bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute intraperitoneal rupture of hydatid cysts of the liver
Authors: Mejri Atef , Arfaoui Khaoula , Omry Ahmed , Yaakoubi Jasser , Mseddi Mohammed Ali , Rchidi Jasser , Saad Sarra , Ellouze Mohammed Marouen
Published: December 2021

Hydatid cyst is a parasitic infection caused mainly by Echinococcus granulosus, which is generally considered benign. However, the hepatic hydatid cyst rupture in the abdominal cavity is a life-threatening incident that requires urgent and multidisciplinary management (emergency physicians, radiologists, anesthetists, and surgeons). This study describes clinical and paraclinical liver hydatid cyst rupture in the peritoneal cavity and details the appropriate treatment.

A retrospective review of clinical records of patients hospitalized in Jendouba Hospital for liver hydatid cyst was performed over 8 years, from January 1, 2012 to December 31, 2019. Fifteen cases of liver hydatid cyst complicated with acute rupture into the abdominal cavity were collected out of 625 hydatid liver cysts. All patients underwent emergency laparotomy allowing conservative unroofing procedure associated with peritoneal lavage and external drainage combined with necessary intensive care measures. Clinical features, therapeutic procedures’ details as well as postoperative outcomes are reported. Statistical analysis was performed using the Statistical Package for the Social Sciences for Windows version 20.

There were 9 men and 6 women. Patients’ age ranged from 14 to 59 years, with an average of 38 years. Two patients were admitted with abdominal trauma. Acute abdominal pain was the most common complaint. Only 1 patient had an anaphylactic shock. Abdominal ultrasonography and computed tomography scan showed discontinuous cyst wall associated to intraperitoneal fluid in all cases. Intraoperatively, the intraperitoneal effusion was clear in 13 cases and purulent in 2. All patients underwent unroofing procedures associated with intra-operative peritoneal lavage and external drainage. The mean hospital stay was 6.11 days, and the mean follow-up was 19 months. No case of recurrence was reported among the patients.

In endemic areas, rupture of a hepatic hydatid cyst in the abdominal cavity should be considered in every case of acute abdominal pain, especially if associated with anaphylaxis signs. Early management starting in the emergency room is needed to ensure good outcome.
A retrospective study of azithromycin and ceftizoxime for the management of children with Mycoplasma pneumoniae pneumonia
Authors: Han Li-ping , Xiao Han-yan , Fang Li-li
Published: December 2021

The aim of this study was to compare the clinical efficacy of azithromycin and ceftizoxime (AC) and erythromycin and amoxicillin/sulbactam (EAS) in the treatment of children with Mycoplasma pneumoniae pneumonia (MPP).

In this retrospective study, a total of 92 eligible children with MPP were included, and they were divided into a treatment group (n = 46) and a control group (n = 46). All patients were treated with intravenous ambroxol, and nebulized inhalation of budesonide and terbutaline. In addition, patients in the treatment group received AC. Patients in the control group underwent EAS. All patients in both groups were treated for a total of 10 days. Outcomes consist of erythrocyte sedimentation rate, C-reactive protein, serum lactate dehydrogenase, and interleukin 6, fever clearance time, time of cough disappearance, time of rale disappearance, time of signs disappeared by X-ray, and adverse events. All outcomes were measured after 10-day treatment.

After treatment, patients who received AC exerted better improvements in erythrocyte sedimentation rate (P < .01), C-reactive protein (P < .01), serum lactate dehydrogenase (P < .01), interleukin 6 (P < .01), fever clearance time (P < .01), time of cough disappearance (P < .01), time of rale disappearance (P < .01), and time of signs disappeared by X-ray (P < .01), than those in patients who received EAS. In addition, there were not significant differences in adverse events between 2 groups.

The results of this study showed that AC may benefit more than EAS for the children with MPP.
Association between RGS4 gene polymorphisms and schizophrenia
Authors: Xu Feng-Ling , Yao Jun , Wang Bao-Jie
Published: December 2021

Background:

Schizophrenia is a complex brain disorder, the pathogenesis of which remains unclear. Regulator of G-protein signaling 4 is regarded as a candidate gene for schizophrenia risk. The association between the regulator of G-protein signaling 4 gene and the risk of schizophrenia is complicated and controversial, thus, an updated meta-analysis is needed.

Methods:

A search strategy using Medical Subject Headings was developed in English (PubMed, SZGene) and Chinese (CNKI, Wanfang, and Weipu) databases. Inclusion and exclusion criteria were used to screen for eligible studies. Parameters, such as P value of Hardy–Weinberg equilibrium, odds ratios, 95% confidence intervals, P values of association, heterogeneity (P

h
), and publication bias, were analyzed by the Stata software using a random effects model. Subgroup analyses were performed to detect heterogeneity.

Results:

There were 15 articles regarding rs10917670 (8046 cases and 8837 controls), 16 regarding rs951436 (8990 cases and 10,568 controls), 15 regarding rs951439 (7995 cases and 8646 controls), 15 regarding rs2661319 (8320 cases and 9440 controls), and 4 regarding rs10759 (2752 cases and 2866 controls). The frequencies of rs10917670 and rs951439 were not significantly different between the case and control groups (P > .05). As shown by the East Asian and hospital-based subgroup analyses, the genotype TT of rs951436 might be related to the risk of schizophrenia. The genotypes CC + CT of rs2661319 and CC + CA of rs10759 were statistically different between the 2 groups, and the East Asian population contributed to these differences.

