Canine gastrointestinal tract (GIT) parasites are of public health and veterinary concern and are harmful to both humans and animals. The risk of transmitting GIT parasites can be minimized depending on dog owners’ knowledge and management practices. Therefore, this study aimed to assess dog owners’ general knowledge and practices regarding GIT parasites.A structured questionnaire containing 10-point Likert statements was administered to 130 respondents in Cebu, Philippines, to obtain information about their profile  and data regarding their home environment, number of dogs and other pets owned, and their knowledge and practices regarding canine GIT parasites. These respondents had previously provided canine stool samples for fecalysis.Most respondents were female (65.4%), 18–24 years old (55.4%), single (71.5%), and educated to college level (49.2%). Housing styles were mostly gated (76.9%), and >50% had a garden. The majority owned 1–3 dogs (56.9%) and did not own any other pets (73.8%). All knew about canine GIT parasites. There was a significant association between GIT parasite positivity in dogs and the owner’s sex (p = 0.005). Gastrointestinal parasite positivity was also associated with the owner’s knowledge about the transmission of parasites from the mother’s milk to her puppies (p = 0.001), canine intestinal parasites potentially causing weight loss, diarrhea, and vomiting (p = 0.001), and dogs potentially becoming infected with parasites from licking or sniffing the soil or grass where other animals have been (p = 0.005). Moreover, there was a significant association between GIT parasite positivity and the owner’s practice of daily cleaning of the areas where the dog defecated (p = 0.001), deworming every 6–12 months (p = 0.001), and unfailingly following the vaccination and deworming schedule (p = 0.006). Finally, the summative knowledge and practice level of the owners were significantly associated with GIT parasite positivity (p = 0.001).This study highlights the need for continuous education of dog owners to maintain good knowledge and practices to prevent GIT parasite infection. Frequent deworming (once a month) of adult dogs is recommended. Pet dogs live closely with their human owners, contributing to each other’s overall well-being . They prAncylostoma, Trichuris, and Toxocara spp. [Canine GIT parasites are of veterinary and public health importance and cause morbidity in dogs and humans . Infectiara spp. .Pet owners may be unaware that their dogs may carry zoonotic parasites and be unfamiliar with their modes of transmission . WithoutTo the best of the author’s knowledge, no recent studies in Cebu, Philippines, have assessed the knowledge and practices of household dog owners in relation to the presence of GIT parasites in their respective dogs. Thus, this study was conducted.The study was conducted according to the principles of the Helsinki Declaration developed by the World Medical Association. The protocol was approved by the University of the Visayas – Institutional Review Board. Written informed consent was obtained from the respondents.The study was conducted from January 2017 to May 2017 in Cebu, Philippines.The study participants included 130 dog owners from different households aged 18–64 years and above from Cebu, Philippines. Only respondents who had previously collected a stool sample from their dogs for fecalysis in February to May 2017 were included in the study. Hence, the census method of data collection was employed.A structured questionnaire was administered to gather information about the owners’ profiles, such as age, sex, civil status, and educational attainment, and data about their home environment and the number of dogs and other pets owned. The questionnaire also assessed the owner’s general knowledge of GIT parasites as follows: (1) potential transmission of parasites to dogs by other animals, (2) transmission of parasites to puppies through their mother’s milk, (3) transmission of parasites from dogs and humans through the fecal-oral route, (4) intestinal parasites in dogs causing weight loss, diarrhea, and vomiting, and (5) dogs obtaining parasites from licking or sniffling the soil or grass where other animals have been. The dog owners were also asked about the following practices related to GIT parasites: (1) feeding raw meat, (2) daily cleaning of areas where the dog had defecated, (3) deworming every 6–12 months, (4) following the vaccination and deworming appointments for their dogs as set by the veterinarian, and (5) maintaining a clean environment where the dogs usually stay. Before administration, the questionnaires were subjected to face validation by three identified experts and pretested on 25 respondents. The Cronbach alpha value was computed (0.64) and deemed acceptable.The 10-point Likert scale answers were scored. The summative scores obtained by the owners were categorized and given a score of 5 (very high) if they scored 41–50 points, 4 (high) if they scored 32–40 points, 3 (moderate) if they scored 23–31 points, 2 (low) if they obtained scored 15–22 points, and 1 (very low) if scored below 15. On the other hand, the number of infected dogs and the specific parasite prevalence rates were estimated.The data were encoded in Microsoft Excel spreadsheets and analyzed using descriptive statistics. Chi-square test was used to determine the statistical significance between the owner’s profile, knowledge, and practices and the rate of GIT parasite positivity of their respective dogs. Results were considered significant when p ≤ 0.05.More than half of the respondents were 18–24 years old (55.4%), with an average age of 29.9 years. Most were female (65.4%), predominantly single (71.5%), and educated to college level (49.2%). Concerning housing styles, 76.9% were gated, and >50% had a lawn or garden. Finally, over half of the households owned one to three dogs (56.9%), and the majority did not own any other animals (73.8%) . The ownRegarding the knowledge of dog owners about GIT parasites, most were either undecided or did not agree that other animals can transmit parasites to dogs. Most were undecided or agreed that puppies can become infected with parasites from their mother’s milk. The majority were aware that GIT parasites can be transmitted to humans through the fecal-oral route; that they can cause weight loss, diarrhea, and vomiting; and that dogs can become infected with parasites from licking or sniffling the soil or grass where other animals have been. With the different statements, there were undecided respondents (10.8–43.8) concerning basic relevant facts about GIT parasites. Regarding the practices, almost all respondents did not feed their dogs raw meat. Most cleaned the areas where their dogs defecated. Most dewormed their dogs every 6–12 months and unfailingly followed the vaccinations and deworming appointments the veterinarian had set for their dogs. The importance of maintaining a clean environment where the dogs usually stay was almost recognized .Overall, the knowledge and practices of most owners scored high (56.9%) and very high (39.3%). The dog owners appeared well informed, which may be attributed to better access to veterinary services and better living standards of owners . AlthougThere was a significant association between dogs positive for GIT parasites and their owner’s sex (p = 0.005). The dog owner’s sex may be associated with the severity of GIT parasitism, with those owned by females having higher tendencies to harbor GIT parasites . HoweverSeveral knowledge factors were associated with GIT parasite positivity in dogs, including the owner’s knowledge about puppies becoming infected with parasites from their mother’s milk (p = 0.001). Transplacental and transmammary parasitic transmission from the mother to her puppies are possible , 23. ThuKnowledge about GIT parasites potentially causing weight loss, diarrhea, and vomiting (p = 0.001) was associated with the GIT parasite positivity in the dogs. These are commonly observed clinical signs in dogs with parasites , 24. OwnKnowledge about dogs potentially becoming infected with parasites from licking or sniffing the soil or grass where other animals have been (p = 0.005) and the owner’s practice of daily cleaning of the areas where the dog has defecated p = 0.001) was significantly associated with GIT parasite positivity. Soil contact is an identified risk factor  was sign. This coThe practice of deworming the dogs every 6–12 months was significantly associated with GIT parasite positivity (p = 0.001). Deworming is critical in preventing GIT parasitism , and thiOwners who unfailingly follow vaccination and deworming appointments for their dogs with the veterinarian were also significantly associated with GIT parasite positivity (p = 0.006). Frequent veterinary visits can motivate dog owners to comply with recommended GIT prevention and control measures, including deworming and proper feces disposal . The rouOverall, the summative knowledge and practices of the dog owners were significantly associated with the presence of GIT parasites (p = 0.001) . In otheMaintaining good knowledge and practices for the prevention and control of GIT parasites in dogs are essential. Dog owners should be continuously educated about proper dog management, particularly for GIT parasites.Dog owners should continue to sustain good practices and remain up to date with the latest knowledge and products for GIT parasite prevention and control. In addition, frequent deworming (once a month) of adult dogs is recommended.APY, MFMU, and RHDY: Equal authors and conceptualized the study, conducted the research and finalized the manuscript. ESD: Data analysis and drafted the manuscript. All the authors have read, reviewed, and approved the final manuscript.


