Thelansis

Ventilator-associated pneumonia (VAP) is pneumonia or infection in lung parenchyma acquired in patients after invasive mechanical ventilation after 48–72 hours. New or progressive infiltrates, systemic disease (fever, altered white blood cell counts), changes in sputum characteristics, and the detection of a causative agent are seen in VAP patients. VAP is the most common ICU-acquired pneumonia among invasive mechanically ventilated patients. VAP is recognized as a significant issue worldwide and a common healthcare-associated infection (HAI) among developing countries associated with mortality, a longer length of stay, and associated cost burden among patients. The VAP rate varies across studies due to differences in diagnostic criteria, ICUs type, patients' characteristics, and also varying causative microorganisms associated with patients' characteristics, length of stay, and antibiotic use in hospitals. Oropharyngeal and gastric colonization, thermal injuries; posttraumatic

Thyroid carcinomas are relatively uncommon tumors. They include disease types that range from indolent behaviour, such as papillary carcinomas, to fulminant and lethal anaplastic disease. It originates from 2 types of thyroid endocrine cells; Follicular thyroid and parafollicular cells. This accounts for >90% of thyroid malignancies and including papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC). Of note, PTC and FTC are classified as differentiated thyroid cancer (DTC). There are two classical signalling pathways, the MAPK and the PI3K-AKT pathways. Both pathways are coupled to the receptor tyrosine kinase (RTK) at the cell membrane, which transduces an extracellular growth stimulus that prompts downstream intracellular signalling. The MAPK pathway has a fundamental role in regulating cell proliferation, differentiation, apoptosis, and survival and has been linked to tumorigenesis when d

 T-cell large granular lymphocyte leukemia (T-LGL) is a heterogeneous lymphoproliferative disorder of CD3-positive T cells. The median age of T-LGL diagnosis is 60, with an equal male-to-female ratio and an indolent clinical course. A positive rheumatoid factor is found in 60%, polyclonal hypergammaglobulinemia in 10–40%, and a positive Coombs test in 15% of patients. The diagnostic criteria for LGL include a persistent increase in circulating LGLs, confirmatory immunophenotype, and, ideally clonal T cell receptor (TCR) rearrangements. T-LGL leukemia has a mature T cell immunophenotype, with 80% of patients expressing CD3, CD8, and TCRab, but not CD4, and discrepant weak CD5 or CD7 expression. Rare variants may be CD4þ and CD8– or co-expression of CD4 and CD8. Large granular lymphocytes form part of the cellular immune response and produce tumor necrosis factor a and interferon g, leading to cell lysis of damaged cells, such as virally infected cells. Secondary to chronic activation of

 Relapsed or Refractory Adult T-cell lymphoma/leukemia (ATL) is a rare lymphoproliferative neoplasm of mature CD4+ CD25+ T cells caused by infection with the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Nearly 90% of patients experience relapse, and consolidation of the first remission with allogeneic stem-cell transplantation is strongly considered. The aggressive subtypes of ATL carry some of the poorest prognoses of any of the non-Hodgkin lymphomas. In an extensive retrospective analysis, patients with ATL had 5-year failure-free and overall survival (OS) of only 12% and 14%, respectively. However, the clinical course can vary with this disease's chronic and smouldering variants. In patients without histologically proven tumor lesions, at least 5% of circulating abnormal T lymphocytes are required to diagnose ATL. These cells typically express the surface T-cell lymphocytic markers CD2, CD4, CD5, CD29, CD45RO, and T-cell receptor (TCR) αβ and are usually negative for C

 Proliferative vitreoretinopathy (PVR) is the most common cause of failure of rhegmatogenous retinal detachment repair. It is characterised by the growth and contraction of cellular membranes within the vitreous cavity and on both sides of the retinal surface and intraretinal fibrosis. Contraction of these membranes can cause the retina to redetach and transform a rhegmatogenous detachment into a tractional detachment. It is most common as a clinical complication of surgical procedures to correct rhegmatogenous retinal detachments, which are detachments that follow the formation of a retinal tear or hole. Tractional forces produced by the scar tissue-like PVR membranes can be transmitted to the retina, resulting in complete retinal detachment, retinal degeneration, and permanent blindness. PVR has also been reported to be common following posterior segment procedures or disorders such as giant retinal tears, macular relocation surgery, tumors endoresection, and chip implantation. PVR h

