-
Journal of Family Medicine and Primary... May 2024Postmenopausal bleeding (PMB) refers to any uterine bleeding in a menopausal women. In the early menopausal years, endometrial hyperplasia, polyps and submucosal...
INTRODUCTION
Postmenopausal bleeding (PMB) refers to any uterine bleeding in a menopausal women. In the early menopausal years, endometrial hyperplasia, polyps and submucosal fibroids are common etiologies of post menopausal bleeding. The most common cause of postmenopausal bleeding is endometrial atrophy, comprises of 60-80%, while endometrial hyperplasia and endometrial cancer contribute to only 11% of Post menopausal bleeding. The aim of study is to analyses histomorphological pattern of endometrium in patients presenting with post-menopausal bleeding in Jharkhand.
MATERIALS AND METHODS
103 postmenopausal women presenting to tertiary center of Jharkhand in 2020-22 with bleeding were subjected to endometrial curettage for histopathology. Analysis is based on morphological criteria to assess endometrium. Endometrial histology is of four categories: Proliferative, Secretory, premalignant and carcinoma.
RESULTS
The highest incidence of postmenopausal bleeding was noticed in age group of < 60 years and incidence of malignancy was higher after 57 years of age. The majority of patients had parity between 1 and 3 (78.6%). Malignant & premalignant lesions comprises about 22.3% among that 77.7% were due to benign causes. Among the benign causes of postmenopausal bleeding, proliferative endometrium was the commonest finding. Types of hyperplasia encountered were simple hyperplasia without atypia (6.8%), Complex hyperplasia without atypia (3.9%),Complex hyperplasia with atypia (4.8%) and Simple hyperplasia with atypia (4.8%). 21.4% of cases of postmenopausal bleeding were associated with atrophic endometrium. Secretory endometrium seen in 17.5% of women. Endometrial carcinoma accounted for 12.6% of cases of postmenopausal bleeding. Out of these 69.2% were of endometroid type of endometrial carcinoma, 15.3% were of papillary serous carcinoma and 15.3% had clear cell carcinoma. The mean age of patients with endometrium carcinoma was 62.3 years. All cases of endometrial carcinoma were associated with 1 or more risk factor like diabetes/hypertension/Nulligravida.
CONCLUSION
Proliferative Endometrium was a major cause of postmenopausal bleeding. Among the malignant causes, endometrial adenocarcinoma of endometroid type was most frequent with a lower mean age at presentation than other high grade cancers like papillary serous carcinoma & clear cell carcinoma.
PubMed: 38948580
DOI: 10.4103/jfmpc.jfmpc_1331_23 -
Cancer Innovation Jun 2024With the emergence of cytotoxic T lymphocyte-associated protein-4 (CTLA-4) inhibitors, the outcomes of patients with malignant tumors have improved significantly....
BACKGROUND
With the emergence of cytotoxic T lymphocyte-associated protein-4 (CTLA-4) inhibitors, the outcomes of patients with malignant tumors have improved significantly. However, the incidence of cardiovascular adverse events has also increased, which can affect tumor treatment. In this study, we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy.
METHODS
Randomized clinical trials published in English from January 1, 2013, to November 30, 2022, were searched using the Cochrane Library and PubMed databases. All included trials examined all grade and grades 3-5 cardiac and vascular adverse events. These involved comparisons of CTLA-4 inhibitors to placebo, CTLA-4 inhibitors plus chemotherapy to chemotherapy alone, CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone, and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method.
RESULTS
Overall, 20 trials were included. CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity (OR = 1.33, 95% CI: 1.00-1.75, = 0.05). The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors (OR = 1.73, 95% CI: 1.13-2.65, = 0.01), as well as the incidence rate of grades 3-5 cardiovascular adverse events (OR = 2.00, 95% CI: 1.08-3.70, = 0.03). Compared with the non-CTLA-4 inhibitor group, CTLA-4 inhibitors plus chemotherapy, PD-1/PD-L1 inhibitors, or target agent did not significantly affect the incidence of cardiac and vascular toxicity. The incidence of grades 3-5 cardiac failure, hypertension, pericardial effusion, myocarditis, and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor, but the data were not statistically significant.
