A 35 Yrs Old Male Patient With No H/o Past illness. Comes With complain Of Dyspnea & Having Problem In Breathing. No Fever, No Body Ache, No Cough & Cold, No Taste Change & No Smell Changes So No Suspect of Covid But Advised RTPCR for Confirmation. Please Help To Conclude Dx & Management? Thank You *Chief Complaints* Dyspnea on Exertion, Tiredness

Goldenseal: A Natural Antibiotic & Cancer Fighter Goldenseal is one of the five top-selling herbal products in the U.S. Native Americans historically used goldenseal for various health concerns including skin diseases, ulcer symptoms and gonorrhea. Today’s traditional uses of goldenseal have broadened to include the natural treatment and prevention of colds , respiratory tract infections, allergies , eye infections, digestive issues, canker sores, vaginitis, urinary tract infections and even cancer. Goldenseal contains berberine , which has been been proven to be antimicrobial , anti-tumor , anti-inflammatory and blood glucose–lowering . Goldenseal has also gained popularity after a rumor spread that taking the herb can help block a positive test for illegal drugs. However, there is no scientific evidence that has proven this rumor to be correct. Yet fortunately there is research to support the medicinal use of goldenseal. What Is Goldenseal? Goldenseal ( Hydrastis canadensis), also known as orange root, yellow root or yellow puccoon, is a perennial herb belonging to the buttercup family, Ranunculaceae . It is a low, sprawling plant native to the rich, shady soil of the deciduous forests of North America growing from southern Quebec to northern Georgia and west to Missouri. Due to overharvesting, goldenseal is now mostly commercially grown on farms in the U.S. Goldenseal plants have hairy stems with jagged five to seven lobed leaves and small white flowers that turn into raspberry-like red berries. The bitter tasting roots of the goldenseal plant are bright yellow or brown, twisted and wrinkled. The dried underground stems (rhizomes) and roots of the goldenseal plant are used to make teas, liquid extracts, tablets, and capsules as well as natural skin care products. Goldenseal’s potent properties are primarily due to the alkaloids berberine , canadine and hydrastine. These phytochemical alkaloids produce a powerful astringent effect on mucous membranes, reduce disease-causing inflammation and have antiseptic effects. 5 Health Benefits of Goldenseal 1. Improves Digestive Issues Goldenseal is an excellent digestive aid since it is very bitter, which stimulates the appetite, aids digestion and encourages bile secretion. Goldenseal contains berberine, which has been used in Traditional Chinese Medicine (TCM) and Ayurvedic medicine for thousands of years to treat dysentery and infectious diarrhea. This is not surprising since the berberine in goldenseal has shown antimicrobial activity against certain pathogens that cause bacterial diarrhea, including E. coli and V. cholera . Goldenseal can also be helpful to people experiencing small intestine bacterial overgrowth (SIBO) symptoms . Current conventional treatment of SIBO is limited to oral antibiotics with inconsistent success. The objective of a study published by Global Advances in Health and Medicine was to determine the remission rate of SIBO using an antibiotic versus an herbal remedy. It found that the herbal treatment, which included berberine, worked just as well as antibiotic treatment and was equally safe. Some people also use goldenseal for stomach swelling (gastritis), peptic ulcers, ulcerative colitis , diarrhea, constipation, hemorrhoids and intestinal gas. Another impressive study found that among several herbs tested in vitro, goldenseal extract was the most active in inhibiting the growth of H. pylori, a type of bacteria which can lead to gastritis, ulcers and even stomach cancer. Goldenseal truly treats a wide range of problems when it comes to the gastrointestinal system. 2. Natural Antibiotic & Immune System Booster Goldenseal is often found in herbal remedies for allergies, colds, and the flu because of its natural antibiotic and immune-boosting capabilities. One study found that goldenseal might help boost white blood cells, which is a measure of the infection-fighting ability of the immune system. Scientific research also suggests that medicinal plants like goldenseal and echinacea may enhance immune function by increasing antigen-specific antibody production. A product containing goldenseal and echinacea is an awesome natural bronchitis remedy . Additionally, research at the University of Texas-Houston Medical School has shown goldenseal’s medicinal effectiveness as an immune stimulant may be due to its ability to reduce the pro-inflammatory response, which indirectly leads to the limiting of clinical symptoms during infection. Goldenseal is also recommended to treat urinary tract infections (UTIs) , which are caused by bacterial overgrowth in the bladder’s interior walls. The berberine in goldenseal actually prevents the E. coli from binding to urinary tract walls. 3. Fights Cancer According to Memorial Sloan Kettering Cancer Center , the berberine in goldenseal has been found to induces cell cycle arrest and apoptosis (programmed cell death) in cancer cells in multiple studies . One in vitro study found that berberine inhibited the growth of breast cancer cells to a greater extent than doxorubicin (a chemotherapy drug). In another study, berberine alkaloids produced an average of 91% tumor inhibition against 6 malignant brain tumor cell lines both in vivo in mice and in vitro against human brain tumors. Berberine alkaloids were also shown to have potent cancer cell killing activity against tumor cells. Research has also been performed on a series of human malignant brain tumor cells and rat brain tumor cells in which berberine was used alone at a dose of 150 mcg/ml and had an average cancer cell kill rate of 91% . In contrast, the chemotherapy drug carmustine had a cell kill rate of only 43%. The rats treated with berberine at 10 mg/kg had an 81% kill rate. Research will continue, but so far goldenseal is being shown to hold some serious anti-cancer abilities. 