Lung cancer immunotherapy: progress, pitfalls, and promises.

Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are gaining ground in the treatment of lung cancer. Recent advances in adoptive cell therapy (CAR T, TCR, TIL), the associated clinical trials on lung cancer, and associated hurdles are discussed in this review. Recent trials on lung cancer patients (without a targetable oncogenic driver alteration) reveal significant and sustained responses when treated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint blockade immunotherapies. Accumulating evidence indicates that a loss of effective anti-tumor immunity is associated with lung tumor evolution. Therapeutic cancer vaccines combined with immune checkpoint inhibitors (ICI) can achieve better therapeutic effects. To this end, the present article encompasses a detailed overview of the recent developments in the immunotherapeutic landscape in targeting small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Additionally, the review also explores the implication of nanomedicine in lung cancer immunotherapy as well as the combinatorial application of traditional therapy along with immunotherapy regimens. Finally, ongoing clinical trials, significant obstacles, and the future outlook of this treatment strategy are also highlighted to boost further research in the field.

Consensus guidelines for the management of HR-positive HER2/neu negative early breast cancer in India, SAARC region and other LMIC by DELPHI survey method.

BACKGROUND: Precise prognostication is the key to optimum and effective treatment planning for early-stage hormone receptor (HR) positive, HER2/neu negative breast cancer patients. Differences in the breast cancer incidence and tumor anatomical features at diagnosis, pharmacogenomics data between Western and Indian women along with the vast diversity in the economic status and differences in insurance policies of these regions; suggest recommendations put forward for Western women might not be applicable to Indian/Asian women. Opinions from oncologists through a voting survey on various prognostic factors/tools to be considered for planning adjuvant therapy are consolidated in this report for the benefit of oncologists of the sub-continent, SAARC and Asia's LMIC (low and middle-income countries). METHODS: A three-phase DELPHI survey was conducted to collect opinions on prognostic factors considered for planning adjuvant therapy in early-stage HR+/HER2/neu negative breast cancer patients. A panel of 25 oncologists with expertise in breast cancer participated in the survey conducted in 2021. The experts provided opinions as 'agree' or disagree' or 'not sure' in phases-1 and 2 which were conducted virtually; in the final phase-3, all the panel experts met in person and concluded the survey. RESULTS: Opinions on 41 statements related to prognostic factors/tools and their implications in planning adjuvant endocrine/chemotherapy were collected. All the statements were supported by the latest data from the clinical trials (prospective/retrospective). The statements with opinions of consensus less than 66% were disseminated in phase-2, and later in phase-3 with supporting literature. In phase-3, all the opinions from panelists were consolidated and guidelines were framed. CONCLUSIONS: This consensus guideline will assist oncologists of India, SAARC and LMIC countries in informed clinical decision-making on adjuvant treatment in early HR+/HER2/neu negative breast cancer patients.

Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic- or accelerated-phase chronic myeloid leukemia: Results with 24 months of follow-up.

BACKGROUND: Omacetaxine, a protein synthesis inhibitor, is indicated in the United States for the treatment of patients with chronic-phase (CP) or accelerated-phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors. METHODS: The final analysis, with 24 months of follow-up, included additional efficacy and safety analyses to assess the benefit of long-term omacetaxine administration (1.25 mg/m(2) twice daily for 14 days every 28 days followed by 7 days every 28 days) in CP-CML and AP-CML patients receiving >3 cycles. RESULTS: Eighteen percent of CP-CML patients achieved a major cytogenetic response (MCyR) with a median duration of 12.5 months (95% confidence interval [CI], 3.5 months to not reached [NR]); responses were maintained for ≥12 months in 3 of 14 responders, and the median overall survival (OS) was 40.3 months (95% CI, 23.8 months to NR). Among patients with AP-CML, 14% achieved or maintained a major hematologic response for a median of 4.7 months (95% CI, 3.6 months to NR); MCyR was not achieved, and the median OS was 14.3 months (95% CI, 6.7-18.7 months). In patients with CP-CML and patients with AP-CML who received >3 cycles of treatment (n = 50 and n = 14, respectively), the median OS was 49.3 months (95% CI, 23.8 months to NR) and 24.6 months (95% CI, 12-37.2 months), respectively. Grade 3 or higher hematologic toxicities were the major side effects (79% and 73% for CP-CML and AP-CML, respectively), with discontinuation due to toxicity in 10% of CP patients and in 5% of AP patients. CONCLUSIONS: These results suggest that the long-term administration of omacetaxine is feasible with dose adjustments to manage toxicities and that omacetaxine provides a durable benefit for some patients.