CONCLUSION
Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors. In addition, the risk of serious cardiovascular toxic events was independent of the type of adverse event. From these results, physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignancies.
PubMed: 38947758
DOI: 10.1002/cai2.116 -
The Journal of Pain Jun 2024Chronic pain (CP) significantly impacts quality of life and increases non-communicable disease risk, with recent U.S. data showing a 6.3% incidence rate, surpassing...
Chronic pain (CP) significantly impacts quality of life and increases non-communicable disease risk, with recent U.S. data showing a 6.3% incidence rate, surpassing diabetes, depression, and hypertension. International studies suggest higher mortality in CP populations, yet prior U.S. data is inconclusive. To investigate CP's mortality risk, we analyzed National Health Interview Survey (NHIS) and National Death Index (NDI) data. We hypothesized individuals with CP and high-impact CP (HICP, (≥1 activity limitation) would exhibit higher mortality rates. NHIS provided demographics, pain reporting, lifestyle, and psychosocial data, matched with NDI mortality records. Chi-Square analyses explored relationships between CP/HICP and demographics, lifestyle factors, psychosocial variables, and mortality. Cox proportional hazards models assessed mortality risk between groups. The weighted sample was 245,899,776; 20% reported CP and 8% HICP, both groups exhibiting higher mortality rates than pain-free individuals (CP: 5.55%, HICP: 8.79%, total: 2.82%). Hazard ratios indicated nearly double the mortality risk for CP and two-and-a-half times higher risk for HICP compared to those without these conditions. Adjusting for lifestyle and psychosocial factors reduced mortality risk but remained elevated compared to non-CP individuals. Heart disease, malignant neoplasms, and chronic lower respiratory diseases accounted for a higher percentage of deaths in CP cases. CP individuals showed higher rates of smoking, alcohol consumption, obesity, inactivity, depression, anxiety, emotional problems, and sleep disturbances. CP and HICP significantly influence mortality outcomes, leading to excess deaths compared to pain-free individuals. Given the relationship between pain, lifestyle, psychosocial variables, and mortality, further investigations are needed into CP causation and prevention strategies. PERSPECTIVE: This article presents evidence regarding the relationship between chronic pain, high impact chronic pain, and mortality. Additional findings are discussed regarding the impact of demographics, lifestyle, and psychosocial variables on mortality in those with versus without chronic pain and high impact chronic pain. These findings are crucial for informing future research, prevention, and healthcare management strategies.
PubMed: 38942415
DOI: 10.1016/j.jpain.2024.104620 -
European Journal of Pharmacology Jun 2024Pulmonary hypertension (PH) is a malignant pulmonary vascular disease with a poor prognosis. Although the development of targeted drugs for this disease has made some...
Pulmonary hypertension (PH) is a malignant pulmonary vascular disease with a poor prognosis. Although the development of targeted drugs for this disease has made some breakthroughs in recent decades, PH remains incurable. Therefore, innovative clinical treatment methods and drugs for PH are still urgently needed. DYZY01 is a new drug whose main ingredient is high-purity cannabidiol, a non-psychoactive constituent of cannabinoids that was demonstrated to have anti-inflammatory and anti-pyroptosis properties. Several recent studies have found cannabidiol could improve experimental PH, whereas the mechanistic effect of it warrants further investigation. Thus, this study aimed to investigate whether DYZY01 can treat PH by inhibiting inflammation and pyroptosis and to reveal its underlying mechanism. We established hypoxia and monocrotaline (MCT)-induced PH rat models in vivo and treated them with either DYZY01 (10,50 mg/kg/d) or Riociguat (10 mg/kg/d) by oral administration. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVHI), and extent of vascular remodeling were measured. Meanwhile, the effect of DYZY01 on human pulmonary arterial endothelial cells (HPAECs) was assessed in vitro. The results indicated that DYZY01 significantly reduced mPAP and RVHI in PH rats and reversed the extent of pulmonary vascular remodeling. This improvement may have been achieved by reducing endothelial cell pyroptosis via inhibiting the NF-κB/NLRP3/Caspase-1 pathway. Furthermore, DYZY01 could improve endothelial vascular function, possibly by regulating the secretion of vasodilator factors and inhibiting the proliferation and migration of pulmonary endothelial cells.