Breast cancer is the second most common diagnosed type of cancer in women. Chronic neuropathic pain after mastectomy occurs frequently and is a serious health problem. In our previous single-center, prospective, randomized controlled clinical study, we demonstrated that the combination of serratus anterior plane block (SAM) and pectoral nerve block type I (PECS I) with general anesthesia reduced acute postoperative pain. The present report describes a prospective follow-up study of this published study to investigate the development of chronic neuropathic pain 12 months after mastectomy by comparing the use of general anesthesia alone and general anesthesia with SAM + PECS I. Additionally, the use of analgesic medication, quality of life, depressive symptoms, and possible correlations between plasma levels of interleukin (IL)-1 beta, IL-6, and IL-10 collected before and 24 h after surgery as predictors of pain and depression were evaluated. The results showed that the use of SAM + PECS I with general anesthesia reduced numbness, hypoesthesia to touch, the incidence of patients with chronic pain in other body regions and depressive symptoms, however, did not significantly reduce the incidence of chronic neuropathic pain after mastectomy. Additionally, there was no difference in the consumption of analgesic medication and quality of life. Furthermore, no correlation was observed between IL-1 beta, IL-6, and IL-10 levels and pain and depression. The combination of general anesthesia with SAM + PECS I reduced the occurrence of specific neuropathic pain descriptors and depressive symptoms. These results could promote the use of SAM + PECS I blocks for the prevention of specific neuropathic pain symptoms after mastectomy.Registration of clinical trial: The Research Ethics Board of the Hospital Sirio-Libanes/Brazil approved the study (CAAE 48721715.0.0000.5461). This study is registered at Registro Brasileiro de Ensaios Clinicos (ReBEC), and ClinicalTrials.gov, Identifier: NCT02647385. A potentially debilitating problem that afflicts patients with breast cancer after surgery is the chronic pain after mastectomy, which affects 25–60% of the patients3, severely impacts the quality of life4, and is often comorbid with depression5.Breast cancer is the second most common cancer in women with a reported incidence of 19.3 million cases worldwide and 10 million cancer-related deaths7. The chronic neuropathic pain has different characteristics depending on the surgical treatment or nerve damage9. The intensity of pain after surgery and consumption of analgesic medication have been reported to increase the risk of neuropathic pain10. The complexity and difficulty of its treatment could be because of neuroinflammation involving the release of inflammatory interleukins, such as interleukin (IL)-1 beta, IL-6, and IL-1011. “Plasmatic inflammatory markers could be used as prognostic predictors of pain in large interval of time12, it has been proposed that patients who developed neuropathic pain syndrome seem to have higher levels of IL-6 in plasma14. Also, IL-6 concentration is positively correlated with pain severity13, and is a risk factor for increased intensity of pain15. IL-1 Beta has been used as prognostic biomarker predictors for the severity of pain in breast cancer17. In the same line of thinking, inflammatory biomarkers have been considered effective potential biomarkers for depression20”.Post-mastectomy pain syndrome or post-breast surgery pain syndrome has been described as a mixed syndrome that occurs 6 months after the procedure, characterized by persistent moderate pain with neuropathic characteristics located in the anterior thorax, axilla, and/or medial upper arm22. The serratus anterior plane (SAM) block and pectoral nerves block type I (PECS I) are safe and effective in breast surgery, resulting in excellent postoperative analgesia25. The combination of SAM and PECS I blocks promotes effective analgesia and reduction of intraoperative fentanyl and intravenous morphine usage during mastectomy with the axillary approach and reconstruction26.Regional anesthesia has been suggested to play a protective role in the development of chronic neuropathic pain after mastectomy26 to investigate the presence of chronic neuropathic pain 12 months after mastectomy in patients who received general anesthesia only or general anesthesia with SAM + PECS I blocks. As secondary goals, the use of analgesic medication, quality of life, depressive symptoms, and possible correlations between plasma levels of interleukin (IL)-1 beta, IL-6, and IL-10 as predictors of pain and depression were evaluated. The rational for the choice of those outcome variables is that chronic pain in general could be exacerbated by neuropathic pain-generating mechanisms leading to both the physical and emotional suffering of patients that negatively impacts the quality of life.Despite all the advances in regional anesthesia for breast cancer, the role of SAM and PECS I blocks in the development of chronic pain has not been evaluated. The present report describes a prospective follow-up study of a previously published study26. The Ethics in Research Committee of the Hospital Sirio-Libanes/Brazil Platform approved the project (CAAE 48721715.0.0000.5461), it is registered at Registro Brasileiro de Ensaios Clinicos (ReBEC), ClinicalTrials.gov, Identifier: NCT02647385, and the date of registration is 06/01/2016. All methods were performed in accordance with relevant guidelines and regulations.A prospective follow-up study of a previously published randomized controlled clinical study was conducted26. Female patients within the age range of 18–75 years, with American Society of Anesthesiology (ASA) physical status I or II, suitable for radical mastectomy with axillary node dissection and breast reconstruction, who provided written informed consent were included. Exclusion criteria for enrollment in the previous study were allergy to medications used in the study, history of mental disorders and chronic pain. The reason is that history of chronic pain is an independent risk factor for neuropathic chronic pain after mastectomy27. Additional exclusion criteria for this report was lost to follow-up.The main inclusion criterion was patients enrolled in our previous study26, patients were randomly allocated to general anesthesia alone or general anesthesia with SAM + PECS I blocks.In our previous studyThe block randomization method for the clinical study was designed to randomize subjects into 1 of the possible groups, i.e. group I: general anesthesia, group II: SAM + PECS-1 block. After generation of the randomization codes by the corresponding author, the allocation was registered in opaque sealed envelopes, and the patients were kept blind to this process. An anesthesiologist recruited participants from the ambulatory care unit of Hospital Sirio-Libanes.−1), propofol (2–3 mg kg−1), and cisatracurium (0.1 mg kg−1) or rocuronium (0.6 mg kg−1). Anesthesia was maintained using sevoflurane (1.5–2.0%) and 50% oxygen delivered via a circle system. Additional fentanyl boluses were administered if necessary.The patients received midazolam (7.5 mg) orally as a premedication 1 h before surgery. Anesthesia was induced using fentanyl . For the PECS I block, 10 mL of 0.375% ropivacaine was injected in the fascia between minor and major pectoral muscles. Needle position was confirmed using visualization of the separation of the layers with dispersion of the injected volume.The SAM and PECS I blocks were performed by a team composed of three experienced anesthetists, as described previouslyAll patients received a standardized postoperative analgesic regimen consisting of metamizole (1 g every 6 h), ketoprofen (100 mg every 12 h), and patient-controlled analgesia (PCA) rescue with intravenous morphine at the end of the surgical procedure.29.Numeric Rating Scale (NRS) is a standard scoring system to assess immediate pain levels, ranging from scores 0 (no pain) to 10 (worst pain). Chronic pain can be defined as NRS score > 0 on a 0–10 scale at least 3 months after the surgical procedureDouleur Neuropathique 4 (DN4) questionnaire accesses seven domains of neuropathic pain  and tree domains related to sensorial examination 31. In this study, the surgical area, axilla, medial arm, breast, or chest wall were evaluated, and a score equal or greater than 4 points characterized neuropathic pain32.Short-Form Health Survey (SF-36) is a health status questionnaire consisted of eight domains including functional capacity, physical aspects, general state of health, vitality, social aspects, pain, emotional aspects, and mental health ranging from zero  to 100 .33.Patient Health Questionnaire-9 (PHQ-9) is an instrument assessing nine depressive symptoms along with a functional health assessment. Scores range from 0 (none) to 27 (severe) to identify depressive statesThe patients were interviewed using the following scales:26.Blood samples were collected in EDTA-Vacutainer tubes before and 24 h after the surgical procedure, and the plasma levels of IL-1 beta, IL-6, and IL-10 were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits (R&D Systems), as described previously26. In this study, patients that completed 1-year follow-up were included in the analysis. Power analysis for this new study was calculated based on using www.openepi.com, based on the results of Qian et al.29, who evaluated SAM block (lidocaine) versus control group  and produced an effect size of 1.5 for NRS. Twenty patients per group were required to achieve significant results with an alpha of 0.05 and a beta of 90%. In this study, 22 patients were included in each treatment group.The sample size for the clinical study was previously calculated and can be found in our previous publication30. The patients were evaluated using the Numeric Rating Scale (NRS) and the Douleur Neuropathique 4 (DN4) questionnaire Also, the incidence of pain in other body regions was performed.The primary outcome measure was evaluation of chronic neuropathic pain development 12 months after the mastectomy. All patients were evaluated by an anesthesiologist specialist in pain management. The diagnosis of neuropathic pain is based on clinical evaluation based on the history and physical examination to evaluate signs and symptoms. The DN-4 survey was used as a screening tool to better understand the chronic neuropathic pain after mastectomy and was performed as previous describedDemographic, clinical, surgical, and nonsurgical treatment data were collected. The current use of analgesic medication and the quality of life