Category: Nevin Manimala

Langenbecks Arch Surg. 2023 May 4;408(1):175. doi: 10.1007/s00423-023-02898-1.

ABSTRACT

PURPOSE: Laparoscopic ileal pouch-anal anastomosis (IPAA) surgery offers improved short-term outcomes over open surgery but can be technically challenging. Robotic surgery has been increasingly used for IPAA surgery, but there is limited evidence supporting its use. This study aims to compare the short-term outcomes of laparoscopic and robotic IPAA procedures.

METHODS: All consecutive patients receiving laparoscopic and robotic IPAA surgery at 3 centres, from 3 countries, between 2008 and 2019 were identified from prospectively collated databases. Robotic surgery patients were propensity score matched with laparoscopic patients for gender, previous abdominal surgery, ASA grade (I, II vs III, IV) and procedure performed (proctocolectomy vs completion proctectomy). Their short-term outcomes were examined.

RESULTS: A total of 89 patients were identified (73 laparoscopic, 16 robotic). The 16 patients that received robotic surgery were matched with 15 laparoscopic patients. Baseline characteristics were similar between the two groups. There were no statistically significant differences in any of the investigated short-term outcomes. Length of stay trend was higher for laparoscopic surgery (9 vs 7 days, p = 0.072) CONCLUSION: Robotic IPAA surgery is safe and feasible and offers similar short-term outcomes to laparoscopic surgery. Length of stay may be lower for robotic IPAA surgery, but further larger scale studies are required in order to demonstrate this.

PMID:37140753 | DOI:10.1007/s00423-023-02898-1

Ann Surg Oncol. 2023 May 4. doi: 10.1245/s10434-023-13528-x. Online ahead of print.

ABSTRACT

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignancy with a historically poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as an effective therapy for patients with peritoneal malignancies. A contemporary analysis of trends in management of and survival from MPM is warranted.

METHODS: Patients with MPM were identified from the National Cancer Database (2004-2018). Patients were categorized by treatment (CRS-HIPEC, CRS-chemotherapy, CRS only, chemotherapy only, no treatment), and joinpoint regression was employed to compute the annual percent change (APC) in treatment over time. Multivariable Cox proportional hazards models were used to analyze factors associated with survival.

RESULTS: Of 2683 patients with MPM, 19.1% underwent CRS-HIPEC, and 21.1% received no treatment. Joinpoint regression revealed a statistically significant increase in the proportion of patients undergoing CRS-HIPEC over time (APC 3.21, p = 0.01), and a concurrent decrease in the proportion of patients who underwent no treatment (APC – 2.21, p = 0.02). Median overall survival was 19.5 months. Factors independently associated with survival included CRS-HIPEC, CRS, histology, sex, age, race, Charlson Comorbidity Index, insurance, and hospital type. Although there was a strong association between year of diagnosis and survival on univariate analysis (2016-2018 HR 0.67, p < 0.001), this association was attenuated after adjustment for treatment.

CONCLUSIONS: CRS-HIPEC is increasingly employed as a treatment for MPM. In parallel, there has been a decrease in patients receiving no treatment with an increase in overall survival. These findings suggest that patients with MPM may be receiving more appropriate therapy; however, a substantial proportion of patients may remain undertreated.

PMID:37140748 | DOI:10.1245/s10434-023-13528-x

Eur J Popul. 2023 May 4;39(1):15. doi: 10.1007/s10680-023-09662-7.

ABSTRACT

Theoretically, whether a more loosely regulated labour market inhibits or fosters fertility in a society is ambiguous. Empirically, the few studies analysing the relationship between the strictness of employment protection legislation-the norms and procedures regulating labour markets’ hiring and firing processes-and fertility have found mixed evidence. This paper reconciles the ambivalent conclusions of previous studies by analysing the impact of employment protection legislation and labour market dualism on total fertility across 19 European countries between 1990 and 2019. Our results indicate that an increase in employment protection for regular workers positively affects total fertility. Nonetheless, an increasing gap between the regulation of regular and temporary employment-that is, labour market dualism-negatively impacts total fertility. These effects, of small-to-moderate intensity, are relatively homogeneous across age groups and geographical areas and are especially pronounced among the lower educated. We conclude that labour market dualism, rather than a “rigid” employment protection legislation, discourages fertility.

