The weepy cry - short neural signal bursts in intraoperative neuromonitoring.

PURPOSE: This study aimed to establish an in-vitro alternative to existing in-vivo systems to analyze nerve dysfunction using continuous neuromonitoring (C-IONM). METHODS: Three hundred sixty-three recurrent laryngeal nerves (RLN) (N(pigs) = 304, N(cattle) = 59) from food industry cadavers were exposed by microsurgical dissection following euthanasia. After rinsing with Ringer's lactate, they were tempered at 22 °C. Signal evaluation using C-IONM was performed for 10 min at 2 min intervals, and traction forces of up to 2N were applied for a median time of 60 s. Based on their post-traumatic electrophysiological response, RLNs were classified into four groups: Group A: Amplitude ≥ 100%, Group B: loss of function (LOS) 0-25%, Group C: ≥ 25-50%, and Group D: > 50%. RESULTS: A viable in-vitro neuromonitoring system was established. The median post-traumatic amplitudes were 112%, 88%, 59%, and 9% in groups A, B, C, and D, respectively. A time-dependent further dynamic LOS was observed during the 10 min after cessation of strain. Surprisingly, following initial post-traumatic hyperconductivity, complete LOS occurred in up to 20% of the nerves in group A. The critical threshold for triggering LOS was 2N in all four groups, resulting in immediate paralysis of up to 51.4% of the nerves studied. CONCLUSION: Consistent with in-vivo studies, RLN exhibit significant intrinsic electrophysiological variability in response to tensile forces. Moreover, nerve damage progresses even after the complete cessation of strain. Up to 20% of nerves with transiently increased post-traumatic amplitudes above 100% developed complete LOS, which we termed the "weepy cry." This time-delayed response must be considered during the interpretation of C-IONM signals.

Associations between Covariates and Pneumothorax Observations in CT-Guided Lung Biopsies.

The purpose of this study is to assess the effect of nine covariates on the occurrence or absence of stable or symptomatic pneumothorax. Forty-three patients underwent CT-guided lung biopsies from January 2020 to January 2022 (24 m, 19 f, median age 70 years). All the interventions were carried out with a semi-automatic 18G needle and a 17G trocar in a prone or supine position. Different covariates were measured and correlated to the rate and severity of the pneumothoraces observed. Nominal two-sided t-test p-values for the continuous variables and Fisher's exact test results for the categorical variables were conducted. The data included the lesion size, distance to the pleura, needle-pleura angle, age, gender, position during the procedure, and the presence of chronic obstructive pulmonary disease. Patients with an observed pneumothorax had an average angle between the needle and the pleura of 74.00° compared to 94.68° in patients with no pneumothorax (p-value = 0.028). A smaller angle measurement correlated with a higher risk of pneumothorax development. The needle-pleural angle plays a vital role in the outcome of a CT-guided lung biopsy. Correctly adjusting the needle-pleural angle can diminish the pneumothorax risk associated with a CT-guided lung biopsy. The study results show that as the needle's angle deviates from the perpendicular, the pleural surface area experiencing trauma increases, and pneumothorax is more likely to occur.

The weepy nerve-different sensitivity of left and right recurrent laryngeal nerves under tensile stress in a porcine model.

PURPOSE: Recurrent laryngeal nerve palsy in thyroid surgery is still a threatening complication. Our aim was to analyze the impact of prolonged tensile stress on the recurrent laryngeal nerve (RLN) in an animal model using continuous intraoperative neuromonitoring (C-IONM). METHODS: Constant tensile stress was applied to left and right RLNs in 20 pigs (40 RLN). In a pilot study, five animals were subjected to a tensile force of 0.34 ± 0.07 N for 10 min and changes in amplitude were documented using C-IONM. In the main study, a force of 1.2 N was applied until the signal amplitude was reduced by 85 %, in 15 pigs. Nerve conductivity was analyzed by threshold current measurements. RESULTS: Good correlation was found between stress and amplitude decrease in the pilot study as well as between signal decrease and duration of trauma in the main study. Great variations were found inter- and intra-individually. These variations were most prominent at 85 % signal reduction (median 36 min, range 0.3-171 min). There was no side specificity (left 0.3-171 min, right 0.3-168 min, respectively, p = 0.19). However, in each individual animal, there was a sensitive (0.3-98.9 min) and less sensitive nerve (26.8-171 min). These differences became highly significant at 85 % of signal reduction (p = 0.008), where the vulnerability is 1.4 to 146.4 times higher on one side (mean 4.3). CONCLUSIONS: Our study demonstrates the presence of a sensitive RLN that was 4.3 times more vulnerable than the contralateral nerve (range 1.4-146.4 times, p = 0.008). Thus, the right and the left nerves cannot be assumed to be of equal sensitivity to trauma. In our data, the more sensitive nerve does not occur predominantly on one side and was named the "weepy nerve."

