Discoveries (Craiova, Romania)最新文献

Hip fractures are a serious global health concern with a substantial impact on senior patients' mobility, quality of life, and morbidity. Patients with psychiatric pathology may experience heightened levels of distress, making pain management more challenging. The presence of multiple comorbidities may complicate the therapeutic management of hip fractures. Treatment plans must be carefully tailored to accommodate each individual's unique medical history and current health status. We looked for improving pain evaluation and management in patients with dementia and choosing the best treatment according to age and comorbidities. This study highlights the mortality rate in surgically and non-surgically treated patients and possible correlations with other factors. We conducted a prospective study on 184 patients over 60 years old, with dementia and hip fractures, between 2018 and 2020 in Romania, within the Galati County Clinical Hospital. We applied the Charlson Comorbidity Index, ACE III test, EQ5D5L, and Harris test scores to assess the comorbidities, respectively, pain levels, mobilization in daily life activities, self-care and severity of dementia to exert the optimal treatment for patients with dementia and hip fracture. Our study pointed out that pain was frequently excruciating in non-operated patients compared to those who were operated. Most non-operated patients were immobilized in bed, they required careful and permanent care, while most of the operated patients experienced lower pain levels. While some risk factors of morbidity and mortality, such as comorbidities, severity of dementia, high age, and previous living situations are not preventable, delayed surgery, and general anesthesia risks may be prevented. Despite the treatment, mortality was high both at 6 months and 2 years, with increased survival rate in surgical treated patients. Our study addresses issues such as the importance of mental state evaluation in elderly patients in therapeutic decisions, the surgical intervention and the particularities in pre- and postoperative pain control in patients with dementia, topics that are insufficiently established in the current practical guidelines.

A large number of products are synthesized and packaged in membrane vesicles to be secreted from cells to carry out essential physiological functions such as nerve transmission, digestion and immune response. How do cells secrete with great precision a portion of the vesicle contents?These questions have been answered through the work of Dr. Bhanu P. Jena, a cell physiologist and chemist at Wayne State University School of Medicine in Detroit Already in the mid 1990s he discovered that pancreatic acinar cells possess secretory portals (porosomes) at the cell plasma membrane that govern the transport and secretion of digestive enzymes. During the next twenty-five years, Jena characterized in great detail the molecular mechanisms underlying this secretory process. He also showed that similar "secretory portals", or "porosomes", are present in all cell types including endocrine cells secreting hormones and brain neurons secreting neurotransmitters.The principles discovered and described by Bhanu P. Jena turned out to be universal, operating similarly in all animal cells. A number of human hereditary diseases are caused by mutations in some of the nearly 30 proteins composing the porosome complex. Jena's discovery of the porosome, in addition to providing a deep understanding of cell secretion, has also contributed to the establishment of a drug development platform (https://www.porosome.com) for the treatment of a wide range of diseases. Among the therapeutic application is porosome reconstitution in stem cell derived beta cells, for the treatment of Type 1 diabetes and holds great promise for the cure of cystic fibrosis.

Background: Platelet Inhibition and Clinical Outcomes (PLATO) was a multicenter, randomized double-blind trial assessing efficacy and safety of ticagrelor versus clopidogrel in patients with acute coronary syndrome. The reported mortality benefit of ticagrelor in the PLATO trial has been challenged for over decade, and never confirmed in later trials.

Objective: To compare if there were any differences when deaths were reported to the FDAby the sponsors or by independent Contract Research Organizations (CRO).

Methods: We obtained the complete PLATO deaths dataset reported to the FDA and revealed that some events were inaccurately reported favoring ticagrelor. The entire FDA list contains precisely detailed 938 PLATO deaths. The CRO reported outcomes from the USA, Russia, Georgia, and most of Ukraine, while sites in 39 other countries were controlled by the trial sponsors. We compared vascular- (code "11"), non-vascular- (code "12"), and unknown (code "97") deaths triaged by the reporting source.

Results: Overall, most PLATO deaths were vascular (n=677), less non-vascular (n=159) andunexpectedly many of "other" (n=7) or "unknown" (n=95) origin reported either by sponsors (n=807) or CRO (n=131). The trial sponsors reported more clopidogrel deaths from vascular (313 vs.239), non-vascular (86 vs.58) and unknown (53 vs. 26) causes.In contrast, CRO-monitored sites reported significantly (72 vs. 53; p<0.01) more ticagrelordeaths than after clopidogrel from vascular (51 vs.39), non-vascular (8 vs.7) and unknown (10 vs. 4) causes.

Conclusion: Deaths were reported differently by sponsors and CRO within the same trial. Since some deaths were misreported by PLATO sponsors, only the CRO data seems mostly reliable. Among all countries, the CRO - reported PLATO-USA outcomes represent the largest and most realistic dataset of realistic evidence suggesting ticagrelor inferiority to clopidogrel for all primary endpoint components including vascular death.

