Category: Nevin Manimala

Am J Med Sci. 2023 Mar 16:S0002-9629(23)01070-4. doi: 10.1016/j.amjms.2023.03.012. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) and portopulmonary hypertension (POPH) can be limitations towards listing for liver transplantation (LT). Our study evaluates the correlation of right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) on transthoracic echocardiogram (TTE) compared to mPAP on right heart catheterization (RHC).

METHODS: We performed a retrospective review of 723 patients who underwent LT evaluation at our institution between 2012 and 2020. Our cohort consisted of patients with RVSP and mPAP measured on TTE. A Wald t-test and area under the curve analysis were used for statistical analyses.

RESULTS: Patients with higher mPAP values on TTE (N=33) did not correlate with mPAP ≥ 35 mmHg on RHC, while patients with higher RVSP values (N=147) on TTE were associated with mPAP ≥ 35 mmHg on RHC. The cutoff value of RVSP ≥ 48 mmHg on TTE was associated with mPAP ≥ 35 mmHg on RHC.

CONCLUSIONS: Our data suggest that RVSP compared to mPAP on TTE is a better indicator for mPAP ≥ 35 mmHg on RHC. RVSP can be used as a marker on echocardiography for identifying patients with a higher likelihood of PH being a barrier to LT listing.

PMID:36933862 | DOI:10.1016/j.amjms.2023.03.012

Int J Radiat Oncol Biol Phys. 2023 Mar 16:S0360-3016(23)00289-4. doi: 10.1016/j.ijrobp.2023.03.047. Online ahead of print.

ABSTRACT

PURPOSE: Radiotherapy-induced xerostomia (RIX) significantly affects quality of life in head and neck cancer (HNC) survivors. Neuro-electrostimulation of the salivary glands may safely increase natural salivation and reduce dry mouth symptoms.

METHODS AND MATERIALS: Multicentre double-masked randomised sham-controlled clinical trial to assess the long-term effects of a commercially available intra-oral neuro-electrostimulating device in lessening xerostomia symptoms, increasing salivary flow and improving quality of life in individuals with RIX. Using a computer-generated randomization list, participants were assigned (1:1) to an active intra-oral custom-made removable electrostimulating device or a sham device to be used for 12 months. The primary outcome was the proportion of patients reporting a 30% improvement on the xerostomia VAS at 12 months. A number of secondary and exploratory outcomes were also assessed through validated measurements (sialometry and VAS) and quality of life questionnaires (EORTC QLQ-H&N35, OH-QoL16 and SF-36).

RESULTS: As per protocol, 86 participants were recruited. Intention-to-treat analyses showed no statistical evidence of a difference between the study groups with respect to the primary outcome or for any of the secondary clinical or quality of life outcomes. Exploratory analyses showed a statistically significant difference in the changes over time of the dry mouth sub-scale score of the EORTC QLQ-H&N35 in favour of the active intervention.

CONCLUSION: LEONIDAS-2 did not meet the primary and secondary outcomes.

FUNDING: NIHR Research for Patient Benefit Programme.

PMID:36933846 | DOI:10.1016/j.ijrobp.2023.03.047

Sci Total Environ. 2023 Mar 16:162921. doi: 10.1016/j.scitotenv.2023.162921. Online ahead of print.

ABSTRACT

Locust outbreaks were one of the primary biological disasters in ancient China. Using historical data from the Ming and Qing Dynasties, the temporal and spatial relationships between the changes in the aquatic environment and the locust dynamics in the downstream areas of the Yellow River were investigated via quantitative statistics, and other factors affecting locust outbreaks were also studied. This study demonstrated that locust, drought and flood outbreaks were spatiotemporally correlated. Locusts and droughts were synchronous for long-term series, but locust outbreaks were weakly correlated with floods. In drought years, the probability of a locust outbreak occurring in the same month as a drought was higher than that in other years and months. The probability of a locust outbreak was higher in the one to two years following a flood than in other years, but locusts were not easily triggered by extreme flooding. In the waterlogged and riverine locust breeding areas, locust outbreaks were more closely related to flooding and drought than in other breeding areas. Affected by the diversion of the Yellow River, the areas of frequent locust outbreaks were around riverine areas. In addition, climate change affects the hydrothermal conditions in which locusts occur, and human activities influence the occurrence of locusts by changing their habitats. Analyzing the relationship between historical locust outbreaks and water system changes provides valuable information for formulating and implementing disaster prevention and mitigation policies in this region.

PMID:36933725 | DOI:10.1016/j.scitotenv.2023.162921

Sci Total Environ. 2023 Mar 17:162865. doi: 10.1016/j.scitotenv.2023.162865. Online ahead of print.

