bluuebunny/crossref_metadata_2025 huggingface dataset:
CCL1 As a Biomarker of Engraftment Syndrome of Hematological Stem Cell Transplantation
Authors: Maki Hiroaki , Honda Akira , Masamoto Yosuke , Kurokawa Mineo
Published: December 2023

BACKGROUND

Many complications occur in the practice of hematopoietic stem cell transplantation, especially those presenting with fever, which can be caused by infection as well as engraftment syndrome (ES), which is difficult to distinguish. The mechanism of ES is unknown, and no characteristic biomarkers have been identified.

METHODS

We attempted to identify cytokines specific to the engraftment syndrome by cytokine array analysis of sera from 7 patients who underwent HSCT at our institution from January 2019 to March 2022 and who developed fever between 1 week before and the day of engraftment.

Cases in which pathogens were detected in blood culture at the time of fever were diagnosed as infections, and cases in which blood culture was negative or clinically treated as engraftment syndrome or fever associated with engraftment were diagnosed as engraftment syndrome. Cases that did not present with fever from infusion to engraftment were used as negative controls.

RESULTS.

Three of the seven patients had fever due to infection and four had fever due to engraftment syndrome. Median age was 41 (21-62) years, 5 males and 2 females. Four patients had acute leukemia, one had chronic myelomonocytic leukemia, and two had nonhematologic tumors. The donors were blood related in 3 cases, unrelated in 3 cases, and cord blood in 2 cases. Pretreatment was myeloablative (MAC) in 2 patients and reduced intensity pretreatment (RIC) in 5 patients.

Cytokine arrays identified five cytokines that were elevated in the ES group. Of these, cytokine The cytokine CCL1 (I-309) tended to be elevated in the ES group (p=0.06). The validity of CCL1 with respect to the diagnosis of fever of engraftment was examined using sera from another 16 hematopoietic stem cell transplant cases performed at the same period, and the results showed that CCL1 was only mildly elevated in cases diagnosed with infection, regardless of the elevated values of fever and inflammatory response, but tended to be elevated in fever of engraftment (area under ROC curve: 0.74 (95% confidence interval 0.422-1)).

CONCLUSIONS.

CCL1 was identified as a cytokine specific for ES, indicating that CCL1 may be useful in differentiating ES from infection. CCL1 is mainly secreted by T lymphocytes and its oversecretion during the hematopoietic recovery process may be involved in immune activation and the engraftment syndrome.
Voltage-Dependent Anion Channel 2 (VDAC2) Drives Rituximab Resistance Via Inhibiting Ferroptosis in Diffuse Large B Cell Lymphoma
Authors: Li Qiong , Xia Jing , Li Xinlei , Zhang Xi , Rao Jun
Published: December 2023

Background: The underlying mechanism of rituximab resistance is still unclear; it is important to explore novel therapeutic targets to improve the outcomes of the patients. Here, we tried to identify the effects of Voltage-dependent anion channel 2 (VDAC2) on rituximab resistance as well as its therapeutic value in diffuse large B-cell lymphoma (DLBCL).

Methods: VDAC2 was identified by transcriptome and proteome sequencing analysis of rituximab-resistance cells. The effects of VDAC2 in rituximab resistance were investigated by gain-of-loss function experiments. The effects of VDAC2 regulating ferroptosis was evaluated with lipid ROS, MDA and GSH detection assays. Evaluate effect of VDAC2 on therapeutic efficacy was performed by Xenograft mouse model.

Results: Transcriptome and proteome sequencing analysis of rituximab-resistance and control DLBCL cells identified that VDAC2 was highly expressed in rituximab-resistance cells, and we found that VDAC2 could predict the prognosis of patients treated with RCHOP regimens, but not CHOP regimen. Knock-down of VDAC2 significantly inhibited cell proliferation and arrested cell cycle in S phase, as well as enhanced sensitivity to rituximab. Moreover, we found that knockdown expression VDAC2 significantly repressed lactate production, the extracellular acidification rate, treatment with exogenous lactate could abrogated the effects mediated by VDAC2. Meanwhile, we further found that ferroptosis was responsible for VDAC2 mediated rituximab resistance. Knockdown expression of VDAC2 increased lipid ROS and MDA levels, decreased the GSH levels, and repressed expression of SLC7A11 and Gpx4. Moreover, the lactate administration could rescue ferroptosis and sensitivity to rituximab induced by knockdown expression of VDAC2.

Conclusions: This study revealed a novel mechanism of rituximab resistance mediated by VDAC2 via inhibiting ferroptosis, which provides a potential therapeutic target for overcoming rituximab resistance in DLBCL patients.

Keywords: Diffuse large B cell lymphoma, rituximab resistance, VDAC2, Ferroptosis
Steroid-Refractory Paroxysmal Cold Hemoglobinuria in a 6-Year-Old Male
Authors: Donahue Nolan , Kanakis Constantine , Krum Kristen
Published: December 2023

Background

Paroxysmal Cold Hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia (AIHA) that is often seen as a sequela of viral upper respiratory tract infections and immunizations in children. It is characterized by a positive Coombs test with a biphasic auto anti-P IgG known as the “Donath-Landsteiner antibody,” which sensitizes red cells and fixes complement at 0-4°C, and hemolyzes red cells near body temperature. The mainstay treatment of PCH includes cold avoidance, intravenous hydration, and supportive blood transfusions. Glucocorticoids may be used in the setting of significant hemolysis, with debated efficacy. We present a case of steroid-refractory PCH in a 6-year-old boy secondary to human rhinovirus/enterovirus.

