Clinical Phenomenon Research Articles

Identification and validation of hub genes in drug induced acute kidney injury basing on integrated transcriptomic analysis.

Drug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of medicines. The lack of a specialized treatment and the instability of traditional kidney injury markers to detect DI-AKI frequently result in the development of chronic kidney disease. Thus, it is crucial to continue screening for DI-AKI hub genes and specific biomarkers. Differentially expressed genes (DEGs) of group iohexol, cisplatin, and vancomycin's were analyzed using Limma package, and the intersection was calculated. DEGs were then put into String database to create a network of protein-protein interactions (PPI). Ten algorithms are used in the Cytohubba plugin to find the common hub genes. Three DI-AKI models' hub gene expression was verified in vivo and in vitro using PCR and western blot. To investigate the hub gene's potential as a biomarker, protein levels of mouse serum and urine were measured by ELISA kits. The UUO, IRI and aristolochic acid I-induced nephrotoxicity (AAN) datasets in the GEO database were utilized for external data verification by WGCNA and Limma package. Finally, the Elisa kit was used to identify DI-AKI patient samples. 95 up-regulated common DEGs and 32 down-regulated common DEGs were obtained using Limma package. A PPI network with 84 nodes and 24 edges was built with confidence >0.4. Four hub genes were obtained by Algorithms of Cytohubba plugin, including TLR4, AOC3, IRF4 and TNFAIP6. Then, we discovered that the protein and mRNA levels of four hub genes were significantly changed in the DI-AKI model in vivo and in vitro. External data validation revealed that only the AAN model, which also belonged to DI-AKI model, had significant difference in these hub genes, whereas IRI and UUO did not. Finally, we found that plasma TLR4 levels were higher in patients with DI-AKI, especially in vancomycin-induced AKI. The immune system and inflammation are key factors in DI-AKI. We discovered the immunological and inflammatory-related genes TLR4, AOC3, IRF4, and TNFAIP6, which may be promising specific biomarkers and essential hub genes for the prevention and identification of DI-AKI.

Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure

Maternal immune dysregulation is a prenatal risk factor for autism spectrum disorder (ASD). Importantly, a clinically relevant connection exists between inflammation and metabolic stress that can result in aberrant cytokine signaling and autoimmunity. In this study we examined the potential for maternal autoantibodies (aAbs) to disrupt metabolic signaling and induce neuroanatomical changes in the brains of exposed offspring. To accomplish this, we developed a model of maternal aAb exposure in rats based on the clinical phenomenon of maternal autoantibody-related ASD (MAR-ASD). Following confirmation of aAb production in rat dams and antigen-specific immunoglobulin G (IgG) transfer to offspring, we assessed offspring behavior and brain structure longitudinally. MAR-ASD rat offspring displayed a reduction in pup ultrasonic vocalizations and a pronounced deficit in social play behavior when allowed to freely interact with a novel partner. Additionally, longitudinal in vivo structural magnetic resonance imaging (sMRI) at postnatal day 30 (PND30) and PND70, conducted in a separate cohort of animals, revealed sex-specific differences in total and regional brain volume. Treatment-specific effects by region appeared to converge on midbrain and cerebellar structures in MAR-ASD offspring. Simultaneously, in vivo 1H magnetic resonance spectroscopy (1H-MRS) data were collected to examine brain metabolite levels in the medial prefrontal cortex. Results showed that MAR-ASD offspring displayed decreased levels of choline-containing compounds and glutathione, accompanied by increased taurine compared to control animals. Overall, we found that rats exposed to MAR-ASD aAbs present with alterations in behavior, brain structure, and neurometabolites; reminiscent of findings observed in clinical ASD.

Establishing a Xenograft Model with CD-1 Nude Mice to Study Human Skin Wound Repair.

