For over 15 years, Dr Anthony Shum, a pulmonologist at the University of California, San Francisco has been studying a rare genetic disorder called the COPA Syndrome. It stands for coatomer subunit alpha and is a rare, inherited disorder that affects the lungs, joint, and kidney. The National Organization for Rare Disorder also notes that it is a genetic autoimmune disorder that is caused by mutations in the COPA gene. This disease affects families unpredictably—some individuals with the mutation develop severe lung damage early in life, while others remain completely healthy. Now, Shum’s team has discovered a protective genetic variant that may offer new hope for treatment.

A Breakthrough

Researchers found that some relatives of COPA Syndrome patients stayed healthy despite carrying the same COPA gene mutation that causes the disease. The key difference? These unaffected individuals had a protective version of another gene called HAQ-STING.

When scientists introduced HAQ-STING into diseased lung cells from COPA patients, the cells returned to a balanced state, suggesting that this gene could be used as a therapy.

“We really think HAQ-STING could be a gene therapy tool and a step toward a cure,” said Shum, whose findings were published in the Journal of Experimental Medicine.

Families Who Solved The Mystery

Shum’s journey into COPA Syndrome research began in 2011 when he treated a young woman, Letasha, who had severe lung bleeding. Her mother, Betty Towe, mentioned that Letasha’s sister, Kristina, had suffered from similar symptoms. Over the years, Betty had taken both daughters on a four-hour trip to UCSF for treatment. After tracing their family history, Shum discovered that their distant relatives in Texas and Oakland also had lung problems and arthritis. In 2015, Shum, along with scientists from Baylor College of Medicine and Texas Children’s Hospital identified the COPA gene mutation. They realized that it was the common factor behind the illness. However, only some of the 30 individuals with the mutation actually developed symptoms, leaving a major question unanswered.

The Domino Effect

It was established that it occurs when a mutated COPA gene causes another gene STING to go overdrive. The STING that helps fight infections in COPA patients, remain permanently active, which leads to chronic inflammation that damages the lungs, kidneys, and joints. In 2020, while studying STING’s role in the disease, researchers discovered a key variation: HAQ-STING. This version of STING, present in about one-third of the population, appeared to neutralize the harmful effects of the COPA mutation.

To confirm their theory, the scientists needed both affected and unaffected family members to participate in the testing. Letasha, Kristina and Betty immediately volunteered. The researchers then analyzed DNA samples from 26 COPA patients and their healthy relatives. They also conducted CT scans and blood tests to ensure that unaffected members did not have any hidden symptoms. When the findings were all clear, it was revealed that all the healthy individuals had HAQ-STING, while none of the COPA patients did. This was the first known case of a common gene variant completely protecting against a severe genetic disease.

Encouraged by this discovery, researchers tested HAQ-STING’s effects in a lab setting. They introduced it into diseased lung cells from COPA patients, and the cells returned to normal function.

Way Ahead

Shum believes HAQ-STING could lead to game-changing treatments, including:

• Prenatal gene therapy for babies diagnosed with COPA Syndrome before birth
• Aerosol delivery of HAQ-STING for adults, directly targeting the lungs

Before publishing their findings, Shum called Betty with the news—her own HAQ-STING gene had protected her from the disease. He also informed Letasha and Kristina, who were overwhelmed with relief and joy.

“We always believed Dr. Shum would get to the bottom of it,” said Letasha. “This discovery is going to change lives.”

Melanoma is often considered one of the more challenging cancers to treat, particularly when it has spread to distant organs. For early-stage disease, surgery remains an important treatment option. But once melanoma reaches stage IV, treatment becomes considerably more complex.

Understanding The Biology Of Advanced Melanoma

According to Dr. Mandeep Singh Malhotra, Cheif Mentor AOHC, cytotoxic chemotherapy has traditionally had a limited role in melanoma, while immunotherapy has changed the treatment landscape for many patients.

When melanoma is detected at an early stage and can be completely removed, surgery is generally considered the preferred treatment. Depending on the disease, this can involve removal of the primary tumour and assessment or treatment of regional lymph nodes.

But stage IV melanoma presents a very different challenge.