Methods

Patient clinical data was abstracted from the electronic medical record. Blood bank testing was performed through the in-house blood bank. Donath-Landsteiner testing was performed at a reference laboratory.

Findings

A 6-year-old male with a history of mild upper respiratory tract infection 1 week prior presented to the emergency department with abdominal pain, dark urine, and jaundice. Initial laboratory evaluation uncovered anemia with hemoglobinuria, hyperbilirubinemia, elevated LDH, and decreased haptoglobin, raising concerns for acute hemolytic anemia (Table 1). Follow-up blood bank testing revealed a cold autoantibody. Viral PCR was positive for human rhinoenterovirus.

Despite supportive therapy through intravenous fluids and warming, the patient's anemia worsened significantly (Hgb 5.1g/dL) and packed red blood cell (pRBC) transfusion was required. Methylprednisolone 0.8 mg/kg IV twice daily was initiated as empiric therapy for autoimmune hemolysis without significant improvement. Blood was sent for Donath-Landsteiner antibody testing at a reference laboratory and revealed a bi-phasic hemolysin consistent with paroxysmal cold hemoglobinuria. The patient required an additional pRBC transfusion and was discharged after 4 days inpatient.

Conclusion

Our case supports a growing body of evidence that finds steroid therapy inefficacious in the treatment of hemolysis in the setting of PCH.
Blood Basophil Concentration at Diagnosis Corelates with Prognosis in Newly-Diagnosed Persons with Chronic Myeloid Leukaemia
Authors: Vrablova Lucia , Zhang Xiaoshuai , Kriegova Eva , Kudelka Milos , Radvansky Martin , Yang Sen , Juranova Jaroslava , Papajik Tomas , Gale Robert Peter , Jiang Qian , Faber Edgar
Published: December 2023

Background Basophilia is common in chronic myeloid leukaemia (CML) and is associated with a poor prognosis. Previously it was quantified by percentage and a binary < or ≥ 20%. However, blood basophil concentration at diagnosis may be a better prognostic co-variate.

Methods The hypothesis generating cohort was a 135 newly-diagnosed subjects with BCR::ABL1-positive CML receiving a tyrosine kinase-inhibitor (TKI). Median follow-up was 6.3 years (range, 4-16 years). Data were analyzed by Kaplan-Meier curves and multi-variable patient similarity network (PSN). A cohort of 1919 subjects was used to validate the test hypothesis. Subject gave informed consent for non-interventional data collection and the study was approved by Ethics Committees.

Results Multi-variable PSNs of the hypothesis generating cohort indicated 5 subject clusters. Incidence of TKI switch was highest in clusters 1 (45%), 5 (40%) and 4 (30%) which were characterized by the increased basophil concentrations at diagnosis compared with clusters 2 (13%) and 3 (14%) with the low basophil concentrations at diagnosis. PSNs identified the combination of basophil concentration ≥ 8x10E+9/L, basophil percentage ≥ 5 % and WBC ≥ 164x10E+9/L to be associated with significantly worse FFS (p < 0.001) and PFS ( p = 0.02) but not survival ( p = 0.18). Basophil concentration ≥ 8x10E+9/L and WBC concentration ≥ 164x10E+9/L were associated with worse EFS (p < 0.001), (FFS (p < 0.001; Figure 1) but not PFS or survival. Basophil percentage at diagnosis had no impact on outcomes using ≥ 5% or ≥ 20% cutoffs. In the validation cohort the combination of basophil concentration ≥ 8x10E+9/L, basophil percentage ≥ 5% and WBC ≥ 164x10E+9/L at diagnosis was associated with worse FFS ( p < 0.001) but not PFS or survival. Basophils ≥ 5% was associated with worse survival ( p = 0.04) and ≥ 20% with worse FFS ( p = 0.04) and survival ( p = 0.009). Basophil concentration ≥ 8×10E+9/L was associated with worse PFS ( p < 0.001; Figure 1) and survival ( p = 0.03). There was no effect of WBC concentration on any outcome.

Conclusion We show blood basophil concentration at diagnosis correlates with diverse outcomes in newly-diagnosed persons with CML receiving TKI-therapy.

Support IGA_LF_2023_05, MH_CZ-DRO (FNOL, 00098892)
Risk of Bleeding and Thrombosis with CAR T-Cell Therapy: A Scoping Review
Authors: Abufarhaneh Mohammed , Pandya Rudra , Lazo-Langner Alejandro , Iansavitchene Alla , Dematagoda Dewmini
Published: December 2023

Introduction:

Chimeric antigen receptor (CAR) T-cell therapy is emerging as a novel and revolutionary therapy in the treatment of relapsed or refractory lymphoma and other hematological malignancies. Patients with hematological malignancies are at risk of bleeding and thrombosis due to multiple risks factors. As there is an ongoing exploration of the incidence and characteristics of bleeding and thrombosis after CAR T-cell therapy, there is no existing published data that incorporates both peer-reviewed and non-peer-reviewed literature.

Aim:

Assess the risk of bleeding and thrombosis in CAR T-cell recipients for hematological malignancies.

Method:

We conducted a systematic literature search in MEDLINE, EMBASE, and CENTRAL electronic databases from inception to October 2022 using a combination of subject headings and text words. We included studies that assessed thrombotic and bleeding complications in patients eighteen or older who underwent CAR T-cell therapy for a hematologic malignancy. Our search strategy yielded 14 studies in the form of abstracts and full-text articles. The review process consisted of two levels of screening: (1) a title and abstract review and (2) a full-text review.

