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The gold standard for central arch defects of the mandible is reconstruction with vascularized bone free flap. Free flap repair is always not an option due to lack of resources and in patients who are not healthy enough for lengthy surgery. In these situations, a standardized method of repair is by reconstruction plate and wrapping it with a regional flap like pectoralis major myocutaneous flap (PMMC). However, this method of repair has increased risk of plate exposure, plate fracture, partial or complete flap necrosis, and delayed decannulation, swallowing, adjuvant treatment. Hence, we describe a new technique of incorporating titanium  R econstruction plate i n the S ubstance of PMMC (RISP technique) and address the drawbacks of the conventional method. The aim of the study is (1) to assess the feasibility of a novel method for mandibular reconstruction that incorporates a reconstruction plate within the substance of PMMC and (2) to compare the conventional method of repair of wrapping the reconstruction plate with RISP technique. Our case series of 22 patients who had arch mandibulectomy for cancer of oral cavity serves as the basis for our description of a novel technique of Recon plate in the Substance of PMMC (RISP technique) in 15 cases and comparison with 7 cases of old conventional technique for arch defects. A total of 22 eligible patients were included in the study. Of the 22 patients, 8 were males and 14 were females. Majority of the patients were above 55 years ( n  = 15, 68.1%); median age in RISP technique cohort is 64 years and 57 years in conventional technique. The mean duration of follow-up for the cohort was 27 months (7–47 months). The most common subsite was the buccal mucosa ( n  = 9, 40.9%). Majority of the patients had squamous cell carcinoma as histology except one had osteosarcoma. Plate-related morbidities were more commonly seen with conventional method (6 out of 7 had plate exposure). Flap-related morbidities were similar in both techniques. On multivariate analysis, technique of plating was the only factor predictive of plate-related complications ( p  < 0.001). The average time to starting oral feeds was 15 to 25 days for patients who have undergone plating with new technique as compared to 19–90 days for patients with conventional method. Patients operated with the newer technique had earlier decannulation and shorter duration of hospital stay when compared to conventional method. The average Functional Oral Intake Score was 5 to 6 in RISP technique. Our novel technique of inserting reconstruction plate within the substance of PMMC is a feasible alternative for mandibular arch defects with less complications and better functional outcome.

The COVID-19 pandemic has placed unprecedented pressure on healthcare services. Deprioritisation of nonemergency clinical services and growing concerns of adverse outcomes of COVID-19 in cancer patients is having a deleterious impact across oncologic practice. We report cancer surgery outcomes taking into account the acuity of the COVID-19 situation. A prospectively maintained database of the Department of Surgical Oncology was analysed from 1st May to 30th June, 2020, to evaluate the perioperative outcomes, morbidity and mortality following major surgical procedures. A total of 359, preoperatively, tested negative for COVID-19 underwent surgery. Median age was 52 years with 26.7% ( n  = 96) above the age of 60 years. Sixty-one percent ( n  = 219) patients were American Society of Anaesthesiology grades II–III. As per surgical complexity grading, 36.8% ( n  = 132) cases were lower grades (I–III) and 63.2% ( n  = 227) were complex surgeries (IV–VI). 5.3% ( n  = 19) had ≥ grade III Clavien-Dindo complication, and the postoperative mortality rate was 0.27% ( n  = 1). Major complication rates in patients > 60 years were 9.3% in comparison to 4.1% in < 60 years ( p  = 0·63). The median hospital stay was 1–10 days across subspecialties. Postoperatively, repeat COVID 19 testing in 2 suspected patients were negative. Our study showed that after screening, triaging and prioritisation, asymptomatic cases may undergo cancer surgeries without increased morbidity during COVID-19 pandemic.

