A Drosophila model to screen Alport syndrome COL4A5 variants for their functional pathogenicity.

Alport syndrome is a hereditary chronic kidney disease, attributed to rare pathogenic variants in either of three collagen genes (COL4A3/4/5) with most localized in COL4A5. Trimeric type IV Collagen α3α4α5 is essential for the glomerular basement membrane that forms the kidney filtration barrier. A means to functionally assess the many candidate variants and determine pathogenicity is urgently needed. We used Drosophila, an established model for kidney disease, and identify Col4a1 as the functional homolog of human COL4A5 in the fly nephrocyte (equivalent of human podocyte). Fly nephrocytes deficient for Col4a1 showed an irregular and thickened basement membrane and significantly reduced nephrocyte filtration function. This phenotype was restored by expressing human reference (wildtype) COL4A5, but not by COL4A5 carrying any of three established pathogenic patient-derived variants. We then screened seven additional patient COL4A5 variants; their ClinVar classification was either likely pathogenic or of uncertain significance. The findings support pathogenicity for four of these variants; the three others were found benign. Thus, demonstrating the effectiveness of this Drosophila in vivo kidney platform in providing the urgently needed variant-level functional validation.

Effectiveness of Exercise Interventions on Body Composition, Exercise Capacity, Fatigue, and Quality of Life in Patients with Liver Cirrhosis: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Diminished muscle protein synthesis in cirrhosis leads to reduced strength and mass, impacting daily activities and overall quality of life. AIMS: This study aimed to examine the effectiveness of exercise intervention in body composition, exercise capacity, fatigue, and quality of life in patients with liver cirrhosis. METHODS: A systematic search of medical databases, including PubMed, Embase, Cochrane, and CINAHL, was executed from their inception to November 2022. The inclusion criteria were randomized controlled trials comparing exercise interventions with a control group that did not receive exercise interventions. RESULTS: From the initially identified 2,565 articles, eight studies with a total of 220 patients were eligible for inclusion in this meta-analysis. According to the meta-analysis, exercise significantly improved the six-minute walk distance (6MWD) by 68.93 m (95% CI 14.29-123.57) compared to the control group. Furthermore, the subgroup analysis revealed that combing exercise with amino acid supplementation had a greater positive effect on the 6MWD (MD = 144.72, 95% CI 87.44-202.01). Exercise also significantly increased thigh circumference (MD = 1.26, 95% CI 0.12-2.39) and the thigh ultrasound average compression index (MD = 0.07, 95% CI 0.00-0.14). Moreover, exercise significantly decreased fatigue levels by 0.7 points in patients with liver cirrhosis (95% CI 0.38-1.03). However, no significant effects were observed on body mass index (BMI), fat mass, fat-free mass, and quality of life. CONCLUSIONS: Exercise can improve exercise capacity, thigh muscle thickness, and fatigue in patients with cirrhosis, but it does not have a significant impact on fat mass, BMI, or quality of life.

Hematologic and Serum Biochemical Values Associated With Different Stages of Hospital-Acquired Pressure Injuries in Patients: A Retrospective Study.

PURPOSE: The primary purpose of this study was to determine whether hematologic and serum biochemical values used as indicators of nutritional status, anemia, and/or infection were associated with the risk of hospital-acquired pressure injuries (PIs) and stage of PIs in patients. DESIGN: A retrospective review of medical records. SUBJECTS AND SETTING: Data were collected from medical records including official PI records and PI incident reports of inpatients at a teaching hospital in Taiwan between January 2019 and October 2020. METHODS: We collected demographic variables of the inpatients and their hematologic and serum biochemical values within 1 day of PI occurrence (including the day of PI occurrence), 6 to 7 days before PI occurrence, and 13 to 14 days before PI occurrence. RESULTS: Among the 309 inpatients with official PI records, 105 (34.0%) had Stage 1 PIs, 131 (42.4%) had Stage 2 or 3 PIs, and 73 (23.6%) had unstageable or suspected deep tissue injuries. After controlling for the type of department where PIs occurred and length of hospital stay up to the day of PI occurrence, we found significant differences in levels of hemoglobin (odds ratio [OR] = 0.47, P = .009) within 1 day of PI occurrence and in albumin (OR = 0.30, P = .001) 13 to 14 days before PI occurrence. CONCLUSIONS: Study findings suggest that lower hemoglobin levels on the day of PI occurrence and lower albumin levels 2 weeks before PI occurrence resulted in a significantly higher risk of developing unstageable or suspected deep tissue injuries than of developing Stage 1 PIs.