indicator of overall health status were evaluated using the Short-Form Health Survey (SF-36), and depressive symptoms were evaluated using the Patient Health Questionnaire-9 (PHQ-9). IL-1 beta, IL-6, and IL-10 levels before and 24 h after the surgical procedure were evaluated as predictors of pain and depression.26 were interviewed, by a blinded experimenter, with the NRS, DN4, SF-36, PHQ-9, and asked about the use of analgesic medication at that time set point. The plasma levels of IL-1 beta, IL-6, and IL-10 were correlated with the NRS, DN4, and PHQ-9 scales as predictors of pain and depression. All data were entered into the REDCap (Research Electronic Data Capture) database.Twelve months after the surgical procedure, the blinded patients included in the previous studyThe Shapiro–Wilk test was used to investigate data distribution and showed that the data analyzed in this study presented with normal distribution. Demographic, quality of life (SF-36), and pain (NRS) data were analyzed using the Mann–Whitney test. Analgesic medication and neuropathic pain (DN4) were analyzed using Pearson’s chi-square test and corrected with Yates’ continuity correction where applicable. Depressive symptoms (PHQ-9) were analyzed using Cochran’s Q test. Correlations were analyzed using Pearson’s correlation coefficient. Statistical significance was set at p ≤ 0.05.From 182 breast cancer surgeries performed between December 2015 and April 2016, 133 cases did not meet inclusion criteria because different types of surgery were performed including mastectomy only, lumpectomy or other breast-sparing surgery. A total of 49 patients were randomized and allocated to the Group II—general anesthesia with SAM + PECS I protocol (n = 25) or Group I general anesthesia only protocol (n = 24). For the follow-up in this study, which was performed 12 months after surgery, five patients were excluded. A total of 44 patients (22 in each group) were included in the analysis  was observed in the NRS pain scores reported by the two patient groups 12 months after mastectomy  was observed in the percentage of patients reporting DN4 punctuation > 4, as illustrated in Fig. Figure Group II showed a reduction in the percentage of patients showing pain in other body regions in comparison with Group I p = 0.014), as shown in Fig. , as showNo significant difference in the use of analgesic medication 12 months after the surgical procedure was noted between groups (p = 0.112), as shown in Fig. Data referring to the PHQ-9 scale are shown in Fig. Table Table 34 the role of SAM + PECS1 focus on this subgroup of interest.To our knowledge, this is the first follow-up study evaluating chronic neuropathic pain after mastectomy in patients who were administered general anesthesia with SAM and PECS I blocks compared with those who received general anesthesia during the surgical procedure. The results showed that 12 months after mastectomy with axillary approach and reconstruction, the patients who received general anesthesia with SAM and PECS 1 blocks did not have a decreased incidence of chronic neuropathic pain; however, they presented a reduction in the descriptors numbness and hypoesthesia; and in the incidence of patients that present chronic pain in other body regions. Importantly, there was a reduction in depressive symptoms in the general anesthesia with SAM and PECS I blocks group. We had chosen not including different types of surgical procedures in our study to have a homogenous sampling and being able to further understand and describe35. It is suggested that body mass index may be an important predictor of post-mastectomy chronic pain development36. The age of onset of menopause is important for guiding treatment strategies37. However, in the present study, these parameters did not influence the development of chronic pain. Regarding axillary lymph node dissection, which has been considered a major risk factor for chronic neuropathic pain after mastectomy36, our data showed no statistically significant difference between groups. Chemotherapy and radiation may lead to the development of chronic persistent post-surgical pain38. Also, the lymphatic system dysfunction could affect lymph drainage39 and contribute to chronic pain in general, functional impairment, and depression41. It is important to point that our data did not showed difference between groups in those parameters.Demographic data showed no difference between the groups regarding age, body mass index, menopausal age, and duration of the surgical procedure. Our data agree with the median age at diagnosis of breast cancer in middle-aged and older women42. Therefore, it is important to emphasize that there were no significant differences between the two groups in terms of these parameters that could influence the development of chronic neuropathic pain after mastectomy.Additionally, the duration of surgery could increase the severity of acute pain and consequently, has been associated with persistent pain43. Also, this type of chronic pain has no purposes of adaptation, devoid of biological value, not respond to typical treatment and last more than six months, causing suffering, distress and contributing to deteriorate the quality of life of the patients44. Several screening tools have been developed to identify possible symptoms of neuropathic pain owing to their varied manifestations45. The DN4 questionnaire is a valuable tool for investigating neuropathic pain profile and assessing its possible mechanisms46. DN-4 questionnaire has high sensitivity and specificity in distinguish chronic neuropathic pain from chronic nonneuropathic pain48 and is a reliable tool for evaluating chronic neuropathic pain and the effect of regional anesthesia as protecting strategies after breast cancer surgery49. Our study performed a detailed analysis of DN4 items to better understand the chronic neuropathic pain after mastectomy of these patients. Our data are in accordance with the literature, showing that hypoesthesia to touch is a sensory dysfunction, followed by numbness50, also there was a reduction in the incidence of patients reporting chronic pain in other regions. General anesthesia with SAM and PECS I blocks reduced the occurrence of hypoesthesia to touch and numbness compared with general anesthesia alone. A possible explanation could be that the patients who received SAM and PECS I blocks experienced a reduction in postoperative pain26. Chronic pain in general is associated with inadequate postoperative pain control8. In addition, the analgesic pattern offered by the SAM + PECS 1 blocks provide excellent analgesia to the breast and axillary regions54.Chronic neuropathic pain after mastectomy is caused by lesions or diseases of the somatosensory nervous system, which may lead to increased pain sensitivity, spontaneous pain, and loss of function55. The use of SAM block was also shown to reduce its prevalence 6 months after mastectomy29, which is consistent with our findings. In the pathophysiology of chronic pain after mastectomy, the neuropathic categories are attributed to nerve damage or traction during surgery, particularly targeting the intercostobrachial, medial pectoral, lateral pectoral, thoracodorsal, and long thoracic nerves57. Thus, it has been postulated that nerve injury, neuroma, phantom breast pain, anatomic changes, axillary web syndrome, and lymphedema could be responsible for the neuropathic pain observed after breast surgery, and local anesthetic blockade of this region could be an alternative to prevent this type of pain56.The use of the PECS block has been shown to induce a lower incidence of chronic postsurgical pain in general 3 months after breast surgery58 or no effect59. The analgesic pattern of the paravertebral block reaches the sympathetic and intercostal nerves, while the combination of SAM + PECS I blocks can reach the thoracodorsal and long thoracic nerves, which are thought to be involved in the pathophysiology of chronic post-mastectomy neuropathic pain52. The analgesic pattern of SAM and PECS I blocks could explain the reduction in neuropathic symptoms, such as numbness and hypoesthesia.It is important to highlight that most of the studies that evaluated the development of chronic pain in general were performed with paravertebral blocks and demonstrated controversial results, showing pain reduction60 to evaluate quality of life and was used in the present study to identify possible confounding factors in the assessment of chronic pain.Our data showed no difference between the two groups regarding the SF-36 questionnaire domains. This tool has been routinely used in patients with breast cancer61. Psychological determinants, such as depression, is associated with more pain complaints and greater intensity of pain62. The PHQ-9 scale has been reported as a useful tool in assessing depressive symptoms33. Our data showed that patients who received general anesthesia with SAM and PECS I blocks had a lower incidence of depressive symptoms. To our knowledge, there is no association between the use of regional anesthesia and depression. A possible explanation could be that pain and depression share the same neuroanatomical substrate including biological pathways and neurotransmitters and the presence of pain negatively affect the recognition of depression62. In this sense, the use of regional anesthesia could decrease the neuronal reorganization contributing to simultaneously reduce pain and depression63. Also, it could be proposed that the use of SAM and PECS I blocks contributed to decreasing postoperative pain26 and consequently reducing the negative impact of the surgical procedure on the psychological aspects64.The diagnosis and identification of depression can be challenging in view of the wide variety of symptoms presented by patients. Pain and depression are common symptoms exhibited after mastectomy65. The mechanisms responsible for this depression-pain syndrome are not fully understood, but it is thought to involve neuronal reorganization in response to neuroinflammation in brain areas responsible for emotional processing and pain perception67.Because of the intrinsic clinical relationship between chronic pain in general and depression, this association has been called depression-pain syndrome or depression-pain dyad and has a direct impact on the quality of life and individual health care68. These data are in accordance with our results regarding the group subjected to general anesthesia only, while the patients who received regional and general anesthesia had a lower percentage of analgesic medication consumption. However, there was