Determining the impact of individual ventral hernia repair complications on patient-reported quality of life.

PURPOSE: Ventral hernia repair (VHR) postoperative complications vary in presentation, management, and severity. The aim of this study is to determine the impact of individual postoperative complications on long-term quality of life (QoL) after VHR. METHODS: Data from the Abdominal Core Health Quality Collaborative were analyzed retrospectively. Propensity score matching compared 1-year postoperative Hernia-Related Quality of Life Survey (HerQLes) summary scores between non-wound events (NWE), surgical site infection (SSI), and surgical site occurrence requiring procedural intervention (SSOPI) versus No-Complications. RESULTS: 2796 patients who underwent VHR between 2013 and 2022 met the study criteria. Patients with SSI and SSOPI had lower QoL vs No-Complications (median (Interquartile range): 71 (40-92) vs 83 (52-94), P = 0.02; 68 (40-90) vs 78 (55-95), P = 0.008). NWE vs no-complications HerQLes score differences were similar (83 (53-92) vs 83 (60-93), P = 0.19). CONCLUSION: Wound events seem to have larger impact on patients' long-term QoL compared to NWE. Continued and aggressive efforts including preoperative optimization, technical points, and appropriate use of minimally invasive techniques can continue to reduce impactful wound events.

Long-term outcomes of seromas after ventral hernia repair: a propensity score-matched analysis of the Abdominal Core Health Quality Collaborative.

PURPOSE: Seromas can occur after ventral hernia repairs (VHR), but little is known about their relevance to short- and long-term outcomes. We aimed to determine if there is a correlation between seroma occurrence after clean VHR with mesh and patient-reported and clinical outcomes. METHODS: Patients with and without seromas in the Abdominal Core Health Quality Collaborative registry were compared using a propensity score-matched analysis. Outcomes included hospital readmissions, postoperative antibiotics use, and procedural interventions. Pain and hernia-related quality of life were assessed at 30 days and 1 year. Composite hernia recurrence rates were compared at 1 year. RESULTS: Propensity score matching compared 218 patients with a seroma to 649 without a seroma. At 30 days, patients with seromas were more likely to be readmitted (27 (12%) vs 28 (4%), respectively; P < 0.001), receive postoperative antibiotics (25 (12%) vs 18 (3%), respectively; P < 0.001), and undergo procedural interventions (41 (19%) vs 23 (4%), respectively; P < 0.001) than patients without seromas. Surgical site occurrences were more common in patients with seromas than those without seromas at 1 year (12 (11%) vs 12 (4%), respectively; P = 0.01).Pain and hernia-related quality of life were similar for both groups at 30 days and 1 year. Composite hernia recurrence rates were similar for both groups at 1 year (37 seroma (17%) vs 115 no seroma (18%); P = 0.80). CONCLUSION: Seromas after clean VHR with mesh were associated with short- and long-term morbidity, but they did not significantly impact quality of life or hernia recurrences at 1 year.

Robotic versus open lateral abdominal hernia repair: a multicenter propensity score matched analysis of perioperative and 1-year outcomes.

PURPOSE: Lateral abdominal hernias are inherently challenging surgical entities. As such, there has been an increase in the adoption of robotic platforms to approach these challenging hernias. Our study aims to assess and compare outcomes between open (oLAHR) and robotic (rLAHR) lateral abdominal hernia repair using a national hernia-specific database. METHODS: A retrospective review of prospectively collected data from the Abdominal Core Health Quality Collaborative was performed to include all adult patients who underwent elective lateral hernia repair. A propensity score match analysis was conducted, and univariate analyses were conducted to compare these two surgical modalities across perioperative timeframes. RESULTS: The database identified 2569 patients. Our analysis matched 665 patients to either the open or robotic groups. The median length of stay, surgical site occurrences (SSO), and surgical site occurrences requiring procedural interventions (SSOPI) were higher in the oLAHR versus the rLAHR group. Overall, oLAHR had a significantly higher rate of having any post-operative complications or any SSO/SSOPI. There was no difference in quality-of-life measures between groups at 30 days and 1 year. CONCLUSION: Robotic abdominal hernia repair is a safe alternative compared to the open repair of lateral abdominal hernias with better perioperative outcomes. Despite having a longer operative time, the robotic approach can offer a significantly shorter length of stay and an overall lower rate of complications. Ultimately, there is no difference in the quality-of-life measures both at 30 days and 1 year between the open and robotic approaches.