The gold standard for central arch defects of the mandible is reconstruction with vascularized bone free flap. Free flap repair is always not an option due to lack of resources and in patients who are not healthy enough for lengthy surgery. In these situations, a standardized method of repair is by reconstruction plate and wrapping it with a regional flap like pectoralis major myocutaneous flap (PMMC). However, this method of repair has increased risk of plate exposure, plate fracture, partial or complete flap necrosis, and delayed decannulation, swallowing, adjuvant treatment. Hence, we describe a new technique of incorporating titanium  econstruction plate n the ubstance of PMMC (RISP technique) and address the drawbacks of the conventional method. The aim of the study is (1) to assess the feasibility of a novel method for mandibular reconstruction that incorporates a reconstruction plate within the substance of PMMC and (2) to compare the conventional method of repair of wrapping the reconstruction plate with RISP technique. Our case series of 22 patients who had arch mandibulectomy for cancer of oral cavity serves as the basis for our description of a novel technique of Recon plate in the Substance of PMMC (RISP technique) in 15 cases and comparison with 7 cases of old conventional technique for arch defects. A total of 22 eligible patients were included in the study. Of the 22 patients, 8 were males and 14 were females. Majority of the patients were above 55 years (  = 15, 68.1%); median age in RISP technique cohort is 64 years and 57 years in conventional technique. The mean duration of follow-up for the cohort was 27 months (7-47 months). The most common subsite was the buccal mucosa (  = 9, 40.9%). Majority of the patients had squamous cell carcinoma as histology except one had osteosarcoma. Plate-related morbidities were more commonly seen with conventional method (6 out of 7 had plate exposure). Flap-related morbidities were similar in both techniques. On multivariate analysis, technique of plating was the only factor predictive of plate-related complications (  < 0.001). The average time to starting oral feeds was 15 to 25 days for patients who have undergone plating with new technique as compared to 19-90 days for patients with conventional method. Patients operated with the newer technique had earlier decannulation and shorter duration of hospital stay when compared to conventional method. The average Functional Oral Intake Score was 5 to 6 in RISP technique. Our novel technique of inserting reconstruction plate within the substance of PMMC is a feasible alternative for mandibular arch defects with less complications and better functional outcome.

Venous thromboembolism (VTE) is an important cause of morbidity and mortality in the United States (US). The increasing rates of VTE in the US resulted in the surgeon general issuing a call to action to reduce VTE in 2008. The objective of our study was to analyze the national trends of inpatient VTE in the US from 2004 to 2013 (5 years before and after 2008). We used the dataset National Inpatient Sample, Healthcare Cost and Utilization Project and measured trends of inpatient VTE by annual % change using joinpoint regression software. From 2004 to 2013 the National Inpatient Sample contained data on 78 million hospitalizations (weighted n = 385 million). In these 1.6 million had a diagnosis of VTE (2.0%, weighted n = 7.7 million) including 1.2 million with deep venous thrombosis (DVT) (1.53%, weighted n = 5.9 million) and 588,878 with pulmonary embolism (PE) (0.74%, weighted n = 2.8 million). Joinpoint regression analysis showed that rates of DVT and PE are increasing consistently from 2004 to 2013(1.27% to 1.80% for DVT and 0.52% to 0.92% for PE). The increasing rates of DVT and PE were consistent in all subgroups except few exceptions. In conclusion inpatient VTE rates continue to rise even after 5 years from the surgeon general's a call to action except in certain high-risk patients. Further research is needed to curb the VTE in patients especially among those perceived to be at lower risk of VTE.

ImmunoPET/CT imaging using a labeled SIV-specific antibody can identify sites of viralinfection in SIV-infected macaques without the need for tissue biopsies, even if viral load in the blood is below the detection limit. The detection of viral dynamics and localization in the context of controlled HIV infection remains a challenge and is limited to blood and biopsies. We developed a method to capture total-body simian immunodeficiency virus (SIV) replication using immunoPET (antibody-targeted positron emission tomography). The administration of a poly(ethylene glycol)-modified, 64 Cu-labeled SIV Gp120–specific antibody led to readily detectable signals in the gastrointestinal and respiratory tract, lymphoid tissues and reproductive organs of viremic monkeys. Viral signals were reduced in aviremic antiretroviral-treated monkeys but detectable in colon, select lymph nodes, small bowel, nasal turbinates, the genital tract and lung. In elite controllers, virus was detected primarily in foci in the small bowel, select lymphoid areas and the male reproductive tract, as confirmed by quantitative reverse-transcription PCR (qRT-PCR) and immunohistochemistry. This real-time, in vivo viral imaging method has broad applications to the study of immunodeficiency virus pathogenesis, drug and vaccine development, and the potential for clinical translation.

The coronavirus disease 2019 (COVID-19) is a viral disease caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that affects the respiratory system of infected individuals. COVID-19 spreads between humans through respiratory droplets produced when an infected person coughs or sneezes. The COVID-19 outbreak originated in Wuhan, China at the end of 2019. As of 29 Sept 2020, over 235 countries, areas or territories across the globe reported a total of 33,441,919 confirmed cases, and 1,003,497 confirmed deaths due to COVID-19. Individuals of all ages are at risk for infection, but in most cases disease severity is associated with age and pre-existing diseases that compromise immunity, like cancer. Numerous reports suggest that people with cancer can be at higher risk of severe illness and related deaths from COVID-19. Therefore, managing cancer care under this pandemic is challenging and requires a collaborative multidisciplinary approach for optimal care of cancer patients in hospital settings. In this comprehensive review, we discuss the impact of the COVID-19 pandemic on cancer patients, their care, and treatment. Further, this review covers the SARS-CoV-2 pandemic, genome characterization, COVID-19 pathophysiology, and associated signaling pathways in cancer, and the choice of anticancer agents as repurposed drugs for treating COVID-19.

