Toolbox of individual-level interventions against online misinformation.

The spread of misinformation through media and social networks threatens many aspects of society, including public health and the state of democracies. One approach to mitigating the effect of misinformation focuses on individual-level interventions, equipping policymakers and the public with essential tools to curb the spread and influence of falsehoods. Here we introduce a toolbox of individual-level interventions for reducing harm from online misinformation. Comprising an up-to-date account of interventions featured in 81 scientific papers from across the globe, the toolbox provides both a conceptual overview of nine main types of interventions, including their target, scope and examples, and a summary of the empirical evidence supporting the interventions, including the methods and experimental paradigms used to test them. The nine types of interventions covered are accuracy prompts, debunking and rebuttals, friction, inoculation, lateral reading and verification strategies, media-literacy tips, social norms, source-credibility labels, and warning and fact-checking labels.

Long-term Outcomes of Surgery and Radiation Treatment for Adult Patients with Craniopharyngioma.

OBJECTIVE: Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in the adult population undergoing GTR versus STR-RT. METHODS: A total of 115 patients in 5 institutions were enrolled in this retrospective study on adult craniopharyngiomas. Patients with STR received postoperative RT with stereotactic radiosurgery (SRS) or fractionated radiation therapy (FRT) per institutional preference and ability to spare optic structures. RESULTS: Median age was 44 years (19 - 79 years). GTR was achieved in 34 patients and STR-RT in 81 patients with median follow up of 78.9 months (1 - 268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection there was no difference in local control (p = 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STR-RT. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in STR-RT patients that were underdosed with FRT (p = 0.03) or SRS (p = 0.04). CONCLUSIONS: There is good long-term control for adult craniopharyngioma that underwent STR-RT or GTR with no significant difference in local control. First-line treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long term morbidity.

Does That Go There? A Rare Occurrence of Spontaneous Sternocleidomastoid Abscess without Trauma in a Diabetic Individual.

BACKGROUND Spontaneous abscesses are generally typical in patients with significant risk factors and have been linked to numerous muscle groups. The sternocleidomastoid muscle, however, piqued our interest as an unusual location, especially in this patient who, other than diabetes mellitus, had no associated risk factors or signs of trauma. CASE REPORT A 61-year-old man appeared with neck pain, erythema, and swelling that had been present for 9 days and for which he had previously been examined in the Emergency Department. He was discharged on oral doxycycline after initial computed tomography (CT) of the neck revealed infiltration without collection. He returned with worsening symptoms and new-onset fever and chills. Vital signs were normal on assessment, with no evidence of trauma. Swelling was observed near the right sternocleidomastoid muscle insertion. A repeat CT scan of the neck revealed an abscess 2.5 cm in diameter. He was originally treated with empiric antibiotics before being moved to targeted medications. Incision and drainage were completed without complication. The patient was given a 6-week course of oral antibiotics. CONCLUSIONS Spontaneous intramuscular abscesses are uncommon in people who have had no previous trauma or other known risk factors, but could be encountered in diabetic patients with non-optimal blood glucose levels, due to bacteremia. As a result, these cases require a high level of suspicion to be recognized and treated early. The scarcity of literature on this illness makes determining the cause challenging. However, by highlighting this case, we intend to raise awareness and facilitate early diagnosis and treatment.

Group A Streptococcus Pneumonia in a Previously Healthy Individual: Is It Still a Thing?

Group A streptococcus (GAS) is known to cause many different kinds of infections, including invasive pneumonia in rare cases. When it is the causative agent, it is associated with a more severe disease course, but it can often be adequately treated if caught early enough. We hereby present the case of a 32-year-old male with no past medical history who presented with fever, hemoptysis, and tachycardia. Laboratory results showed leukocytosis, hyponatremia, mild transaminitis, and elevated creatine kinase. Initial imaging findings and clinical presentation were concerning for tuberculosis (TB) vs. community-acquired pneumonia (CAP), as it yielded a consolidation in the right upper lobe. The patient had no obvious risk factor except for imprisonment two years prior to symptoms onset. Empirical antibiotics and steroids were started. Quantiferon and acid-fast bacteria (AFB) were negative, but sputum and blood cultures were positive for Streptococcus pyogenes, ruling out TB. Antibiotic therapy was narrowed down. The patient responded well to therapy, with subsequent resolution of symptoms. The current body of knowledge regarding respiratory infections caused by GAS is limited by multiple factors, including its relative rarity and the diversity of how it can present, especially in a developed country. Its mimicry characteristics of other clinical entities, such as TB, can be deceiving, which can delay appropriate treatment if it occurs in settings where the diagnostic tools are not readily available. By sharing more cases and atypical presentations of this disease, the clinical presentations of this pathogen can be more fully understood, and it can be more rapidly identified and treated.