Predictors of low and high opioid tablet consumption after inguinal hernia repair: an ACHQC opioid reduction task force analysis.

PURPOSE: Prescribing and consumption of opioids remain highly variable. Using a national hernia registry, we aimed to identify patient and surgery specific factors associated with low and high opioid tablet consumption after inguinal hernia repair. METHODS: This was a retrospective cross-sectional study evaluating patients undergoing elective inguinal hernia repair with 30-day follow-up and patient-reported opioid consumption from March 2019 to March 2021 using the Abdominal Core Health Quality Collaborative. Clinically significant patient demographics, comorbidities, operative details, quality-of-life measurements, and surgeon prescribing data were entered into a multivariable logistic regression model to identify statistically significant predictors of patients who took no opioid tablets or >10 tablets. RESULTS: A total of 1937 patients were analyzed. Operations included 59% laparoscopic or robotic, 35% open mesh, and 6% open non-mesh repairs. Of these patients, 50% reported taking zero, 42% took 1-10, and 8% took ≥10 opioid tablets at 30-day follow-up. Patients who were older (OR 1.55, 95% CI 1.34-1.79, p-value <0.001), ASA ≤ 2 (OR 1.56, 95% CI 1.2-2.01, p-value <0.001), had no preoperative opioid use at baseline (OR 2.29, 95% CI 1.31-4.03, p-value = 0.004), had local anesthetic with general anesthesia (OR 1.39, 95% CI 1.0.5-1.85, p-value = 0.022), or prescribed <7 opioid tablets (OR 2.27, 95% CI 1.96-2.62, p-value <0.001) were more likely to take no opioid tablets. CONCLUSION: Older, healthier, opioid naïve patients with local anesthetic administered during elective inguinal hernia repair are most likely to not require opioids. Surgeon prescribing-arguably the most modifiable factor-independently correlates with both low and high opioid consumption.

Management of ventral hernia defect during enterocutaneous fistula takedown: practice patterns and short-term outcomes from the Abdominal Core Health Quality Collaborative.

BACKGROUND: An enterocutaneous fistula (ECF) with an associated large hernia defect poses a significant challenge for the reconstructive surgeon. We aim to describe operative details and 30-day outcomes of elective hernia repair with an ECF when performed by surgeons participating in the Abdominal Core Health Quality Collaborative (ACHQC). STUDY DESIGN: Patients undergoing concomitant hernia and ECF elective repair were identified within the ACHQC. Outcomes of interest were operative details and 30-day rates of surgical site infections (SSI), surgical site occurrences requiring procedural intervention (SSOPI), medical complications, and mortality. RESULTS: 170 patients were identified (mean age 60 years, 52.4% females, mean BMI 32.3 kg/m2). 106 patients (62%) had small-bowel ECFs, mostly managed with resection without diversion. 30 patients (18%) had colonic ECFs, which were managed with resection without diversion (14%) or resection with diversion (6%). 100 (59%) had a prior mesh in place, which was removed in 90% of patients. Hernias measured 14 cm ± 7 in width, and 68 (40%) had a myofascial release performed (41 TARs). Mesh was placed in 115 cases (68%), 72% as a sublay, and more frequently of biologic (44%) or permanent synthetic (34%) material. 30-day SSI was 18% (37% superficial, 40% deep), and 30-day SSOPI was 21%. 19 patients (11%) were re-operated: 8 (8%) due to a wound complication and 4 (2%) due to a missed enterotomy. Two infected meshes were removed, one biologic and one synthetic. CONCLUSIONS: Surgeons participating in the ACHQC predominantly resect ECFs and repair the associated hernias with sublay mesh with or without a myofascial release. Morbidity remains high, most closely related to wound complications, as such, concomitant definitive repairs should be entertained with caution.