Conclusion:

The genotypes CC + CT of rs2661319 and CC + CA of rs10759 might be associated with the risk of schizophrenia.
Primary tonsillar tuberculosis in a pediatric patient
Authors: Moisa Stefana Maria , Miron Ingrith , Adam-Raileanu Anca , Lupu Vasile Valeriu , Lupu Ancuta , Tarca Elena
Published: December 2021

Rationale:

Tuberculosis is an entity that usually affects the lungs, although extrapulmonary sites can also be involved. Tonsils are rarely affected, especially in the absence of pulmonary disease, primary tonsillar tuberculosis being a diagnostic challenge for the clinician.

Patient concerns:

We present the case of a 14-year-old female teenager, presented to our Pediatric Service with a 14-day history of dysphagia, odynophagia and left reflex otalgia associated with a 5 kg weight loss. Clinical examination revealed mild pharyngeal erythema, marked enlargement of the left tonsil infiltrating the lateral pharyngeal wall and the uvula and painful, mobile, nonadherent to deep bilateral latero-cervical adenopathy.

Diagnosis:

Positive interferon-gamma release assay (QuantiFERON-TB gold). Mantoux test reading was 16 mm.

Interventions:

During hospitalization, the patient received Clindamycin and Gentamicin for 3 days i.v., with discrete relief of symptoms and inflammatory markers. On the 4th day of hospitalization, treatment with Imipenem/Cilastin is started for 7 days in micro-perfusion, with tonsil hypertrophy decrease in size and favorable clinical evolution.

Outcome:

Tonsil hypertrophy decreased in size and patient had a favorable clinical evolution. At discharge, the patient was given a 6-month course of anti-tuberculous drug.

Lessons:

The particularity of this case is represented by the rarity of primary tuberculosis of tonsils in children, with unilateral involvement, displaying at the same time a common issue encountered in the current practice: the limitations and the difficult course of setting the diagnosis due to the involvement of relatives in the medical act.
Translation, validation, and diagnostic accuracy of the Arabic version of the Michigan neuropathy screening instrument
Authors: Abuzinadah Ahmad R. , Alkully Hussien S. , Alanazy Mohammed H. , Alrawaili Moafaq S. , Milyani Haneen A. , AlAmri Bashayr , AlShareef Aysha A. , Bamaga Ahmed K.
Published: December 2021

The Michigan Neuropathy Screening Instrument (MNSI) is used to screen patients for diabetic neuropathy (DNP). We aimed to translate the MNSI questionnaire into Arabic (MNSIq-Ar) and to assess the validity and diagnostic performance of the MNSI Arabic version (MNSI-Ar).

Cronbach alpha α and the interclass correlation coefficient were used to measure the reliability and reproducibility of the MNSIq-Ar. The instrument's validity was assessed by Spearman correlation with the Utah Early Neuropathy Scale (UENS), the Modified Toronto Neuropathy Score (mTCNS), diabetic neuropathy symptoms (DNS), and sural nerve amplitude (SNA). The construct validity of the MNSI-Ar was assessed by its ability to differentiate the severity of DNP (using the Kruskal–Wallis test). The diagnostic performance was assessed through the receiver operator curve area.

We recruited 89 participants (mean [SD] age, 50.8 [12.3] years; 48% men). The MNSIq-Ar showed an α of 0.81 and intraclass correlation coefficient = 0.94, and the correlation coefficients with UENS, mTCNS, DNS, and sural nerve amplitude were 0.67, 0.83, 0.73, and −0.49, respectively (all P < .0001). The MNSI-Ar was able to differentiate the different severities of DNP. The receiver operator curve area was 0.93 with a high sensitivity of 95.9% and 100% for probable and confirmed DNP, respectively.

MNSI-Ar is a reliable and valid tool to screen for diabetic neuropathy in the Arabic language with a good diagnostic performance and high sensitivity.
Automatic segmentation of paravertebral muscles in abdominal CT scan by U-Net
Authors: Tsai Kuen-Jang , Chang Chih-Chun , Lo Lun-Chien , Chiang John Y. , Chang Chao-Sung , Huang Yu-Jung
Published: December 2021

Sarcopenia, characterized by a decline of skeletal muscle mass, has emerged as an important prognostic factor for cancer patients. Trunk computed tomography (CT) is a commonly used modality for assessment of cancer disease extent and treatment outcome. CT images can also be used to analyze the skeletal muscle mass filtered by the appropriate range of Hounsfield scale. However, a manual depiction of skeletal muscle in CT scan images for assessing skeletal muscle mass is labor-intensive and unrealistic in clinical practice. In this paper, we propose a novel U-Net based segmentation system for CT scan of paravertebral muscles in the third and fourth lumbar spines. Since the number of training samples is limited (i.e., 1024 CT images only), it is well-known that the performance of the deep learning approach is restricted due to overfitting. A data augmentation strategy to enlarge the diversity of the training set to boost the performance further is employed. On the other hand, we also discuss how the number of features in our U-Net affects the performance of the semantic segmentation. The efficacies of the proposed methodology based on w/ and w/o data augmentation and different feature maps are compared in the experiments. We show that the Jaccard score is approximately 95.0% based on the proposed data augmentation method with only 16 feature maps used in U-Net. The stability and efficiency of the proposed U-Net are verified in the experiments in a cross-validation manner.
Short- and long-term mortality after intravenous thrombolysis for acute ischemic stroke
Authors: Heo Nam Hun , Lee Man Ryul , Yang Ki Hwa , Hong Ock Ran , Shin Ji Hyeon , Lee Bo Yeon , Lee Ji Young , Ahn Jae Min , Oh Hyuk Jin , Oh Jae Sang
Published: December 2021

It remains unknown whether intravenous thrombolysis (IVT), thrombectomy, or poststroke antithrombotic medication lower short- and long-term mortality in acute ischemic stroke (AIS). This study aimed to investigate the efficacy of IVT in AIS using propensity score matching, to determine whether IVT could reduce short- and long-term mortality, and to identify risk factors influencing short- and long-term mortality in AIS.