ABSTRACT

Glycol ethers are solvents used in a plethora of occupational and household products exposing the users to potential toxic effects. Several glycol ethers derived from ethylene glycol induce hematological toxicity, such as anemia in workers. The exposure effects on blood cells of glycol ethers derived from propylene glycol are unknown in humans. The aim of our study was to evaluate blood parameters indicative of red blood cell (RBC) hemolysis and oxidative stress in participants exposed to propylene glycol (propylene glycol monobutyl ether (PGBE) and propylene glycol monomethyl ether (PGME), two extensively used propylene glycol derivatives worldwide). Seventeen participants were exposed 2 h in a control inhalation exposure chamber to low PGME (35 ppm) and PGBE (15 ppm) air concentrations. Blood was regularly collected before, during (15, 30, 60, and 120 min), and 60 min after exposure for RBC and oxidative stress analyses. Urine was also collected for clinical effects related to hemolysis. Under the study conditions, our results showed that the blood parameters such as RBCs, hemoglobin concentration, and white blood cells tended to increase in response to PGME and PGBE exposures. These results raise questions about the possible effects in people regularly exposed to higher concentrations, such as workers.

PMID:36933710 | DOI:10.1016/j.scitotenv.2023.162865

J Am Pharm Assoc (2003). 2023 Mar 16:S1544-3191(23)00068-7. doi: 10.1016/j.japh.2023.03.002. Online ahead of print.

ABSTRACT

BACKGROUND: Statin use in people with type 2 diabetes (T2D) reduces cardiovascular events, yet adherence remains suboptimal.

OBJECTIVE(S): This study evaluated the impact of a community pharmacist intervention on statin adherence in new users with T2D.

METHODS: As part of a quasi-experimental study, community pharmacy staff proactively identified adult patients with T2D who were not prescribed a statin. When appropriate, the pharmacist prescribed a statin via a collaborative practice agreement or facilitated acquisition of a prescription from another prescriber. Patients received individualized education and follow up and monitoring for one year. Adherence was defined as the proportion of days covered (PDC) by a statin over 12 months. Linear and logistic regression were used to compare the effect of the intervention on continuous and a binary adherence threshold, defined as PDC > 80%, respectively.

RESULTS: Overall, 185 patients started statin therapy and were matched to 370 control patients for analysis. Adjusted average PDC was 3.1% higher in the intervention group (95% CI: -0.037, 0.098). Patients in the intervention group were 21.2% more likely to have PDC > 80% (95% CI: 0.828, 1.774).

CONCLUSION: The intervention resulted in higher statin adherence compared to usual care; however, the differences were not statistically significant.

PMID:36933697 | DOI:10.1016/j.japh.2023.03.002

Transplant Cell Ther. 2023 Mar 16:S2666-6367(23)01171-5. doi: 10.1016/j.jtct.2023.03.012. Online ahead of print.

ABSTRACT

BACKGROUND: Risks of B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy for patients with multiple myeloma (MM) include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, and infections. The efficacy and safety of BCMA CAR-T therapy in the geriatric setting, including complications such as falls and delirium which may be more prevalent in older patients, have not been fully analyzed.

OBJECTIVES: To analyze the efficacy and safety of BCMA CAR-T therapy among older patients (age ≥70 at infusion) versus younger patients with MM.

STUDY DESIGN: We analyzed all patients with MM who received any autologous BCMA CAR-T therapy over a 5-year period at our institution. Key endpoints included CRS, ICANS incidence, days to absolute neutrophil count (ANC) recovery, incidence of hypogammaglobulinemia (IgG < 400 mg/dL), infections within 6 months, progression-free survival (PFS), and overall survival (OS).

RESULTS: Of 83 analyzed patients (age range 33-77), 22 (27%) were aged ≥70 at infusion. The older cohort had lower creatinine clearances (median 67.3 vs 91.9 mL/min, p<0.001) and a higher proportion of patients with performance status ≥1 (59% vs 30%, p=0.02) but were otherwise similar. Rates of any-grade CRS, any-grade ICANS, and days to ANC recovery were similar between groups. Rates of baseline hypogammaglobulinemia were 36% in older patients and 30% in younger patients (p=0.60), while post-infusion hypogammaglobulinemia occurred in 82% vs 72% respectively (p=0.57). Infections occurred in 36% (n=8) of the older cohort versus 52% (n=32) of the younger cohort (p=0.22). There were no statistically significant differences between the older and younger cohorts in terms of documented falls (9% vs 15%, p=0.72) or non-ICANS delirium (5% vs 7%, p=1.0). Median PFS was 13.1 months in older patients (95% CI 9.2-not reached [NR]) vs 12.5 months in younger patients (95% CI 11.3-22.5, p=0.42. Median OS was not reached in the older cohort (95% CI: NR-NR) vs 31.4 months in the younger cohort (95% CI 24.8-NR) with p=0.04. However, age ≥70 was not a significant predictor of OS after adjusting for high-risk cytogenetics, triple-class refractoriness, extramedullary disease, and bone marrow plasma cell burden.