Diagnostic Accuracy of Bayley III Screening Tool to Detect Developmental Delay in Moderate to High-Risk Indian Preterm Children.

The present study aimed to evaluate the ability of the Bayley III screening tool to detect developmental delay in moderate to high-risk preterm children in India. In this cross-sectional study, 94 preterm babies were enrolled. The Bayley III screener (index test) and the gold-standard, Developmental assessment scale for Indian Infants (DASII) test were administered to all the enrolled children. Researchers were blinded while performing the tests. Diagnostic accuracy parameters were compared. The Bayley III screener's sensitivity and specificity for predicting the delay (with a DASII cut-off of <70) were 84.62% and 85.18% in the mental domain and 61.11% and 96.05% in the motor domain, respectively. When the DASII cut-off was raised to 85, the sensitivity and specificity in the mental domain were 60.61% and 95.08%, respectively, whereas they were 36.11% and 98.27%, respectively, in the motor domain. The Bayley III screener is found to have good specificity rather than sensitivity with good predictive values.

Post-Infection Oscillometry and Pulmonary Metrics in SARS-CoV-2 Patients: A 40-Day Follow-Up Study.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had significant impacts on pulmonary function. This study aimed to comprehensively evaluate pulmonary function and structure in patients 40 days post-SARS-CoV-2 infection, employing an array of testing methodologies including spirometry, plethysmography, forced oscillometry, and CT scanning. It also sought to establish potential correlations between these metrics and evaluate if forced oscillometry could provide additional value in post-infective lung function assessment. A 40-day post-infection follow-up observational study was conducted involving 66 patients with confirmed SARS-CoV-2 infection. The results revealed decreases in FVC and FEF25-75 with the increasing severity of COVID-19. Specifically, patients with severe symptoms exhibited statistically significant decreases in FVC (mean = 86.8) compared with those with mild symptoms (mean = 106.0; p = 0.018). The FEF25-75 showed a similar trend, with severe patients exhibiting a mean of 77.7 compared with 82.9 in the mild group (p = 0.017). Furthermore, resonant frequency (RF) increased with disease severity, with the severe group exhibiting a statistically significant increase (mean = 17.4) compared with the mild group (mean = 14.3; p = 0.042). CT scans showed an increase in ground-glass opacities with disease severity, with 81.8% of severe patients demonstrating this finding (p = 0.037). Multiple regression analysis revealed that Reactance at 4 Hz (X4), Forced Expiratory Flow 25-75% (FEF25-75), and Resonant Frequency (RF) were significantly related to COVID-19 severity. Specifically, for each unit increase in these factors, the risk of the event was estimated to increase by a factor of 3.16, 2.09, and 1.90, respectively. Conversely, Resistance at 4 Hz (R4) and Airway Resistance (RAW) were found to significantly decrease the event hazard, highlighting their potential protective role. Spirometry, plethysmography, and forced oscillometry are effective in assessing these changes. Forced oscillometry may be particularly beneficial in identifying subtle changes in lung function post-COVID-19. Further studies are warranted to validate these findings and develop strategies to manage post-infective pulmonary changes in SARS-CoV-2 patients.

Nivolumab and ipilimumab in combination with radiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Exploratory endpoints included the association of baseline programmed death-ligand 1 (PD-L1) expression as well as on-treatment changes in immune bias with treatment outcomes. RESULTS: Twenty-four patients were enrolled. With a median follow-up of 36.1 months, grade 3 or higher treatment-related adverse events were reported in 21 individuals (88%); 5 individuals developed in-field soft tissue ulceration during consolidation immunotherapy, resulting in one fatality. The 3-year PFS and OS rates were 74% (95% CI 58% to 94%) and 96% (95% CI 88% to 100%), respectively. PD-L1 combined positive score (CPS) did not correlate with death or disease progression. Decreases in extracellular vesicle PD-L1 within the concurrent RIT phase were associated with prolonged PFS (p=0.006). Also, interval decreases in circulating interleukin (IL)4, IL9, IL12, and IL17a during concurrent RIT were associated with subsequent ulceration. CONCLUSIONS: Definitive RIT with nivolumab and ipilimumab has sufficient clinical activity to support further development. Early changes in circulating biomarkers appear able to predict treatment outcomes as well as ensuing in-field soft tissue ulceration. TRIAL REGISTRATION NUMBER: NCT03162731.