Successful radiation treatment of chylous ascites following pancreaticoduodenectomy.

Chylous ascites is a rare complication following pancreaticoduodenectomy. We report on a case of chylous ascites following pancreaticoduodenectomy in a 76-year-old patient diagnosed with pancreatic cancer. There are various known conservative management strategies, including dietary measures or total parenteral nutrition. Unfortunately, conservative treatment-with total parenteral nutrition and fasting over a period of 4 weeks-was not successful in the present case. The daily output volume of chylous ascites was up to 2500 ml/day. Based on clinical experiences with successfully treated lymphocutaneous fistulas, low-dose radiotherapy was initiated. External beam radiotherapy comprising a total dose of 8.0 Gy to the paraaortic lymph node region was administered in daily single fractions of 1.0 Gy (five fractions/week). Throughout the course of external beam radiotherapy, the secretion of abdominal ascites rapidly decreased, resulting in complete resolution after 2 weeks. There was no clinical evidence of chylous ascites on follow-up. As a result of this experience, we believe that external beam radiotherapy should be considered as an alternative therapy in refractory cases of chylous ascites.

Natural Orifice Transluminal Endoscopic Surgery (NOTES) for colon resections--analysis of the first 139 patients of the German NOTES Registry (GNR).

BACKGROUND: The German NOTES registry (GNR) is the largest published database for natural orifice transluminal endoscopic surgery (NOTES) worldwide. Although transvaginal cholecystectomy is the most frequent procedure in the GNR, the number of colorectal resections is increasing. The objective of this study was to analyze the first 139 colonic procedures of the GNR. METHODS: All colonic procedures from the GNR were analyzed regarding patient- and therapy-related parameters. A multivariate analysis was conducted for transvaginal sigmoid resections regarding procedural time, hospital stay, conversion rate, and rate of complications. RESULTS: From October 2008 to January 2013, 139 colon NOTES procedures (12 male, 127 female) were registered. Main diagnoses were sigmoid diverticulitis (85.6 %), colon carcinoma (9.4 %), and ulcerative colitis (3.6 %). Sigmoid resections (87.1 %), proctocolectomies (3.6 %), right-sided resections (2.9 %), left-sided resections (3.6 %), segmental resections (2.2 %), and 1 ileocecal resection (0.7 %) were performed. All procedures were conducted in transvaginal (87.8 %) or transrectal (12.2 %) hybrid technique, with a median of 3 percutaneous trocars. Conversions to laparoscopic technique were necessary in 3.6 % (none to conventional technique). Intraoperative complications were recorded in 2.9 % and postoperative complications in 12.2 %. The institutional case number in transvaginal sigmoid resections correlated negatively with procedural time (p = 0.041) and the number of percutaneous trocars (p = 0.002). CONCLUSION: The analysis of the first 139 colon NOTES operations of the GNR shows the feasibility of co on operations in hybrid technique, especially for transvaginal sigmoid resection as the most frequent procedure.

Prolonged capnoperitoneum does not cause postoperative ileus in pigs: safety of prolonged capnoperitoneum.

INTRODUCTION: Operative time is an accepted risk factor for the development of postoperative ileus (POI). Innovative surgical procedures such as robotic surgery and natural orifice transluminal endoscopic surgery (NOTES) will be associated with longer operative times. Although intraabdominal manipulation is a major factor for POI the impact of prolonged capnoperitoneum on postoperative gastrointestinal transit time (GIT-TT) has rarely been studied. MATERIAL AND METHODS: IRB approved survival pilot study to assess postoperative GIT-TT using fecal collection and chromium-oxide (Cr2O3) labeling in pigs. Twelve female pigs were randomly assigned to three groups of four animals each. Group A received eight hours anesthesia and pressure-controlled high flow capnoperitoneum (15 mmHg), group B eight hours of anesthesia only and group C no intervention. No intraoperative manipulation. The pilot study was terminated after eight days. RESULTS: None of the animals developed POI. In Group A one animal died after eight hours of general anesthesia. No differences in postoperative fecal output, Cr2O3 excretion rate or weight gain were found. CONCLUSION: This study is the first to investigate eight hours of capnoperitoneum in a survival model. GIT-TT is not affected by prolonged capnoperitoneum in pigs. No POI occurred with prolonged capnoperitoneum. Prolonged capnoperitoneum is safe regarding postoperative gastrointestinal function in innovative surgical procedures.