A Complex Case With Multiple Tumour Sites

Dr. Malhotra recalls the case of Sarah, who came to the team with multiple nodules in the scapular region. There were also lesions on both legs and a lesion in the pancreas. So there were multiple nodules. One in the right side of the leg, another in the left side of the leg. And there was a lesion in the pancreas.

Rather than relying on a standard treatment approach alone, the team first tried to understand the biology of the disease. As a standard protocol for this type of case, we first try to understand the disease biology. In Sarah’s case, the team used extensive testing, including chemosensitivity testing, transcriptomic analysis and next-generation sequencing.

Also read: Cancer Should Be Made Notifiable In India, Say Experts: Here’s Why

When Imaging Initially Suggests Progression

The results suggested sensitivity to certain drugs. When we analysed those reports, we were able to understand that cytotoxic drugs like temozolomide were effective. And checkpoint inhibitors like pembrolizumab, nivolumab were effective.

Based on these findings, the team developed a treatment protocol in which the main component was an immune checkpoint inhibitor along with low-dose temozolomide. Other agents, including lower doses of anti-VEGF, anti-FGF and CDK inhibitors, were also incorporated based on the analysis.

After around four weeks, the response became difficult to interpret on imaging. The PET scan suggested that all the lesions have had a pseudo progression.

Pseudo progression is a recognised phenomenon during immunotherapy. A tumour may appear larger initially because of immune-cell infiltration, even when the treatment is actually producing an anti-tumour response.

This is particularly relevant in melanoma treated with immune checkpoint inhibitors. However, doctors cannot simply assume that every apparent progression is pseudo-progression; true progression must also be considered and confirmed through Histopathology

Also read: French Court Links Flight Attendant’s Breast Cancer To Workplace Radiation; How Does Flying Increase Cancer Risk?

Histopathology Reveals A Dramatic Treatment Response

The team then proceeded with surgery, removing the nodules from the scapular region and both thighs. The specimens were sent for histopathological examination. And histopathology results were amazing. The tumours had gone necrotic.

The pathology showed extensive treatment-related changes, with inflammation and fibrosis around the nodules and only small areas containing viable melanoma cells.

Also read: _{Daraxonrasib: US FDA Approves Once-Daily Pill for Metastatic Pancreatic Cancer}

What Comes Next For The Patient?

For now, the plan is to continue the treatment for a few more cycles and then reassess the pancreatic lesion. The team is considering NanoKnife (irreversible electroporation) for the pancreatic lesion followed by Vaccines.

Certain cancer vaccines are being developed in certain labs in Germany and Europe and they are available for our patients in India on compassionate grounds. It's a very, very good response. And to achieve disease NED in stage four melanoma, I think we are really lucky and it's all due to the grace of God.

Why Individualised Treatment Matters In Stage IV Disease

The case also highlights an important point about advanced melanoma: treatment may need to be individualised according to the biology of the disease and the patient's response. At the same time, he stresses the need for hope. I hope that more people can benefit from this protocol and use this protocol to treat melanomas across the world.

For Sarah, the journey is still ongoing. The next step will be to reassess the pancreatic lesion and determine whether further local treatment can help achieve no evidence of disease (NED). A stage IV melanoma involving multiple sites, including the pancreas, reaching a point where NED may become a possibility is certainly an encouraging development. But it remains an individual clinical experience, rather than proof that the same protocol will work for every patient with metastatic melanoma.

By Dr. Mandeep Singh Malhotra, Director of Surgical Oncology at CK Birla Hospital and Chief Mentor at AOHC

People living with obesity and diabetes often feel healthy in their day-to-day life, but some of the most dangerous changes may be happening silently inside their bodies.

The liver is one of the first organs to be affected. In many cases, fat slowly accumulates in the liver without causing any pain, discomfort, or obvious symptoms. This is why fatty liver disease is often called a “silent condition.” By the time it is detected, it may already have progressed to an irreversible stage.

Excess body fat, particularly around the abdomen, disrupts how the body processes sugar and fats, placing continuous stress on the liver. Because of this silent progression, experts now strongly recommend that people living with obesity and type 2 diabetes should proactively check their liver health, even when they feel completely well.