During 2013 to 2014, the nationwide Korea Acute Stroke Assessment registry enrolled 14,394 patients with first-ever recorded ischemic stroke. Propensity score matching was used to match IVT and control cases with a 1:1 ratio. The primary outcome was survival up to 3 months, 1 year, and 5 years, as assessed using Kaplan–Meier estimates and Cox proportional hazards.

In total, 1317 patients treated with IVT were matched with 1317 patients not treated with IVT. Survival was higher in the IVT group (median, 3.53 years) than in the non-IVT group (median, 3.37 years, stratified log-rank test, P < .001). Compared with the non-IVT group, thrombolysis performed within 2 hours significantly reduced the risk of 3-month mortality by 37%, and thrombolysis performed between 2 and 4.5 hours significantly reduced the risk of 3-month mortality by 26%. Thrombectomy significantly reduced the risk of 3-month mortality by 28%. Compared with no poststroke medication, poststroke antiplatelet medication was associated with 51%, 55%, and 52% decreases in 3-month, 1-year, and 5-year mortality risk, respectively. Poststroke anticoagulant medication was associated with 51%, 54%, and 44% decreases in the risk of 3-month, 1-year, and 5-year mortality, respectively.

IVT and mechanical thrombectomy showed improvement in short-term survival. To improve long-term outcomes, the use of poststroke antithrombotic medication is important in AIS.
Soluble fms-like tyrosine kinase 1, placental growth factor and procalcitonin as biomarkers of gram-negative sepsis
Authors: Vittoros Vasileios , Kyriazopoulou Evdoxia , Lada Malvina , Tsangaris Iraklis , Koutelidakis Ioannis M. , Giamarellos-Bourboulis Evangelos J.
Published: December 2021

Further improvement of the diagnostic and prognostic performance of biomarkers for the critically ill is needed. Procalcitonin (PCT), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 raise interest for sepsis diagnosis and prognosis.

Serum samples from 2 cohorts of 172 patients (derivation cohort) and of 164 patients (validation cohort) comprising only patients with microbiologically confirmed gram-negative infections were analyzed. PlGF, s-Flt-1 and procalcitonin (PCT) were measured in serum within 24 hours from sepsis onset and repeated on days 3 and 7.

PCT and s-Flt-1 baseline levels were higher in sepsis and septic shock compared to non-sepsis; this was not the case for PlGF. s-Flt-1 at concentrations greater than 60 pg/ml diagnosed sepsis with sensitivity 72.3% and specificity 54.9% whereas at concentrations greater than 70 pg/ml predicted unfavorable outcome with specificity 73.0% and sensitivity 63.7%. At least 80% decrease of PCT and/or PCT less than 0.5 ng/ml on day 7 was protective from sepsis-associated death.

Both s-Flt-1 and PCT should be measured in the critically ill since they provide additive information for sepsis diagnosis and prognosis.

ClinicalTrials.gov numbers NCT01223690 and NCT00297674.
Clinical and radiological results of treating lumbar spondylosis with cortical bone trajectory screws
Authors: Bielecki Mateusz , Kunert Przemysław , Balasa Artur , Kujawski Sławomir , Marchel Andrzej
Published: December 2021

The cortical bone trajectory screws technique (CBTT) is a popular minimally invasive spine surgery. Few studies have reported long-term outcomes. We aimed to evaluate the complication profile and long-term follow-up results of patients with lumbar degenerative disease treated with the CBTT.

This retrospective analysis included the first 40 consecutive patients that underwent the CBTT. The indication for surgery was critical stenosis of the intervertebral foramen, which required removal of the entire intervertebral joint, on at least 1 side, during decompression.

The last follow-up showed minimal clinically important differences in the numerical rating scale of leg pain, the numerical rating scale of back pain, and the Oswestry Disability Index, in 97%, 95%, and 95% of patients, respectively. Thirty-nine patients completed long-term radiological follow-up. Computed tomography demonstrated solid bone union on 47 (92%) operated levels, collapsed union on 2 (4%) levels, nonunion on 1 (2%) level, and 1 (2%) patient was lost to follow-up. Seven patients experienced complications (4 hardware-related). Three patients required 4 revision surgeries.

The CBTT effectively achieved spinal fusion; over 90% of patients achieved clinical improvement at a mean follow-up of 4.4 years (range: 3–5.75 years).
The development of the cure of the functional intestinal disorder based on the differences of gut microbiota in aged patients
Authors: Matsuura Toshihiro , Kyokane Kazuhiro , Yamada Satoru , Kuno Yuji
Published: December 2021

Background:

Constipation, which is not an organic disease in the lower gastrointestinal tract, is a gastrointestinal symptom characteristic of elderly patients. Complaints of dyschezia increase with age, and it is difficult to treat in many cases. This study aimed to determine the appropriate treatment and its effects on intestinal immunity in elderly patients experiencing chronic constipation.