Objective: The long-term extrapulmonary sequelae of COVID-19 after recovery from the critical stage at the intensive care unit (ICU) are still unclear. Some post-COVID symptoms are prevalent even after a one-year follow-up. To explore the relationship between high sensitivity C-reactive protein (hs-CRP) and hyperglycemia with cardiovascular diseases in non-diabetic COVID-19 patients. To determine whether increased fasting blood sugar (FBS) levels are associated with elevated hs-CRP and to explore whether hs-CRP can serve as a prognostic indicator to predict cardiovascular outcome.

Methods: FBS and hs-CRP values of 26 non-diabetic COVID-19 patients were collected from their medical records at JIPMER hospital. In one-year follow-up of these 26 patients, 2mL of blood sample was collected for the analysis of FBS, HbA1c, and hs-CRP.

Results: hs-CRP increased in 23% of follow-up patients who were at high risk, and 42.3% of participants were at average risk for cardiovascular disease. High and average-risk groups of survivors showed a positive correlation of hs-CRP with FBS and HbA1c levels, and these patients should be carefully monitored.

Conclusion: ICU survivors with elevated hs-CRP need periodic check-ups for cardiovascular diseases. We suggest that hs-CRP could be used as an early prognostic indicator of cardiovascular diseases and can reduce the risk.

Unusual presentations and uncommon clinical manifestations of Monkeypox (Mpox) in the current outbreak highlight the need to focus on cardiac symptoms of the virus. Owing to limited discussion regarding cardiac involvement in recent cases of Mpox, we conducted a scoping review to determine the range of existing research and provide a descriptive overview of the current literature on these manifestations. This review was conducted using a previously developed six-stage methodological approach and keeping in view the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR). Records retrieved from PubMed, ScienceDirect and Google Scholar, using a two-step search strategy, were subjected to title and abstract screening, followed by full text screening of remaining articles against specified eligibility criteria. Relevant information was extracted and summarized. Our search yielded 707 records. Following title and abstract screening, 23 articles were retrieved for full text screening. Finally, a total of nine articles were included in this review (three case series and six case reports discussing a total of 13 patients). Myocarditis was identified as the most frequently reported cardiac manifestation of Mpox. Novel clinical presentations included pharyngitis, sore throat, proctalgia, and perianal irritation. Most patients reported chest pain as the primary symptom of cardiac system involvement. Elevated troponin was the most commonly reported investigation finding followed by an elevated C- Reactive Protein. There exists a lack of high-quality studies investigating cardiac system involvement in the current outbreak of Mpox. More information is needed regarding risk factors for cardiac complications, disease progression, and cardio tropism and immunological response to improve preventive/therapeutic strategies. We highlight the paucity of relevant data and call for further discussion to improve the understanding of cardiac manifestations of Mpox. This scoping review sheds light on the underexplored cardiac manifestations of Mpox and highlights the need for heightened awareness of cardiac symptoms in the current outbreak.

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug induced hypersensitivity (DiHS) is a rare, however a severe hypersensitivity reaction with a mortality rate of up to 10%, accounting for 10 to 20% of all cutaneous drug reactions in hospitalized patients. The clinical features of DRESS/DiHS may be challenging to recognize and diagnose, since they are delayed, stepwise, and heterogeneous. The classic presentation of DRRSS/DiHS involves a combination of cutaneous, hematologic, and internal organ involvement with a 2 to 8 weeks latency between drug exposure and the onset of symptoms. Finding the culprit drug in our case was difficult as the patient was taking multiple antibiotics. Drugs such as vancomycin and cefepime used before the rash outbreak for post-reconstructive surgery for left toal knee arthroplasty (TKA) approximately four weeks before the onset of the rash are likely offending agents. This patient also had multi-visceral involvement with eosinophilia and systemic symptoms. The current treatment guidelines for DRESS/DiHS are primarily based on expert opinion, as no randomized control trials exist. After the prompt withdrawal of the offending drug, systemic corticosteroids seem to have shown the best outcome for patients. Delaying discontinuing offending medications and initiating corticosteroid treatment may lead to poor results. The present case emphasizes that the close observation of patients with drug eruption induced by antibiotics is imperative. Primary care team should be able to promptly diagnose patients with DRESS syndrome, detect causative drug, and play a crucial role in the timely evaluation and treatment to reduce mortality rate. The later phase disease relapse or autoimmune complications may occur up to 5 years following the initial presentation. Therefore, we advised the patient to have an outpatient follow up for appropriate testing, including but not limited to genetic susceptibility due to the high risk of relapse and emerging risk of autoimmune diseases.

