Tag: nevin manimala

JAMA Netw Open. 2023 Jul 3;6(7):e2326127. doi: 10.1001/jamanetworkopen.2023.26127.

ABSTRACT

IMPORTANCE: Unlike substantial evidence in the prevention of chemotherapy-induced nausea and vomiting (CINV), research in the prevention of nausea and vomiting caused by concurrent chemoradiotherapy (CCRT) is currently lacking.

OBJECTIVE: To compare the efficacy and safety of fosaprepitant weekly vs every 3 weeks for the prevention of nausea and emesis caused by CCRT among patients with nasopharyngeal carcinoma.

DESIGN, SETTING, AND PARTICIPANTS: This pilot randomized clinical trial was conducted at a single cancer center from November 24, 2020, to July 26, 2021, among patients with nasopharyngeal carcinoma who had achieved CINV control after 2 to 3 cycles of induction chemotherapy. Efficacy analyses were performed in the intention-to-treat population. Data were analyzed on November 4, 2022.

INTERVENTIONS: Eligible patients were randomly assigned (1:1) to receive fosaprepitant either weekly or every 3 weeks.

MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients with sustained complete response (defined as no emesis and no rescue therapy) during CCRT. Secondary end points were sustained no emesis, no nausea, no significant nausea, mean time to first emetic episode, quality of life, and 1-year progression-free survival (PFS).

RESULTS: A total of 100 patients (mean [SD] age, 46.6 [10.9] years; 83 [83.0%] male) who had achieved CINV control after induction chemotherapy were randomly assigned to receive fosaprepitant weekly (50 patients) or every 3 weeks (50 patients). There was no significantly significant difference in cumulative risk of emesis or rescue therapy in the group that received weekly fosaprepitant compared with those who received fosaprepitant every 3 weeks (subhazard ratio, 0.66 [95% CI, 0.43-1.02]; P = .06). The proportion of patients with sustained no emesis (38% vs 14%; P = .003) or no significant nausea (92% vs 72%; P = .002) was significantly higher in the group that received fosaprepitant weekly vs those who received fosaprepitant every 3 weeks. Treatments were well tolerated. Patients in the weekly group had improved scores for multiple quality-of-life measures. There was no significant difference in survival outcomes between groups (91.8% vs 93.7%; P = .99). In the mean brainstem dose subgroups, a possible treatment interaction effect was observed in sustained complete response (mean brainstem dose ≥36 Gy: hazard ratio [HR], 0.32 [95% CI, 0.15-0.69]; mean brainstem dose <36 Gy: HR, 0.95 [95% CI, 0.55-1.63]) and sustained no emesis (mean brainstem dose ≥36 Gy: HR, 0.21 [95% CI, 0.08-0.53]; mean brainstem dose <36 Gy: HR, 0.73 [95% CI, 0.41-1.28]).

CONCLUSIONS AND RELEVANCE: In this pilot randomized clinical trial, there was no statistically significant difference in the complete response primary end point, but patients receiving weekly fosaprepitant were less likely to experience emesis compared with those who received fosaprepitant every 3 weeks, especially in the subgroup with a mean brainstem dose of 36 Gy or more. Weekly fosaprepitant was well tolerated and improved quality of life of patients without compromising survival.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04636632.

PMID:37498596 | DOI:10.1001/jamanetworkopen.2023.26127

Mol Biol Evol. 2023 Jul 27:msad169. doi: 10.1093/molbev/msad169. Online ahead of print.

ABSTRACT

Variation in gene expression across lineages is thought to explain much of the observed phenotypic variation and adaptation. The protein is closer to the target of natural selection but gene expression is typically measured as the amount of mRNA. The broad assumption that mRNA levels are good proxies for protein levels has been undermined by a number of studies reporting moderate or weak correlations between the two measures across species. One biological explanation for this discrepancy is that there has been compensatory evolution between the mRNA level and regulation of translation. However, we do not understand the evolutionary conditions necessary for this to occur nor the expected strength of the corelation between mRNA and protein levels. Here we develop a theoretical model for the coevolution of mRNA and protein levels and investigate the dynamics of themodel over time. We find that compensatory evolution is widespread when there is stabilizing selection on the protein level; this observation held true across a variety of regulatory pathways. When the protein level is under directional selection, the mRNA level of a gene and the translation rate of the same gene were negatively correlated across lineages but positively correlated across genes. These findings help explain results from comparative studies of gene xpression and potentially enable researchers to disentangle biological and statistical hypotheses for the mismatch between transcriptomic and proteomic data.

PMID:37498582 | DOI:10.1093/molbev/msad169

Acta Oncol. 2023 Jul 27:1-6. doi: 10.1080/0284186X.2023.2238550. Online ahead of print.