Methods:

Patients experiencing difficulty defecating were randomly divided into 2 groups. Group A was given only laxatives, whereas Group B was given laxatives combined with probiotics as an intervention. Both groups were compared based on the degree of improvement in constipation and its effects on the intestinal environment.

Results:

There was a significant improvement in constipation of elderly patients when probiotics were administered in combination with a laxative, suggesting that it may be a more effective treatment. Furthermore, the changes in the intestinal flora, examined before and after the intervention, tended to be associated with improvement of constipation.

Conclusion:

The results indicated that the improvement of intestinal flora was somewhat achieved by relieving constipation. Because intestinal bacteria significantly influence intestinal immunity and, thus, systemic immunity of the entire body, the development of better treatments for constipation would help to improve both the intestinal environment and immune function in the elderly.
The limited value of triage vital signs in predicting influenza infection in children aged 5 years and under in the emergency department
Authors: Lam Rex Pui Kin , Chan Kin Ling , Cheung Arthur Chi Kin , Wong Kin Wa , Lau Eric Ho Yin , Chen Lujie , Chaang Vi Ka , Woo Patrick Chiu Yat
Published: December 2021

Diagnosing influenza in children aged 5 years and under can be challenging because of their difficulty in verbalizing symptoms. This study aimed to explore the value of the triage heart rate (HR), respiratory rate (RR), and temperature, either alone or when combined with individual symptoms and signs, in predicting influenza infection in this age group.

This was a retrospective study covering 4 influenza seasons from 2017 to 2019 in an emergency department (ED) in Hong Kong. We recruited patients ≤5 years of age who had an reverse transcription polymerase chain reaction influenza test within 48 hours of ED presentation. The diagnostic performance of the triage HR, RR, and temperature was evaluated as dichotomized or categorized values with diagnostic odds ratios (DORs) calculated based on different age-appropriate thresholds. Linear discriminant analysis was performed to assess the combined discriminatory effect of age, HR, RR, and temperature as continuous variables.

Of 322 patients (median age 26 months), 99 had influenza A and 13 had influenza B infection. For HR and RR dichotomized based on age-appropriate thresholds, the DORs ranged from 1.16 to 1.54 and 0.78 to 1.53, respectively. A triage temperature ≥39.0 °C had the highest DOR (3.32) among different degrees of elevation of temperature. The diagnostic criteria that were based on the presence of fever and cough and/or rhinitis symptoms had a higher DOR compared with the Centers for Disease Control and Prevention influenza-like illness criteria (4.42 vs 2.41). However, combining HR, RR, or temperature with such diagnostic criteria added very little to the diagnostic performance. The linear discriminant analysis model had a high specificity of 92.5%, but the sensitivity (18.3%) was too low for clinical use.

Triage HR, RR, and temperature had limited value in the diagnosis of influenza in children ≤5 years of age in the ED. Fever and cough and/or rhinitis symptoms had a better diagnostic performance than the Centers for Disease Control and Prevention influenza-like illness criteria in predicting influenza in this age group.
A retrospective study of enteral nutrition on immune and inflammatory factors after liver cancer surgery
Authors: Xu Yao , Wei Feng-xiang
Published: December 2021

This retrospective study aimed to explore the effect of enteral nutrition (EN) on immune and inflammatory factors after liver cancer surgery (LCS).

It was retrospectively conducted on enrolled LCS patients between January 2017 and May 2020. The medical records of 528 patient case records were collected and reviewed. After selection, a total of 80 eligible patient case records were finally included. All those patients received routine diet, and they were allocated to a treatment group (n = 40) and a control group (n = 40). In addition, patients in the treatment group also received EN. The primary outcomes were immune factors (CD4+, CD8+, CD4+/CD8+) and inflammatory factors (interleukin-1, interleukin-6, and tumor necrosis factor-α). The secondary outcomes were postoperative hospital stay (day), time to first bowel sounds (hour), time to first flatus (day), time to first defecation (day), and complications.

There were not significant differences in CD4+/CD8+ (P = .34), postoperative hospital stay (P = .39), and time to first bowel sounds (P = .17) between 2 groups. However, there were significant differences in CD4+ (P < .01), CD8+ (P < .01), interleukin-1 (P < .01), interleukin-6 (P < .01), tumor necrosis factor-α (P < .01), time to first flatus (P < .01), and time to first defecation (P < .01) between 2 groups. As for complications, there were not significant differences between 2 groups (P > .05).

The results of this study found that EN may benefit for patients after LCS during the recovery period. Future high quality prospective studies are needed to warrant the present conclusion.
Predictors of oral pre-exposure prophylaxis (PrEP) uptake among individuals in a HIV vaccine preparedness cohort in Masaka, Uganda
Authors: Kusemererwa Sylvia , Kansiime Sheila , Mutonyi Gertrude , Namirembe Aeron , Katana Safina , Kitonsa Jonathan , Kakande Ayoub , Okello Joseph Mugisha , Kaleebu Pontiano , Ruzagira Eugene
Published: December 2021

Oral pre-exposure prophylaxis (PrEP) significantly reduces human immunodeficiency virus (HIV) acquisition risk. However, data on predictors of PrEP uptake in sub-Saharan Africa are limited. We assessed predictors of PrEP uptake among HIV-uninfected high risk individuals enrolled in a HIV vaccine preparedness study in Masaka, Uganda.