Bidirectional relationship between late-onset epilepsy (LOE) and dementia: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: To explore the bidirectional relationship of late-onset epilepsy (LOE) with dementia and Alzheimer's disease (AD). METHODS: Using the common electronic databases, including PubMed, Cochrane Library databases and EMBASE, we systematically reviewed published cohort studies that assessed the risk of LOE in individuals comorbid with dementia or AD, and those with dementia or AD comorbid with LOE that had been published up to 31 March 2023. The data extraction process was carried out independently by two authors. The summary adjusted relative ratio (aRR) was calculated by employing Rev Man 5.3 for the inclusion of studies. To investigate the origins of heterogeneity, we conducted both subgroup and sensitivity analyses. In the presence of heterogeneity, a random-effects model was employed. To evaluate potential publication bias, we utilized the funnel plot and conducted Begg's and Egger's tests. RESULTS: We included 20 eligible studies in the final analysis after a rigorous screening process. Pooled results indicated that LOE was association with an increased risk of all-cause dementia (aRR: 1.34, 95% confidence interval [CI]: 1.13-1.59) and AD (aRR: 2.49, 95% CI: 1.16-5.32). In addition, the pooled effect size for LOE associated with baseline AD and all-cause dementia were 3.51 (95% CI: 3.47-3.56) and 2.53 (95% CI: 2.39-2.67), respectively. Both sensitivity and subgroup analyses showed that these positive correlations persisted. According to the results of the Egger's and Begg's tests, as well as visual inspection of funnel plots, none of the studies appeared to be biased by publication. CONCLUSION: The findings suggested that LOE is a potential risk factor for dementia and AD, and vice versa, dementia and AD are both potential risk indicators for LOE. Since there is substantial heterogeneity among the cohorts analyzed and more cohort studies should be conducted to confirm the correlations found in the current study.

Reliability of predicting low-burden (≤ 2) positive axillary lymph nodes indicating sentinel lymph node biopsy in primary operable breast cancer - a retrospective comparative study with PET/CT and breast MRI.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in early breast cancer patients with low-burden axillary metastasis (≤ 2 positive nodes). This study aimed to determine the diagnostic performances of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and breast magnetic resonance imaging in detecting axillary lymph node (ALN) metastases and the reliability to predict ALN burden. METHODS: A total of 275 patients with primary operable breast cancer receiving preoperative PET/CT and upfront surgery from January 2001 to December 2022 in a single institution were enrolled. A total of 244 (88.7%) of them also received breast MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT and breast MRI were assessed. The predictive values to determine ALN burden were evaluated using radio-histopathological concordance. RESULTS: PET/CT demonstrated a sensitivity of 53.4%, specificity of 82.1%, PPV of 65.5%, NPV of 73.5%, and accuracy of 70.9% for detecting ALN metastasis, and the corresponding values for MRI were 71.8%, 67.8%, 56%, 80.8%, and 69.2%, respectively. Combining PET/CT and MRI showed a significantly higher PPV than MRI (72.7% vs 56% for MRI alone, p = 0.037) and a significantly higher NPV than PET/CT (84% vs 73.5% for PET/CT alone, p = 0.041). For predicting low-burden axillary metastasis (1-2 positive nodes), the PPVs were 35.9% for PET/CT, 36.7% for MRI, and 55% for combined PET/CT and MRI. Regarding patients with 0-2 positive ALNs in imaging, who were indicated for SLNB, the predictive correctness was 96.1% for combined PET/CT and MRI, 95.7% for MRI alone, and 88.6% for PET/CT alone. CONCLUSIONS: PET/CT and breast MRI exhibit high predictive values for identifying low-burden axillary metastasis in patients with operable breast cancer with ≦ 2 positive ALNs on imaging.

Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy.

Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions.

