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Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study

  • Melanie Galliardt , Ulrich Betz , Frank Birklein , Philipp Drees and Christian Geber EMAIL logo
Published/Copyright: May 27, 2023
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Open Medicine
From the journal Open Medicine Volume 18 Issue 1

Abstract

This prospective cohort study aimed to characterise the impact of oxaliplatin-based chemotherapy and its neurotoxic side effects (i.e., chemotherapy-induced neuropathy) on functional fall-risk and falls. Twenty chemotherapy-naïve participants (mean age, 59 years; 16 males) were consecutively included. A multimodal fall risk assessment was performed at four time points within 6 months. Polyneuropathy was assessed using the Neurologic Disability Scale; the fall risk was assessed by functional tests (Tinetti Test, Chair-Rising Test, and Timed up and Go Test). Patient-reported outcomes comprised the Hospitality Anxiety and Depression Scale (HADS), the Falls Efficacy Scale – International (FES-I) to assess the fear of falling, and the Physical Activity for the Elderly (PASE) questionnaire. Three falls occurred during the study. All fallen participants had a high fall risk-index (≥4 more risk factors) compared to only 30% of the non-fallen participants (p = 0.03) and suffered more frequently from pre-existing mild polyneuropathy (p = 0.049). Study discontinuation (n = 12) was associated with a higher rate of polypharmacy (p = 0.045), anxiety (HADS-A, p = 0.03), and specific fear of falling (FES-I, p = 0.025). In contrast, study completers (n = 8) reported an improvement in physical activity (PASE) (p = 0.018). In summary, pre-existing fall-risk factors impacted more falls than chemotherapy. A fall risk index offers a time-efficient screening option in an outpatient oncological setting.

Keywords: chemotherapy; fall-risk-index; outpatient setting; polyneuropathy; neurotoxicity

1 Introduction

Falls and associated mobility impairment are a major public health concern, with the fall risk being strongly associated with age and chronic disease [1,2]. Cancer patients are at particular risk of falls, as is the general elderly population, due to the disease- and treatment-related effects on physical function [3,4,5,6]. As the population ages and cancer diagnosis and treatment strategies improve, the number of cancer survivors at a high risk of falls is increasing [5,7,8]. Non-modifiable (age and gender) and modifiable risk factors (environmental hazards, sensory deficits, balance/gait disorders, and medication problems) contribute to the high risk of falls [9]. This means that fall risk must be defined as a dynamic process and reassessed during chemotherapy.

From a neurological perspective, chemotherapy-induced neuropathy (CIPN) is one of the most common side effects in cancer treatment. The prevalence ranges from 30 to 75% [10,11] depending on chemotherapeutic agents, cumulative dose, and pre-existing medical conditions [12,13,14]. The risk increases with higher doses of neurotoxic substances, and the resulting neuropathic symptoms (CIPN) indicate an increased risk of falling at different stages of cancer treatment [15,16,17].

While the incidence, clinical symptoms, and pathomechanisms of CIPN have been intensively studied [18,19,20], the functional and dynamic changes in balance and mobility disorders associated with CIPN have been less well studied, mostly in cross-sectional and retrospective studies [21,22]. Prospective clinical observations are rare and do not functionally examine the effects of CIPN on physical performance and fall risk [8,16].

Therefore, our study aims to provide new insights into the dynamics of functional risk and risk of falls during early oxaliplatin therapy intervals using validated tests of physical performance and mobility (e.g., Tinetti test and timed-up-and-go test), self-assessment of activities of daily living (ADL), and psychometric questionnaires under close monitoring of sensorimotor impairment. The chemotherapeutic agent under investigation – the platinum derivative oxaliplatin – has a known neurotoxic risk profile, with a high CIPN incidence of up to 75% in early phases of treatment and a minimum dose-related threshold of 540 mg/m² [23]. We hypothesised that functional fall risk would increase with higher doses of chemotherapy and that the severity of CIPN would correlate with increased fall risk.

