Optimizing Choice of Skin Surrogates for Surface-Guided Stereotactic Body Radiotherapy of Lung Lesions Using Four-Dimensional Computed Tomography.

Image-guided radiotherapy supported by surface guidance can help to track lower lung lesions' respiratory motion while reducing a patient's exposure to ionizing radiation. However, it is not always clear how the skin's respiratory motion magnitude and its correlation with the lung lesion's respiratory motion vary between different skin regions of interest (ROI). Four-dimensional computed tomography (4DCT) images provide information on both the skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. An analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on the respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing a lower lung lobe lesion, as well as the respiratory motion correlations between the nine ROIs and the TS. The effects of gender and the adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between the ROIs in both the respiratory motion magnitudes and their correlations with the TS have been detected. An overall negative correlation between the ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between the adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. The respiratory magnitudes in regions without rib support tend to be larger for men than for women, but no differences in the ROI-to-TS correlation between sexes have been detected. The described findings should be considered when choosing skin surrogates for lower lung lesion motion management.

Comparison of 116 Radiosurgery Treatment Plans for Multi-Leaf and Cone Collimator on a Varian Edge Linac: Are Cones Superior in the Daily Routine?

Delivering focused radiation doses via linear accelerators is a crucial component of stereotactic radiosurgery (SRS) for brain metastases. The Varian Edge linear accelerator provides highly conformal radiation therapy through a high-definition multi-leaf collimator (HD120 MLC) and conical collimator (CC). HD120 MLC adapts to the shape of the target volume using movable tungsten leaves, while CC has a block of conical shape (cones). CC in SRS treatments of small brain metastases is preferred due to its mechanical stability and steeper dose fall-off, potentially sparing organs at risk (OARs) and the brain better than HD120 MLC. This study aims to determine if CC offers significant advantages over HD120 MLC for SRS treatments. For 116 metastatic lesions, CC and HD120 MLC treatment plans were created in Varian Eclipse TPS and compared based on various dose parameters, robustness tests, and QA measurements. The results indicate that CC provides no significant advantages over HD120 MLC, except for slight, clinically insignificant benefits in brain sparing and dose fall-off for the smallest lesions. HD120 MLC outperforms CC in almost every aspect, making it a better choice for irradiating brain metastases with 0.1 cm3 or higher volumes.

Antimicrobial Peptides-Mechanisms of Action, Antimicrobial Effects and Clinical Applications.

The growing emergence of antimicrobial resistance represents a global problem that not only influences healthcare systems but also has grave implications for political and economic processes. As the discovery of novel antimicrobial agents is lagging, one of the solutions is innovative therapeutic options that would expand our armamentarium against this hazard. Compounds of interest in many such studies are antimicrobial peptides (AMPs), which actually represent the host's first line of defense against pathogens and are involved in innate immunity. They have a broad range of antimicrobial activity against Gram-negative and Gram-positive bacteria, fungi, and viruses, with specific mechanisms of action utilized by different AMPs. Coupled with a lower propensity for resistance development, it is becoming clear that AMPs can be seen as emerging and very promising candidates for more pervasive usage in the treatment of infectious diseases. However, their use in quotidian clinical practice is not without challenges. In this review, we aimed to summarize state-of-the-art evidence on the structure and mechanisms of action of AMPs, as well as to provide detailed information on their antimicrobial activity. We also aimed to present contemporary evidence of clinical trials and application of AMPs and highlight their use beyond infectious diseases and potential challenges that may arise with their increasing availability.

Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer Using Optical Surface Management System - AlignRT as an Optical Body Surface Motion Management in Deep Breath Hold Patients: Results from a Single-Arm Retrospective Study.