N-acetylcysteine and Hydroxychloroquine Ameliorate ADMA-Induced Fetal Growth Restriction in Mice via Regulating Oxidative Stress and Autophagy.

Fetal growth restriction (FGR) seriously threatens perinatal health. The main cause of FGR is placental malperfusion, but the specific mechanism is still unclear, and there is no effective treatment for FGR. We constructed a FGR mouse model by adding exogenous asymmetric dimethylarginine (ADMA) through in vivo experiments and found that ADMA could cause placental dysplasia and induce the occurrence of FGR. Compared with the control group, reactive oxygen species (ROS) production in the placenta was increased in mice with FGR, and the expression of autophagy-related proteins p-AKT/AKT, p-mTOR/mTOR, and P62 was significantly decreased, while the expression of Beclin-1 and LC3-II was significantly increased in the FGR group. Furthermore, ADMA had a favorable effect in promoting the formation of autophagosomes. Hydroxychloroquine (HCQ) and N-acetylcysteine (NAC) improved ADMA-induced disorders of placental development and alleviated ADMA-induced FGR. This study found that ADMA could cause excessive autophagy of trophoblasts by increasing the level of oxidative stress, ultimately leading to the occurrence of FGR, and HCQ and NAC had therapeutic effects on ADMA-induced FGR.

Influence of body mass index on severity of rotator cuff tears.

BACKGROUND: Research on the relationship between obesity and rotator cuff tears (RCTs) has been limited to the impact of obesity on the results of arthroscopic repair of RCTs; thus, a need for rigorous research controlling for other factors affecting RCTs is warranted, especially to better understand the impact of body mass index (BMI) on RCT severity. METHODS: A retrospective study of admission records contained in electronic medical records pertaining to patients who were admitted for RCT repair on 1 shoulder between January 2018 and July 2022 was conducted. In total, 386 patients were included. In accordance with guidance regarding obesity from Taiwan's Ministry of Health and Welfare, patients were divided into three groups: underweight or normal weight (BMI <24.0 kg/m2), overweight (BMI 24.0-26.9 kg/m2), or obese (BMI ≥27.0 kg/m2). Magnetic resonance imaging was used to assess RCT severity in terms of four parameters: Patte stage (PS), fatty infiltration (FI), anteroposterior tear size (AP), and retraction size. Multinomial logistic regression analysis was performed on PS and FI grade data, and multiple linear regression analysis was performed on AP tear size and retraction size in order to analyze impact. RESULTS: Our results revealed that the average age of the 386 patients was 63.41 years (SD = 9.29) and the mean BMI was 25.88 (SD = 3.72) kg/m2. We found significant differences in PS (P = .003), FI (P < .001), retraction size (P = .001), and AP tear size (P = .001) among patients who were underweight or normal weight, overweight, and obese. After controlling for other risk factors, including age, gender, RCT-prone occupation, duration of shoulder pain prior to surgery, history of shoulder injury, and tobacco use, we found that obese patients had higher severity levels in PS (B = 1.21, OR = 3.36, P = .029), FI (B = 1.38, OR = 3.96, P < .001), retraction size (ß = 0.18, P = .001), and AP tear size (ß = 0.18, P = .001) compared to underweight or normal weight patients. CONCLUSIONS: Our study demonstrates that a correlation exists between BMI-measured obesity and RCT severity. We therefore suggest that adults control their weight given that maintaining a healthy weight is highly associated with better shoulder health.

Influence of severity of illnesses on risk of death in intensive care unit patients with severity of pressure injuries as mediating variable.

This study was to verify whether the severity of pressure injuries (PIs) in intensive care unit (ICU) patients plays a mediating role in the relationship between severity of their illnesses and risk of death. I examined adult patients admitted to the ICUs between 1 January 2014 and 31 August 2021. The average follow-up period was 11.34 months. A total of 390 ICU patients suffered from PIs. The influences of the APACHE II score of the ICU patients on the mediating variable 'unstageable & DTPIs vs. Stage 1&2 PIs' and on risk of death were significant. After controlling the influence of APACHE II score on risk of death, the influences of mediating variables 'Stage 3&4 PIs vs. Stage 1&2 PIs' and 'unstageable & DTPIs vs. Stage 1&2 PIs' on risk of death were also significant. The regression coefficient of APACHE II score of the ICU patients declined after the severity of PIs was included. The Sobel test on the indirect effects also reached the level of significance. The severity of illnesses is a factor that is beyond my control, severe PIs should still be prevented to lower the risk of death.

