Baseline corticosteroid use of ≥ 10 mg of prednisone equivalent was associated with poorer outcome in patients with non-small-cell lung cancer who were treated with PD-(L)1 blockade. Prudent use of corticosteroids at the time of initiating PD-(L)1 blockade is recommended.

Background: Intrapulmonary percussive ventilation is used in various clinical settings to promote secretion clearance, reverse or treat atelectasis and improve gas exchange. Despite a few studies reporting the use of intrapulmonary percussive ventilation in critical care, the available data remain insufficient, contributing to weaker evidence toward its effectiveness. Also, there is a paucity of studies evaluating the safety and feasibility of intrapulmonary percussive ventilation application in critical care. This retrospective pilot study has evaluated the safety and feasibility of intrapulmonary percussive ventilation intervention in non-intubated patients admitted to an intensive care unit. Methods: The medical records of 35 subjects were reviewed, including 22 subjects who received intrapulmonary percussive ventilation intervention and 13 subjects matched for age, sex, and primary diagnosis who received chest physiotherapy. The records were audited for feasibility, safety, changes in oxygen saturation, chest X-ray changes, and intensive care unit length of stay. Results: A total of 104 treatment sessions (IPV 65 and CPT 39) were delivered to subjects admitted with a range of respiratory conditions in critical care. Subjects completed 97% of IPV sessions. No major adverse events were reported with intrapulmonary percussive ventilation intervention. Intensive care unit length of stay in the intrapulmonary percussive ventilation group was 9.6 AE 6 days, and in the CPT group, it was 11 AE 9 days (p ¼ 0.59). Peripheral oxygen saturation pre to post intervention was 92% AE 4 to 96% AE 4 in IPV group and 95% AE 4 to 95% AE 3 in the CPT group. Conclusion: Application of intrapulmonary percussive ventilation intervention was feasible and safe in non-ventilated adult patients in critical care.

Background Pulmonary complications such as pneumonia, pulmonary atelectasis, and subsequent respiratory failure leading to ventilatory support are a common occurrence in critically ill patients. Intrapulmonary percussive ventilation (IPV) is used to improve gas exchange and promote airway clearance in these patients. The current evidence regarding the effectiveness of intrapulmonary percussive ventilation in critical care settings remains unclear. This systematic review aims to summarise the evidence of the effectiveness of intrapulmonary percussive ventilation on intensive care unit length of stay (ICU-LOS) and respiratory outcomes in critically ill patients. Research question In critically ill patients, is intrapulmonary percussive ventilation effective in improving respiratory outcomes and reducing intensive care unit length of stay. Methods A systematic search of intrapulmonary percussive ventilation in intensive care unit (ICU) was performed on five databases from 1979 to 2021. Studies were considered for inclusion if they evaluated the effectiveness of IPV in patients aged ≥16 years receiving invasive or non-invasive ventilation or breathing spontaneously in critical care or high dependency units. Study titles and abstracts were screened, followed by data extraction by a full-text review. Due to a small number of studies and observed heterogeneities in the study methodology and patient population, a meta-analysis could not be included in this review. Outcomes of interest were summarised narratively. Results Out of 306 identified abstracts, seven studies (630 patients) met the eligibility criteria. Results of the included studies provide weak evidence to support the effectiveness of intrapulmonary percussive ventilation in reducing ICU-LOS, improving gas exchange, and reducing respiratory rate. Interpretation Based on the findings of this review, the evidence to support the role of IPV in reducing ICU-LOS, improving gas exchange, and reducing respiratory rate is weak. The therapeutic value of IPV in airway clearance, preventing pneumonia, and treating pulmonary atelectasis requires further investigation.

Supplementary Data from Rb Tumor Suppressor in Small Cell Lung Cancer: Combined Genomic and IHC Analysis with a Description of a Distinct Rb-Proficient Subset

Supplementary Data from Rb Tumor Suppressor in Small Cell Lung Cancer: Combined Genomic and IHC Analysis with a Description of a Distinct Rb-Proficient Subset

<div>AbstractPurpose:<p><i>RB1</i> mutations and loss of retinoblastoma (Rb) expression represent consistent but not entirely invariable hallmarks of small cell lung cancer (SCLC). The prevalence and characteristics of SCLC retaining wild-type Rb are not well-established. Furthermore, the performance of targeted next-generation sequencing (NGS) versus immunohistochemistry for Rb assessment is not well-defined.</p>Experimental Design:<p>A total of 208 clinical SCLC samples were analyzed by comprehensive targeted NGS, covering all exons of <i>RB1</i>, and Rb IHC. On the basis of established coordination of Rb/p16/cyclinD1 expression, p16-high/cyclinD1-low profile was used as a marker of constitutive Rb deficiency.</p>Results:<p>Fourteen of 208 (6%) SCLC expressed wild-type Rb, accompanied by a unique p16-low/cyclinD1-high profile supporting Rb proficiency. Rb-proficient SCLC was associated with neuroendocrine-low phenotype, combined SCLC with non-SCLC (NSCLC) histology and aggressive behavior. These tumors exclusively harbored <i>CCND1</i> amplification (29%), and were markedly enriched in <i>CDKN2A</i> mutations (50%) and NSCLC-type alterations (<i>KEAP1</i>, <i>STK11, FGFR1</i>). The remaining 194 of 208 SCLC were Rb-deficient (p16-high/cyclinD1-low), including 184 cases with Rb loss (of which 29% lacked detectable <i>RB1</i> alterations by clinical NGS pipeline), and 10 cases with mutated but expressed Rb.</p>Conclusions:<p>This is the largest study to date to concurrently analyze Rb by NGS and IHC in SCLC, identifying a 6% rate of Rb proficiency. Pathologic-genomic data implicate NSCLC-related progenitors as a putative source of Rb-proficient SCLC. Consistent upstream Rb inactivation via <i>CDKN2A</i>/p16^↓ and <i>CCND1</i>/cyclinD1^↑ suggests the potential utility of CDK4/6 inhibitors in this aggressive SCLC subset. The study also clarifies technical aspects of Rb status determination in clinical practice, highlighting the limitations of exon-only sequencing for <i>RB1</i> interrogation.</p><p><i><a href="https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-22-2187" target="_blank">See related commentary by Mahadevan and Sholl, p. 4603</a></i></p></div>

Hypophysitis is the inflammation of the pituitary gland with varying effects on hormone function that may be present secondary to the use of certain medications, infections, systemic inflammatory disorders, and other etiologies. Immunotherapy-related hypophysitis is a rare phenomenon. However, it representsan indicationof treatment interruption.We report a 60-year-old female with renal clear cell carcinoma onNivolumab and Ipilimumab(NIVO/IPI) intravenously (IV). After the second cycle of therapy, the patient reported a fall, with associatedlightheadedness, dizziness, nausea, vomiting, and hotflashes. The patient's symptoms and history were concerning for hypophysitis, so early treatment and cessation of the checkpoint inhibitors led to the patient's clinical improvement.

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