2 Methods

2.1 Study design

The multimodal fall risk assessment was performed at week 0 (T1) of the first chemotherapy administration and repeated at 6 (T2), 12 (T3), and 24 (T4) weeks. The study visits T2–T4 were performed with a time interval of up to 7 days from the last oxaliplatin administration to minimise bias due to acute cytostatic side effects (nausea, etc.). Each study appointment included a standardised neurological and psychometric assessment, physical performance tests (see below), and a history collection on the extrinsic and intrinsic fall risk profile of the participants. Oxaliplatin doses were recorded cumulatively (mg/m2) for the three follow-up dates (T2–T4) on an individual basis. Participants’ records were also reviewed for medications and concomitant circumstances (e.g., interruptions in chemotherapy). Each examination session lasted approximately 45–60 min (Figure 1).

Figure 1 Flow chart: study design and risk assessment.
Figure 1

Flow chart: study design and risk assessment.

2.2 Clinical assessment and performance tests

2.2.1 Standardised neurological examination

The Neuropathy Deficit Score (NDS) [24] was used as a standardised neurological examination. It includes the ankle reflex, vibration threshold, temperature (cold object), and pin-prick sensation of the great toe of each leg. The reflexes were scored as present (= 2), present with reinforcement (= 1), or absent (= 0). The sensory modalities were scored as either present (= 0) or reduced/absent (= 1) on each side, resulting in a clinical score of 0–10 points, indicating mild (3–5 points), moderate (6–8 points), or severe (9–10 points) neuropathic signs. The cut-off of 3 points was set for relevant neuropathic deficits indicating polyneuropathy.

2.2.2 Assessment of mobility and physical performance

The Tinetti assessment tool, also called POMA (Performance Orientated Mobility Assessment), measures an older adult’s gait and balance abilities. A low-performance score is associated with a high fall risk in an individual. The Tinetti test has been validated as a robust fall risk instrument and predictor of falls in the elderly (>65 years) [25]. The maximum score is 28, with a cut-off below 21 indicating an increased fall risk.

The additional physical performance measures and questionnaires were used to obtain a comprehensive overview of the participants’ functional risk status. The Chair Rising Test assesses the muscle strength of the lower limb by measuring the time duration of the transfer from a seated to a standing position and back to sitting five times. A cut-off of 10 s or more correlates significantly with an increased frequency of falls [26].

The Timed-up-and-Go tool (TUG) assesses dynamic balance and functional mobility. Subjects were instructed to sit back in a standard armchair and to stand up, walk a marked path of 3 m, turn around, and sit back down in the chair. The cut-off value was set at 12 s based on the reference value for geriatric adults [27].

2.3 Patient-reported outcomes

2.3.1 Hospital anxiety and depression scale (HADS)

Patients were asked to fill in the HADS questionnaire to identify signs of common psychological burden. This psychometric tool contains 14 questions, which led to an anxiety subscale (HADS-A) and a depression subscale (HADS-D) score ranging 0–21 points each. A minimum of 7 points indicated mild depression or anxiety with higher scores indicating severe affective symptoms [28].

2.3.2 Falls Efficacy Scale - International (FES-I)

The FES-I is a self-completion questionnaire that measures participants’ fear of falling in all everyday situations or activities. Sixteen items are scored on a 4-point ordinal scale (0 = no fear of falling to 4 = severe fear of falling), resulting in a maximum score (highest fear) of 64 [29].

2.3.3 Physical activity scale for the elderly (PASE)

The PASE instrument assesses a person’s physical activity over the past week using a detailed quantitative and qualitative scoring system. Information on frequency, duration, and intensity of typical leisure, household, or work-related activities led to a scale ranging 0–793 points, with higher scores indicating greater physical activity [30].

2.4 Study population

Twenty participants (mean age, 59 years; 16 males) from the outpatient clinic for tumours of the gastrointestinal tract, pancreas, and bile ducts (University Medical Centre of the Johannes Gutenberg-University Mainz) and a medical practice for haematology and oncology at Mainz were prospectively included during a 2.5-year period (2012–2014). Participants were examined at the outpatient clinic of the Department of Neurology and the Institute for Physical Therapy, Prevention and Rehabilitation of the Johannes Gutenberg-University Medical Centre, Mainz.