no statistically significant difference between the two groups, probably because the sample size was calculated for acute pain26. Specifically, our patients had been using a wide variety of medications, including nonopioid analgesics, opioid analgesics, anxiolytics, antidepressants, anticonvulsants, and muscle relaxants. These data are in accordance with a systematic review focusing on analgesic medications for breast surgery, suggesting that anticonvulsants may decrease the incidence of chronic pain; however, the beneficial role of combinations of analgesic medications is not completely understood69.Considering the consumption of analgesic medication after mastectomy, a previous study showed that approximately 40% of patients take analgesic medication for chronic pain in general70. Chemotherapy, hormone therapy, and radiotherapy have been proposed to be significantly associated with higher scores for the development of chronic pain36. Our results showed no differences in these parameters, supporting that the reduction in neuropathic descriptors in the regional anesthesia group was independent of the treatment therapies.Treatment therapies are important variables that contribute independently to the prediction of chronic pain in general71. In addition, neuroinflammation could be responsible for the depletion of brain serotonin, dysregulation of the hypothalamus–pituitary–adrenal axis, and hippocampal neurogenesis alteration, which contribute to depressive symptoms. It has been shown that IL-6 has a pivotal role in the development of pathological pain72, IL-1 drives chronic pain73 and IL-10 could suppress proinflammatory cytokines that modulates chronic pain74. Also, considering depression, IL-6 and IL-10 could be a potential biomarker of prognosis and severity77, while IL-1 levels could predict probability of response to antidepressants78. However, in this study, no correlation was observed between the levels of IL-1 beta, IL-6, and IL-10 before and 24 h after surgery, and the NRS, DN4, and PHQ-9 scores obtained 12 months after surgery. A possible explanation for the lack of differences could be attributed to the fact that we evaluated plasma cytokines, which serve as biomarkers, but do not directly reflect the neuroinflammation process, which could be better visualized using the cerebrospinal fluid79.We performed correlation tests using the plasma levels of cytokines and the chronic pain and depression. The rationale for this correlation is that a sustained increase in cytokine levels could contribute to central sensitization that is responsible for the maintenance of chronic painOur current study had some limitations. First, we evaluated chronic neuropathic pain at a single time point. Second, sample size calculation was performed for acute pain and is relatively small but is important to highlight the homogeneity of our patient sample. Also, postoperative pain therapies were not standardized and could be a potential source of bias in the results. Future research could address these limitations.In conclusion, our results suggest that the SAM and PECS I blocks associated with general anesthesia reduce the occurrence of two neuropathic pain descriptors, including numbness and hypoesthesia to touch and decrease the incidence of depressive symptoms after mastectomy.


The occurrence of autoantibodies in human immunodeficiency virus (HIV)-infected patients has been previously reported, with a prevalence ranging from 20 to 83%. There are also a few reports of clinically relevant autoantibody profiles in HIV-positive patients that lead to true systemic autoimmune disease; these possible life-threatening diseases have to be considered and treated accordingly.Here, we present the case of a 29-year-old female patient with a history of well-controlled HIV infection in the last 6 years who was admitted to our department for the evaluation of acute kidney injury and nephrotic syndrome with active urinary sediment. A diagnosis of systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal and pulmonary involvement was established. The patient was treated with cyclophosphamide, rituximab and tapering glucocorticoids,and the diffuse alveolar hemorrhage resolved, but the evolution of kidney function was unfavorable, which led to the need to initiate hemodialysis. We highlight the importance of establishing the correct diagnosis, treating the disease accordingly and the possible clinical issues that can appear in a patient with HIV infection during immunosuppressant treatment as induction treatment. Additionally, we performed a thorough literature review of ANCA positivity in HIV-infected patients to properly understand the current evidence.Although it is not clear whether HIV infection and AAV are causally or coincidentally related, the possibility of this systemic autoimmune phenomenon should be acknowledged by physicians to establish the correct diagnosis and treat the disease accordingly by maintaining a balance between the risks and benefits of immunosuppression in this category of patients, with treatment decisions being made by the members of a multidisciplinary team in centers with experience in AAV. Despite remarkable advances in antiretroviral therapy, the prolonged survival of human immunodeficiency virus (HIV)-infected patients has increased their risk of developing kidney disease , 2. AlonThe occurrence of autoantibodies in HIV-infected patients has been previously reported, with a prevalence ranging from 20 to 83% , 6. As rHere, we present the case of a female patient with a history of well-controlled HIV infection who was diagnosed in our department with systemic AAV with renal and pulmonary involvement. We highlight the importance of establishing the correct diagnosis, treating the disease accordingly and the possible clinical issues that can appear during induction immunosuppression therapy in a patient with HIV infection. Additionally, we performed a thorough literature review of ANCA positivity in HIV-infected patients to properly understand the current evidence.3(939 cells/mm3 at admission). She did not have any history of drug abuse, and no opportunistic/concomitant infections were found during the standard screening . Her antiretroviral therapy at that time consisted of ritonavir, darunavir and raltegravir. Previously, the renal function of the patient was normal (serum creatinine of 70.7 µmol/L), and no urinary abnormalities or electrolyte disturbances were recorded during the periodical follow-ups in the Infectious Disease Unit. There were six weeks between the first signs of renal involvement and admission to our nephrology department.A 29-year-old female patient without a significant family history was admitted to our nephrology department for the evaluation of acute kidney injury and nephrotic syndrome with active urinary sediment. Her past medical history included a well-controlled sexually transmitted HIV infection in the last 6 years with undetectable viral loads and CD4 counts over 500 cells/mmAt admission, her physical examination revealed a normal body temperature, an altered general status, pitting edema, a blood pressure of 150/70 mmHg and a heart rate of 92/minute. Auscultation revealed regular heartbeats and diminished breath sounds in the lung bases with an oxygen saturation of 92% on room air. She reported hemoptysis in the past 2 weeks before admission. Abdominal palpation did not reveal any hepatomegaly, splenomegaly or signs of ascites. Her urine output was 1000 ml/day.The initial laboratory evaluation showed an increased serum creatinine of 503.8 µmol/L and urea of 45.78 mmol/L;metabolic acidosis, with a serum bicarbonate of 12.4 mmol/l;and serum sodium and potassium within normal ranges. Urinalysis was positive for red blood cells (127 cells/µl) and proteins; 24-hour proteinuria was 7 g with a serum albumin of 2.4 g/dl. Anemia was diagnosed, with a hemoglobin of 6.2 g/dl and low erythrocyte indices; no thrombocytopenia was recorded during follow-up. The mean cellular volume was 68.4 fL, the serum iron was 101 µg/dL, the ferritin was 899 ng/ml and the transferrin was 156 mg/dl. White blood cell counts were in the normal ranges.Immunological screening was performed and revealed positivity for ANCA (titer of anti-myeloperoxidase antibody (anti-MPO) of 52.4 IU/ml), and a low complement C3 fraction(67 mg/dl). Tests for anti-GBM antibodies were negative, and the value of C-reactive protein was elevated (10 µg/mL).A percutaneous ultrasound-guided kidney biopsy was performed. The immunofluorescence was pauci-immune. Under light microscopy, there were 8 glomeruli for examination,of which 5 were globally sclerosed. The functional glomeruli presented fibrocellular crescents Fig. A and B aAdditionally, computed tomography was performed and revealed alveolar infiltrates suggestive of diffuse alveolar hemorrhage Fig. C and D.A diagnosis of systemic AAV with renal and pulmonary involvement was established, with a Birmingham Vasculitis Activity Score (BVAS) of 18 points. The patient was started on a remission induction immunosuppressive treatment regimen consisting of a combination of cyclophosphamide, rituximab and tapering corticosteroids,which led to resolution of the diffuse alveolar hemorrhage and immunological remission, but owing to renal function loss,hemodialysis was initiated Fig. . The patDespite the improvement in survival after the introduction of antiretroviral therapy, HIV-infected patients have an increased risk of developing kidney disease , 2. AlonThe dysregulation of the B and T lymphocyte interaction, molecular mimicry, viral triggers (such as Epstein‒Barr virus (EBV)), cytokine production (such as tumor necrosis factor-α (TNFα)) and polyclonal activation of B lymphocytes may favor the development of autoantibodies in patients with HIV infection , 15, 17,Most of the studies were conducted in the preantiretroviral therapy era with a population of patients presenting at a more advanced disease stage, but in the last ten years, systematic investigations have started to appear with the purpose of describing the prevalence of autoantibodies in the antiretroviral therapy era when a higher proportion of patients have a good immunovirological status , 7, 18. Another contrasting hypothesis is that autoimmune diseases and HIV infection are coincidental pathologies and that autoimmune phenomena are possibly being modified in the context of immune deficiency secondary to HIV infection; in this situation, highly active antiretroviral therapy (HAART) might hasten the onset of autoimmune diseases . Additio3 and a high viral load, autoimmune diseases are not found based on this classification, with the exception of those diseases that are driven by CD8 + T lymphocytes [3. We believe that in this particular situation, autoimmunity has been favored by the restoration of immune competence with functional T-cell reconstitution in a patient with probably altered immune regulation and/or genetic susceptibility.According to the hypothesis proposed by Zandman-Goddard and Yehuda Shoenfeld in 2002 , there aphocytes . We can The incidence of vasculitis in HIV-positive patients is estimated to be less than 1% , 13. In 3. 