PMID:37140731 | DOI:10.1007/s10680-023-09662-7

Clin Pharmacokinet. 2023 May 4. doi: 10.1007/s40262-023-01239-1. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Cotadutide is a balanced glucagon-like peptide-1 and glucagon receptor dual agonist under development for the treatment of non-alcoholic steatohepatitis and type 2 diabetes with chronic kidney disease. We evaluated the pharmacokinetics (PK), safety and immunogenicity of a single dose of cotadutide in individuals with varying degrees of renal impairment.

METHODS: In this phase I bridging study, individuals 18-85 years of age, with a body mass index of 17-40 kg/m² and varying degrees of renal function {end-stage renal disease (ESRD; creatinine clearance [CrCl] < 20 mL/min); severe renal impairment (CrCl ≥ 20 to < 30 mL/min); lower moderate renal impairment (CrCl ≥ 30 to < 44 mL/min); upper moderate renal impairment (CrCl ≥ 45 to < 60 mL/min); normal renal function (CrCl ≥ 90 mL/min)} were treated with a single dose of subcutaneous cotadutide 100 µg under fasted conditions in the lower abdomen. The co-primary endpoints were area under the plasma concentration-time curve from time zero to 48 h (AUC₄₈) and the maximum observed plasma concentration (C_max) for cotadutide. Safety and immunogenicity were secondary endpoints. This trial is registered with ClinicalTrials.gov (NCT03235375).

RESULTS: A total of 37 individuals were enrolled in the study (only three enrolled in the ESRD group, therefore this group was excluded from the primary PK analysis). AUC₄₈ and C_max values for cotadutide were similar across all renal function groups {severe renal impairment vs. normal renal function: AUC₄₈ geometric mean ratio (GMR) 0.99 (90% confidence interval [CI] 0.76-1.29); lower moderate renal impairment versus normal renal function: AUC₄₈ GMR 1.01 (90% CI 0.79-1.30); upper moderate renal impairment versus normal renal function: AUC₄₈ GMR 1.09 (90% CI 0.82-1.43)}. A sensitivity analysis that combined the ESRD and severe renal impairment groups did not show notable changes in the AUC₄₈ and C_max GMRs. The incidences of treatment-emergent adverse events (TEAE) ranged from 42.9 to 72.7% across all groups and were mostly mild to moderate in severity. Only one patient had a grade III or worse TEAE during the study period. No positive antidrug antibody results were observed.

CONCLUSIONS: These results suggest that the PK and tolerability of cotadutide are unaffected by renal function and that dose adjustments may not be required in individuals with renal impairment.

PMID:37140727 | DOI:10.1007/s40262-023-01239-1

Obes Surg. 2023 May 4. doi: 10.1007/s11695-023-06625-z. Online ahead of print.

ABSTRACT

PURPOSE: Laparoscopy is advised under the lowest possible intra-peritoneal pressure. The aim of this study is to analyze the safety/feasibility of low pneumoperitoneum pressure (LPP) during laparoscopic sleeve gastrectomy (LSG).

MATERIALS AND METHODS: All primary LSGs who completed a 3-month follow-up were included. Re-do operations and LSGs performed with concomitant procedures were excluded. All LSGs were performed by the senior author. Upon trocar insertions, pressure was set to 10 mmHg, and the procedure was started. The pressure was increased step-wise, according to the senior author’s assessment of the quality of exposure. Doing so, three pressure groups were formed: groups 1 (10 mmHg), 2 (11-13 mmHg), and 3 (14 mmHg). All data was retrieved from our database. Statistical analysis was performed using one-way ANOVA/Tukey’s HSD test/Chi-square test. P values < 0.05 were regarded as significant.

RESULTS: Between February 2018 and October 2022, 708 consecutive/primary LSGs were studied. No mortality/conversion/thromboembolic event was observed. Groups 1, 2, and 3 comprised 376 (53.1%), 243 (34.3%), and 89 (12.6%) patients, respectively. Demographics, initial weight, duration of surgery, history for abdominoplasty, drain output, length of stay, and %total weight loss were evenly distributed among groups. Among 16 bleeding episodes, 14 occurred in the LPP group (p = 0.019). Including the only leak and stenosis, 8/9 of Clavien-Dindo 3b + 4 complications were observed in the LPP group (p = 0.092).

