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Federal officials have ordered a temporary halt to the planned shutdowns of two coal-burning Indiana power plants amid President Donald Trump’s attempts to boost the coal mining industry.

The U.S. Department of Energy orders issued Tuesday require Northern Indiana Public Service Co. and CenterPoint Energy to keep those generating plants operating despite their intentions of closing them this month.

The 90-day orders say the two coal-burning units set for closure at NIPSCO’s Schahfer Generating Station near Wheatfield and one at CenterPoint’s Culley Generating Station along the Ohio River near Newburgh must remain “available to operate” until at least March 23.

The orders come as Trump has pushed policies to promote the coal industry while deriding the shift toward solar and wind energy as sources of electricity.

The Energy Department said the Indiana plants orders were needed because the “reliable supply of power from these coal plants is essential for keeping the region’s electric grid stable.” Both orders cited the growing power demands of data centers among the reasons for keeping the plants in operation.

“Keeping these coal plants online has the potential to save lives and is just common sense,” Energy Secretary Chris Wright said in a statement. “Americans deserve reliable power regardless of whether the wind is blowing or the sun is shining during extreme winter conditions.”

The federal agency has issued similar orders for power plants in other states in recent months, including a large coal-burning station in Michigan.

Companies’ response

Indiana’s major utilities have over many years been shifting away from coal-powered plants toward using natural gas and renewable sources for electricity generation.

It was not immediately clear Wednesday how NIPSCO and Centerpoint would abide with the orders to keep the coal-burning plants in operations.

NIPSCO, which has more than 450,000 electric customers across northern Indiana, said it would comply with the order and was “reviewing the overall impact to our customers and company.”

“We recognize the importance of both reliability and cost management for our customers, and we will continue to engage with federal, state and local stakeholders as we adapt to evolving regulatory requirements,” Vince Parisi, NIPSCO’s president and chief operating officer, said in a statement.

CenterPoint, which serves about 150,000 customers in the Evansville area, announced plans in 2023 to convert its last coal-burning unit at the Culley Generation Station to natural gas by 2027.

The company said its plans would reduce costs while preserving the Culley station’s generating capacity and adding solar and wind power sources in the coming years.

CenterPoint said Wednesday it would “continue to work collaboratively with our federal, state and local partners and remain focused on prioritizing affordability and energy security.”

“Working together, we will help contribute to regional electric reliability efforts to focus on what is most important — safe and reliable service for our customers and fellow Hoosiers during the upcoming winter months,” the company said in a statement.

The NIPSCO units set for closure generate about 850 megawatts of electricity and date to the 1980s, according to the federal orders. The CenterPoint unit generates about 100 megawatts and began operations in 1966.

Coal foes blast orders

Environmental groups and consumer advocates denounced the Energy Department orders, arguing they would force “households to pay more for coal’s deadly air and toxic water pollution.”

“The federal government’s order to force extremely expensive and unreliable coal units to stay open will result in higher bills for Hoosiers who are already reeling from record-high rate increases in 2025,” said Ben Inskeep, program director for the Citizens Action Coalition of Indiana. “We can’t afford this costly and unfounded federal overreach.”

An analysis by the Citizens Action Coalition released in July of Indiana’s five investor-owned electric utilities found that residential bills spiked by 17.5% in one year, or $28 a month on average statewide.

Ashley Williams, executive director of Just Transition Northwest Indiana, called NIPSCO’s Schahfer plant “one of the most notorious polluters in the country.”

“On-site coal ash contamination of groundwater, along with a proposed massive gas plant and AI data center, compounds an extremely dire situation and creates an unconscionable environmental burden,” Williams said. “The Trump administration is trying to steal away our futures by keeping us tethered to the dirty coal energy of the past.”

Metastatic gastric cancer (mGC) remains a lethal disease, and while systemic therapy has gradually extended survival in clinical practice, outcomes are still poor overall. Immune checkpoint inhibitors (ICIs), particularly PD-1 blockade, have improved outcomes in multiple solid tumors, and nivolumab is an established later-line option in mGC based on prior randomized evidence.

A growing body of work suggests that circadian biology can shape immune function—immune-cell trafficking, antigen presentation, cytokine release, and effector activation fluctuate over a 24-hour cycle. “Chronotherapy” applies this concept by aligning treatment delivery with the body’s internal clock to potentially improve efficacy and safety. However, until this analysis, there had been no dedicated report in mGC evaluating whether nivolumab infusion timingcorrelates with outcomes.

Study Design and Methods

This was a single-center, retrospective study of patients with unresectable advanced or recurrent gastric/GEJ adenocarcinoma treated with nivolumab monotherapy as third-line or later therapy between December 2014 and December 2022.

• Treatment: nivolumab 3 mg/kg or 240 mg every 2 weeks, or 480 mg every 4 weeks.
• Eligibility highlights: age ≥20, ECOG PS 0–2, ≥2 prior regimens including fluoropyrimidine + taxane, and at least two nivolumab infusions.

