Biology of glucose metabolization in cancer cells

Cancer is a disease at the cellular level involving heritable disorders in cellular control mechanism. Cancer cells also need to adapt their metabolism to survive and multiply under the metabolically compromised conditions provided by the tumor microenvironment. Tumor cells alter their metabolism to maintain unregulated cellular proliferation and survival, but this transformation leaves them reliant on constant supply of nutrients and energy. They alter their metabolism to support their rapid prolif- eration and expansion across the body. After the discovery of based on the altered cancer cell metabolism in 1930, loads of studies have shed light on several aspects of cancer metabolism with a common goal to fi nd new ways for effectively eliminating tumor cells by targeting their energy metabolism. Research has directed most of its resources to elucidate the causes, prevention and possible cure for cancer, yet the process has been elusive claiming human lives more than ever. This disease is a manifestation of etio- logical and pathological disturbances of mechanisms that control cell division, differentiation and metabolism. 50% of all human tumors carry genetic alterations that lead to the inactivation of some tumor suppressor proteins. Cancer cells are shown to experience characteristic changes in their meta- bolic programs, including increased uptake of glucose, enhanced rates of glutaminolysis and fatty acids synthesis, suggesting that metabolic shifts supports tumor cells growth and survival. In this review, we summarized the major concepts of glucose metabolization and explore the molecular basis of aerobic glycolysis of cancer cell

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Rhinosinusitis in the Pediatric Patient with Cystic Fibrosis

Cystic fibrosis (CF) is a common autosomal recessive genetic disorder where a deletion mutation and subsequent downstream alteration in transmembrane regulator proteins results in increased mucus viscosity. CF manifests clinically with chronic multisystem inflammation and recurrent infections. Nearly all children with CF have chronic sinusitis, and a large majority will have concurrent sinonasal polyposis. Chronic sinusitis and sinonasal polyposis in pediatric patients with CF can be managed conservatively initially, though most will fail medical management and require surgical intervention. Unfortunately, symptom resolution is marginal and polyp recurrence rates are high. Currently, no cure exists for CF and the mainstay of treatment is to provide symptomatic relief, and minimize disease morbidity

Distant pseudomeningoceles of the ventral skull base: a report of 2 cases

The objective of this case series was to report what is to the best of our knowledge the first reports of nasopharyngeal and soft palate pseudomeningoceles tracking submucosally from the sphenoid sinus. Analysis of cases through medical records. Two cases of middle-aged male patients presented to our tertiary care university teaching hospital for recurrent meningitis and a history of cerebrospinal fluid (CSF) rhinorrhea. Both were found to have pseudomeningoceles distant from the sphenoid sinus. One was tracking to the mucosa of the Eustachian tube, and the other to the dorsum of the soft palate. Both were found to be tracking submucosally from the sphenoid sinus, to the vidian canal, to the lateral nasopharyngeal wall, to their respective locations at the Eustachian tube and dorsum of the soft palate. CSF closure was performed with a transnasal endoscopic repair using the pedicled nasoseptal flap for 1 patient and Alloderm for the other, both with successful cessation of CSF rhinorrhea. We present these cases of distant spontaneous CSF leaks. We review the literature and discuss case management

Transoral laser microsurgery in previously irradiated patients with laryngeal cancer

Early laryngeal cancer is successfully managed with transoral laser microsurgery. Previously radiated patients may experience more post-operative complications. We investigate disease-free survival and secondarily prolonged pain and chondronecrosis. Retrospective review of 52 patients undergoing transoral laser microsurgery after previous radiation. Mean disease-free survival was 36.7 months. Overall disease-free survival was 57.6% at 3-year and 48.4% at 5-year follow-up, with no significant difference between surgery within as opposed to after 60 months of radiation or within as opposed to after 12 months of radiation. Thirteen patients, all with surgery within 60 months of radiation, experienced prolonged pain. Twelve experienced chondronecrosis, all within 12 months of surgery. Transoral laser microsurgery for early laryngeal cancer is an adequate therapeutic option in patients with history of radiation with comparable disease-free survival to other reports. Patients undergoing transoral laser microsurgery within 60 months of radiation treatment are more likely to experience prolonged pain