Current practice patterns for initial umbilical hernia repair in the United States.

PURPOSE: The approach to repairing an initial umbilical hernia (IUH) varies substantially, and this likely depends on hernia size, patient age, sex, BMI, comorbidities including diabetes mellitus, and surgeon preference. Of these, only hernia size has been widely studied. This cross-sectional study aims to look at the practice pattern of umbilical hernia repair in the United States. METHODS: A retrospective study was performed using data from the America Hernia Society Quality Collaborative. Patient characteristics included age, sex, hernia width, BMI, smoking status, and diabetes. Outcomes were use of mesh for repair, as well as surgical approach (open vs minimally invasive). Multivariate logistic regression was performed to assess the independent effect of age, sex, hernia width, BMI, smoking status, and diabetes on use of mesh and approach to repair. RESULTS: 3475 patients were included. 74% were men. Mesh use was more common in men (67% vs 60%, P < 0.001). Mesh was used in 33% of repairs ≤ 1 cm, and 82% of repairs > 1 cm (P < 0.001). Younger patients were less likely to receive a mesh repair (54% if age ≤ 35 vs 67% for age > 35, P < 0.001). However, on multivariate analysis, mesh use was associated with increasing hernia width (OR 5.474, 95% CI 4.7-6.3) as well as BMI (OR 1.8, 95% CI 1.5-2.1) but not with age or sex. CONCLUSION: The majority of IUH are performed open. Patient BMI and hernia defect size contribute to choice of surgical technique including use of mesh. The use of mesh in 33% of hernias below 1 cm demonstrates a gap between evidence and practice. Patient factors including patient age and sex had no impact on operative approach or use of mesh.

Hybrid robotic transversus abdominis release versus open: propensity-matched analysis of 30-day outcomes.

PURPOSE: To examine the hospital length of stay (LOS) and 30 day outcomes of hybrid robotic transversus abdominis release (hrTAR) compared with open transversus abdominis release (oTAR). METHODS: Patients receiving hrTAR were selected from the AHSQC database and propensity matched with a contemporary cohort of oTAR patients. RESULTS: The cohort included 95 hrTAR and 285 oTAR patients. There was a significantly shorter median LOS in the hrTAR cohort (3 vs. 5 days, p < 0.001). The rate of surgical site occurrences in the hrTAR cohort was also lower than for oTAR (5% vs. 15%, p = 0.015). Readmission rates were not different between hrTAR and oTAR (6% vs. 8%, p = 0.65). CONCLUSION: hrTAR demonstrates improved LOS compared to oTAR as well as fewer surgical site related occurrences. Further studies are needed to investigate the etiology behind the improved LOS and to confirm appropriate long-term outcomes from hybrid robotic TAR.

Non-coated versus coated mesh for retrorectus ventral hernia repair: a propensity score-matched analysis of the Americas Hernia Society Quality Collaborative (AHSQC).

PURPOSE: The outcomes of utilizing anti-adhesive barrier-coated mesh in the retrorectus position during open ventral hernia repair are unknown. We compared the wound-related outcomes between non-coated (NCM) and coated mesh (CM) placed in the retrorectus space. METHODS: Patients undergoing elective, open, clean ventral hernia repair with retrorectus mesh were retrospectively identified in the Americas Hernia Society Quality Collaborative. Propensity score matching was performed based on clinically relevant demographic and operative covariates. The primary outcome was wound morbidity, defined as surgical site infection (SSI), surgical site occurrence (SSO), and SSO requiring procedural intervention (SSOPI). RESULTS: 3609 patients were included (3281 NCM, 328 CM). Following 2:1 propensity score matching, rates of myofascial release remained the only statistically different matching parameter; external oblique releases were performed more frequently in the CM group (8% vs. 15%; p = 0.03). Rates of SSI (3% vs. 4%; p = 0.16) were similar between groups. Increased rates of SSO (13% vs. 18%; p = 0.045) and SSOPI (4% vs. 8%; p = 0.038) were observed in the CM group. The CM group had a higher rate of postoperative seroma (3% vs. 7%; p = 0.027) compared to the NCM group. CONCLUSION: Barrier-coated mesh in the retrorectus position was associated with increased wound morbidity requiring procedural intervention. Due to a lack of clinical benefit, the use of more costly barrier-coated mesh in the retrorectus position is not justified for routine, open ventral hernia repairs at this time.

