Effects of pulmonary rehabilitation on functional and psychological parameters in post-acute sequelae of SARS-CoV-2 infection (PASC) patients.

BACKGROUND: COVID-19 survivors may develop long-term symptoms of fatigue, dyspnea, mental health issues, and functional limitations: a condition termed post-acute sequelae of COVID-19 (PASC). Pulmonary rehabilitation (PR) is a recommended treatment for PASC; however, there is a lack of data regarding PR's effect on multiple health indices and the factors that influence patient outcomes. The aim of our study is to evaluate the impact of pulmonary rehabilitation on functional and psychological parameters in patients diagnosed with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), thereby offering insights into the efficacy of such interventions in improving the quality of life and clinical outcomes for these individuals. METHODS: We extracted patient demographic, comorbidity, and outcome data from Allegheny Health Network's electronic medical records. Functionality test results were compared before and after PR, including 6-minute walk test (6MWT), chair rise repetitions (CR reps), timed up and go test (TUG), gait speed (Rehab gait), modified medical research council scale (MMRC), shortness of breath questionnaire (SOBQ), hospital anxiety and depression scale (HADS) and chronic obstructive pulmonary disease assessment test (CAT) scores. Multiple regression analysis was done to evaluate the effect of comorbidities and patient factors on patient responses to PR. RESULTS: The 55 patients included in this study had a mean time of 4 months between the initial COVID-19 diagnosis and the subsequent PASC diagnosis. Following pulmonary rehabilitation (PR), significant improvements were observed across various metrics. The distance covered in the 6-minute walk test (6MWT) increased markedly from a pre-rehabilitation average of 895 feet (SD 290) to 1,300 feet (SD 335) post-rehabilitation, with a mean change of 405 feet (95% CI [333, 477]). Chair rise repetitions (CR reps) saw an increase from 9 (SD 3) reps to 13 (SD 3) reps, with a change of 4 reps (95% CI [3.7, 4.9]). The timed up and go test (TUG) time decreased significantly from 13 s (SD 5) to 10 s (SD 2), reflecting a mean reduction of 3 s (95% CI [-4.5, -2.5]). Rehabilitation gait speed improved from 1.0 m/s to 1.3 m/s, changing by 0.3 m/s (95% CI [0.2, 0.3]). The Modified Medical Research Council (MMRC) dyspnea scale showed a notable decrease from a mean of 2 (SD 1) to 1 (SD 1), a change of -1 (95% CI [-1.5, -1]). The Shortness of Breath Questionnaire (SOBQ) scores reduced significantly from 51 (SD 21) to 22 (SD 18), with a change of -29 (95% CI [-34, -23]). The Hospital Anxiety and Depression Scale (HADS) scores decreased from 11 (SD 7) to 8 (SD 7), a reduction of -4 (95% CI [-5, -2]). Lastly, the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) scores significantly dropped from 18 (SD 7) to 9 (SD 7), changing by -10 (95% CI [-11, -8]). However, the presence of hypertension, diabetes, chronic lung diseases, outpatient status, and receipt of specific pharmacologic treatments (decadron, decadron + remdesivir, and decadron + remdesivir + tocilizumab) were identified as factors associated with a poor response to PR. CONCLUSION: Our study supports PR as an integrated model of care for PASC patients to improve several physical and mental health indices. The long-term effects of PR on patients' functional status should be investigated in the future.

Iron coatings on carbonate rocks shape the attached bacterial aquifer community.

Most studies of groundwater ecosystems target planktonic microbes, which are easily obtained via water samples. In contrast, little is known about the diversity and function of microbes adhering to rock surfaces, particularly to consolidated rocks. To investigate microbial attachment to rock surfaces, we incubated rock chips from fractured aquifers in limestone-mudstone alternations in bioreactors fed with groundwater from two wells representing oxic and anoxic conditions. Half of the chips were coated with iron oxides, representing common secondary mineralization in fractured rock. Our time-series analysis showed bacteria colonizing the chips within two days, reaching cell numbers up to 4.16 × 105 cells/mm2 after 44 days. Scanning electron microscopy analyses revealed extensive colonization but no multi-layered biofilms, with chips from oxic bioreactors more densely colonized than from anoxic ones. Estimated attached-to-planktonic cell ratios yielded values of up to 106: 1 and 103: 1, for oxic and anoxic aquifers, respectively. We identified distinct attached and planktonic communities with an overlap between 17 % and 42 %. Oxic bioreactors were dominated by proteobacterial genera Aquabacterium and Rhodoferax, while Rheinheimera and Simplicispira were the key players of anoxic bioreactors. Motility, attachment, and biofilm formation traits were predicted in major genera based on groundwater metagenome-assembled genomes and reference genomes. Early rock colonizers appeared to be facultative autotrophs, capable of fixing CO2 to synthesize biomass and a biofilm matrix. Late colonizers were predicted to possess biofilm degrading enzymes such as beta-glucosidase, beta-galactosidase, amylases. Fe-coated chips of both bioreactors featured more potential iron reducers and oxidizers than bare rock chips. As secondary minerals can also serve as energy source, they might favor primary production and thus contribute to subsurface ecosystem services like carbon fixation. Since most subsurface microbes seem to be attached, their contribution to ecosystem services should be considered in future studies.