The oral cavity is home to diverse microbial content, collectively called as the oral microbiome. The latest technological advancements have unraveled the intricacies of the oral microbiome.  It can be of great importance for oral health care givers to know the fundamentals and latest developments in the field of the oral microbiome, as oral dysbiosis is associated with many common diseases frequently seen and managed by them. These diseases include dental caries, periodontitis, mucosal diseases (such as oral leukoplakia, oral lichen planus, and systemic lupus erythematosus), oral cancers, and even co-infections related to the current COVID-19 pandemic. The emergence of new genomic and molecular biology methodologies has been pivotal for understanding the role of the human microbiome in health and disease. The current review compiles oral microbiome in health and disease with a multidisciplinary dental approach. The insight into the oral microbiome, which is provided dental specialty wise in the current article will initiate and guide researchers of various disciplines in developing microbiome-based therapeutic or prophylactic management strategies, managing public health challenges by microbiome-based boarder interventions and divert resources for preserving and achieving a balanced oral microbiome.

The incidence of tumor metastases in the brain is many times more frequent than primary brain tumors, affecting a very large share of patients suffering from systemic cancer. Advanced malignant melanoma is well known for its ability to invade the brain space and current treatment options, such as surgery and radiation therapy, are not very efficient and cause notable complications and morbidity. The aim of this review is to explore the recent advances and future potential of using immunotherapy in the treatment of melanoma brain metastases. Several FDA approved immunotherapeutic drugs have shown to be able to at least double the overall survival rates in such patients. Clinical trials of varying phases are underway and available results are promising, significantly prolonging survival rates in patients with previously untreated melanoma brain metastases. Nevertheless, not all patients respond to these immunotherapies, facing a high percentage of resistant cases, without yet knowing the mechanisms and causes of resistance behind. Also, at the time of immunotherapy, a small percentage of patients is affected by pseudoprogression, which can be difficult to distinguish from true progression given the similarity of symptoms. Therefore, there is a pressing need for future research about treatment effectiveness in patients with brain metastases from melanoma, including outcomes from the perspective of patients.

Advancements in molecular biology and neuroscience have uncovered calcitonin gene-related peptide (CGRP), a neuropeptide consisting of thirty-seven amino acids that plays a crucial role in migraine pathogenesis. CGRP receptor antagonist or gepant is an oral medication that can impede the nociceptive signaling pathway related to CGRP. Atogepant, the latest CGRP antagonist approved by the Food and Drug Administration (FDA) for prophylaxis of episodic migraine, works by non-competitively blocking CGRP receptors, thereby curtailing neurogenic inflammation and pain sensitization. Numerous trials have demonstrated that atogepant is an effective therapy for migraine prevention, with its extended half-life and minimal risks of cardiovascular or liver toxicity making it the first drug in its class primarily authorized for that purpose. In terms of monthly migraine days, monthly headache days, and acute medication usage days, atogepant demonstrated a statistically significant difference from baseline.  It was well-tolerated with low adverse event rates. The most commonly reported adverse events were constipation and nausea. Atogepant appears to be beneficial for migraine prevention, and it may be more useful in those who do not want to take the medication as an injection or who do not require a lengthy duration of pharmacological impact. In this article, we provide a systematic review of the literature on atogepant and migraine, emphasizing current achievements in this field of study.

Background: Hairy Cell Leukemia (HCL) is an uncommon, indolent lymphoproliferative disorder of mature B lymphoid cells, accounting for 2% of all lymphoid tumors. The present study evaluated the clinical-hematological profile of HCL patients diagnosed at a single tertiary care center over a 11-year period.

Methods: The retrospective observational study was done between October 2010 and September 2021. The relevant clinical and laboratory information were retrieved from hospital medical records and electronic databases. The statistical analysis was performed using version 23.0 of SPSS.

Results: 66 (5.9%) of 1125 cases of chronic lymphoproliferative disorder were HCL. Splenomegaly was found in 47 (71.2%), hepatomegaly in 26 (39.5%), and lymphadenopathy in 17 (25.7%) of the cases. The mean hemoglobin, total leukocytes count, and platelets count were 8.04 g/dl, 6.76 X 109/L, and 77 X 109/L, respectively. Pancytopenia was detected in 40 cases (60.61 %). Bone marrow biopsies were majorly hypercellular and showed predominantly diffuse infiltration by atypical lymphoid cells. In two patients, initially thought of having refractory/hypoplastic anemia, the bone marrow biopsy and flow cytometry revealed HCL involvement.  42 cases of HCL underwent flow cytometry. CD20, CD 11c, CD 25 and CD 103 were positive in all the cases. The aberrant expression of CD5, CD10, and CD23 was found in frequencies of 5.71 %, 31.42 %, and 19.35%, respectively. In 40 cases for which follow-up information was available, there was full remission in 26 patients (65%), and later three showed relapse (7.5%) of which one died, and persistent leukemic activity in five (10%).  Eight patients (20%) died even before the initiation of treatment. One patient died within one month of therapy. No patient was examined for BRAF V600E mutation analysis.

Conclusion: CD 10+ HCL was the most prevalent atypical immunophenotypic subgroup. Bone marrow biopsy and flow cytometry are crucial diagnostic tools to rule out hairy cell leukemia. However, BRAF V600E mutation analysis should be performed in cases with unusual presentation or resistance to treatment.