Influence of Antiphospholipid Antibody-Associated Thrombophilia on the Risk of Preterm Birth: A Systematic Review.

Antiphospholipid antibody (aPL)-associated thrombophilia has been implicated in various adverse pregnancy outcomes, including preterm birth and impaired fetal development. This systematic review aimed to elucidate the relationship between aPL-associated thrombophilia and these outcomes, as well as to identify potential modifiers of this relationship such as maternal age, coexisting maternal medical conditions, type of aPL antibodies involved, and the timing of thrombophilia diagnosis during gestation. We conducted a comprehensive literature search in PubMed, Web of Science, Cochrane, and Scopus in May 2023, covering literature published within the last 10 years. Eight articles, involving 2935 patients, were eligible for inclusion in the review. Single aCL was the most common type of aPL found in patients, with rates up to 61.0% in some studies, followed by single LA and single ab2GPI. Multiple aPL antibody positivity was found to be associated with a higher risk of preterm birth, with odds ratios ranging from 1.29 to 9.61. Patient characteristics and previous pregnancy history varied significantly across the studies. Risk factors such as diabetes mellitus, thrombosis, and systemic lupus erythematosus were also variable across the studies, but presence of these risk factors did not consistently affect the risk of preterm birth. Furthermore, although a triple positive aPL test was the most important risk factor for preterm birth, it was observed that thrombophilia treatment during pregnancy significantly reduced the risk by 2.44 times (95% CI = 1.18-6.20). This review supports the evidence for aPL-associated thrombophilia being a significant contributor to preterm birth and fetal developmental abnormalities. Further research is required to investigate the exact mechanisms and to determine the best clinical management for patients with aPL-associated thrombophilia during pregnancy.

Differences in clinical outcomes based on molecular markers in glioblastoma patients treated with concurrent tumor-treating fields and chemoradiation: exploratory analysis of the SPARE trial.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite enormous research efforts, GBM remains a deadly disease. The standard-of-care treatment for patients with newly diagnosed with GBM as per the National Cancer Comprehensive Cancer Network (NCCN) is maximal safe surgical resection followed by concurrent chemoradiation and maintenance temozolomide (TMZ) with adjuvant tumor treating fields (TTF). TTF is a non-pharmacological intervention that delivers low-intensity, intermediate frequency alternating electric fields that arrests cell proliferation by disrupting the mitotic spindle. TTF have been shown in a large clinical trial to improve patient outcomes when added to radiation and chemotherapy. The SPARE trail (Scalp-sparing radiation with concurrent temozolomide and tumor treating fields) evaluated adding TTF concomitantly to radiation and chemotherapy. METHODS: This study is an exploratory analysis of the SPARE trial looking at the prognostic significance of common GBM molecular alterations, namely MGMT, EGFR, TP53, PTEN and telomerase reverse transcriptase (TERT), in this cohort of patients treated with concomitant TTF with radiation and chemotherapy. RESULTS: As expected, MGMT promoter methylation was associated with improved overall survival (OS) and progression-free survival (PFS) in this cohort. In addition, TERT promoter mutation was associated with improved OS and PFS in this cohort as well. CONCLUSIONS: Leveraging the molecular characterization of GBM alongside advancing treatments such as chemoradiation with TTF presents a new opportunity to improve precision oncology and outcomes for GBM patients.

Multiple myeloma and its rare paraneoplastic manifestations simmering under the surface.