Assessment of Phase 3 Randomized Clinical Trials Including Patients With Leptomeningeal Disease: A Systematic Review.

This systematic review examines the proportion of patients with leptomeningeal disease included in phase 3 randomized clinical trials for patients with metastatic breast cancer, lung cancer, and melanoma.

Gender differences in pulmonology and critical care authorship and editorial boards.

OBJECTIVE: This study aims to characterize the gender distribution of first authors, senior authors, and editorial board members across several high-impact factor journals in PCCM. METHODS: In this cross-sectional study, we analysed gender disparities in critical care authorship and editorial boards, based on publications from 1 January 2019 to 31 December 2021 from the top 20 high impact journals based on the Journal of Citation Reports. RESULTS: Among 20 journals (median impact factor of 6.66), 25% of editors-in-chief and 28.8% of editorial board members were female. From 2019 to 2021, a total of 23,994 articles were published. Female first authors and last authors made up 29.1% and 21.2% of the authorship, respectively (n = 6637 articles). CONCLUSIONS: Our study demonstrates significant gender disparities in critical care authorship and editorial boards, with males predominantly filling the roles of editors in chief, editorial members, and first and senior authors. Despite this significant difference in gender distribution, there was no statistically significant correlation between authorship and editor gender.

Exclusion of Patients With Brain Metastases in Published Phase III Clinical Trials for Advanced Breast Cancer.

Metastatic HER2-positive (HER2+) and triple-negative breast cancer (TNBC) confer a 30% or higher risk of developing brain metastases (BrM), but BrM is typically an exclusion criteria for clinical trials, which limits the generalizability of trial results to these patients. We therefore analysed trends in the enrollment of patients with BrM, as well as the use of outcomes specific to the central nervous system (CNS), in phase III clinical trials evaluating systemic therapy for patients with advanced HER2+ and/or TNBC. Notably, 10 of the 34 trials (29%, 95% confidence interval = 15.1%-47.5%) evaluated CNS-specific outcomes and trials that completely excluded patients with BrM were significantly less likely to meet their primary endpoint (n = 6/17, 35%) than those that permitted conditional enrollment (n = 13/15, 87%) (P = .005), suggesting that enrollment of patients with BrM is not detrimental to trial success.

A Rare Case of Coexisting Psychogenic Polydipsia and Nephrogenic Diabetes Insipidus With Lithium Therapy.

Lithium is a commonly used medication for mood stabilization and a well-known cause of nephrogenic diabetes insipidus (DI). Coexistent psychogenic polydipsia with nephrogenic DI is uncommon, and its management is challenging due to the wide variation in serum sodium based on fluctuations in water intake. Here, we describe the case of a 56-year-old male with psychogenic polydipsia and nephrogenic DI which manifested in wide swings of serum sodium over a short interval. He initially presented with hyponatremia with low urine osmolality consistent with psychogenic polydipsia. His serum sodium began to improve after free water restriction. However, later in the course, he developed an increase in serum sodium levels and polyuria with persistent low urine osmolality consistent with DI.

A Case Series of Statin-Induced Necrotizing Autoimmune Myopathy.