4. Aids Eye & Mouth Problems Goldenseal is also commonly used as a mouthwash for sore throats, gum complaints, and canker sores (small ulcers in the mouth). For any of these concerns, goldenseal mouth rinse can help by reducing inflammation and getting rid of any nasty bacteria. You can purchase a mouthwash that already contains goldenseal or you can easily make some goldenseal mouthwash at home. Simply make a cup of goldenseal tea and let it cool down before using it to rinse your mouth. Or you can add five drops of liquid goldenseal extract to eight ounces of warm water with a teaspoon of salt and mix well. Goldenseal has been utilized as an eyewash for eye inflammation and eye infections like conjunctivitis or “pink eye.” Since the use of goldenseal in the eyes is somewhat controversial, consult a health practitioner before using goldenseal in this way. 5. Boosts Heart Health The cardiovascular effects of the berberine found in goldenseal suggest its possible clinical usefulness in the treatment of arrhythmias and/or heart failure . For this reason, goldenseal is believed to possibly be helpful for chronic congestive heart failure (CHF) and heart function in general. A 2006 study demonstrated that the root extract of goldenseal is highly effective in regulation of the liver’s LDL (“bad cholesterol) receptors and in reducing plasma cholesterol. Overall, the findings identified goldenseal as a natural LDL-lowering agent . In combination with a healthy diet and lifestyle, goldenseal can help to lower cholesterol naturally . Berberine also helps heart health by helping to keep blood sugar levels under control and obesity in check, both of which can raise the risk of coronary heart disease . Berberine also stimulates the release of nitric oxide, a signaling molecule that relaxes the arteries, increases blood flow, reduces blood pressure and protects against arteriosclerosis. Goldenseal History & Interesting Facts Goldenseal gets its name from the golden-yellow scars that form on the base of the stem when it is broken. The scars resemble a gold wax letter seal hence the name goldenseal. It has been said that the powers of goldenseal were first introduced to European settlers by Native Americans, who harvested its rhizomes and roots to treat a variety of health complaints including eye, skin and digestive issues. Native Americans also mixed goldenseal with bear grease for use as an insect repellent and they used the color-rich roots to dye clothing. Goldenseal has become one of the top selling herbs of North America. In Canada, there are currently around 40 over-the-counter drugs containing goldenseal or its active ingredients in the form of elixirs, tablets, capsules, or suppositories. Health products combining goldenseal and echinacea are very common and are created with immune system enhancement in mind. Despite rumors, goldenseal will not cause a false-negative result for marijuana, cocaine, amphetamines, or any other illegal drugs. The idea of using goldenseal to alter drug test results came from the novel Stringtown on the Pike , by the pharmacist John Uri Lloyd. However, in this book, goldenseal caused a false-positive for strychnine (a poison), not illegal drugs, in a murder case. Possible Side Effects of Goldenseal Goldenseal is considered safe for short-term use in adults at recommended dosages. Rare side effects may include nausea and/or vomiting. Discontinue use of goldenseal if any negative reactions like these occur. Goldenseal is not meant for long-term use. If you are currently taking any prescription or over-the-counter medications or have any health issues, check with your doctor before taking goldenseal. People with high blood pressure, liver disease, or heart disease should consult their healthcare provider before taking goldenseal. Goldenseal is not suggested for use in children or infants. Pregnant or breastfeeding women should also avoid using goldenseal. Recommended Use of Goldenseal Goldenseal can easily be found in tea or supplement form at your local health store or online. Depending on which goldenseal product you purchase, make sure to read the label for each brand’s recommended dosage. For powdered goldenseal root and rhizome, 4–6 grams per day in tablet or capsule form is sometimes recommended. For liquid herbal extracts, a typical recommended dosage is 2 milliliters (40 drops) in 2 ounces of water or juice 3-5 times per day. Continuous use of goldenseal should not exceed three weeks, with a break of at least two weeks between each use. You can also talk to your health practitioner about what amount of goldenseal would be best for you and your particular health concern(s). Goldenseal is best taken internally between meals. For external use of goldenseal, there is no standard recommended dosage, but read the label of the topical goldenseal product for instructions. Most likely, it will recommend that you use the product on the area of concern at least once a day.

✍️✍️Late Effects Of Blood And Marrow Transplantation ___________________________________________ Abstract Hematopoietic cell transplantation is a curative treatment for a variety of hematologic diseases. Advances in transplantation technology have reduced early transplant-relatedmortality and expanded application of transplantation to older patients and to a wider variety of diseases. Management of late effects after transplantation is increasingly important for a growing number of long-term survivors that is estimated to be half a million worldwide. Many studies have shown that transplant survivors suffer from significant late effects that adversely affect morbidity, mortality, working status and quality of life. Late effects include diseases of the cardiovascular, pulmonary, and endocrine systems, dysfunction of the thyroid gland, gonads, liver and kidneys, infertility, iron overload, bone diseases, infection, solid cancer, and neuropsychological effects. The leading causes of late mortality include recurrent malignancy, lung diseases, infection, secondary cancers and chronic graft-versus-host disease. The aim of this review is to facilitate better care of adult transplant survivors by summarizing accumulated evidence, new insights, and practical information about individual late effects. Further research is needed to understand the biology of late effects allowing better prevention and treatment strategies to be developed. Introduction Hematopoietic cell transplantation (HCT) is a curative treatment for a variety of hematologic diseases.1 The safety of HCT has improved over the decades,2 indications for HCT have expanded to older patients,3 and almost all patients are able to find suitable allogeneic donors by the growing use of cord blood4 and haploidentical transplantation.5 These current conditions have contributed to a growing number of HCT survivors, estimated to be half a million worldwide.6 Patients who are disease-free at two or five years after HCT have a greater than 80% subsequent 10-year survival rate,7–10 but many studies show that HCT survivors suffer from significant late effects that adversely affect morbidity, mortality, working status and quality of life.7–13 A prospective observational study of 1022 survivors who underwent HCT between 1974 and 1998 showed that 66% of the survivors had at least one chronic condition and 