Purpose: To assess the efficacy and safety of stereotactic body radiotherapy for patients with unresectable, locally advanced pancreatic cancer using Optical Surface Management System - AlignRT (OSMS-AlignRT) as an optical body surface motion management in deep breath hold. Patients and Methods: Forty-five patients diagnosed with locally advanced pancreatic cancer were treated with stereotactic body radiotherapy in 3 or 5 fractions, and received varying BED10 (median 79.5 Gy) from April 2017 to December 2020. All patients were treated in deep breath hold with OSMS-AlignRT used as optical body surface motion management. Thirty-three patients received systemic treatment before and/or after stereotactic body radiotherapy, and twelve patients received no systemic treatment. In this retrospective, observational, single-arm study, primary endpoints were overall survival and freedom from local progression (ie, local control). Secondary endpoints were progression-free survival and toxicity. Actuarial survival analysis and univariate analysis were investigated. Results: Data from forty-five patients were analyzed. Median follow-up was 15 months. One-year freedom from local progression and survival were 95.5% and 71.1%, respectively. Median progression-free survival was 14 months. Median overall survival from diagnosis for all patients was 17 months, and 19 months for patients alive at the time of analysis. No patient had >G2 toxicity. Conclusion: Stereotactic body radiotherapy for locally advanced pancreatic cancer using OSMS-AlignRT as optical body surface motion management in deep breath hold patients is an effective and safe local treatment option, with no >G2 toxicity, and could be a promising therapeutic option with acceptable toxicity, either as a single treatment or in a multimodal regimen. OSMS-AlignRT provided accurate and reliable body surface motion management during stereotactic body radiotherapy.

Stereotactic Ablative Radiotherapy Using CALYPSO® Extracranial Tracking for Intrafractional Tumor Motion Management-A New Potential Local Treatment for Unresectable Locally Advanced Pancreatic Cancer? Results from a Retrospective Study.

(1) Background: The aim of this study was to evaluate the efficacy and safety of SABR for LAPC using Calypso® Extracranial Tracking for intrafractional, fiducial-based motion management, to present this motion management technique, as there are yet no published data on usage of Calypso® during SABR for LAPC, and to report on our clinical outcomes. (2) Methods: Fifty-four patients were treated with SABR in one, three, or five fractions, receiving median BED10 = 112.5 Gy. Thirty-eight patients received systemic treatment. End points were OS, FFLP, PFS, and toxicity. Actuarial survival analysis and univariate analysis were investigated. (3) Results: Median follow-up was 20 months. Median OS was 24 months. One-year FFLP and one-year OS were 100% and 90.7%, respectively. Median PFS was 18 months, and one-year PFS was 72.2%. Twenty-five patients (46.3%) were alive at the time of analysis, and both median FU and OS for this subgroup were 26 months. No acute/late toxicity > G2 was reported. (4) Conclusions: SABR for LAPC using Calypso® presented as an effective and safe treatment and could be a promising local therapeutic option with very acceptable toxicity, either as a single treatment or in a multimodality regimen. Dose escalation to the tumor combined with systemic treatment could yield better clinical outcomes.

An Evaluation of Total Internal Motions of Locally Advanced Pancreatic Cancer during SABR Using Calypso® Extracranial Tracking, and Its Possible Clinical Impact on Motion Management.

(1) Background: the aims of this study were to determine the total extent of pancreatic cancer's internal motions, using Calypso® extracranial tracking, and to indicate possible clinical advantages of continuous intrafractional fiducial-based tumor motion tracking during SABR. (2) Methods: thirty-four patients were treated with SABR for LAPC using Calypso® for motion management. Planning MSCTs in FB and DBH, and 4D-CTs were performed. Using data from Calypso® and 4D-CTs, the movements of the lesions in the CC, AP and LR directions, as well as the volumes of the 4D-CT-based ITV and the volumes of the Calypso®-based ITV were compared. (3) Results: significantly larger medians of tumor excursions were found with Calypso® than with 4D-CT: CC: 29 mm (p < 0.001); AP: 14 mm (p < 0.001) and LR: 11 mm (p < 0.039). The median volume of the Calypso®-based ITV was significantly larger than that of the 4D-CT based ITV (p < 0.001). (4) Conclusion: beside known respiratory-induced internal motions, pancreatic cancer seems to have significant additional motions which should be considered during respiratory motion management. Only direct and continuous intrafractional fiducial-based motion tracking seems to provide complete coverage of the target lesion with the prescribed isodose, which could allow for safe tumor dose escalation.

