Day: 01/19/2023

Post-Transplant Triplet Bests Lenalidomide Maintenance Alone in Myeloma

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Longer PFS with carfilzomib, lenalidomide, and dexamethasone, interim analysis shows

A micrograph of multiple myeloma cells.

Use of a triple-drug maintenance combination appeared to improve progression-free survival (PFS) in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem-cell transplantation, an interim analysis of the phase III ATLAS trialopens in a new tab or window suggested.

In an intention-to-treat analysis, the median PFS was 59.1 months for patients treated with carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) compared with 41.4 months for those treated with lenalidomide alone (HR 0.51, 95% CI 0.31-0.86, P=0.012) at a median follow-up of 33.8 months, reported Andrzej J. Jakubowiak, PhD, of the University of Chicago Medical Center, and colleagues.

In addition, the minimal residual disease (MRD) negativity rate, as evaluated after six treatment cycles, was 53% in the KRd group compared with 31% in the lenalidomide group (P=0.0035), they noted in Lancet Oncologyopens in a new tab or window.

“To our knowledge, this study is the first randomized phase III trial suggesting superiority of an alternative maintenance therapy to lenalidomide alone,” the authors wrote.

“Longer follow-up of ATLAS will allow confirmation of these results and assessment of sustained minimal residual disease negativity, efficacy in patients with high-risk disease, and overall survival,” they added.

At data cutoff, 76% of patients in the KRd group versus 71% in the lenalidomide group reached complete response or better, with no significant difference seen in terms of depth of response.

There were nine deaths in the KRd group and 11 in the lenalidomide group. Jakubowiak and team observed no statistically significant difference in overall survival between the groups.

In an accompanying commentaryopens in a new tab or window, Monika Engelhardt, MD, and Ralph Wäsch, MD, both of the University of Freiburg in Germany, noted that “ATLAS is a key trial suggesting that maintenance approaches with more than one drug, including lenalidomide, should be studied further.”

“These results also align with those of the FORTE trialopens in a new tab or window, in which carfilzomib plus lenalidomide maintenance improved progression-free survival compared with lenalidomide alone after carfilzomib-based induction with or without autologous stem-cell transplantation,” they continued.

Regarding safety, the most common grade 3 and 4 adverse events were neutropenia (48% in the KRd group vs 60% in the lenalidomide group), thrombocytopenia (13% vs 7%), and lower respiratory tract infections (8% vs 1%). Serious adverse events were reported in 30% of patients in the KRd group and 22% in the lenalidomide group.

One treatment-related adverse event led to death — respiratory failure due to severe pneumonia — in the KRd group.

Jakubowiak and colleagues acknowledged that, as expected, there were more toxic effects observed in the KRd group than the lenalidomide-alone group, but with “an acceptable level of safety and tolerability.”

Moreover, they pointed out that “using a minimal residual disease-directed and risk-adapted design, we show that to reduce the number of toxic effects with extended carfilzomib, lenalidomide, and dexamethasone treatment, patients with standard-risk disease who reach minimal residual disease negativity after six cycles of treatment can de-escalate to maintenance with lenalidomide alone while maintaining the benefit conferred by carfilzomib, lenalidomide, and dexamethasone.”

Engelhardt and Wäsch noted that carfilzomib combinations involve more intensive treatment and visits compared with lenalidomide alone, adding that clinicians will need to decide who will benefit from this combination in routine practice.

Additionally, they suggested that questions remain about the best regimen for high-risk patients, treatment length, and which combination doses and schedules should be used.

“Molecular analysis and minimal residual disease assessment to detect those who might benefit most from treatment are required,” they concluded. “Until the primary analysis of ATLAS is available, the interim data suggest that carfilzomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation can be considered.”

ATLAS is an ongoing investigator-initiated, open-label, randomized trial, which is being conducted across 12 centers in the U.S. and Poland among 180 patients with newly diagnosed multiple myeloma. All patients had completed a type of induction and had stable disease or better, had undergone autologous stem-cell transplantation within 100 days, initiated induction 12 months before enrollment, and had an Eastern Cooperative Oncology Group performance status of 0 or 1.

Patients were assigned to KRd (n=93) or lenalidomide alone (n=87) from June 2016 to October 2020. Median age was 59, and 53% were men. Both groups received treatment for up to 3 years (36 cycles). Patients in the KRd group who had no detectable MRD, as well as standard-risk cytogenetics, received lenalidomide alone after completion of cycle eight.

Sodium Nitrite in Food, Water Tied to Type 2 Diabetes Risk

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Observational study serves up “new piece of evidence” for debate over additives

A photo of a plate of a variety of processed meats

Greater daily exposure to nitrites in food and water may increase the risk for type 2 diabetes, French researchers reported.

Compared with those in the lowest tertile of total nitrite exposure (mean 3.3 mg/day), those exposed to the most nitrites — a mean 8.6 mg/day — had a 27% greater risk for type 2 diabetes (HR 1.27, 95% CI 1.04-1.54, P=0.009 for trend), according to Bernard Srour, PhD, PharmD, MPH, of Sorbonne Paris Nord University, and colleagues.

Meanwhile, those in the middle tertile for total nitrite exposure — a mean 5.1 mg/day — did not have a significantly higher type 2 diabetes risk, they wrote in PLOS Medicineopens in a new tab or window.