Result:

Of 3354 records, we included 14 studies based on our inclusion criteria [figure 1]. Majorities of the studies were retrospective. Most of the patients in these studies received CAR T-cell therapy for refractory diffuse large B-cell lymphoma. Patients received at least 2 lines of therapy or more before CAR T-cell treatment. Different types of CAR T-cell therapy were used. Based on the included studies, the risk of bleeding was higher than thrombosis [figure 2]. Bleeding sites were variable, but gastrointestinal (GI) bleeding was predominant. In Ma et al, GI bleeding occurred in 11 (42.3%) patients. In Qi et al and Johnsrud et al, bleeding occurred in 44 (11%) and 12 (9.4%) patients respectively. Variable sites of thrombosis were noticed. In Hashmi et al incidence of thrombosis was 10.8%. Although there are some risk factors associated with bleeding and thrombosis in this population, the exact mechanism is still unknown. We think future studies to determine the exact mechanism of this toxicity and to assess the underlying risk factors would be crucial to decrease morbidity and mortality in this population and to develop risk assessment tools.
Helical Tomotherapy and Melphalan As the Conditioning Regimen in Autologous Stem Cell Transplantation for Multiple Myeloma with Extramedullary Plasmacytoma: A Single Center Clinical Research
Authors: Liu Pan , Wang Qian , Zhou Fuling
Published: December 2023

Background

Multiple myeloma(MM) is the second hematologic malignancy. Extramedullary myeloma indicates a poorer prognosis and survival. High dose Melphalan is the most widely used conditioning regimen. Helical tomotherapy(TOMO) is one of the most advanced intensity-modulated conformal radiotherapy technologies. We applied the combination of TOMO and Melphalan as the conditioning regimen in MM patients, and analyzed its efficacy and safety.

Methods

Clinical data were collected and compared between TOMO combined with melphalan group and non-TOMO group. SPSS V.25.0 was used for statistical analysis.

Results

Two methods were not significant difference by statistics analysis. The complete response rate of 100d in non-TOMO group significantly decreased compared to 1 month after transplantation (P=0.001). The 1-year PFS rate in the TOMO group was 86%, while non-TOMO group was 91%. There was no myeloma related death in the two groups within one year. TOMO group showed earlier enter platelet count below 20x109/L (P=0.003) and granulocyte deficiency (P=0.000). In terms of platelet implantation time,TOMO group was superior in platelet implantation time (P=0.041). No atrial fibrillation, heart failure, hepatic small vein occlusion, or transplant related death occurred during the transplantation period.

Conclusion: The combination of TOMO and reduced dose Melphalan conditioning regimen is clinically feasible in terms of safety and efficacy evaluation. This scheme could improve the long-term survival of MM patients with extramedullary plasmacytoma.
High Prevalence of MYD88 and CD79B Mutations and PD-L1 Alterations in Bone Marrow Large B Cell Lymphoma Associated with Hemophagocytic Lymphohistiocytosis
Authors: Shi Wenyu , Miao Yi , Shi Yu , Zhu Huayuan , Li Jianyong
Published: December 2023

Introduction: Bone marrow large B cell lymphoma associated with hemophagocytic lymphohistiocytosis (HLH) is a rare disease with a highly aggressive clinical course. Until now, the molecular genomics of bone marrow large B cell lymphoma associated with HLH remains undetermined.

Methods: Cases of bone marrow large B cell lymphoma with HLH were included. The inclusion criteria were as follows: (1) diagnosis of large B cell lymphoma presenting initially in the bone marrow; (2) no overt lymph node involvement or tumor formation; (3) fulfillment of five or more of the eight HLH-2004 diagnostic criteria. (4) cases with available samples. Genomic DNA was extracted from bone marrow cells or the plasma. A panel comprising 475 hematological malignancy-related genes were used for targeted gene sequencing. The prepared library was sequenced using Illumina HiSeq 4000. Molecular classification was predicted by using the LymphGen algorithm.

Results: A total of 23 cases were included. The median age was 63. 71.4% of patients were the non-GCB subtype (10/14) based on the Hans algorithm and 50% (9/18) of cases showed CD5 expression. Somatic mutations were identified in all the cases. The most common disrupted genes were PIM1 (12/23, 52.2%), PD-L1 (9/23, 39.1%), MYD88 (8/23, 34.8%), BCL6 (6/23, 26.1%), CD79B (6/23, 26.1%), IRF4 (6/23, 26.1%) and TET2 (6/23, 26.1%) (Figure 1). For nine cases with PD-L1 aberrations, seven cases had PD-L1 structural variants (SVs) and one case showed PD-L1 amplification (Figure 2). All the six cases with BCL6 aberrations showed BCL6 SVs (Figure 2). For six cases with BCL6 SVs, four cases showed immunoglobulin heavy chain ( IGH)- BCL6 translocations and two cases harbored IKZF1- BCL6 translocations. Regarding molecular classification, eight cases (34.8%) were classified as the MCD subtype, two cases the BN2 subtype, two cases the ST2 subtype, and two cases the composite subtype.