80% of the patients were on at least one antiretroviral agent, with only 13% being on a three antiretroviral agent protocol [A retrospective study conducted by Peraldi  includedprotocol . Vali etprotocol  reportedprotocol .3. Seven of the patients needed immunosuppression, and the treatment consisted of corticosteroids in 7 patients, cyclophosphamide in 1 patient, intravenous immunoglobulins in 1 patient, methotrexate in 2 patients and plasmapheresis in 1 patient; HAART was started in 9 patients. The patients’ conditions showed a good evolution, as 8 of the patients achieved complete remission [In a review conducted by Reville in 2000  with theThe results of the literature review of reported study cohorts/case reports of patients with ANCA positivity are presented in Table There are some reports of true AAV , 14–16. 3, was started on an induction immunosuppressive treatment regimen consisting of a combination of cyclophosphamide, rituximab and tapering corticosteroids,which led to the resolution of the diffuse alveolar hemorrhage and immunological remission, but owing to renal function loss,dialysis was initiated. In this case, correct antibiotic prophylaxis prevented infectious complications despite the patient being under aggressive combined immunosuppressive therapy.The treatments reported in patients with HIVand AAV was based on glucocorticosteroids –16, 23, According to the aforementioned studies in Table 2 or alveolar hemorrhage [The KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases  recommenmorrhage .For HIV-related kidney disease, there is no consensus regarding immunosuppressant treatment in addition to antiretroviral therapy . ImmunosIn conclusion, although it is not clear whether HIV infection and AAV are causally or coincidentally related, the possibility of this systemic autoimmune phenomenon should be acknowledged by physicians to establish the correct diagnosis and treat the disease accordingly by maintaining a balance between the risks and benefits of immunosuppression in this category of patients, with the treatment decisions being made by the members of a multidisciplinary team in centers with experience in AAV.


This article describes a comprehensive Synthetic Aperture Radar (SAR) satellite based ships dataset for use in state of the art object detection algorithms. The dataset comprises 11,590 image tiles containing 27,885 ships examples. Each image tile has spatial dimensions of 512 × 512 pixels and is exported in JPEG format. The dataset contains a wide variety of inshore and offshore scenes under varying background settings and sea conditions to generate an all-inclusive understanding of the ship detection task in SAR satellite images. The dataset is generated using images from six different satellite sensors covering a wide range of electromagnetic spectrum including C, L and X band radar imaging frequencies. All the sensors have different resolutions and imaging modes. The dataset is randomly distributed into training, validation and test sets in the ratio of 70:20:10, respectively, for ease of comparison and bench-marking. The dataset was conceptualized, processed, labeled and verified at the Artificial Intelligence and Computer Vision (iVision) Lab at the Institute of Space Technology, Pakistan. To the best of our knowledge, this is the most diverse satellite based SAR ships dataset available in the public domain in terms of satellite sensors, radar imaging frequencies and background settings. The dataset can be used to train and optimize deep learning based object detection algorithms to develop generic models with high detection performance for any SAR sensor and background condition. Specifications Table1•The dataset is intended for the usage and exploration of possibilities for ship detection in multi-resolution SAR satellite images.•This is a diverse dataset consisting of multi-spatial resolution images from six different SAR satellite sensors covering C, L and X bands of the radar imaging frequencies.•The dataset showcases unique characteristics and challenges associated with SAR satellite images and can be used for training, validation and testing as well as modification and optimization of state of the art, deep learning based object detection models.•The dataset contains 11,590 labeled tiles containing 27,885 ship examples. It includes a mix of inshore and offshore scenes under different sea conditions as well as complex backgrounds including land features such as ports, harbors, islands and sea clutter.•Due to the diversity of the dataset, it can be used to develop generalized SAR ship detection models that can achieve high ship detection performance on any kind of SAR sensor under different background settings.2SAR satellite sensors are considered excellent for maritime applications as they can image during both day and night times. Moreover, they are also unaffected by cloud coverage and hence can provide unrestricted coverage over the coastal areas 33.1Currently, there are only five significant satellite based SAR ship datasets available in the open source. These include SSDD 3.2The proposed Multi-Resolution SAR Ship Detection dataset contains 11,590 images along with the same number of label files. The image format is JPEG, whereas the label files are in text format. Each image tile has a standard height and width of 512 × 512 pixels. The dataset contains 27,885 ships of varying sizes ranging from small boats to large container ships. MRSSD has a ship/image ratio of 2.405 which means that on average, each image contains about 2.405 ships. Moreover, the dataset contains a mix of inshore and offshore images with varying background scenes including open sea, islands, ports, harbors and sea clutter. These different background settings can help the detection models in learning generic features and perform better under different conditions. An image that includes any form of land feature is termed as an inshore scene, whereas images that solely contain water in the background are called offshore images. The dataset is based on images from six different SAR satellite sensors. The satellite sensors include Capella Space The dataset labels follow the YOLO5 series annotation format where a text file is generated against each image tile with the same name. The text files consist of five different fields containing information regarding object category, normalized row and column values of the object as well as its normalized height and width. The dataset is randomly split into training, validation and test sets in the ratio of 70:20:10, respectively. This is done to achieve standardized sets for the purpose of comparison and benchmarking on various object detection models. 44.1All the satellite images used were acquired from online resources under the creative commons (CC BY) license. Images of Capella Space, ICEYE and Sentinel-1 were accessed and downloaded from direct open access archives of respective satellites. Whereas for images pertaining to TerraSAR-X, Paz and Alos-PALSAR, online request forms describing the purpose for the use of satellite images were submitted to European Space Agency (ESA) for access to their online data archives. The respective data archives were searched for the availability of desired satellite images with high concentration of ships. Consequently, selected images were downloaded in TIFF and GRD formats.4.2These images were processed in specialized GIS software including ArcGIS and SNAP. Specifically, histogram equalization, brightness/contrast adjustment and noise reduction techniques were applied for enhancement of ships against image backgrounds and suppression of unwanted noise. The processed images were then exported in high resolution JPEG format. Further, all the images were sliced into 512 × 512 tiles using Python script to achieve standard dimensions capable of being handled by deep learning based object detection models. Tiles pertaining to edge and corner cases where the dimensions were not exactly 512 × 512 pixels were removed. Moreover, the images were sliced such that each tile has a 50 percent overlap with the subsequent tile horizontally as well as vertically.4.3After the generation of trainable tiles, all the tiles were carefully labeled with the help of SAR imagery and maritime domain experts. An open source tool named Modified Open Labeling 4.4The dataset was randomly divided into train, validation and test sets in the ratio of 70: 20: 10, respectively, using Python based library split-folders http://creativecommons.org/licenses/by/4.0/).All the satellite images were acquired with the consent of relevant data owners under the creative commons (CC BY) license (Expert guidance was received from SAR and maritime domain experts with their consent and were informed in advance about the purpose and objectives of the research.Muhammad Farhan Humayun: Conceptualization, Methodology, Software, Formal analysis, Investigation, Data curation, Writing – original draft, Visualization. Farrukh Aziz Bhatti: Methodology, Investigation, Resources, Writing – review & editing, Project administration, Funding acquisition. Khurram Khurshid: Validation, Resources, Writing – review & editing, Project administration, Supervision, Funding acquisition.