Essentially the same level of risk was seen when looking at people who fell into the highest tertile for food- and water-originated nitrite exposure compared with the lowest exposure group over a median 7.3-year follow-up (HR 1.26, 95% CI 1.03-1.54, P=0.02).

When looking just at nitrite originating from additives — mostly sodium nitrite e250, which is often used as a color fixer — there was an even stronger relationship between the highest levels of exposure versus the lowest levels (0.56 mg/day vs 0.14 mg/day) with type 2 diabetes risk (HR 1.53, 95% CI 1.24-1.88).

The greatest risk for type 2 diabetes was seen when the researchers restricted the data to just sodium nitrite exposure. People falling into the highest daily exposure to sodium nitrite specifically saw a 54% higher risk for type 2 diabetes than the lowest exposure group (0.47 mg/day vs 0.14 mg/day).

On the other hand, there wasn’t a significant link between any amount of nitrate exposure with type 2 diabetes risk. This included exposure to total nitrates, food and water-originated nitrates, additive-originated nitrates, and potassium nitrate.

“[T]hese results provide a new piece of evidence in the context of current discussions regarding the need for a reduction of nitrite additives’ use in processed meats by the food industry and could support the need for better regulation of soil contamination by fertilizers, as highlighted by the latest report of the French Agency for Food, Environmental and Occupational Health and Safety,” Srour’s group pointed out.

They added that “in the meantime, several public health authorities worldwide already recommend citizens to limit their consumption of foods containing controversial additives, among which sodium nitrite, in the name of the precautionary principle.”

Nitrites are quite pervasive across prepackaged foods. For reference, Srour’s group noted that over 15,000 packaged items currently on the French market contain added nitrites or nitrates.

“Dietary exposure to nitrites and nitrates also includes food additives, as they can be used as preservatives to improve shelf life, also providing a pink coloration to ham and several processed meats,” the authors explained. As for food-originated nitrites, they noted that the most common sources are green leafy vegetables and beetroots, as they’re naturally occurring in water and soil, and also often added for fertilizer.

They acknowledged that fruit and vegetables, and leafy greens in particular, are an important source of nitrites, but that several meta-analysesopens in a new tab or window have shown “low to very low quality of evidence for the association of cruciferous green leafy vegetables with [type 2 diabetes] risk.”

The current analysis drew upon data on 104,168 adults in the French NutriNet-Santé cohort study. The cohort was about 80% female and the average age was 43. Nitrite and nitrate exposure was deduced from 24-hour dietary recalls linked with a food composition database. Over the course of the follow-up period, a total of 969 new cases of type 2 diabetes were identified.

The authors cautioned that no “causal link can be established from this observational study.” Other study limitations included potential selection bias tied to the healthier behaviors of the cohort participants versus the general population.

Higher BMI May Blunt Effects of Vitamin D Supplementation

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In VITAL study, lower increases in total 25-OHD levels seen for those with greater body weight

A photo of a woman holding a glass of water and a vitamin D supplement in her palm.

Weight may be linked to a modified response to vitamin D supplementation, according to a post-hoc analysis of the Vitamin D and Omega-3 Trial (VITAL)opens in a new tab or window.

While supplementation with vitamin D 2,000 IU/day was associated with an increase in serum total 25-hydroxyvitamin D (25-OHD) levels compared with placebo at 2-year follow-up, increases were significantly lower with higher body mass index (BMI; P<0.001), reported Deirdre K. Tobias, ScD, of Brigham and Women’s Hospital in Boston, and colleagues in JAMA Network Openopens in a new tab or window.

Based on data from over 16,000 participants, those with a BMI of 35 or higher had the lowest total 25-OHD levels before randomization (P<0.001 for linear trend):

  • Underweight: 32.3 ng/mL
  • Normal weight: 32.3 ng/mL
  • Overweight: 30.5 ng/mL
  • Obesity class I: 29.0 ng/mL
  • Obesity class II: 28.0 ng/mL

Among the 2,742 participants with repeated blood samples at 2 years, multivariable-adjusted mean total 25-OHD levels were 44 mg/mL for those with a BMI under 25 who received vitamin D supplementation compared with 41.2 ng/mL for those in the 25-29.9 BMI range, and 39.4 ng/mL and 37.9 ng/mL, respectively, for those with class I and II obesity.

This pattern held true for 25-OHD3 (43.8 ng/mL for BMI <25 vs 37.6 for BMI 35+), free vitamin D (10.20 pg/mL vs 7.04 pg/mL, respectively), and bioavailable vitamin D (3.8 ng/mL vs 2.7 ng/mL).

“Increases in vitamin D availability and bioactivity achieved with supplementation may be modestly or moderately diminished with excess adiposity,” Tobias and team wrote. “These trends were also observed among the subgroup of participants with low vitamin D levels at baseline, suggesting that, even when insufficient for vitamin D, obesity may still blunt the response to supplementation.”

This may be due to, at least in part, the “sequestering” of circulating vitamin D and its metabolites into adipose tissue, which may dampen the effectiveness of supplementation, they suggested.

That being said, vitamin D supplementation did not significantly move the needle when it came to vitamin D binding protein, albumin, or calcium levels at 2 years, regardless of BMI. Moreover, parathyroid hormone levels followed the exact opposite pattern — higher baseline levels at higher BMIs.

In an accompanying commentaryopens in a new tab or window, Katherine Bachmann, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, noted that the study “provide[d] novel evidence that responses to vitamin D supplementation may be attenuated in individuals with overweight and obesity,” adding that this may explain some of the different outcomes seen in VITAL.