Between July 2018 and October 2020, we recruited adults (18–40 years) from sex work hotspots along the trans-African highway and Lake Victoria fishing communities. We collected baseline data on socio-demographics and PrEP awareness, and provided HIV counselling and testing, information on PrEP, and PrEP referrals at quarterly visits. Urine pregnancy tests (women) and data collection on sexual risk behaviour and PrEP uptake were performed every 6 months. We analysed PrEP uptake among participants who had completed 6 months of follow-up.

Of the 588 cohort participants, 362 (62%) were included in this analysis. Of these, 176 (49%) were female, 181 (50%) were aged ≤24 years, 104 (29%) worked in sex work hotspots, 74 (20%) were fisher folk. Only 75 (21%) participants initiated PrEP. Predictors of PrEP uptake included having ≥6 sex partners (adjusted odds ratio [aOR] = 2.29; 95% confidence interval [CI] 1.26–4.17), engaging in transactional sex (aOR = 2.23; 95% CI 0.95–5.20), and residence in a nonfishing community (aOR = 2.40; 95% CI 1.14–5.08). The commonest reasons for not starting PrEP were pill burden (38%) and needing more time to decide (27%).

PrEP uptake was low and associated with HIV risk indicators in this cohort. Interventions are needed to improve access to PrEP especially in fishing communities.
Ruxolitinib (a JAK2 inhibitor) as an emerging therapy for refractory pruritis in a patient with low-risk polycythemia vera
Authors: Al-Mashdali Abdulrahman F. , Kashgary Waail R. , Yassin Mohamed A.
Published: December 2021

Introduction:

Polycythemia vera (PV) is a Philadelphia-negative myeloproliferative neoplasm (MPN) characterized by the overproduction of red blood cells. The presence of JAK2 mutation is detected in up to 99% of patients with PV. Pruritis is commonly encountered in patients with PV and is considered the most troublesome symptom. Multiple treatment modalities are used for treatment; however, their efficacy is variable. Sometimes, pruritis will not improve even by the use of combined therapies. Recently, Ruxolitinib (a JAK2 inhibitor) has been shown to be very effective, especially in patients with refractory pruritis in the setting of other treatment modalities failure.

Patient concern:

We describe a 55-year-old male with history of low risk PV presented with severe itching despite using different therapies, including phlebotomy and hydroxyurea. His laboratory results on presentation were significant for red blood cells (RBC) of 8.2 × 106/uL (normal = 4.5–5.5), hematocrit (Hct) of 52.8% (normal = 40–50%), platelet count of 519 × 103/uL (normal = 150–400), white blood cells count of 12.3 × 103/uL (normal = 4–10), and basophils count of 0.22 × 103/uL (normal < 0.1).

Diagnosis:

PV related refractory pruritis.

Intervention:

Pruritis improved dramatically after starting Ruxolitinib therapy with an improvement of hematological parameters (both hematocrit and platelet count).

Conclusion:

Different treatment modalities have shown to be beneficial in treating PV-related pruritis, but the clinical outcomes are highly variable. This case report aims to shed light on Ruxolitinib as an emerging therapy for the treatment of refractory cases of PV-related pruritis.
Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma
Authors: Yagi Yu , Kanemasa Yusuke , Ohigashi An , Morita Yuka , Tamura Taichi , Nakamura Shohei , Otsuka Yuki , Kishida Yuya , Kageyama Akihiko , Shimizuguchi Takuya , Toya Takashi , Shimizu Hiroaki , Najima Yuho , Kobayashi Takeshi , Haraguchi Kyoko , Doki Noriko , Okuyama Yoshiki , Omuro Yasushi , Shimoyama Tatsu
Published: December 2021

Rationale:

Chimeric antigen receptor (CAR) T-cell therapy is effective in treating relapsed and refractory B-cell non-Hodgkin lymphoma. However, because of the mortality risk associated with immune effector cell-associated neurotoxicity syndrome and pseudoprogression, patients with central nervous system (CNS) involvement are less likely to receive CAR T-cell therapy.

Patients concerns:

We report a case of a 61-year-old, male patient with intravascular large B-cell lymphoma who suffered a CNS relapse after standard chemotherapy.

Diagnosis:

A diagnosis of intravascular large B-cell lymphoma with CNS involvement was made.

Interventions:

We treated the patient using CAR T-cell therapy following a conditioning regimen consisting of thiotepa and busulfan and autologous stem cell transplantation. Although he experienced grade 1 cytokine release syndrome, no other serious adverse events, such as immune effector cell-associated neurotoxicity syndrome or pseudoprogression, were observed.

Outcomes:

The patient achieved complete remission after the CAR T-cell infusion.

Lessons:

CAR T-cell therapy following autologous stem cell transplantation is a viable option for relapsed/refractory lymphoma with CNS infiltration. Further clinical studies are warranted to verify its safety and efficacy.
Palliative inter-professional learning via cased based tele-videoconference
Authors: Lin Huang-Ren , Wang Jen-Hung , Hsieh Jyh-Gang , Wang Ying-Wei
Published: December 2021

Palliative care in rural areas can be difficult to assess and, often is of lower quality compared to more densely populated regions. A program of multicenter palliative care discussion forum via tele-videoconference may be a promising tool for exchanging valuable experience and constructing a comprehensive hospice care system in Taiwan and China.