Intrathoracic major duodenal papilla with transhiatal herniation of the pancreas and duodenum: A case report and review of the literature.

Transhiatal herniation of the pancreas is an extremely rare condition. In the published literature we found only eleven cases reported in the period of 1958 to 2011. A coincidental hiatal herniation of the duodenum is described in two cases only. To our knowledge, we report the first case with a hiatal herniation of the complete duodenum and proximal pancreas presenting an intrathoracic major duodenal papilla with consecutive intrahepatic and extrahepatic cholestasis. A 72-year-old Caucasian woman was admitted to our department with a hiatal hernia grade IV for further evaluation. According to our recommendation of surgical hernia repair soon after the diagnosis of a transhiatal herniation of the proximal pancreas and entire duodenum, we had to respect the declared intention of the patient for a conservative procedure. So we were forced to wait for surgical repair within an emergency situation complicated by a myocardial infarction and reduced general condition. We discuss the therapeutic decision making process and a complete literature review of this rare entity.

Auditory support for resection guidance in navigated liver surgery.

BACKGROUND: An alternative mode of interaction with navigation systems for open liver surgery was requested. Surgeons who use such systems are impeded by having to constantly switch between viewing the navigation system screen and the patient during an operation. METHODS: To this end, an auditory display system for open liver surgery is introduced with support for guiding the tracked instrument towards and remaining on a predefined resection line. To evaluate the method, a clinically orientated user study with 12 surgeons was conducted. RESULTS: It is shown in qualitative results from the user study that the proposed auditory display is recognized as a useful addition to the current visual mode of interaction. It was revealed in a statistical analysis that participants spent less time looking on the screen (10% vs. 96%). Accuracy for resection guidance was significantly improved when using auditory display as an additional information channel (0.6 vs. 1.4 mm); however, the overall time for the resection task was shorter without auditory display (47 vs. 24 s). CONCLUSIONS: By reducing dependence on the visual modality during resection guidance, the auditory display is well suited to become integrated in navigation systems for liver surgery.

Safety analysis of vagal nerve stimulation for continuous nerve monitoring during thyroid surgery.

OBJECTIVES/HYPOTHESIS: Intraoperative neuromonitoring (IONM) facilitates recurrent laryngeal nerve (RLN) identification, but various studies affirm virtually unchanged postoperative RLN palsy rates. Several authors meanwhile suggest continuous intraoperative neuromonitoring (CIONM) via vagal nerve stimulation (VNS) to improve RLN protection. However, knowledge of side effects of electrical VNS derives mainly from its therapeutic applications in the fields of neurology and psychiatry. The presented study was conducted to further evaluate the safety of CIONM and identify possible VNS related side effects. STUDY DESIGN: Prospective nonrandomized controlled trail. METHODS: Forty patients scheduled for thyroid or parathyroid surgery were enrolled in the trail. The intervention group consisted of 22 patients receiving VNS for CIONM. Eighteen patients were operated on with routine IONM. To assess VNS-induced effects on the autonomic nervous system (ANS), heart rate variability analysis (HRVA) was applied. Serum cytokine levels of tumor necrosis factor (TNF)-α were monitored to evaluate immunomodulatory effects of VNS. RESULTS: HRVA revealed significantly increased vagal activity during CIONM. This parasympathetic predominance was not countered by the sympathetic nervous system. Despite a significant increase of vagal tone, no hemodynamic events occurred; in fact, no significant changes in median heart rate or in median arterial blood pressure were detected. Even though anti-inflammatory effects of VNS have been reported, no attenuation of cytokine release of TNF-α was measured. CONCLUSIONS: VNS for CIONM resulted in increased vagal activity assessable via HRVA. The increased parasympathetic tone affected neither hemodynamics nor levels of the proinflammatory cytokine TNF-α. VNS for CIONM appears safe with the applied settings.