Obesity is closely linked with liver damage through a series of metabolic changes that develop over time. When the body becomes resistant to insulin, fat begins to accumulate in liver cells, triggering inflammation and gradual injury.

If this continues unchecked, the condition can progress from simple fat accumulation to more serious stages, including metabolic dysfunction-associated steatohepatitis (MASH), where inflammation and liver cell damage become more significant.

Over time, this may lead to fibrosis (scarring of the liver), and in advanced cases, cirrhosis, which can severely affect liver function. Further, patients with fatty liver may directly present with liver cancer, which can occur in up to 20% of patients.

How Common Is Fatty Liver In People With Diabetes And Obesity?

In India, the burden of metabolic dysfunction-associated steatotic liver disease (MASLD) or fatty liver is rising and is now recognised as a common metabolic condition. Studies from the Indian subcontinent estimate that 1 in 3 people may have MASLD. Fatty liver is particularly common among individuals with metabolic risk factors.

It is seen in nearly 40–80% of people with type 2 diabetes and 30–90% of those with obesity, often without clear symptoms.iv Hospital-based trends also suggest increasing detection in younger age groups, reflecting changes in diet, reduced physical activity, and more sedentary lifestyles.

Also read: Post-Menopausal Women Face A Higher Risk Of Fatty Liver Disease: How Falling Estrogen Levels Impact Liver Health

What Liver Checks And Preventive Measures Should You Follow?

Preventive measures to be followed:

• If you live with excess weight/obesity and type 2 diabetes or PCOS (polycystic ovarian syndrome) or dyslipidemia, seek early consultation with a physician or hepatologist.

• Your doctor may request routine metabolic screening:

• Regular liver function tests as part of annual health check-ups

• Ultrasound screening for individuals with obesity or diabetes

• Monitoring blood sugar, cholesterol, and triglyceride levels

• Liver scarring scan (annually for patients with diabetes/obesity)

• Avoiding long-term neglect of “mild” or borderline test results

Also read: From Liver Inflammation to Cancer: When Hepatitis Becomes a Serious Warning Sign

With rising obesity rates in India, early liver screening should become a routine part of preventive healthcare. Even modest weight reduction, improved diet quality, and regular exercise (approximately 150 minutes per week of moderate-intensity exercise (example: brisk walking, gardening, swimming, cycling) or 75 minutes of vigorous exercise (example: weight training) can significantly reduce liver fat and inflammation within 3-6 months.

However, once the disease progresses to MASH or fibrosis, reversal becomes more difficult and may require long-term medical management. Early-stage fatty liver disease is reversible in many cases. In fact, medications can even reverse liver fibrosis (early scarring), but in only 25% of patients. Simple homemade food is sufficient to prevent these lifestyle diseases, and there is no need for “fancy online diets or supplements”.

Our forefathers lived longer by consuming homemade food and water without any supplements. Newly approved therapies such as semaglutide (GLP1 analogues) have been shown to resolve steatohepatitis and reduce liver fibrosis. These liver benefits do not appear to be explained solely by weight loss, suggesting a broader potential impact on liver health.

The absence of symptoms does not mean the absence of risk. Taking care of the liver early is not just about preventing disease; it is about protecting long-term health, energy, and quality of life.

By Dr. Anand V. Kulkarni, Senior Consultant Hepatologist & Director – Critical Care Hepatology, AIG Hospitals, Hyderabad

There is a conversation that comes up in almost every consultation, and it is rarely the one the patient came prepared for. After graft numbers, hairline design, cost and downtime have been discussed, the question of smoking and drinking inevitably follows — and the answer is usually a shrug: occasionally, socially, nothing serious.

Yet of all the variable that determines what a patient sees in the mirror eighteen months later, these two are among the very few fully within their control, and among the most underestimated.

What Smoking and Alcohol Do to the Scalp

The hair follicle is one of the most metabolically demanding structures in the body, dividing faster than almost any other cell population and depending entirely on a dense network of microscopic vessels feeding its base. Nicotine constricts those vessels; over years, repeated narrowing combined with low-grade inflammation contributes to perifollicular fibrosis — scarring that gradually chokes the follicle.