Written informed consent was obtained from all participants, and the Rhineland-Palatinate Ethics Committee approved the study (processing number: 837.193.12(8294-F)).

All participants were chemotherapy-naïve and scheduled to receive a FOLFOX (FOLFOXIRI, XELOX [capecitabine and oxaliplatin]) regimen as their first-line chemotherapy. Individual oxaliplatin dosing per cycle varied 70–130 mg/m2.

Risk assessment at baseline included sex, age >65 years, BMI >30 kg/m2, history of falls, walking disability (use of a walking aid), and visual impairment (assessed with visual acuity cards). Participants’ records were reviewed for comorbidities and fall-related medication (e.g., benzodiazepines, diuretics, antiarrhythmics, and neuroleptics) and polypharmacy (>4 medications/day). Other comorbidities such as arterial hypertension, diabetes mellitus, musculoskeletal disorders, or postsurgical pain were grouped as fall risk factors because they may indicate increased frailty (Tables 1 and 2). A high fall-risk-index is defined by four or more risk factors per person [31].

Table 1

Risk factor profile at baseline (T1)

Risk factor Baseline cohort (T1) (n = 20) No (%)
Age >65 years n = 7 (35%)
Sex (female) n = 4 (20%)
Obesity (BMI >30 kg/m²) n = 3 (15%)
Walking aid n = 3 (15%)
Visus deficit n = 15 (75%)
Polypharmacy (>4 med.) n = 5 (25%)
Fall-associated medication n = 11 (55%)
Comorbidities+ n = 17 (75%)

+comorbidities such as arterial hypertension, diabetes mellitus, musculoskeletal disorders, or postsurgical pain were grouped together as fall risk factors because they may indicate increased frailty.

Table 2

Risk factor differences between dropouts and completers at T1

Risk factor Completers (n = 8) Dropouts (n = 12) p-value (completers vs dropouts)
Age (>65 years) 2 (25%) 5 (42%) 0.64
Sex (female) 1 (12.5%) 3 (25%) 0.62
Obesity (BMI >30 kg/m²) 0 3 (25%) 0.24
Visual impairment 7 (87.5%) 8 (75%) 0.10
Polypharmacy (>4 med.) 0 5 (42%) 0.045*
Fall-associated medication 4 (50%) 7 (58%) 1
Walking aid 0 3 (25%) 0.24
Comorbidities 6 (75%) 11 (95%) 0.34

*p < 0.05.

Exclusion criteria comprised previous antineoplastic chemotherapy or pre-diagnosed peripheral polyneuropathy. Due to the physically challenging examination procedure, patients with acute pain, dizziness, and cognitive impairment were excluded.

2.5 Statistical analysis

Statistical analyses were performed using IBM SPSS statistical package version 25. Correlation analyses were applied to study the association between 1) cumulative chemotherapy doses (= Δ mg/m2) and changes in functional fall risk (Δ Tinetti score) and 2) changes in the polyneuropathy score (= Δ NDS score) and changes in functional fall risk (Δ Tinetti score).

Correlation analyses were performed based on the data of the follow-up cohort (n = 12) after 12 weeks (T1–T3). Univariate linear regression was performed to analyse the effect of cumulative oxaliplatin dosage on functional fall risk and the effect of changes in polyneuropathy severity on functional fall risk. Linear dependence of the variables was determined by Pearson correlation. Statistical significance for the two main questions was assumed at a p-value of <0.025 (Bonferroni correction for multiple testing).

In a retrospective explorative approach, we compared baseline data from study participants who discontinued the study (n = 12) with those who completed the study (n = 8), as well as those who fell during the study (n = 3) and those who did not (n = 17). At T1, we examined these samples for differences as possible predictors of study discontinuation or falls. Fisher’s exact test (categorical variables) or the Mann–Whitney U-test (continuous variables) was used.

We also performed a follow-up assessment of changes in risk factors after 12 weeks (n = 12) and in the sample of completers (n = 8) during 24 weeks of oxaliplatin-based chemotherapy. The McNemar (categorical variables) and Wilcoxon signed-rank (continuous variables) tests were applied. Without adjustment for multiple testing, a p-value of <0.05 was considered significant.

