Dr Ranjit Kumar Poriya Homeopathy Very Very Nice Informative Helpful Post Doctor Sub Sexual Dysfunction. Mental Depression Family Economical Problem Long yrs Taken Alcohol Night Hold Chain Smoker, Effects Sexual Dysfunction. Thanks Doctor Rajesh Gupta Ji.
Burning Issues of the 21 Century.
उपयोगी एवं महत्त्वपूर्ण जानकारी दी गई है धन्यवाद देता हूं।
Most powerful and essential information Sir
Very Nice Sharing Doctor.
Amazing Doctor useful Informative subject thank you very much sir
Informative post sir
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Friends today I am again discussing on sexual problem facing by most of the peoples. Sexual Dysfunction Sexual dysfunction refers to a problem(s)that prevents the individual or couple from experiencing satisfaction from sexual activity. Some 43 percent of women and 31 percent of men report some degree of sexual dysfunction. Sexual dysfunction refers to a problem occurring during any phase of the sexual response cycle that prevents the individual or couple from experiencing satisfaction from the sexual activity. The sexual response cycle traditionally includes excitement, plateau, orgasm, and resolution. Desire and arousal are both part of the excitement phase of the sexual response. Sexual dysfunction generally is classified into four categories: Desire disorders —lack of sexual desire or interest in sex Arousal disorders —inability to become physically aroused or excited during sexual activity Orgasm disorders —delay or absence of orgasm (climax) Pain disorders — pain during intercourse Who is affected by sexual dysfunction? Sexual dysfunction can affect any age, although it is more common in those over 40 because it is often related to a decline in health associated with aging. Symptoms of sexual dysfunction? In men: Inability to achieve or maintain an erection suitable for intercourse (erectile dysfunction) Absent or delayed ejaculation despite adequate sexual stimulation (retarded ejaculation) Inability to control the timing of ejaculation (early or premature ejaculation) In women: Inability to achieve orgasm Inadequate vaginal lubrication before and during intercourse Inability to relax the vaginal muscles enough to allow intercourse In men and women: Lack of interest in or desire for sex Inability to become aroused Pain with intercourse Causes of sexual dysfunction Physical causes — Many physical and/or medical conditions can cause problems with sexual function. These conditions include diabetes, heart and vascular (blood vessel) disease, neurological disorders, hormonal imbalances, chronic diseases such as kidney or liver failure, and alcoholism and drug abuse. In addition, the side effects of some medications, including some antidepressant drugs, can affect sexual function. Psychological causes — These include work-related stress and anxiety, concern about sexual performance, marital or relationship problems, depression, feelings of guilt, concerns about body image, and the effects of a past sexual trauma.Dr. Rajesh Gupta3 Likes7 Answers
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*Impotency - Homeopathic Medicines* It is also called Erectyle Dysfunction. Defination - It is abnormal physical or psychological state of a male characterized by inability to engage in sexual intercourse because of failure to have or maintain an erection. *Causes* These include both emotional and physical disorders. An estimated 50 percent of men ages 40 to 70 experience some ED at one time or another. The risk of impotence increases with age. *1. Endocrine Diseases* Diabetes is an example of an endocrine disease that can cause a person to experience impotence. Diabetes affects the body’s ability to utilize the hormone insulin. One of the side effects associated with chronic diabetes is nerve damage. This affects penis sensations. Other complications associated with diabetes are impaired blood flow and hormone levels. *2. Neurological and Nerve Disorders* Several neurologic conditions can increase the risk for impotence. Nerve conditions affect the brain’s ability to communicate with the reproductive system. This can prevent a person from achieving an erection. Neurological disorders associated with impotence include: * Alzheimer’s disease * Parkinson’s disease * brain or spinal tumors * multiple sclerosis * stroke * temporal lobe epilepsy *3. Taking Medications* Taking certain medications can affect blood flow, which can lead to ED Examples of medications known to cause impotence include: * alpha-adrenergic blockers, including tamsulosin (Flomax) * beta-blockers, such as carvedilol (Coreg) and metoprolol (Lopressor) * cancer chemotherapy medications, such as cimetidine (Tagamet) * central nervous system depressants, such as alprazolam (Xanax), diazepam (Valium), and codeine (found in various brand name drugs) * central nervous system stimulants, such as cocaine or amphetamines * diuretics, such as furosemide (Lasix) and spironolactone (Aldactone) * selective serotonin reuptake inhibitors or SSRIs (Prozac, Paxil) * synthetic hormones, such as leuprolide (Eligard) *4. Cardiac-Related Conditions* Conditions that affect the heart and its ability to pump blood well can cause impotence. Without enough blood flow to the penis, a person can’t achieve an erection. Atherosclerosis, a condition that causes the blood vessels to become clogged, can cause impotence. High cholesterol and high blood pressure (hypertension) are also associated with increased risks for impotence. *5. Lifestyle Factors and Emotional Disorders* To achieve an erection, a person must first go through what’s known as an excitement phase. This phase can be an emotional response. If a person has an emotional disorder, this affects their ability to become sexually excited. Depression and anxiety are associated with increased risk for impotence. Performance anxiety can be another cause of impotence. If a person wasn’t able to achieve an erection in the past, he may fear he won’t be able to achieve an erection in the future. Abuse of drugs like cocaine and amphetamines can also cause impotence. Alcohol abuse and alcoholism can affect a person’s ability to achieve or maintain an erection as well. Impotence or Erectile Dysfunction is a condition in which there is a problem in getting or maintaining an erection sufficient for sexual intercourse. Here I am giving few medicines which are most effective may be prescribed according to symptoms. *Agnus Castus 30* 1. There is no penile erection during the sexual act. 2. The penis remain relaxed and flaccid during sex. 3. Penis cold. 4. No desire for sex and decreased physical strength. 5. Erectle dysfunction with history of gonorrhoea. 6. There is sadness and depression. 7. It relieves the sadness, enhancing the desire to have sex and achieving erections. *Caladium 30* 1. No erection but great sexual desire. 2. No erection after an embrace. 4. The penis remains in a relaxed condition and there is no erection. 5. There is a sexual weakness due to mental depression. 6. The erectyle dysfunction is due to tobacco addiction. There is tobacco addiction. *Selenium 200* 1. The erection is too weak and slow. 2. The complete inability to have an erection. 3. The erection is insufficient and remains for a very short period. 4. The pt has sexual desire but they lack of erectyle power. 5 Irritability and excessive weakness after the sexual. 6. Involuntary emission of seminal discharge during sleep. 7. A few may also complain of dribbling of semen while passing stool or urine. *Lycopodium 1M* 1. It is good for both young and pls people. 2. Erectile Dysfunction resulting from excessive masturbation in young person. 3. In elderly people, erectylw dysfunction is after of more indulgence in sexual activity. 4. The desire for sexual act is present but the erection is not adequate. At times, 5. There is premature ejaculation. 6. In old age imperfect erection with prostate enlargement.. *Avena Sativa Q* 1. It can be used as a tonic for enhancing the sexual power of males. 2. This medicine helps in to remove extreme exhaustion and deficient erections. 3. Erectile Dysfunction after overindulgence in sexual activity or masturbation. *Lecithin 3x* Increase the exual desire and also increases the strength of penile erection by supplying more blood to it. *Nux Vomica 200* 1. When the patient has lived a high life with lots of indulgences like wine, women, tobacco and other stimulants, 2. The patient is short tempered and an aggressive. 3. He may have remained under a lot of stress related to his business and trying to achieve whatever he set his sights on. *Tribulus Terrestris ( Iksugandha ) Q* 1. There is presence of urinary troubles along with Erectile Dysfunction. 2. The sexual organs are weak and pain is experienced while passing urine. *Nuphar Luteum 6* 1. Erectile Dysfunction with no sexual desire and relaxed genitalia. Erectile Dysfunction with zero desire for sex. 2. Seminal discharges during passing stool or urine. *Yohimbinum Q* 1. This medicine acts as a agent to increase sexual desire. 2. It is also the best remedy for Neurasthenic Impotency, like lack of interest in sexual activity, deficient erection, extreme weakness, irritability and sadness. *Acid Phos 30* 1. Erectyle dysfunction with diabetes mellitus 2. The sex power is very weak. 3. The genitals are relaxed. 4. Seminal emissions while the pt is asleep. 5. The pt suffers from extreme physical debility and mental exhaustion.. *Moschus 30* *Cuprum Met 30* Impotent due to diabetes. *Agnus Castus and Nuphar Luteum* *Agnus Castus* is the best medicine to increase the the desire to have sex who have complete impotency and a marked aversion to sex *Nuphar Luteum* is used for exactly the same condition as in *Agnus Castus*. But the additional symptom over *Agnus Castus* to increase the sexual desire is the involuntary semen discharge while passing stool or urine or while sleeping.Dr. Sanjay Gupta6 Likes4 Answers