18% had severe or life-threatening conditions.14 A retrospective study of 1087 contemporary survivors also showed that the cumulative incidence of any non-malignant late effect at five years after HCT was 45% among autologous and 79% among allogeneic recipients, and 2.5% of autologous and 26% of allogeneic recipients had three or more late effects.15 Life expectancy among 5-year survivors remained 30% lower compared with the general population, regardless of their current ages and years since HCT.9 The leading causes of excess deaths in 5-year survivors included secondary malignancies (27%) and recurrent disease (14%), followed by infections (12%), chronic graft-versus-host disease (GvHD) (11%), cardiovascular diseases (11%), and respiratory diseases (7%).9 The aim of this review is to facilitate better care of adult HCT survivors by summarizing accumulated evidence, new insights, and practical information about individual late effects (Figure 1). Recurrent disease and chronic GvHD are not discussed and readers are referred to other reviews.16–20 Figure 1. Download figure Open in new tab Download powerpoint Figure 1. Late effects of blood and marrow transplantation. Cardiovascular diseases Cardiovascular diseases (CVD) after HCT include cardiomyopathy, congestive heart failure, valvular dysfunction, arrhythmia, pericarditis, and coronary artery disease.21 Their cumulative incidences were 5%–10% at ten years after HCT,22–24 accounting for 2%–11% of mortality among long-term survivors.8,9,25 The incidence of CVD and its associated mortality were 1.4–3.5-fold higher compared with the general population.8,9,24,25 HCT survivors are more likely to have conventional risk factors such as dyslipidemia and diabetes than the general population.26 Early diagnosis and treatment of modifiable risk factors is important. We usually treat hypertension more than 140/90 mmHg on 2 separate visits or more than 130/80 mmHg for patients with diabetes or renal disease.27 The first step is lifestyle modification including weight reduction, dietary sodium reduction and regular physical activity, followed by initiating antihypertensive drugs such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Anthracycline exposure and chest radiation are the major risk factors for CVD after HCT.21 Several studies showed that dexrazoxane, ACE inhibitors, ARBs and beta-blockers can prevent anthracycline-related cardiomyopathy in the non-HCT setting.28–32 Once cardiomyopathy is established, it is important to initiate appropriate treatment. ACE inhibitors and beta-blockers have been effective in improving left ventricular function.33 Pulmonary diseases Non-infectious late complications of the lung include bronchiolitis obliterans syndrome (BOS), cryptogenic organizing pneumonia (COP) and pulmonary hypertension. BOS represents chronic GvHD of the lung, and is characterized by the new onset of fixed airflow obstruction after allogeneic HCT.34 According to the strict 2005 National Institutes of Health (NIH) diagnostic criteria for chronic GvHD, incidence of BOS was 5.5% and its prevalence was 15% among patients with chronic GvHD.35 Symptoms of BOS include dyspnea on exertion, cough and wheezing, but early BOS may be asymptomatic until significant lung function is lost.36 One study showed rapid decline in %FEV1 during the six months before BOS diagnosis, with a lower %FEV1 at diagnosis associated with worse survival.37 In our practice, we perform pulmonary function tests every three months including %FEV1 and FEV1/FVC among patients with active chronic GvHD. When testing shows significant new airflow obstruction, we repeat testing every month until stability is confirmed.38 Plasma matrix metalloproteinase 3 levels39 and parametric response mapping from CT scans40 might be useful diagnostic tests for BOS but these have not yet entered clinical practice. Standard treatment of BOS is prednisone at 1 mg/kg per day, followed by a taper to reach a lower, alternate-day regimen.38 A multicenter prospective study showed that addition of FAM (inhaled fluticasone propionate at 440 μg twice a day, azithromycin at 250 mg taken 3 days per week, and montelukast at 10 mg nightly) to prednisone treatment stabilized pulmonary function in 70% of patients with newly diagnosed BOS and permitted systemic steroid exposure to be reduced.41 Cryptogenic organizing pneumonia is a disorder involving bronchioles, alveolar ducts, and alveoli, the lumen of which become filled with buds of granulation tissue consisting of fibroblasts.42 Clinical symptoms include dry cough, shortness of breath, and fever. Bronchoalveolar lavage is performed to exclude infection. Lung biopsy is required for definitive diagnosis, but an empiric diagnosis is often based on radiographic findings of diffuse, peripheral, fluffy infiltrates consistent with airspace consolidation. Pulmonary function testing shows restrictive changes and low diffusing capacity of the lungs for carbon monoxide. The incidence of COP is 2%–10%,43,44 and it is strongly associated with acute and chronic GvHD.45 COP usually responds within 5–7 days to prednisone at 1 mg/kg per day, which is continued for one month followed by a slow taper over five months because COP can often recur. Small case series suggest potential benefits of macrolides for treatment of COP.46 Pulmonary hypertension is an uncommon but potentially fatal complication after HCT, with a reported prevalence of 2.4%.47 The most common symptoms are hypoxia, tachypnea, dyspnea, and acute respiratory failure,48 and if untreated, pulmonary hypertension can result in a progressive increase in pulmonary vascular resistance, right ventricular failure and death. Since initial symptoms are non-specific, it is likely to be underdiagnosed after HCT. Although cardiac catheterization is the gold standard for diagnosis of pulmonary hypertension, high-resolution chest computed tomography and echocardiography are non-invasive and useful diagnostic modalities. The most common types are pulmonary arterial hypertension and pulmonary veno-occlusive disease, sometimes associated with transplant-associated microangiopathy and inherited or acquired hemolytic anemia.48 First-line therapies are supplemental oxygen and phosphodiesterase-5 inhibitors, followed by inhaled nitric oxide, diuretics, bipyridine inotropes and after-load reducing agents.48 Endocrine diseases Major late effects in the endocrine system include thyroid dysfunction, diabetes, dyslipidemia, and adrenal insufficiency. Hypothyroidism occurs in 30% of patients by 25 years after HCT.49 Risk factors include age under ten years, conditioning containing radiation, busulfan or cyclophosphamide, and hematologic malignancies.49,50 The international guidelines recommend