Alcohol takes a different route, depleting the zinc, iron, folate, B12 and protein hair is built from, while fragmenting sleep and raising cortisol — both of which push follicles prematurely into their resting phase. For a transplant candidate, this matters twice over: it reflects donor-area quality, and it signals the kind of healing environment the grafts are about to enter.

Also read: The Hidden Health Risk of Sitting for Long Hours: What Young Professionals Need to Know

Why the First Week After Surgery Is So Critical

For the first few days after surgery, a transplanted follicle is essentially cut off from its blood supply, surviving on nutrients diffusing in from surrounding tissue.

New capillaries begin connecting around day four or five, with full revascularisation taking seven to ten days — the most vulnerable window in the graft's life. Smoking attacks it from two directions: nicotine causes sustained vasoconstriction after every cigarette, while carbon monoxide binds haemoglobin more readily than oxygen, so the reduced blood reaching the scalp also carries less oxygen.

The result is rarely dramatic — just poorer graft survival, patchier density, and a final outcome thinner than the graft count promised. Patients often read this as bad luck; it usually isn't. Notably, this applies equally to vaping, hookah and smokeless tobacco like gutkha or khaini — the delivery method changes, but the nicotine doesn't.

Also read: Ozempic/Wegovy Vs Zepbound/Mounjaro: Which Weight Loss Drug Is More Likely To Cause Hair Loss? Study Finds

Alcohol's More Immediate Risk

Alcohol's damage is more mechanical. It causes vasodilation and impairs clotting, meaning patients who've been drinking beforehand bleed more during surgery — which makes graft placement less precise and can dislodge grafts already sited.

Afterward, the same vasodilation worsens normal post-op swelling, its diuretic effect fights the hydration healing tissue needs, and its immune-suppressing effect arrives just as the scalp carries thousands of small open wounds. There's a medication risk too: alcohol combined with post-op antibiotics, anti-inflammatories or steroids raises the chance of gastric irritation or a genuinely unpleasant systemic reaction.

Recommended Windows

For smoking: stop at least two weeks before surgery (four is better), and stay off it for two weeks to a month afterwards — the long lead-in accounts for how slowly small-vessel and immune function normalise, and the long tail covers graft revascularisation.

For alcohol: stop five to seven days before, and avoid it for ten to fourteen days after, or as long as medication continues, since its effects reverse faster. One caveat worth repeating: patients often say they've "stopped" when they've merely cut back. A single cigarette produces measurable scalp vasoconstriction — in this window, occasional isn't the same as fine.

Also read: Love Travelling? Here's How Flying Frequently Impacts Your Health

The Myth That Lifestyle Stops Mattering

A costly misconception is that once surgery is done, lifestyle no longer matters. It's a half-truth: transplanted follicles, taken from the DHT-resistant back and sides of the scalp, are permanent and won't miniaturise. But a transplant only redistributes existing hair — every native follicle remains susceptible to ongoing loss.

If that native hair keeps thinning, overall density falls even though every graft survives, and patients often mistake this for transplant failure. In reality, the surroundings have receded, accelerated by smoking, poor sleep, chronic stress and poor nutrition. Surgery buys a foundation; lifestyle determines how long the picture around it holds.

Practical Guidance

Honesty at consultation matters — knowing a patient smokes heavily changes the surgical plan toward more conservative density and staging, which protects the result. The pre- and post-op window should be treated as non-negotiable, even if permanent quitting feels distant; a defined four-week commitment is far more achievable than an open-ended one.

Switching to vaping or nicotine gum isn't automatically safe — it removes carbon monoxide and tar, but nicotine, the actual vasoconstrictor, remains, so replacement therapy should be discussed with the surgeon. Fundamentals also help: adequate protein, iron and vitamin D, seven to eight hours of sleep, hydration, and gentle movement once cleared.

Turning Surgery into Leverage

Finally, surgery itself can be motivating. Patients who've just invested significant money and recovery time in their appearance are often more driven to quit than at any other point in

By Dr. Harikiran Chekuri, Hair Transplant Surgeon, Founder and Chief Plastic Surgeon, Redefine Hair Transplant & Plastic Surgery Center