Adipogenesis as a Potential Anti-Obesity Target: A Review of Pharmacological Treatment and Natural Products.

Obesity is recognized as a severe threat to overall human health and is associated with type 2 diabetes mellitus, dyslipidemia, hypertension, and cardiovascular diseases. Abnormal expansion of white adipose tissue involves increasing the existing adipocytes' cell size or increasing the number through the differentiation of new adipocytes. Adipogenesis is a process of proliferation and differentiation of adipocyte precursor cells in mature adipocytes. As a key process in determining the number of adipocytes, it is a possible therapeutic approach for obesity. Therefore, it is necessary to identify the molecular mechanisms involved in adipogenesis that could serve as suitable therapeutic targets. Reducing bodyweight is regarded as a major health benefit. Limited efficacy and possible side effects and drug interactions of available anti-obesity treatment highlight a constant need for finding novel efficient and safe anti-obesity ingredients. Numerous studies have recently investigated the inhibitory effects of natural products on adipocyte differentiation and lipid accumulation. Possible anti-obesity effects of natural products include the induction of apoptosis, cell-cycle arrest or delayed progression, and interference with transcription factor cascade or intracellular signaling pathways during the early phase of adipogenesis.

Therapy of umbilical hernia during laparoscopic cholecystectomy.

The aim of this study is to show our experience with umbilical hernia herniorrhaphy and laparoscopic cholecystectomy, both in the same act. During last 10 years we operated 89 patients with cholecystitis and pre-existing umbilical hernia. In 61 of them we performed standard laparoscopic cholecystectomy and additional sutures of abdominal wall, and in 28 patients we performed in the same act laparoscopic cholecystectomy and herniorrhaphy of umbilical hernia. We observed incidence of postoperative herniation, and compared patients recovery after herniorrhaphy combined with laparoscopic cholecystectomy in the same act, and patients after standard laparoscopic cholecystectomy and additional sutures of abdominal wall. Patients, who had in the same time umbilical hernia herniorrhaphy and laparoscopic cholecystectomy, shown better postoperative recovery and lower incidence of postoperative umbilical hernias then patients with standard laparoscopic cholecystectomy and additional abdominal wall sutures.

Preemptive use of diclofenac in combination with ketamine in patients undergoing laparoscopic cholecystectomy: a randomized, double-blind, placebo-controlled study.

BACKGROUND: To examine the combined preemptive effects of low-dose ketamine, diclofenac, and their combination on postoperative pain in patients undergoing laparoscopic cholecystectomy. METHODS: A total of 80 consecutive patients, American Society of Anesthesiologists physical status I or II, were recruited to the study. Patients were randomized to one of the following groups: group 1 received 100-mL isotonic saline intravenously (i.v.) 20 minutes before the induction of anesthesia and 5-mL isotonic saline i.v. before skin incision as a placebo; group 2 received 100-mL isotonic saline i.v. 20 minutes before the induction of anesthesia and 0.15-mg/kg ketamine diluted in 5-mL isotonic saline i.v. before skin incision; group 3 received diclofenac 1 mg/kg diluted in 100-mL isotonic saline i.v. 20 minutes before the induction of anesthesia and 5-mL isotonic saline i.v. before skin incision; and group 4 received a combination of the same diclofenac sodium and ketamine doses at the same time. Abdominal and shoulder pain intensity was assessed using the visual analog scale and verbal rating scale during 24 hours postoperatively. RESULTS: Patients receiving diclofenac had a significantly lower pain score between 2 and 6 hours after surgery compared with patients receiving placebo. One hour after surgery, patients receiving a combination of diclofenac and ketamine had a significantly lower pain score compared with patients receiving placebo and ketamine alone. Patients from all the 4 study groups required postoperative analgesic; however, the time to diclofenac sodium request was longer in patients receiving a combination of diclofenac and ketamine compared with patients receiving placebo (p<0.001), ketamine (p<0.001), or diclofenac (p=0.03) alone. CONCLUSIONS: The preemptive administration of a combination of low-dose ketamine plus diclofenac sodium improved postoperative analgesia after laparoscopic cholecystectomy, whereas ketamine at a dose of 0.15 mg/kg did not elicit a preemptive analgesic effect.