Hotspots and frontiers of the relationship between gastric cancer and depression: A bibliometric study.

BACKGROUND: A significant relationship between gastric cancer (GC) and depression has been found in the last 20 years. However, there is no comprehensive information that helps researchers find popular and potential research directions on GC and depression. AIM: To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between GC and depression. METHODS: We used the Web of Science Core Collection to search and collate the literature on GC and depression from 2000 to 2022 on 31 May, 2023. Then, visualization analysis was performed using VOSviewer software (version 1.6.19) and the Bibliometrix package in R software. RESULTS: We retrieved 153 pertinent publications from 2000 to 2022. The annual publication count showed an overall upward trend. China had the most prominent publications and significant contributions to this field (n = 64, 41.83%). Before 2020, most studies focused on "the effect of GC on the development and progression of depression in patients." The latest research trends indicate that "the effect of depression on the occurrence and development of GC and its mechanism" will receive more attention in the future. CONCLUSION: The study of "the effect of depression on the occurrence and development of GC and its mechanism" has emerged as a novel research theme over the past two years, which may become a research hotspot in this field. This study provides new insights into the hotpots and frontiers of the relationship between GC and depression, potentially guiding researchers toward hot research topics in the future.

A SNARE protective pool antagonizes APOL1 renal toxicity in Drosophila nephrocytes.

BACKGROUND: People of Sub-Saharan African ancestry are at higher risk of developing chronic kidney disease (CKD), attributed to the Apolipoprotein L1 (APOL1) gene risk alleles (RA) G1 and G2. The underlying mechanisms by which the APOL1-RA precipitate CKD remain elusive, hindering the development of potential treatments. RESULTS: Using a Drosophila genetic modifier screen, we found that SNARE proteins (Syx7, Ykt6, and Syb) play an important role in preventing APOL1 cytotoxicity. Reducing the expression of these SNARE proteins significantly increased APOL1 cytotoxicity in fly nephrocytes, the equivalent of mammalian podocytes, whereas overexpression of Syx7, Ykt6, or Syb attenuated their toxicity in nephrocytes. These SNARE proteins bound to APOL1-G0 with higher affinity than APOL1-G1/G2, and attenuated APOL1-G0 cytotoxicity to a greater extent than either APOL1-RA. CONCLUSIONS: Using a Drosophila screen, we identified SNARE proteins (Syx7, Ykt6, and Syb) as antagonists of APOL1-induced cytotoxicity by directly binding APOL1. These data uncovered a new potential protective role for certain SNARE proteins in the pathogenesis of APOL1-CKD and provide novel therapeutic targets for APOL1-associated nephropathies.

Diagnostic Accuracy for Acute Rib Fractures: A Cross-sectional Study Utilizing Automatic Rib Unfolding and 3D Volume-Rendered Reformation.

RATIONALE AND OBJECTIVES: The aim of this study was to compare the use of computed tomography (CT) with automatic rib unfolding and three-dimensional (3D) volume-rendered imaging in the detection and characterization of rib fractures and flail chest. MATERIALS AND METHODS: A total of 130 patients with blunt chest trauma underwent whole-body CT, and five independent readers assessed the presence and characterization of rib fractures using traditional CT images, automatic rib unfolding, and 3D volume-rendered images in separate readout sessions at least 2 weeks apart. A gold standard was established by consensus among the readers based on the combined analysis of conventional and reformatted images. RESULTS: Automatic rib unfolding significantly reduced mean reading time by 47.5%-74.9% (P < 0.0001) while maintaining a comparable diagnostic performance for rib fractures (positive predictive value [PPV] of 82.1%-93.5%, negative predictive value [NPV] of 96.8%-98.2%, and 69.4%-94.2% and 96.9%-99.1% for conventional axial images and 70.4%-85.1% and 95.2%-96.6% for 3D images) and better interobserver agreement (kappa of 0.74-0.87). For flail chest, automatic rib unfolding showed a PPV of 85.7%-100%, NPV of 90.4%-99.0%, and 80.0%-100% and 89.7%-100% for conventional axial images and 76.9%-100% and 89.0%-92.1% for 3D images. CONCLUSION: Automatic rib unfolding demonstrated equivalent diagnostic performance to conventional images in detecting acute rib fractures and flail chest, with good interobserver agreement and time-saving benefits.