A significant gap exists in the translatability of small-animal models to human subjects. One important factor is poor laboratory models involving human tissue. Thus, the authors have created a viable postnatal human skin xenograft model using athymic mice. Discarded human foreskins were collected following circumcision. All subcutaneous tissue was removed from these samples sterilely. Host CD-1 nude mice were then anesthetized, and dorsal skin was sterilized. A 1.2-cm-diameter, full-thickness section of dorsal skin was excised. The foreskin sample was then placed into the full-thickness defect in the host mice and sutured into place. Xenografts underwent dermal wounding using a 4-mm punch biopsy after engraftment. Xenografts were monitored for 14 days after wounding and then harvested. At 14 days postoperatively, all mice survived the procedure. Grossly, the xenograft wounds showed formation of a human scar at postoperative day 14. Hematoxylin and eosin and Masson trichome staining confirmed scar formation in the wounded human skin. Using a novel artificial intelligence algorithm using picrosirius red staining, scar formation was confirmed in human wounded skin compared with the unwounded skin. Histologically, CD31 + immunostaining confirmed vascularization of the xenograft. The xenograft exclusively showed human collagen type I, CD26 + , and human nuclear antigen in the human scar without any staining of these human markers in the murine skin. The proposed model demonstrates wound healing to be a local response from tissue resident human fibroblasts and allows for reproducible evaluation of human skin wound repair in a preclinical model. Radiation-induced fibrosis is a widely prevalent clinical phenomenon without a well-defined treatment at this time. This study will help establish a small-animal model to better understand and develop novel therapeutics to treat irradiated human skin.

Examining substitution behaviors in a non-treatment sample of current drinkers: an exploratory study

ABSTRACT In a sample of adults who reported cutting down on their alcohol use in the past 3 months, study goals were to Identify how many increased consumption of licit substances (called ‘substituters’); and analyze the psychological profiles of substituters compared to non-substituters. Participants (25.6% Latinx, 46.2% female) were recruited using Amazon’s Mturk and completed questionnaires on substance use substitution (i.e. any increased use of a substance while cutting down on another substance) and stress, depression, and anxiety. Among those reporting decreases in alcohol use (N = 78), 78% substituted (N = 61), defined as concomitant increases in food, cannabis, or nicotine. Substituters had higher levels of pysychological distress, reported greater polysubstance use and significantly higher levels of problems related to use than non-substituters. All of the Latinx participants (n = 20) reported substitution and reported significantly higher psychological distress than non-Latinx substituters. Latinxs who reported substitution had more serious psychological profiles and problems related to substance use. The findings provide evidence for a clinical phenomenon involving substitution in a non-treatment sample. Future studies should examine this phenomenon among people in addiction treatment and among Latinxs.

Macrophage-Derived MMP-9 and MMP-2 are Closely Related to the Rupture of the Fibrous Capsule of Hepatocellular Carcinoma Leading to Tumor Invasion

BackgroundHepatocellular carcinoma (HCC) is an aggressive tumor with a poor clinical prognosis. Rupture of the fibrous capsule (FC) is a very important clinical phenomenon in the invasion and metastasis of HCC. FC is mainly composed of type I collagen (COL1A1). However, it is not clear what caused the FC rupture. In this study, we aimed to determine whether the rupture of FC in HCC patients was related to macrophage-derived MMP-9 and MMP-2, and their clinical diagnostic value for FC rupture.ResultsBy performing immunohistochemical and immunofluorescence staining of ruptured FC and intact FC, the results showed that the ruptured area of FC aggregated a large number of macrophages with MMP-9 and MMP-2. Western blot analysis and Quantitative real-time PCR were used to assess the expression of MMP-9 and MMP-2 in the ruptured and relatively intact area of FC in ruptured FC patients, and the results revealed a significantly different expression of MMP-9 and MMP-2. ELISA experiments show that we could discriminate effectively between ruptured FC and intact FC by MMP-9 and MMP-2.ConclusionsTaken together, macrophage-derived MMP-9 and MMP-2 were closely related to the rupture of the FC of HCC and subsequently led to the migration and invasion of the tumor cells through the ruptured area of FC to the para cancer. It is suggested that when performing surgical resection, it is necessary to expand the range of tumor resection for patients with ruptured FC and hence reduce the possibility of recurrence and metastasis in HCC patients.

