This study examines the impact of the COVID-19 pandemic on health care–associated infection (HAI) incidence in low- and middle-income countries (LMICs). Patients from 7 LMICs were followed up during hospital intensive care unit (ICU) stays from January 2019 to May 2020. HAI rates were calculated using the International Nosocomial Infection Control Consortium (INICC) Surveillance Online System applying the Centers for Disease Control and Prevention's National Healthcare Safety Network (CDC-NHSN) criteria. Pre–COVID-19 rates for 2019 were compared with COVID-19 era rates for 2020 for central line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), mortality, and length of stay (LOS). A total of 7,775 patients were followed up for 49,506 bed days. The 2019 to 2020 rate comparisons were 2.54 and 4.73 CLABSIs per 1,000 central line days (risk ratio [RR] = 1.85, p = .0006), 9.71 and 12.58 VAEs per 1,000 mechanical ventilator days (RR = 1.29, p = .10), and 1.64 and 1.43 CAUTIs per 1,000 urinary catheter days (RR = 1.14; p = .69). Mortality rates were 15.2% and 23.2% for 2019 and 2020 (RR = 1.42; p < .0001), respectively. Mean LOS for 2019 and 2020 were 6.02 and 7.54 days (RR = 1.21, p < .0001), respectively. This study documents an increase in HAI rates in 7 LMICs during the first 5 months of the COVID-19 pandemic and highlights the need to reprioritize and return to conventional infection prevention practices.

Russia’s military incursion into Ukraine triggered the mass displacement of two-thirds of Ukrainian children and adolescents, creating a cascade of population health consequences and producing extraordinary challenges for monitoring and controlling preventable pediatric infectious diseases. From the onset of the war, infectious disease surveillance and healthcare systems were severely disrupted. Prior to the reestablishment of dependable infectious disease surveillance systems, and during the early months of the conflict, our international team of pediatricians, infectious disease specialists, and population health scientists assessed the health implications for child and adolescent populations. The invasion occurred just as the COVID-19 Omicron surge was peaking throughout Europe and Ukrainian children had not received COVID-19 vaccines. In addition, vaccine coverage for multiple vaccine-preventable diseases, most notably measles, was alarmingly low as Ukrainian children and adolescents were forced to migrate from their home communities, living precariously as internally displaced persons inside Ukraine or streaming into European border nations as refugees. The incursion created immediate impediments in accessing HIV treatment services, aimed at preventing serial transmission from HIV-positive persons to adolescent sexual or drug-injection partners and to prevent vertical transmission from HIV-positive pregnant women to their newborns. The war also led to new-onset, conflict-associated, preventable infectious diseases in children and adolescents. First, children and adolescents were at risk of wound infections from medical trauma sustained during bombardment and other acts of war. Second, young people were at risk of sexually transmitted infections resulting from sexual assault perpetrated by invading Russian military personnel on youth trapped in occupied territories or from sexual assault perpetrated on vulnerable youth attempting to migrate to safety. Given the cascading risks that Ukrainian children and adolescents faced in the early months of the war—and will likely continue to face—infectious disease specialists and pediatricians are using their international networks to assist refugee-receiving host nations to improve infectious disease screening and interventions.

Cancer cells alter their metabolism to support growth and survival, most notably by fermenting glucose to lactate even in the presence of oxygen, a phenomenon known as the Warburg effect. Although this metabolic state has been recognized for decades, its bioenergetic advantages remain unclear, as fermentation produces less net ATP than mitochondrial respiration. How aerobic fermentation contributes to cellular energy balance therefore remains unresolved. Here, we show that extracellular acidification generated by lactate export creates a proton gradient across the plasma membrane that is harnessed by ectopic ATP synthases to drive intracellular ATP production. We find that ATP synthase and proton-shuttling components of the mitochondrial respiratory chain translocate to the plasma membrane in cancer cells and are preferentially oriented to exploit this gradient, linking a hallmark of aerobic fermentation directly to energy supplementation. This work provides a mechanistic resolution to the apparent energetic inefficiency of the Warburg paradigm and identifies a previously unrecognized pathway for energy complementation in cancer.

Cancer cells undergo extensive metabolic reprogramming and can become dependent on glutamine to replenish the tricarboxylic acid cycle when glucose-derived carbon is diverted to lactate production, yet the transcriptional programs coordinating this response remain incompletely defined. We previously identified estrogen-related receptor gamma (ESRRG) as a driver of hypoxic adaptation in retinoblastoma (Rb), and here we show that ESRRG also regulates glutamine-responsive metabolism. ESRRG knockdown reduced transcriptional programs associated with glycolysis and glutamine utilization, while pharmacological inhibition with GSK5182 attenuated glutamine-dependent viability and survival. Conversely, ESRRG overexpression increased sensitivity to glutamine withdrawal in mesenchymal stem cells. Mechanistically, glutamine enhanced basal and maximal respiration, spare respiratory capacity, and ATP-linked respiration in Rb cells, whereas these responses were attenuated by GSK5182. Targeted LC-MS/MS profiling further showed reduced glutamine-responsive accumulation of intracellular glutamine, glutamate, α-ketoglutarate, and downstream TCA-associated metabolites following ESRRG inhibition. These findings identify ESRRG as a regulator of glutamine dependence and mitochondrial metabolic flexibility in Rb and nominate ESRRG-associated glutamine utilization as a potential metabolic vulnerability.

Cancer cells alter their metabolism to support growth and survival, most notably by fermenting glucose to lactate even in the presence of oxygen, a phenomenon known as the Warburg effect. Although this metabolic state has been recognized for decades, its bioenergetic advantages remain unclear, as fermentation produces less net ATP than mitochondrial respiration. How aerobic fermentation contributes to cellular energy balance therefore remains unresolved. Here, we show that extracellular acidification generated by lactate export creates a proton gradient across the plasma membrane that is harnessed by ectopic ATP synthases to drive intracellular ATP production. We find that ATP synthase and proton-shuttling components of the mitochondrial respiratory chain translocate to the plasma membrane in cancer cells and are preferentially oriented to exploit this gradient, linking a hallmark of aerobic fermentation directly to energy supplementation. This work provides a mechanistic resolution to the apparent energetic inefficiency of the Warburg paradigm and identifies a previously unrecognized pathway for energy complementation in cancer.