Data are presented using means and standard deviations (SD) for continuous data and percentages for dichotomous data, e.g., cut-off values (Figure 2).

Figure 2 Consort chart of sub-samples and analyses.
Figure 2

Consort chart of sub-samples and analyses.

3 Results

In total, 60% (n = 12) of all participants dropped out of the study. Reasons for discontinuation included worsening health (n = 5), death (n = 2), change of chemotherapeutic agent (n = 1), and at their own request/no information available (n = 4), with eight participants discontinuing in the first half of the study (before T3).

At baseline, seven participants (35%) presented with a high fall-risk index (T1), defined by four or more risk factors per person [31].

The two main correlation analyses revealed no association between 1) cumulative chemotherapy dosages and changes in functional fall risk (r = 0.51; p = 0.088) and 2) changes in polyneuropathy severity and functional fall risk (r = 0.23, p = 0.47).

3.1 Explorative analyses

3.1.1 Baseline comparison of study dropouts vs completers (T1)

Participants who discontinued the study (n = 12) initially reported higher psychological distress, such as anxiety (HADS-A: 7.5 ± 4.2 vs 3.63 ± 4.3; p = 0.031) and fear of falling (FES-I: 21.8 ± 4.6 vs 16.8 ± 4.7; p = 0.025). Polypharmacy was more frequent in participants who discontinued (n = 5; 42%) than among those who did not (n = 0; p = 0.045) (Tables 2 and 3).

Table 3

Risk assessment differences between dropouts and completers at T1

Fall-risk-assessment (T1, n = 20) Completers (n = 8) Dropouts (n = 12) p-value (completers vs dropouts)
Tinetti score 25.75 ± 3p 21.55 ± 7p 0.21
Neuropathy deficit score (NDS) 1.25 ± 1.5p 3.67 ± 3.6p 0.14
HADS-A 3.63 ± 4.53p 7.5 ± 3.2p 0.03*
HADS-D 4.5 ± 4.63p 6.17 ± 3.9p 0.34
FESI (range 16–64p) 16.75 ± 1.17p 21.75 ± 5.05p 0.025*
PASE (range 0–793p) 107 ± 55p 70.3 ± 49p 0.152
Chair-rising test (CRT) 11.88 ± 1.9s 14.25 ± 4s 0.14
Timed up and Go (TUG) 9.1 ± 3.3s 11.75 ± 6.3s 0.38

p: points; s: seconds.

*p < 0.05.

3.1.2 Baseline comparison of fallers versus non-fallers

A fall was defined as an event that results in a person unintentionally coming to rest on the floor, ground, or other lower level. We excluded falls caused by serious intrinsic events such as epileptic seizures, strokes, or paralysis and by precipitating external events such as car accidents, sports, or weather conditions. Accordingly, three falls were reported in the first half of the study (T1–T3) and were eligible for inclusion. Two further falls were not eligible for analysis because they were clearly triggered by environment (black ice) and behaviour (tennis).

A retrospective comparison of the cohort’s (n = 20) fall risk profile at baseline (T1) revealed differences between participants who fell and those who did not. Falls were associated with a high fall risk index (i.e., ≥4RF/person) in fallen (100%) versus non-fallen participants (30%; p = 0.003) and mild pre-existing PNP clinically defined by an NDS score of 3–5/10 points (100% vs 42%; p = 0.049).

3.1.3 Longitudinal analysis of risk factor changes over 12 weeks (n = 12)

None of the assessed risk factors (ΔT1–T3 [Table 2]) changed during the 12-week observation period (mean oxaliplatin administration 563 ± 128 mg/m2).

The results of the neurological examination did not reveal a clinically measurable CIPN development (Table 4).