 Laryngeal cancer (LC) represents one-third of all head and neck cancers and is a significant cause of morbidity and mortality. They can involve different subsites of the larynx, with varying implications in symptomatic presentation, patterns of spread, and treatment paradigms. Early-stage disease is highly curable with surgical or radiation monotherapy, often larynx-preserving. In contrast, the late-stage disease has a worse outcome, warrants multimodal therapy, and is less often larynx-preserving. The laryngeal cancers vast majority are well-differentiated squamous cell carcinoma. A minority of cases show squamous cell variants, including neuroendocrine carcinoma, sarcomatoid carcinoma, and verrucous carcinoma. Historically, verrucous and sarcomatoid carcinomas were thought to be radioresistant, though recent experience contradicts this notion. Spread patterns depend on the location of the primary mass and the inherent lymphatic supply at that location. Laryngeal cancers are divided

 Kaposi’s sarcoma (KS) is a malignant neoplasm of the vascular endothelium that is multifocal, involving the skin and other organs. Based on epidemiological features, four types of Kaposi’s sarcoma have been recognised: classic, endemic, iatrogenic and epidemic (AIDS related). The course of KS ranges from indolent, with only skin manifestations, to fulminant, with extensive visceral involvement. Because of its broad morphologic spectrum and similarities to many benign vasoproliferative lesions (e.g., microvenular hemangioma, bacillary angiomatosis, and pyogenic granuloma) and tumors with a prominent spindle cell component, KS poses difficulties in histologic diagnosis. The variability in the behavior of KS among individuals in the same group remains enigmatic. Clinically, Kaposi sarcoma is a vascular lesion that frequently manifests as a violaceous pink to the purple plaque on the skin or mucocutaneous surfaces. Lesions can be painful, especially if they are associated with lymphedema

 Hemolytic-uremic syndrome (HUS) is a group of diseases characterized by the triad of nonimmune, microangiopathic hemolytic anaemia, thrombocytopenia, and decreased renal function. The first injury is to the endothelium (mainly renal), causing cell swelling and later detachment, leading to the formation of thrombocyte aggregates, microthrombi, mechanical hemolytic anemia, and organ dysfunction, mainly of the kidneys and brain. Different primary triggers cause the different types of Hemolytic-uremic syndrome (HUS). The pathophysiology underlying the initial endothelial damage is diverse, as are the various epidemiologies, disease course, recurrence risks, treatments, and prognoses. This leads to the pathological lesion termed thrombotic microangiopathy, which mainly affects the kidney and other organs. Although the underlying cause may differ, HUS is associated with endothelial cell injury and platelet activation. The majority of HUS is associated with gastrointestinal infection with Sh

 Gallbladder cancer (GC) is a rare malignancy but represents almost half of all biliary tract cancer. The chronic inflammation of the bile duct tissue accumulates successive genomic mutations that lead to malignant transformation. The most common mutations described are oncogenes K-RAS and tumor suppressors beta-catenin (CTNNB1). The majority of histopathology changes in gallbladder cancer appear as adenocarcinomas (90%). Gallbladder cancer patients are frequently asymptomatic at presentation or describe vague symptoms such as abdominal pain, anorexia, indigestion, weakness, nausea or vomiting, loss of appetite, and weight loss, and can present with jaundice, which can easily be misdiagnosed as cholecystitis. Biliary obstruction by cancer causes jaundice, clay-coloured stools, cola-colored urine, and skin pruritus. ·        The incidence of Gallbladder cancer (GC) ranges from 3 to 4 per 100,000 in the USA. Thelansis’s “Gallbladder Cancer (GC) Market Outlook, Epidemiology, Competiti

 Cryptococcus is an invasive fungus transmitted through the inhalation of spores that causes cryptococcosis, an infection commonly associated with immunosuppressive individuals. Patients present with headache, malaise, fever, photophobia and neck stiffness as cryptococcal meningitis sets in. The fungus capsule comprises polysaccharides glucuronoxylomannan and glucuronoxylomannogalactan, which significantly contribute to the pathogen's virulence. Infection is usually caused by inhaling spores from the environment. The initial condition is mostly asymptomatic and is contained in healthy individuals. The spread of the disease from the initial site of infection occurs through hematogenous dissemination in immune-suppressed patients. Another mechanism through which the condition can develop is the reactivation of the organism at the initial site of infection after several years when the patient becomes immunocompromised. ·        In the United States, the incidence of cryptococcosis i

