th day, there was partial necrosis and blackening of the glans. The glans completely healed, and the patient was able to urinate smoothly on the 60th day after local cleaning and debridement, the administration of pain relief, anti-inflammatory and anti-infection agents, and external application of burn ointment.

Conclusion

Penile glans ischemic necrosis after PAE is rare. The symptoms include pain, congestion, swelling, and cyanosis in the glans.
A 50-year-old refugee woman with a lithopedion and a lifetime of trauma: a case report
Authors: Sous Waseem , Sous Michaela , Soipe Ayorinde , Brown Amy E. Caruso , Shaw Andrea V.
Published: March 2023

Background

Lithopedion is a term that refers to a fetus that has calcified or changed to bone. The calcification may involve the fetus, membranes, placenta, or any combination of these structures. It is an extremely rare complication of pregnancy and can remain asymptomatic or present with gastrointestinal and/or genitourinary symptoms.

Case presentation

A 50-year-old Congolese refugee with a nine-year history of retained fetus after a fetal demise was resettled to the United States (U.S.). She had chronic symptoms of abdominal pain and discomfort, dyspepsia, and gurgling sensation after eating. She experienced stigmatization from healthcare professionals in Tanzania at the time of the fetal demise and subsequently avoided healthcare interaction whenever possible. Upon arrival to the U.S., evaluation of her abdominal mass included abdominopelvic imaging which confirmed the diagnosis of lithopedion. She was referred to gynecologic oncology for surgical consultation given intermittent bowel obstruction from underlying abdominal mass. However, she declined intervention due to fear of surgery and elected for symptom monitoring. Unfortunately, she passed away due to severe malnutrition in the context of recurrent bowel obstruction due to the lithopedion and continued fear of seeking medical care.

Conclusion

This case demonstrated a rare medical phenomenon and the impact of medical distrust, poor health awareness, and limited access to healthcare among populations most likely to be affected by a lithopedion. This case highlighted the need for a community care model to bridge the gap between the healthcare team and newly resettled refugees.
Correction: Protective effects of Xinji′erkang on myocardial infarction induced cardiac injury in mice
Authors: Hu Juan , Zhang Yong-xue , Wang Li , Ding Ling , Huang Guang-yao , Cai Guo-wei , Gao Shan
Published: March 2023

An amendment to this paper has been published and can be accessed via the original article.
Clinical associations for traditional and complementary medicine use among Norwegian cancer survivors in the seventh survey of the Tromsø study: a cross-sectional study
Authors: Nakandi Kiwumulo , Stub Trine , Kristoffersen Agnete E.
Published: March 2023

Background

Cancer survivors are a diverse group with varying needs that are patient-, disease-, and/or treatment-specific. Cancer survivors have reported supplementing conventional anti-cancer treatment with Traditional and Complementary Medicine (T&CM). Although female cancer survivors are reported to have more severe anticancer adverse effects, little is known about the association between anticancer treatment and T&CM use among Norwegian cancer survivors. The aims of this study are therefore to investigate (1) associations between cancer diagnosis characteristics and T&CM utilization and (2) associations between anticancer treatment and T&CM utilization among cancer survivors in the seventh survey of the Tromsø study.

Methods

Data was collected from the seventh survey of the Tromsø Study conducted in 2015-16 among all inhabitants of Tromsø municipality aged 40 and above (response rate 65%), where inhabitants received online and paper form questionnaires. Data from the data linkage to the Cancer Registry of Norway for cancer diagnosis characteristics was also used. The final study sample was made up of 1307 participants with a cancer diagnosis. Categorical variables were compared using Pearson’s Chi-square test or Fisher’s exact test while independent sample t-test was used to compare continuous variables.

Results

The use of T&CM the preceding 12 months was reported by 31.2% of the participants with natural remedies as the most reported modality of T&CM (18.2%, n = 238), followed by self-help practices of meditation, yoga, qigong, or tai chi, which was reported by 8.7% (n = 114). Users of T&CM were significantly younger (p = .001) and more likely to be female (p < .001) than the non-users, with higher use of T&CM among female survivors with poor self-reported health and being 1–5 years post-diagnosis. Lower use of T&CM was found among female survivors who received a combination of surgery with hormone therapy and those who received a combination of surgery with hormone therapy and radiotherapy. Similar usage was seen in male survivors, but not at a significant level. For both male and female survivors, T&CM was most frequently used by those with only one cancer diagnosis (p = .046).