Correlation between hemoglobin levels and depression in late-stage cancer patients with irritability as mediating variable.

PURPOSE: In late-stage cancer, the cancer itself or the side effects of cancer treatment are known to affect the hemoglobin (Hgb) levels or emotions of patients. We to investigate the relationship between Hgb levels and depression in late-stage cancer patients and verified whether irritability has a mediating effect on this relationship. METHOD: The research tools included a patient basic information form, the Irritability Scale-Initial Version (TISi), and the Hamilton Depression Rating Scale (HAMD). We first compared the Hgb levels, HAMD scores, and TISi scores of the cancer patients with different attributes, performed multiple hierarchical regression analysis, and then analyzed the mediating effects of TISi scores using the Sobel test. RESULTS: In the 117 late-stage cancer patients, Hgb levels of patients with a BMI<18.5 kg/m2 were lower than those of the patients with a BMI 24.0 kg/m2. Hgb levels had a negative influence on both TISi scores (B = -2.74, p = .001) and HAMD scores (B = -0.75, p = .010). TISi scores mediated the relationship between Hgb levels and HAMD scores (Z = 2.06, p = .040). CONCLUSIONS: Irritability is a mediating variable of the influence of Hgb levels on depression, meaning that lower Hgb levels in late-stage cancer patients may be detrimental to emotional stability, induce irritability, and thereby cause depression. Thus, in the psychological care of late-stage cancer patients, medical teams should be more vigilant in monitoring Hgb levels and anemia treatment.

Genetic stock structure of the silky shark Carcharhinus falciformis in the Indo-Pacific Ocean.

The silky shark, Carcharhinus falciformis, is a cosmopolitan species commonly caught as a bycatch for longline fisheries. However, the genetic stock structure for the Indo-Pacific Ocean is not well-defined yet. Here, we used eight microsatellite loci to examine the genetic stock structure and effective population size of 307 silky sharks across 5 Indo-Pacific sampling locations. A major genetic break was found between Aceh and the remaining locations (FST = 0.0505-0.0828, p = 0.001). The Indian Ocean displayed a slightly lower effective population estimate (Ne) compared to the Pacific Ocean, potentially due to the higher fishing pressure in the Indian Ocean region. The lowest Ne was found in the Aceh population (Ne = 2.3), suggesting it might be a small and endemic population. These findings offer valuable information for the conservation and management of the silky shark. We suggest that the population around Aceh waters constitutes a distinct stock and should be managed independently. Further investigations into migratory and movement patterns are needed to define the boundaries of different stocks, ensuring effective management the silky shark across the Indo-Pacific region.

Gout/hyperuricemia reduces the risk of Alzheimer's disease: A meta-analysis based on latest evidence.

OBJECTIVE: Previous studies have found the potential role of gout or hyperuricemia in subsequent development of Alzheimer's disease (AD) but reported inconsistent results. We conducted the current meta-analysis to evaluate whether an association exists between gout/ hyperuricemia and AD. METHODS: We systematically searched PubMed and EMBASE for the published cohort studies that measured the risk of AD in subject with gout/ hyperuricemia up to May 20, 2023. Data extraction was employed by two authors independently. Rev Man 5.3 and Stata 15.0 software were used to calculate the relative ratio (RR) or hazard ratio (HR) for including studies. Subgroup analysis was performed to assess the sources of heterogeneity. A random-effects model was adopted when heterogeneity was present. The funnel plot, Begg's test, and and Egger's test were used to assess publication bias. RESULTS: After rigorous screening, seven eligible studies were included in the final analyses. Pooled results indicated that gout or hyperuricemia decreases the risk of AD (RR: 0.69, 95% CI: 0.64∼0.72), with a high heterogeneity of 93%. Subgroup analyses showed that regional distribution was the source of heterogeneity. Egger's and Begg's tests as well as visual inspection of funnel plot suggested no publication bias in the studies. CONCLUSION: The findings suggested that gout or hyperuricemia might have a protective effect against AD. This negative correlation should be verified by more cohort studies due to the existence of substantial heterogeneity.