Pembrolizumab related central diabetes insipidus

This case report describes a case of anti-programmed cell death protein 1 (PD-1) antibody-related central diabetes insipidus without features of infiltrative process on neuroimaging. It involved a 63-year old man who was initially admitted for immunotherapy-related pneumonitis and was subsequently diagnosed with new central diabetes insipidus on the background of advanced non-small cell lung cancer treated with pembrolizumab. This clinical phenomenon is exceedingly rare and has been reported with anti-cytotoxic T lymphocytes-4 (CTLA-4) agent [1]. Central diabetes insipidus associated with anti-PD-1 monotherapy has only been described in three case reports [2-4]. Neuroimaging plays an important role to identify other process including metastatic infiltration. Multi-disciplinary patient care remains the key in managing patients with immunotherapyrelated endocrinopathies.

M.U.P.S (Medically Unexplained Physical Symptoms): Is the Accurate Diagnosis Necessary for the Rehab-Team?

Background: Physiatrists often treat patients with medically unexplained symptoms (MUPS), which suggest various psychiatric, psychosomatic or physical diagnoses. Some patients are finally diagnosed with somatoform, dissociative or factitious disorders, while some experience psychological factors affecting physical conditions. It happens that patients are admitted to rehabilitative medical facilities without a clear diagnosis. Apparently, there are overlapping symptoms between chronic fatigue syndrome, PTSD (post-traumatic stress disorder), "Gulf War syndrome", fibromyalgia, CRPS, and others.Aims: To assess recognition of medically unexplained physical symptoms (MUPS) by physicians, mostly specialists in physical and rehabilitative medicine are engaged.Methods: All information was collected from scientific database site, and derived from the authors' nearly 50 years of clinical experience.Results: Cognitive-affective disturbance, chronic muscle and joint pain, panic disorder, chronic fatigue syndrome, malingering, and others can be described in the medical literature as unexplained physical symptoms.Conclusions: Treatment should comprise a multidisciplinary-integrative approach, by practitioners from medicine, psychology, allied health professionals and social work. MUPS is not a "non-disease" entity, but rather, an unexplained clinical phenomenon. Patients are entitled to benefit from the rehabilitative medicine model of treatment even if their clinical diagnosis is not accurate or clear.

An analysis of the prevalence and impact of obsessive-compulsive personality disorder on the course of obsessive-compulsive disorder

Introduction Obsessive-compulsive disorder (OCD) is a disorder diagnosed on the basis of the presence of obsessions (persistently recurring, intrusive thoughts, images, impulses) and compulsions (compulsive and transiently satisfying actions performed in response to obsessions). A separate clinical phenomenon in the broadly understood anankastic spectrum is obsessive-compulsive disorder (OCPD). OCPD is characterized by scrupulousness, over-normative morality, perfectionism and an inability to make concessions in terms of cooperation. It is assumed that the incidence of OCPD in the course of OCD is 25-32% and it is a report with an unfavorable course and a more difficult therapeutic prognosis. It also means an early onset of OCD with a greater intensity of compulsions and a predominance of symptoms related to the sphere of purity, symmetry and gathering. Objectives The main aims of the study were as follows: 1. To assess the prevalence of OCPD in OCD patients. 2. To compare both groups of patients for the severity, level of insight, aggression, impulsiveness and affective symptoms. 3. To verify whether the presence of OCPD depend on factors such as age, gender, treatment duration and delay in starting treatment. Methods The study was conducted in a group of 78 patients diagnosed with and treated for OCD. The patients were divided into two groups: patients with OCD and OCPD (group 1, n=43) and patients with OCD without OCPD (group 2, n=35). The groups were subsequently compared for the severity of anankastic symptoms, the level of insight, aggression, impulsiveness and its components and affective symptoms (depression, mania). The following tools were used for the diagnosis: Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Depression-Rating Scale (HDRS), Young Mania Rating Scale (YMRS), Buss-Perry Aggression Questionnaire (BPAQ), Barratt Impulsiveness Scale (BIS-11), Brown Assessment of Beliefs Scale (BABS) and DSM 5 criteria for OCPD. Results Our results confirmed that OCPD is common in OCD and occurred in 55,12% of patients with OCD (n=43; m=21; f=22). The study shows that the presence of OCPD in the course of OCD negatively affects the severity of obsessive-compulsive symptoms, the level of insight, the level of aggression and impulsiveness, and affective disorders. Patients with OCPD obtained higher scores on the YBOCS, BABS, HDRS, and YMRS scales compared to patients with OCD without OCPD. The occurrence of OCPD in the study group did not depend on gender, duration of OCD treatment, or delay in starting it. Conclusions The occurrence of OCPD is common in OCD and can cause delay of treatment, worse course, greater intensity of egosyntonic symptoms, and thus worse insight. The presence of OCPD can lead to more hostility and more affective disorders. Screening for OCPD in patients with OCD should be an integral part of an OCD diagnostic process. Disclosure of Interest None Declared