“This blunted response may also play a role in the diminished benefit of cancer risk reductionopens in a new tab or window observed in individuals with overweight and obesity from the original VITAL,” Bachmann wrote. “Interestingly, the reduction in cancer incidence did not appear to be affected by other plausible predictors, including the presence of baseline vitamin D insufficiency.”

The VITAL study was a randomized, double-blind, placebo-controlled trial for the primary prevention of cancer and cardiovascular disease, which was conducted from July 2010 to November 2018. The current analysis included a subset of 16,515 VITAL participants who provided a blood sample at baseline and a subset of 2,742 participants with a repeated sample at 2-year follow-up.

Mean age was 67.7, 50.7% were women, and 76.9% were white. Participants with overweight (40.5%) or obesity (27.0%) were, on average, younger and more likely to self-report Black race and ethnicity, a lower household annual income, and a lower achieved educational level compared with participants with normal body weight. Participants with obesity were less likely to be physically active or report alcohol intake, but smoking status was similar across BMI levels.

Epstein-Barr Virus Tracking After Liver Transplant May Cut Rare Complication

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Observational study provides suggestive evidence

A photo of a blue rubber gloved hand holding a test tube labeled: EPSTEIN-BARR VIRUS (EBV) TEST

Monitoring Epstein-Barr virus (EBV) levels after liver transplantation to avoid over-immunosuppression showed a signal for less post-transplant lymphoproliferative disease (PTLD) over the long term in an observational study.

Standardized incidence of PTLD was consistently numerically lower over time at a hospital that used EBV monitoring for liver transplant patients compared with one that didn’t, reported Bart van Hoek, MD, PhD, of Leiden University Medical Center in the Netherlands, and colleagues in the Annals of Internal Medicineopens in a new tab or window.

Accounting for decreasing PTLD rates over time by looking at the difference between hospitals for the contemporary period versus a historical period at the same hospital, the estimates ranged from 28.7 to 70.6 fewer incident PTLD cases with monitoring per 1,000 patients over 5 to 15 years of follow-up.

However, none of the differences in differences were statistically significant.

The monitoring strategy hospital had more patients require rejection treatment, especially in the first 3 months after transplantation, compared with the control hospital, “which could be associated with a reduction in immunosuppression,” van Hoek and team noted. However, “all of these rejections were easily treatable and did not lead to graft loss.”

By contrast, PTLD is associated with morbidity and mortality, and is thus of “utmost importance” to avoid, they argued. While EBV infection or reactivation is asymptomatic in most liver transplant patients, approximately 70% of PTLD cases that do occur are related to this highly prevalent virus.

“The current data contradict the conclusion from [a prior retrospective] studyopens in a new tab or window that EBV viremia is benign, and on the basis of the current data, we consider detectable EBV VL [viral load] as a sign of over-immunosuppression, which can lead to B-lymphocyte proliferation and PTLD,” van Hoek’s group wrote.

Despite the limitations of the retrospective observational study, “we strongly believe that the reported results merit serious consideration of the EBV VL monitoring policy in an attempt to reduce the incidence of PTLD after LT [liver transplant] in adults,” they noted. “At least such a strategy seems safe.”

van Hoek and colleagues examined health records for adult recipients of a first liver transplant at Leiden University Medical Center after it started routine EBV DNA monitoring on liver transplant patients in September 2003. The program involved weekly monitoring in the first month after transplantation, biweekly monitoring in the second month, and then monthly or when patients came for additional visits for the rest of the first year. Thereafter, the viral load was measured at least yearly.

The 302 patients treated under the EBV viral load monitoring strategy through January 2017 were compared with 116 historical controls with corresponding transplants from September 1992 until the start of monitoring.

Among the 12% of monitored patients who had two or more positive viral load measurements within 2 months in the first year after transplant, 89% had their immunosuppression regimen reduced as required by the protocol. Of the 21% of the monitored patients with a single positive viral load result followed by an undetectable level on the repeat test, 44% had their immunosuppression reduced based on physician judgment. Altogether, 33% had at least one detectable EBV viral load measurement in the first year, and 60% of this group had their immunosuppression reduced.

After the first year, 25% of patients had at least one positive EBV viral load result, with 46% having their immunosuppressive medication reduced.

Another contemporary control group at a second university medical center who didn’t undergo EBV monitoring included 579 liver transplant patients from September 2003 through January 2017. A fourth group, of historical controls at that center, included 284 patients from 1986 through January 2003.

The historical control group at both centers had numerically but not significantly more PTLD events compared with the contemporary era (crude incidence 25.5 vs 13.3 per 1,000 patients at the control center and 40.4 vs 4.2 per 1,000 at the monitoring center), which the researchers suggested was “likely to be related to less immunosuppression in contemporary versus historical patients, similar to renal transplant.”

Their main results utilized an inverse probability of treatment-weighted number of patients for PTLD, because distributions showed “many influential outliers.” Replacing scores above the 95th percentile with the 95th percentile and those below the fifth percentile with the fifth percentile improved but did not achieve complete balance in initial characteristics.

The cohort had an average age of 46.2 to 53.2 across groups, and 53.2% to 71.9% were men. EBV immunoglobulin G positivity was 96.0% to 99.1%.