Conclusion

Our results indicate that the profile of the Norwegian cancer survivor who uses T&M is slightly changing compared to previous findings. Additionally, compared to male survivors, more clinical factors are associated with use of T&CM among female cancer survivors. These results should serve as a reminder to conventional health care providers to discuss the use of T&CM with patients across the entire cancer survivorship continuum to promote safe use, especially among female survivors.
Higher HbA1c variability is associated with increased arterial stiffness in individuals with type 1 diabetes
Authors: Tynjälä Anniina , Harjutsalo Valma , Jansson Sigfrids Fanny , Groop Per-Henrik , Gordin Daniel ,   the FinnDiane Study Group
Published: March 2023

Background

Both long-term glycaemic variability and arterial stiffness have been recognized as cardiovascular risk factors. This study aims to investigate whether an association between these phenomena exists in individuals with type 1 diabetes.

Methods

This cross-sectional study included 673 adults (305 men, 368 women) with type 1 diabetes and combined available retrospective laboratory data on HbA1c from the preceding 10 years with outcome data on arterial stiffness and clinical variables from a comprehensive study visit. HbA1c variability was calculated as adjusted standard deviation (adj-HbA1c-SD), coefficient of variation (HbA1c-CV) and average real variability (HbA1c-ARV). As measures of arterial stiffness, carotid-femoral pulse wave velocity (cfPWV; n = 335) and augmentation index (AIx; n = 653) were assessed using applanation tonometry.

Results

The study population had a mean age of 47.1 (± 12.0) years and a median duration of diabetes of 31.2 (21.2–41.3) years. The median number of HbA1c assessments per individual was 17 (12–26). All three indices of HbA1c variability were significantly correlated with both cfPWV and AIx after adjustment for sex and age (p < 0.001). In separate multivariable linear regression models, adj-HbA1c-SD and HbA1c-CV were significantly associated with cfPWV (p = 0.032 and p = 0.046, respectively) and AIx (p = 0.028 and p = 0.049, respectively), even after adjustment for HbA1c-mean. HbA1c-ARV was not associated with cfPWV or AIx in the fully adjusted models.

Conclusions

An association independent of HbA1c-mean was found between HbA1c variability and arterial stiffness, suggesting a need to consider multiple HbA1c metrics in studies assessing cardiovascular risk in type 1 diabetes. Longitudinal and interventional studies are needed to confirm any causal relationship and to find strategies for reducing long-term glycaemic variability.
The joint association of diabetes status and NT-ProBNP with adverse cardiac outcomes in patients with non-ST-segment elevation acute coronary syndrome: a prospective cohort study
Authors: Wang Man , Su Wen , Chen Hui , Li Hongwei
Published: March 2023

Aims

To examine the joint association of diabetes status and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with subsequent risk of major adverse cardio-cerebral events (MACCEs) and all-cause mortality in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).

Methods

A total of 7956 NSTE-ACS patients recruited from the Cardiovascular Center Beijing Friendship Hospital Database Bank were included in this cohort study. Patients were divided into nine groups according to diabetes status (normoglycemia, prediabetes, diabetes) and NT-proBNP tertiles (< 92 pg/ml, 92–335 pg/ml, ≥ 336 pg/ml). Multivariable Cox proportional hazards models were used to estimate the individual and joint association of diabetes status and NT-proBNP with the risk of MACCEs and all-cause mortality.

Results

During 20,257.9 person-years of follow-up, 1070 MACCEs were documented. In the fully adjusted model, diabetes and a higher level of NT-proBNP were independently associated with MACCEs risk (HR 1.42, 95% CI: 1.20–1.68; HR 1.72, 95% CI: 1.40–2.11) and all-cause mortality (HR 1.37, 95% CI: 1.05–1.78; HR 2.80, 95% CI: 1.89–4.17). Compared with patients with normoglycemia and NT-proBNP < 92 pg/ml, the strongest numerical adjusted hazards for MACCEs and all-cause mortality were observed in patients with diabetes and NT-proBNP ≥ 336 pg/ml (HR 2.67, 95% CI: 1.83–3.89; HR 2.98, 95% CI: 1.48–6.00). The association between MACCEs and all-cause mortality with various combinations of NT-proBNP level, HbA1c, and fasting plasma glucose was studied.