Table 4

Fall-risk profile changes in the T3-follow-up cohort (T1–3)

Fall-risk-assessment (n = 12) T3 ΔT1–T3 p-value (ΔT1–T3)
Tinetti score 25.5 ± 4.2p 0.4 ± 0.7p 0.83
Tinetti cut-off (<21p) n = 2 (17%) 0% 1.0
Neuropathy deficit score (NDS) 1.5 ± 1.2p 0.17 ± 0.7p 0.73
NDS cut-off (>3p) n = 2 (17%) 1 (8.5%) 0.5
HADS-A 3.67 ± 2.9p 1.6 ± 1.3p 0.28
HADS-D 3.33 ± 3.3p 1.33 ± 0.55p 0.21
FESI (16–64p) 19.25 ± 3.8p 0.75 ± 0p 0.16
PASE (0–793p) 97.5 ± 43.4p 1.5 ± 16.1p 0.48
Chair-rising test (CRT) 10.83 ± 2.5s 1.25 ± 0.4s 0.057
Timed up and Go (TUG) 8.3 ± 2s 0.84 ± 0.8s 0.21

p: points; s: seconds.

3.1.4 Longitudinal analysis of risk factor changes over 24 weeks (completers; n = 8)

Changes in the intraindividual risk factor profile of the eight participants who completed the study were assessed descriptively. In this subsample, no falls occurred during the observation period of 6 months. The mean cumulative oxaliplatin dosage was 1,013 ± 36 mg/m2 at T4.

None of these participants developed clinically manifesting polyneuropathy (mean NDS score: 1.25 ± 1.5p; cut-off: 3), with only marginal progress by the end of the study (ΔNDS T1–T4: +0.25p; p = 0.57). Functional assessments of mobility, balance, and strength remained stable between T1 and T4 (Tinetti: T1: 25.75 ± 2.96p; T4: 26.9 ± 2.23p; p = 0.22; cut-off: <21) or even slightly improved (stand-up test: T1–T4: 11.9 ± 1.9 s vs 9.9 ± 1.5 s; p = 0.046) at the end of the study. The screening for anxiety and depression (HADS) remained below the threshold (7 P) until the end of the study. Concerns about falling (FES-I) remained almost unchanged at about 17 points near the minimum level (16p).

Self-assessment of weekly activity (PASE) improved from T1 to T4 (PASE T1–T4: 106.8 ± 55p vs 158.5 ± 57.2p; p = 0.018) and reached the reference range of a healthy age-matched population (= 144p) [60].

4 Discussion

This prospective observational study investigated the effects of oxaliplatin-based CIPN on functional fall risk in patients with gastrointestinal tumours over a period of 6 months.

4.1 Main results

Participants did not develop clinically manifest polyneuropathy during the early phase of oxaliplatin-based chemotherapy (time interval, 0–3 months) and falls occurred exclusively in participants with high pre-existing morbidity indicated by a high fall risk index (>4 RF/person) and mild pre-existing polyneuropathy. While physical performance tests failed to predict falls, the PASE-self-assessment provided useful and detailed information about the physical status of outpatients undergoing chemotherapy. Polypharmacy, anxiety (HADS), and fear of falling (FES-I) were more frequent at baseline in participants who discontinued the study.

4.2 Impact of peripheral neuropathy on falls

Independent of the aetiology of polyneuropathy, polyneuropathic sensorimotor deficits impair balance and are a well-recognised risk factor for falling [32,33,34,35].

The neurotoxic effects on the peripheral nervous system in cancer therapy are a relevant dose-limiting factor in cancer therapy, with CIPN incidences of 70% depending on the chemotherapeutic agents [10]. The association between CIPN and falls has been documented at various stages of the antineoplastic therapy but the direct functional relationship remains unclear. Previous study data are heterogeneous in respect of the applied chemotherapeutic agents, cancer population, and CIPN assessment (e.g., rating scales) [15,17,22].

In our prospective study, we assessed sensorimotor symptoms by clinical neurological examination and found no relevant progress of the initial neuropathic score (NDS) within the first 3 months of the oxaliplatin-based chemotherapy. Literature on the neurotoxic profile of oxaliplatin predominantly describes sensory neuropathies with dosages exceeding >540 mg/m2 [36], while the mean dose in the present study was 562 mg/m2. Furthermore, we had to adjust the time interval provided for correlation analysis from 6 to 3 months because of the high dropout rate (60%). A higher oxaliplatin dosage was reached only in those participants that completed the study (n = 8) of which only 50% reached oxaliplatin doses above 1,000 mg/m2 (max. 1,500 mg/m2). High-grade and persistent CIPN with motor dysfunction, including impaired coordination and mobility, is described with advanced oxaliplatin administration above 1,000 mg/m2 or 12 cycles [12,13,37,38,39]. The small number of participants combined with the low cumulative doses – only slightly higher than the mean minimum neurotoxic dose – are the most likely reasons that we found no relevant CIPN.