ABSTRACT

BACKGROUND: The benefit of combining immunotherapy with photon irradiation has been shown pre-clinically and clinically. This current pre-clinical study was designed to investigate the anti-tumour action of combining immunotherapy with protons.

MATERIALS AND METHODS: Male CDF1 mice, with a C3H mammary carcinoma inoculated on the right rear foot, were locally irradiated with single radiation doses when tumours reached 200mm³. Radiation was delivered with an 83-107MeV pencil scanning proton beam in the centre of a 3 cm spread out Bragg peak. Following irradiation (day 0), mice were injected intraperitoneal with anti-CTLA-4, anti-PD-1, or anti-PD-L1 (10 mg/kg) twice weekly for two weeks. Endpoints were tumour growth time (TGT3; time to reach 3 times treatment volume) or local tumour control (percent of mice showing tumour control at 90 days). A Student’s T-test (tumour growth) or Chi-squared test (tumour control) were used for statistical analysis; significance levels of p < 0.05.

RESULTS: Untreated tumours had a mean (± 1 S.E.) TGT3 of 4.6 days (± 0.4). None of the checkpoint inhibitors changed this TGT3. A linear increase in TGT3 was seen with increasing radiation doses (5-20 Gy), reaching 17.2 days (± 0.7) with 20 Gy. Anti-CTLA-4 had no effect on radiation doses up to 15 Gy, but significantly enhanced 20 Gy; the TGT3 being 23.0 days (± 1.3). Higher radiation doses (35-60 Gy) were investigated using a tumour control assay. Logit analysis of the dose response curve, resulted in a TCD50 value (radiation dose causing 50% tumour control; with 95% confidence intervals) of 48 Gy (44-53) for radiation only. This significantly decreased to 43 Gy (38-49) when mice were treated with anti-CTLA-4. Neither anti-PD-1 nor anti-PD-L1 significantly affected tumour control.

CONCLUSION: Checkpoint inhibitors enhanced the response of this C3H mammary carcinoma to proton irradiation. However, this enhancement depended on the checkpoint inhibitor and radiation dose.

PMID:37498559 | DOI:10.1080/0284186X.2023.2238550

Plast Reconstr Surg. 2023 Jul 25. doi: 10.1097/PRS.0000000000010947. Online ahead of print.

ABSTRACT

BACKGROUND: Conjoint fascial sheath (CFS) suspension has been gradually recognized and accepted for the treatment of congenital severe blepharoptosis in recent years. To address the problem of postoperative upper eyelid position regression of only CFS suspension, we designed and implemented a CFS combined Levator muscle (CFS+LM) complex flap. This research aims to analyze the surgical efficacy of CFS+LM and FMF suspension surgery.

METHODS: Patients diagnosed with congenital severe ptosis with levator muscle function ≦4 mm were enrolled. According to the surgical method, the patients were divided into the CFS+LM and FMF groups. To compare and statistically analyze the postoperative effect between CFS+LM and FMF suspension.

RESULTS: Data from 182 patients (220 eyes) were collected in this study, including 89 patients (103 eyes) in the CFS+LM group and 93 patients (117 eyes) in the FMF group. The full correction rate, patient satisfaction, postoperative upper eyelid excursion and lagophthalmos in the CFS+LM group were significantly better than those in the FMF group. The eyelid retraction rate was significantly higher in the FMF group than in the CFS+LM group. The complication rate in the CFS+LM group was significantly lower than that in the FMF group.

CONCLUSION: CFS+LM suspension had better outcomes than FMF. Considering that the CFS tissue could be weak in patients under 5 years old and have poor muscle elasticity in patients with levator muscle function ≤1 mm, FMF suspension is firstly recommended. For patients over 5 years old with severe ptosis, CFS+LM suspension is recommended.

PMID:37498527 | DOI:10.1097/PRS.0000000000010947

J Osteopath Med. 2023 Jul 28. doi: 10.1515/jom-2023-0087. Online ahead of print.

ABSTRACT

CONTEXT: With the growing number of robotic knee arthroplasties being performed, new outcomes must be analyzed to provide a database for comparing robotic and nonrobotic surgeries. These results can be utilized in the future to properly assess the significance of utilizing robotic technology in the operating room regarding patient outcomes and cost.

OBJECTIVES: The aims of this study are to: (1) analyze adverse outcomes from robotic-assisted knee arthroplasty and its relation to sex, body mass index (BMI), and age; and (2) explore any possible differences in outcomes among robotic-assisted unicompartmental knee arthroplasty (UKA) and robotic-assisted total knee arthroplasty (TKA). It is hypothesized that sex, BMI, and age will play a role in adverse events experienced among robotic-assisted knee arthroplasty. It is hypothesized that adverse outcomes will differ in robotic-assisted TKA v UKA.