 Autosomal dominant osteopetrosis type 2 is characterized by segmentary osteosclerosis, predominantly at the vertebral endplates, iliac wings, and skull base. Clinical manifestations include cranial nerve palsies, osteoarthritis of the hip, mandibular osteomyelitis, and nontraumatic fractures, particularly of the long bones. OPTA2 is responsible for 70% of autosomal dominant osteopetrosis cases. Symptoms and severity can vary greatly, ranging from the neonatal onset with life-threatening complications to the incidental finding of osteopetrosis on X-ray. Depending on the severity and age of onset, features may include fractures, short stature, compressive neuropathies, hypocalcemia with attendant tetanic seizures, and life-threatening pancytopenia. There may be neurological impairment or involvement of other body systems in rare cases. Osteopetrosis is classified based on clinical features, mode of inheritance and molecular mechanism. There are various clinical features and genes involv

 Unipolar depression as a standard and widespread illness is continually increasing. A combination of two symptoms characterises unipolar depression: emotional-cognitive and neurovegetative are directly related to the body (such as insomnia/hypersomnia, dysregulated eating, fatigue, and decreased energy). Morbidity risk for unipolar depression has been estimated between 13.9% and 18.4% in families diagnosed with the unipolar disease earlier. The unipolar designation indicates that depression does not alter between the two mood states. Unipolar depression can occur alongside several physical health issues, including cancer, physical trauma, chronic pain, cardiac problems, chronic health concern, and terminal stage illnesses. Some medications, such as interferon and beta-blocker treatments, can mimic or trigger depressive symptoms. ·        The prevalence of polar depression varies widely in adults and elderly patients, from 3% in Japan, 11% in Britain, and 10% in the US. Thelansis’s

 Primary hyperoxalurias are inborn errors in glyoxylate and oxalate metabolism. They are characterized by excessive oxalate production, a metabolic emend product. The most common type of PH, PH1, is caused by a deficiency of the liver-specific peroxisomal, pyridoxal phosphate-dependent enzyme alanine: glyoxylate aminotransferase. The second type, PH2 is caused by a deficiency in glyoxylate reductase/ hydroxypyruvate reductase, a cytosolic enzyme. The recently identified PH type 3 is linked to the gene DHDPSL, encoding a mitochondrial enzyme, although the metabolic reactions involved remain to be confirmed. Including AGXT, over twenty-five different mutations have been identified so far, and around 30% of patients have the G630A mutations leading to Gly170A amino-acid substitutions. Primary hyperoxaluria types 1, 2, and 3 are caused by mutations in the AGXT, GRHPR, and HOGA1 genes. These genes provide instructions for making enzymes that help with the breakdown and processing of protein

 Osteoporosis is a skeleton disease characterised by micro-architectural degradation of bone tissue and loss of bone mass. Osteoporosis increases bone fragility and susceptibility to fracture. The average bone turnover involves a balance between bone resorption and bone formation in which osteoclasts remove bone through acidification and proteolytic digestion, and osteoblasts secrete osteoid into the resorption cavity. In postmenopausal women, the rate of bone turnover increases rapidly and remains increased up to 40 years after cessation of ovarian function resulting in progressive bone loss. Risk factors include smoking, low body index, poor nutrition, vitamin D deficiency, low dietary calcium, age, gender, change in hormones, previous fracture, family history of osteoporosis, menopause, certain medications, and other disease conditions. Once osteoporosis is detected early and treated, the outcomes are good. However, if the state remains untreated, it can lead to chronic pain and fra

 Natural killer (NK)/T-cell lymphomas are aggressive cancers that are classified as nasal, non-nasal, and disseminated subtypes. Nasal NK/T-cell lymphomas affect the nasal cavity as well as the upper aerodigestive tract. Skin, testis, gastrointestinal tract, and other extranodal sites are all affected by non-nasal NK/T-cell lymphomas. Disseminated NK/T-cell lymphoma affects multiple organs and rarely presents with a leukemic phase. CD3 (not surface CD3), cytotoxic molecules, CD56, and EBV-encoded small RNA are all found in lymphoma cells. Natural killer (NK) cells arise from a common lymphoid progenitor that can differentiate into all lymphoid lineages. Expression of the transcription regulators STAT5, RUNX3, NOTCH, PU.1, TCF1, NFIL3 and CBFB leads to NK lineage commitment. NK cells are part of the innate immune system and are responsible for detecting and killing tumours or virally infected cells. They are strategically located at mucosal surfaces, the skin and the gut and circulate b