Paraneoplastic syndromes are complex clinical manifestations that occur because of the underlying malignancy in which the malignant cells produce hormones, cytokines, peptides or antibodies that causes symptoms and may affect multiple organ systems. These paraneoplastic conditions may be associated with different solid and hematological malignancies. Multiple Myeloma (MM) accounts for 10-15 % of hematological malignancies and 1-2 % of all malignancies. It is associated with some atypical clinical and laboratory paraneoplastic manifestations. Although there is a low incidence of these paraneoplastic, significant knowledge of these manifestations may assist in making a differential diagnosis in cases of doubt. The clinical presentation may vary and be evident even before or after the diagnosis of malignancy. These include vascular, neurological, dermatological, physiological, and other atypical conditions. Furthermore, these rare paraneoplastic manifestations need more valid, relevant scientific information, as most information about these conditions is derived from case reports. After the literature search, we have reported the paraneoplastic manifestations associated with multiple myeloma, published in the English literature, and the cognate management in this review article. To our knowledge, this is the first review article discussing various paraneoplastic manifestations of multiple myeloma.

The aftermath of the COVID-19 pandemic on pediatric mental health: A pediatric emergency department's perspective.

BACKGROUND: Pediatric mental health visits in the United States has become a public health crisis. Pediatric emergency departments (PED) encounter these patients during mental health emergencies. The COVID-19 pandemic disrupted the social environment of pediatric patients which potentially lead to new and worsening mental health issues. This study examined the proportion of mental health visits to PED around the first wave of the COVID-19 pandemic. METHODS: This retrospective cohort study assessed the proportion of mental health visits at a urban, PED between September 2019 to February 2022. Inclusion criteria were subjects aged 6 to 18 years with a holding order assigned, and one of identified mental health International Classification of Disease, Tenth Division (ICD-10) codes: F01-F99, T14.19, R45, R46.89. Proportion of mental health visits were compared in 6-month periods with the first 6-months representing the pre-COVID-19 period. Secondary analysis compared demographic information and ICD-10 codes. RESULTS: A total of 1036 charts were studied: 126 charts from 2019 to 2020, 512 from 2020 to 2021, and 398 from 2021 to 2022. The proportion of mental health visits from September 2019 to February 2020 was 1.4%, and for the following 6-month periods, the proportion of mental health visits was 1.2%, 7.5%, 4.9%, and 5.7%. There was a statistically significant difference (p < 0.001) demonstrating a higher proportion of mental health visits after the start of the COVID-19 pandemic. Secondary analysis demonstrated statistically significant difference in both median age (p < 0.001) and median length of hospitalization (p < 0.001). CONCLUSION: This study demonstrated a significant increase in pediatric mental health visits following the start of the COVID-19 pandemic. We believe further investigation into the needs and management during acute surges will improve the care we provide to this vulnerable population.

Biofabrication of silver nanoparticles using Spirulina platensis: In vitro anti-coagulant, thrombolytic and catalytic dye degradation activity.

Green synthesis of nanoparticles is an emerging field due to it's biosafety and promising results. Biological systems due to their biodiversity are employed in different production processes. In this study Spirulina platensis mediated silver nanoparticles (S-AgNPs) production was done. The Uv spectra, FTIR and SEM analysis was performed for the characterization of biosynthesized S-AgNPs. The biocompatibility evaluation of S-AgNPs was done through hemolysis analysis. S-AgNPs were also evaluated for anticoagulant and thrombolytic potential. In addition to the medical applications of S-AgNPs, silver nanoparticles have been known to show potential industrial applications among which one application is the utilization of silver nanoparticles in the degradation of toxic industrial dyes. Therefore, degradation assay of Eosin Y and Methylene Blue dyes was estimated. The SEM analysis of S-AgNPs showed the particle size of 50-65 nm, whereas the biocompatibility analysis showed that these S-AgNPs are biocompatible at ≤400 µM concentration. The S-AgNPs showed good anticoagulant potential and thrombolytic potential and were able to degrade 44% of the thrombus. The S-AgNPs significantly degraded 76% of Eosin Y within 30 min, whereas Methylene Blue was 80% degraded within 20 min (P-value ≤ .001). To the best of our knowledge, the dye degradation of Eosin Y, thrombolytic activity and anticoagulant activity of S-AgNPs produced from the biomass of Spirulina platensis has been reported for the first time. In the current study, we conclude that our biosynthesized S-AgNPs showed promising medical and industrial applications and these nanoparticles can be further evaluated and upscaled for large scale applications.

Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection.