Differences Between Patients With Diabetes Mellitus and Obese Patients in Occurrence of Peri-Prosthetic Joint Infection: A Systemic Review and Meta-Analysis.

Background: To understand the differences between patients with diabetes mellitus and obese patients with respect to the occurrence of peri-prosthetic joint infection (PJI) after lower-extremity joint arthroplasty as well as to identify differences in PJI occurrence at different time periods. Patients and Methods: The Cochrane Library, CINAHL, MEDLINE, and PubMed were searched for literature published between January 2000 and July 2022. Our targets were studies involving patients with PJI who had already been diagnosed as having diabetes mellitus or being obese before receiving lower-extremity joint arthroplasty. Analysis was performed using Comprehensive Meta-Analysis Software (CMA) Version 3 (Biostat, Inc., Englewood, NJ, USA). Results: A total of 53,522 patients with diabetes mellitus and 360,018 obese patients were included. The forest plot for patients with and without diabetes mellitus indicated that patients with diabetes mellitus were more likely to contract PJIs than were patients without diabetes mellitus (odds ratio, 1.84; 95% confidence interval [CI], 1.56-2.16) and that no differences existed among early, delayed, and late PJI occurrence in patients with diabetes mellitus. The forest plot for obese and non-obese patients indicated that obese patients were more likely to contract PJIs than were non-obese patients (odds ratio, 1.86; 95% CI, 1.53-2.14) and that among obese patients, early PJI occurrence was higher than was late PJI occurrence. In addition, the mixed model indicated that obese patients were more likely to develop early PJIs than were patients with diabetes mellitus. Conclusions: Patients with diabetes mellitus and obese patients were more likely to develop PJIs than were patients without diabetes mellitus and non-obese patients, and that obese patients were more likely to develop early PJIs than late PJIs. Also, obese patients were more likely to develop early PJIs than patients with diabetes mellitus.

Primary pulmonary epithelioid hemangioendothelioma.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare tumour of vascular origin with low to intermediate malignancy. Typical radiological finding on CT is multiple small nodules in bilateral lungs, and some will have punctate calcifications and pleural thickening. The diagnosis of PEH is confirmed by histopathological findings and positive immunohistochemistry staining. We report a case of a woman in her 50s with a medical history of lung adenocarcinoma. Later, regular chest CT during a routine cancer follow-up revealed multiple small pulmonary nodules and increased sizes of these nodules on serial images, initially misdiagnosed as multiple lung metastases. The histopathological diagnosis was made on a pulmonary wedge resection. Finally, PEH was diagnosed on the basis of positive immunohistochemical staining for CD31, ERF and TFE3. In the current study, the clinicopathological features and review of the literature were investigated. Our case highlights the importance of a histological diagnosis to avoid misdiagnosis.

Effectiveness of Cryotherapy on Cancer Therapy-Induced Oral Mucositis: An Umbrella Review.

BACKGROUND: Oral mucositis (OM) considerably affects the experience of patients with cancer during treatment. This study investigated the effects of cryotherapy on cancer therapy-induced OM. OBJECTIVE: This study aimed to systematically appraise evidence on whether cryotherapy can reduce the incidence and severity of OM. METHODS: We conducted an umbrella review to examine the effect of cryotherapy on cancer-related OM. The primary outcome was the incidence and severity of OM. We performed a subgroup analysis including solid cancers and hematological malignancies. RESULTS: Five meta-analyses were included. Cryotherapy could more effectively reduce the incidence of severe OM (risk ratio [RR], 0.37; 95% prediction interval [PI], 0.22-0.64). In the subgroup analyses of solid cancers or hematological malignancies, cryotherapy significantly reduced the incidence of grades 2 to 4 OM in patients with solid cancers (RR, 0.51; 95% PI, 0.34-0.78 and RR, 0.52; 95% PI, 0.36-0.74). However, no significant difference was observed in the incidence of OM in patients with hematological malignancies regarding any grade or grade 3 or 4 OM. Moreover, cryotherapy did not significantly reduce the OM duration (mean difference, -0.13; 95% PI, -20.89 to 20.63; mean difference, -2.99, 95% PI, -8.10 to 2.12). CONCLUSION: Cryotherapy can reduce the incidence of severe OM induced by chemotherapy or radiotherapy. IMPLICATION FOR PRACTICE: We recommend the inclusion of this safe, simple, and convenient intervention in chemotherapy or radiotherapy plans. Additional clinical trials are warranted to extend the limited evidence on the effectiveness of cryotherapy in reducing the severity and duration of OM.