Intrahepatic cholangiocarcinoma (iCCA) is a rare, highly aggressive, and often fatal primary epithelial cancer arising within the liver. iCCAs are diagnosed mainly at an advanced non-curable stage and usually occur sporadically in patients without recognizable risk factors. More than 90% of iCCAs are adenocarcinomas exhibiting biliary differentiation biomarkers and can be subdivided by genomic and epigenomic profiling into etiologically distinct subtypes. Unlike hepatocellular carcinoma (HCC), most iCCAs develop in the non-cirrhotic liver, although it has been reported that about 8–10% of all it occurs in patients with liver cirrhosis. Unlike conventional HCCs, mass-forming iCCAs are typically characterized by a prominent desmoplastic and hypovascularized tumor stroma, which often represents the dominant histological feature of the tumor. Curative intent surgical resection is the best option for achieving long-term survival outcomes. However, only a fraction of iCCA patients are candid

Extranodal NK/T-cell lymphoma is a rare form of non-Hodgkin lymphoma that is strongly linked to the Epstein-Barr virus (EBV). The most common cause of this so-called "lethal midline granuloma" manifests almost exclusively in non-nodal sites, most commonly as stage IE/IIE disease in the nose, nasopharynx, oropharynx, and upper aerodigestive tract. Other skin and gastrointestinal tract sites can be involved in more advanced stages. Lymph nodes may have secondary involvement but are generally not the disease's primary site. Given the typical anatomic sites of involvement, the majority of patients present with nasal obstruction or epistaxis; some present with destructive masses involving the nose, sinuses, or palate. Approximately 3% of patients with ENKTL present with hemophagocytic lymphohistiocytosis syndrome characterised by high fevers, cytopenia, abnormal liver function tests, and high ferritin levels due to pathologic immune activation. The typical immunophenotype of E

 Dyslipidemia is the imbalance of lipids such as cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein (HDL). According to the Frederickson phenotype, dyslipidemia is classified into five categories. Phenotype I is a chylomicron abnormality that results in triglycerides higher than the 99 percentiles. Phenotype IIa is characterised primarily by LDL cholesterol abnormalities, with total cholesterol concentrations greater than the 90th percentile and possible apolipoprotein B more significant than the 90 percentile. The phenotype IIb consists of abnormality in LDL and very low-density lipoprotein (VLDL) cholesterol. The most critical complication of dyslipidemia is cardiovascular disease. This can lead to sudden cardiac death, acute myocardial infarction, or stroke. Multiple studies have shown that statins and appropriate dyslipidemia treatment reduce the risk of all-cause mortality, cardiovascular events, and cardiovascular mortality signi

Carcinoid syndrome (CS) is a paraneoplastic syndrome caused by the discharge of serotonin and different substances from well-differentiated neuroendocrine tumors (NETs). CS is a paraneoplastic syndrome associated with the secretion of around 40 vasoactive hormones, the majority of which are 5-hydroxytryptamine (5-HT). CS also involves the secretion of histamine (primary gastric NETs), prostaglandins E and F, kallikrein, and tachykinins. The hallmark symptoms of carcinoid syndrome are diarrhea and flushing; atypical signs and symptoms can include wheezing, pellagra, valvular heart disease, telangiectasias, abdominal pain, and the complications of mesenteric fibrosis, including ureteral obstruction, bowel ischemia, and bowel obstruction. These symptoms are mediated by the release of serotonin (5-HT), prostaglandins, kallikrein, histamine, and tachykinins. These symptoms, as well as the corresponding elevations in lab tests, are required for the diagnosis of CS. Surgery and medical manage

Intrahepatic cholangiocarcinoma (iCCA) is a rare, highly aggressive, and often fatal primary epithelial cancer arising within the liver. iCCAs are diagnosed mainly at an advanced non-curable stage and usually occur sporadically in patients without recognizable risk factors. More than 90% of iCCAs are adenocarcinomas exhibiting biliary differentiation biomarkers and can be subdivided by genomic and epigenomic profiling into etiologically distinct subtypes. Unlike hepatocellular carcinoma (HCC), most iCCAs develop in the non-cirrhotic liver, although it has been reported that about 8–10% of all it occurs in patients with liver cirrhosis. Unlike conventional HCCs, mass-forming iCCAs are typically characterized by a prominent desmoplastic and hypovascularized tumor stroma, which often represents the dominant histological feature of the tumor. Curative intent surgical resection is the best option for achieving long-term survival outcomes. However, only a fraction of iCCA patients are candid