The use of statins has been increasing over the past decade for the primary and secondary prevention of cardiovascular disease worldwide. Subsequently, various side effects have also been unfolding. Muscle-related side effects secondary to statins range from myalgia to rhabdomyolysis and need close monitoring for early detection. Statin-induced necrotizing autoimmune myopathy (SINAM) in particular is unique given its pathophysiology, trigger factor, genetic predisposition, and aggressive management strategy. We present two cases of SINAM and discuss the clinical aspects of diagnosis, investigation, and management. Statin-induced necrotizing autoimmune myopathy usually presents with proximal myopathy along with increased creatinine kinase (CK) levels which do not resolve with only statin discontinuation. Diagnosis should be made with biopsy and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody detection. The investigation should also be directed to rule out other etiology of proximal myopathy. In most cases, rechallenge with a statin is unsuccessful and immunosuppressive treatment is essential.

A Case of Diffuse Alveolar Hemorrhage With COVID-19 Vaccination.

With the growing rates of vaccination against coronavirus disease 2019 (COVID-19) across the globe, rare side effects have been increasingly noticed on a post-marketing basis. Cases of myocarditis and pericarditis have been reported in the literature following COVID messenger RNA (mRNA) vaccination. However, diffuse alveolar hemorrhage (DAH) following vaccination has not been reported. DAH is a life-threatening clinicopathological entity characterized by bleeding into the alveolar space from pulmonary microvasculature. It presents a diagnostic challenge in the setting of acute respiratory failure, requiring prompt suspicion and workup. We report a case of a 59-year-old male with a recent COVID-19 infection who presented with DAH within eight hours of the first dose of mRNA vaccination (Moderna, Cambridge, MA). Bronchial alveolar lavage was performed, along with imaging of the chest, to confirm the diagnosis. Immunological workup with rheumatoid factor, anti-citrullinated peptide, anti-neutrophil cytoplasmic antibodies (P-ANCA and C-ANCA), anti-glomerular basement antibodies, Anti-double-stranded DNA, C3 and C4 complement levels, and cryoglobulin were all negative. Infectious workup with cultures and PCR from bronchial lavage was also negative. In the absence of any other causes, the etiology was likely deemed to be vaccine-induced DAH. Herein, we also discuss the possible mechanism of vaccine-related DAH and emphasize the need for further studies on vaccine-related adverse events.

Outcomes of Palliative Radiotherapy in Metastatic Epidural Spinal Cord Compression in Lung Cancer-A Prospective Observational Study from Tata Memorial Hospital.

Background Metastatic epidural spinal cord compression (MESCC) secondary to lung cancer (LC) is a debilitating complication associated with poor prognosis and is commonly treated with radiotherapy (RT). There is no consensus for RT dose fractionation in spinal cord compression. Methods Forty consecutive patients of LC with radiological evidence of MESCC treated with palliative RT were evaluated for functional outcomes (pain, ambulation, and sphincter function) at 2-, 4-, and 24-week post RT completion. Pain assessment was done using visual analogue scale (VAS) and response was categorized according to international consensus criteria, ambulation status (AS) using Tomita's scale, and sphincter function by the presence or absence of a catheter. Overall survival (OS) was assessed using Kaplan-Meier method and compared using log-rank test. Impact of potential prognostic factors on survival was also analyzed and p -value ≤0.05 was considered significant. Results Sixteen, 22, and two patients received 8 Gy single fraction (SF), 20 Gy in five fractions (20/5), and 30 Gy in 10 fractions (30/10), respectively. At 2 weeks, overall response (OR) rates of pain, ambulation, and sphincter control were 73, 81, and 81%, respectively. At 4 and 24 weeks, 93.7, 84.3, 87.5% and 88, 94, 76.5% had OR, respectively. Median OS was 4 months. Six- and 12-months OS was 50 and 37.5%. Nonsignificant difference in OS was seen between SF and 20/5 fractions (median 2.2 vs. 7.1 months, p = 0.39). Age ≤50 years was the only significant factor ( p <0.05) in univariate analysis for OS. Conclusion Radiotherapy provided equivalent pain control, ambulation, and sphincter function compared with reported literature in MESCC. Nonsignificant difference in OS exists between SF and multifraction RT regimens.

Chemo-brain: An activation likelihood estimation meta-analysis of functional magnetic resonance imaging studies.