Nevertheless, our clinical neurological screening detected mild sensorimotor deficits at baseline in 40% of participants that were not pre-diagnosed. In this regard, our retrospective analysis confirmed that pre-existing polyneuropathy is a risk factor for future falls. Our prospective neurological evaluation provided a more nuanced view of the aetiology of sensorimotor deficits in the early chemotherapy intervals. CIPN is commonly assessed using subjective rating scales and retrospective examinations, which may be insensitive in distinguishing between prior polyneuropathy as a predictor of falls and the development of CIPN [40]. Thereby, our findings confirm recommendations in oncological treatment that a brief neurological examination before and during ongoing chemotherapy is essential in supportive oncological management [41].

4.3 Falls

Falls in oncology are more common than in the general population because cancer and its treatment put oncology patients at risk of severe impairment; in particular, neurotoxic chemotherapy drugs and an advanced stage of cancer are specific risk factors in oncology [15,17]. Clinically, impairment in ADL is strongly associated with falls in older adults with cancer and is a dynamic risk factor during chemotherapy [42,43]. Moreover, the risk of falling in oncology patients increases with the number of comorbidities [1]. Although fall risk is multifactorial and may vary over time, continuous and time-efficient screening has not yet been implemented in outpatient oncology. In this way, the fall risk index applied in our study summarises established markers of morbidity and frailty in hospitalised and outpatient oncology settings such as age, medication type and number, use of assistive devices or visual impairment [7,42,44]. Among community-dwelling older persons, the predicted 1-year risk of falling increased to 80% when four or more risk factors were present [31]. All fallers in our study exceeded the threshold of four risk factors and were identified as high-risk at baseline assessment, whereas none of the included risk index variables were independently associated with falls. Our results therefore underline the multifactorial aetiology of falls in an outpatient oncological setting. The characteristics of falls in our specific cohort did not differ from those in geriatric patients [45].

4.4 Measurements of physical performance

In contrast, previous studies proved the Tinetti test as a solid screening and follow-up instrument for mobility and fall risk in populations with severe physical limitations and in geriatric individuals [46,47,48]. Previous evaluations described single-task instruments (e.g., TUG) as well as physical performance batteries as feasible methods of performance evaluation to assess the potential for falls in geriatric oncology clinics [42,49].

In contrast, our clinical performance measurements did not detect changes in functional fall risk. We found high to maximal scores in mobility and balance tests (TUG, Tinetti) and robust scores for lower limb muscle strength (CRT) that remained almost unchanged over 3 and 6 months, indicating no physical deterioration. These results are most likely due to ceiling effects, which are consistent with previous evaluations, e.g., of the Tinetti test, which found low sensitivity in predicting falls in individuals with mild balance disorders due to coarse scaling [48]. Although we accounted for age-related performance thresholds on other tests, such as the TUG tool, there were no significant results related to fall risk [50].

We summarise that the selected geriatric assessment tools are not applicable to our predominantly younger (mean age of cohort: 59 years) and very mobile adults at the start of oxaliplatin treatment. In future studies, mobility assessments using more finely graded scales, such as the Berg Balance Scale [51], may be more appropriate to screen physically fit adults with a cancer diagnosis.

4.5 Screening physical activity during oxaliplatin treatment

In the present study, the PASE proved to be a discriminative screening tool for physical functioning during the first 6 months of chemotherapy. PASE has been shown to be an objective, discriminative, and dynamic instrument for physical activity and health-related quality of life in various cancers [52,53,54] and in outpatient oncology [55,56,57].