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Evidence for outcome improvement is limited for using 5% human albumin solution  in pediatric intensive care units (PICUs). However, 5% albumin was injudiciously used in our PICU. Therefore, we aimed to decrease 5% albumin use in pediatric patients (17 years old or younger) in the PICU by 50% in 12 months to improve health care efficiency.We plotted the mean 5% albumin volume used per PICU admission monthly on statistical process control charts through 3 study periods: baseline period before intervention (July 2019–June 2020), phase 1 (August 2020–April 2021), and phase 2 (May 2021–April 2022). With intervention 1, education, feedback, and an alert sign on 5% albumin stocks began in July 2020. This intervention continued until May 2021, when we executed intervention 2, removing 5% albumin from the PICU inventory. We also examined the lengths of invasive mechanical ventilation and PICU stay as balancing measures across the 3 periods.Mean 5% albumin consumption per PICU admission decreased significantly from 48.1 to 22.4 mL after intervention 1 and 8.3 mL after intervention 2, with the intervention effects persisting for 12 months. Costs associated with 5% albumin per PICU admission significantly decreased by 82%. In terms of patient characteristics and balancing measures, the 3 periods were not different.Stepwise quality improvement interventions, including the system change with the elimination of the 5% albumin inventory from the PICU, were effective in reducing 5% albumin use in the PICU with sustained reduction. However, based on clinical data and the revised Starling equation, the colloids used for fluid resuscitation may have little advantage over the administration of crystalloids.3 Indeed, several studies have provided evidence against the use of albumin compared with crystalloids in pediatric patients, especially those with septic shock or undergoing cardiac surgery.5 Strong evidence for utilizing albumin to improve outcomes is limited to several clinical situations,6 which are rare in the pediatric intensive care unit (PICU). Despite a lack of evidence of its beneficial effects, critically ill children frequently receive colloids.8Excessive fluid administration has been associated with poor outcomes in children.9 These practices appear to have their roots in the belief that albumin is more effective than crystalloids in improving hemodynamics and/or leading to better fluid balance. Another problem is that once a continuous albumin infusion has begun, as in the case of crystalloids, unless a physician deliberately placed a discontinuation order, the nurse would renew a bottle or syringe containing the albumin without notifying a physician. Cost-conscious physicians would often be frustrated to discover that a nurse renewed an albumin bottle before realizing that they should discontinue the albumin infusion.Automated dispensing cabinets are rarely implemented in Japanese hospitals. Instead, commonly used drugs and fluids were stored in cabinets and made readily available in our PICU. The pharmacy restocked the cabinet daily, including 5% albumin. ICU physicians frequently used 5% albumin as an alternative to crystalloids, either as a bolus or a continuous infusion. When considering the prospect of a fluid bolus in a patient with hemodynamic instability, some of our physicians occasionally draw 5% albumin into a syringe; such behavior is not uncommon in Japan, illustrating Japan’s lag in task shifting—the rational redistribution of tasks among health workforce teams.We gathered information from our key stakeholders, the ICU physicians, and nurses. As a result, we identified problems including 1) lack of knowledge that, based on the current evidence, 5% albumin is rarely indicated for fluid resuscitation, (2) lack of awareness and/or knowledge that albumin is a costly and valuable blood product, (3) lack of system where nurses notify physicians before renewing albumin, and (4) the convenience of 5% albumin administration with no prescription required. Therefore, our quality improvement (QI) team designed a key driver diagram . The QI purpose was to improve health care efficiency without worsening the patient’s clinical outcome.We aimed to decrease the 5% albumin volume used per patient by 50% in 12 months among pediatric patients who were 17 years or younger and survived a PICU stay without extracorporeal membrane oxygenation, hemodialysis, and plasma exchange or replacement .The Osaka Women’s and Children’s Hospital is a tertiary care freestanding children’s hospital with 198 general pediatric wards. The 12-bed PICU and an 8-bed step-down unit admit approximately 800 medical and surgical patients, including nearly 200 patients undergoing cardiothoracic surgery annually. Seven to 8 attending physicians oversee the PICU and the step-down unit, along with several fellows and pediatric residents.The PICU, like many ICUs in Japan, uses 2 distinct electronic medical records (EMRs) made by different companies: an EMR used across the hospital  and an EMR used only in the ICU and OR . Due to the weak interoperability of the 2 EMRs, a drug administration order in the ICU EMR does not automatically generate the corresponding prescription order in the general EMR. Therefore, frequently used IV drugs and fluids, including albumin, were kept in PICU cabinets to be administered promptly without being prescribed in the general EMR. In our hospital, the PICU was the only ward stocked with albumin in the drug cabinet, but all code carts, including one in the PICU, contained 5% albumin.An extemporary team of a few staff physicians and nurse leaders led a series of interventions Fig. . AlthougSupplemental Digital Content 1, An alert message card on albumin bottles, http://links.lww.com/PQ9/A496).” We also gave the staff ongoing education and feedback. We also reviewed articles reporting the potential albumin complication and the lack of evidence supporting the use of albumin for fluid resuscitation in the journal club to educate physicians. During the morning rounds, the physicians leading the QI discussed the injudicious use of albumin when it was noted. Likewise, when they observed unintended albumin renewals, they would educate the nurse on the value of albumin and encourage him/her to consult a physician before renewal.A card with an alert message was placed on albumin bottles inside the cabinet so that nurses would easily notice the alert when picking a bottle. The message stated, “Human albumin solution is a blood product. Before renewal, please ask a physician if it needs to be continued  charts through 3 study periods: baseline (July 2019–June 2020), phase 1 (August 2020–April 2021), and phase 2 (May 2021–April 2022)  albumin bottle was opened for a certain patient, we calculated 100 mL as the used volume regardless of the exact volume the patient received because the primary concern was health care efficiency rather than the albumin effect on the individual patient. Similarly, 250 mL was measured after opening a 12.5 g/250 mL (5%) bottle.Secondary outcome measures were the patient percentage exposed to any 5% albumin amount, the patient percentage exposed to multiple 5% albumin bottles, the mean number of 5% albumin bottles used among patients with 5% albumin exposure, and the total 5% albumin cost per month and per PICU admission. The cost was calculated based on the official prices approved by the Ministry of Health, Labour and Welfare in Japan; albumin costs ¥2,507 for a 5 g/100 mL (5%) bottle and ¥3,906 for a 12.5 g/250 mL (5%) bottle, whereas a commonly used 500 mL bag of crystalloid costs around ¥200 in Japan.Balancing measures were the duration of invasive mechanical ventilation and the PICU length of stay.11 Basic statistics were performed by calculating the mean and median of the processes analyzed. The χ2 and Kruskal-Wallis tests were used to compare categorical and continuous data.SPC charts for trend analysis were created using Microsoft Excel and QI Macros. Established statistical control chart QI rules were applied to discerning special versus common cause variation.Intervention 1 began in July 2020 and continued until May 2021, when intervention 2 was executed. As part of intervention 1, we placed the alert sign on the albumin stock in July 2020 to encourage prudent albumin use and gave nurses and physicians ongoing education and feedback. These interventions appeared effective in raising awareness of the problem among physicians and nurses. As a result, the mean 5% albumin volume per PICU admission decreased by 53%, from 48.1 to 22.4 mL, after intervention 1 . Physicians were now mandated to order albumin from the transfusion department before administering it to patients.After intervention 2, the mean 5% albumin volume per PICU admission dropped by 63%, from 22.4 to 8.3 mL, for a total of 83% reduction from baseline. Furthermore, the reduction in 5% albumin use persisted for 12 months after intervention 2 , phase 1 (August 2020–April 2021), and phase 2 (May 2021–April 2022) . According to a recent study using Japanese nationwide inpatient record data, patients admitted to hospitals with a transfusion management system, where the transfusion department stores and dispenses albumin and promotes appropriate albumin use, were less likely to receive albumin than patients admitted to hospitals without such a system.18 Creating guidelines and evaluating albumin use appropriateness would be our next goal since our institution lacks institutional guidelines on albumin use and albumin stewardship.In the current study, the decision to use 5% albumin was left at the individual physician’s discretion. However, in a recent study, a clinical pharmacist-led strategy intervening on all albumin orders noncompliant with institutional guidelines significantly reduced inappropriate albumin use and costs in hospitalized patients.14 Second, the long intervention periods may have allowed changes in the patient population and the severity of the illness to confound the intervention effects. However, given the similarities in patient characteristics, such confounding is probably negligible. Third, we excluded patients from the analyses who required extracorporeal membrane oxygenation, hemodialysis, and plasma exchange or replacement and those who died in the PICU. The number of excluded cases was 88 during the study period, that is, 5% of the total patients. Due to the small number of excluded patients, evaluating how current QI interventions affected them was impossible.There are several limitations to this study. First, our finding is unlikely to apply directly to places without an albumin ward inventory. Nevertheless, our strategies to guide health care providers’ choices through default changes and to address their psychological barriers in advance may apply to other situations.The system change involving the removal of albumin stock from the PICU reduced 5% albumin use and improved health care efficiency. A similar framework of interventions may be applied to the control of other fluids or medications. Consideration should be given to raising awareness of QI activities among the staff before implementing any drastic system change.Assistance with the study: The authors would like to thank Mr. Kenji Hirai for his assistance with the data curation.The authors have no financial interest to declare in relation to the content of this article.


