Diseases (Basel, Switzerland)最新文献

Background: Hypercalcemia is a frequently encountered laboratory finding in endocrinology, warranting accurate clinical and laboratory evaluation to identify its cause. While primary hyperparathyroidism and malignancies represent the most common causes, many other etiologies have been described, including some reports of hypercalcemia secondary to adrenal insufficiency. On the contrary, hypoparathyroidism is a relatively common cause of hypocalcemia, often arising as a complication of thyroid surgery. In real-world clinical practice, however, many challenges come into play, and a comprehensive approach may not be enough to establish a diagnosis. Case presentation: we describe a peculiar case of severe hypercalcemia occurring in a 47-year-old woman with a previous history of post-surgical permanent hypoparathyroidism treated with calcitriol (0.5 µg bid) and calcium carbonate (1 g qd), which persisted after withdrawal of these drugs. During her follow-up, an ACTH-independent Cushing syndrome was diagnosed, leading to a unilateral right adrenalectomy. In the two months following surgery, she was admitted to the emergency ward on three occasions because of severe, persistent, idiopathic hypercalcemia. On each occasion, parathyroid hormone levels were confirmed to be undetectable, with low vitamin D levels. Common and rare causes of hypercalcemia were excluded, and the persistence of severely elevated calcium levels led to the empirical use of intravenous clodronate, achieving remission of both hypercalcemia and, unexpectedly, hypoparathyroidism. After 8 months, due to borderline-reduced calcium, calcitriol at 0.5 µg qd was restarted. After 18 months of follow-up, the patient is well and normocalcemic, with low-dose calcitriol. Notably, the patient had no acute adrenal insufficiency, distinguishing this case from other post-adrenalectomy hypercalcemia reports. Conclusions: the history of hypoparathyroidism makes this case even more unusual, and it encourages careful follow-up of hypoparathyroid patients with Cushing syndrome. Ongoing observation, as well as new research on the physiopathology of cortisol and calcium metabolism, are needed to clarify the pathogenesis of this case.

Radiation therapy or radiotherapy is a medical treatment that uses high doses of ionizing radiation to eliminate cancer cells and shrink tumors. It works by targeting the DNA within the tumor cells restricting their proliferation. Radiotherapy has been used for treating cancer for more than 100 years. Along with surgery and chemotherapy, it is one of the three main and most common approaches used in cancer therapy. Nowadays, radiotherapy has become a standard treatment option for a wide range of cancers around the world, including lung, breast, cervical, and colorectal cancers. Around 50% of all patients will require radiotherapy, 60% of whom are treated with curative intent. Moreover, it is commonly used for palliative treatment. Radiotherapy provides 5-year local control and overall survival benefit in 10.4% and 2.4% of all cancer patients, respectively. The highest local control benefit is reported for cervical (33%), head and neck (32%), and prostate (26%) cancers. But no benefit is observed in pancreas, ovary, liver, kidney, and colon cancers. Such relatively low efficiency is related to the development of radiation resistance, which results in cancer recurrence, metastatic dissemination, and poor prognosis. The identification of radioresistance biomarkers allows for improving the treatment outcome. These biomarkers mainly include proteins involved in metabolism and cell signaling pathways.

Background: Posterior urethral valves (PUVs) represent the most common cause of male congenital lower urinary tract obstruction, often responsible for renal dysplasia and chronic renal failure. Despite recent improvements in patients' outcomes thanks to prenatal ultrasound early diagnosis, PUVs can still impact sexual function and fertility. This study aims to review the available evidence on fertility in PUV patients, examining paternity rates and semen parameters.

Methods: A review was conducted of the PubMed, Cochrane, Scopus, and Embase databases. Studies focusing on fertility and paternity outcomes in PUV patients were selected, including case reports, case series, and retrospective and prospective studies.

Results: A total of 15 studies met the inclusion criteria. The review revealed that PUV patients often exhibit compromised semen parameters, including low sperm count, reduced motility, and abnormal morphology, as well as alterations in seminal plasma. PUV diagnoses are common in adults exhibiting infertility and ejaculation disorders, suggesting PUVs cannot be considered only a pediatric disease. Paternity rates among PUV patients were rarely reported in extenso, hampering the correct assessment of the overall medium paternity rate and its comparison with that of healthy individuals. Lastly, seminal parameters were assessed in a minimal cohort of patients, therefore, they could not be considered representative.

Conclusions: Fertility and seminal parameters in PUV patients represent an under-investigated area. PUVs can variably and non-univocally affect fatherhood, and they may be associated with compromised semen quality. Early intervention and long-term follow-up are essential to address potential fertility issues. Future research should focus on developing targeted strategies to preserve and enhance fertility in this patient population.

