Senescence-associated secretory proteins induced in lung adenocarcinoma by extended treatment with dexamethasone enhance migration and activation of lymphocytes.

There is a need to improve response rates of immunotherapies in lung adenocarcinoma (AC). Extended (7-14 days) treatment of high glucocorticoid receptor (GR) expressing lung AC cells with dexamethasone (Dex) induces an irreversible senescence phenotype through chronic induction of p27. As the senescence-associated secretory phenotype (SASP) may have either tumor supporting or antitumor immunomodulatory effects, it was interest to examine the effects of Dex-induced senescence of lung AC cells on immune cells. Dex-induced senescence resulted in sustained production of CCL2, CCL4, CXCL1 and CXCL2, both in vitro and in vivo. After Dex withdrawal, secretion of these chemokines by the senescent cells attracted peripheral blood monocytes, T-cells, and NK cells. Following treatment with Dex-induced SASP protein(s), the peripheral blood lymphocytes exhibited higher cell count and tumor cytolytic activity along with enhanced Ki67 and perforin expression in T and NK cells. This cytolytic activity was partially attributed to NKG2D, which was upregulated in NK cells by SASP while its ligand MICA/B was upregulated in the senescent cells. Enhanced infiltrations of T and NK cells were observed in human lung AC xenografts in humanized NSG mice, following treatment with Dex. The findings substantiate the idea that induction of irreversible senescence in high-GR expressing subpopulations of lung AC tumors using Dex pretreatment enhances tumor immune infiltration and may subsequently improve the clinical outcome of current immunotherapies.

Progression of aortic root based on long-term imaging studies after acute type A dissection repair.

BACKGROUND: To determine the progression of aortic root in acute type A aortic dissection (ATAAD) patients after aortic root repair (ARr) or replacement (ARR) based on long-term follow-up imaging studies. METHODS: From 1996 to 2019, 732 patients had ATAAD repair at our institution. Six hundred and seven of these patients had either ARr, (n = 383) or ARR (n = 224). Eighty-one patients were excluded due to a lack of postoperative imaging. Three hundred and thirty-two patients were included in the repair group and 194 patients in the replacement group for long-term follow-up imaging study. RESULTS: Compared to the ARR group, the ARr group was significantly older (60 years vs. 55 years) and had more patients with hypertension (79% vs. 63%) but less male patients (63% vs. 79%) and connective tissue disorder (1.8% vs 8%). The ARr group had more zone two arch replacement (22% vs. 11%), similar HCA time (35 min vs. 31 min), shorter cardiopulmonary bypass time (203 min vs. 266 min), aortic cross-clamp time (128 min vs. 214 min), and fewer concomitant coronary artery bypass (3.9% vs. 8.9%). The root growth rate over 12 years was similar between the repair and replacement group (0.20 mm/year vs. 0.18 mm/year, p = .75). Both the repair and replacement group had similar 15-year cumulative incidence of reoperation (6.9% vs. 5.9%; p = .67), operative mortality (7.8% vs. 8.5%; p = .78), and 15-year survival (51% vs. 52%; p = .40). CONCLUSIONS: There was minimal growth of the aortic root after root repair or replacement for ATAAD patients. Both aortic root repair and replacement were acceptable techniques for ATAAD surgery in select patients.

The challenges and main recommendations to fight measles in India: A mini review.

The measles virus is an RNA virus belonging to the Paramyxoviridae family. It leads to an acute communicable illness that primarily involves the respiratory tract. Vaccination has significantly reduced the overall incidence and mortality worldwide; however, outbreaks still occur globally each year due to several factors. The SARS-CoV-2 pandemic has been a major hurdle since 2020. Despite the World Health Organization's goal to eradicate measles by 2023, there has been an increase in measles incidence in India, with 61,562 cases in 2022. Vaccination is a crucial preventive measure, and coverage needs to be increased through education, advocacy, and outreach to isolated communities.