The multicenter palliative care discussion forum began 1997 and 2010 in Taiwan and China, respectively. In every forum, 1 to 2 cases were presented by multiple field specialists, and multi-dimensional problems were discussed. All of these case reports and reference materials from the forums were analyzed.

The conference discussed 199 and 143 cases in Taiwan and China, including 172 and 143 cancer patients. The most common mentioned symptom was pain (66.3% in Taiwan, 96.95% in China). As time went on, the rate of discussion in pain management issues decreased, but the social and psycho-spiritual issues increased in Taiwan. After some major legal and social changes, the discussion of ethical issues increased rapidly. In China, the trends and ranking in discussion of nonpain management issues stabilized and showed most frequently in psycho-spiritual issues, followed by social, ethical and legal issues.

Sharing palliative experience via tele-videoconferences is an effective tool to improve the quality of care, and also saves a significant amount of time and expense. Experts in different professions from different hospitals should discuss any palliative problems, share their valuable experience, and ponder a comprehensive hospice care.
Association of Antidepressant Prescription Filling With Treatment Indication and Prior Prescription Filling Behaviors and Medication Experiences
Authors: Wong Jenna , Kurteva Siyana , Motulsky Aude , Tamblyn Robyn
Published: December 2021

Background:

Given the wide range of uses for antidepressants, understanding indication-specific patterns of prescription filling for antidepressants provide valuable insights into how patients use these medications in real-world settings.

Objective:

The objective of this study was to determine the association of antidepressant prescription filling with treatment indication, as well as prior prescription filling behaviors and medication experiences.

Design:

This retrospective cohort study took place in Quebec, Canada.

Participants:

Adults with public drug insurance prescribed antidepressants using MOXXI (Medical Office of the XXIst Century)—an electronic prescribing system requiring primary care physicians to document treatment indications and reasons for prescription stops or changes.

Measures:

MOXXI provided information on treatment indications, past prescriptions, and prior medication experiences (treatment ineffectiveness and adverse drug reactions). Linked claims data provided information on dispensed medications and other patient-related factors. Multivariable logistic regression models estimated the independent association of not filling an antidepressant prescription (within 90 d) with treatment indication and patients’ prior prescription filling behaviors and medication experiences.

Results:

Among 38,751 prescriptions, the prevalence of unfilled prescriptions for new and ongoing antidepressant therapy was 34.2% and 4.1%, respectively. Compared with depression, odds of not filling an antidepressant prescription varied from 0.74 to 1.57 by indication and therapy status. The odds of not filling an antidepressant prescription was higher among adults filling < 50% of their medication prescriptions in the past year and adults with an antidepressant prescription stopped or changed in the past year due to treatment ineffectiveness.

Conclusion:

Antidepressant prescription filling behaviors differed by treatment indication and were lower among patients with a history of poor prescription filling or ineffective treatment with antidepressants.
Development of an International Tool for Students to Record and Reflect on Patient Safety Learning Experiences
Authors: Steven Alison , Pearson Pauline , Turunen Hannele , Myhre Kristin , Sasso Loredana , Vizcaya-Moreno Maria Flores , Pérez-Cañaveras Rosa María , Sara-Aho Arja , Bagnasco Annamaria , Aleo Giuseppe , Patterson Lucy , Larkin Valerie , Zanini Milko , Porras Jari , Khakurel Jayden , Azimirad Mina , Ringstad Øystein , Johnsen Lasse , Haatainen Kaisa , Wilson Gemma , Rossi Silvia , Morey Sarah , Tella Susanna
Published: December 2021

Background:

Underpinning all nursing education is the development of safe practitioners who provide quality care. Learning in practice settings is important, but student experiences vary.

Purpose:

This study aimed to systematically develop a robust multilingual, multiprofessional data collection tool, which prompts students to describe and reflect on patient safety experiences.

Approach:

Core to a 3-year, 5-country, European project was development of the SLIPPS (Sharing Learning from Practice for Patient Safety) Learning Event Recording Tool (SLERT). Tool construction drew on literature, theory, multinational and multidisciplinary experience, and involved pretesting and translation. Piloting included assessing usability and an initial exploration of impact via student interviews.

Outcomes:

The final SLERT (provided for readers) is freely available in 5 languages and has face validity for nursing across 5 countries. Student reports (n = 368) were collected using the tool.

Conclusions:

The tool functions well in assisting student learning and for collecting data. Interviews indicated the tool promoted individual learning and has potential for wider clinical teams.
Multiple RNA virus matrix proteins interact with SLD5 to manipulate host cell cycle
Authors: Zhu Li , Li Xinyu , Xu Henan , Fu Lifeng , Gao George Fu , Liu Wenjun , Zhao Linqing , Wang Xiaojun , Jiang Wei , Fang Min
Published: December 2021