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections (sLRIs) in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet (LFD) led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell (pDC) recruitment and perturbation of regulatory T cell expansion in the lungs. LFD altered the composition of the maternal milk microbiome and assembling infant gut microbiome. These microbial changes reduced the secretion of the DC growth factor Flt3L by neonatal intestinal epithelial cells and impaired downstream pDC hematopoiesis. Therapy with a propionate-producing bacteria isolated from the milk of high-fiber diet-fed mothers, or supplementation with propionate, conferred protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that promotes pDC hematopoiesis in early life and confers disease resistance against sLRIs.

A national pilot of donation after circulatory death (DCD) heart transplantation within the United Kingdom.

BACKGROUND: The United Kingdom (UK) was one of the first countries to pioneer heart transplantation from donation after circulatory death (DCD) donors. To facilitate equity of access to DCD hearts by all UK heart transplant centers and expand the retrieval zone nationwide, a Joint Innovation Fund (JIF) pilot was provided by NHS Blood and Transplant (NHSBT) and NHS England (NHSE). The activity and outcomes of this national DCD heart pilot program are reported. METHODS: This is a national multi-center, retrospective cohort study examining early outcomes of DCD heart transplants performed across 7 heart transplant centers, adult and pediatric, throughout the UK. Hearts were retrieved using the direct procurement and perfusion (DPP) technique by 3 specialist retrieval teams trained in ex-situ normothermic machine perfusion. Outcomes were compared against DCD heart transplants before the national pilot era and against contemporaneous donation after brain death (DBD) heart transplants, and analyzed using Kaplan-Meier analysis, chi-square test, and Wilcoxon's rank-sum. RESULTS: From September 7, 2020 to February 28, 2022, 215 potential DCD hearts were offered of which 98 (46%) were accepted and attended. There were 77 potential donors (36%) which proceeded to death within 2 hours, with 57 (27%) donor hearts successfully retrieved and perfused ex situ and 50 (23%) DCD hearts going on to be transplanted. During this same period, 179 DBD hearts were transplanted. Overall, there was no difference in the 30-day survival rate between DCD and DBD (94% vs 93%) or 90 day survival (90% vs 90%) respectively. There was a higher rate of ECMO use post-DCD heart transplants compared to DBD (40% vs 16%, p = 0.0006), and DCD hearts in the pre pilot era, (17%, p = 0.002). There was no difference in length of ICU stay (9 DCD vs 8 days DBD, p = 0.13) nor hospital stay (28 DCD vs 27 DBD days, p = 0.46). CONCLUSION: During this pilot study, 3 specialist retrieval teams were able to retrieve DCD hearts nationally for all 7 UK heart transplant centers. DCD donors increased overall heart transplantation in the UK by 28% with equivalent early posttransplant survival compared with DBD donors.

Safety and quality assessment of street-vended barbecue chicken samples from Faisalabad, Pakistan.

The current study was designed to assess the safety and quality status of street-vended barbecue chicken samples. The samples were collected from four regions of Faisalabad city: Ghulam Mohammad Abad (R1), Jhang Road (R2), Sargodha Road (R3), and Satiana Road (R4); and compared with the self-prepared barbecue chicken sample (R0). Purposely, all the collected samples were subjected to assess the quality aspects by physicochemical analyses. The results of the physicochemical analysis showed that moisture content varied from 54% to 60%, crude protein 26.97% to 32.87%, crude fat 7.25% to 9.00%, crude ash 1.61% to 1.72%, pH 5.60 to 6.30, free fatty acid value 1.00% to 1.39%, and peroxide value 0.63 to 0.84 meq/Kg. Results pertaining to the enumeration of total microbial load and total coliform count exhibit 2.39-5.17 and 1.20-3.20 log cfu/g, respectively. The samples were assessed for heavy metals (Pb, Zn, Cd, and Fe) by atomic absorption spectrophotometer (AAS). The concentration of highly toxic metals Pb and Cd was found to be much higher than recommended value as they ranged from 1.90 to 3.70 mg/kg for Pb and 0.10 to 0.90 mg/kg for Cd. However, the level of essential metals (Fe and Zn) in barbecue chicken samples ranged from 67.10 to 180 and 8.30 to 35.80 mg/kg which was much higher than their safe limits for Fe (15 ppm) and Zn (5 ppm), respectively. The study concludes that the consumption of street-vended barbecue chicken possesses to be a serious public health risk for consumers.