CONCLUSIONS: While limited by small sample size and unmeasured confounders, our retrospective analysis did not demonstrate significant increases in CAR-T toxicity among older patients. This included toxicities associated with geriatric populations such as falls and delirium. Our paradoxical finding of borderline better OS among patients aged ≥70, which was not significant in regression modeling, may have been due to selection bias in favor of disproportionately healthy CAR-T candidates in the geriatric population. Overall, BCMA CAR-T remains a safe and effective option for older patients with MM.

PMID:36933659 | DOI:10.1016/j.jtct.2023.03.012

J Shoulder Elbow Surg. 2023 Mar 16:S1058-2746(23)00243-4. doi: 10.1016/j.jse.2023.02.116. Online ahead of print.

ABSTRACT

BACKGROUND: Recent evidence indicates that combined upper extremity blood flow restriction (BFR, applied distally to the shoulder) and low-load resistance exercise (LIX) augments clinically meaningful responses in shoulder region tissues proximal to the occlusion site. The purpose of this investigation was to determine the efficacy of BFR-LIX for the shoulder when added to standard offseason training in Division IA collegiate baseball pitchers. We hypothesized that BFR-LIX would augment training-induced increases in shoulder-region lean mass, rotator cuff strength, and endurance. As secondary outcomes, we sought to explore the impact of BFR-LIX rotator cuff training on pitching mechanics.

METHODS: Twenty-eight collegiate baseball pitchers were randomized into 2 groups (BFR^N=15, NOBFR^N=13) that, in conjunction with offseason training, performed 8wks of shoulder LIX [Throwing arm only; 2/wk, 4 sets (30/15/15/fatigue), 20%isometric max] using 4 exercises [cable external and internal rotation (ER/IR), dumbbell scaption, and side-lying dumbbell ER]. The BFR group also trained with an automated tourniquet on the proximal arm (50%-occlusion). Regional lean mass (dual-energy x-ray absorptiometry), rotator cuff strength (dynamometry: IR0&90, ° ER0&90, ° Scaption, Flexion), and fastball biomechanics were assessed pre- and post-training. Achievable workload (sets × reps × resistance) was also recorded. An ANCOVA (covaried on baseline measures) repeated on training timepoint was used to detect within-group and between-group differences in outcome measures (α=0.05). For significant pairwise comparisons, effect size (ES) was calculated using a Cohen’s d statistic and interpreted as: 0-0.1, negligible(N); 0.1-0.3, small(S); 0.3-0.5, moderate(M); 0.5-0.7, large(L); >0.7, very large(VL).

RESULTS: Following training, the BFR group experienced greater increases in shoulder-region lean mass [BFR: ↑227±60g, NOBFR: ↑75±37g, P=0.018, ES=1.0(VL)] and isometric strength for IR90° (↑2.4±2.3kg, P=0.041, ES=0.9VL). The NOBFR group experienced decreased shoulder flexion (↓1.6±0.8kg, P=0.007, ES=1.4VL) and IR at 0°(↓2.9±1.5kg, P=0.004, ES=1.1VL). The BFR group had a greater increase in achievable workload for the scaption exercise (BFR: ↑190±3.2kg, NOBFR: ↑90±3.3kg, P=0.005, ES=0.8VL). Only the NOBFR group was observed to experience changes in pitching mechanics following training with increased shoulder external rotation at lead foot contact (↑9.0°±7.9, P=0.028, ES=0.8VL) as well as reduced forward (↓3.6°±2.1, P=0.001, ES=1.2VL) and lateral (↓4.6°±3.4, P=0.007, ES=1.0VL) trunk tilt at ball release.

CONCLUSION: BFR-LIX rotator cuff training performed in conjunction with a collegiate offseason program augments increases in shoulder lean mass as well as muscular endurance while maintaining rotator cuff strength and possibly pitching mechanics in a manner that may contribute to favorable outcomes and injury prevention in baseball pitching athletes.

PMID:36933646 | DOI:10.1016/j.jse.2023.02.116

Environ Res. 2023 Mar 16:115683. doi: 10.1016/j.envres.2023.115683. Online ahead of print.