Abstract ED12-2: Mechanisms of sensitivity and resistance to HRD targeting agents in breast cancer – PARPi and beyond

Abstract Although PARP inhibitors (PARPi) deliver significant and sustained anti-tumour responses in those with HR defective cancers, PARPi resistance is a common clinical phenomenon and limits the overall effectiveness of these agents. I will discuss how reversion mutations in BRCA1 and BRCA2 cause PARPi resistance and how the emergence of reversions might be targeted by immune responses against the neopeptides caused by reversion mutations. I will also discuss how other mechanisms of PARPi resistance such as 53BP1/Shieldin complex dysfunction could be targeted by evolutionary “double binds” using drugs such as Pol-theta inhibitors that exploit new vulnerabilities put in place by emerging PARPi resistance mechanisms Citation Format: Christopher Lord. Mechanisms of sensitivity and resistance to HRD targeting agents in breast cancer – PARPi and beyond [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED12-2.

Novel Dual-Target Kinase Inhibitors of EGFR and ALK Were Designed, Synthesized, and Induced Cell Apoptosis in Non-Small Cell Lung Cancer

ALK-positive NSCLC coexisting with EGFR mutations is a frequently occurring clinical phenomenon. Targeting ALK and EGFR simultaneously may be an effective way to treat these cancer patients. In this study, we designed and synthesized ten new dual-target EGFR/ALK inhibitors. Among them, the optimal compound 9j exhibited good activity with IC50 values of 0.07829 ± 0.03 μM and 0.08183 ± 0.02 μM against H1975 (EGFR T790M/L858R) and H2228 (EML4-ALK) cells, respectively. Immunofluorescence assays indicated that the compound could simultaneously inhibit the expression of phosphorylated EGFR and ALK proteins. A kinase assay demonstrated that compound 9j could inhibit both EGFR and ALK kinases; thus, exerting an antitumor effect. Additionally, compound 9j induced apoptosis in a dose-dependent manner and inhibited the invasion and migration of tumor cells. All of these results indicate that 9j is worthy of further study.

Prevalence and predictors of Twiddler's syndrome.

Twiddler's syndrome is a poorly understood clinical phenomenon when patients either consciously or subconsciously rotate their cardiac device resulting in lead dislodgement. We aimed to determine the true prevalence and risk factors associated with Twiddler's syndrome in a real-world population. A retrospective chart review was performed on all patients who underwent cardiac device implantation from January 1st 2017 until Jan 1st 2022. We specifically searched for the terms "Twiddler" or "Twiddler's" imbedded within the text of the medical chart. Demographic and clinical variables were collected from the electronic medical record system. We utilized multivariable logistic regression analysis as well as Kaplan-Meier prediction models to determine independent clinical predictors of Twiddler's syndrome as well as associated mortality, respectively. Twenty one out of 1793 patients (1.2%) were identified as having Twiddler's syndrome after chart review. Independent variables associated with Twiddler's syndrome were female sex (OR 3.76; 95% CI 1.29-10.95), antidepressant medications (OR 3.58; 95% CI 1.07-11.99), and BMI (OR 1.08; 95% CI 1.03-1.31). There was no increased six-month mortality via Kaplan-Meier analysis. Our study shows that 1.2% of patients in our real-world population had evidence of Twiddler's syndrome. Independent predictors of Twiddler's syndrome include female sex, antidepressant medications as well as BMI.