Conclusion: To the best of our knowledge, this is the first study exploring the molecular genetics of bone marrow large B cell lymphoma with HLH. Our study suggesting bone marrow large B cell lymphoma with HLH showed frequent MYD88/CD79B and PD-L1 alterations. Our study provided clues for the pathogenesis of bone marrow large B cell lymphoma with HLH and identified potential druggable targets for future clinical trials.
Comparison of Therapeutic Effects between Young Haploidentical Donors and Elderly HLA-Matched Relative Donors for AML Patients Who Undergoing Allogeneic Hematopoietic Stem Cell Transplantation with Conditioning Regime Including ATG
Authors: Zhang Haixiao , Jiang Erlie
Published: December 2023

Objective: Donor selection is one of the issues faced in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aims to compare the impact of young haploidentical donors and elderly matched relative donors on the outcomes of AML patients undergoing allo-HSCT with conditioning regime including ATG, providing reference for donor selection.

Methods: A retrospective analysis was conducted on 708 AML patients who underwent allo-HSCT at our hospital from 2014 to 2021. Among them, 354 patients were included in this study, with 289 patients receiving haploidentical transplantation from donors under the age of 50 (haplo group) and 65 patients receiving fully matched sibling transplantation from donors over the age of 50 (MSD group). Clinical characteristics and transplantation outcomes of both groups of patients and donors were compared.

Results: Among the 354 AML-MRC patients, there were 178 males and 176 females, with a median age of 41 (18~56) years. The median follow-up time was 35 (95% CI 30~49) months, and the median overall survival (OS) was 78 (95% CI 23~) months. The 3-year OS rate was 63.1% (95% CI 45.6%~81.4%), the 3-year event-free survival (EFS) rate was 59.0% (95% CI 40.8%~66.1%), the cumulative incidence of relapse (CIR) was 26.8% (95% CI 16.6%~30.0%), and the transplantation-related mortality (TRM) was 22.7% (95% CI 13.2%~33.8%). There were no statistically significant baseline differences between the haplo group and MSD group. The 3-year OS rates for haplo group vs. MSD group were 0.660 (95% CI 0.597-0.731) vs. 0.670 (95% CI 0.558-0.806) (p=0.7), the 3-year EFS rates were 0.620 (95% CI 0.543-0.720) vs. 0.570 (95% CI 0.458-0.656) (p=0.6), and the TRM rates were 0.165 (95% CI 0.121-0.282) vs. 0.134 (95% CI 0.062-0.234) (p=0.6). The CIR rates were 0.199 (95% CI 0.147-0.250) vs. 0.275 (95% CI 0.165-0.397) (p=0.196), and the cumulative incidence of grade II-IV aGVHD was 0.288 (0.237-0.342) vs. 0.309 (95% 0.200-0.424) (P=0.891). The incidence of cGVHD was 0.140 (0.099-0.188) vs. 0.250 (95% 0.147-0.367) (p=0.032).

Conclusion: For AML patients undergoing allo-HSCT with conditioning regime including ATG, compared to elderly fully matched donors, young haploidentical donors may reduce the occurrence of post-transplant cGHVD.
Bone Marrow Cellularity at Diagnosis Predicts Outcomes of Patients with Myelodysplastic Syndrome with Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Ahn Seo-Yeon , Kim Mihee , Song Ga-Young , Jung Sung-Hoon , Ahn Jae-Sook , Yang Deok-Hwan , Lee Je-Jung , Kim Hyeoung-Joon
Published: December 2023

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only known curative therapy for myelodysplastic syndromes (MDS). The decision of allo-HSCT depends on prognostic scoring models such as revised international prognostic scoring system (IPSS-R) which include cytogenetic abnormalities, cytopenia, and % of bone marrow (BM) blasts. Recently, the prognostic role of genomic profile in MDS patients is arising. However, it is hard to conduct the next generation sequencing to all MDS patients in the real-world. Therefore, we aimed to evaluate the prognostic impact of BM cellularity at diagnosis as a new clinical prognostic factor of MDS with allo-HSCT.

A total of 122 patients with MDS patients who underwent allo-HSCT between July 2009 to August 2022 in single center were analyzed retrospectively. Overall survival (OS) was analyzed using the Kaplan-Meier survival curves according to the BM cellularity at diagnosis. The potential prognostic parameters were evaluated for OS by uni-and multivariate cox-regression analysis.

All patients were eligible for allo-HSCT and median age of 61.5 years (range: 19-71). Median follow-up duration was 36.9 (IQR 17.6-72.4) months. The 3-year and 5-year OS were 60.1% (95% CI 51.6-69.0) and 52.5% (95% CI 42.8-61.3), respectively. IPSS-R risk group was classified as very low (6, 4.9%), low (15, 12.2%), intermediate (40, 32.8%), high (37, 30.3%) and very high (24, 19.7%). Seventeen patients (13.9%) had complex karyotype at diagnosis. Seventy-seven patients (63.1%) were treated with hypomethylating agents before allo-HSCT. Most patients (70, 57.4%) had less than 5% BM blasts at allo-HSCT. The majority (74, 60.7%) received reduced intensity conditioning.

OS significantly differed between patients with hypercellular BM and normo- to hypocellular BM at diagnosis by the log-rank test ( P <0.001) (Figure 1). In multivariate analysis for OS, complex karyotype at diagnosis ( P<0.001; HR 6.00; 95% CI 3.08-11.66), age ( P=0.04; HR 1.03; 95% CI 1.00-1.06) and hypercellular BM at diagnosis ( P=0.005; HR 2.16; 95% CI 1.26-3.72) were associated with worse outcome (Table 1).