Comparing 30-day outcomes between different mesh fixation techniques in minimally invasive inguinal hernia repair.

PURPOSE: The association of postoperative patient-reported outcomes and type of mesh fixation during minimally invasive inguinal hernia repair has not been well characterized. We aimed to compare the 30-day quality of life outcomes between various mesh fixation techniques utilizing the AHSQC prospective registry. METHODS: All minimally invasive inguinal hernias with completed 30-day follow-up were abstracted from the AHSQC, excluding patients with primary indication for surgery being chronic groin pain. Mesh fixation was categorized as (1) atraumatic fixation (AF) (2) traumatic non-suture (TNS), (3) traumatic suture (TS). Our outcomes of interest were pain at site at 30-day and EuraHS quality of life assessment. RESULTS: After applying inclusion and exclusion criteria, 864 patients had surgical site pain and quality of life outcomes reported; 253 (AF), 451 (TNS), and 160 (TS). After adjusting for identified confounders, there was no statistically significant difference between any fixation method when evaluating pain as a binary variable (Yes/No). However, when looking at the EuraHS evaluation for pain and quality of life outcomes, AF was associated with better scores than both TNS and TS fixation in the cosmetic, restrictions, and overall EuraHS domains. AF was only better than TS fixation in the pain domain. CONCLUSION: Our study suggests that AF had a significantly improved hernia-specific quality of life in all domains at 30-days postoperatively. We also identified that pain as a binary variable is inadequate for its states purpose. Thus, the overall well-being and morbidity should be taken into account when evaluating hernia patients postoperatively.

Review of inguinal hernia repair techniques within the Americas Hernia Society Quality Collaborative.

PURPOSE: As the ultimate procedure which each surgeon decides to perform for a unilateral uncomplicated inguinal hernia remains controversial, we queried the Americas Hernia Society Quality Collaborative (AHSQC) database to report the collective experience of surgeons in the United States whom contribute to AHSQC to provide a view of the surgical approaches performed. METHODS: The AHSQC data registry was queried for all adult patients who underwent a primary, unilateral, elective, inguinal hernia repair. A retrospective review was conducted to analyze patient demographics, hernia characteristics, operative details, and post-operative outcomes. Our main outcomes of interest were 30-day surgical site infections (SSI), surgical site occurrences (SSO), 30-day patient-reported outcomes, and 1-year recurrence rates. RESULTS: 4613 patients met inclusion criteria. 1925 were repaired using an open technique (42%), 1841 were repaired using a laparoscopic technique (40%), and 847 were repaired using a robotic technique (18%). The Shouldice technique remains the most common tissue-based repair performed in the AHSQC. The Lichtenstein repair is the most common open mesh-based repair. Minimally invasive approaches to unilateral inguinal hernia repairs remained very common in our series. The robotic approach accounted for nearly one-third of the minimally invasive inguinal hernia repairs. CONCLUSION: In general, all of the repair techniques reported similar and low rates of 30-day complications. The AHSQC continues on-going efforts to improve long-term follow-up and looks forward to addressing long-term outcomes such as recurrence and chronic pain with increasing data acquisition.

Early repair of ventral incisional hernia may improve quality of life after surgery for abdominal malignancy: a prospective observational cohort study.