Other limitations to the study included the use of persistently detectable EBV viral levels as the threshold for treatment decisions, although the level above which action is required has not been well established and even the same plasma assay analyzed in a different laboratory could generate a different detection limit cutoff, as the researchers noted.

“An EBV VL monitoring strategy with immunosuppression reduction may reduce the incidence of PTLD in other adult patients with long-term immunosuppression and may contribute to tumor surveillance and prevention of other infections; however, future studies should confirm this,” they concluded.

Anti-inflammatory Diets Improve Fertility, Survey Finds

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Can the Mediterranean diet – long popular for its overall wellbeing benefits – also increase fertility?

It’s possible, according to a review of research at Monash University, the University of the Sunshine Coast, and the University of South Australia (UniSA).

The Mediterranean diet promotes eating foods such as whole grains, fish, extra virgin olive oil, vegetables, and nuts, while limiting red and processed meats. Studies have said it lowers the risk of cardiovascular diseases, improves mortality, and helps bring other health benefits.

The new results say that the diet’s anti-inflammatory properties increase conception chances by boosting fertility in men and women.

“Adherence to an anti-inflammatory dietary pattern is generally associated with improved female (menstrual cyclicity, endometriosis-related measures, embryo quality, and live birth) and male (sperm quality) fertility-related outcomes, which are thought to occur through mediation of anti-inflammatory pathways,” says the survey, published in MDPI.

Evangeline Mantzioris, researcher at UniSA, told Men’s Health, “We wanted to see how a diet that reduces inflammation – such as the Mediterranean diet – might improve fertility outcomes.

“Encouragingly, we found consistent evidence that by adhering to an anti-inflammatory diet – one that includes lots of polyunsaturated or ‘healthy’ fats, flavonoids (such as leafy green vegetables), and a limited amount of red and processed meat – we can improve fertility.”

Typical American diets include saturated fats, refined carbohydrates, and animal proteins, Men’s Health says, while lacking fiber, vitamins, and minerals – all associated with higher levels of inflammation.

How to Deal With Mania and Manic Episodes

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If your doctor has diagnosed you with bipolar disorder, you know what a manic episode feels like. To be diagnosed, you must have had at least one episode of mania or its milder form, hypomania.

During these stretches, you may feel fabulous, with lots of energy and an “up” mood. But in the case of bipolar disorder,” those feelings are a symptom of mental illness. So it’s important to recognize the early signs that mania is developing.

Warning Signs

Just because you’re extra-energetic and in a good mood doesn’t mean you’re starting a manic episode. But be aware of patterns, such as when:

  • You feel you’re on top of your life even if it’s not really going well.
  • You have anxiety that can’t be explained by a stressful event, such as an upcoming exam.
  • Your thoughts race and you’re irritable.
  • You’re sleeping less and not taking good care of yourself.
  • You talk too much or faster than usual.
  • Your sex drive is revved up.
  • You turn more often to alcohol or drugs or do other risky things like drive dangerously.

Management

Once you’re in a full-blown manic state, you may not think you need help or be willing to accept it. That’s why the best way to deal with mania is to address it early on.

If you think you’re heading into a manic stretch, first get in touch with your doctor. They may need to change your medication dose or recommend that you try another one.

Take your medicine exactly as your doctor prescribes, even if you don’t think you need it. Tell your doctor about any supplements or herbs you’re taking. They may cause worrisome side effects.

Other things that may help:

  • Review what’s happening in your life and your stress level. See if you can dial back your commitments a bit. If you slow down now, you may avoid having to take more time off later because your symptoms got worse.
  • See a counselor or therapist. If you aren’t already in therapy, find someone who treats people with bipolar disorder. They can help you learn ways to identify and cope with troubling thoughts, emotions, or behavior.
  • Look for ways to relax. When you talk with others, focus on listening. Carve out time to read, listen to your favorite music, or watch a show.
  • Get enough sleep. This is not a time to skimp on your ZZZs. You need at least 6 hours a night.
  • Watch out for caffeine. Steer clear not only of caffeine in beverages, like sodas and energy drinks, but in over-the-counter medications.
  • Stay away from drugs and alcohol. They can affect your mood and may interact with medications you’re taking.
  • Above all, don’t postpone seeking help so you can continue to ride the manic “high.” The higher your manic episode rises, the further your mood may tumble after it ends.

Reducing Risk

Talk to your doctor or therapist about what you should do when you’re already in a manic state. And plan ahead. You might ask trusted friends or relatives to call your doctor if they notice signs of mania.

Here are some practical ways to protect yourself while you’re in a manic episode:

  • Keep up your normal routine. As much as possible, try to maintain a stable daily schedule. This includes your sleep, eating, and exercise patterns.
  • Guard your finances: Limit how much cash you carry. Consider temporarily giving your credit cards to someone you trust to avoid impulse purchases.
  • Delay big decisions. Don’t make any major changes before you talk to someone, such as a mental health clinician or a relative. At the least, give yourself time to reflect before you take action.
  • Bypass risky situations. This isn’t the right time to begin a new relationship or sort through a conflict with a friend.

Prevention

Once you feel better, keep up your healthy habits. That includes exercise, which can improve both mood and sleep. Build up your toolbox of strategies to reduce the intensity of future episodes:

  • Look at what boosts your stress level. Lots of aspects of your life, whether it’s your job or a person you deal with, may affect your mood.
  • Think about what may have been early signs of previous episodes. Was missing sleep for a few nights an early signal? Tell loved ones about those signs so they can watch out for them, too.
  • Track your mood each day. When you keep a daily mood diary, you and your doctor or therapist can look for patterns. How do medication, sleep patterns, and life events affect how you feel?
  • Once your mood is stable, reflect on how mania affects you in good and bad ways. Write down those thoughts. Then you can remind yourself of the downside when you’re tempted to ignore the early signs of mania.

