Postmortem Study of Organ-Specific Toxicity in Glioblastoma Patients Treated with a Combination of Temozolomide, Irinotecan and Bevacizumab

Purpose Systemic monotherapy with temozolomide (TMZ) or bevacizumab (BEV); two-drug combinations, such as Irinotecan (IRI) and BEV, TMZ and BEV and a three-drug combination with TMZ, IRI and BEV (TIB) have been used in treating patients with progressive high-grade gliomas including glioblastoma. Most patients tolerated these regimens well with well-established sides effects of hypertension, proteinuria, and reversible clinical myelosuppression (CM). However, organ-specific toxicities have never been examined by postmortem studies. Methods Postmortem tissues (from all major organs) were prospectively collected and examined by standard institution autopsy and brain cutting procedures from 76 decedents, including gliomas (N=68, 44/M, and 24/F) and brain metastases (N=8, 5/M, and 3/F) between 2009 and 2019. Standard hematoxylin and eosin (H&E) were performed on all major organs and brain samples harvested. Electronic microscopic (EM) study was carried on selected subjects kidney samples per standard EM protocol. Results Twenty-four glioma subjects were treated with TIB [median: 5.5 (range: 1-25) cycles] at glioma recurrence. Exposure to IRI significantly increased the frequency of CM (p=0.05). No unexpected adverse events were detected clinically or permenant end-organ damage by postmortem examination among subjects who received TIB compared to subjects who received standard of care (SOC) therapies. Among glioma decedents, the most common causes of death (COD) were tumor progression (63.2%, N=43), followed by aspiration pneumonia (48.5%, N=33). No COD was attributed to acute toxicity from TIB. The study also demonstrated that postmortem kidney specimen is unsuitable for studying renal ultrastructural pathological changes due to autolysis. Conclusion IRI, but not the extended use of TMZ, significantly increased CM in recurrent glioma patients. There is no permanent organ-specific toxicity among glioma decedents who received prolonged BEV, TMZ or TIB regimen based chemotherapies except expected occasional myelosuppresson. COD are most commonly resulted from glioma tumor progression and aspiration pneumonia.

Case Report: Next-Generation Sequencing in Diagnosis of Atypical Aspiration Pneumonia

Since the pandemic of Corona Virus Disease 2019 (COVID-19), especially in the centers most affected, the symptoms such as fever, cough, myalgia or fatigue, and radioactive signs typically related to COVID-19 like ground-glass opacity (GGO) often distract the attention of physicians from other diseases. Aspiration pneumonia and COVID-19 share similarities in some aspects. There may be risk of misdiagnosis in the case of considering radiological patterns of pneumonia. Early diagnosis and treatment often greatly improve prognosis. We herein reported a case of 40-year-old patient who underwent chest CT scan with the discovery of ground-glass opacity, intralobular reticular opacity and interlobular septal thickening, consolidation, and air bronchogram sign, which were mainly located in the middle and upper lobes of the right lung. It was considered to be infection related pneumonia based on the negative reverse transcription-PCR (RT-PCR) result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF) was performed and detected nucleic acid sequences of Klebsiella sp. Consequently, the patient accepted sensitive intravenous antibiotics therapy for 13 days and had a remarkable clinical and radiological improvement. His case was followed up through imaging procedures. Because of possible radiologic and clinical similarities between aspiration and COVID-19 pneumonia, COVID-19 can be of some value in proposing a differential diagnosis of aspiration pneumonia. Clinicians could suggest a correct diagnosis by careful examination of the CT images together with attention to the clinical history and judicious utilization of NGS, especially.

Association Between Timing of Speech and Language Therapy Initiation and Outcomes Among Post-Extubation Dysphagia Patients: A Multicenter Retrospective Cohort Study

Background: Post-extubation dysphagia (PED) is recognized as a common complication in the intensive care unit (ICU). Speech and language therapy (SLT) can potentially help improve PED; however, the impact of the timing of SLT initiation on persistent PED has not been well investigated. This study aimed to examine the timing of SLT initiation and its effect on patient outcomes after extubation in the ICU.Methods: We conducted this multicenter, retrospective, cohort study, collecting data from eight ICUs in Japan from patients treated between 2017 and 2020. Patients aged ≥ 20 years with orotracheal intubation and mechanical ventilation for longer than 48 hours, and those who received SLT due to PED, defined as patients with modified water swallowing test scores of 3 or lower, were included. The primary outcome was dysphagia at hospital discharge, defined as functional oral intake scale score <5 or death after extubation. Secondary outcomes included dysphagia or death at the seventh, 14th, or 28th day after extubation, aspiration pneumonia, and in-hospital mortality. Associations between the timing of SLT initiation and outcomes were determined using multivariable logistic regression. Results: Two hundred and seventy-two patients met the study inclusion criteria. Of them, 82 (30.1%) patients exhibited dysphagia or death at hospital discharge, and their time spans from extubation to SLT initiation was 1.0 days. The primary outcome revealed that every day of delay in SLT initiation post-extubation was associated with dysphagia or death at hospital discharge (adjusted odds ratio (AOR), 1.09; 95% CI, 1.02 to 1.18). Similarly, secondary outcomes showed associations between this per day delay in SLT initiation and dysphagia or death at the seventh day (AOR, 1.28; 95% CI, 1.05 to 1.55), 14th day (AOR, 1.34; 95% CI, 1.13 to 1.58), or 28th day (AOR, 1.21; 95% CI, 1.07 to 1.36) after extubation and occurrence of aspiration pneumonia (AOR, 1.09; 95% CI, 1.02 to 1.17), while per day delay in post-extubation SLT initiation did not affect in-hospital mortality (AOR, 1.04; 95% CI, 0.97 to 1.12). Conclusions: Delayed initiation of SLT in PED patients was associated with persistent dysphagia or death. Early initiation of SLT may prevent this complication post-extubation.