METHODS: A retrospective analysis was performed utilizing 1,300 patient cases from a single surgeon that underwent robotic-assisted UKA or TKA utilizing a robotic surgical system. Demographics were sorted by age, sex, and BMI. Outcomes were sorted by the type of adverse event. The most common adverse event was further statistically analyzed by age, sex, and BMI and then compared to the total cohort. The most common adverse event was also broken down by TKA vs. UKA.

RESULTS: The average age of the individuals undergoing this procedure was 63.6 years, with 52.3 % being female. The average BMI was 32.2. Of the 87 patients who experienced adverse events, 111 total events were documented. Manipulation under anesthesia (MUA) was the highest experienced adverse event. Among the MUA events, 79.5 % had a BMI over 30 (p=0.067), 72.8 % were female (p=0.014), and the average age was 59 years (p=0.019). Among the MUA adverse events, 76.9 % (n=30) were following a TKA and 23.1 % were following a UKA. When considering the entire sample (n=1,300), there was a statistically significant 12.6 times greater odds that an MUA occurred among those who had a TKA vs. UKA (p<0.001). Similar results were discovered when only considering those who had experienced an adverse event (n=87) because the odds of an MUA occurring among those who underwent a TKA was 4.67 times greater than those who underwent a UKA (p<0.001).

CONCLUSIONS: MUA was the most common adverse event in this cohort of robotic-assisted knee arthroplasties. The other adverse events did not yield large enough cohort sizes to analyze statistically in relation to specific patient demographics. Younger patients and females were at significantly greater odds of needing MUA. A BMI over 30 was not found to have a statistically significant risk of needing an MUA after robotic-assisted knee arthroplasty. Among the total cohort, those who underwent a TKA were at a 12.6 times greater odds of needing an MUA than those who received a UKA.

PMID:37498518 | DOI:10.1515/jom-2023-0087

Telemed J E Health. 2023 Jul 26. doi: 10.1089/tmj.2023.0018. Online ahead of print.

ABSTRACT

Aim: Aim of this study is to investigate the effects of interactive telerehabilitation exercises in office workers with chronic nonspecific neck pain. Methods: Office workers (n = 120) were randomly divided into three groups between February and July 2022, taking into account the inclusion and exclusion criteria, and office ergonomics training was given to all of the participants. Group 1 participants were given an interactive telerehabilitation program (strengthening, motor control, and posture correction exercises) for 45 min per day, 3 days a week, for a total of 6 weeks. Group 2 participants were trained to do the home exercise program on their own for 45 min per day, 3 days a week, for a total of 6 weeks. Only office ergonomics training was given to Group 3 patients. Results: Statistically significant improvement in pain (p < 0.001), range of motion (ROM) (p < 0.001), neck disability status (p < 0.001), functional status (p < 0.001), and quality of life (p < 0.001) of 6-week interactive telerehabilitation application in office workers was found. Discussion: In addition to office ergonomics training, interactive telerehabilitation program is the most effective method on pain, ROM, and neck disability compared with home exercise program and office ergonomics training alone, and studies are needed on the long-term effectiveness of telerehabilitation applications and telerehabilitation treatment diversity.

PMID:37498517 | DOI:10.1089/tmj.2023.0018

J Comput Aided Mol Des. 2023 Jul 27. doi: 10.1007/s10822-023-00518-0. Online ahead of print.

ABSTRACT

When designing peptide ligands based on the structure of a protein receptor, it can be very useful to narrow down the possible binding positions and bound conformations of the ligand without the need to choose its amino acid sequence in advance. Here, we construct and benchmark a tool for this purpose based on a recently reported statistical energy model named SCUBA (Sidechain-Unknown Backbone Arrangement) for designing protein backbones without considering specific amino acid sequences. With this tool, backbone fragments of different local conformation types are generated and optimized with SCUBA-driven stochastic simulations and simulated annealing, and then ranked and clustered to obtain representative backbone fragment poses of strong SCUBA interaction energies with the receptor. We computationally benchmarked the tool on 111 known protein-peptide complex structures. When the bound ligands are in the strand conformation, the method is able to generate backbone fragments of both low SCUBA energies and low root mean square deviations from experimental structures of peptide ligands. When the bound ligands are helices or coils, low-energy backbone fragments with binding poses similar to experimental structures have been generated for approximately 50% of benchmark cases. We have examined a number of predicted ligand-receptor complexes by atomistic molecular dynamics simulations, in which the peptide ligands have been found to stay at the predicted binding sites and to maintain their local conformations. These results suggest that promising backbone structures of peptides bound to protein receptors can be designed by identifying outstanding minima on the SCUBA-modeled backbone energy landscape.

PMID:37498491 | DOI:10.1007/s10822-023-00518-0

Infection. 2023 Jul 27. doi: 10.1007/s15010-023-02078-9. Online ahead of print.

