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Nevin Manimala Statistics

Surgical aspects and early morbidity of patients undergoing open recurrent inguinal hernia repair

Hernia. 2023 May 4. doi: 10.1007/s10029-023-02801-3. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to characterize the patterns of recurrence associated with specific types of primary inguinal hernia repair techniques used for and their respective correlations with early morbidity, in patients undergoing open repair for their first hernia recurrence.

METHODS: After ethics approval was obtained, a retrospective review of charts from patients who underwent open surgery for repair of a first recurrence after a previous inguinal hernia repair during 2013-2017 was completed. Statistical analyses were performed and p-values < .05 are reported as statistically significant.

RESULTS: 1393 patients underwent 1453 surgeries for recurrent inguinal hernias at this institution. Operations for recurrence were longer (61.9 ± 21.1 vs. 49.3 ± 11.9; p < .001), required more frequent intra-operative surgical consultation (1% vs. 0.2%; p < .001) and had a higher incidence of surgical-site infections (0.8% vs. 0.4%; p = .03) than primary inguinal hernia repairs. When comparing the patterns of recurrence among different techniques of primary repairs, patients undergoing laparoscopic hernia repair presented with a higher incidence of indirect recurrences. Reoperations after a Shouldice repair and open mesh repair represented markers for higher surgical difficulty in the recurrent operation (longer operative time, higher identification of heavy scarring, less nerve identification, and higher frequency of intra-operative consultation), but not higher rates of complications when compared with other techniques.

CONCLUSIONS: Open reoperations for inguinal hernia first recurrences are more complex, with noticeable differences according to the index operation, and associated with higher morbidity when compared with primary hernia repairs. This complexity varies according to the type of primary surgery, with a previous Shouldice repair and open hernia repair with mesh presenting higher surgical difficulties although this did not translate to higher incidence of early complications. This information may allow adequate allocation of surgeons with an expertise in recurrent hernias and choice of recurrent repair method (laparoscopic or open) based on the primary surgery.

PMID:37140758 | DOI:10.1007/s10029-023-02801-3

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Nevin Manimala Statistics

Ecological niche modelling and population genetic analysis of Indian temperate bamboo Drepanostachyum falcatum in the western Himalayas

J Plant Res. 2023 May 4. doi: 10.1007/s10265-023-01465-5. Online ahead of print.

ABSTRACT

The present study was conducted to understand the key ecological and biological questions of conservation importance in Drepanostachyum falcatum which aimed to map potential distribution in the western Himalayas and decipher spatial genetic structure. Eco-distribution maps were generated through ecological niche modelling using the Maximum Entropy (MaxEnt) algorithm implemented with 228 geocoordinates of species presence and 12 bioclimatic variables. Concomitantly, 26 natural populations in the western Himalayas were genetically analysed using ten genomic sequence-tagged microsatellite (STMS) markers. Model-derived distribution was adequately supported with appropriate statistical measures, such as area under the ‘receiver operating characteristics (ROC)’ curve (AUC; 0.917 ± 0.034)”, Kappa (K; 0.418), normalized mutual information (NMI; 0.673) and true skill statistic (TSS; 0.715). Further, Jackknife test and response curves showed that the precipitation (pre- and post-monsoon) and temperature (average throughout the year and pre-monsoon) maximize the probabilistic distribution of D. falcatum. We recorded a wide and abundant (4096.86 km2) distribution of D. falcatum in the western Himalayas with maximum occurrence at 1500 to 2500 m asl. Furthermore, marker analysis exemplified high gene diversity with low genetic differentiation in D. falcatum. Relatively, the populations of Uttarakhand are more genetically diverse than Himachal Pradesh, whereas within the Uttarakhand, the Garhwal region captured a higher allelic diversity than Kumaon. Clustering and structure analysis indicated two major gene pools, where genetic admixing appeared to be controlled by long-distance gene flow, horizontal geographical distance, aspect, and precipitation. Both the species distribution map and population genetic structure derived herein may serve as valuable resources for conservation and management of Himalayan hill bamboos.

PMID:37140755 | DOI:10.1007/s10265-023-01465-5

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Nevin Manimala Statistics

Short-term outcomes in robotic vs laparoscopic ileal pouch-anal anastomosis surgery: a propensity score match study

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

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Nevin Manimala Statistics

National Practice Patterns in Malignant Peritoneal Mesothelioma: Updates in Management and Survival

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

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Nevin Manimala Statistics

Employment Protection Legislation, Labour Market Dualism, and Fertility in Europe

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

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Nevin Manimala Statistics

Pharmacokinetics and Safety of Cotadutide, a GLP-1 and Glucagon Receptor Dual Agonist, in Individuals with Renal Impairment: A Single-Dose, Phase I, Bridging Study

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 (Cmax) 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 Cmax 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 Cmax 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

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Nevin Manimala Statistics

Low-Pressure Pneumoperitoneum During Laparoscopic Sleeve Gastrectomy: a Safety and Feasibility Analysis

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

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Nevin Manimala Statistics

Safety and Effectiveness of Vedolizumab in Patients with Moderate-to-Severe Ulcerative Colitis: An Interim Analysis of a Japanese Post-Marketing Surveillance Study

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

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Nevin Manimala Statistics

A biophysical and statistical modeling paradigm for connecting neural physiology and function

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

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Nevin Manimala Statistics

Differences in risk factors and outcome after acute stroke in patients with tandem occlusion and those with isolated intracranial occlusion after endovascular treatment

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