checking serum thyroid-stimulating hormone and free thyroxine levels every year.21 For patients who received radiolabeled iodine antibody therapy, thyroid function should be checked earlier starting at three and six months after HCT, and other times as clinically indicated. Standard criteria are used to initiate replacement therapy for hypothyroidism. Some patients develop hyperthyroidism after HCT as a rare complication.51 Diabetes occurs in 8%–41% of patients after allogeneic HCT and in 3% of patients after autologous HCT.15,52,53 Its incidence after allogeneic HCT is 3.65 times higher compared with their siblings.54 Initial treatment is therapeutic lifestyle counseling, but many patients require hypoglycemic agents or insulin. Dyslipidemia occurs in 9%–61% of HCT survivors.53,55 Despite no established consensus for management of dyslipidemia after HCT, our practice is to initiate therapeutic lifestyle counseling followed by statin therapy when LDL cholesterol exceeds 130–190 mg/dL according to the estimated risk of CVD, based on the National Cholesterol Education Program Adult Treatment Panel III guidelines56 and the recently suggested approach after allogeneic HCT.57 The 2013 ACC/AHA guidelines do not specify the targeted levels for LDL cholesterol, and addition of statin therapy is based on calculated risk for future cardiovascular events.58 Addition of omega-3-acid ethyl esters or fibrate is considered when fasting triglycerides exceed 200–499 mg/dL. Adrenal insufficiency occurs in 13% of patients after allogeneic HCT and 1% of patients after autologous HCT,15 and can be confirmed by a cortisol-stimulation test. Once adrenal insufficiency is diagnosed, physiological glucocorticoid replacement and a very slow terminal taper is needed. Patients should carry notification that they have adrenal insufficiency to alert emergency medical providers. For chronic GvHD therapy, the risk of adrenal insufficiency is lower with alternate-day administration of corticosteroids than with daily dosing,59 although patients with brittle diabetes need daily dosing to allow for optimal glucose control. Male gonadal dysfunction and infertility Hypogonadism is common after HCT. Impaired spermatogenesis, erectile dysfunction, low testosterone, and low libido occur in male patients. Erectile dysfunction and low libido have been associated with both physical and psychosocial factors.60,61 Testosterone replacement may be considered for patients with low testosterone levels and has improved sexual function, libido and bone mass, although monitoring prostate-specific antigen and testosterone levels is necessary.62,63 Azoospermia occurred in 70% of male patients, and spermatogenesis recovered in 90% of patients conditioned with cyclophosphamide alone, in 50% of patients conditioned with cyclophosphamide plus busulfan or thiotepa, and in 17% of patients conditioned with total body irradiation (TBI).64 Semen banking or cryopreservation of testicular tissue should be discussed before HCT with patients desiring fertility. Female gonadal dysfunction, infertility and pregnancy Ovarian insufficiency, vaginal changes and low libido occur in female patients. A historical study showed that ovarian failure occurred in more than 90% of female patients after HCT and recovered in 92% of patients conditioned with cyclophosphamide alone, but only in 24% of patients conditioned with cyclophosphamide and TBI.65 A pilot study showed that only 10% of patients had ovarian failure after reduced-intensity allogeneic HCT.66 The use of hormone replacement therapy for premature ovarian failure should be individualized based on the patient age, severity of menopausal symptoms, low bone density, risk of breast cancer, clotting predisposition and liver abnormalities.67 Since efficacy of gonadotropin-releasing hormone agonists in preserving fertility in cancer patients is controversial,68,69 cryopreservation of oocytes, ovarian tissue, or embryos should be discussed with patients desiring fertility.70 The largest study of pregnancy after HCT showed that 0.87% of patients or their partners had pregnancies after allogeneic HCT, and 0.36% of those after autologous HCT.71 We generally recommend that women wait 2–5 years after HCT before attempting conception since rates of relapse are generally highest in the first two years after HCT. Another concern is the theoretical risk of recurrent malignancy because of disturbance of the graft-versus-leukemia effect, and some cases of recurrent chronic myeloid leukemia after conception have been reported.71 Pregnancy outcomes are generally good with no increase in the risk of fetal malformations, although these pregnancies are considered high risk because of higher maternal risks of pregnancy complications.71 Iron overload Iron overload is rare after autologous HCT72 but common after allogeneic HCT.73,74 Previous prospective studies showed that 30%–60% of long-term survivors of allogeneic HCT had elevated serum ferritin levels and 25%–50% had elevated liver iron concentration on T2* magnetic resonance imaging (MRI).73,74 Since serum ferritin does not specifically reflect iron overload and can be elevated in hepatic and systemic inflammation, additional testing is required if the ferritin is elevated. We favor transferrin saturation, which is widely available and defined as the ratio of serum iron concentration divided by total iron-binding capacity.75 Normal transferrin saturation is less than 50% in males and less than 45% in females. Patients with iron overload usually have saturation more than 60%. HFE genotyping is considered in patients with a family history of hemochromatosis and in patients of Northern or Western European ethnicity. When saturation is not elevated, other etiologies for an elevated ferritin including inflammation, metabolic syndrome, and alcoholism should be ruled out. The most accurate test of tissue iron concentration is liver biopsy, but the procedure is invasive and may cause serious complications. Thus, T2* MRI and other modalities (FerriScan and superconducting quantum interference device) have been increasingly used.76 Importantly, liver tests are often normal among long-term survivors with iron overload, so hepatitis and GvHD should also be considered when results of liver tests are elevated.77 Iron overload may cause cardiomyopathy. Studies of thalassemia patients showed that cardiomyopathy typically took more than ten years to be clinically evident,78 and that many patients improved with intensive chelation therapy.79 Although a prospective study and a meta-analysis showed no statistical association of liver iron concentration with mortality after allogeneic HCT,80,81 our practice is to start phlebotomy of 5 mL/kg or 250–300 mL every 3–4 