ABSTRACT

PURPOSE: Posaconazole is an antifungal drug currently being used for prophylaxis and treatment of invasive fungal infections such as aspergillosis. To date, therapeutic drug monitoring (TDM) of posaconazole is recommended with the use of oral suspension, but the potential need of TDM with the use of IV formulations is rising. Therefore, we aimed to investigate the pharmacokinetics of IV posaconazole in critically ill patients.

METHODS: In a prospective study, we analysed 168 consecutivelly collected posaconazole levels from 10 critically ill patients drawn during a 7 day curse. Posaconazole concentrations were measured using a chromatographic method. Demographic and laboratory data were collected, and the data was analysed using descriptive statistics.

RESULTS: We included 168 posaconazole levels, resulting in a median trough of 0.62 [0.29-1.05] mg/L with 58% not reaching the suggested target of 0.5 mg/L for fungal prophylaxis. Moreover, 74% of the trough levels were under the target of 1 mg/L which is proposed for the treatment of aspergillosis.

CONCLUSION: Posaconazole exposure is highly variable in critically ill patients resulting in potentially insufficient drug concentrations in many cases. TDM is highly recommended to identify and avoid underexposure.

TRIAL REGISTRATION NUMBER: NCT05275179, March 11, 2022.

PMID:37498488 | DOI:10.1007/s15010-023-02078-9

Updates Surg. 2023 Jul 27. doi: 10.1007/s13304-023-01598-1. Online ahead of print.

ABSTRACT

Liver transplantation (LT) represents the best cure for several acute and chronic liver diseases. Several studies reported excellent mid-term survivals after LT. However, lesser evidence has been reported on very long (10- and 20-year) follow-up results. This study aims to analyze the monocentric LT experience of the Sapienza University of Rome to identify the pre-operatively available parameters limiting a 10-year post-transplant survival. A total of 491 patients transplanted between 1982 and 2012 were enrolled. The cohort was split into two groups, namely the Short Surviving Group (< 10 years; n = 228, 46.4%) and the Long Surviving Group (≥ 10 years; n = 263, 53.6%). Several differences were reported between the two groups regarding initial liver function, surgical techniques adopted, and immunosuppression. Four variables emerged as statistically relevant as independent risk factors for not reaching at least 10 years of follow-up: recipient age (OR = 1.02; P = 0.01), donor age (OR = 1.01; P = 0.03), being transplanted during the eighties (OR = 6.46; P < 0.0001) and nineties (OR = 2.63; P < 0.0001), and the UNOS status 1-2A (OR = 2.62; P < 0.0001). LT confirms to be an extraordinary therapy for several severe liver diseases, consenting to reach in half of the transplanted cases even more than 20 years of follow-up. The initial liver function and the donor and recipient ages are relevant in impacting long-term survival after transplantation. A broad commitment from many professional groups, including surgeons, hepatologists, and anesthesiologists, is necessary. The achievement of excellent results in terms of long-term survival is proof of the effectiveness of this multidisciplinary collaboration.

PMID:37498485 | DOI:10.1007/s13304-023-01598-1

Ir J Med Sci. 2023 Jul 27. doi: 10.1007/s11845-023-03478-4. Online ahead of print.

ABSTRACT

OBJECTIVE: High levels of insulin-like growth factor 1 (IGF-1) in patients with acromegaly cause structural and functional changes specific to the disease. These changes lead to mortality if the disease is not treated. Circadian blood pressure (BP) rhythm as measured by 24-h ambulatory blood pressure monitoring (ABPM) can change with a decrease in BP during sleep and a sudden increase in wakefulness.

AIM: We aim to evaluate the relationship between changes in BP and IGF-1 levels in patients with acromegaly.

METHODS: Patients who were diagnosed with acromegaly and the patient group with hypertension were included. Serum biochemistry parameters, serum IGF-1 level and ABPM follow-ups were compared in these patients.

RESULTS: In our study, 30 patients with acromegaly and 30 patients with hypertension without acromegaly were included. Thirty of the patients were male and 30 were female. There was a statistically significant difference between the groups in terms of IGF-1(p = < 0.001) and GH(p = 0.004). There was no significant difference between patients’ office systolic/diastolic BP measurements, day/night, systolic/diastolic BP measurements and all systolic/diastolic BP measurements in ambulatory blood pressure follow-ups. There was a significant difference in morning blood pressure surge(p = < 0.001). A statistically significant difference was found between the acromegaly patient groups with MBPS below and above 25 mmHg in terms of IGF-1 (p = 0.025) and platelet levels (p = 0.004).

CONCLUSION: As a result, cardiovascular disease risks can be predicted in patients with high serum IGF-1 levels by planning ambulatory blood pressure in the early period.

PMID:37498476 | DOI:10.1007/s11845-023-03478-4