Management of Marjolin's ulcer with popliteal lymphadenopathy with surgical resection and lymphadenectomy in a young patient, an uncommon lesion and overlooked entity: A case report.

Key Clinical Message: In non-healing ulcers with a previous history of burns, clinicians should have a high index of suspicion for Marjolin's ulcer and a low threshold for biopsy, irrespective of age. Abstract: Marjolin's ulcer is a rare malignancy arising from chronic inflammation and commonly manifests in burn scars. Thus, in cases of chronic wounds or non-healing ulcers, health professionals should have a high index of suspicion and a low threshold for biopsy, irrespective of age. Early diagnosis and timely management of tumors can improve the prognosis and overall survival rate. Moreover, further studies are needed to develop an evidence-based management approach for Marjolin's ulcer.

Reflections on the surge in malaria cases after unprecedented flooding in Pakistan-A commentary.

Background: Malaria is a parasitic infection primarily caused by four main species of the genus Plasmodium, that is, Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, and Plasmodium malariae. It is transmitted through the bite of the female Anopheles mosquito. It holds the status of one of the leading causes of death in the developing world. Malaria is endemic to Pakistan, and the country experienced the worst floods in its history from April to October 2022. The stagnant flood water served as a breeding ground for mosquitoes, culminating in an alarming spike in malaria cases. According to the World Health Organization (WHO), the number of cases reported till August 2022 was more than in the whole year of 2021. There was more than a twofold rise in cumulative cases in 62 high-burden Pakistani Districts in August 2022 as compared to August 2021. Aims: This commentary aims to bring this emerging issue to notice and highlight the most effective probable measures to help eliminate and prevent the hazards the current outbreak poses. Results: Rapid planning and execution are needed to ensure the most efficient and rapid elimination of malaria. To educate the general public, the national government must start public awareness efforts in electronic, print, and social media and deploy solar-powered mobile healthcare units to far-flung areas. Prophylactic and postexposure treatments should be planned because larvicidal preventive measures are less practical in flood-affected vicinities. Conclusion: The most effective preventive strategy is drug prophylaxis, followed by insecticide-treated nets, indoor residual spraying, and untreated nets. Scientists should intensify their investigations for effective medications to alleviate the malaria burden in Pakistan.

Radiological manifestation of optic nerve infarction in a patient with invasive mucormycosis secondary to diabetic ketoacidosis in Pakistan.

A 35 years old male patient presented in the hospital with complaints of left-sided facial swelling, blindness in the left eye, and left eye proptosis. He had a concomitant history of diabetic ketoacidosis. Magnetic resonance imaging was advised, which revealed infected tissue of the left cheek, optic nerve infarction, intracranial extension, and leptomeningeal involvement by the disease process.

Double cortex syndrome (subcortical band heterotopia): A case report.

Double cortex syndrome is an uncommon familial syndrome with X-linked dominant inheritance and most commonly presents with developmental delay and seizures. We present a case of a 14-year-old girl who came to neurology department of the hospital with severe generalized tonic-clonic fits and loss of consciousness. The mother of child gave history of uneventful antenatal period and labor. There was history of immediate cry and normal APGAR score. She was achieving milestones normally until at the age of 3 years when she suffered decline in her speech and vision. She had problems with learning with lack of concentration during her schooling. Physical examination was also unremarkable. Her lab values including complete blood count, serum calcium, and arterial blood gas tests, all were within normal limits. Electroencephalogram showed significant changes suggestive of epilepsy. Magnetic resonance imaging of brain showed continuous band of gray matter that was located deep and paralleling the cortex in both cerebral hemispheres suggestive of band heterotopia or double cortex syndrome. She was discharged and prescribed antiepileptics; and was advised regular outpatient follow-up.

An infant with Joubert syndrome: A case report.