Purpose of this study was to compare image quality of the skull base in standard 20s protocol flat panel computed tomography (FPCT) with the new time and dose improved 10s protocol as well as with 128 slice multidetector computed tomography (MDCT).10 whole skull preparations were scanned with either 128 slice MDCT or FPCT  using 10s or 20s protocol.FPCT provides significantly better image quality and improved delimitation of clinically relevant structures in the anterior, temporal and posterior skull base compared to 128 slice MDCT. The 20s FPCT protocol yielded best delimitability of evaluated skull base structures. However, the shorter, dose saving 10s FPCT protocol was still significantly superior to 128 slice MDCT regarding delimitability of skull base structures and additionally showed no significant inferiority compared with the 20s FPCT protocol.The 10s FPCT protocol yields a significantly better image quality at a comparable radiation dose exposure in imaging skull base structures compared to MDCT.371/2017BO2. Minimally invasive surgical access to the skull base has become a widely used technique, as endoscopic equipment and image guided navigation systems are evolving.While intraoperative navigation systems have been in use since the 1980 for neurosurgical interventions, they are today available in approximately 75% of U.S. hospitals and 25% of European hospitals .Image guided surgery in skull base operations is being used by the majority of neurosurgeons for recurrence operations and extended skull base approach, and from 50% of neurosurgeons in case of complex anatomy, as reported by Esposito et al. in a Global Survey from 2012 .Other conditions where image guided surgery is recommended by The American Academy of Otolaryngology Head and Neck Surgery are changed anatomy due to trauma, pathologies affecting frontal, ethmoidal or sphenoidal sinuses, disease that reaches skull base, orbita, optic nerve or carotid artery .Development in Computed Tomography (CT)-technique has made high spatial resolution imaging together with radiation dose reduction possible by improving image acquisition physics , as wellFlat Panel CT (FPCT) holds a notably higher spatial resolution than multidetector-CT (MDCT) , and is While image quality of flat panel CT and multidetector-CT in temporal bone imaging has already been compared in various publications, showing an advantage for flat panel CT , 24, 25,The objective of this work is to evaluate image quality of 2 different computed tomography systems, a 128 row multidetector –CT (MDCT) versus a flat panel-CT (FPCT), and the image quality of 2 different FPCT protocols with an acquisition time of 10s and 20s respectively, using 10 whole skull preparations to mimic clinical application.10 whole skull preparations were scanned with either 128 slice mdct , or fpct  using 10 or 20s protocol. The study was approved by the institutional research board (IRB) of the Medical Faculty at the Eberhard Karls University Tuebingen. Anatomical specimens were obtained from the body donation program of the Institute of Clinical Anatomy and Cell Analysis of the University of Tuebingen, with written permission of the donors. Additionally at our University every study that is done using anatomical specimens is separately assessed by the local ethics committee.Flat Panel CT (FPCT) measurements were performed using a robot-driven C-arm system ). Manufacturer-specified programs, 20sDR-H and 10sDR-H, were used to perform a whole head acquisition with following parameters:20s FPCT: tube potential: 84 kV, tube current: 237mA; dose area product: 6537.4µGym²; frames: 30 F/s; rotation angle: 200°; 98 RAO.10s FPCT: tube potential: 84 kV, tube current: 246mA; dose area product: 3324.7µGym²; frames: 30 F/s; rotation angle: 200°; 98 RAO.Slice thickness for both acquisition programs was: 0.139 mm, reconstruction diameter was: 512. A convolution kernel HU (Hounsfield Units) sharp bone was used.Multidetector CT measurements were performed using a Siemens Somatom Definition AS+. Manufacturer-specified Head protocol was used with following parameters:Tube voltage: 120 kV, tube current: 220 mAs, collimation: 64 × 0.6 mm, pitch: 0.8 mm, average CT dose index (CTDIvol): 38.93 mGy. DLP: 633 mGycm.Reconstruction was done at the workstation of the scanner with a high resolution bone kernel: H70h and a FOV of 200 mm, with a slice thickness of 0.6 mm and an increment of 0.6 mm.Bilaterally present structures were evaluated for each side of the skull base. The craniopharyngeal canal is a midline structure and therefore not bilaterally present.For inconsistent anatomical structures, frequency of occurrence and lateralization was recorded.For quantitative imaging analysis the signal-to-noise-ratio (SNR) and contrast to- noise-ratio (CNR) were assessed for each CT examination. Two regions of interest (ROI) were placed within the clivus and the cerebellum. Mean Hounsfield Units (HU) and standard deviation (SD) values were measured. The SNR was calculated using the mean value of clivus divided by the standard deviation of clivus;(clivus) / SD(clivus).SNR = mean valueThe CNR was calculated using the difference of mean values of clivus and cerebellum divided by the standard deviation of cerebellum;(clivus) – mean value(cerebellum)) / SD(cerebellum).CNR= .For the qualitative analysis of the skull base structures, imaging data of FPCT and MDCT was transferred to Syngo.via multimodality reading software  for multiplanar reconstruction (MPR) in transversal and coronal planes. Transverse MPRs of FPCT and MDCT were angulated to be parallel to the anterior skull base. Coronal MPRs were angulated to be perpendicular to the transversal MPRs. Sagittal MPRs were angulated to be parallel to the midline of the skull base. According to the in-plane resolution of the different imaging data, slice thickness of multiplanar reconstructions was 0.2 mm for FPCT and 0.6 mm for MDCT. Qualitative image evaluation was performed by an experienced neuroradiologist (M.S.) and an experienced neuro-otologist (K.R.), who were blinded to all subject data and the technical information of the images. The delineation of the structures within the temporal bone was assessed using a 4 point visual analogue scale for image quality with 0 = not delimitable; 1 = poor delimitable; 2 = well delimitable; 3 = very good delimitable. The readers were asked to assess the edge definition for the following anatomical structures of the anterior skull base:the anterior and posterior ethmoidal canals, the lamina cribrosa, the pterygoid canal, the palatovaginal canal and the inconsistent meningoorbital foramen.Within the central skull base, readers assessed the delimitability of the foramen rotundum, foramen ovale, foramen spinosum and the inconsistent foramen venosum, as well as the inconsistent midline structure, the craniopharyngeal canal. Additionally, the delimitability of the sulcus of major petrosal nerve was evaluated.Edge definition in the posterior skull base was evaluated for the following anatomical structures: hypoglossal canal, jugular foramen, the inferior tympanic canaliculus, and the mastoid canaliculus, both inconsistent, as well as the petromastoideal canal and the nerve canal of the facial nerve within the temporal bone respectively.Anatomical structures were assessed on transversal MPRs, except for lamina cribrosa, foramen rotundum, inferior tympanic canaliculus, mastoid canaliculus, and nerve canal of facial nerve, which were assessed on coronal MPRs, while palatovaginal canal and craniopharyngeal canal were evaluated on sagittal MPRs. All these structures were rated in respect to their delimitation of anatomical boundaries.Quantitative and qualitative image analysis results are expressed as mean and standard deviation. Qualitative image analysis was evaluated using the Dunn All Pairs Test for Joint Ranks after Bonferroni adjustment for multiple testing, a p-value < 0.05 is considered significant.Interrater agreement was calculated using the weighted Cohen`s kappa coefficient, classified as: 0-0.20, slight agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate agreement; 0.61–0.80, substantial agreement; 0.81-1.00, almost perfect agreement . StatistThe evaluated anatomical structures are