The effect of spinal versus general anesthesia on postoperative pain and analgesic requirements in patients undergoing peripheral vascular surgery.

The optimal anesthetic technique for peripheral vascular surgery remains controversial. The purpose of this study was to evaluate the effect of spinal versus general anesthesia on postoperative pain, analgesic requirements and postoperative comfort in patients undergoing peripheral vascular surgery. A total of 40 patients scheduled for peripheral vascular surgery were randomly assigned to two groups of 20 patients each to receive general anesthesia (GA) or spinal anesthesia (SA). In GA group, anesthesia was induced using thiopental and fentanyl. Vecuronium was used for muscle relaxation. Anaesthesia was maintained with isoflurane and nitrous oxide. In the SA group, hyperbaric 0.5% bupivacaine was injected into the subarachnoid space. Postoperative pain was assessed for 24 hours by a visual analog scale during three assessment periods: 0-4, 4-12 and 12-24 h as well as analgesic requirements. Patients were also asked to assess their postoperative state as satisfactory or unsatisfactory with regard to the pain, side effects and postoperative nausea and vomiting. Visual analogue scale (VAS) pain score was significantly lower in the group SA compared with group GA. This effect was mainly due to the lower pain score during the first study period. The patients received general anesthesia also reported a significantly higher rate of unsatisfactory postoperative comfort than those receiving spinal anesthesia. We conclude that spinal anesthesia is superior to general anesthesia when considering patients' satisfaction, side effects and early postoperative analgesic management.

Efficacy of antimicrobial triclosan-coated polyglactin 910 (Vicryl* Plus) suture for closure of the abdominal wall after colorectal surgery.

This study compared Triclosan coated polyglactin 910 (Vicryl* Plus) with polyglactin 910 (Vicryl*) on abdominal wall healing in colorectal surgery patients. 184 patients with colorectal cancer were included in the study. In 91, the abdominal wall was closed with the Vicryl* Plus, and in 93 patients with Vicryl*. Demographic characteristics, biochemical inflammatory parameters, wound appearance, length of hospital stay, postoperative wound complications and post-incisional hernia were recorded. In the Vicryl* Plus group there was a shorter hospital stay (13.2 +/- 1.3 days; 21.4 +/- 2.8 respectively). In the Vicryl* Plus group inflammatory parameters decreased to normal within the first week whereas in the Vicryl* group remained increased. In the Vicryl* Plus group four patients had a wound discharge, seven had inflammatory reactions to the skin sutures. One dehiscence was noticed. In the Vicryl* group 12 patients had an SSI, 14 patients had inflammatory reactions to the skin sutures and 7 patients had a wound dehiscence. Closure of the abdominal wall using Vicryl* Plus decreases postoperative wound complications, length of hospital stay and is associated with a more rapid return of inflammatory markers to normal.

Single incision laparoscopic cholecystectomy--a new advantage of gallbladder surgery.

In this study is demonstrated our experience in single incision laparoscopic cholecystectomy (SILS), compared to standard laparoscopic cholecystectomy. There were 48 single incision laparoscopic cholecystectomies (SILS) performed during one-year period (A group) and results have been compared with a group of 50 patients who underwent standard laparoscopic cholecystectomy (B group). Outcome measures included operative time, need for conversion, complications, additional analgesia for pain control after procedure, hospital stay and cosmetic outcome. The mean operative time was 46 +/- 3.5 min in A group, and 43 +/- 4 min in B patients group. Early postoperative complications were not detected. The mean hospitalization period was 2 days in both groups. Our experience suggests that SILS cholecystectomy can be performed with outcome similar to standard laparoscopic surgery while affording better cosmesis.

Pelvic peritonization after laparoscopic abdominoperineal resection for low-rectal carcinoma treatment: surgical technique.