Joubert syndrome is a rare neurological and developmental malfunction represented by decreased muscle tone, ataxia, and delayed developmental milestones. Joubert syndrome-related disorders, besides central nervous system, can involve other systems and thus can lead to multi-organ malfunction. We report a case of pure Joubert syndrome who presented with developmental delay, decreased muscle tone, and ataxia. Identification of molar tooth sign on magnetic resonance imaging studies assisted to make a definitive diagnosis. Detailed examination revealed no other significant findings of any organ of the body. Patient was managed conservatively with symptomatic treatment. Although these types of cases are rarely encountered, they can lead to multiple organ disabilities. Therefore, clinicians should always keep this diagnosis in mind whenever an infant presents with the aforementioned neurodevelopmental symptoms.

Year-round dengue fever in Pakistan, highlighting the surge amidst ongoing flood havoc and the COVID-19 pandemic: a comprehensive review.

Dengue fever (DF) is an arthropod-borne viral infection caused by four serotypes of dengue virus (DENV 1-4) transmitted to the host by the vector mosquito Aedes, which causes fever, vomiting, headache, joint pain, muscle pain, and a distinctive itching and skin rash, ultimately leading to dengue hemorrhagic fever and dengue shock syndrome. The first case of DF in Pakistan was documented in 1994, but outbreak patterns began in 2005. As of 20 August 2022, Pakistan has 875 confirmed cases, raising alarming concerns. Misdiagnosis due to mutual symptoms, lack of an effective vaccine, the weakened and overburdened health system of Pakistan, irrational urbanization, climate change in Pakistan, insufficient waste management system, and a lack of awareness are the significant challenges Pakistan faces and result in recurrent dengue outbreaks every year. The recent flood in Pakistan has caused massive destruction, and stagnant dirty water has facilitated mosquito breeding. Sanitization and spraying, proper waste management, an adequate and advanced diagnostic system, control of population size, public awareness, and promotion of medical research and global collaboration, especially amidst flood devastation, are recommended to combat this deadly infection in Pakistan. This article aims to comprehensively review the year-round DF in Pakistan, highlighting the surge amidst ongoing flood havoc and the coronavirus disease 2019 pandemic.

Diseases caused by floods with a spotlight on the present situation of unprecedented floods in Pakistan: a short communication.

Few natural calamities surpass floods in their destructive capabilities. The recent floods in Pakistan were declared the world's deadliest since the South Asian floods of 2020 and were, by far, the most destructive floods in the country's history. They have resulted in significant loss of life and property and have served as the harbingers of cutaneous and noncutaneous diseases. These floods have dealt a critical blow to the country's already struggling healthcare system, which lacks resources for the prompt mobilization of medical personnel and resources to the flood-hit areas. Having lost their houses, the flood victims are wholly exposed to the elements. Lack of access to a clean water supply has predisposed them to a myriad of diseases. We believe that the consolidation of efforts by the national and international community will put an end to the plight of these flood victims. Our article highlights the significant diseases associated with floods, the challenges faced by the flood victims, and recommendations on how their situation can be improved.

Diphtheria in Pakistan post-COVID-19, a potential public health threat: an update.

Diphtheria, a vaccine-preventable disease, remains a concern in Pakistan as cases have risen post-COVID-19 pandemic causing more than 45 deaths in Pakistan in the year 2022. The respiratory variant of the disease is more common and can lead to serious complications, such as myocarditis and respiratory insufficiency. Diphtheria has caused havoc in the past killing millions of people worldwide before the development of its vaccine. Although the diphtheria toxoid vaccine is effective against toxigenic strains, there have been cases of treatment-resistant strains, particularly the non-toxigenic strains of C. diphtheriae. Pakistan's economic and health systems have suffered setbacks, which have been exacerbated by the COVID-19 pandemic. The pandemic has disrupted routine vaccination programs, and recent floods have contributed to an increase in diphtheria cases and rendered millions homeless. Poor immunization services, inadequate training of vaccination teams, and wealth inequality have all contributed to unequal vaccination coverage in Pakistan. The rising cases of diphtheria call for prompt action, including booster shots, updating vaccination records and administering immediate doses of the toxoid to close contacts.