weeks as long as hematocrit is more than 35% until serum ferritin falls below 1000 ng/mL. Deferasirox, an oral chelating agent, is considered for patients with anemia precluding phlebotomy. Liver diseases Late liver diseases include chronic hepatitis B, chronic hepatitis C, liver cirrhosis, nodular regenerative hyperplasia and focal nodular hyperplasia.77 Hepatitis B-infected patients have an increased risk of fulminant liver failure. One study reported a 35% risk of HBV reactivation after HCT even among patients with isolated anti-HBc antibodies, mostly during steroid treatment for GvHD.82 Patients treated with anti-CD20 antibodies have an increased risk of HBV reactivation. Antiviral prophylaxis using entecavir or lamivudine will prevent almost all fulminant cases if initiated before the start of conditioning regimens in patients with positive blood HBV DNA levels.83 Patients with latent HBV (i.e. anti-HBc+/HBV DNA−) should be monitored monthly with HBV DNA levels after HCT and antiviral treatment should be initiated when viremia is detected.83 Hepatitis C virus infection in HCT survivors almost always results in chronic hepatitis.84,85 Typically, asymptomatic elevation of alanine aminotransferase occurs 2–4 months after HCT, coinciding with tapering of immunosuppressive medications. There may be little liver-related mortality in the first ten years after HCT,84 but liver cirrhosis occurs later with a cumulative incidence of 4%–24% at 20 years.85,86 A large retrospective study showed that hepatitis C-infected patients had an increased risk of 2-year non-relapse mortality due to hepatic problems and bacterial infection.87 Antiviral therapy for HCV has not been given early after HCT, but may improve both oncological and hepatic outcomes after HCT.88 Ribavirin and interferon-based therapy have been used for patients who have discontinued all immunosuppressive medications without active GvHD, but it can cause pancytopenia and GvHD. Recently, highly effective and well tolerated direct acting antiviral agents with more than 90% rates of sustained virological response have been developed, and interferon-free regimens are now the treatments of choice.89,90 Nodular regenerative hyperplasia is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules.77 This process is usually asymptomatic unless portal hypertension develops. Focal nodular hyperplasia occurs in 12% of HCT survivors, and possibly reflects sinusoidal injury caused by myeloablative conditioning regimens.91 Kidney diseases Chronic kidney disease (CKD) is defined as an elevated serum creatinine level, or a decreased glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 for three months or longer.92 CKD occurs in approximately 20% of HCT recipients.93–95 There are three major etiologies of CKD after HCT: thrombotic microangiopathy (TMA), nephrotic syndrome and idiopathic CKD. Other etiologies include persistent acute kidney injury and BK virus nephropathy.96 Whenever possible, renal biopsy should be considered to accurately diagnose the etiology of CKD and to provide appropriate management.97 Thrombotic microangiopathy occurs in 2%–21% of patients after HCT, and is characterized by renal dysfunction, thrombocytopenia, neurological dysfunction, hemolytic anemia with schistocytes, elevated lactate dehydrogenase and decreased haptoglobin.98,99 Risk factors of TMA include TBI, calcineurin inhibitors, and acute and chronic GvHD.100–102 TMA-related kidney injury often improves with tapering or stopping calcineurin inhibitors, but full renal function is rarely restored.103 In some cases TMA did not improve until GvHD was treated.104 Efficacy of plasma exchange is limited.105 Nephrotic syndrome occurs in 6%–8% of patients after allogeneic HCT.106,107 Membranous nephropathy comprised 61% of cases, and minimal change disease comprised 22% of cases, with a median onset of 14 months and eight months after HCT, respectively.108 Mechanisms of membranous nephropathy are thought to be formation of immune complexes through allo- or auto-antibodies recognizing antigens expressed by the podocyte, while T cells are implicated with minimal change disease.109 Nephrotic syndrome after HCT is often associated with chronic GvHD and tapering of immunosuppressive medications. Initial treatment is prednisone 1 mg/kg/day in addition to calcineurin inhibitors. Complete response was observed in 90% of patients with minimal change in disease, but only in 27% of patients with membranous nephropathy.108 Refractory cases may be treated with rituximab or mycophenolate mofetil.110 Idiopathic CKD comprises most cases of CKD. Risk factors include acute GvHD, chronic GvHD, acute kidney injury, long-term use of calcineurin inhibitors and previous autologous HCT,94,111 suggesting that GvHD, accompanying treatment and inflammatory conditions may have pathogenic roles in this entity. Associations of TBI with risk of CKD have been controversial.94,112 ACE inhibitors and ARBs have been used to treat CKD and hypertension associated with CKD.113 Bone diseases Late complications of bone include osteopenia, osteoporosis and avascular necrosis (AVN).114 Osteoporosis has been reported in as many as 50% of HCT recipients.115,116 The diagnoses of osteopenia and osteoporosis are made by measuring T-scores with dual-energy X-ray absorptiometry. A T-score between −1.0 and −2.5 indicates osteopenia, and a T-score less than −2.5 or presence of a fragility fracture indicates osteoporosis.117 Multiple risk factors are implicated including chemotherapy, radiation, corticosteroids, calcineurin inhibitors, vitamin D deficiency, and gonadal failure.116,118 Bone loss occurs within 6–12 months after HCT, and recovery of bone mineral density (BMD) begins from the lumber spine, followed by a slower recovery in the femoral neck. The use of corticosteroids is the strongest risk factor for osteoporosis. General preventative recommendations include adequate intake of calcium of 1200 mg per day or over and vitamin D of 1000 IU (25 μg) per day or over, regular weight-bearing exercise, and avoidance of smoking and excessive alcohol. Bisphosphonates are the primary treatment for bone loss.119 Patients who are taking 5 mg or more daily prednisone-equivalent steroids for three months or more should have screening BMD tests for osteoporosis, and bisphosphonate treatment may be indicated until corticosteroid treatment is discontinued or for up to five years.120 Second-line treatment includes calcitonin, raloxifene, denusomab, romosozumab, and blosozumab, though their reported use in HCT recipients is limited and adverse effects may be more prominent than with the bisphosphonates. Avascular necrosis occurs in 4%–19% of HCT survivors with a cumulative incidence of 3%–10% at five