Regional variation in identified cancer care needs of early-career oncologists in China, India, and Pakistan.

BACKGROUND: Cancer incidence and mortality is increasing in the developing world. Inequities between low-, middle-, and high-income countries affect disease burden and the infrastructure needs in response to cancer. We surveyed early-career oncologists attending workshops in clinical research in three countries with emerging economies about their perception of the evolving cancer burden. METHODS: A cross-sectional survey questionnaire was distributed at clinical trial concept development workshops held in Beijing, Lahore, Karachi, and Mumbai at major hospitals to acquire information regarding home-country health conditions and needs. RESULTS: A total of 100 respondents participated in the workshops held at major hospitals in the region (India = 29, China = 25, Pakistan = 42, and other = 4). Expected consensus on many issues (e.g., emergence of cancer as a significant health issue) was balanced with significant variation in priorities, opportunities, and challenges. Chinese respondents prioritized improvements in cancer-specific care and palliative care, Indian respondents favored improved cancer detection and advancing research in cancer care, and Pakistani respondents prioritized awareness of cancer and improvements in disease detection and cancer care research. For all, the most frequently cited opportunity was help in improving professional cancer education and training. CONCLUSION: Predominantly early-career oncologists attending clinical research workshops (in China, India, and Pakistan) identified needs for increasing clinical cancer research, professional education, and public awareness of cancer. Decision makers supporting efforts to reduce the burden of cancer worldwide will need to factor the specific needs and aspirations of health care providers in their country in prioritizing health policies and budgets.

Challenges to effective cancer control in China, India, and Russia.

Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement.

Neuralink and Brain-Computer Interface-Exciting Times for Artificial Intelligence.

Purvish Mahendra ParikhBrain-computer interfaces are becoming a tangible reality, capable of significantly aiding patients in real-world scenarios. The recent approval by the U.S. Food and Drug Administration for clinical human trials of Neuralink marks a monumental stride, comparable to Mr. Armstrong's moonwalk. Numerous other companies are also pioneering innovative solutions in this domain. Presently, over 150,000 patients in the United States possess brain implants. As technology advances, it holds the potential to alleviate various conditions, notably motor paralysis, cerebral palsy, and involuntary movements.

Practical Consensus Guidelines for the Use of S-1 in GI Malignancies.

Purvish M ParikhS-1 (5-fluorouracil prodrug [tegafur] in combination with 5-chloro-2,4-dihydroxypyridine [CDHP] and potassium oxonate [OXO]) was first approved in 1999. In order to make it easy for community oncologists, we decided to put together this expert consensus guideline for its use in gastrointestinal (GI) malignancies. A total of 15 subject matter experts used modified Delphi method to discuss, analyze, and vote on key aspects regarding practical approach to use of S-1 in GI cancers, a process involving 6 months of work. The consensus guidelines specify how S-1 use can be optimized in patients with colorectal, gastric, and pancreatic tumors. The voting for the 17 key points resulted in a majority consensus for all the statements (approval ranging from 13/15 [87%] to 15/15 [100%]). S-1 is a combination of three drugs (tegafur, CDHP, and OXO) specifically designed to reduce toxicity and enhance efficacy; clinical data and meta-analysis confirm both factors; and it is recommended as standard of care for GI cancers. S-1 is approved and one of the standards of care for all lines of therapy in colorectal cancer and pancreatic cancers. S-1 with oxaliplatin is the standard of care for gastric cancers.

Ayurvedic Doctors Cannot Prescribe Allopathic Medicines-National Consumer Dispute Redressal Commission Judgement.

Purvish M. ParikhWe describe the facts of the matter and the court's decision in a case of an Ayurveda, Yoga & Naturopathy, Unani, Siddha, and Homeopathy (AYUSH) doctor being found guilty of deficiency of service by prescribing allopathic medicines that were associated with known complications. The case details include the allegation, the defense, and the court's judgement. Details of the concerned acts, circulars, and regulations, as well as court case laws, are described. The regulations allow AYUSH doctors to prescribe allopathic medicines under certain circumstances, which were not adhered to in this case.

Unmet Needs in Geriatric Oncology.