Increased Platelet Activation demonstrated by Elevated CD36 and P-Selectin Expression in 1-Year Post-Recovered COVID-19 Patients.

Coronavirus disease 2019 (COVID-19)-associated hypercoagulability and platelet hyperactivity are characteristic of COVID-19 infection and contribute to an increased thrombotic burden. This clinical phenomenon is observed during acute illness and the immediate post-recovery period. In addition to findings of hypercoagulability, endotheliopathy, and inflammation from our previous study of 39 COVID-19 survivors at a time point approximating 1 year after their recovery from COVID-19,[1] we evaluated the platelet activation profile of a subset of 36 patients, demonstrating increased platelet activation with elevated CD36 and P-selectin expression compared with healthy individuals without COVID-19 infection.

Relative Bradycardia in Critically Ill Patients with Novel Coronavirus 19: A Case Series

Severe coronavirus 2019 (COVID-19) infection is associated with myocardial injury and arrhythmia. Bradycardia is a newly recognized consequence of COVID-19. Relative bradycardia and its effects in 4 critically ill patients with COVID-19 was described in this case series. The 4 cases showed the same clinical phenomenon: sinus bradycardia without a compensatory increase in heart rate in response to elevation of body temperature. Typically, heart rate decreases as body temperature rises. The 4 patients were all men with an average age of 67 years. Patient 1 was a 78-year-old man with no major medical history who died from COVID-19 pneumonia. The other 3 patients recovered.

Parents Rate Problematic Video Streaming in Adolescents: Conceptualization and External Assessment of a New Clinical Phenomenon Based on the ICD-11 Criteria of Gaming Disorder.

In recent years, video streaming (VS) increased substantially. Adolescents are at significant risk of presenting problematic VS patterns associated with a spectrum of mental-health difficulties. Because VS platforms rely on similar mechanisms as digital games, the ICD-11 criteria for Gaming Disorder (GD) have been successfully implemented to measure Streaming Disorder (StrD) in adolescents. For proper diagnoses, external rating scales are urgently required in addition to self-reports. The Streaming Disorder Scale for Parents (STREDIS-P) was created and validated in a representative sample of n = 891 adolescent-parent dyads. Mental health problems were assessed with standardized instruments. Confirmatory factor analysis was conducted to examine the underlying factor structure. Cutoff scores were determined using ROC analysis. Accordance between parental and adolescents' self-ratings was calculated. Consistent with the results of previous validation studies for screening instruments assessing similar phenomena based on ICD-11-GD criteria, two factors, cognitive-behavioral symptoms and negative consequences, were confirmed. STREDIS-P demonstrated good to excellent internal consistency, criterion validity, and discriminatory power. Accordance with adolescents' self-ratings was moderate. STREDIS-P is the first screening tool for assessing StrD in adolescents by parental ratings. It is highly relevant for conceptualizing a new phenomenon in clinical routine and academic research.

Amelioratory Effect of Melatonin on Cognition Dysfunction Induced by Sevoflurane Anesthesia in Aged Mice.