Conclusions

Diabetes status and elevated NT-proBNP were independently and jointly associated with MACCEs and all-cause mortality in patients with NSTE-ACS.
Membrane-based continuous fermentation with cell recycling for propionic acid production from glycerol by Acidipropionibacterium acidipropionici
Authors: Cavero-Olguin Victor Hugo , Dishisha Tarek , Hatti-Kaul Rajni
Published: March 2023

Background

Microbial production of propionic acid (PA) from renewable resources is limited by the slow growth of the producer bacteria and product-mediated inhibition. The present study evaluates high cell density continuous PA fermentation from glycerol (Gly) using Acidipropionibacterium acidipropionici DSM 4900 in a membrane-based cell recycling system. A ceramic tubular membrane filter of 0.22 μm pore size was used as the filtering device for cell recycling. The continuous fermentations were run sequentially at dilution rates of 0.05 and 0.025 1/h using varying glycerol concentrations and two different yeast extract concentrations.

Results

PA volumetric productivity of 0.98 g/L.h with a product yield of 0.38 gPA/gGly was obtained with 51.40 g/L glycerol at a yeast extract concentration of 10 g/L. Increasing the glycerol and yeast extract concentrations to 64.50 g/L and 20 g/L, respectively, increased in PA productivity, product yield, and concentration to 1.82 g/L.h, 0.79 gPA/gGly, and 38.37 g/L, respectively. However, lowering the dilution rate to 0.025 1/h reduced the production efficiency. The cell density increased from 5.80 to 91.83 gCDW/L throughout the operation, which lasted for a period of 5 months. A tolerant variant of A. acidipropoinici exhibiting growth at a PA concentration of 20 g/L was isolated at the end of the experiment.

Conclusions

Applying the current approach for PA fermentation can overcome several limitations for process industrialization.
Accuracy of diagnosis among clinical malaria patients: comparing microscopy, RDT and a highly sensitive quantitative PCR looking at the implications for submicroscopic infections
Authors: Opoku Afriyie Stephen , Addison Thomas Kwame , Gebre Yilekal , Mutala Abdul-Hakim , Antwi Kwasi Baako , Abbas Dawood Ackom , Addo Kofi Agyapong , Tweneboah Austine , Ayisi-Boateng Nana Kwame , Koepfli Cristian , Badu Kingsley
Published: March 2023

Background

The World Health Organization recommends parasitological confirmation of all suspected malaria cases by microscopy or rapid diagnostic tests (RDTs) before treatment. These conventional tools are widely used for point-of-care diagnosis in spite of their poor sensitivity at low parasite density. Previous studies in Ghana have compared microscopy and RDT using standard 18S rRNA PCR as reference with varying outcomes. However, how these conventional tools compare with ultrasensitive varATS qPCR has not been studied. This study, therefore, sought to investigate the clinical performance of microscopy and RDT assuming highly sensitive varATS qPCR as gold standard.

Methods

1040 suspected malaria patients were recruited from two primary health care centers in the Ashanti Region of Ghana and tested for malaria by microscopy, RDT, and varATS qPCR. The sensitivity, specificity, and predictive values were assessed using varATS qPCR as gold standard.

Results

Parasite prevalence was 17.5%, 24.5%, and 42.1% by microscopy, RDT, and varATS qPCR respectively. Using varATS qPCR as the standard, RDT was more sensitive (55.7% vs 39.3%), equally specific (98.2% vs 98.3%), and reported higher positive (95.7% vs 94.5%) and negative predictive values (75.3% vs 69.0%) than microscopy. Consequently, RDT recorded better diagnostic agreement (kappa = 0.571) with varATS qPCR than microscopy (kappa = 0.409) for clinical detection of malaria.

Conclusions

RDT outperformed microscopy for the diagnosis of Plasmodium falciparum malaria in the study. However, both tests missed over 40% of infections that were detected by varATS qPCR. Novel tools are needed to ensure prompt diagnosis of all clinical malaria cases.
The spatial signature of Plasmodium vivax and Plasmodium falciparum infections: quantifying the clustering of infections in cross-sectional surveys and cohort studies
Authors: Sandfort Mirco , Monteiro Wuelton , Lacerda Marcus , Nguitragool Wang , Sattabongkot Jetsumon , Waltmann Andreea , Salje Henrik , Vantaux Amélie , Witkowski Benoit , Robinson Leanne J. , Mueller Ivo , White Michael
Published: March 2023

Background

Over the last decades, enormous successes have been achieved in reducing malaria burden globally. In Latin America, South East Asia, and the Western Pacific, many countries now pursue the goal of malaria elimination by 2030. It is widely acknowledged that Plasmodium spp. infections cluster spatially so that interventions need to be spatially informed, e.g. spatially targeted reactive case detection strategies. Here, the spatial signature method is introduced as a tool to quantify the distance around an index infection within which other infections significantly cluster.