shown in Table In the anterior skull base anterior ethmoidal canals, posterior ethmoidal canals, lamina cribrosa and pterygoid canal were present bilaterally in all skull preparations.The inconsistent meningoorbital foramen was found bilaterally in 3 skull preparations.Within the central skull base bilaterally present structures in all skull preparations were the foramen rotundum, foramen ovale and the foramen spinosum as well as the sulcus of major petrosal nerve.Foramen venosus was present in 7 preparations, of which 6 showed bilateral localizations and one preparation an unilateral localization on the right side.The inconsistent midline structure craniopharyngeal canal was only present in one skull preparation.The inconsistent canaliculus innominatus between foramen ovale and foramen spinosum was not present in the evaluated skull preparations.In the posterior skull base, hypoglossal canal, jugular foramen, petromastoideal canal, and the nerve canal of the facial nerve, within the temporal, bone were present on both sides in all skull preparations.Inferior tympanic canaliculus was found in 3 preparations, one bilateral and 2 unilateral, both on the left side.Mastoid canaliculus was only present in one preparation on the right side.Signal-to-noise ratio decreased from 0.83 (FPCT 20s), to 0.77 (FPCT 10s) and to 0.48 (MDCT).Contrast-to-noise ratio also decreased from FPCT 20s images to FPCT 10s images to MDCT images, from 0.69 to 0.65 and to 0.39 accordingly  = 0.68–0.94, for FPCT 10s of 0.84; 95% CI = 0.78–0.91 and for MDCT of 0.88; 95% CI = 0.84–0.94, indicating an almost perfect interrater agreement.In the anterior skull base, lamina cribrosa and palatovaginal canal Fig. , in the Anatomical structures in the anterior skull base showed significantly better edge definition for all evaluated structures, except for the inconsistent foramen meningoorbitale Fig. A.In the central skull base, all anatomical structures, except the inconsistent craniopharyngeal canal, which was only present in one whole head preparation, showed significantly superior results for FPCT Fig. B.In the posterior skull base, inferior tympanic canaliculus (inconsistent), petromastoideal canal Fig.  and canaResults of significantly better delimitability of anatomical structures correspond to the results of the comparison of 20s FPCT with MDCT, except for the inconsistent inferior tympanic canaliculus, which did not show significant difference. However, delimitability was not as good as for 20s FPCT protocol.Flat panel CT offers an isotropic spatial resolution which is about two-fold higher than multidetector CT .Imaging of the complex bony and neurovascular anatomy of the skull base profits from high spatial resolution. While some preclinical studies showed no difference in imaging the skull base between MDCT and FPCT  or superThe 20s FPCT protocol (20s scan time) yielded best delimitability of bony skull base structures compared with 10s FPCT - which holds half the scan time and half the radiation exposure of the 20sFPCT – and the MDCT protocol. Statistically significant difference in delimitability of nearly all anatomical structures was seen in anterior and central skull base for 20s FPCT and 10s FPCT compared to MDCT, while in posterior skull base differences were not statistically significant between FPCT and MDCT.Skull base foramina of the middle cranial fossa transmit important neural and vascular structures. The foramen rotundum connects the middle cranial fossa with the pterygopalatine fossa, the second branch of the trigeminal nerve (maxillary nerve) and emissary veins run through it .Asymmetric widening of the foramen rotundum may be a sign of tumoral spread along the maxillary nerve.The Foramen venosum  is an inconsistent communication between the middle cranial fossa and the scaphoid fossa. It transmits a dural sinus, which connects the cavernous sinus with the pterygoid venous plexus , its incAsymmetry of the Foramen venosum may be due to e.g. carotid cavernosus fistula, tumor and neurofibromatosis  or causeForamen ovale forms the communication between the middle cranial fossa and the infratemporal fossa. It carries the third branch of the trigeminal nerve (mandibular nerve), it may contain an accessory meningeal branch of the internal maxillary artery which supplies the trigeminal ganglion (gasserian ganglion) and in the absence of the inconsistent canaliculus innominatus – as in our cohort - it transmits the lesser superficial petrosal nerve, which originates from the tympanic branch of the glossopharyngeal nerve and additionally holds fibers from the facial nerve.In our cohort foramen ovale was well delimited from neighboring skull base foramina, e.g., foramen lacerum, which sometimes lacks its lateral wall and then communicates with foramen ovale .Foramen spinosum was present bilaterally in all our preparations. It communicates as the foramen ovale between middle cranial fossa and fossa infratemporalis and holds the middle meningeal branch of the external carotid artery, the middle meningeal vein and the recurrent branch of the mandibular nerve .Hypoplasia or absence of the foramen spinosum exists in case of an aberrant middle meningeal artery. This situation arises either due to a fault in embryological development of the stapedial artery, which originates as a branch of the second aortic arch and therefore the internal carotid artery. If the communication between the stapedial artery and the external carotid artery fails to evolve during embryological development, aberrant middle meningeal artery originates from the ophthalmic artery and courses through the superior orbital fissure.The other cause for an aberrant middle meningeal artery is a persistent stapedial artery which transmits through the tympanic cavity, the facial nerve canal, and the facial hiatus  to become the middle meningeal artery.Clinically important structures in the anterior skull base are the anterior and posterior ethmoidal canals which transmit the anterior ethmoidal artery, vein and nerve and the posterior ethmoidal ethmoidal artery, vein and and nerve respectively. The course of these arteries is variable and therefore important regarding paranasal surgery.Radiation dose of FPCT has been mentioned by several authors , 23.Struffert et al. showed  that FPCTherefore, the FPCT with a scan time of 10s can be considered comparable to the MDCT protocol regarding radiation dose in our study.Reduction of dose results in reduction of signal to noise (SNR) which is in line with the qualitative image rating in our study.Additionally, contrast to noise (CNR) measurements showed decreased ratios for 10s FPCT and MDCT compared to 20s FPCT, nevertheless all FPCT and MDCT images held diagnostic image quality.In a recent global survey of usage patterns and the role of intraoperative neuronavigation nearly 25% of skull base surgeons reported using neuronavigation in all cases, main image modalities used were magnetic resonance imaging (MRI) and CT in over 56% of cases . Most inTo achieve an accurate navigation, correct registration of CT data to the head of the patient is pivotal. Registration can be done with externally fixed systems  or surface registration  at which externally fixed systems yield the highest accuracy , 17. TaeNonetheless, FPCT carries in contrast to MDCT the advantage of being available as a mobile device, and therefore being suitable for intraoperative scanning, which allows for adaption of navigation to surgery-related anatomical changes, or robot assisted stereotactic surgery .Comparative studies regarding skull base CT imaging, dealing with image quality and resolution, were predominantly performed in explanted skull base preparations or 3D printing models.In our study on whole-head preparations, we show that clinically relevant skull base structures are significantly better delimitable using FPCT compared to MDCT.Regarding the radiation-reduced 10s FPCT protocol, there were only 4 of 18 evaluated anatomical structures significantly inferior delimitable in comparison to the 20s FPCT protocol, while image quality was better than that of MDCT.In conclusion, 10s FPCT protocol serves as a substantiated tool whenever a high spatial resolution imaging of the skull base is needed.