In this study, we demonstrated the BM hypercellularity at diagnosis independently predicts the inferior outcome of MDS patients with allo-HSCT. Although further validation with a larger cohort would be needed, it could be helpful to decide the treatment strategy of transplantation eligible MDS patients.
Analysis of GATA transcription factors and their expression patterns under abiotic stress in grapevine (Vitis vinifera L.)
Authors: Zhang Xiuming , Ma Jiahui , Yang Shijin , Yao Wenkong , Zhang Ningbo , Hao Xinyi , Xu Weirong
Published: December 2023

Background

GATA transcription factors are type IV zinc-finger proteins that play key roles in plant growth and responses to environmental stimuli. Although these proteins have been studied in model plants, the related studies of GATA gene family under abiotic stresses are rarely reported in grapevine (Vitis vinifera L.).

Results

In the current study, a total of 23 VviGATA genes were identified in grapevine and classified into four groups (I, II, III, and IV), based on phylogenetic analysis. The proteins in the same group exhibited similar exon–intron structures and conserved motifs and were found to be unevenly distributed among the thirteen grapevine chromosomes. Accordingly, it is likely that segmental and tandem duplication events contributed to the expansion of the VviGATA gene family. Analysis of cis-acting regulatory elements in their promoters suggested that VviGATA genes respond to light and are influenced by multiple hormones and stresses. Organ/tissue expression profiles showed tissue specificity for most of the VviGATA genes, and five were preferentially upregulated in different fruit developmental stages, while others were strongly induced by drought, salt and cold stress treatments. Heterologously expressed VamGATA5a, VamGATA8b, VamGATA24a, VamGATA24c and VamGATA24d from cold-resistant V. amurensis ‘Shuangyou’ showed nuclear localization and transcriptional activity was shown for VamGATA5a, VamGATA8b and VamGATA24d.

Conclusions

The results of this study provide useful information for GATA gene function analysis and aid in the understanding of stress responses in grapevine for future molecular breeding initiatives.
Effect of magnesium sulfate perioperative infusion on postoperative catheter-related bladder discomfort in male patients undergoing laparoscopic radical resection of gastrointestinal cancer: a prospective, randomized and controlled study
Authors: Jiang Wencai , Zeng Xu , Zhou Xinyu , Liao Ou , Ju Feng , Zhao Zhifu , Zhang Xianjie
Published: December 2023

Background

Laparoscopic radical resection of gastrointestinal cancer is associated with a high incidence of postoperative catheter-related bladder discomfort (CRBD). Studies on the benefits of magnesium sulfate intravenous infusion during the perioperative period post-laparoscopic surgery are yet lacking.

Methods

A total of 88 gastrointestinal cancer male patients scheduled for laparoscopic radical resection were randomly divided into two groups: normal saline (control) and magnesium. In the magnesium group, a 40 mg/kg loading dose of intravenous magnesium sulfate was administered for 10 min just after the induction of anesthesia, followed by continuous intravenous infusion of 15 mg/kg/h magnesium sulfate until the end of the surgery; the control group was administered the same dose of normal saline. Subsequently, 2 μg/kg sufentanil was continuously infused intravenously by a postoperative patient-controlled intravenous analgesia (PCIA) device. The primary outcome was the incidence of CRBD at 0 h after the surgery. The secondary outcomes included incidence of CRBD at 1, 2, and 6 h postsurgery, the severity of CRBD at 0, 1, 2, and 6 h postsurgery. Remifentanil requirement during surgery, sufentanil requirement within 24 h postsurgery, the postoperative numerical rating scale (NRS) score at 48 h after the surgery, magnesium-related side effects and rescue medication (morphine) requirement were also assessed.

Results

The incidence of CRBD at 0, 1, 2, and 6 h postoperatively was lower in the magnesium group than the control group (0 h: P = 0.01; 1 h: P = 0.003; 2 h: P = 0.001; 6 h: P = 0.006). The incidence of moderate to severe CRBD was higher in the control group at postoperative 0 and 1 h (0 h: P = 0.002; 1 h: P = 0.028), remifentanil requirement during surgery were significantly lower in the magnesium group than the control group. Sufentanil requirements during the 24 h postoperative period were significantly lower in the magnesium group than the control group. The NRS score was reduced in the magnesium group compared to the control group in the early postoperative period. Magnesium-related side effects and rescue medication (morphine) did not differ significantly between the two groups.

Conclusions

Intravenous magnesium sulfate administration reduces the incidence and severity of CRBD and remifentanil requirement in male patients undergoing radical resection of gastrointestinal cancer. Also, no significant side effects were observed.

Trial registration

Chictr.org.cn ChiCTR2100053073. The study was registered on 10/11/2021.
Needs and challenges among general practitioners in the management of actinic keratosis: a qualitative study
Authors: Verhoeven Charlotte , Claessens Zilke , Lubeek Satish F.K. , Schers Henk J.
Published: December 2023

Background

Because of the increasing incidence of actinic keratosis (AK), optimal use of limited healthcare resources is essential. Although most patients can be managed in primary care, dermatology referrals are common. More profound knowledge of general practitioners’ (GPs) considerations might assist in enhancing AK care.

Methods

The aim of the current study was to gain insight into AK management in primary care by exploring the needs and challenges among GPs in the Netherlands. A qualitative study was conducted based on semi-structured in-depth interviews with 15 conveniently sampled Dutch GPs, focusing on the needs and challenges in AK management. A literature-informed, predefined topic list guided the interviews, which were recorded, transcribed ad verbatim, and thematically analysed using the Framework Method.