Exposure definition (timing groups)

Infusion start times were pulled from medical records:

• Early infusion group (EA): ≥70% of infusions before 14:00
• Late infusion group (LA): <70% of infusions before 14:00

The 14:00 cutoff was chosen because it matched the most frequent infusion time window (13:30–14:00) and aligned with a prior chronotherapy report design.

Results

Between December 2014 and December 2022, 296 patients received nivolumab, of whom 248 met the eligibility criteria for analysis. Patients were divided according to infusion timing into an early administration (EA) group (n = 140) and a late administration (LA) group (n = 108). Overall, baseline clinicopathologic characteristics were well balanced between the two groups. However, patients in the EA group showed slightly more favorable inflammatory profiles, with a higher proportion of patients having a neutrophil-to-lymphocyte ratio (NLR) <2.4 (59% vs 38%) and a trend toward lower modified Glasgow prognostic scores (mGPS). As expected, the median infusion start time differed substantially between groups (11:50 in the EA group vs 14:22 in the LA group).

Tumor response

Among the 149 patients with measurable disease, treatment efficacy differed markedly by infusion timing. The objective response rate (ORR) was significantly higher in the EA group (17%) compared with the LA group (3%). Similarly, the disease control rate (DCR) was more than doubled in the EA group (47% vs 20%). In contrast, progressive disease was substantially more frequent among patients receiving late-day infusions.

gastric cancer

Survival outcomes

Survival analyses consistently favored early nivolumab administration. Median progression-free survival (PFS) was 2.3 months in the EA group compared with 1.6 months in the LA group, corresponding to a hazard ratio (HR) of 0.65, which was statistically significant. Median overall survival (OS) was also significantly prolonged with early administration (7.6 months vs 3.9 months; HR 0.64).

Importantly, infusion timing remained an independent prognostic factor after multivariable adjustment, with adjusted HRs of 0.70 for PFS and 0.67 for OS, confirming that the observed survival advantage was not solely explained by baseline imbalances.

Sensitivity and robustness analyses

Additional analyses supported the robustness of these findings. When alternative cutoff values were tested, the survival benefit of early administration persisted and became evident once more than approximately 50% of infusions were delivered earlier in the day. Furthermore, in a three-group model stratified by the proportion of early versus late infusions, outcomes followed a clear stepwise pattern: patients treated predominantly in the early hours experienced the most favorable outcomes, those with mixed timing had intermediate results, and patients treated mostly later in the day had the poorest survival.

Safety

• About one-third experienced at least one irAE.
• Most common irAEs: skin toxicity (rash/pruritus), thyroid dysfunction, and transaminase elevation.
• Any-grade irAEs were numerically higher in EA (40.7% vs 29.6%), and skin irAEs were significantly more frequent in EA.
• Grade 3/4 irAEs were similar between groups (~6–7%).
• No treatment-related deaths.

This pattern fits prior observations in ICI practice where the presence of certain irAEs—especially skin toxicities—can correlate with improved outcomes, although causality cannot be inferred here.

Insights

This analysis strengthens a provocative, clinically practical idea: the same drug, given earlier in the day, may be associated with better outcomes—even in a setting as difficult as later-line mGC.

The proposed biological rationale is not about nivolumab’s long plasma half-life; rather it centers on shorter-timescale pharmacodynamics and immune trafficking: if nivolumab distribution to lymphoid tissues and tumor-draining nodes coincides with periods when naïve and memory T cells preferentially localize to lymph nodes, antigen presentation and priming may be more effectively “unblocked,” translating into deeper or more frequent responses. The study also highlights how systemic inflammation markers (like NLR and mGPS) remain powerful prognostic variables in real-world ICI-treated mGC—and timing appeared to retain independent prognostic impact even when accounting for these.

Key Takeaway Messages

In this real-world cohort of third-line+ nivolumab monotherapy for mGC, receiving nivolumab mostly before 14:00 was associated with:

• Higher ORR (17% vs 3%)
• Higher DCR (47% vs 20%)
• Longer PFS (2.3 vs 1.6 months)
• Longer OS (7.6 vs 3.9 months)

The observed association persisted after adjustment in multivariable analyses, confirming infusion timing as an independent factor. Early administration was associated with a higher incidence of immune-related adverse events of any grade, most notably cutaneous toxicities, while no increase in severe (grade 3–4) irAEs was observed. These findings should be interpreted as hypothesis-generating, given the retrospective study design and the potential influence of post-progression treatments on overall survival. Accordingly, prospective, randomized studies are required to validate these observations.

Conclusion

This study suggests that chronotherapy may be an actionable, zero-cost optimization for nivolumab in metastatic gastric cancer—potentially improving efficacy without adding toxicity burden. While the mechanism is not yet defined and confounding is unavoidable in retrospective research, the signal is consistent with chronobiology-informed immunotherapy data from other tumors. The next step is clear: prospective randomized trials and translational work integrating immune-cell dynamics, cortisol rhythms, lymphocyte trafficking, and tissue pharmacokinetics to determine whether “treating earlier” can become a reproducible standard in ICI delivery.

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