CONCLUSIONS: LSG with LPP is feasible in about half of the patients. However, almost all potentially life-threatening complications occurred in the LPP group where a significantly higher rate of bleeding was observed. Our findings suggest caution for routinely using LPP during LSG.

PMID:37140721 | DOI:10.1007/s11695-023-06625-z

Adv Ther. 2023 May 4. doi: 10.1007/s12325-023-02500-6. Online ahead of print.

ABSTRACT

INTRODUCTION: This ongoing post-marketing surveillance monitors the long-term safety and effectiveness of vedolizumab in routine clinical practice in patients with moderate-to-severe ulcerative colitis (UC) in Japan. This interim analysis assessed induction-phase data, covering the initial three doses of vedolizumab.

METHODS: Patients were enrolled via a web-based electronic data capture system from approximately 250 institutions. Incidence of adverse events and treatment responses were assessed by the physicians after the patient had received three doses of vedolizumab or when the drug was discontinued, whichever occurred first. Therapeutic response was defined as any treatment response, including remission or improvement of complete or partial Mayo score, and was assessed in the total and stratified patient populations according to prior tumor necrosis factor alpha (TNFα) inhibitor treatments and/or baseline partial Mayo score.

RESULTS: The total incidence of adverse drug reactions (ADRs) was 4.10% (11/268). Common ADRs were dizziness, nausea, and arthralgia, each reported in 0.75% of patients (2/268). Serious ADRs were herpes zoster oticus and UC, each reported in 0.37% of patients (1/268). Therapeutic response was reported in 84.5% (218/258) of all patients, 85.8% (127/148) of TNFα inhibitor-naïve patients, and 82.7% (91/110) of TNFα inhibitor-experienced patients. Among patients with partial Mayo score of ≥ 4 at baseline, partial Mayo score remission in patients without or with prior TNFα inhibitor treatment was 62.5% (60/96) and 45.6% (36/79), respectively.

CONCLUSION: The results confirm a safety and effectiveness profile of vedolizumab consistent with that observed in previous trials.

CLINICAL TRIAL REGISTRATION: JapicCTI-194603, NCT03824561.

PMID:37140705 | DOI:10.1007/s12325-023-02500-6

J Comput Neurosci. 2023 May 4. doi: 10.1007/s10827-023-00847-x. Online ahead of print.

ABSTRACT

To understand single neuron computation, it is necessary to know how specific physiological parameters affect neural spiking patterns that emerge in response to specific stimuli. Here we present a computational pipeline combining biophysical and statistical models that provides a link between variation in functional ion channel expression and changes in single neuron stimulus encoding. More specifically, we create a mapping from biophysical model parameters to stimulus encoding statistical model parameters. Biophysical models provide mechanistic insight, whereas statistical models can identify associations between spiking patterns and the stimuli they encode. We used public biophysical models of two morphologically and functionally distinct projection neuron cell types: mitral cells (MCs) of the main olfactory bulb, and layer V cortical pyramidal cells (PCs). We first simulated sequences of action potentials according to certain stimuli while scaling individual ion channel conductances. We then fitted point process generalized linear models (PP-GLMs), and we constructed a mapping between the parameters in the two types of models. This framework lets us detect effects on stimulus encoding of changing an ion channel conductance. The computational pipeline combines models across scales and can be applied as a screen of channels, in any cell type of interest, to identify ways that channel properties influence single neuron computation.

PMID:37140691 | DOI:10.1007/s10827-023-00847-x

Neurosurg Rev. 2023 May 4;46(1):103. doi: 10.1007/s10143-023-02013-4.

ABSTRACT

OBJECTIVE: This study aimed to compare the clinical features, treatment, and clinical outcome of patients with tandem occlusion and isolated intracranial occlusion through endovascular treatment (EVT).