Nikhil PathiIndia's population is aging, with the number of people aged 60 and over projected to reach 340 million by 2050. This is expected to lead to an increase in the number of older adults with cancer. Geriatric oncology is a rapidly growing field in India that is facing several challenges. Some of these include inadequate access to cancer screening and early detection programs in elderly, leading to late diagnoses and poor outcomes, lack of specialized geriatric oncology services, cancer-specific treatment guidelines and protocols in elderly, limited availability of treatment options due to accessibility, finances and other logistic issues, lack of trained healthcare professionals with expertise in geriatric oncology, lack of awareness, and access to early integrated palliative care services. There are several challenges faced by elderly in this journey like financial dependency, social isolation, difficulty in transportation to healthcare for treatments, and psychosocial aspects attributed to cancer. Awareness about availability of resources, patient assistance programs to reduce financial burdens, education campaigns, use of telemedicine and telehealth services to bypass transportation issues in remote and underserved areas, and integration of geriatric oncology into mainstream oncology services might be some solutions. Additionally, there is a need for more research on the unique characteristics and needs of older cancer patients in India, as well as the development of culturally appropriate interventions to address these needs. Development of India-specific geriatric assessment scales encompassing medical, psychosocial, and functional problems in elderly identifies areas of vulnerability. A multidisciplinary team-based decision-making is required at various levels. There is a need for increased investment in geriatric oncology research, training, and integrated palliative care services in India. Geriatric oncology is slowly being recognized as a separate subspeciality and more geriatric oncology centers and clinics are being set up in major cities in India that should be the way forward.

Challenges in Cervical Cancer Prevention: Real-World Scenario in India.

Satinder KaurIn spite of global falling trends, cervical cancer remains a major healthcare challenge for India, South Asia Association for Regional Cooperation region, and other low- and middle-income countries. Our survey was to document the real-world challenges that still exist in India. A total of 316 eligible and complete responses to the 21 questions were analyzed. Screening of mothers and vaccinating their daughters was considered as the most important strategy to prevent cervical cancer by 65.8% (208/316). Screening was offered to all asymptomatic eligible females by 79% (250/316). Improvement in screening rates requires promoting the national program (67.7%; 214/316), strengthening existing infrastructure (62%; 196/316), regular training of primary healthcare workers (57.6%; 182/316), and increasing awareness among schools and colleges (57.9%; 183/316). Almost all responders (93%; 294/316) wanted to have human papillomavirus (HPV) vaccination included in the national immunization schedule. Cost of vaccine was considered a major roadblock. If it became available at INR 250 per dose, 96.8% (306/316) respondents would recommend it for all eligible patients. With the impending availability of this indigenous tetravalent HPV vaccine jointly produced by Department of Biotechnology, Govt of India and Serum Institute of India, the war against cervical cancer just got easier.

Cervical Cancer in SAARC Countries.

Purvish M. ParikhIn the year 2020, a total of 342 000 women were estimated to die of cervical cancer, of which 90%) were expected amongst low- and middle-income countries (LMIC). Globally incidence of cervical cancer has reduced as a result of improved personal hygiene, better living conditions and higher application of opportunistic screening programs. Yet GLOBOCAN shows that absolute number of cases are still increasing. We therefore conducted a 21 question multiple choice questionnaire online survey in Jan 2023 amongst 9 SAARC countries. A total of 367 replies were received and the representative answers for each country are being reported in this manuscript. A good possibility of achieving World Health Assembly target (Nov 17, 2020) was felt only by Bhutan and Nepal. For screening, most countries (Bhutan, India, Myanmar, Nepal, Pakistan and Sri Lanka) recommend for all asymptomatic eligible patients. Public health experts have suggested VIA / VILI as the best solution for LMICs. However, a dual screening strategy (HPV DNA plus) cytology was preferred by doctors in Afghanistan, Bhutan, India, Myanmar, Pakistan and Sri Lanka. Screening, triage and then treatment was the preferred by Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, Sri Lanka. HPV vaccination was recommended in all girls between ages 10 to 26 years in Bangladesh, India, Myanmar, Nepal, Pakistan and Sri Lanka. All the 9 countries would use HPV vaccination to all eligible patients if the cost of the vaccine was reasonably low. Our survey clearly outlines challenges faced in tackling cervical cancer in SAARC countries. We also provide consensus regarding several potential solutions that can be used in both public and private cervical cancer control programs.

Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non-Small-Cell Lung Cancer.

PURPOSE: Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. PATIENTS AND METHODS: This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. RESULTS: Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P ≤ .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common. CONCLUSION: In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

Practical Clinical Consensus Guidelines for the Management of Cancer Associated Anemia in Low- and Middle-Income Countries.