What You Should Know About Bipolar Disorder

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What Is It?

What Is It?

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Sometimes called manic depression, bipolar disorder causes extreme shifts in mood. People who have it may spend weeks feeling like they’re on top of the world before plunging into a deep depression. The length of each high and low varies greatly from person to person.

What the Depression Phase Is Like

What the Depression Phase Is Like

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Without treatment, a person with bipolar disorder may have intense episodes of depression. Symptoms include sadness, anxiety, loss of energy, hopelessness, and trouble concentrating. They may lose interest in activities that they used to enjoy. It’s also common to gain or lose weight, sleep too much or too little, and even think about suicide.

When Someone Is Manic

When Someone Is Manic

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During this phase, people feel super-charged and think they can do anything. Their self-esteem soars out of control and it’s hard for them to sit still. They talk more, are easily distracted, their thoughts race, and they don’t sleep enough. It often leads to reckless behavior, such as spending sprees, cheating, fast driving, and substance abuse. Three or more of these symptoms nearly every day for a week accompanied by feelings of intense excitement may signal a manic episode.

Bipolar I vs. Bipolar II

Bipolar I vs. Bipolar II

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People with bipolar I disorder have manic phases for at least a week. Many also have separate depression phases, too.

Those with bipolar ll have bouts of major depression, but instead of full manic episodes, they have low-grade hypomanic swings that are less intense and may last less than a week. They may seem fine, even like the “life of the party,” though family and friends notice their mood changes.

What's a "Mixed Episode"?

What’s a “Mixed Episode”?

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When people with bipolar disorder have depression and mania symptoms at the same time, or very close together, this is called a manic or depressive episode with mixed features. This can lead to unpredictable behavior, such as taking dangerous risks when feeling hopeless and suicidal but energized and agitated. Mood episodes involving mixed features may be somewhat more common in women and in people who develop bipolar disorder at a young age.

What Are the Causes?

What Are the Causes?

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Doctors don’t know exactly what causes bipolar disorder. Current theories hold that the disorder may result from a combination of genetic and other biological — as well as environmental — factors. Scientists think that brain circuits involved in the regulation of mood, energy, thinking, and biological rhythms may function abnormally in people with bipolar disorder resulting in the mood and other changes associated with the illness.

Who Is at Risk?

Who Is at Risk?

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Men and women both get bipolar disorder. In most cases, symptoms usually start in people who are 15-30 years old. More rarely,  it can begin in childhood. The condition can sometimes run in families, but not everyone in a family may have it.

How It Affects Daily Life

How It Affects Daily Life

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When it’s not under control, bipolar disorder can cause problems in many areas of life, including your job, relationships, sleep, health, and money. It can lead to risky behavior. It can be stressful for the people who care about you and aren’t sure how to help or may not understand what’s going on.

Risky Behavior

Risky Behavior

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Many people with bipolar disorder have trouble with drugs or alcohol. They may drink or abuse drugs to ease the uncomfortable symptoms of their mood swings. Substance misuse also may be prone to occur as part of the recklessness and pleasure-seeking associated with mania.

Suicidal Thinking

Suicidal Thinking

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People with bipolar disorder are 10-20 times more likely to commit suicide than others. Warning signs include talking about suicide, putting their affairs in order, and doing very risky things. If you know someone who may be at risk, call one of these hotlines: 800-SUICIDE (800-784-2433) and 800-273-TALK (800-273-8255). If the person has a plan to commit suicide, call 911 or help them get to an  emergency room immediately. 

How Doctors Diagnose It

How Doctors Diagnose It

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A key step is to rule out other possible causes of extreme mood swings, including other conditions or side effects of some medicines. Your doctor will give you a checkup and ask you questions. You may get lab tests, too. A psychiatrist usually makes the diagnosis after carefully considering all of these things. They may also talk to people who know you well to find out if your mood and behavior have had major changes.

Which Medicines Treat It?

Which Medicines Treat It?

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There are several types of prescription drugs for bipolar disorder. They include mood stabilizers that prevent  episodes of ups and downs, as well as antidepressants and antipsychotic drugs. When they aren’t in a manic or depressive phase, people usually take maintenance medications to avoid a relapse.

Talk Therapy for Bipolar Disorder

Talk Therapy for Bipolar Disorder

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Counseling can help people stay on medication and manage their lives. Cognitive behavioral therapy focuses on changing thoughts and behaviors that accompany mood swings. Interpersonal therapy aims to ease the strain bipolar disorder puts on personal relationships. Social rhythm therapy helps people develop and maintain daily routines.

What You Can Do

What You Can Do

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Everyday habits can’t cure bipolar disorder. But it helps to make sure you get enough sleep, eat regular meals, and exercise. Avoid alcohol and recreational drugs, since they can make symptoms worse. If you have bipolar disorder, you should learn what your “red flags” are — signs that the condition is active — and have a plan for what to do if that happens, so you get help ASAP.