Clinical consequences of Hypotension in patient with organophosphate poisoning

Objective: Aim of study is to describe the clinical consequences of hypotension in patient with organophosphate poisoning. Method: In the retrospective cohort study, we analyzed data of 66 patients with organophosphate poisoning who were treated at Bir Hospital, Nams Kathmandu. Data from those with hypotension and normal blood pressure were compared to identify significant clinical consequences. Results: All together 66 patients were enrolled in this study out of which 44(66.7%) were female and 22(33.3%) were male. After analyzing data, we found 18.2% of case with severe poisoning (ACHE < 700 U/L). Among all, 41(62%) were found to have normal blood pressure and 25(37.9%) were found to have low blood pressure. Among those with hypotension, around 56% were found to have prolonged QTc interval, p < 0.003 and there was statistically significant association between QTc prolongation and vasopressor requirement, X2(1) = 22.98, P < 0.001. Patients requiring higher dose to reach atropinization had statistically significant hypotension, P < 0.001. Those with low blood pressure were found to require more days of hospital admission, P < 0.001. Patients with hypotension were found to have severe poisoning both on the basis of POP Score severity grading, 16(64%) P <0.002 and ACHE Severity scale, 7(28%) P < 0.05. In comparison with normal blood pressure group, low blood pressure group had significantly more chance of developing complications like septic shock (2), aspiration pneumonia (5), ARDS (1) and bed sore, P = 0.002. Vasopressor requirement was significantly more among those with low blood pressure, P < 0.001. Most of hypotensive patients were needing ICU care, found to have higher WBC count P = 0.002 and lower GCS Score at admission P < 0.001. There was positive correlation between hypotension and POP Score at admission P < 0.001. Conclusion: Hypotension is a common complication in patient with organophosphate poisoning and is associated with higher POP Score, lower ACHE level, lower GCS Score, increased vasopressor requirement, more hospital stays, increasing ICU admission, more chance of developing septic shock and aspiration pneumonia.

Low incidence of postoperative nausea, vomiting, regurgitation, and aspiration pneumonia in geriatric dogs receiving maropitant, famotidine, and fentanyl as part of an anesthesia protocol

OBJECTIVE To determine the incidence of and potential risk factors for postoperative regurgitation and vomiting (PORV), postoperative nausea and vomiting (PONV), and aspiration pneumonia in geriatric dogs using premedication with maropitant and famotidine, intraoperative fentanyl, and postoperative fentanyl as part of an anesthetic protocol. ANIMALS 105 client-owned geriatric dogs that underwent general anesthesia for a major surgical procedure between January 2019 and March 2020. PROCEDURES Medical records were reviewed to collect data on signalment, historical gastrointestinal signs, American Society of Anesthesiologists (ASA) score, indication for surgery, duration of anesthesia and surgery, patient position during surgery, mode of ventilation, and perioperative administration of maropitant, famotidine, anticholinergics, opioids, colloidal support, NSAID, corticosteroids, and appetite stimulants. The incidence of postoperative regurgitation, vomiting, nausea, and aspiration pneumonia was calculated, and variables were each analyzed for their association with these outcomes. RESULTS 2 of 105 (1.9%) dogs regurgitated, 1 of 105 (1.0%) dogs developed aspiration pneumonia, 4 of 105 (3.8%) dogs exhibited nausea, and no dogs vomited. Identified possible risk factors included older age (≥ 13 years old) for postoperative regurgitation, regurgitation for postoperative aspiration pneumonia, and high ASA score (≥ 4) for both regurgitation and aspiration pneumonia. CONCLUSIONS AND CLINICAL RELEVANCE The use of an antiemetic protocol including maropitant, famotidine, and fentanyl in geriatric dogs resulted in very low incidences of PORV, PONV, and aspiration pneumonia. Future prospective studies are warranted to further evaluate and mitigate postoperative risks.

Preprocedural fasting for contrast-enhanced CT: when experience meets evidence

Traditional preparatory fasting policy prior to iodinated contrast media (ICM) assisted contrast-enhanced CT (CECT) examinations lacks methodologically acceptable evidence. Considering the possible negative effects of preprocedural fasting, the latest European Society of Urogenital Radiology guidelines V10.0 and American Committee of Radiology 2021 guidelines clearly state that preprocedural fasting is not recommended prior to routine intravenous ICM administration. This comprehensive and detailed Review presents the current global dietary preparation policies, potential harm of excessive fasting, and a systematical and well-bedded description of practice advancements of dietary preparation. The evidences revealed that there has been no single instance of vomiting-associated aspiration pneumonia due to the undemanding implementation of preparatory fasting prior to CECT yet. Non-fasting would not increase the incidence of emetic symptoms and the risk of aspiration pneumonia. Not every patient should undergo all CECT examinations without preparatory fasting. There is still much more refinement to be done on the preparatory fasting policy. Changes in traditional preparatory fasting policy will make positive and significant implications on clinical practice. This Review aims to provide operational guidance and suggestions for practitioners and policymakers, motivate efficient, reasonable, safe and normative ICM usage, and achieve optimal patient clinical benefits and high-quality radiological care practices.