Purvish M. ParikhCancer-associated anemia (CAA) remains a major unmet need that compromises overall survival (OS) and quality of life (QoL). Currently, available guidelines do not take into consideration the unique challenges in low- and middle-income countries (LMIC). Our CAA patients have to battle preexisting impaired nutritional status, depleted body iron stores, financial limitations, and difficulty in having easily accessible affordable healthcare. Hence, we fulfilled the need of guidelines for LMIC. A group of subject experts were put together, given background literature, met in a face-to-face discussion, voted using Delphi process, and finally agreed on the contents of this guideline document. As many as 50% of cancer patients will have significant anemia (hemoglobin < 10 g/dL) at initial diagnosis. It is most commonly seen with gastrointestinal malignancies, head and neck cancers, and acute leukemias. The hemoglobin falls further after initiation of cancer directed therapy, due to chemotherapy itself or heightened nutritional deficiency. Its evaluation should include tests for complete blood count, red blood cell morphology, reticulocyte count, Coombs test, and levels of vitamin B12 and folic acid. Iron status should be monitored using test to measure serum iron, total iron binding capacity, transferring saturation, and serum ferritin levels. A minimum of 50% of cancer patients with anemia require iron supplements. The preferred mode of therapy is with intravenous (IV) iron using ferric carboxymaltose (FCM). Most patients respond satisfactorily to single dose of 1000 mg. It is also safe and does not require use of a test dose. Significant anemia is found in at least half of all cancer patients in India, South Asian Association for Regional Cooperation region, and other LMIC countries. Its awareness among healthcare professionals will prevent it from remaining undiagnosed (in up to 70% of all cancer patients) and adversely affecting OS and QoL. The benefits of treating them with IV iron therapy are quick replenishment of iron stores, hemoglobin returning to normal, better QoL, and avoiding risk of infections/reactions with blood transfusions. Many publications have proven the value of single-dose FCM in such clinical situations. CAA has been proven to be an independent prognostic factor that adversely affects both QoL and OS in cancer patients. Use of FCM as single IV dose of 1000 mg is safe and effective in the majority of patients with CAA.

Communication in non-communicable diseases (NCDs) and role of immunomodulatory nutraceuticals in their management.

Conveyance of pathogens between organisms causes communicable diseases. On the other hand, a non-communicable disease (NCD) was always thought to have no causative transmissible infective agents. Today, this clear distinction is increasingly getting blurred and NCDs are found to be associated with some transmissible components. The human microbiota carries a congregation of microbes, the majority and the most widely studied being bacteria in the gut. The adult human gut harbors ginormous inhabitant microbes, and the microbiome accommodates 150-fold more genes than the host genome. Microbial communities share a mutually beneficial relationship with the host, especially with respect to host physiology including digestion, immune responses, and metabolism. This review delineates the connection between environmental factors such as infections leading to gut dysbiosis and NCDs and explores the evidence regarding possible causal link between them. We also discuss the evidence regarding the value of appropriate therapeutic immunomodulatory nutritional interventions to reduce the development of such diseases. We behold such immunomodulatory effects have the potential to influence in various NCDs and restore homeostasis. We believe that the beginning of the era of microbiota-oriented personalized treatment modalities is not far away.

Has Convalescent Plasma Therapy Hesitancy Increased COVID-19 Mortality?

We bring to you our viewpoint and a snapshot of the journey of convalescent plasma therapy (CPT) in the management of ongoing coronavirus disease 2019 (COVID-19) pandemic. We also discuss how best to use the updated data on this important treatment option and maximize benefit for our patients, thereby saving lives, especially in resource constraint settings.

Robust Protective Effect of COVID-19 Vaccination in India-Results of Survey in the Midst of Pandemic's Second Wave.

Introduction Our objective was to document the incidence of COVID-19 in vaccinated health care professionals and related personnel. Method We conducted an online survey to ascertain the incidence of COVID-19 symptoms, reverse transcriptase polymerase chain reaction (RT-PCR) positivity, effect on normal activity, need for anti-COVID-19 medication, hospitalization, and death among individuals who had completed both doses of COVID vaccination at least 2 weeks earlier. Results A total of 351 unique valid responses were received. Among the 340 people who had been vaccinated in India, 5% (17/340) had COVID-19 symptoms, 4.7% (16) became COVID-19 RT-PCR positive, 12 (3.5%) had sickness preventing normal daily activity, 2.65% (9) required anti-COVID-19 medication, and 1.18% (4) required hospitalization. Among family members living with the survey responders, the corresponding incidence was even lower. There was one death in this group. Discussion Being health care professionals, the responders would be at higher risk of daily exposure to COVID-19. Even in this high risk group, the vaccine efficacy is good. Vulture journalists should stop spreading fake news and misinformation that makes people hesitate taking the vaccine or be afflicted analysis paralysis. Every person who chooses to remain unvaccinated increases the risk for our entire community. We also need to follow universal precautions (wearing mask, physical distancing, handwashing) diligently without letting down our guard.