The Role of Fine-Needle Aspiration in Parotid Pleomorphic Adenoma

Objective: Fine-needle aspiration (FNA) biopsy is often used as a well-accepted and both sensitive and specific diagnostic adjunct in the workup of parotid masses. In the case of pleomorphic adenoma, the most common benign tumor of the parotid gland, we examine cytopathologic reports to assess the performance of FNA for this particular histologic diagnosis. Method: A total of 317 patients who underwent parotidectomy over the past 5 years and met eligibility criteria of 1) primary parotid tumor, 2) age greater than 18 years, and 3) availability of pathology (FNA, intraoperative frozen section, final pathology) were reviewed. Clinical history and demographics, physical exam findings, and intraoperative findings were noted. Results: Pleomorphic adenoma was noted on final pathology in 136 patients (42.9%). Interestingly 24 (17.6%) of these patients had initially undergone FNA and been given a incorrect diagnosis, despite the FNA being “diagnostic.” One patient received false positive diagnosis of malignancy by FNA. Of the 24 patients with incorrect diagnosis on FNA, 15 (62.5%) received the correct diagnosis of pleomorphic adenoma with intraoperative frozen section, though one patient received a false positive for malignancy and underwent surgical upstage unnecessarily. For pleomorphic adenoma, it appears that diagnostic sensitivity increases from 82% for FNA to 92% with frozen section. Conclusion: While FNA is commonly used as preoperative diagnostic adjunct for parotid masses, one must exercise caution, even in the context of a diagnostic sample, as nearly 18% of pleomorphic adenomas were not identified. Fortunately, misdiagnosis was benign 95% of time, and subsequently had no surgical implications

Incidence of Occult Nodal Disease in Patients Treated with Salvage Laryngectomy with Radiologically Negative Neck

Objectives: The National Comprehensive Cancer Network guidelines address neck dissection in the setting of primary tumor treatment but do not provide a clear guideline for negative nodal disease in recurrent advanced laryngeal cancer. We often extrapolate the indication of neck dissection for recurrent disease based on the guidelines of primary disease. It is controversial whether there is a survival benefit for patients with clinically and radiologically negative (N0) necks to receive a neck dissection versus conservative management. This study aims to determine survival outcomes and incidence of post-operative complications in patients who underwent neck dissection at the time of salvage laryngectomy with clinically and radiologically negative neck. Methods: Single institution case series at a tertiary care university hospital. We identified 424 cases of total laryngectomy between 2000-2010.We reviewed the subset of N0 patients who had salvage laryngectomy and divided them into neck dissection versus conservative management. We reviewed demographic variables, final pathological stage of dissected neck specimen, and post-operative course and survival. Results: Patients who had a neck dissection at salvage laryngectomy with clinically N0 disease as compared to those treated conservatively may have no significant difference in survival; there may be a significant difference in the complication rate and perioperative mortality rate between the two groups. Conclusions: The data reviewed in this large series of patients will be useful for clinicians to determine the survival and complications that are frequently experienced by patients following neck dissection with salvage laryngectomy in the setting of previous radiation

Changing trends of speech outcomes after total laryngectomy in the 21st century: a single-center study

To describe the speech rehabilitation outcomes of patients undergoing total laryngectomy (TL) in the 21st century. Retrospective chart review. Tertiary academic center Retrospective review of 167 patients who underwent TL from June 2000 to February 2012. Demographics, disease variables, and surgical factors were reviewed. Primary alaryngeal speech modality, speech outcome, and tracheoesophageal puncture (TEP) complication rates were assessed. Overall TEP speech success rate (primary or secondary) was 72%. Overall TEP speech success rate was 76% for those with primary TEP and was 68% for those with secondary TEP. TEP speech success rates at first, second, and beyond second year were 75%, 72%, and 70%, respectively. Success rates for primary TL, salvage TL, primary TL with pharyngeal reconstruction, or salvage TL with pharyngeal reconstruction groups were 71%, 72%, 73%, and 71%, respectively. TEP-related complications occurred in 43% of patients, with no difference in complication rates between primary versus salvage TL or primary versus secondary TEP. For those with complications, TEP success rate was 65%. This study showed TEP speech-outcome success rates lower than what has been historically reported. There was no significant difference in TEP speech outcome between primary versus salvage TL or primary versus secondary TEP. Patients with TEP-related complications had TEP speech-outcome success rates comparable to those without any complication. TEP may continue to be a superior option as a mode of speech in patients with TL, including those undergoing salvage TL. 4