PubMed: 38942262
DOI: 10.1016/j.ejphar.2024.176785 -
Medicine Jun 2024Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary... (Review)
Review
RATIONALE
Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy.
PATIENT CONCERNS
Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension.
DIAGNOSES
One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy.
INTERVENTIONS
The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause.
OUTCOMES
Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm.
LESSONS
PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis.
Topics: Humans; Female; Thrombotic Microangiopathies; Middle Aged; Fatal Outcome; Hypertension, Pulmonary; Gastrointestinal Neoplasms; Lung Neoplasms
PubMed: 38941435
DOI: 10.1097/MD.0000000000038618 -
BMJ Case Reports Jun 2024A man in his early 30s presented with sudden-onset respiratory distress, haemoptysis and reduced urine output. He was in volume overload with a blood pressure recording...
A man in his early 30s presented with sudden-onset respiratory distress, haemoptysis and reduced urine output. He was in volume overload with a blood pressure recording of 240/180 mm Hg. Pulmonary renal syndrome was suspected and he was initiated on plasmapheresis, followed by steroid pulse therapy. Chest radiography and the presence of fragmented red cells on the peripheral smear were unexplained. These were later explained by hypertensive nephropathy and thrombotic microangiopathy changes on renal biopsy. His respiratory and haematological parameters improved with blood pressure control. Malignant hypertension closely resembles pulmonary renal syndrome, which must be remembered in order to avoid plasmapheresis and high-dose immunosuppressive therapy.
Topics: Humans; Male; Hypertension, Malignant; Adult; Nephritis; Diagnosis, Differential; Hemoptysis; Hypertension, Renal
PubMed: 38925671
DOI: 10.1136/bcr-2024-259742 -
Frontiers in Immunology 2024Therapeutic antibodies have become a major strategy to treat oncologic diseases. For chronic lymphocytic leukemia, antibodies against CD20 are used to target and elicit...
INTRODUCTION
Therapeutic antibodies have become a major strategy to treat oncologic diseases. For chronic lymphocytic leukemia, antibodies against CD20 are used to target and elicit cytotoxic responses against malignant B cells. However, efficacy is often compromised due to a suppressive microenvironment that interferes with cellular immune responses. To overcome this suppression, agonists of pattern recognition receptors have been studied which promote direct cytotoxicity or elicit anti-tumoral immune responses. NOD2 is an intracellular pattern recognition receptor that participates in the detection of peptidoglycan, a key component of bacterial cell walls. This detection then mediates the activation of multiple signaling pathways in myeloid cells. Although several NOD2 agonists are being used worldwide, the potential benefit of these agents in the context of antibody therapy has not been explored.
METHODS
Primary cells from healthy-donor volunteers (PBMCs, monocytes) or CLL patients (monocytes) were treated with versus without the NOD2 agonist L18-MDP, then antibody-mediated responses were assessed. In vivo, the Eµ-TCL1 mouse model of CLL was used to test the effects of L18-MDP treatment alone and in combination with anti-CD20 antibody.
RESULTS
Treatment of peripheral blood mononuclear cells with L18-MDP led to activation of monocytes from both healthy donors and CLL patients. In addition, there was an upregulation of activating FcγR in monocytes and a subsequent increase in antibody-mediated phagocytosis. This effect required the NF-κB and p38 signaling pathways. Treatment with L18-MDP plus anti-CD20 antibody in the Eµ-TCL model of CLL led to a significant reduction of CLL load, as well as to phenotypic changes in splenic monocytes and macrophages.
CONCLUSIONS
Taken together, these results suggest that NOD2 agonists help overturn the suppression of myeloid cells, and may improve the efficacy of antibody therapy for CLL.
Topics: Nod2 Signaling Adaptor Protein; Animals; Humans; Receptors, IgG; Mice; Macrophages; Leukemia, Lymphocytic, Chronic, B-Cell; Acetylmuramyl-Alanyl-Isoglutamine; Female; Mice, Inbred C57BL; Signal Transduction; Phagocytosis; Rituximab
PubMed: 38919608
DOI: 10.3389/fimmu.2024.1409333 -
Scientific Reports Jun 2024The rapid perfusion of cerebral arteries leads to a significant increase in intracranial blood volume, exposing patients with traumatic brain injury to the risk of...