PURPOSE: Recent work has shown that over 40% of patients undergoing surgery for abdominal malignancy develop ventral incisional hernias (VIH) within 2 years. We hypothesized that early repair of VIH for cancer survivors could improve long-term quality of life (QoL). METHODS: All patients presenting with a history of surgery for abdominal malignancy and a VIH were prospectively enrolled. QoL was assessed at baseline and 3-, 6-, 12-, 18-, and 24-month follow-up using abdominal wall-specific (HerQLes) and cancer-specific (FACT-G) instruments. At the study's conclusion, patients were divided into 2 groups-those that underwent VIH repair during the study's course (Repair Group) and those that did not (Control Group). Categorical variables were analyzed using Pearson's Chi-square and continuous variables with Wilcoxon rank sum test. RESULTS: Eighty-four patients were enrolled. Overall, 46 patients (55%) underwent VIH repair, with 36 repairs (78%) occurring within 3 months of initial evaluation. Sixty-six (79%) had complete 1-year follow-up data, and 30 (36%) had 2-year data, with a median follow-up duration of 15.6 months. At baseline, both groups were similar with respect to demographics, cancer stage, and HerQLes/FACT-G scores. Compared to the Controls, the Repair Group showed greater improvements over baseline HerQLes Summary Scores at the 3-, 6-, 12-, and 18-month time points (median increase, 37 vs. 26 points), and in FACT-G total scores at the 3-, 6-, and 12-month time points (median increase, 6 vs. 4 points). CONCLUSIONS: Repair of VIH after surgery for abdominal malignancy may improve abdominal wall-specific and cancer-specific QoL, making post-resection abdominal wall reconstruction an important aspect of cancer survivorship.

Frequency of endoscopic surveillance for Barrett's esophagus is influenced by health insurance status: results from a population-based analysis.

Factors that influence the frequency of surveillance endoscopy for nondysplastic Barrett's esophagus are not well understood. The objective of this study is to assess factors which influence the frequency of endoscopic surveillance for Barrett's esophagus, including health insurance/third-party payer status. Cases of nondysplastic Barrett's esophagus undergoing esophagogastroduodenoscopy with biopsy were identified using longitudinal data from the Healthcare Utilization Project database in 2005-2006 and followed through 2011. The threshold for appropriate surveillance utilization was defined as two to four surveillance esophagogastroduodenoscopies over a standardized 5-year period. Patients' insurance status was designated as either Medicare, Medicaid, private, or noninsured. 36,676 cases of nondysplastic Barrett's esophagus were identified. Among these, 4,632 patients (12.6%) underwent between two and four surveillance esophagogastroduodenoscopies in 5 years of follow-up versus 31,975 patients (87.3%) who underwent fewer than two esophagogastroduodenoscopies during follow-up. Multivariate analysis found that Barrett's patients insured through Medicaid (OR 1.273; 95% CI = 1.065-1.522) or without insurance (OR = 2.453; 95% CI = 1.67-3.603) were at increased likelihood of being under-surveilled. This study identified a difference in frequency of surveillance esophagogastroduodenoscopy for Barrett's esophagus by payer status. Patients without health insurance and those whose primary insurance was Medicaid were at increased odds for under-surveillance. These data suggest that a more robust system for tracking and ensuring longitudinal follow-up of patients with Barrett's esophagus, with attention to the uninsured and underinsured population, may be needed to ensure optimal surveillance.

CATTLE (CAncer treatment treasury with linked evidence): An integrated knowledge base for personalized oncology research and practice.

Despite the existence of various databases cataloging cancer drugs, there is an emerging need to support the development and application of personalized therapies, where an integrated understanding of the clinical factors and drug mechanism of action and its gene targets is necessary. We have developed CATTLE (CAncer Treatment Treasury with Linked Evidence), a comprehensive cancer drug knowledge base providing information across the complete spectrum of the drug life cycle. The CATTLE system collects relevant data from 22 heterogeneous databases, integrates them into a unified model centralized on drugs, and presents comprehensive drug information via an interactive web portal with a download function. A total of 2,323 unique cancer drugs are currently linked to rich information from these databases in CATTLE. Through two use cases, we demonstrate that CATTLE can be used in supporting both research and practice in personalized oncology.

[Spatio-temporal distribution of scrub typhus and related influencing factors in coastal beach area of Yancheng, China].