Adults with non-central nervous system (CNS) cancers frequently report problems in attention, memory and executive function during or after chemotherapy, referred to as cancer-related cognitive dysfunction (CRCD). Despite numerous studies investigating CRCD, there is no consensus regarding the brain areas implicated. We sought to determine if there are brain areas that consistently show either hyper- or hypo-activation in people treated with chemotherapy for non-CNS cancer (Chemo+). Using activation likelihood estimation on brain coordinates from 14 fMRI studies yielding 25 contrasts from 375 Chemo+ and 429 chemotherapy-naive controls while they performed cognitive tasks, the meta-analysis yielded two significant clusters which are part of the frontoparietal attention network, both showing lower activation in Chemo+. One cluster peaked in the left superior parietal cortex, extending into precuneus, inferior parietal lobule, and angular gyrus. The other peaked in the right superior prefrontal areas, extending into inferior prefrontal cortex. We propose that these observed lower activations reflect a dysfunction in mobilizing and/or sustaining attention due to depletion of cognitive resources. This could explain higher level of mental fatigue reported by Chemo+ and why cancer survivors report problems in a wide variety of cognitive domains.

Type 2 diabetes is associated with increased risk of critical respiratory illness in patients COVID-19 in a community hospital.

BACKGROUND: Type 2 diabetes (T2D) is the leading non-communicable disease worldwide and is associated with several microvascular and macrovascular complications. Individuals with T2D are more prone to acquiring selected types of infections and are more susceptible to complications due to these infections. This study aimed to evaluate the relationship between T2D and COVID-19 in the community setting. METHODS: This was a single-center retrospective analysis that included 147 adult patients with laboratory-confirmed COVID-19 admitted to a community hospital. Demographics, medical history, symptoms and signs, laboratory findings, complications during the hospital course, and treatments were collected and analyzed. The Kaplan-Meier method was used to describe the probability of intubation in patients with T2D as compared with patients without T2D. The hazard ratio for intubation in the survival analysis was estimated using a bivariable Cox proportional-hazards model. RESULTS: Of 147 patients, 73 (49.7%) had a history of T2D. Patients with T2D had higher requirement of ICU admission (31.5% vs 12.2%; p = .004), higher incidence of ARDS (35.6% vs 16.2%, p = .007), higher rates of intubation (32.9% vs 12.2%, p = .003), and higher use neuromuscular blocking agents (23.3% vs 9.5%, p = .02). In the survival analysis at 28 days of follow-up, patients with T2D showed an increased hazard for intubation (HR 3.00; 95% CI, 1.39 to 6.46). CONCLUSION: In our patient population, patients with COVID-19 and T2D showed significantly higher ARDS incidence and intubation rates. The survival analysis also showed that after 28 days of follow-up, patients with T2D presented an increased risk for shorter time to intubation.

A Premature Ventricular Contraction Associated With Transient Worsening Pulsus Alternans: A Case Report.

Pulsus alternans is a rare condition characterized by alternation between strong and weak pulses during regular heart rhythm. Although pulsus alternans occurs mostly in severe heart failure, it can also be seen in other conditions that alternate ventricular contraction such as rapid tachycardia and extrasystole. Here, we report the case of a patient with peripartum cardiomyopathy who developed worsening pulsus alternans after a premature ventricular contraction.

Management of oligo-metastatic and oligo-recurrent cervical cancer: A pattern of care survey within the EMBRACE research network.

BACKGROUND: In the metastatic or recurrent cervical cancer, systemic chemotherapy constitutes the main treatment. Though there is an increasing use of high dose external radiation and brachytherapy in the metastatic setting, no consensus exists. METHODS: A 17-item survey was designed with additional case-based questions to explore present management of oligo-metastatic and oligo-recurrent cervix cancer within EMBRACE research group participating sites. The questions were designed to elicit prevailing practices in the management of de-novo oligo-metastasis and oligo-recurrent setting after completing the primary treatment of cervix cancer. The survey was sent electronically with two rounds of email reminders to respond over a 2-week survey period. The online survey was designed such that it was mandatory to complete all questions. The responses were recorded and results were summarized as proportions and summary statistics were generated. RESULTS: Twenty-two centers responded to this survey. A majority (90%) of respondents reported a low incidence of de-novo oligo-metastatic cervical cancer in their practice (<5%), with a higher proportion of patients with oligo-recurrence after completing primary treatment (5-10%). All responding sites preferred to treat pelvic disease in the de-novo oligo-metastatic setting albeit with different fractionation regimens. While 68.2% of respondents recommended chemo-radiation and brachytherapy, 31.8% considered additional systemic therapy. Overall 77.3% centers recommended the use of stereotactic ablative radiation therapy to oligo-metastasis. For out-of-field nodal recurrences, 63.7% of respondents considered treating with curative intent, while 59% preferred treating in-field recurrence with palliative intent. A vast majority of the participating centers (90%) have stereotactic radiation therapy capacity and would consider a clinical trial addressing oligo-metastatic and oligo-recurrent cervical cancer. CONCLUSION: Although contemporary practice is variable, a substantial proportion of EMBRACE centers consider high dose radiation in de-novo metastatic and oligo-recurrence settings. However, there is clear need for a joint clinical protocol and prospective studies to address the role of high dose radiation within oligo-recurrent and oligo-metastatic scenarios.