Electroconvulsive Therapy (ECT)

Electroconvulsive Therapy (ECT)

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This treatment, done while you are asleep under general anesthesia, can rapidly improve mood symptoms of  bipolar disorder. It uses an electric current to cause a seizure in the brain. It’s one of the fastest ways to ease severe symptoms. ECT is often a safe and effective treatment option for severe mood episodes when medications have not led to meaningful symptom improvement. It’s a safe and highly effective treatment.

Let People In

Let People In

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If you have bipolar disorder, you may want to consider telling the people you are closest to, like your partner or your immediate family, so they can help you manage the condition. Try to explain how it affects you and what you need. With their support, you may feel more connected and motivated to stick with your treatment plan.

Concerned About Someone?

Concerned About Someone?

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Many people with bipolar disorder don’t realize they have a problem or avoid getting help. If you think a friend or family member may have it, you may want to encourage them to talk with a doctor or mental health expert who can look into what’s going on and start them toward treatment. Be sensitive to their feelings, and remember that it takes an expert to diagnose it. But if it is bipolar disorder, or another mental illness, treatment can help.

How the periodic table survived a war to secure chemistry’s future

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A century ago, the discovery of hafnium confirmed the validity of the periodic table — but only thanks to scientists who stood up for evidence at a time of global turmoil.

Close-up of Hafnium on the periodic table of elements
Hafnium is a transition metal named after the Latin name for Copenhagen (Hafnia), where the element was discovered.

Hafnium isn’t a particularly remarkable element. It’s not your explosive sodium, shimmering mercury or stinky sulfur. It’s a greyish metal and is commonly used as a neutron absorber in the control rods of nuclear power plants and nuclear submarines, and as an insulator in computer chips. But hafnium’s discovery, which was reported in Nature a century ago this week1, was of disproportionate importance. The element was identified by two scientists working in Copenhagen: Dutch physicist Dirk Coster and Hungarian chemist Georg von Hevesy. The find secured not only the periodic table’s legacy but also the future of chemistry. Hafnium also came to represent a hard-won victory against those determined to undermine evidence-based discovery.

Dmitri Mendeleev’s periodic table of elements, created in 1869, emerged from the realization that chemical elements such as oxygen and hydrogen share certain relationships. Mendeleev’s contribution, and that of the German chemist Julius Lothar Meyer, working independently, provided an order for the elements, along with criteria for classifying them into neat groups. Remarkably, both Mendeleev’s and Lothar Meyer’s schemes were based on elements’ subatomic structure — several decades before the discovery of electrons and protons.

When Mendeleev devised the periodic table’s rough form, he started with 63 known elements. To make the table work, he had to leave gaps where as-yet undiscovered elements might be placed. These elements soon began to turn up. For example, the predicted ‘element 68’, gallium, was identified a few years later, in 1875. By 1914, just seven gaps remained.

A breakthrough occurred in 1913, when Henry Moseley, a British physicist, showed that elements could be arranged by their atomic number, or their number of protons. Moseley’s work provided both a more accurate ‘gap map’ and a method for identifying elements from the spectra produced by exposing candidate elements to X-rays.The battle behind the periodic table’s latest additions

But the discovery (and naming) of element 72, hafnium, was anything but straightforward. The French chemist Georges Urbain originally proposed, in 1911, that element 72 belonged among the periodic table’s rare earth elements, and named it celtium. But around a decade later, the Danish physicist Niels Bohr — who used quantum theory to develop a model of the atom in which electrons orbit the nucleus — predicted that element 72 would be among the transition metals, and closer to zirconium (element 40). This was finally confirmed by Coster and von Hevesy — both working at Bohr’s lab in Copenhagen — who searched zirconium minerals for the element2. The duo named their discovery hafnium, after the Latin name for Copenhagen. They obtained the X-ray spectra in December 1922 and their paper1 followed in January 1923.

But this was far from the end of the controversy, because Urbain stubbornly refused to give up, even though he had already had warning that the material he called celtium did not conform to the criteria for element 72. In 1914, Moseley and Urbain had collaborated on an unpublished X-ray study that failed to show that celtium was element 72. Urbain explained this away, saying that the X-ray method was simply not sensitive enough3 — an assessment that the New Zealand-born physicist Ernest Rutherford, writing in Nature, agreed with4. Urbain also suggested that the Copenhagen team were trying to take credit for his work5; in their response, Coster and von Hevesy refused to personalize the dispute and argued on the basis of their results6.

Debate continued, with scientists from the Netherlands, Germany and Scandinavia on the side of the Copenhagen team, while those from France and the United Kingdom (who were backing a boycott of German science in the wake of the First World War) took the counter position. Hafnium was accepted by the International Union of Pure and Applied Chemistry only in 1930, a few years after the boycott formally ended. In France, celtium continued to occupy the place of element 72 among the rare earth elements until the early 1940s2.

One hundred years on from hafnium’s discovery, the periodic table remains both robust and relevant, even at a time when reams of data on an element can be accessed at the click of a mouse. The table offers, at a glance, a reference to how an element might behave in a chemical reaction, and clues to its similarity to other elements in a group.

So far, there are 118 confirmed elements, with the addition of four superheavy synthetic elements in 2015. But a time will surely come when there will be no new elements to make and the periodic table will reach its limits. As yet there is no consensus on when this is likely to happen or how big the last element will be, but chemists say its atomic number could exceed 170.