Re-emergence of Lassa fever in Nigeria: A new challenge for public health authorities.

The Lassa virus is an RNA virus belonging to the Arenaviridae family. It is responsible for Lassa fever, an acute viral zoonosis of the severe hemorrhagic fever type with manifestations of fever, muscle pain, sore throat, nausea, vomiting, and chest and abdominal pain. Lassa fever is endemic in West Africa, where the first case was reported in 1969 in Lassa, a town in Nigeria, more than 50 years ago, and it is estimated that nearly 5000 deaths occur in West Africa each year. Nigeria is one of the endemic hotspots and has experienced numerous recurrent outbreaks of Lassa fever due to the increased multiplication of the host reservoir, Mastomys natalensis. For the Lassa epidemics in 2022 and January 2023 alone, Nigeria accounts for a quarter of the annual deaths from this disease. Poor lifestyle and hygiene, difficulty in diagnosis due to nonspecific symptomatology, lack of effective treatment based on clinical evidence, an ineffective human immunization program combined with a health system that is not adapted or equipped to control and prevent recurrent deadly epidemics, and an outdated regional disease surveillance system in West Africa are some of the challenges that must be overcome to rapidly and effectively eradicate this disease, whose area of spread is constantly expanding as a result of the movement of populations in the context of economic and socio-cultural activities.

Crimean-Congo hemorrhagic fever outbreak in Pakistan, 2022: A warning bell amidst unprecedented floods and COVID 19 pandemic.

Crimean-Congo hemorrhagic fever (CCHF) is an infection caused by a tick-borne virus (genus: Nairovirus, family: Bunyaviridae). The most important vector for CCHF is the ixodid tick. Along with tick bite, direct contact with the virus-affected animal is responsible for its spread. Pakistan witnessed its first case of CCHF in 1976 and has been a major victim of CCHF for years, but spikes in cases are seen after Eid-ul-Adha, an Islamic festival involving the sacrifice of cattle. The disease, in particular, is common among butchers, veterinarians, and livestock workers. From the start of this year till June 22, 2022, a total of four cases have been reported across the country. Pakistan faces major challenges in combating CCHF every year due to its specific geographical position and a majority of the population being involved with animal husbandry. There is no approved vaccine for its prevention. All these factors contribute to the burden on the already weakened healthcare system of Pakistan. Strict actions should be taken to contain the spread of the disease. The need of the hour is to engage the general population, raise awareness, and develop policies to ensure disease surveillance. This should be accompanied by fostering collaboration among animal and human health departments for efficient communication and early intervention. The focus should be on medical research to find an efficacious treatment and prophylaxis for the CCHF virus, which will be the cornerstone of future CCHF prevention and control strategies.

Rift Valley fever virus outbreak in Mauritania yet again in 2022: No room for complacency.

Rift Valley fever is an important yet ignored viral hemorrhagic fever claiming many lives of African and Arabian countries over the past decade. Unfortunately, a recent outbreak of Rift Valley fever is currently ravaging in Mauritania. Death toll is rising continuously with 23 deaths reported in the month of October, 2022. Our article aims to shed light on the ongoing Rift Valley fever outbreak and recommendations to eradicate this potential threat to public health. Online databases including PubMed, the Lancet, and Science Direct as well as conferences, news, and press releases were used to for data collection. All the available medical literature related to Rift Valley fever in Mauritania were taken into consideration while writing the manuscript. As of October 17, 2022, 47 cases have been documented out of which 23 are dead. Case fatality rate has been reached to 49% which has given a wakeup call to the authorities. Efforts are being made by the concerned authorities and World Health Organization to halt the progression of this outbreak. Further investigations are required to completely eradicate the recurrent outbreaks in Mauritania especially in the area of vaccine development. Active involvement of public with the government authorities is of extreme significance in combating this disease.