Neuroblastoma (NB) is a highly aggressive pediatric cancer that originates from immature nerve cells, presenting significant treatment challenges due to therapy resistance. Despite intensive treatment, approximately 50% of high-risk NB cases exhibit therapy resistance or experience relapse, resulting in poor outcomes often associated with tumor immune evasion. B7-H3 is an immune checkpoint protein known to inhibit immune responses. MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation. Our study aims to explore the impact of miRNAs on B7-H3 regulation, the anti-tumor immune response, and tumorigenicity in NB. Analysis of NB patients and patient-derived xenograft tumors revealed a correlation between higher B7-H3 expression and poorer patient survival. Notably, deceased patients exhibited a depletion of miR-29 family members (miR-29a, miR-29b, and miR-29c), which displayed an inverse association with B7-H3 expression in NB patients. Overexpression and knockdown experiments demonstrated that these miRNAs degrade B7-H3 mRNA, resulting in enhanced NK cell activation and cytotoxicity. In vivo, experiments provided further evidence that miR-29 family members reduce tumorigenicity, macrophage infiltration, and microvessel density, promote infiltration and activation of NK cells, and induce tumor cell apoptosis. These findings offer a rationale for developing more effective combination treatments that leverage miRNAs to target B7-H3 in NB patients.

Ultra-long-acting integrase strand transfer inhibitors were created by screening a library of monomeric and dimeric dolutegravir (DTG) prodrug nanoformulations. This led to an 18-carbon chain modified ester prodrug nanocrystal (coined NM2DTG) with the potential to sustain yearly dosing. Here, we show that the physiochemical and pharmacokinetic (PK) formulation properties facilitate slow drug release from tissue macrophage depot stores at the muscle injection site and adjacent lymphoid tissues following single parenteral injection. Significant plasma drug levels are recorded up to a year following injection. Tissue sites for prodrug hydrolysis are dependent on nanocrystal dissolution and prodrug release, drug-depot volume, perfusion, and cell-tissue pH. Each affect an extended NM2DTG apparent half-life recorded by PK parameters. The NM2DTG product can impact therapeutic adherence, tolerability, and access of a widely used integrase inhibitor in both resource limited and rich settings to reduce HIV-1 transmission and achieve optimal treatment outcomes. Here, using animal models, Deodhar et al . single parenteral dose of dolutegravir (DTG) prodrug nanocrystals sustains drug protein-adjusted 90% inhibitory concentration for up to a year, without injection site reactions or systemic toxicities.

A recent study found that approximately 1 in every 6 patients hospitalized for the 1st episode of syncope had an underlying pulmonary embolism (PE). As current guidelines do not strongly emphasize evaluation for PE in the workup of syncope, we hypothesize that there might be a higher rate of 30-day readmission due to untreated venous thromboembolism (VTE). The objective of this study is to measure the 30-day readmission rate due to VTE and identify predictors of 30-day readmission with VTE among syncope patients. We identified patients admitted with syncope with ICD9 diagnoses code 780.2 in the Nationwide Readmission Database (NRD-2013), Healthcare Cost and Utilization Project (HCUP). The 30-day readmission rate was calculated using methods described by HCUP. Logistic-regression was used to identify predictors of 30-day readmission with VTE. Discharge weights provided by HCUP were used to generate national estimates. In 2013, NRD included 207,339 eligible patients admitted with syncope. The prevalence rates of PE and DVT were 1.1% and 1.4%, respectively. At least one syncope associated condition was present in 60.9% of the patients. Among the patients who were not diagnosed with VTE during index admission for syncope (N = 188,015), 30-day readmission rate with VTE was 0.5% (0.2% with PE and 0.4% with DVT). In conclusion, low prevalence of VTE in patients with syncope and extremely low 30-day readmission rate with VTE argues against missed diagnoses of VTE in index admission for syncope. These results warrant further studies to determine clinical impact of work up for PE in syncope patients without risk factors.

Antiretroviral drug therapy (ART) effectively suppresses replication of both the immunodeficiency viruses, human (HIV) and simian (SIV); however, virus rebounds soon after ART is withdrawn. SIV-infected monkeys were treated with a 90-day course of ART initiated at 5 weeks post infection followed at 9 weeks post infection by infusions of a primatized monoclonal antibody against the α₄β₇ integrin administered every 3 weeks until week 32. These animals subsequently maintained low to undetectable viral loads and normal CD4⁺ cell counts in plasma and gastrointestinal tissues for more than 9 months, even after all treatment was withdrawn. This combination therapy allows macaques to effectively control viremia and reconstitute their immune systems without a need for further therapy.