Assessment of cerebrovascular alterations induced by inflammatory response and oxidative-nitrative stress after traumatic intracranial hypertension and a potential mitigation strategy.
The rapid perfusion of cerebral arteries leads to a significant increase in intracranial blood volume, exposing patients with traumatic brain injury to the risk of diffuse brain swelling or malignant brain herniation during decompressive craniectomy. The microcirculation and venous system are also involved in this process, but the precise mechanisms remain unclear. A physiological model of extremely high intracranial pressure was created in rats. This development triggered the TNF-α/NF-κB/iNOS axis in microglia, and released many inflammatory factors and reactive oxygen species/reactive nitrogen species, generating an excessive amount of peroxynitrite. Subsequently, the capillary wall cells especially pericytes exhibited severe degeneration and injury, the blood-brain barrier was disrupted, and a large number of blood cells were deposited within the microcirculation, resulting in a significant delay in the recovery of the microcirculation and venous blood flow compared to arterial flow, and this still persisted after decompressive craniectomy. Infliximab is a monoclonal antibody bound to TNF-α that effectively reduces the activity of TNF-α/NF-κB/iNOS axis. Treatment with Infliximab resulted in downregulation of inflammatory and oxidative-nitrative stress related factors, attenuation of capillary wall cells injury, and relative reduction of capillary hemostasis. These improved the delay in recovery of microcirculation and venous blood flow.
Topics: Animals; Oxidative Stress; Rats; Intracranial Hypertension; Male; Tumor Necrosis Factor-alpha; Inflammation; Microcirculation; Cerebrovascular Circulation; Rats, Sprague-Dawley; Brain Injuries, Traumatic; Infliximab; Disease Models, Animal; Blood-Brain Barrier; Reactive Oxygen Species; Reactive Nitrogen Species; Microglia
PubMed: 38914585
DOI: 10.1038/s41598-024-64940-6 -
The Journal of International Medical... Jun 2024Malignant hyperthermia (MH), characterized by severe myoclonus, pyrexia, tachycardia, hypertension, elevated muscle enzymes, and hypercapnia, often occurs in patients...
Malignant hyperthermia (MH), characterized by severe myoclonus, pyrexia, tachycardia, hypertension, elevated muscle enzymes, and hypercapnia, often occurs in patients with congenital deformities or genetic disorders. Although the reported incidence rate is as low as 1:5000 to 1:100,000, patients with MH exhibit rapid aggravation and an elevated mortality rate. Thus, MH is associated with substantial perioperative risk. Successful treatment of patients with MH largely depends on early diagnosis and timely effective treatment. This clinical report provides a detailed description of a patient with newly diagnosed MH who developed a rapid rise in body temperature, end-tidal carbon dioxide, and heart rate during maxillary osteotomy. After successful rescue, the patient recovered smoothly during the postoperative period, indicating the importance of intraoperative monitoring, early diagnosis, effective treatment, and postoperative monitoring. This case is expected to serve as a reference for future interventions and healthcare practices in managing other patients with MH.
Topics: Humans; Malignant Hyperthermia; Anesthesia, General; Male; Female; Adult; Osteotomy
PubMed: 38907364
DOI: 10.1177/03000605241261962 -
Archivos de La Sociedad Espanola de... Jun 2024Non-arteritic anterior ischemic optic neuropathy (NAION) is after glaucoma the most common optic neuropathy in patients over 50 years. It is known that high blood...
Non-arteritic anterior ischemic optic neuropathy (NAION) is after glaucoma the most common optic neuropathy in patients over 50 years. It is known that high blood pressure (HBP) is an important risk factor for the development of NAION. It is also known that malignant arterial hypertension (MAH) could be accompanied by optic disc edema. However, MAH has not classically been considered a cause of NAION. We report the case of a 32-year-old patient who presented irreversible visual loss with a pattern compatible with NAION as the only manifestation of a hypertensive crisis.
PubMed: 38901612
DOI: 10.1016/j.oftale.2024.06.007