years after HCT.121,122 AVN causes severe bone pain and bone destruction, causing significant impairment in quality of life. AVN typically affects the femoral heads, but sometimes affects other joints such as the knee and shoulders.21 Risk factors for AVN include corticosteroids, calcineurin inhibitors, older age and TBI conditioning.114 When AVN is suspected, diagnostic MRI should be performed. Early involvement of an orthopedic specialist is important for management of AVN, including conservative treatment, joint-preserving surgery and joint replacement surgery.21,114 Infectious diseases All HCT survivors have some degree of immunodeficiency, particularly during the first year after HCT.123 If patients are able to stop immunosuppressive medications without GvHD or recurrent disease, many recover adequate immune function by one year after HCT. Patients with chronic GvHD, however, remain immunodeficient and have a high risk of infections. Common late infections are caused by Pneumocystis jirovecii, encapsulated bacteria, fungi, varicella-zoster virus (VZV), cytomegalovirus, and respiratory viruses. Patients may report more frequent episodes of upper respiratory infections and sinusitis. All patients should receive prophylaxis against Pneumocystis jirovecii for at least one year after HCT or until 3–6 months after all immunosuppressive medication is discontinued, whichever occurs later. The preferred drug is trimethoprim-sulfamethoxazole, but dapsone or atovaquone could be substituted for patients who are allergic to or intolerant of trimethoprim-sulfamethoxazole. In particular, patients with chronic GvHD are highly susceptible to encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis due to low levels of opsonizing antibodies, low CD4+ T-cell counts, poor reticuloendothelial function and suppressive effects of immunosuppressive medications on phagocytosis. Vaccination against these bacteria is recommended.124 Efficacy of vaccination in increasing antibody levels has been shown in several prospective studies.125,126 Chemoprophylaxis is always recommended due to the unpredictable protection provided by vaccination. The first-line drug is trimethoprim-sulfamethoxazole, but if it is not tolerated, penicillin or azithromycin is substituted until 3–6 months after discontinuation of all immunosuppressive medications. Invasive fungal infection occurs in 1% of patients after autologous HCT and in 6%–8% of patients after allogeneic HCT.127 GvHD and long-term use of corticosteroids have been a major risk factor associated with onset of invasive fungal infection.128 As recommended in the European guidelines, mold prophylaxis with posaconazole or voriconazole may be considered for patients with GvHD requiring high-dose corticosteroid treatment.129 Varicella-zoster virus-seropositive patients should receive prophylaxis with acyclovir or valacyclovir during the first year after HCT or until six months after discontinuation of immunosuppressive medications. A standard dose of acyclovir is 800 mg twice daily,130 but some studies showed that 200 mg once daily was effective in preventing VZV reactivation.131 Acyclovir should be started empirically if the patient presents with an acute abdomen or hepatitis typical of fulminant visceral VZV infection.132 CMV monitoring in blood is continued beyond 100 days after HCT until one year for patients at risk of late CMV disease, including CMV-seropositive patients receiving high-dose corticosteroids, those who have already experienced CMV reactivation, and cord blood transplantation.133 Pre-emptive therapy is usually considered for CMV levels of 250 IU/mL or more (equivalent to ≥1000 copies/mL) or a positive antigenemia test. Community-acquired respiratory virus infections are an important cause of morbidity and mortality after HCT. The most frequent viruses include rhinovirus, respiratory syncytial virus (RSV), parainfluenza viruses (PIV), human metapneumovirus, and influenza viruses as these frequently cause lower respiratory tract disease associated with 12%–100% mortality.134 An immunodeficiency scoring index can predict severity of RSV infection.135 Aerosolized ribavirin showed efficacy in treating lower tract RSV after HCT.136 Combination therapy with immunomodulators such as intravenous immunoglobulin or palivizumab has been seen to have variable success.137 Treatment for PIV infection has not been established. Efficacy of ribavirin has been limited for patients with lower respiratory tract infection of PIV.138 Novel drugs such as a recombinant sialidase fusion protein and a hemagglutinin-neuraminidase inhibitor are under investigation.138 Solid cancers There is an increased risk of solid cancers following both autologous and allogeneic HCT compared with the general population. The cumulative incidence is 1%–6% at ten years after HCT, and continues to rise over time without a plateau.139–142 The most common sites include oral cavity, skin, breast and thyroid, but rates are also elevated in esophagus, liver, nervous system, bone and connective tissues compared with the general population.143 Myeloablative TBI, young age at HCT, chronic GvHD and prolonged immunosuppressive medications beyond two years are well-documented risk factors for many types of cancers.143 All HCT recipients should be advised of the risk of second cancers and should be encouraged to undergo recommended screening tests based on their predisposition.143 The 5-year overall survival rates after diagnosis of solid cancers varied by cancer site, with 88%–100% for thyroid, testis and melanoma, approximately 50% for breast, mouth, soft tissue and female reproductive organs, and 20% or less for bone, lower gastrointestinal tract, and central nervous system.144 These rates were similar to those of de novo cancers, except that rates were lower for female reproductive organs, bone, colorectum, and central nervous system, although further studies are warranted to confirm this observation. There is emerging evidence that human papilloma virus (HPV) is involved in the pathogenesis of squamous cell cancer after HCT.145,146 The efficacy of HPV vaccination in preventing squamous cell cancer after HCT remains to be determined in prospective studies.147 Neuropsychological effects Neuropsychological effects after HCT are being increasingly recognized and include, among others, depression, post-traumatic stress disorder, and neurocognitive deficits. Depression occurs in 12%–30% of HCT survivors and is more frequent in female patients, younger patients and those with poor social support, history of recurrent disease, chronic pain, and chronic GvHD.148 Post-traumatic stress disorder occurs in 28% of patients at six months after HCT and may persist for 5%–13% of