In line with previous studies, PASE underlined – in contrast to the functional measurements – that cancer patients are physically less active compared to a non-cancer population [54,58]. Since physical activity is directly linked to quality of life [59,60] and tumour survival [61,62,63,64], it should be monitored during active cancer therapy. PASE has been validated for this purpose with objective markers of functional health such as grip strength, balance, and lower limb strength [65]. Even among the more physically fit participants that completed the study, PASE still discriminated changes in leisure time and household activities well; that is, no ceiling effect was detected. High discriminatory power of assessment tools may become even more important in the future, as early cancer diagnosis in combination with increasing safety and more favourable side effect profiles of cancer therapies are expected to result in a higher prevalence of cancer survivors with low functional impairment in long-term clinical supportive management. In contrast, scales rated by clinicians such as the Karnofsky performance status, and ECOG, which remain integral to health assessment in clinical disease management and research, have limited predictive value for chemotherapy-related toxicity in patients with good to excellent health [66,67].

Therefore, we recommend PASE not only for prognostic evaluations, but also as a therapeutic tool, since self-monitoring increases the individual awareness of patients to maintain activity during chemotherapy [68].

4.6 Baseline comparison of dropouts versus completers

In the present study, high levels of psychological distress and polypharmacy at baseline were correlated with study discontinuation. In addition to fear of falling and anxiety as major causes of limited physical activity [69], cancer and treatment-related side effects are also barriers to daily physical activity [70]. Targeted interventions can support patients with poor health-related behaviours and attitudes to avoid or reduce the additional risks associated with a new cancer diagnosis [71].

In addition to the above-mentioned psychological factors, participants who dropped out of the study had a higher incidence of polypharmacy than those who completed the study. Polypharmacy is not only a marker of morbidity but also a strong predictor of falls [72,73], as reflected in our index screening for falls. This may be due to the fact that cancer patients are more susceptible to adverse drug interactions and are particularly likely to take unfavourable drug classes or combinations as part of their cytostatic treatment [44].

4.7 Limitations

The single-centre approach extended participant recruitment over a two-year period. The elaborate, in-depth examinations in our study were time-consuming and required a high individual effort for participants during chemotherapy as the main barrier to study participation. The small sample size and resulting low statistical power limited our ability to detect potentially weaker associations between the selected objective markers of physical functioning and chemotherapy-induced neurotoxicity. Therefore, results must be interpreted cautiously.

We did not include measures of postural sway, which would have allowed a more accurate assessment of the effects of latent neuropathy (i.e., even in the absence of CIPN) on balance control and indirectly on fall risk [74].

Because of the limited value of oncological scales such as Karnofsky or ECOG [66,67], with respect to our study objectives, we focused on more specific assessment tools, but this may limit the comparability of our study cohort with other oncological study cohorts.

This study was intended as an initial project to determine whether CIPN-associated fall risk could be appropriately assessed using physical performance tools. As we were confronted with the limitations of these tools, the focus of further investigations in an outpatient oncology setting may be to verify and validate the fall risk index as a preventive assessment tool.

5 Conclusions

In this prospective observational cohort study, we could show that pre-chemotherapy conditions contributed more to falls than treatment-related factors in outpatients undergoing oxaliplatin-based chemotherapy. Therefore, a fall risk index including general frailty and morbidity markers [31] might be a promising predictor of falls and should be implemented and validated in a larger multicenter trial. Moreover, we recommend self-monitoring of physical activity during chemotherapy (PASE) since self-monitoring increases the individual awareness of patients to maintain activity during chemotherapy [68].

# Shared first authorship.

tel: +49-6131-988-539

Acknowledgements

We thank C. Schimanski for his support in recruiting patients from the oncology outpatient clinic.

  1. Funding information: Intramural grant of the Johannes Gutenberg University Mainz.

  2. Conflict of interest: The authors declare that they have no conflict of interest.

  3. Data availability statement: The data sets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Received: 2022-10-15
Revised: 2023-02-21
Accepted: 2023-03-20
Published Online: 2023-05-27

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0696
Keywords for this article
chemotherapy; fall-risk-index; outpatient setting; polyneuropathy; neurotoxicity
Creative Commons
BY 4.0

Articles in the same Issue

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  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
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  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
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  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
  24. Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
  25. Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
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  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
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  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
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  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
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  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
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  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
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  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
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  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
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  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
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  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
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  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
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  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
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  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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