Postoperative cognitive dysfunction (POCD) can be described as a clinical phenomenon characterized by cognitive impairment in patients, particularly elderly patients, after anesthesia and surgery. Researchers have focused on the probable effect of general anesthesia drugs on cognitive functioning status in older adults. Melatonin is an indole-type neuroendocrine hormone with broad biological activity and potent anti-inflammatory, anti-apoptotic, and neuroprotective effects. This study investigated the effects of melatonin on cognitive behavior in aged mice anesthetized with sevoflurane. In addition, melatonin's molecular mechanism was determined. This study aimed to investigate the mechanisms of melatonin against sevoflurane-induced neurotoxicity. A total of 94 aged C57BL/6J mice were categorized into different groups, namely control (control + melatonin (10 mg/kg)), sevoflurane (sevoflurane + melatonin (10 mg/kg)), sevoflurane + melatonin (10 mg/kg) + phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) inhibitor LY294002 (30 mg/kg), and sevoflurane + melatonin (10 mg/kg) + mammalian target of rapamycin (mTOR) inhibitor (10 mg/kg). The open field and Morris water maze tests were utilized to assess the neuroprotective effects of melatonin on sevoflurane-induced cognitive impairment in aged mice. The expression levels of the apoptosis-linked proteins, PI3K/Akt/mTOR signaling pathway, and pro-inflammatory cytokines in the brain's hippocampus region were determined using the Western blotting technique. The apoptosis of the hippocampal neurons was observed using the hematoxylin and eosin staining technique. Neurological deficits in aged, sevoflurane-exposed mice were significantly decreased after melatonin treatment. Mechanistically, melatonin treatment restored sevoflurane-induced down-regulated PI3K/Akt/mTOR expression and significantly attenuated sevoflurane-induced apoptotic cells and neuroinflammation. The findings of this study have highlighted the neuroprotective effect of melatonin on sevoflurane-induced cognitive impairment via regulating the PI3K/Akt/mTOR pathway, which might be effective in the clinical treatment of elderly patients with anesthesia-induced POCD.

Tachykinin receptor 3 in the lateral habenula alleviates pain and anxiety comorbidity in mice.

The coexistence of chronic pain and anxiety is a common clinical phenomenon. Here, the role of tachykinin receptor 3 (NK3R) in the lateral habenula (LHb) in trigeminal neuralgia and in pain-associated anxiety was systematically investigated. First, electrophysiological recording showed that bilateral LHb neurons are hyperactive in a mouse model of trigeminal neuralgia made by partial transection of the infraorbital nerve (pT-ION). Chemicogenetic activation of bilateral LHb glutamatergic neurons in naive mice induced orofacial allodynia and anxiety-like behaviors, and pharmacological activation of NK3R in the LHb attenuated allodynia and anxiety-like behaviors induced by pT-ION. Electrophysiological recording showed that pharmacological activation of NK3R suppressed the abnormal excitation of LHb neurons. In parallel, pharmacological inhibition of NK3R induced orofacial allodynia and anxiety-like behavior in naive mice. The electrophysiological recording showed that pharmacological inhibition of NK3R activates LHb neurons. Neurokinin B (NKB) is an endogenous high-affinity ligand of NK3R, which binds NK3R and activates it to perform physiological functions, and further neuron projection tracing showed that the front section of the periaqueductal gray (fPAG) projects NKB-positive nerve fibers to the LHb. Optogenetics combined with electrophysiology recordings characterize the functional connections in this fPAG NKB → LHb pathway. In addition, electrophysiological recording showed that NKB-positive neurons in the fPAG were more active than NKB-negative neurons in pT-ION mice. Finally, inhibition of NKB release from the fPAG reversed the analgesic and anxiolytic effects of LHb Tacr3 overexpression in pT-ION mice, indicating that fPAG NKB → LHb regulates orofacial allodynia and pain-induced anxious behaviors. These findings for NK3R suggest the cellular mechanism behind pT-ION in the LHb and suggest that the fPAG NKB → LHb circuit is involved in pain and anxiety comorbidity. This previously unrecognized pathway might provide a potential approach for relieving the pain and anxiety associated with trigeminal neuralgia by targeting NK3R.

Trunnions and Modularity in Total Hip Arthroplasty: A Historical Review With Current Clinical Implications.

Trunnion in total hip arthroplasty refers to the interface between the neck of a femoral stem and the femoral head. Clinical complications arising from damage to this junction, whether it be due to mechanical wear, corrosion, or a combination, are referred to as mechanically assisted crevice corrosion (MACC), also commonly known as trunnionosis. With the use of modular hip prostheses, which help customize offset and leg length to an individual patient's anatomy, the incidence of MACC and revision due to MACC has increased in recent years. Although the cause of MACC is multifactorial, with patient factors and technique factors contributing to this condition, taper design and geometry, metallurgical properties of implants, and size mismatch of the bearing couple are some of the implant factors that have also been implicated in this clinical phenomenon. Understanding the history of taper design and geometry, the track record of older implants, and the rationale behind the development of current prostheses can help surgeons choose the right implants for their patients and accurately assess the pros and cons of new implants being introduced to the market each year.