When that time comes, the periodic table will still remain, a map guiding scientists through the vastness of chemical space — all the molecules that have ever formed, and all those yet to be discovered, whether on Earth or elsewhere in the Universe. It’s a tribute to the enduring values of international scientific cooperation and the steadfastness of researchers that an unremarkable transition metal, discovered 100 years ago in the aftermath of one of the world’s greatest conflicts, made the periodic table what it is today.

Nature

Love Everything, Be Attached To Nothing

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Love Everything, Be Attached To Nothing

“People try to hold on to life because they fear dying. But learning to live isn’t about grasping on to things. It isn’t about clinging to everything and everyone. It’s about learning to let go. Learning to live is learning to let go. Learning to let go is learning to be happy.” ~ Luminita D. Saviuc, 15 Things You Should Give Up to Be Happy

We get so attached to everything we have and everything we do. We get attached to our ideas, our way of doing things, to places, to things and the many people present in our lives, not knowing that being all attached to them will only bring us anguish, sorrow, and suffering.

Learning to Love Everything and Be Attached To Nothing

Many of us can’t seem to grasp this idea of loving everything and being attached to nothing. Years ago I couldn’t understand it either, but as time went by and as I started to ponder upon this idea and as I started to practice it, I got better at it. 

Be attached to nothing.

I am not saying I am at the level where I can have things, where I can move from one place to another, where I can leave or be left by those I love without feeling sad. I really believe it takes time and practice to get there, but I am definitely way better at it than I was years ago.

It will be so much easier if we could appreciate what we have if we could appreciate our friends, our family if we could love all of them without being attached to them. I know it might sound crazy, insane, you name it, but think about it for a second, nothing in this world lasts forever…

Learning to Love Everything and Be Attached To Nothing

The people you love, they will leave you one day; the career you now have, one day it will be gone; the house you live in, one day will no longer be yours; the body you have, your beauty, your youth, they will all be gone eventually, and if that’s the case, why continue to pretend as if you are going to inherit the planet?

“Can you step back from you own mind and thus understand all things? Giving birth and nourishing, having without possessing, acting with no expectations, leading and not trying to control: this is the supreme virtue.” ~ Lao Tzu

You see, most of us want to have many friends, to be loved, have beautiful things, the more expensive the better, to travel to beautiful places, live in big and beautiful houses, etc.. And I can tell you that I want most of these things as well, I want them all, but this isn’t the problem.

The problem is that most of us get so attached to all of these things, attached to all of these people, all of these places, and once we lose them, and one day we will all go through this, we will be heartbroken, devastated, and the pain will be so hard to bear. For me, being so attached to it all is a very dangerous approach to life.

Unfortunately, there are people who aren’t that strong, people who can’t deal with all the pain that comes from losing these things, and they might end up losing their minds, while others, may even end up taking their lives. Isn’t this a tragedy?

This is why we need to understand that nothing lasts forever – people come and go; things come and go. There are days when we will have more, while others when we will have less. There will be days when we will be healthy while others when we might be sick; Days when we might feel safe, and days when we might feel unsafe.

It goes on, and on, and on. You can’t be so attached to it.

We can’t identify ourselves with this world – with what we have and what we don’t have; with what we do and what we don’t do. We can’t identify ourselves with our minds – what we know, because, when we will be without those things when we will no longer do the things we used to do, have the looks we used to have, etc. , we will feel lost, abandoned and empty.

Be Attached to Nothing

If we are what we do then when we don’t we aren’t right?

Don’t you think it’s crazy?

What does this even mean? That when we are born, we are nothing, nobody and as we go along, as we grow older and as we are being shaped by our family, school and society, we start becoming something and somebody?

Does this make any sense to you?

Isn’t it interesting how some of us are considered more valuable just because we were born in a certain part of the world, while others not so valuable? Isn’t it interesting how some of us are seen as being more valuable because of our skin color and the language we speak? The clothes we wear, the friends we have, the schools we go to, the parents we have, etc.?

Why do we do this to ourselves? Why do we put labels on people, things, places, ideas? Why are we so attached to all of this?

I guide my life based on the idea that the way you treat others will determine how others will treat you, and the way you treat life will determine how life will treat you and I try to empathize with others and I try to help as much as I can, whenever I can. I try to keep my mind open and allow new people, new ideas to enter my life, for I believe that they are all teachers of mine.

Learning to Love Everything and Be Attached To Nothing

If a person is sweeping floors for a living while you are the owner of that building, that does not give you the right to be disrespectful to that person. That does not make him less of a person.

You might think it does, but that’s not true. If it were to put you both in a room, naked, no clothes on, who will even know the difference between the rich and the poor, between the special and not so special?

I don’t believe, I KNOW, that we are all born equal, we are all one, and because we think otherwise, we live the life we live, in the world that we live in. We can’t say that we live in a harmonious world.

How can that even be possible, when we are constantly racing with one another?

We are always trying to be better than everybody else, we are always trying to make more money, have bigger houses, bigger cars, expensive things so that we can differentiate ourselves from the not so special ones. More, more, more!

I know people who are so identified with what they do, the places they live in, the clothes they wear, the money they have, that they lost all of their humanity, they lost track of who they really are. This kind of people has won the world but lost their souls.

They think that money, power, fame, and fortune is all that life is about, always looking to gain more, to be better than everybody, to be number one etc., but how many of them are really content with the life they have?

I guess you have all heard the stories of those wealthy people who lost their fortunes, and because of that, they decided to put an end to their lives. This is what happens when you only live for accumulating more, and more, and more, and this is what happens when you identify yourself with all of them.