OBJECTIVE: In order to provide better programs on monitoring, early warning and prevention of Scrub Typhus in the coastal beach area, temporal-spatial distribution characteristics of scrub typhus were summarized. Relationships between temporal-spatial clustering of Scrub Typhus, meteorological factors, rodent distribution and the biological characteristics in coastal beach area of Yancheng city, were studied. METHODS: Reports on network-based Scrub Typhus epidemics and information on population, weather situation through monitoring those stations, from 2005 to 2014 were collected and processed, in the coastal beach area of Yancheng city. Distribution, density of the population concerned and seasonal fluctuation on rodents were monitored in coastal beach area, from April 2011 to December, 2013. METHODS as descriptive statistics, space-time permutation scantistics, autocorrelation and Cross-correlation analysis etc, were used to analyze the temporal-spatial distribution of Scrub Typhus and correlation with rodent distribution, density fluctuation and meteorological indexes. Zero-inflated Pearson (ZIP) regression model was contributed according to the distribution of related data. All methods were calculated under Excel 2003, SPSS 16.0, Mapinfo 11.0, Satscan 9.0 and Stata/SE 10.0 softwares. RESULTS: (1) The incidence of Scrub Typhus was gradually increasing and the highest incidence of the year was seen in 2014, as 5.81/10 million. There was an autumn peak of Scrub typhus, with the highest incidence rate as 12.02/10 million in November. The incidence rate of Scrub typhus appeared high in Binhai, Dafeng and Xiangshui, with the average incidence rates appeared as 3.30/10 million, 3.21/10 million and 2.79/10 million, respectively. There were 12 towns with high incidence rates in the coastal beach area, with incidence rate showed between 4.41/10 and 10.03/10 million. (2) There were three incidence clusters of Scrub typhus seen in 25 towns, between October 2012 and November 2012 in Dongtai, Dafeng, Sheyang areas and 5 towns between October and November, 2014 in Xiangshui area, together with another 6 towns in November of 2006, in Binhai area. (3) Apodemus agrarius appeared the dominant species in the coastal area, with the constituent ratio as 89.19%. The rodent density appeared two peaks in winter and summer in 2011 and 2013. The winter peak was seen in January and the summer peak lasting for 5-8 months. Scrub Typhus was seen 10-11 months in a year and the incidence was increasing, parallel with the peak of the rodent density. The peak incidence of Scrub Typhus showed a temperature/rainfall-related peak. Rodent density, temperature, rainfalls were correlated with the incidence of Scrub Typhus, under the Cross correlation analysis. Rains, Mean minimum temperature of a 3-month lagging were directly correlated but the duration of sunshine and relative humidity were negatively correlated with the incidence of Scrub Typhus, under the Zero-inflated Pearson (ZIP) regression model. CONCLUSION: Temporal-spatial clustering and factors as media creature and weather condition of Scrub Typhu were discovered, which provided evidence for effective measures on prevention and control of the disease.

Nest building is a novel method for indexing severity of alcohol withdrawal in mice.

Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2-4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1-2 but not days 2-3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4 g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice.

Simultaneous determination of aflatoxin M1, ochratoxin A, zearalenone and α-zearalenol in milk by UHPLC-MS/MS.

In this study, a sensitive and rapid method has been developed for the simultaneous determination of aflatoxin M1, ochratoxin A, zearalenone and α-zearalenol in milk by ultra high performance liquid chromatography combined with electrospray ionisation triple quadrupole tandem mass spectrometry (UHPLC-ESI-MS/MS). The milk samples were purified using Oasis HLB cartridge. The matrix effects were evaluated by determining the signal suppression-enhancement (SSE) and corrected by external matrix-matched calibration. The limits of quantity (LOQ) of the mycotoxins were in the range of 0.003-0.015µgkg(-1). The high correlation coefficients (R(2)⩾0.996) were obtained in the range of 0.01-1.00µgkg(-1) of the mycotoxins, along with good recovery (87.0-109%), repeatability (3.4-9.9%) and intra-laboratory reproducibility (4.0-9.9%) at the concentrations of 0.025, 0.1 and 0.5µgkg(-1). The detected rates of the mycotoxins were from 16.7% to 96.7% in raw milk, liquid milk and milk powder samples collected from the dairy farms and supermarkets in Beijing. The method proposed is suitable for the simultaneous determination of aflatoxin M1, ochratoxin A, zearalenone, and α-zearalenol, and could be performed for analysing the mycotoxins in milk.