Distal Aortic Progression After Hemiarch, Zones 1-3 Arch Replacement in Acute Type A Aortic Dissection.

BACKGROUND: There is debate regarding aortic arch repair extent for acute type A aortic dissection (ATAAD) patients. METHODS: From 1996 to 2021, 756 ATAAD patients underwent open arch replacement. The cohort was divided into hemiarch (n = 481), zone 1 (n = 65), zone 2 (n = 148), and zone 3 (n = 62) arch replacement groups. Cross-group comparison of aortic growth was modeled using data from interval postoperative computed tomography or magnetic resonance imaging of the distal aorta. RESULTS: Demographics were not significantly different except the hemiarch group had more coronary artery disease and less stroke. Intraoperatively, zones 1, 2, and 3 had greater cardiopulmonary bypass, cross-clamp, and hypothermic circulatory arrest times and required more intraoperative blood transfusion than the hemiarch group. Perioperative outcomes were similar among groups except zone 3 had more reoperation for bleeding. Ten-year cumulative incidence of reoperation was hemiarch, 16.7%; zone 1, 16.3%; zone 2, 21.5%; and zone 3, 17.6% (P = .70). Ten-year survival was similar: hemiarch, 66%; zone 1, 60.3%; zone 2, 68.0%); and zone 3 66.1% (P = .20). Aortic arch, descending aorta, and abdominal aorta growth rates were not significantly different among groups over 10 years. In the whole cohort, the growth rate over time for aortic arch was 0.38 mm per year (P < .001), descending aorta 0.84 mm per year (P < .001), and abdominal aorta 0.69 mm per year (P < .001). CONCLUSIONS: There was no significant difference in long-term survival, distal aorta growth, or reoperation rate for distal aortic aneurysm after hemiarch or zones 1, 2, or 3 arch replacement. Patient-specific arch replacement strategies may be used rather than defaulting to aggressive arch replacement for all ATAAD patients.

Impella Versus Extracorporeal Membranous Oxygenation (ECMO) for Cardiogenic Shock: A Systematic Review and Meta-analysis.

The use of mechanical circulatory support (MCS) in cardiogenic shock (CS) is increasing. We conducted a systematic review and meta-analysis to compare the outcomes of Impella use with extracorporeal membranous oxygenation (ECMO) support in patients with CS. We searched the Medline, EMBASE, Cochrane, and Clinicaltrials.gov databases for observational studies comparing Impella to ECMO in patients with CS. Risk ratios (RRs) for categorical variables and standardized mean differences (SMDs) for continuous variables were calculated with 95% confidence intervals (CIs) using a random-effects model. Twelve retrospective studies and one prospective study (Impella n=6652, ECMO n=1232) were identified. Impella use was associated with lower incidence of in-hospital mortality (RR 0.88 [95% CI 0.80-0.94], P=0.0004), stroke (RR 0.30 [0.21-0.42], P<0.00001), access-site bleeding (RR 0.50 [0.37-0.69], P<0.0001), major bleeding (RR 0.56 [0.39-0.80], P=0.002), and limb ischemia (RR 0.42 [0.27-0.65], P=0.0001). Baseline lactate levels were significantly lower in the Impella group (SMD -0.52 [-0.73- -0.31], P<0.00001). There was no significant difference in mortality at 6-12 months, MCS duration, need for MCS escalation, bridge-to-LVAD or heart transplant, and renal replacement therapy use between Impella and ECMO groups. In patients with CS, Impella device use was associated with lower in-hospital mortality, stroke, and device-related complications than ECMO. However, patients in the ECMO group had higher baseline lactate levels.

COVID-19 and Cardiovascular Diseases: A Literature Review From Pathogenesis to Diagnosis.