Benefits and Challenges of Video Consulting for Mental Health Diagnosis and Follow-Up: A Qualitative Study in Community Care.

Mental health services continue to experience rising demand that exceeds capacity. The COVID-19 pandemic exacerbated this crisis, with access to services being reduced. Although video consultations (VCs) are a solution, usage in UK community mental healthcare settings remains limited. This study aims to investigate psychiatrists' and general practitioners' (GPs) perceptions of the benefits and challenges of VC for the diagnosis and follow-up of general adult mental health patients in the community during the COVID-19 pandemic. Semi-structured interviews in NHS community mental healthcare settings were conducted. Psychiatrists (n = 11) and GPs (n = 12) were recruited through purposive sampling. An explorative qualitative approach was employed. Data were analysed using thematic analysis. Four key themes were identified: (1) patient access to VC, (2) suitability of VC for mental health consultations, (3) information gathering with VC and (4) clinician satisfaction with VC. This study provides valuable insights into the experiences of psychiatrists and GPs working in the UK during the COVID-19 pandemic. To facilitate a digital-first future for the NHS, greater investment in remote technologies is required, particularly in the context of growing mental healthcare demand. Though face-to-face consultations remain the gold standard, VC provides an efficient way of communicating with patients, particularly those with less severe forms of mental illness.

No difference in treatment outcome between patients with nodal versus extranodal diffuse large B-cell lymphoma.

Background and Aim: Diffuse large B-cell lymphoma (DLBCL) has been classified using various parameters, including the site of origin. Studies have reported conflicting outcomes when DLBLC patients were stratified according to the site of origin. This study aimed to investigate the response rate and survival outcomes in nodal versus extranodal DLBCL and compare the results to a region-matched study covering the 1988 - 2005 period. Methods: A single-center retrospective cohort study was conducted on all patients diagnosed with DLBCL and treated in a tertiary care hospital in Pakistan during 2014 - 2019. We calculated the mean and median for continuous variables and frequency and percentages for all categorical variables. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier survival curves. A Cox proportional hazards model was used to determine the hazard ratio (HR) for OS. Results: Of the 118 patients, 49 patients (41.5%) had nodal disease and 69 patients (58.5%) were diagnosed with extranodal DLBCL. The majority of patients in the nodal and extranodal cohorts presented with Stages III and IV disease (73.4% and 62.3%, respectively). A complete response to (immuno) chemotherapy was achieved in 71.4% of nodal DLBCL patients and 65.2% of extranodal DLBCL patients. The 5-year PFS and median PFS in the entire cohort were 0.8% and 17 m, respectively. The PFS and median PFS in the nodal and extranodal DLBCL cohort were 0% and 1.4%, respectively, and 15 m and 19 m, respectively. The 5-year OS and median OS in the entire cohort were 16.1% and 19 m, respectively. The OS and median OS in the nodal and extranodal DLBCL cohort were 8.2% and 21.7%, respectively, and 19 m and 21 m, respectively. Multivariable linear regression revealed that the ABC phenotype (nodal, HR = 1.37, 95% CI = 1.37 - 3.20; extranodal, HR = 1.65, 95% CI = 1.46 - 3.17; GBC as reference) and double and triple hit DLBCL (nodal, HR = 1.29, 95% CI = 1.19 - 2.81; extranodal, HR = 1.87, 95% CI = 1.28 - 2.43; and non-expressors as reference) are independent negative predictors of OS. Conclusions: DLBCL incidence in the Karachi region has remained comparable but patient composition in the extranodal DLBCL cohort has shifted to predominantly advanced stage. Nodal and extranodal DLBCL were associated with similar PFS and OS profiles and first- and second-line treatment responses. Cell of origin and antigen expression status was independent negative predictors of OS, disfavoring the ABC phenotype and lesions with c-MYC and BCL2 and/or BCL6 overexpression. Relevance for Patients: DLBCL is an aggressive type of non-Hodgkin's lymphoma, however; patients respond well to standard systemic chemotherapy. Extranodal type of DLBCL patients tend to have more residual disease after first-line systemic chemotherapy, but physicians should keep in mind that the subsequent line treatment mitigates its negative impact on survival.