New backstrap vagus electrode for continuous intraoperative neuromonitoring in thyroid surgery.

INTRODUCTION: Continuous intraoperative neuromonitoring (CIONM) via vagal nerve stimulation allows real-time surveillance of the recurrent laryngeal nerve during thyroid surgery. However, for effective CIONM, subtle changes in recurrent laryngeal nerve conductivity have to be detected. A newly developed stimulation electrode that provides stable nerve stimulation and safe application is presented. METHODS: For electrode validation, current distribution was simulated with the finite element method. Mechanical characteristics were assessed through bench testing. Clinical evaluation was initiated with 11 thyroid surgeries. RESULTS: Experimental and clinical results led to the development of a tripolar gold/polyimide electrode mounted onto a backstrap-shaped silicone body. It facilitated rapid electrode implantation and extraction (median implantation time 4 ± 19 seconds). Peak extraction force was 570 mN. Median supramaximal stimulation currents were 2.00 ± 0.95 mA and resulted in reliable electromyogram responses (median 3.1 ± 3.0 mV). No intraoperative electrode dislocations occurred, and no postoperative nerve palsy was observed. CONCLUSION: The new backstrap vagal stimulation electrode meets the requirements for reliable CIONM.

Sashimi NOTES--extraction of bulky specimens in no-scar operations.

A major obstacle in no-scar surgery is the extraction of large, bulky or rigid specimen. Thus, a method is needed that allows for extraction of large specimens without situs contamination in women and men. It should enable safe treatment of infectious or malignant disease while preserving pathologic workup. Five patients suffering from diverticulitis with expected bulky and rigid specimen were enrolled into this early series. Preparation was performed transumbilically in single-port technique. To prevent new scar formation, the incision was limited to the base of the umbilicus without extension onto the sound abdominal skin. A functionally and topologically extracorporeal compartment was created within the abdomen by introduction and insufflation of a tear-proof impermeable retrieval bag. The specimen was sliced in a controlled fashion inside the compartment along a pre-marked geometry. Controlled specimen dissection in a dedicated intraabdominal resection compartment was feasible. The dissected specimen could be retrieved through the 1.5 cm umbilical incision without spillage of material. The geometry of the extracted organ was reconstructed in detail allowing for uncompromised pathological workup. Extraction of bulky and rigid specimen is possible through natural orifices by the proposed controlled dissection method enabling the pathologist to reconstruct anatomical affiliation.

Impact of continuous intraoperative neuromonitoring on autonomic nervous system during thyroid surgery.

BACKGROUND: Continuous intraoperative neuromonitoring (CIONM) via vagal nerve stimulation (VNS) is a new option for recurrent laryngeal nerve (RLN) protection during thyroid surgery. The aim of this study was to evaluate the safety of VNS for CIONM and to assess its effects on the autonomic nervous system (ANS) through analyzing heart rate variability (HRV). METHODS: In a prospective, nonrandomized controlled study 5 patients received VNS for CIONM and 5 were operated on with conventional intermittent intraoperative neuromonitoring (IONM). HRV was analyzed in accord with patient-specific reference values. RESULTS: VNS resulted in significantly altered ANS balance. Relative parasympathetic activity increased during VNS. Yet, no relevant cardiac arrhythmias or hemodynamic alterations were observed during VNS. CONCLUSION: HRV analysis revealed a distinct impact of VNS for CIONM on ANS balance. VNS caused parasympathetic predominance that was not countered by increased sympathetic activity.

Snake charmer NOTES: a two-luminal access for hybrid NOS operations.

Despite recent advances in NOTES, NOS, SILS and related techniques, the feasibility of performing extensive surgery is still limited. Colon surgery usually requires additional access sites or complex technical means for triangulation and retraction. A method is presented that enables single-port colon surgery, supported by flexible colonoscopy. Single-port sigmoidectomy was performed in five cases on the porcine model. Flexible colonoscopy was used to manoeuvre the colon and expose its mesentery for dissection. The specimen was retrieved transrectally by invagination. Single-port sigmoidectomy supported by colonoscopy was feasible in all cases. The method provided a fixed framework, excellent organ guidance and exposition of the mesentery and enabled bowel-close mesocolic preparation. The access angle for preparation and visualisation could be altered during the procedure using the colonoscope. During autopsy on day 21, competent anastomotic healing with only rare interenteric adhesions was observed. One animal had a small preperitoneal abscess in the umbilical region while demonstrating completed skin healing. Flexible colonoscopy provided a fixed reference frame that enabled single-port preparation and dissection of the sigmoid colon. Under colonoscopic guidance, the access angle for dissection could be adapted according to the surgeon's needs. The procedures could be performed safely and effectively.