The matrix protein of many enveloped RNA viruses regulates multiple stages of viral life cycle and has the characteristics of nucleocytoplasmic shuttling. We have previously demonstrated that matrix protein 1 (M1) of an RNA virus, influenza virus, blocks host cell cycle progression by interacting with SLD5, a member of the GINS complex, which is required for normal cell cycle progression. In this study, we found that M protein of several other RNA viruses, including VSV, SeV and HIV, interacted with SLD5. Furthermore, VSV/SeV infection and M protein of VSV/SeV/HIV induced cell cycle arrest at G0/G1 phase. Importantly, overexpression of SLD5 partially rescued the cell cycle arrest by VSV/SeV infection and VSV M protein. In addition, SLD5 suppressed VSV replication in vitro and in vivo, and enhanced type Ⅰ interferon signalling. Taken together, our results suggest that targeting SLD5 by M protein might be a common strategy used by multiple enveloped RNA viruses to block host cell cycle. Our findings provide new mechanistic insights for virus to manipulate cell cycle progression by hijacking host replication factor SLD5 during infection.
A proteomic perspective and involvement of cytokines in SARS-CoV-2 infection
Authors: Banu Sarena , Idris Mohammed M , Nagaraj Ramakrishnan
Published: December 2021

Infection with the SARS-CoV-2 virus results in manifestation of several clinical observations from asymptomatic to multi-organ failure. Biochemically, the serious effects are due to what is described as cytokine storm. The initial infection region for COVID-19 is the nasopharyngeal/oropharyngeal region which is the site where samples are taken to examine the presence of virus. We have earlier shown that several defensin genes are down regulated in cells from this region in patients who tested positive in the RTPCR test. We have now carried out detailed proteomic analysis of the nasopharyngeal/oropharyngeal swab samples collected from normal individuals and those tested positive for SARS-CoV-2 by RTPCR, involving high throughput quantitative proteomics analysis. Several proteins like annexins, cytokines and histones were found differentially regulated in the host human cells following SARS-CoV-2 infection. Genes for these proteins were also observed to be differentially regulated when their expression was analyzed. Majority of the cytokine proteins were found to be up regulated in the infected individuals. Cell to Cell signaling interaction, Immune cell trafficking and inflammatory response pathways were found associated with the differentially regulated proteins based on network pathway analysis.
Microbiota composition in the lower respiratory tract is associated with severity in patients with acute respiratory distress by influenza
Authors: Hernández-Terán Alejandra , Vega-Sánchez Angel E. , Mejía-Nepomuceno Fidencio , Serna-Muñoz Ricardo , Rodríguez-Llamazares Sebastián , Salido-Guadarrama Iván , Romero-Espinoza Jose A. , Guadarrama-Pérez Cristobal , Sandoval JL , Campos Fernando , Mondragón-Rivero Erika N. , Ramírez-Venegas Alejandra , Castillejos-López Manuel , Téllez-Navarrete Norma A. , Ormsby Christopher E. , Pérez- Padilla Rogelio , Vázquez-Pérez Joel A.
Published: December 2021

Several factors are associated with the severity of the respiratory disease caused by the influenza virus. Although viral factors are one of the most studied, in recent years the role of the microbiota and co-infections in severe and fatal outcomes has been recognized. However, most of the work has focused on the microbiota of the upper respiratory tract (URT), hindering potential insights from the lower respiratory tract (LRT) that may help to understand the role of the microbiota in Influenza disease. In this work, we characterized the microbiota of the LRT of patients with Influenza A using 16S rRNA sequencing. We tested if patients with different outcomes (deceased/recovered), use of antibiotics, and different days of symptoms onset differ in their microbial community composition. We found striking differences in the diversity and composition of the microbiota depending on the days of symptoms onset and with mortality of the studied patients. We detected a high abundance of opportunistic pathogens such as Enterococcus, Granulicatella, and Staphylococcus in patients either deceased or with antibiotic treatment. Also, we found that antibiotic treatment deeply perturbs the microbial communities in the LRT and affect the probability of survival in Influenza A patients. Altogether, the loss of microbial diversity could, in turn, generate a disequilibrium in the community, potentially compromising the immune response increasing viral infectivity, promoting the growth of potentially pathogenic bacteria that, together with altered biochemical parameters, can be leading to severe forms of the disease. Overall, the present study gives one of the first characterizations of the diversity and composition of microbial communities in the LRT of Influenza patients and its relationship with clinical variables and disease severity.
BSImp: imputing partially observed methylation patterns for evaluating methylation heterogeneity
Authors: Chang Ya-Ting , Yen Ming-Ren , Chen Pao-Yang
Published: December 2021

DNA methylation is one of the most studied epigenetic modifications that has applications ranging from transcriptional regulation to aging, and can be assessed by bisulfite sequencing (BS-seq) at single base-pair resolution. The permutations of methylation statuses at bisulfite converted reads reflect the methylation patterns of individual cells. These patterns at specific genomic locations are sought to be indicative of cellular heterogeneity within a cellular population, which are predictive of developments and diseases; therefore, methylation heterogeneity has potentials in early detection of these changes. Computational methods have been developed to assess methylation heterogeneity using methylation patterns formed by four CpGs, but the nature of shotgun sequencing often give partially observed patterns, which makes very limited data available for downstream analysis. While many programs are developed to impute methylation levels genomewide, currently there is only one method developed for recovering partially observed methylation patterns; however, the program needs lots of data to train and cannot be used directly; therefore, we developed a probabilistic-based imputation method that uses information from neighbouring sites to recover partially observed methylation patterns speedily. It is demonstrated to allow for the evaluation of methylation heterogeneity at three times more regions genome-wide with high accuracy for data with moderate depth. To make it more user-friendly we also provide a computational pipeline for genome-screening, which can be used in both evaluating methylation levels and profiling methylation patterns genomewide for all cytosine contexts, which is the first of its kind. Our method allows for accurate estimation of methylation levels and makes evaluating methylation heterogeneity available for much more data with reasonable coverage, which has important implications in using methylation heterogeneity for monitoring changes within the cellular populations that were impossible to detect for the assessment of development and diseases.
Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its pathological conformational conversion
Authors: Wang Li-Qiang , Ma Yeyang , Yuan Han-Ye , Zhao Kun , Zhang Mu-Ya , Wang Qiang , Huang Xi , Xu Wen-Chang , Chen Jie , Li Dan , Zhang Delin , Zou Liangyu , Yin Ping , Liu Cong , Liang Yi
Published: December 2021