Where is the peace in that?

These people will never be content no matter how much they accumulate for they will always look to those who have more than they have and they will feel that they don’t have enough… living with the fear of losing it all.

I personally am working on being content with who I am at the moment, with what I do and what I have, and I will express my gratitude for everything I have achieved so far, for the wonderful people that are present in my life and for the wonderful people that keep on showing up, for the wonderful person I have become, and I will try to love myself, I will try to love the people who are present and not so present in my life, and I will work on giving up on my being attached to them because I now understand that this is for my own good.

“Things arise and she lets them come; things disappear and she lets them go. She has but doesn’t possess acts but doesn’t expect.” ~ Lao Tzu

Now, it is up to you to decide whatever you think it’s best for you.

Love everything and remember, be attached to nothing.

An mRNA vaccine boost may help CAR T-therapy treat solid cancers

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CAR T-therapy CAR T-cells immunotherapy

While CAR T-therapy has cured some people with blood cancers, this form of immunotherapy has so far produced lackluster results for solid tumors like lung or kidney cancer. But a new early-phase clinical trial presented on Sunday at the American Association for Cancer Research (AACR) conference suggests that CAR T-cells may be able to shrink some solid tumors — as long as it gets a boost from an mRNA vaccine from BioNTech.

BioNTech became a household name thanks to the Covid-19 vaccine it developed with Pfizer. Before the pandemic emerged, the company was a relatively small biotech firm focused on developing mRNA vaccines for treating cancer. Today it’s valued at $42 billion, based on its stock price, and the new data show a preliminary look at how its technology might develop new cancer treatments.

CAR T-cells use chimeric antigen receptors to sense and destroy cancer cells. These engineered receptors attach to a protein on a cancer cell’s surface. Once bound, the CAR can trigger its T-cell to kill the cancer cell. In the work presented at the AACR meeting, researchers used a target called claudin-6, which is commonly found on testicular, ovarian, and endometrial cancer cells, explained John Haanen, a cancer immunotherapy researcher at the Netherlands Cancer Institute and lead author on the study. That enables the CAR T-cell to see and attack these cancer cells.

The new treatment from BioNTech requires a two-stage process. First, a patient is infused with CAR T-cells that can recognize and attack the cancer. A few days later the patient is given the mRNA vaccine, which carries the genetic code for claudin-6. The idea is that immune cells known as antigen-presenting cells will take up the vaccine, produce claudin-6, and then present the protein to the CAR T-cells circulating in the body. That will trigger the engineered T-cells to begin proliferating and producing cytotoxic compounds that can kill cancer cells.

In a press release from AACR, the investigators said that patients received the mRNA vaccine periodically throughout the study after CAR T infusion.

The idea behind the mRNA vaccine, Haanen said in his AACR presentation, was to expand the initial population of CAR T-cells and remain at a high level and in a heightened state of activity. That should help the engineered cells get into a tumor and persist there, killing cancer cells. Based on the early results, Haanen said that appears to have happened. Among 16 patients treated in the study, 14 were evaluated for efficacy and, of those, six saw their tumors shrink or disappear, Haanen said.

“I was quite skeptical at first because CAR T-therapy hadn’t worked before in solid tumors, so we were very excited to see how the metastases disappeared and the patients improved,” Haanen said. “These patients had a wonderful partial response, and one patient had a complete remission that is still ongoing, lasting now for almost six months.”

It’s preliminary work but promising, said Henry Fung, the chair of bone marrow transplant and cellular therapies at Fox Chase Cancer Center in Philadelphia, who was not involved in the trial. “CAR T-cell therapy has become the standard of care for selected patients with [blood cancers,]” Fung said in a statement emailed to STAT. “Prior studies for solid tumors were disappointing. Here, a CAR T-cell product targeting claudin-6 is novel and demonstrated promising results in selected solid tumors — though the impact on outcomes remains unclear.”

Using an mRNA vaccine to augment a patient’s CAR T-cell population is an idea that might well carry into future work in cell therapy, Kristin Anderson, a cell therapy researcher at the Fred Hutchinson Cancer Center who did not work on the trial, told STAT. “Part of the problem with cell therapy in solid tumors is you do all this work to engineer T cells and then they might not get in and infiltrate tumors. But then, if they do, they won’t last long,” she said. “So it’s exciting to see that they have an opportunity to boost their engineered cells in vivo.”

But there are unanswered questions in this research, Anderson added. For one, the results are too early to be able to properly evaluate the clinical efficacy of this approach, she said. A larger number of participants will need to be followed for longer in a more in-depth Phase 2 trial. And while the researchers didn’t see severe toxicity in this initial trial, it’s possible that more toxic side effects could emerge in larger and longer studies, particularly since the patients in this Phase 1 trial showed mild signs of pancreatic toxicity. In rare cases, claudin-6 has been found on healthy adult tissues, including the pancreas.

When the question of off-tumor toxicity was posed to Haanen at AACR, he agreed that the possibility exists. “We don’t know what would happen if we treat patients with a higher dose,” he said. “That is something we still have to learn.”

Cell therapy may also need additional power-ups other than just an mRNA vaccine boost to fully clear cancer for many patients, Anderson added. “I don’t know if just boosting will be sufficient. It’s not to clear tumors from many mouse models in late disease,” she said, raising the possibility that solid tumors may need to be hit harder by combining cell therapy with other immunotherapy drugs to generate deeper responses for many patients.