Impact of body image on patients' attitude towards conventional, minimal invasive, and natural orifice surgery.

PURPOSE: A series of investigations proposed that patients' preference on minimal invasive and scarless surgery may be influenced by age, sex, and surgical as well as endoscopic history of the individual patient. However, it is unknown which psychological criteria lead to the acceptance of increased personal surgical risk or increased personal expenses in patients demanding scarless operations. We investigated whether individual body image contributes to the patient's readiness to assume higher risk in favor of potentially increased cosmesis. MATERIALS AND METHODS: We conducted a nonrandomized survey among 63 consecutive surgical patients after receiving surgery. Individual body image perception was assessed postoperatively applying the FKB-20 questionnaire extended by four additional items. The FKB-20 questionnaire is a validated tool for measuring body image disturbances resulting in a two-dimensional score with negative body image (NBI) and vital body dynamics (VBD) being the two resulting scores. A subgroup analysis was performed according to the conducted operations: conventional open surgery = group 1, traditional laparoscopic surgery = group 2, and no scar surgery = group 3. RESULTS: There was a significant correlation between a negative body image and the preference for scar sparing and scarless surgery indicated by a significantly increased acceptance of surgical risks and the willingness to spend additional money for receiving scarless surgery (r = 0.333; p = 0.0227). Allocated to operation subgroups, 17 of 63 patients belonged to group 1 (OS), 29 to group 2 (minimally invasive surgery), and 17 patients to group 3 (no scar). Although age and sex were unequally distributed, the groups were homogenous regarding body mass index and body image (NBI). Subgroup analysis revealed that postoperative desire for scar sparing approaches was most frequently expressed by patients who received no scar operations. CONCLUSIONS: Patients with an NBI tend towards scarless surgery and are willing to accept increased operative risk and to spend additional money for improved postoperative cosmesis.

Trilumenal hybrid-NOS proctocolectomy.

BACKGROUND: The authors hypothesized that by combining transumbilical, transvaginal, and transrectal accesses, complex bowel operations, including proctocolectomy with restorative J pouch [corrected] reconstruction, might be possible. METHODS AND RESULTS: Out of a series of 30 natural orifice surgery (NOS) operations performed at the authors' institution in the past 12 months, proctocolectomy with ileoanal pouch reconstruction was planned for 3 female patients (31 years, BMI = 30; 50 years, BMI = 31; 30 years, BMI = 21) with extensive disease of ulcerative colitis, and they were operated via a 3-lumenal NOS approach. The first 2 patients received a proctocolectomy with a J-pouch formation. A 3-stage procedure was planned for the third patient, and she received a total colectomy. The colonic specimen was retrieved through the anus obviating dilation of the vagina. The J-pouch was prepared through a horizontal 2-cm incision, which later served as the protective loop ileostomy site. CONCLUSION: Trilumenal NOS proctocolectomy is feasible and safe providing a solution to overcome the lack of triangulation using a single-lumen approach.

Triluminal hybrid NOS as a novel approach for colonic resection with colorectal anastomosis.

BACKGROUND: Minimal invasive surgery has led to a significant decrease in surgical trauma, pain, recovery time and improved cosmesis compared with open surgery. However, scar development and the risk of hot spots for infections and hernias are still present. Natural orifice surgery (NOS) promises to offer even further reduction in invasiveness and thus may lead to even faster recovery. The goal of this study was to establish a NOS colonic resection by using commercially available standard surgical instruments avoiding major abdominal incisions. METHODS AND RESULTS: This article reports a new triluminal hybrid NOS approach for sigmoid and colonic resection (Tri-Port-NOS-SIG), established using rigid laparoscopic instruments through the umbilicus, the vagina, and the rectum, without any major abdominal incision. The specimen was retrieved through the anus avoiding dilatation of the vagina. In an early series of 5 patients the first patient was a 37-year-old woman with a 10-year history of recurrent diverticulitis. She recovered quickly and was discharged on postoperative day 2. She returned to sports activity on day 12 postoperatively and to her heavy-duty job on day 16. The following 4 patients also recovered well and were discharged on postoperative days 7 (2 patients), 8, and 11, respectively. One patient experienced a temporary, mild paresthesia of the left lower dorsal leg, most likely because of intraoperative positioning. No major complications occurred. CONCLUSION: Tri-Port-NOS-SIG offers a feasible scarless approach for abdominal resections using commercially available surgical instruments in experienced hands.