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by the selective death of motor neurons. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial ALS and sporadic ALS. SOD1 fibrils formed in vitro are able to incorporate into cells, transmit intercellularly, and share toxic properties with ALS inclusions. Here we produced amyloid fibrils in vitro from recombinant, full-length apo human SOD1 under semi-reducing conditions and determined the atomic structure using cryo-EM. The SOD1 fibril consists of a single protofibril with a left-handed helix. The fibril core exhibits a serpentine fold comprising N-terminal segment (residues 3 to 55) and C-terminal segment (residues 86 to 153) with a structural break. The two segments are zipped up by three salt bridge pairs. By comparison with the structure of apo SOD1 dimer, we propose that eight β-strands (to form a β-barrel) and one α-helix in the subunit of apo SOD1 convert into thirteen β-strands stabilized by five hydrophobic cavities in the SOD1 fibril. Our data provide insights into how SOD1 converts between structurally and functionally distinct states.
Glioblastoma embryonic-like stem cells exhibit immune-evasive phenotype
Authors: Sesé Borja , Iñiguez-Muñoz Sandra , Ensenyat-Mendez Miquel , Llinàs-Arias Pere , Ramis Guillem , Orozco Javier I. J. , de Mattos Silvia Fernández , Villalonga Priam , Marzese Diego M.
Published: December 2021

Glioma stem cells (GSCs) are a subset of cells with self-renewal and tumor-initiating capacities that are thought to participate in drug resistance and immune evasion mechanisms in glioblastoma (GBM). Given GBM heterogeneity, we hypothesized that GSCs might also display cellular hierarchies associated with different degrees of stemness. We evaluated a single-cell RNA-seq glioblastoma dataset (n = 28) and identified a stem cell population co-expressing high levels of embryonic pluripotency markers, named core glioma stem cells (c-GSCs). This embryonic-like population represents 4.22% ± 0.59 of the tumor cell mass, and pathway analysis revealed an upregulation of stemness and downregulation of immune-associated pathways. Using induced pluripotent stem cell technology, we generated an in vitro model of c-GSCs by reprogramming glioblastoma patient-derived cells into induced c-GSCs (ic-GSCs). Immunostaining of ic-GSCs showed high expression of embryonic pluripotency markers and downregulation of antigen presentation HLA proteins, mimicking its tumoral counterpart. Transcriptomic analysis revealed a strong agreement of enriched biological pathways between tumor c-GSCs and in vitro ic-GSCs (κ = 0.71). Integration of ic-GSC DNA methylation and gene expression with chromatin state analysis of epigenomic maps (n = 833) indicated that polycomb repressive marks downregulate HLA genes in stem-like phenotype. Together, we identified c-GSCs as a GBM cell population with embryonic signatures and poor immunogenicity. Genome-scale transcriptomic and epigenomic profiling provide a valuable resource for studying immune evasion mechanisms governing c-GSCs and identifying potential therapeutic targets for GBM immunotherapy.
Heart age estimated using explainable advanced electrocardiography
Authors: Lindow Thomas , Palencia-Lamela Israel , Schlegel Todd T , Ugander Martin
Published: December 2021

Background

Electrocardiographic (ECG) Heart Age conveying cardiovascular risk has been estimated by both Bayesian and artificial intelligence approaches. We hypothesised that explainable measures from the 10-second 12-lead ECG could successfully predict Bayesian 5-min ECG Heart Age.

Methods

Advanced analysis was performed on ECGs from healthy subjects and patients with cardiovascular risk or proven heart disease. Regression models were used to predict patients’ Bayesian 5-minute ECG Heart Ages from their standard, resting 10-second 12-lead ECGs. The difference between 5-min and 10-second ECG Heart Ages were analyzed, as were the differences between 10-second ECG Heart Age and the chronological age (the Heart Age Gap).

Results

In total, 2,771 subjects were included (n=1682 healthy volunteers, n=305 with cardiovascular risk factors, n=784 with cardiovascular disease). Overall, 10-second Heart Age showed strong agreement with the 5-minute Heart Age (R2=0.94, p<0.001, mean±SD bias 0.0±5.1 years). The Heart Age Gap was 0.0±5.7 years in healthy individuals, 7.4±7.3 years in subjects with cardiovascular risk factors (p<0.001), and 14.3±9.2 years in patients with cardiovascular disease (p<0.001).

Conclusions

Heart Age can be accurately estimated from a 10-second 12-lead ECG in a transparent and explainable fashion based on known ECG measures, without artificial intelligence techniques. The Heart Age Gap increases markedly with cardiovascular risk and disease.