cases, although its risk factors are not yet clear.148–150 Neurocognitive deficits, so called “chemo brain”, have adverse functional impacts on HCT survivors who return to work and daily activities that require short-term memory, information-processing speed, multitasking and co-ordination.151 Neuropsychological tests can help identify neurocognitive deficits. Most evidence is derived from studies of breast cancer survivors, with estimated rates of deficits ranging from 16% to 50% up to ten years after treatment.152,153 Potential mechanisms for chemotherapy-induced neurocognitive changes include cytokine and immune dysregulation, damage to DNA and telomere length through cytotoxic agents, oxidative stress and hormonal changes.154 In cases of HCT survivors, there may be additional deficits derived from neurological complications including nervous system infection (HHV-6, fungi, etc.), immune-mediated damage, and toxicities of calcineurin inhibitors such as TMA and posterior reversible encephalopathy syndrome. A prospective observational study showed that neurocognitive function declined substantially at 80 days after HCT, returned to pre-transplantation levels at one year, and continued to improve between one and five years after HCT, except for motor dexterity and verbal learning and retention.155 Mostly mild, neurocognitive dysfunction according to the Global Deficit Score persisted at five years in 42% of long-term survivors.155 Rehabilitation programs have succeeded in improving neurocognitive functions,156 and methylphenidate and modafinil have demonstrated variable efficacies to improve neurocognitive function in non-HCT cancer patients.157,158 Efficacies of these interventions remaine to be determined among HCT survivors. Influence of newer practices on late effects An understanding of the influence of newer practices such as cord blood transplantation, non-TBI or reduced-intensity conditioning regimens and older patients on the incidence and severity of late effects awaits longer follow up. For example, TBI is associated with an increased risk of many late effects such as cardiovascular diseases, COP, hypothyroidism, diabetes, dyslipidemia, infertility, TMA-related kidney injury, bone density loss, avascular necrosis, and secondary solid cancer.49,54,100,102,114,118,143,159,160 The use of non-TBI conditioning regimens might reduce the burden of these late effects among HCT survivors. Some studies found that cumulative incidences of late effects did not differ much after reduced-intensity regimens compared with myeloablative regimens,15,161 and reduced-intensity conditioning was associated with a higher risk of recurrent malignancy among patients with myeloid malignancy.162 One study showed that the risk of AVN was elevated after cord blood transplantation, but graft source had a limited influence on other long-term health status and QOL.163 Consensus guidelines for late effects and prevention behaviors Incidence, mortality, morbidity and management of individual late effects are summarized in Tables 1 and 2. Recognizing the importance of managing late effects after HCT, the Center for International Blood and Marrow Transplant Research (CIBMTR), the European Group for Blood and Marrow Transplantation (EBMT), and the American Society for Bone Marrow Transplantation (ASBMT) developed recommendations in 2006 for screening and prevention practices for HCT survivors.164 Consensus recommendations were up-dated in 2011 including other international transplant communities.21 The NIH convened working groups to formulate late effects initiatives in 2015.148,165–169 View inlineDownload powerpoint Table 1. Late effects after blood and marrow transplantation View inlineDownload powerpoint Table 2. Tests, preventive approaches and treatment of late effects. Despite higher levels of engagement with health care providers, HCT survivors had similar health and prevention behaviors as matched untransplanted controls, suggesting the need for further education of both HCT survivors and health practitioners.170 Major modifiable predictors of lower adherence to preventive care practices were concerns about medical costs and lack of knowledge.171 Conclusion While the number of HCT survivors is growing, there is no evidence that the burden of late effects is lessening. HCT survivors face myriad late effects that can limit their functioning, require prolonged or life-long medical treatment, reduce their quality of life and also shorten their survival. To the extent that the HCT procedure itself causes these late effects, the transplant community has a responsibility to appropriately monitor, treat and ultimately try to prevent late effects. Given the dispersion of survivors and the varied structure of health care, hematologists, oncologists, primary care physicians and medical subspecialists are all involved in providing this care. Further research is needed to understand the biology of late effects to help identify better prevention and treatment strategies

// Pulmonary embolism // Pulmonary embolism is a blockage in one of the pulmonary arteries in your lungs. In most cases, pulmonary embolism is caused by blood clots that travel to the lungs from the legs or, rarely, other parts of the body (deep vein thrombosis). Because the clots block blood flow to the lungs, pulmonary embolism can be life-threatening. However, prompt treatment greatly reduces the risk of death. Taking measures to prevent blood clots in your legs will help protect you against pulmonary embolism. Symptoms Pulmonary embolism symptoms can vary greatly, depending on how much of your lung is involved, the size of the clots, and whether you have underlying lung or heart disease. Common signs and symptoms include: Shortness of breath. This symptom typically appears suddenly and always gets worse with exertion.Chest pain. You may feel like you're having a heart attack. The pain may become worse when you breathe deeply (pleurisy), cough, eat, bend or stoop. The pain will get worse with exertion but won't go away when you rest.Cough. The cough may produce bloody or blood-streaked sputum. Other signs and symptoms that can occur with pulmonary embolism include: Leg pain or swelling, or both, usually in the calfClammy or discolored skin (cyanosis)FeverExcessive sweatingRapid or irregular heartbeatLightheadedness or dizzinessWhen to see a doctor Pulmonary embolism can be life-threatening. Seek immediate medical attention if you experience unexplained shortness of breath, chest pain or a cough that produces bloody sputum. Causes Pulmonary embolism occurs when a clump of material, most often a blood clot, gets wedged into an artery in your lungs. These blood clots most commonly come from the deep veins of your legs. This