ABSTRACT

Management of cancer metastasis has been associated with remarkable reduction in progression of cancer cells and improving survival rate of patients. Since 90% of mortality are due to cancer metastasis, its suppression can improve ability in cancer fighting. The EMT has been an underlying cause in increasing cancer migration and it is followed by mesenchymal transformation of epithelial cells. HCC is the predominant kind of liver tumor threatening life of many people around the world with poor prognosis. Increasing patient prognosis can be obtained via inhibiting tumor metastasis. HCC metastasis modulation by EMT and HCC therapy by nanoparticles are discussed here. First of all, EMT happens during progression and advanced stages of HCC and therefore, its inhibition can reduce tumor malignancy. Moreover, anti-cancer compounds including all-trans retinoic acid and plumbaging, among others, have been considered as inhibitors of EMT. The EMT association with chemoresistance has been evaluated. Moreover, ZEB1/2, TGF-β, Snail and Twist are EMT modulators in HCC and enhancing cancer invasion. Therefore, EMT mechanism and related molecular mechanisms in HCC are evaluated. The treatment of HCC has not been only emphasized on targeting molecular pathways with pharmacological compounds and since drugs have low bioavailability, their targeted delivery by nanoparticles promotes HCC elimination. Moreover, nanoparticle-mediated phototherapy impairs tumorigenesis in HCC by triggering cell death. Metastasis of HCC and even EMT mechanism can be suppressed by cargo-loaded nanoparticles.

PMID:36933639 | DOI:10.1016/j.envres.2023.115683

Pharmacol Biochem Behav. 2023 Mar 16:173543. doi: 10.1016/j.pbb.2023.173543. Online ahead of print.

ABSTRACT

ProSAAS is one of the most abundant proteins in the brain and is processed into several smaller peptides. One of which, BigLEN, is an endogenous ligand for the G protein-coupled receptor, GPR171. Recent work in rodent models has shown that a small-molecule ligand for GPR171, MS15203, increases morphine antinociception and is effective in lessening chronic pain. While these studies provide evidence for GPR171 as a possible pain target, its abuse liability has not yet been assessed and was evaluated in the current study. We first mapped the distribution of GPR171 and ProSAAS throughout the reward circuit of the brain using immunohistochemistry and showed that GPR171 and ProSAAS are localized in the hippocampus, basolateral amygdala, nucleus accumbens, prefrontal cortex. In the major dopaminergic structure, the ventral tegmental area (VTA), GPR171 appeared to be primarily localized in dopamine neurons while ProSAAS is outside of dopamine neurons. Next, MS15203 was administered to mice with or without morphine, and VTA slices were stained for the immediate early gene c-Fos as a marker of neuronal activation. Quantification of c-Fos-positive cells revealed no statistical difference between MS15203 and saline, suggesting that MS15203 does not increase VTA activation and dopamine release. The results of a conditioned place preference experiment showed that treatment with MS15203 produced no place preference indicating a lack of reward-related behavior. Taken together this data provides evidence that the novel pain therapeutic, MS15203, has minimal reward liability. Therefore, GPR171 deserves further exploration as a pain target. SIGNIFICANCE STATEMENT: MS15203, a drug that activates the receptor GPR171, was previously shown to increase morphine analgesia. The authors use in vivo and histological techniques to show that it fails to activate the rodent reward circuitry, providing support for the continued exploration of MS15203 as a novel pain drug, and GPR171 a novel pain target.

PMID:36933620 | DOI:10.1016/j.pbb.2023.173543

J Neurosurg Pediatr. 2023 Mar 17:1-9. doi: 10.3171/2023.1.PEDS22341. Online ahead of print.

ABSTRACT

OBJECTIVE: Programmable valves have gained increasing popularity in the complex treatment of pediatric hydrocephalus. Over the last decade, adjustable serial valves have gradually replaced fixed-pressure valves in the authors’ department. The present study investigates this development by analyzing shunt- and valve-related outcomes for this vulnerable population.

METHODS: A retrospective analysis of all shunting procedures between January 2009 and January 2021 in children younger than 1 year of age was performed at the authors’ single-center institution. Postoperative complications and surgical revisions were set as outcome parameters. Shunt and valve survival rates were evaluated. Statistical analysis compared children who underwent implantation of the Miethke proGAV/proSA programmable serial valves with those who underwent implantation of the fixed-pressure Miethke paediGAV system.

RESULTS: Eighty-five procedures were evaluated. The paediGAV system was implanted in 39 cases and the proGAV/proSA in 46 cases. The mean ± SD follow-up was 247.7 ± 140 weeks. In 2009 and 2010, paediGAV valves were used exclusively, but by 2019, the use of proGAV/proSA had evolved into the first-line therapy. The paediGAV system was significantly more often revised (p < 0.05). The main indication for revision was proximal occlusion, with or without impairment to the valve. The valve and shunt survival rates of proGAV/proSA were significantly prolonged (p < 0.05). The surgery-free valve survival of proGAV/proSA was 90% after 1 year and 63% after 6 years. There were no overdrainage-related revisions of proGAV/proSA valves.

CONCLUSIONS: Favorable shunt and valve survival validates the increasing use of programmable proGAV/proSA serial valves in this delicate population. Potential benefits in postoperative treatment should be addressed in prospective multicenter studies.

PMID:36933264 | DOI:10.3171/2023.1.PEDS22341