Abdominoperineal resection is a standard method of low-rectum carcinoma treatment. It is associated with significant morbidity and mortality rates, which decreased with the development of preoperative diagnostic procedures, new surgical techniques and new surgical instruments. In this article, laparoscopic pelvic peritonization was used after laparoscopic rectum amputation for low-rectum carcinoma treatment. Pelvic peritonization is performed after laparoscopic recto-sigmoid extirpation, using the extended absorbable intracorporeal suture with titanic clip application after every second suture. The role of titanic clip is to grasp the extended suture and to mark the postoperative irradiation field. Laparoscopic pelvic peritonization after laparoscopic abdominoperineal rectum amputation is a simple procedure with clinical importance in possible adhesion and postirradiatic enteritis prevention. This procedure can satisfy all oncological requirements and minimally invasive surgery principles and is acceptable for every patient in which rectum amputation is indicated.

Impaired esophageal function in patients with irritable bowel syndrome.

The aim of the study was to determine prevalence of the signs and symptoms related to esophageal dysfunction in irritable bowel syndrome (IBS) patients, and to investigate sensorimotor function impairment based on the esophageal manometry study, thus to determine the correlation between them. The study included 30 patients with IBS, 14 of them with diarrhea (IBSd) and 16 with constipation (IBSc) as a predominant discomfort. Control group consisted of 30 healthy subjects. The patients were included in the study on the basis of the Rome criteria for IBS. In addition to thorough history and physical examination patient underwent esophagogastroduodenoscopy and esophageal manometry. The values of esophageal manometry obtained in healthy subjects served as controls in manometry studies. The patients with IBS suffered a great number of both colonic and extracolonic signs and symptoms, however, there was no statistically significant difference in the prevalence of particular symptoms between the two patient subgroups. In comparison with healthy subjects, the patients suffering from IBS showed pathologically altered values in the majority of parameters of esophageal motility. Comparison of the two subgroups of IBS patients according to esophageal motility characteristics yielded differences in only few of them. The results obtained in the study could explain why the patients with IBS quite commonly complain of the symptoms related to upper gastrointestinal tract, such as heartburn and chest pain of noncardiac genesis. The results also suggest that the IBS might be associated with considerably more extensive smooth muscle or innervation changes than presumed before.

Lower gastrointestinal disorders in patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal system characterized by abdominal pain related to bowel emptying, defecation impairment and abdominal distention. The aim of the study was to objectify lower gastrointestinal system disturbances in IBS patients. Thirty IBS patients and 30 healthy subjects were included in the study. IBS patients were divided into two subgroups: IBS with predominant diarrhea (IBSd) and IBS with predominant constipation (IBSc). All study subjects underwent physical examination (including digitorectal examination), standard laboratory testing and anorectal manometry. Endoscopy was performed only in group of IBS patients. A statistically significant difference was recorded in most manometric parameters between healthy subjects and IBS patients, which was even more pronounced in IBSd patients. Study results showed that the intestinal motility disorder underlying IBS could be objectified by use of anorectal manometry.

Clinical course of uremic neuropathy in long-term hemodialysis.

One hundred and thirty-one patients on long-term hemodialysis were examined for the presence of clinical symptoms and signs, and for the effects of dialytic age, age and sex on uremic neuropathy. According to dialysis age, the patients were divided into three subgroups: low dialysis age, < 5 years of dialysis (n = 58); intermediate dialysis age, 5-10 years of hemodialysis (n = 39); and high dialysis age, > 10 years of dialysis (n = 34). Two patient subgroups were differentiated according to mean age of 53.2 years: younger (n = 57) and older (n = 74). Clinical grading of uremic neuropathy was based on Nielsen's criteria. The most common symptoms were restless legs syndrome (47%) and cramps (51%). Sensory symptoms were less common in patients on long-term hemodialysis, most common of them being paresthesia (29%) and burning feet syndrome (28%). Abnormal Achilles reflex (53%) and impaired vibration sense (59%) were the most common clinical signs. Clinically manifested uremic neuropathy was present in more than 80% of all study patients, i.e. mild in 41%, and moderate to severe forms of uremic neuropathy according to Nielsen's criteria in 39%. There was no evident effect of dialytic age and sex on the clinical course of uremic neuropathy, however, there was a clear impact of age. It is concluded that long-term hemodialysis does not influence the clinical course of uremic neuropathy unlike evident deterioration of electroneurophysiologic findings.