Methods

Data were considered from cross-sectional surveys from Brazil, Thailand, Cambodia, and Solomon Islands, conducted between 2012 and 2018. Household locations were recorded by GPS and finger-prick blood samples from participants were tested for Plasmodium infection by PCR. Cohort studies from Brazil and Thailand with monthly sampling over a year from 2013 until 2014 were also included. The prevalence of PCR-confirmed infections was calculated at increasing distance around index infections (and growing time intervals in the cohort studies). Statistical significance was defined as prevalence outside of a 95%-quantile interval of a bootstrap null distribution after random re-allocation of locations of infections.

Results

Prevalence of Plasmodium vivax and Plasmodium falciparum infections was elevated in close proximity around index infections and decreased with distance in most study sites, e.g. from 21.3% at 0 km to the global study prevalence of 6.4% for P. vivax in the Cambodian survey. In the cohort studies, the clustering decreased with longer time windows. The distance from index infections to a 50% reduction of prevalence ranged from 25 m to 3175 m, tending to shorter distances at lower global study prevalence.

Conclusions

The spatial signatures of P. vivax and P. falciparum infections demonstrate spatial clustering across a diverse set of study sites, quantifying the distance within which the clustering occurs. The method offers a novel tool in malaria epidemiology, potentially informing reactive intervention strategies regarding radius choices of operations around detected infections and thus strengthening malaria elimination endeavours.
Maternal and infant outcomes of pregnancy associated with anti-SSA/RO antibodies: a systematic review and meta-analysis
Authors: Sheng Xiangrui , Song Xiaohui , Xiong Yue , Ren Tian , Chang Xin , Wu Jian , Cao Jing , Cheng Tao , Wang Mingjun
Published: March 2023

Objective

The relationship between anti-SSA/RO antibodies and pregnancy has been reported previously, and we aim to visualize the rates of maternal and infant outcomes with anti-SSA/RO.

Methods

We systematically searched records from Pubmed, Cochrane, Embase, and Web of Science databases, pooled incidence rates of adverse outcomes of pregnancy, and 95% confidence intervals (CIs) were performed with RStudio.

Results

A total of 890 records comprising 1675 patients and 1920 pregnancies were searched from the electronic databases. For maternal outcomes, the pooled estimate rates were 4% for termination of pregnancy, 5% for spontaneous abortion, 26% for preterm labor, and 50% for cesarean operation. While for fetal outcomes, the pooled estimate rates were 4% for perinatal death, 3% for intrauterine growth retardation, 6% for endocardial fibroelastosis, 6% for dilated cardiomyopathy, 7% for congenital heart block, 12% for congenital heart block recurrence, 19% for cutaneous neonatal lupus erythematosus, 12% for hepatobiliary disease and 16% for hematological manifestations. A subgroup analysis of congenital heart block prevalence was performed, diagnostic method and study region were found to affect heterogeneity to some extent.

Conclusion

Cumulative analysis of data from real-world studies confirmed adverse pregnancy outcomes of women with anti-SSA/RO, serves as a reference and a guide for the diagnosis and subsequent treatment of these women, thereby enhancing maternal and infant health. Additional studies with real-world cohorts are required to validate these results.
The biomedical securitization of global health
Authors: Holst Jens , van de Pas Remco
Published: March 2023

Background

The COVID-19 outbreak has shifted the course in the global health debate further towards health security and biomedical issues. Even though global health had already played a growing role in the international policy agenda, the pandemic strongly reinforced the interest of the media, the general public and the community in cross-border infectious diseases. This led to a strengthening of the already dominant biomedical understanding of global health and the securitization of health in foreign policy.

Methods

This paper critically provides a narrative, iterative review of the health security literature available to date, with a special focus on the development of the currently prevailing concept of health security and the dual trend towards the securitization and biomedicalization of global health.

Findings

In a world increasingly determined by power asymmetries, unequal distribution of opportunities and resources, and inadequate governance structures, securitizing health has become a key feature of global governance. Health security is predominantly based on a concept that neglects the global burden of disease determined by non-communicable conditions rather than by infectious diseases. Moreover, it exhibits a trend towards biomedical solutions and neglects root causes of global health crises.

Conclusions

As important as health security is, the underlying concept driven by biomedical and technocratic reductionism falls short. It widely neglects the social, economic, political, commercial and environmental determination of health. Beyond improved health care and prevention, health-in-all policies are ultimately required for ensuring health security and reducing one of its main challenges, health inequalities within and between countries. Global health security must first and foremost seek to guarantee the universal right to health and therefore emphasise the social, economic, commercial and political determination of health.