Results

All GPs reported AK to be a clinical diagnosis and most GPs indicated that most AK patients could be managed in primary care. Cryotherapy was preferred and experience with 5-FU therapy was limited. Most GPs applied cryotherapy without discussing other treatment options with patients. Reasons for dermatology referrals included an incomplete treatment response, extensive lesions, difficult-to-treat areas, and serious doubts about the diagnosis. GPs reported a need for more education, especially on 5-FU therapy. Their main challenges were dealing with diagnostic uncertainty, treating extensive lesions, managing treatment-related skin reactions, and reconciling patient misconceptions.

Conclusions

This study shows various AK management approaches among Dutch GPs with suboptimal guideline compliance due to diverse underlying barriers. It suggests that more education might contribute to a more standardised and uniform AK management and supports further transition of AK care from hospital to primary care.
Clinical impact of medication reviews for community-dwelling patients in primary healthcare
Authors: Dobszai Annika , Lenander Cecilia , Borgström Bolmsjö Beata , Wickman Katarina , Modig Sara
Published: December 2023

Background

A high number of drug-related problems has previously been shown among community-dwelling patients in primary healthcare in Skåne County, Sweden. Medication reviews are one way to solve these problems, but their impact is largely dependent on the process. We aimed to evaluate medication reviews for community-dwelling patients regarding the clinical relevance of the pharmacists’ recommendations, and their implementation by general practitioners. We also wanted to investigate if the general practitioners’ tendency to act on drug-related problems was correlated to different factors of the process.

Methods

This was a cohort study, where patients in primary healthcare considered in need of a medication review were selected. Pharmacists identified drug-related problems and gave written recommendations on how to solve the problems to the general practitioner, via the medical record, and in addition in some cases via verbal communication. The clinical relevance of the recommendations was graded according to the Hatoum scale, ranging from one (adverse significance) to six (extremely significant). Descriptive statistics were used regarding the clinical relevance and the general practitioners´ tendency to act on drug-related problems. Multiple logistic regression analysis was used to examine the association between the tendency to act and different factors of the process.

Results

A total of 96.1% of the 384 assessed recommendations from the pharmacists were graded as significant or more for the patient (Hatoum grade 3 or higher). The general practitioners acted on 63.8% of the drug-related problems. Fewer recommendations per patient, as well as verbal communication in addition to written contact, significantly increased the general practitioners’ tendency to act on a drug-related problem. No significant association was seen between the tendency to act and the clinical relevance of the recommendation.

Conclusions

The high proportion of clinically relevant recommendations from the pharmacists in this study strengthens medication reviews as an important tool for reducing drug-related problems. Verbal communication between the pharmacist and the general practitioner is important for measures to be taken. Multiple recommendations for the same patient reduced their likelihood to of being addressed by the general practitioner.
Returning-to-work after mental health-associated sick leave: a qualitative interview study exploring the experiences of general practitioners in Germany
Authors: Geipel Martina , Pelizäus Anna , Hamann Johannes
Published: December 2023

Background and aim

Psychiatric disorders are increasing globally. Especially when these disorders affect working people, this places a financial burden on society due to long-term sick leave, the incapacity to work and the inability to earn and pay taxes. General practitioners (GPs) are often the first health professionals to be consulted by those suffering from mental health disorders.

This study investigated the experiences of GPs regarding their patients with mental health disorders and identified factors that are important for a successful return to work.

Methods

This qualitative study used semi-structured interviews to explore the opinions of GPs (n = 12) working in Munich, Germany, or its metropolitan area. The interviews were audio-recorded, transcribed, and analyzed using the reflexive thematic analysis method.

Results

GPs think of themselves as important players in the rehabilitation process of patients with mental health disorders. In their daily routine, they face many obstacles to ensure the best treatment and outcome for their patients. They also suffer from poor collaboration with other stakeholders, such as psychiatric hospitals, therapists or employers.

They indicate that the mental health disorder of each patient is unique, including the barriers to and possibilities of a successful return to work. Additionally, the workplace appears to play a crucial role in the success rate of re-entry into work. It can exacerbate the course of mental health disorders or support recovery. Fear, shame and stigmatization of the patients are personal factors responsible for prolonged sick leave.

Conclusion

We conclude that GPs believe that they can have a major impact on the rehabilitation of patients with mental health disorders. As such, special focus should be placed on supporting them in this context.
Maternal and obstetric outcomes after Ex-Utero Intrapartum Treatment (EXIT): a single center experience
Authors: Domínguez-Moreno Marta , Chimenea Ángel , García-Díaz Lutgardo , Antiñolo Guillermo
Published: December 2023

Background

The Ex-utero Intrapartum Treatment (EXIT) is a procedure developed to manage a range of fetal conditions, aiming to ensure the maintenance of neonatal airway and preserving the feto-placental circulation. Its goal is to enhance the neonatal ability to successfully transition and adapt to postnatal life, thereby reducing perinatal morbidity and mortality. However, EXIT has been associated with a high risk of maternal complications. This paper provides an overview of the indications and characteristics of the EXIT procedure, as well as the obstetric outcomes and maternal complications.