Cardiovascular safety profile of taxanes and vinca alkaloids: 30 years FDA registry experience.

OBJECTIVE: Antimicrotubular agents are among the most commonly used classes of chemotherapeutic agents, but the risk of cardiovascular adverse events (CVAEs) remains unclear. Our objective was to study the CVAEs associated with antimicrotubular agents. METHODS: The Food and Drug Administration's Adverse Event Reporting System was used to study CVAEs in adults from 1990 to 2020. Reported single-agent (only taxane or vinca alkaloid) CVAEs were compared with combination therapy (with at least one of the four major cardiotoxic drugs: anthracycline, HER2Neu inhibitors, tyrosine kinase inhibitors and checkpoint inhibitors) using adjusted polytomous logistic regression. RESULTS: Over 30 years, 134 398 adverse events were reported, of which 18 426 (13.4%) were CVAEs, with 74.1% due to taxanes and 25.9% due to vinca alkaloids. In 30 years, there has been a reduction in the proportion of reported CVAEs for taxanes from 15% to 11.8% (Cochran-Armitage P-trends <0.001) with no significant change in the proportion of reported CVAEs for vinca alkaloids (9.2%-11.7%; P-trends=0.06). The proportion of reported CVAEs was lower in both taxane and vinca alkaloid monotherapy versus combination therapy (reporting OR=0.50 and 0.55, respectively). Anthracyclines and HER2Neu inhibitor combinations with taxanes or vinca alkaloids primarily drove the higher burden of combination CVAEs. Hypertension requiring hospitalisation and heart failure was significantly lower in monotherapy versus combination antimicrotubular agent therapy. CONCLUSIONS: Antimicrotubular agents are associated with CVAEs, especially in combination chemotherapy regimens. Based on this study, we suggest routine cardiovascular assessment of patients with cancer before initiating antimicrotubular agents in combination therapy.

Practical Consensus Recommendations for Optimizing Risk versus Benefit of Chemotherapy in Patients with HR Positive Her2 Negative Early Breast Cancer in India.

Breast cancer is a public health challenge globally as well as in India. Improving outcome and cure requires appropriate biomarker testing to assign risk and plan treatment. Because it is documented that significant ethnic and geographical variations in biological and genetic features exist worldwide, such biomarkers need to be validated and approved by authorities in the region where these are intended to be used. The use of western guidelines, appropriate for the Caucasian population, can lead to inappropriate overtreatment or undertreatment in Asia and India. A virtual meeting of domain experts discussed the published literature, real-world practical experience, and results of opinion poll involving 185 oncologists treating breast cancer across 58 cities of India. They arrived at a practical consensus recommendation statement to guide community oncologists in the management of hormone positive (HR-positive) Her2-negative early breast cancer (EBC). India has a majority (about 50%) of breast cancer patients who are diagnosed in the premenopausal stage (less than 50 years of age). The only currently available predictive test for HR-positive Her2-negative EBC that has been validated in Indian patients is CanAssist Breast. If this test gives a score indicative of low risk (< 15.5), adjuvant chemotherapy will not increase the chance of metastasis-free survival and should not be given. This is applicable even during the ongoing COVID-19 pandemic.

South Asian Declaration-Consensus Guidelines for COVID-19 Vaccination in Cancer Patients.

We provide the South Asian Declaration, containing the consensus guidelines for coronavirus disease 2019 (COVID-19) vaccination in cancer patients.

Violence against Health Care Professionals and Facilities-Local Insights about a Global Malady.

Acts of violence against health care professionals (especially doctors) as well as facilities are a growing global problem. In our country, it has taken an unfortunate dramatic turn of the involvement of a mob-a ragtag group of persons who organize and perpetrate the crime based on community, caste, religion, or political affiliations. This crucial factor is the fundamental difference in what we face as compared with the so-called Yi Nao phenomenon of China. In India, the mob gathers and indulges in acts of violence, intimidation, and blackmail at the behest of its "leader," often having no direct relationship with the deceased patient. It is premeditated and systematic vandalism. Often it is also associated with financial gain to the perpetrators through extortion and blackmail, adding to the woes of the health care professionals and hospital facility. We discuss what is the primary goal and what is a byproduct in this cycles of violence against the people who are doing their best to save the lives of patients. Unless the governments and the courts take this matter seriously as well as follow-up with corrective measures, the future looks bleak for all stakeholders.