The coronavirus disease 2019 (COVID-19) took the world by storm after the first case of COVID-19 emerged in China on December 8, 2019. The disease is generally considered as an infection of the respiratory system, but serious life-threatening myocardial injuries have been reported with this infection. Coronavirus can damage cardiac myocytes by entering the cell through angiotensin-converting enzyme 2 (ACE-2) receptor binding. Myocardial infarction, myocarditis, heart failure, cardiac arrhythmias, and Takotsubo cardiomyopathy are cardiac clinical manifestations commonly seen among patients affected by COVID-19. These cardiac pathologies are seen both during ongoing infection and post-infection. Elevated levels of myoglobin, troponin, creatine kinase-MB, plasma interleukin-6, lactate dehydrogenase (LDH), and N-terminal pro-b-type natriuretic peptide (NT-proBNP) have been found in COVID-19-associated myocardial injuries. The diagnostic modalities used in myocardial injuries due to COVID-19 include electrocardiography (ECG), cardiac magnetic resonance imaging (CMR), endomyocardial biopsy, echocardiography (Echo), and computerized tomography (CT-Scan). This literature review will discuss, in detail, the pathogenesis, clinical manifestations, and diagnosis of myocardial injuries due to COVID-19.

Poor long-term outcomes of intravenous drug users with infectious endocarditis.

Objectives: The optimal management of active endocarditis in intravenous (IV) drug users is still lacking. Methods: From the years 1997 to 2017, 536 patients with active infectious endocarditis were surgically treated, including 83 (15%) with IV drug use (IVDU) and 453 (85%) without IV drug use (non-IVDU). Initial data were obtained from the Society of Thoracic Surgeons database and supplemented with chart review and national death index data. Results: The IVDU group was significantly younger (43 vs 56 years old) than the non-IVDU group and had greater rates of psychiatric disorders, drug use, and tricuspid valve endocarditis (28% vs 8.6%). Hypertension, dyslipidemia, and diabetes mellitus were significantly more common in the non-IVDU group. Perioperative complications and operative mortality (7.2% vs 7.9%) were similar. IVDU was not a significant risk factor for operative mortality. Kaplan-Meier survival was significantly lower in the IVDU group (5-year survival, 46% vs 67%). Significant risk factors for long-time mortality included IV drug use (hazard ratio [HR], 1.92), age ≥65 years (HR, 1.78), congestive heart failure (HR, 1.87), and enterococcus endocarditis (HR, 1.54). The 5-year rate of reoperation was similar between IVDU and non-IVDU groups (2.4% vs 2.7%). Conclusions: IVDU is a significant risk factor for long-term mortality. A multidisciplinary approach was preferred for IVDU patients to treat both endocarditis and substance use disorder and improve long-term survival.

A rare and novel mutation in a beta-globin gene of thalassemia patient of Pakistan: A case report.

Introduction: Thalassemia is a genetically complex disorder that evolves from a mutation in the beta chain of hemoglobin. Much work has been done on the common mutations, but some rare mutations have been found that impact and diversify the disease spectrum. Case presentation: Our case report is on a young adult who presented with anemia, gall stones, and off-and-on transfusion dependency. A detailed workup revealed that the patient was suffering from thalassemia intermedia. The interesting finding was that the patient, product of non-consanguineous marriage was homozygous for beta thalassemia mutation on genetic analysis. A detailed genetic analysis of the parents revealed them as carriers for the same mutation. It was found that patient was homozygous for a rare and novel mutation -88(C > A)[HBB:c.-138C  >  A] on whole gene sequencing. Discussion: The area of genomics in thalassemia is rapidly growing, and our case report aims to update the current knowledge of thalassemia's genomic information in Pakistan. The mutation found in our patient was -88(C > A)[HBB:c.-138C  >  A], and the data provided by the National Library of Medicine for this mutation as Allele ID: 380597 and variant type of single nucleotide variant shows that only ten such cases exist in the world with this rare mutation. Our case would be the 11th case in the world and 1st in Pakistan according to the literature, reporting above mentioned mutation. Conclusion: Further translational study is required to accurately utilize genomic data as an instrument of precision treatment in thalassemia patients, especially in underdeveloped countries like Pakistan.