Methods

A retrospective analysis was conducted on a cohort of patients undergoing EXIT at our center between January 2007 and December 2022. Maternal outcomes, including demographic information, data related to the surgical procedure, surgical complications, and postoperative complications were analyzed. To assess the severity of the surgical complications, a modified Clavien-Dindo classification was used. Comparative analysis was performed by randomly selecting a sample from elective cesarean deliveries performed at our center.

Results

A total of 34 EXIT procedures were performed. According to the modified Clavien-Dindo classification, we observed no major complications, while minor maternal complications were present in 2.94% of cases. Compared to elective cesarean deliveries (n = 350), there were no significant differences in terms of maternal complications, highlighting the similarity observed in the mean decrease in postoperative hemoglobin (1.15 g/dL in EXIT vs. 1.2 g/dL in elective cesarean deliveries, p = 0.94). In EXIT group, there was a higher rate of polyhydramnios (26.47% vs 6.59%, p < 0.001), as well as the need for amnioreduction (14.71% vs 0%, p = 0.001) and preterm delivery (32.35% vs 6.02%, p = 0.001). There were no cases of endometritis, post-procedural fever, or abruptio placentae following EXIT.

Conclusions

EXIT can be considered a safe procedure when performed under adequate conditions, including appropriate uterine access and proper anesthetic management. In our series, EXIT procedure was not associated with a higher incidence of maternal complications when compared to elective cesarean delivery.

Trial registration

Retrospectively registered.
General practitioner perceptions and experiences of managing perinatal mental health: a scoping review
Authors: Frayne Jacqueline , Seddon Sarah , Lebedevs Tamara , Milroy Talila , Teh Beverly , Nguyen Thinh
Published: December 2023

Background

General Practitioners (GPs) are involved in preconception, pregnancy, and postnatal care. Overall, mental health remains a significant contributor to disease burden affecting 1 in 4 pregnant women. Psychotropic medication prescribing occurs in almost 1 in 12 pregnancies, and appears to be increasing, along with the prevalence of mental health disorders in women of reproductive age. Perinatal mental health management is therefore not an unlikely scenario within their clinical practice. This scoping review aims to map current research related to GPs perceptions and experiences of managing perinatal mental health.

Method

A comprehensive search strategy using nine electronic databases, and grey literature was undertaken between December 2021 and February 2023. Relevant studies were sourced from peer review databases using key terms related to perinatal mental health and general practitioners. Search results were screened on title, abstract and full text to assess those meeting inclusion criteria and relevance to the research question.

Results

After screening, 16 articles were included in the scoping review. The majority focused on perinatal depression. Findings support that GPs express confidence with diagnosing perinatal depression but report issues of stigma navigating a diagnosis. Over the last two decades, prescribing confidence in perinatal mental health remains variable with concerns for the safety profile of medication, low level of confidence in providing information and a strong reliance on personal experience. Despite the establishment of perinatal guidelines by countries, the utilisation of these and other existing resources by GPs appears from current literature to be infrequent. Many challenges exist for GPs around time pressures, a lack of information and resources, and difficulty accessing referral to services.

Conclusion

Recommendations following this scoping review include targeted perinatal education programs specific for GPs and embedded within training programs and the development of practice guidelines and resources specific to general practice that recognises time, services, and funding limitations. To achieve this future research is first needed on how guidelines and resources can be developed and best delivered to optimise GP engagement to improve knowledge and enhance patient care.
Can multiple miniplates improve the treatment of comminuted patellar fracture?
Authors: Yoo Seung Jin , Ok Seungwoo , Lee Jaeryun , Choi Sungwook
Published: December 2023

Background

We have applied primarily multiple locking compression miniplates in treating multifragmentary, comminuted patellar fracture in combination with conventional fixation methods.

Methods

Medical and radiologic data were retrospectively reviewed for the patients surgically fixated with locking compression miniplates in patellar fracture of AO/OTA 34-C3. The primary outcome was bone union at the final follow-up, and the secondary outcomes were functional outcomes and postoperative complications associated with the procedure. For the functional assessment, the Lysholm score, Tegner scores, and the knee range of motion was compared.

Results

A total of twenty patients with AO/OTA 34-C3 patellar fracture were included in the study with an average follow-up period of 15 months (range:11 ~ 18 months) between June 2018 and November 2021. Eleven male and nine female patients presented an average age of 57.15 years. The primary fracture union was seen in all twenty patients, and the average time to the union was 15.6 weeks on serial radiograph follow-up. All patients did not show any postoperative complications, such as fixation failure, infection, or revision operations. Postoperatively, all patients achieved an average range of motion of 130 degrees, and the Lysholm and Tegners scores showed an average of 90.4 and 5.0 at the final follow-up, retrospectively.

Conclusion

Fixations with miniplates in comminuted patellar fractures can be a useful option for effective osteosynthesis due to their versatile, efficient, and low-profile nature.
The role of preoperative aspartate aminotransferase-to-platelet ratio index in predicting complications following total hip arthroplasty
Authors: McLellan M. A. , Donnelly M. R. , Callan K. T. , Lung B. E. , Liu S. , DiGiovanni R. , McMaster W. C. , Stitzlein R. N. , Yang S.
Published: December 2023

Background

The purpose of this study was to investigate the relationship between preoperative aspartate aminotransferase-to-platelet ratio index (APRI) and postoperative complications following total hip arthroplasty (THA).