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Friends today I am discussing about #Sexual #Dysfunction in #males. We at Kamla clinic Railway Road Pathankot. Punjab.India. treat such like problems with holistic medicines without any side effect. Sexual Dysfunction in Males The most common problems related to sexual dysfunction in men include ejaculation disorders, erectile dysfunction, and inhibited sexual desire. These and other sexual dysfunction problems can be corrected by treating the underlying physical or psychological causes. What is sexual dysfunction in males? Sexual dysfunction is any physical or psychological problem that prevents you or your partner from getting sexual satisfaction. Male sexual dysfunction is a common health problem affecting men of all ages, but is more common with increasing age. Treatment can often help men suffering from sexual dysfunction. The main types of male sexual dysfunction are: Erectile dysfunction (difficulty getting/keeping an erection) Premature ejaculation (reaching orgasm too quickly) Delayed or inhibited ejaculation (reaching orgasm too slowly or not at all) Low libido (reduced interest in sex) What causes sexual dysfunction in males? Low testosterone levels Prescription drugs (antidepressants, high blood pressure medicine) Blood vessel disorders such as atherosclerosis (hardening of the arteries) and high blood pressure Stroke or nerve damage from diabetes or surgery Smoking Alcoholism and drug abuse Psychological causes might include: Concern about sexual performance Marital or relationship problems Depression, feelings of guilt Effects of past sexual trauma Work-related stress and anxiety How does sexual dysfunction affect men? The most common problems men face with sexual dysfunction are troubles with ejaculation, getting and keeping an erection, and reduced sexual desire. Ejaculation disorders Premature ejaculation (PE) — ejaculation that occurs before or too soon after penetration Inhibited or delayed ejaculation — ejaculation does not happen or takes a very long time Retrograde ejaculation — at orgasm, the ejaculate is forced back into the bladder rather than through the end of the penis The exact cause of premature ejaculation (PE) is not known. While in many cases PE is due to performance anxiety during sex, other factors may be: Stress Temporary depression History of sexual repression Low self-confidence Lack of communication or unresolved conflict with partner Studies suggest that the breakdown of serotonin (a natural chemical that affects mood) may play a role in PE. Certain drugs, including some antidepressants, may affect ejaculation, as can nerve damage to the back or spinal cord. Physical causes for inhibited or delayed ejaculation may include chronic (long-term) health problems, medication side effects, alcohol abuse, or surgeries. The problem can also be caused by psychological factors such as depression, anxiety, stress, or relationship problems. Retrograde ejaculation is most common in males with diabetes who suffer from diabetic nerve damage. Problems with the nerves in the bladder and the bladder neck force the ejaculate to flow backward. In other men, retrograde ejaculation may be a side effect of some medications, or happen after an operation on the bladder neck or prostate. Erectile dysfunction (ED) Erectile dysfunction (ED) is the inability to get and keep an erection for sexual intercourse. ED is quite common, with studies showing that about one half of American men over age 40 are affected. Causes of ED include: Diseases affecting blood flow such as hardening of the arteries Nerve disorders Stress, relationship conflicts, depression, and performance anxiety Injury to the penis Chronic illness such as diabetes and high blood pressure Unhealthy habits like smoking, drinking too much alcohol, overeating, and lack of exercise Low libido (reduced sexual desire) Low libido means your desire or interest in sex has decreased. The condition is often linked with low levels of the male hormone testosterone. Testosterone maintains sex drive, sperm production, muscle, hair, and bone. Low testosterone can affect your body and mood. Reduced sexual desire may also be caused by depression, anxiety, or relationship difficulties. Diabetes, high blood pressure, and certain medications like antidepressants may also contribute to a low libido. Homeopathy Remedies: 1. Angus Castus Angus Castus is considered as the best Homeopathic remedy for erectile dysfunction. It is especially effective for those who have a history of gonorrhea and suffer from depression. It is known as the Homeopathic Viagra and is extremely helpful to those who have no desire or no physical strength to have sex. 2. Caladium Caladium is prescribed when a man is unable to get an erection despite having sexual urge and desire. Even after caressing and intense foreplay, the person will unable to have erection. Caladium is also very helpful to stop tobacco addiction which is one of the leading causes of erectile dysfunction. Even those men with mental problems such as depression may take caladium to get erections. 