condition is known as deep vein thrombosis (DVT). In most cases, multiple clots are involved but not necessarily all at once. The portions of lung served by each blocked artery are robbed of blood and may die. This is known as pulmonary infarction. This makes it more difficult for your lungs to provide oxygen to the rest of your body. Occasionally, blockages in the blood vessels are caused by substances other than blood clots, such as: Fat from the marrow of a broken long boneCollagen or other tissuePart of a tumorAir bubblesRisk factors Blood clot in leg vein Although anyone can develop blood clots and subsequent pulmonary embolism, certain factors can increase your risk. Medical history You're at higher risk if you or any of your family members have had venous blood clots or pulmonary embolism in the past. This may be due to inherited disorders that affect blood, making it more prone to clot. In addition, some medical conditions and treatments put you at risk, such as: Heart disease. Cardiovascular disease, specifically heart failure, makes clot formation more likely.Cancer. Certain cancers — especially pancreatic, ovarian and lung cancers, and many cancers with metastasis — can increase levels of substances that help blood clot, and chemotherapy further increases the risk. Women with a personal or family history of breast cancer who are taking tamoxifen or raloxifene also are at higher risk of blood clots.Surgery. Surgery is one of the leading causes of problem blood clots. For this reason, medication to prevent clots may be given before and after major surgery such as joint replacement.Prolonged immobility Blood clots are more likely to form during periods of inactivity, such as: Bed rest. Being confined to bed for an extended period after surgery, a heart attack, leg fracture, trauma or any serious illness makes you more vulnerable to blood clots. When the lower extremities are horizontal for long periods, the flow of venous blood slows and blood can pool in the legs.Long trips. Sitting in a cramped position during lengthy plane or car trips slows blood flow in the legs, which contributes to the formation of clots.Other risk factorsSmoking. For reasons that aren't well-understood, tobacco use predisposes some people to blood clot formation, especially when combined with other risk factors.Being overweight. Excess weight increases the risk of blood clots — particularly in women who smoke or have high blood pressure.Supplemental estrogen. The estrogen in birth control pills and in hormone replacement therapy can increase clotting factors in your blood, especially if you smoke or are overweight.Pregnancy. The weight of the baby pressing on veins in the pelvis can slow blood return from the legs. Clots are more likely to form when blood slows or pools.Complications Pulmonary embolism can be life-threatening. About one-third of people with undiagnosed and untreated pulmonary embolism don't survive. When the condition is diagnosed and treated promptly, however, that number drops dramatically. Pulmonary embolism can also lead to pulmonary hypertension, a condition in which the blood pressure in your lungs and in the right side of the heart is too high. When you have obstructions in the arteries inside your lungs, your heart must work harder to push blood through those vessels. This increases the blood pressure within these vessels and the right side of the heart, which can weaken your heart. In rare cases, small emboli occur frequently and develop over time, resulting in chronic pulmonary hypertension, also known as chronic thromboembolic pulmonary hypertension. Prevention Preventing clots in the deep veins in your legs (deep vein thrombosis) will help prevent pulmonary embolism. For this reason, most hospitals are aggressive about taking measures to prevent blood clots, including: Blood thinners (anticoagulants). These medications are often given to people at risk of clots before and after an operation — as well as to people admitted to the hospital with a heart attack, stroke or complications of cancer.Compression stockings. Compression stockings steadily squeeze your legs, helping your veins and leg muscles move blood more efficiently. They offer a safe, simple and inexpensive way to keep blood from stagnating during and after general surgery.Leg elevation. Elevating your legs when possible and during the night also can be very effective.Raise the bottom of your bed 4 to 6 inches with blocks or books.Physical activity. Moving as soon as possible after surgery can help prevent pulmonary embolism and hasten recovery overall. This is one of the main reasons your nurse may push you to get up, even on your day of surgery, and walk despite pain at the site of your surgical incision.Pneumatic compression. This treatment uses thigh-high or calf-high cuffs that automatically inflate with air and deflate every few minutes to massage and squeeze the veins in your legs and improve blood flow.Prevention while traveling The risk of blood clots developing while traveling is low, but increases as travel increases. If you have risk factors for blood clots and you're concerned about traveling, talk with your doctor. Your doctor might suggest the following to help prevent blood clots during travel: Drink plenty of fluids. Water is the best liquid for preventing dehydration, which can contribute to the development of blood clots. Avoid alcohol, which contributes to fluid loss.Take a break from sitting. Move around the airplane cabin once an hour or so. If you're driving, stop every hour and walk around the car a couple of times. Do a few deep knee bends.Fidget in your seat. Flex your ankles every 15 to 30 minutes.Wear support stockings. Your doctor may recommend these to help promote circulation and fluid movement in your legs. Compression stockings are available in a range of stylish colors and textures. There are even devices, called stocking butlers, to help you put on the stockings.

B/L minimal pleural Effusion under Ix. *Chief Complaints* A 65 yr old Male attended Mopd with chest pain since 1 week . No associated Anginal Equivalent or Respiratory symptoms of cough,SOB,Sputum production, fever. Past H/O Hypothyroidism and post Op Lateral Arachnoid Cyst. No H/O HTN,DM,Substance abuse etc. General Examination and Systemic Examination including Chest was normal. Urgent CXR and ECG was advised. CXR showed obliterated CP angle on both side.ECG was NSR. Later Routine blood IX and USG chest and Abdomen was advised. Pleural fluid was minimal to be tapped. Usg showed left sided pleural Effusion with Splenomegaly. Mantoux test is positive,CRP positive and raised ESR. ATT has been started for 1 month on Trial basis. Let's see how pt responds..other opinions are welcome.