T cells, as integral components of the adaptive immune system, recognize diverse antigens through unique T cell receptors (TCRs). To achieve this, during T cell maturation, the thymus generates a wide repertoire of TCRs. This is essential for understanding cancer evolution, progression, and the efficacy of immunotherapies. Myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) are hematological neoplasms that are characterized by immune evasion mechanisms, with immunotherapy giving only modest results thus far. Our review of TCR repertoire dynamics in these diseases reveals distinct patterns: MDS patients show increased TCR clonality with disease progression, while AML exhibits varied TCR signatures depending on disease stage and treatment response. Understanding these patterns has important clinical implications, as TCR repertoire metrics may serve as potential biomarkers for disease progression and treatment response, particularly in the context of immunotherapy and stem cell transplantation. These insights could guide patient stratification and treatment selection, ultimately improving therapeutic outcomes in MDS and AML.

Cervical intraepithelial neoplasia (CIN) is a premalignant cervical condition closely linked to persistent high-risk HPV infection, a major risk factor for cervical cancer. This study aims to investigate the relationship between cervicovaginal infections, HPV infection, and CIN development in 94 Romanian women with cervical lesions. Comprehensive assessments included HPV genotyping, cytology, colposcopy, and histopathology. In 53.20% of cases, vaginal infections were identified, with Candida albicans most frequently associated with HPV. Histopathology revealed 48.94% low-grade CIN, 42.55% high-grade CIN, and 8.51% invasive carcinoma. There was a strong correlation between high-risk HPV types (especially HPV 16 and 18), colposcopic findings, histopathology, and age. This study emphasizes the mutual effect of cervicovaginal infections and HPV infection in increasing the risk of developing CIN and cervical cancer among Romanian women. Persistent infection with high-risk HPV types, particularly HPV 16 and 18, has been confirmed as a primary driver of CIN and cervical cancer progression.

Background/objective: Neurotoxic soluble amyloid-β (Aβ) oligomers are key drivers of Alzheimer's pathology, with evidence suggesting that early targeting of these soluble forms may slow disease progression. Traditional intravenous (IV) monoclonal antibodies (mAbs) face challenges, including limited brain penetration and risks such as amyloid-related imaging abnormalities (ARIA). This hypothetical study aimed to model amyloid dynamics in early-to-moderate Alzheimer's disease (AD) and compare the efficacy of IV mAn with intrathecal pseudodelivery, a novel method that confines mAbs in a subcutaneous reservoir for selective amyloid clearance in cerebrospinal fluid (CSF) without systemic exposure.

Methods: A mathematical framework was employed to simulate Aβ dynamics in patients with early-to-moderate AD. Two therapeutic approaches were compared: IV mAb and intrathecal pseudodelivery of mAb. The model incorporated amyloid kinetics, mAb affinity, protofibril size, and therapy-induced clearance rates to evaluate the impact of both methods on amyloid reduction, PET negativity timelines, and the risk of ARIA.

Results: Intrathecal pseudodelivery significantly accelerated Aβ clearance compared to IV administration, achieving amyloid PET scan negativity by month 132, as opposed to month 150 with IV mAb. This method demonstrated no ARIA risk and reduced amyloid reaccumulation. By targeting soluble Aβ species more effectively, intrathecal pseudodelivery emerged as a safer and more efficient strategy for early AD intervention.

Conclusions: Intrathecal pseudodelivery offers a promising alternative to IV mAbs, overcoming challenges associated with blood-brain barrier penetration and systemic side effects. Further research should focus on optimizing this approach and exploring combination therapies to enhance clinical outcomes in AD.

Background: Fatigue is a prevalent and complex condition with significant impacts on well-being. Existing fatigue assessments often lack comprehensiveness or practicality for general population studies.

Methods: This study validated the REST Questionnaire, a novel fatigue assessment tool, in a sample of 268 adults. Psychometric properties, including internal consistency and construct validity, were evaluated. REST scores were correlated with WHO-5 well-being, BMI, self-rated health, and chronic conditions. Exploratory factor analysis identified underlying dimensions of fatigue.

Results: The REST Questionnaire demonstrated excellent internal consistency (Cronbach's alpha = 0.918) and construct validity. Higher fatigue scores were associated with lower well-being, female gender, and the presence of certain chronic conditions (cancer, kidney stones, gastric ulcers). Two distinct fatigue dimensions, "physical fatigue and functional impacts" and "emotional and social consequences", were identified.

Conclusions: The REST Questionnaire is a reliable and valid tool for assessing fatigue in the general population. Its multidimensional framework and sensitivity to comorbidities offer valuable insights for research and public health applications, with the potential to inform targeted interventions aimed at improving well-being.