3. Selenium Selenium is extremely useful for those who have the sexual urge to perform sex but have a very weak and slow erection. Usually the erection stays for a short period and the act of sex leaves the individual extremely weak and irritated. Those men who suffer from dribbling of semen while passing stool can also consume this. 4. Lycopodium Lycopodium is usually the most helpful to elderly people who have sexual urges but suffer from premature ejaculation or are unable to get an adequate erection. It is also very useful for those men (usually young men) who indulge in excessive masturbation or sexual activities. Lycopodium helps enhance sexual power. 5. Nuphar Luteum This is the most effective treatment for those men who have no desire to indulge in any sexual activity. Taking nuphar luteum helps increase vitality and removes problems such as seminal discharge while passing urine or stool.Dr. Rajesh Gupta7 Likes3 Answers
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Friends Many patients have #sexual#Problems but they are hesitant and don't want to share with anyone not even to their Doctor which can lead to many more health problems..so don't be hesitant and no need to worry just contact me for ur problem.... #sexual problems, refers to a problem during any phase of the sexual response cycle that prevents the individual or couple from experiencing satisfaction from the sexual activity. The sexual response cycle has four phases: excitement, plateau, orgasm, and resolution. While research suggests that sexual dysfunction is common (43% of women and 31% of men report some degree of difficulty), it is a topic that many people are hesitant to discuss. Fortunately, most cases of sexual dysfunction are treatable, so it is important to share your concerns with your partner and doctor. What Causes Sexual Problems? Sexual dysfunction can be a result of a physical or psychological condition. Physical causes: Many physical and/or medical conditions can cause problems with sexual function. These conditions include diabetes, heart and vascular (blood vessel) disease, neurological disorders, hormonal imbalances, chronic diseases such as kidney or liver failure, and alcoholism and drug abuse. In addition, the side effects of certain medications, including some antidepressant drugs, can affect sexual desire and function. Psychological causes: These include work-related stress and anxiety, concern about sexual performance, marital or relationship problems, depression, feelings of guilt, and the effects of a past sexual trauma. Who Is Affected by Sexual Problems? Both men and women are affected by sexual problems. They can occur in adults of all ages. Among those commonly affected are seniors, which may be related to a decline in health associated with aging. How Do Sexual Problems Affect Men? The most common sexual problems in men are ejaculation disorders, erectile dysfunction, and inhibited sexual desire. What Are Ejaculation Disorders? There are different types of ejaculation disorders, including: Premature ejaculation -- This refers to ejaculation that occurs before or very soon after penetration. Inhibited or retarded ejaculation -- This is when ejaculation is slow to occur. Retrograde ejaculation -- This occurs when, at orgasm, the ejaculate is forced back into the bladder rather than through the urethra and out the end of the penis. Premature ejaculation, the most common form of sexual dysfunction in men, often is due to nervousness over how well he will perform during sex. In some cases, premature and inhibited ejaculation are caused by a lack of attraction for a partner, past traumatic events, and psychological factors, including a strict religious background that causes the person to view sex as sinful. Certain drugs, including some antidepressants, may affect ejaculation, as can nerve damage to the spinal cord or back. Retrograde ejaculation is common in males with diabetes who suffer from diabetic neuropathy (nerve damage). This is due to problems with the nerves in the bladder and the bladder neck that allow the ejaculate to flow backward and into the bladder. In other men, retrograde ejaculation occurs after operations on the bladder neck or prostate, or after certain abdominal operations. In addition, certain medications, particularly those used to treat mood disorders, may cause problems with ejaculation. This generally does not require treatment unless it impairs fertility.Dr. Rajesh Gupta4 Likes7 Answers
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✍️✍️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 strategiesDr. Ved Srivastava3 Likes6 Answers