Guidelines for Cancer-Related Pain: A Systematic Review of Complementary and Alternative Medicine Recommendations.

BACKGROUND AND OBJECTIVE: Although up to 85% of patients with cancer use complementary and alternative medicine (CAM), they commonly do not disclose this information to their healthcare providers. Cancer-related pain (CRP) is one of the most common symptoms among those who may seek CAM. This study was conducted to identify the quantity and assess the quality of CAM recommendations across clinical practice guidelines (CPGs) for the treatment and/or management of CRP, as this has not been explored in the literature. METHODS: A systematic review was conducted to identify cancer pain CPGs. MEDLINE, EMBASE, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from 2009 to 2020. The Guideline International Network and the National Centre for Complementary and Integrative Health websites were also searched. Eligible CPGs on CRP in adults were assessed using the Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. RESULTS: Of 771 unique search results, 13 mentioned CAM and 11 made CAM recommendations. Eligible CPGs were published in 2009 or later and focused on the treatment/management of CRP. Scaled domain percentages from highest to lowest ranged from (overall, CAM): 88.1%, 88.1% (for scope and purpose) to 21.0%, 8.5% (for applicability). Quality varied within and across CPGs. One CPG was recommended by both appraisers; 6 were recommended as "Yes" or "Yes with modifications." CONCLUSIONS: The present study has identified and summarized a number of CPGs that clinicians may consult to understand what CAMs are recommended in the context of the treatment and/or management of CRP.

Rare Presentation of Cardiotoxicity Related to 5-Fluorouracil.

5-Fluorouracil (5-FU) is a chemotherapeutic agent frequently used for the treatment of solid tumors. In a few cases, 5-FU can be associated with coronary vasospasm, cardiac ischemia, or life-threatening arrhythmias. Recognition of 5-FU cardiotoxicity is clinically important as after the rapid sensation of therapy, cardiotoxicity can be completely reversible, and on the other hand, readministration may lead to serious damage of the heart and even death. A 70-year-old male came to the emergency department (ED) with chest pain which started while receiving an infusion of 5-FU. The patient did not have a personal history or risk factors of coronary artery disease and his electrocardiogram (ECG) before starting chemotherapy was completely normal. In the ED, his ECG had ischemic changes, troponin was elevated, and echocardiogram showed anterior wall hypokinesis. However, emergent coronary angiogram did not reveal any acute coronary occlusion. 5-FU-induced cardiotoxicity was suspected; the patient was admitted to a progressive care unit for close monitoring and infusion of calcium channel blockers was initiated. The patient's symptoms and ECG findings gradually resolved, and two days later on discharge, patient was chest pain free and ECG was normal. This case supports the vasospastic hypothesis of 5-FU cardiac toxicity, describes its clinical course, and emphasizes the importance of better awareness and early recognition of the rare side effect as it may allow physicians to reduce the risk of life-threatening complications.

Combinatorial Biobleaching of Mixedwood Pulp with Lignolytic and Hemicellulolytic Enzymes for Paper Making.

Microbial enzymes are the safe alternatives to chemical based bleaching of pulp in paper mills. For effective biobleaching, both hemicellulolytic and lignolytic enzymes are required. This study reports laccase (L) + xylanase (X) and laccase (L) + mannanase (M) enzyme concoctions for pulp biobleaching derived from Bacillus sp. LX and Bacillus sp. LM isolated from the decaying organic matter. All enzymes were thermo-alkali-stable, hence were suitable for their application in pulp biobleaching. When a mixture of L + X/L + M was used for mixedwood pulp biobleaching, 46.32/40.25% reduction in kappa number; 13.21/10.01% and 3.36/2.76% improvement in brightness and whiteness was achieved respectively. Moreover, no laccase mediator system was required in the current process. Significant changes in the structure of enzymatically treated pulp were also observed. All these properties make these concoctions of enzymes suitable for their application in pulp and paper mill.