METHODS: Patients with acute cerebral infarction who received EVT in two stroke centers were retrospectively included. According to MRI or CTA results, the patients were divided into tandem occlusion group or isolated intracranial occlusion group. The baseline data, etiological classification, treatment, post-stroke complications, image features, and clinical outcome were compared. Multivariate logistic regression analysis was used to evaluate the related factors affecting the prognosis of patients with EVT.

RESULTS: Among 161 patients with acute cerebral infarction, there were 33 cases (20.5%) in the tandem occlusion group and 128 cases (79.5%) in the isolated intracranial occlusion group. Compared with isolated intracranial occlusion, the patients with tandem occlusion had higher rates of large artery atherosclerosis (P = 0.028), symptomatic intracerebral hemorrhage (sICH) (P = 0.023), bilateral infarction (P = 0.042), and longer time for endovascular procedure (P = 0.026). There was no significant statistical difference in 90-day mRS score between the two groups (P = 0.060). Multivariate logistic regression identified the following independent predictors of poor functional outcome: older age, high fasting blood glucose, infarction area > 1/3, and hemorrhagic transformation.

CONCLUSIONS: Compared with isolated intracranial occlusion, there was not a worse prognosis among patients with tandem occlusion who received EVT.

PMID:37140688 | DOI:10.1007/s10143-023-02013-4

J Cancer Surviv. 2023 May 4. doi: 10.1007/s11764-023-01379-0. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer survivors may have elevated atherosclerotic cardiovascular disease (ASCVD) risk. Therefore, we tested how accurately the American College of Cardiology/American Heart Association 2013 pooled cohort equations (PCEs) predict 10-year ASCVD risk in cancer survivors.

OBJECTIVES: To estimate the calibration and discrimination of the PCEs in cancer survivors compared to non-cancer participants in the Atherosclerosis Risk in Communities (ARIC) study.

METHODS: We evaluated the PCEs’ performance among 1244 cancer survivors and 3849 cancer-free participants who were free of ASCVD at the start of follow-up. Each cancer survivor was incidence-density matched with up to five controls by age, race, sex, and study center. Follow-up began at the first study visit at least 1 year after the diagnosis date of the cancer survivor and finished at the ASCVD event, death, or end of follow-up. Calibration and discrimination were assessed and compared between cancer survivors and cancer-free participants.

RESULTS: Cancer survivors had higher PCE-predicted risk, at 26.1%, compared with 23.1% for cancer-free participants. There were 110 ASCVD events in cancer survivors and 332 ASCVD events in cancer-free participants. The PCEs overestimated ASCVD risk in cancer survivors and cancer-free participants by 45.6% and 47.4%, respectively, with poor discrimination in both groups (C-statistic for cancer survivors = 0.623; for cancer-free participants, C = 0.671).

CONCLUSIONS: The PCEs overestimated ASCVD risk in all participants. The performance of the PCEs was similar in cancer survivors and cancer-free participants.

IMPLICATIONS FOR CANCER SURVIVORS: Our findings suggest that ASCVD risk prediction tools tailored to survivors of adult cancers may not be needed.

PMID:37140677 | DOI:10.1007/s11764-023-01379-0

Eur J Orthop Surg Traumatol. 2023 May 4. doi: 10.1007/s00590-023-03567-1. Online ahead of print.

ABSTRACT

BACKGROUND: The addition of junctions in modular stems implies a greater susceptibility to corrosion.

PURPOSE: The aim of this study is to compare serum chromium and cobalt levels after using a bimodular stem and its monoblock counterpart in primary total hip arthroplasty. Postoperative clinical scores were also compared.

PATIENTS AND METHODS: A prospective cohort study between 2012 and 2015 was designed. One arm of the cohort included patients with the cementless modular neck stem H-Max M® and the other with the cementless monoblock stem counterpart H-Max S®.

RESULTS: No statistically significant difference was found in chromium value between groups (p = 0.621) at two years postoperative. Cobalt value was higher in the modular group (p = < 0.001). No statistically significant difference was found in clinical postoperative scores except for the Harris Hip Score, with better results at six months in modular group (p = 0.007).

CONCLUSIONS: Higher serum cobalt level in the modular group has limited the use of modular stems in our daily practice. Advantages of modular stem were not found.

LEVEL OF EVIDENCE: II.

PMID:37140672 | DOI:10.1007/s00590-023-03567-1