Seroprevalence of Helicobacter pylori infection in dyspeptic patients.

The objective of the study was to assess the effect of age on the seroprevalence of Helicobacter (H.) pylori infection in dyspeptic patients. The results obtained in the patient group were compared with findings on the seroprevalence of H. pylori infection in 2051 blood donors. Serum samples were tested by the commercial ELISA and CFT assays according to manufacturer's instructions. The mean seroprevalence of H. pylori infection as determined by ELISA/CFT was 64.0%/51.7% in the group of blood donors and 92.3%/89.5% in the group of dyspeptic patients. Study results indicated a higher prevalence of H. pylori infection in dyspeptic patients as compared with blood donors in all age groups. In the patient S group, H. pylori seroprevalence was not age dependent.

Gastric myoelectrical activity in a population of healthy Croatian subjects.

Myoelectrical activity of the stomach was estimated in healthy Croatian subjects using the latest multi-channel percutaneous electrogastrograph. The aim of the study was to determine normal values of gastric myoelectrical activity for the population of Croatia. The study included 120 healthy subjects of both sexes, various age groups, body mass index values, and mode of lead placement. The measurement was performed 60 min before and 60 min after test meal. The following parameters of gastric myoelectrical activity were analyzed: dominant frequency (DF, c/min); dominant frequency within normal range (DFNR, %); coefficient of variation for dominant frequency (CVDF); dominant strength (DS, mV); postprandial increase intensity in dominant strength (PPIIDS; %); bradygastria (c/min, %); tachygastria (c/min, %); and arrhythmia. DF for the study group as a whole was around 3 cpm, at the normal range midpoint, and all other parameters were within the normal limits. On postprandial measurement, the rate of arrhythmias showed a significant decline. Age was found to influence DF, CVDF and arrhythmia in preprandial but not in postprandial period, whereas sex influenced DF, DS and bradygastria in preprandial period, and DF, CVDF, PPIIDS and tachygastria in postprandial period. The mode of lead placement had no impact on the electrogastrographic parameters observed. The values of gastric myoelectrical activity recorded in healthy Croatian subjects were within the normal range of the values defined by previous studies across Europe.

The impact of age, sex, body mass index and menstrual cycle phase on gastric myoelectrical activity characteristics in a healthy Croatian population.

The aim of the study was to determine the impact of demographic and anthropometric parameters on the gastric myoelectrical activity characteristics in a healthy Croatian population. The influence of age, sex, body mass index (BMI) and menstrual cycle phase on the gastric myoelectrical activity characteristics was assessed. The study included 120 healthy subjects of both sexes (60 male and 60 female), divided into four age groups (18-35, 36-50, 51-65 and > 65 years) and three BMI groups (BMI < 25, 25-30 and > 30). Female subjects of reproductive age were divided into three groups according to menstrual cycle phase (day 1-3, day 4-8 and day 9-20 of menstruation). All study subjects underwent percutaneous electrogastrography (EGG) for 60 min before and 60 min after a test meal. The following parameters of the gastric myoelectrical activity were observed: dominant frequency (DF); dominant frequency within normal range (DFNR, %); coefficient of variation for dominant frequency (CVDF); dominant strength (DS. mV); postprandial increase intensity in dominant strength (PPIIDS, %); bradygastria (BG, c/min, %); tachygastria (TG, c/min, %); and arrhythmia (AR). Age was found to influence preprandial but not postprandial DFNR, CVDF and AR. Sex influenced preprandial DF, CVDF, DS and BG, and postprandial DF, CVDF, PPIIDS and TG. BMI exerted an impact on preprandial TG and AR, and postprandial DF, CVDF and AR. The phase of menstrual cycle influenced DF in preprandial period and none of EGG parameters in postprandial period.