Recurrent implantation failure: A comprehensive summary from etiology to treatment.

Implantation is the first step in human reproduction. Successful implantation depends on the crosstalk between embryo and endometrium. Recurrent implantation failure (RIF) is a clinical phenomenon characterized by a lack of implantation after the transfer of several embryos and disturbs approximately 10% couples undergoing in vitro fertilization and embryo transfer. Despite increasing literature on RIF, there is still no widely accepted definition or standard protocol for the diagnosis and treatment of RIF. Progress in predicting and preventing RIF has been hampered by a lack of widely accepted definitions. Most couples with RIF can become pregnant after clinical intervention. The prognosis for couples with RIF is related to maternal age. RIF can be caused by immunology, thrombophilias, endometrial receptivity, microbiome, anatomical abnormalities, male factors, and embryo aneuploidy. It is important to determine the most possible etiologies, and individualized treatment aimed at the primary cause seems to be an effective method for increasing the implantation rate. Couples with RIF require psychological support and appropriate clinical intervention. Further studies are required to evaluate diagnostic method and he effectiveness of each therapy, and guide clinical treatment.

Using Buddhist Meditation-informed Hypnotic Techniques to Manage Rumination: Two Case Illustrations

ABSTRACT Rumination is a clinical phenomenon that causes significant distress in clients who suffer from various psychological and physical disorders. It also has a deleterious impact on both therapeutic process and outcome. One approach that holds promise to manage rumination is mindfulness meditation in combination with clinical hypnosis. This article: (1) reviews the concept of and techniques to manage rumination in the Buddhist psychological framework, (2) introduces 2 simple mindfulness-based techniques to deal with rumination, i.e., mindful thought detachment and mindful dereflection, and (3) describes 2 case studies in which these strategies were applied successfully. Hypnosis-informed clinicians are encouraged to integrate these approaches in their practices.

Acute ischemic colitis associated with oral decongestant use: a systematic review

Acute ischemic colitis (IC) has been linked with the use of oral decongestants. However, clinical evidence on this association remains limited. We aim to evaluate the occurrence and clinical outcomes of acute IC following over-the-counter (OTC) use of pseudoephedrine and phenylephrine.We conducted a systematic review of the MEDLINE, Google Scholar, Scopus, and Embase databases between inception and July 20, 2022. Specific search terms were used. The inclusion criteria consisted of English-language articles describing acute IC secondary to pseudoephedrine or phenylephrine.A total of 18 case reports (level of clinical evidence: IV) fulfilled our inclusion criteria. The mean age of patients was 51.6 ± 15.3 years, with 14 (77.8%) cases reported in women. The clinical presentation was mainly related to abdominal pain 16 (88.9%), hematochezia 15 (83.3%), and/or abdominal tenderness 10 (55.6%). The medical background showed that 5 (27.8%) patients were previously healthy. In the 13 (72.2%) patients with comorbidities, hypertension 6 (46.2%), a history of tobacco use 5 (38.5%), and psychiatric illnesses 4 (30.8%) were commonly reported. Leukocytosis was encountered in 13 (72.2%) patients. Diagnostic investigations included a combination of computed tomography scan and colonoscopy in 10 (55.6%), colonoscopy alone in 6 (33.3%), and flexible sigmoidoscopy in 1 (5.6%) patient. Colonoscopic biopsy was the mainstay of diagnosis in 15 (83.3%) patients. Treatment was based on supportive care in 18 (100%), concurrent antibiotic use in 2 (11.1%), and surgical intervention in 1 (5.6%) patient. Recurrent episodes of IC occurred in 4 (22.2%) patients.Acute IC secondary to oral decongestants remains a rare but important clinical phenomenon. Clinical suspicion and imaging findings are important for the early diagnosis.In unexplained cases of IC, clinicians should specifically inquire about oral decongestants since they are OTC and patients commonly fail to reveal their usage. These drugs should be avoided for transient cold symptoms, especially in women.