Background and objectives: Colorectal cancer is a major contributor to global cancer morbidity and mortality. Surgical resection remains the cornerstone of treatment, but postoperative complications can significantly affect patient outcomes. Identifying factors that influence postoperative morbidity and mortality is crucial for optimizing patient care. This study aims to evaluate the impact of preoperative, intraoperative, and postoperative factors on surgical outcomes in patients with colorectal cancer.

Methods: A retrospective cohort study was conducted on 688 patients who underwent colorectal cancer surgery within a 10-year period. Data collected included demographic information, comorbidities, laboratory values, surgical details, and postoperative outcomes. Statistical analyses were performed using chi-square tests for categorical variables and t-tests for continuous variables. Multivariate logistic regression was used to identify independent predictors of postoperative complications and mortality.

Results: Postoperative complications occurred in 28.5% of patients, and the 30-day mortality rate was 5.2%. Preoperative factors such as elevated C-reactive protein (CRP) levels (p < 0.001), low albumin levels (p = 0.003), a high American Society of Anesthesiologists (ASA) score (p < 0.001), and presence of comorbidities like diabetes and hypertension (p = 0.005) were significantly associated with increased postoperative complications. Intraoperative factors such as blood loss greater than 500 mL (p < 0.001) and longer operative time (p = 0.021) were also significant predictors of adverse outcomes. Multivariate analysis identified elevated CRP (OR 2.1, 95% CI 1.5-2.9), low albumin (OR 1.8, 95% CI 1.3-2.5), and blood loss > 500 mL (OR 2.4, 95% CI 1.7-3.4) as independent predictors of postoperative complications.

Conclusions: Preoperative inflammatory markers, nutritional status, ASA score, comorbidities, and intraoperative factors like blood loss significantly influence postoperative outcomes in colorectal cancer surgery. Recognizing these risk factors allows for better preoperative optimization and surgical planning, potentially reducing postoperative morbidity and mortality.

Background: Yaws is an infectious, neglected tropical disease that affects the skin of many children and adolescents who live in poor, rural, low-income communities in humid, tropical areas of Africa, Southeast Asia, and the Pacific Islands. Yaws is currently endemic in at least 15 countries, but adequate surveillance data are lacking. In line with the WHO's effort to improve early detection, diagnosis, and proper management leading to the eventual eradication of yaws, this article reviews the existing literature on yaws in Africa to highlight the epidemiological pattern, genetic variability, diagnosis modalities, treatment, and control strategies, the challenges and prospects for yaws eradication. Methods: We searched PubMed and Scopus databases to identify published data in line with the review objectives. Results: One hundred and eighty-eight peer-reviewed articles were identified by PubMed and Scopus, out of which thirty were eligible. The studies covered 11 African countries, with the reported prevalence ranging from 0.50% to 43.0%. Conclusions: There is a great prospect for eradication if countries capitalize on the availability of simple, inexpensive, and well-tolerated oral treatment that has proven effective, validated point-of-care diagnostic tests and new molecular tests. Countries should embark on integrated disease control efforts to increase sustainability and improve the quality of life for people living with this NTD in poor communities.

Background: Eosinophilic pneumonias denote a rare condition, wherein infiltrating eosinophilic granulocytes accumulate within the lung parenchyma. Although eosinophilic pneumonias may be idiopathic, they are also associated with secondary causes. More than 110 medications have been linked to eosinophilic pneumonia, including several antidepressants. This review presents an analysis of case reports of eosinophilic pneumonia correlated to antidepressants. Objectives: The objectives of this study are to provide a contemporary overview of the literature delineating eosinophilic pneumonia as a potential sequela of antidepressant medication treatment, and to discuss possible pathogenetic mechanisms linking antidepressants to eosinophilic pneumonia. Methods and Data Selection: A literature search was performed in PubMed and Scopus databases from 1963 to October 2024. The search strategy used the terms "eosinophilic pneumonia AND antidepressants". Sources included in this review were screened for relevance, focusing on references discussing eosinophilic pneumonia associated with any class of antidepressants. Case reports meeting the diagnostic criteria for acute eosinophilic pneumonia (AEP) or chronic eosinophilic pneumonia (CEP) were included in the review. Clinical, epidemiological, laboratory, radiology and bronchoscopy data, implicated antidepressant and dosage, and therapeutic interventions were reported. Results: This study found that various types of antidepressants are associated with AEP and CEP. The clinical presentation ranges from mild symptoms to respiratory failure and intubation. Outcomes were favorable in most cases, with complete remission achieved after discontinuation of the causative drug and, in severe cases, a short course of corticosteroids. Conclusions: Although a rare cause, antidepressants may lead to eosinophilic pneumonia, and should be considered in the differential diagnosis of unexplained pulmonary infiltrates. Clinical suspicion must be aroused, as early recognition would prevent unnecessary work-up and navigation of the diagnosis.