Real-time monitoring of the recurrent laryngeal nerve: an observational clinical trial.

BACKGROUND: A variety of tools has been developed to identify nerve structures and to lower the risk of nerval injury during thyroid surgery. These tools are usually based on intermittent electrophysiological tracing of the nerves, but its use is still associated with permanent recurrent laryngeal nerve (RLN) injury. We are now presenting the results of the implementation of a novel real-time nerve monitoring system, based on a new vagal nerve cuff electrode. METHODS: Nineteen consecutive patients scheduled for thyroid surgery (17 with benign, 2 with malignant disease), were enrolled in this observational trial. The flexible cuff electrode was implanted during each operation and atraumatically surrounded the vagal nerve. The evoked potentials were sensed by standard thyroid electrodes. Electrical stimulation and recording were achieved through a multichannel electromyography (EMG) system. The signal analysis was performed in real-time by specially designed software. RESULTS: The cuff electrode did not cause any complications during or after the surgery. In all patients, stable and reproducible signals were easily evoked. The mean time required to place the electrode was 6.5 min. The mean overall vagal nerve stimulation time was 65 min. No permanent RLN lesions were detected in any patient. One patient with a postoperative bleeding from a strap muscle vein required a wound revision, which was performed without nerve monitoring. This patient experienced a temporary partial impairment of the left vocal cord. No hypoparathyroidism was observed in any patient postoperatively. CONCLUSIONS: The presented technique of real-time continuous RLN monitoring by stimulation of the vagal nerve is feasible, safe, reproducible, and easy to perform. In addition, this new system is compatible with existing equipment and can be used as an add-on with conventional nerve monitoring devices during thyroid surgery.

A new system for continuous recurrent laryngeal nerve monitoring.

Existing nerve monitoring devices in thyroid surgery are - except for one - mainly intermittently working nerve identification tools. We present a new vagal electrode which allows true continuous monitoring of the recurrent laryngeal nerve (RLN). The electrode was designed as a tripolar hybrid cuff electrode consisting of polyimide, gold and platinum layers embedded in a flexible silicon cuff which can be opened at the long side for introducing the nerve. It is fully implantable and atraumatic. The evoked potentials are sensed by standard thyroid electrodes. Real-time signal analysis and audio feedback are achieved by specially designed software. Homogeneous and stable signals were recorded throughout the operations. Thus real-time computer-based signal analysis was possible. Evoked potentials reached 300-900 mV. Mean time to place the cuff electrode was 5.5 min. The nerve was stimulated a mean of 63 min (range 55-99 min). No RLN lesions were detected postoperatively. The new vagal electrode was easy to handle and led to stable and reproducible signals. The stimulation current could be kept extremely low due to the special geometry of the electrode. It offers the possibility for uninterrupted, continuous laryngeal nerve monitoring in thyroid surgery. In an ongoing clinical trial its compatibility as an add-on for existing nerve monitoring devices is being tested.

Herpes simplex virus colitis complicating ulcerative colitis: A case report and brief review on superinfections.

In patients with inflammatory bowel disease herpes simplex virus infection has been described as a major cause of morbidity and mortality, especially in immunocompromised individuals. Here we present the case of a 35-year old woman with an exacerbation of ulcerative colitis caused by herlpes simplex virus infection (HSV-2). The diagnosis was confirmed histologically following subtotal colectomy. After intravenous treatment with aciclovir for 2 weeks postoperative hematochezia stopped. Herpes simplex virus colitis is a rare but potentially fatal complication of immunosuppressive treatment in patients with inflammatory bowel disease. Prompt diagnosis and efficient antiviral therapy are mandatory to improve prognosis.