Methods

All THA for osteoarthritis patients from 2007 to 2020 within the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database were included in this study. Subjects were subsequently divided into cohorts based on APRI. Four groups, including normal range, some liver damage, significant fibrosis, and cirrhosis groups, were created. Comparisons between groups were made for demographics, past medical history, and rate of major and minor complications. Other outcomes included readmission, reoperation, discharge destination, mortality, periprosthetic fracture, and postoperative hip dislocation. Multivariate logistic regression analysis was performed to determine the role of preoperative APRI in predicting adverse outcomes. Statistical significance was set at p < 0.05.

Results

In total, 104,633 primary THA patients were included in this study. Of these, 103,678 (99.1%) were in the normal APRI group, 444 (0.4%) had some liver damage, 256 (0.2%) had significant fibrosis, and 253 (0.2%) had cirrhosis. When controlling for demographics and relevant past medical history, the abnormal APRI groups had a significantly higher likelihood of major complication, minor complication, intraoperative or postoperative bleeding requiring transfusion, readmission, and non-home discharge (all p < 0.05) compared to normal APRI individuals.

Conclusions

Abnormal preoperative APRI is linked with an increasing number of adverse outcomes following THA for osteoarthritis for patients across the United States.

Level of evidence

Level I
Reliability and validity of ultrasonography in evaluating the thickness, excursion, stiffness, and strain rate of respiratory muscles in non-hospitalized individuals: a systematic review
Authors: Zhou Emma FengMing , Fu Siu Ngor , Huang Chen , Huang Xiu Ping , Wong Arnold Yu Lok
Published: December 2023

Objective

To summarize the reliability and validity of ultrasonography in evaluating the stiffness, excursion, stiffness, or strain rate of diaphragm, intercostals and abdominal muscles in healthy or non-hospitalized individuals.

Literature search

PubMed, Embase, SPORTDiscus, CINAHL and Cochrane Library were searched from inception to May 30, 2022.

Study selection criteria

Case–control, cross-sectional, and longitudinal studies were included if they investigated the reliability or validity of various ultrasonography technologies (e.g., brightness-mode, motion-mode, shear wave elastography) in measuring the thickness, excursion, stiffness, or strain rate of any respiratory muscles.

Data synthesis

Relevant data were summarized based on healthy and different patient populations. The methodological quality by different checklist depending on study design. The quality of evidence of each psychometric property was graded by the Grading of Recommendations, Assessment, Development and Evaluations, respectively.

Results

This review included 24 studies with 787 healthy or non-hospitalized individuals (e.g., lower back pain (LBP), adolescent idiopathic scoliosis (AIS), and chronic obstructive pulmonary disease (COPD)). Both inspiratory (diaphragm and intercostal muscles) and expiratory muscles (abdominal muscles) were investigated. Moderate-quality evidence supported sufficient (intra-class correlation coefficient > 0.7) within-day intra-rater reliability of B-mode ultrasonography in measuring right diaphragmatic thickness among people with LBP, sufficient between-day intra-rater reliability of M-mode ultrasonography in measuring right diaphragmatic excursion in non-hospitalized individuals. The quality of evidence for all other measurement properties in various populations was low or very low. High-quality evidence supported sufficient positive correlations between diaphragm excursion and forced expiratory volume in the first second or forced vital capacity (r >  = 0.3) in healthy individuals.

Conclusions

Despite the reported sufficient reliability and validity of using ultrasonography to assess the thickness, excursion, stiffness, and strain rate of respiratory muscles in non-hospitalized individuals, further large-scale studies are warranted to improve the quality of evidence regarding using ultrasonography for these measurements in clinical practice. Researchers should establish their own reliability before using various types of ultrasonography to evaluate respiratory muscle functions.

Trial registration

PROSPERO NO. CRD42022322945.
Effect of robot for medication management on home care professionals’ use of working time in older people’s home care: a non-randomized controlled clinical trial
Authors: Kajander-Unkuri Satu , Vaismoradi Mojtaba , Katajisto Jouko , Kangasniemi Mari , Turjamaa Riitta
Published: December 2023

Background

Medication management has a key role in the daily tasks of home care professionals delivered to older clients in home care. The aim of this study was to examine the effect of using a robot for medication management on home care professionals´ use of working time.

Methods

A pragmatic non-randomized controlled clinical trial was conducted. The participants were home care professionals who carried out home care clients’ medication management. Home care clients were allocated into intervention groups (IG) and control groups (CG) (n = 64 and 46, respectively) based on whether or not they received the robot. Data were collected using the Working Time Tracking Form prior to and 1 and 2 months after introducing the intervention. The t-test was used to compare the groups at each three timepoints. Analysis of Covariance was used to examine the groups’ differences for the total time for medications as the number of visits per day as the covariate.

Results

With robot use, the total amount of home visits decreased by 89.4% and 92.4% after 1 and 2 months of intervention use, respectively, compared to pre-intervention (p < 0.001). The total working time used for medication management considering the number of visits per day decreased from 54.2 min (95% CI 49.6–58.8) to 34.9 min (31.4–38.3), i.e., by slightly over 19 min (p < 0.001) in the IG group. During the follow-up, the total working time used for medication management considering the number of visits per day remained the same in the CG group.

Conclusion

Using a robot for medication management had a notable effect on decreasing the use of working time of home care professionals. For health services, decreased use of working time for medication management means that the time saved can be assigned to services that cannot be replaced otherwise. More digital solutions should be developed based on home care clients’ and professionals’ needs to meet the challenge of the growing number of older people in need of home care and ensure their safety.

Trial registration

ClinicalTrials.gov Identifier: NCT05908604 retrospectively registered (18/06/2023).