Diagnostic accuracy of pre-operative breast magnetic resonance imaging (MRI) in predicting axillary lymph node metastasis: variations in intrinsic subtypes, and strategy to improve negative predictive value-an analysis of 2473 invasive breast cancer patients.

BACKGROUND: The value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to test the potential of combining breast MRI and clinicopathologic factors to identify low-risk groups of ALN metastasis and improve diagnostic performance. MATERIAL AND METHODS: Patients with primary operable invasive breast cancer with pre-operative breast MRI and post-operative pathologic reports were retrospectively collected from January 2009 to December 2021 in a single institute. The concordance of MRI and pathology of ALN status were determined, and also analyzed in different intrinsic subtypes. A stepwise strategy was designed to improve MRI-negative predictive value (NPV) on ALN metastasis. RESULTS: 2473 patients were enrolled. The diagnostic performance of MRI in detecting metastatic ALN was significantly different between intrinsic subtypes (p = 0.007). Multivariate analysis identified tumor size and histologic type as independent predictive factors of ALN metastases. Patients with HER-2 (MRI tumor size ≤ 2 cm), or TNBC (MRI tumor size ≤ 2 cm) were found to have MRI-ALN-NPV higher than 90%, and these false cases were limited to low axillary tumor burden. CONCLUSION: The diagnostic performance of MRI to predict ALN metastasis varied according to the intrinsic subtype. Combined pre-operative clinicopathologic factors and intrinsic subtypes may increase ALN MRI NPV, and further identify some groups of patients with low risks of ALN metastasis, high NPV, and low burdens of axillary disease even in false-negative cases.

Use of Magnetic Resonance Imaging for Evaluating Residual Breast Tissue After Robotic-Assisted Nipple-Sparing Mastectomy in Women With Early Breast Cancer.

OBJECTIVE: Prospective studies on postoperative residual breast tissue (RBT) after robotic-assisted nipple-sparing mastectomy (R-NSM) for breast cancer are limited. RBT presents an unknown risk of local recurrence or the development of new cancer after curative or risk-reducing mastectomies. This study investigated the technical feasibility of using magnetic resonance imaging (MRI) to evaluate RBT after R-NSM in women with breast cancer. MATERIALS AND METHODS: In this prospective pilot study, 105 patients, who underwent R-NSM for breast cancer at Changhua Christian Hospital between March 2017 and May 2022, were subjected to postoperative breast MRI to evaluate the presence and location of RBT. The postoperative MRI scans of 43 patients (age, 47.8 ± 8.5 years), with existing preoperative MRI scans, were evaluated for the presence and location of RBT. In total, 54 R-NSM procedures were performed. In parallel, we reviewed the literature on RBT after nipple-sparing mastectomy, considering its prevalence. RESULTS: RBT was detected in 7 (13.0%) of the 54 mastectomies (6 of the 48 therapeutic mastectomies and 1 of the 6 prophylactic mastectomies). The most common location for RBT was behind the nipple-areolar complex (5 of 7 [71.4%]). Another RBT was found in the upper inner quadrant (2 of 7 [28.6%]). Among the six patients who underwent RBT after therapeutic mastectomies, one patient developed a local recurrence of the skin flap. The other five patients with RBT after therapeutic mastectomies remained disease-free. CONCLUSION: R-NSM, a surgical innovation, does not seem to increase the prevalence of RBT, and breast MRI showed feasibility as a noninvasive imaging tool for evaluating the presence and location of RBT.