Changes in occurrence and management of laryngeal fractures at the Helsinki University Hospital during 25 years.

PURPOSE: Laryngeal fracture is a rare but potentially life-threatening trauma. Fractures vary from mild to dislocated and extensive with risk of severe complications. This study investigated the occurrence, clinical characteristics and management of laryngeal fractures in the last 15 years. MATERIAL AND METHODS: A retrospective population-based cohort study reviewing all laryngeal fractures at the Helsinki University Hospital in 2005-2019. Patient records and imaging studies were systematically reviewed for mode of injury, fracture type, secondary complications, treatment modality, possible airway management, length of stay, and mortality. Results were compared with corresponding data from 1995 to 2004. RESULTS: Overall 80 fracture patients were recorded (5.3/year); 79% were men and mean age was 42 years (range 18-78). Altogether 91% were closed and 9% open. While unintentional traumas were most common (54%), an increasing proportion were from intentional injury (10%) or Schaefer Gr IV in severity (35%). Altogether 46% had compromised airway and 21% needed airway intervention; airway narrowing was more common with cricoid (p = 0.042) and multiple fractures (p = 0.07) and correlated positively with amount of dislocation (p = 0.001) and number of fracture lines (p = 0.006). Surgery was performed for 33%, of which 46% were Schaefer Gr IV and 62% from intentional trauma. Mortality was 1.4%. CONCLUSIONS: Deliberate and violence-related laryngeal fractures have increased. These often result in more extensive injuries predisposing to compromised airway and requiring surgical intervention and longer treatment. Most fractures are still treated conservatively with good long-term outcomes. An observation period of 24 h is recommended to detect any delayed complications. Mortality remains low.

Internal carotid artery dissection in a patient with hemophilia A: a case report and literature review.

Spontaneous cervical artery dissection (sCeAD) is the most common cause of ischemic stroke at a young age, but its pathogenetic mechanism and risk factors are not fully elucidated. It is reasonable to think that bleeding propensity, vascular risk factors such as hypertension and head or neck trauma, and constitutional weakness of the arterial wall together play a role in the pathogenesis of sCeAD. Hemophilia A is known to be an X-linked condition that leads to spontaneous bleeding in various tissues and organs. To date, a few cases of acute arterial dissection in patients with hemophilia have been reported, but the relationship between these two diseases has not been studied so far. In addition, there are no guidelines indicating the best antithrombotic treatment option in these patients. We report the case of a man with hemophilia A who developed sCeAD and transient oculo-pyramidal syndrome and was treated with acetylsalicylic acid. We also review previous published cases of arterial dissection in patients with hemophilia, discussing the potential pathogenetic mechanism underlying this rare association and potential antithrombotic therapeutic options.

STRANGULATION-INDUCED ATLANTOAXIAL ROTATORY SUBLUXATION TREATED WITH CLOSED REDUCTION.

BACKGROUND: Cervical subluxation is a broad class of injuries in which there are degrees of misalignment of vertebral bodies in relationship to adjacent vertebra. Atlantoaxial rotatory subluxation (AARS) is a subtype of cervical subluxation resulting from exaggerated rotation of the C1-C2 complex. Inflammatory, infectious, post-surgical, and traumatic etiologies are recognized and well-described. AARS is predominantly seen in children and occurs rarely in adults. CASE REPORT: We submit the case of an otherwise healthy adult male patient presenting to the emergency department with strangulation-induced C1-C2 subluxation with a rotational component that was treated at the bedside by neurosurgery with closed reduction. Why Should an Emergency Physician Be Aware of This? Clinicians must consider a broad range of serious pathologies in a patient presenting with torticollis, especially in the setting of strangulation. Although extremely rare in adults, AARS must be considered in the differential diagnosis, as early identification increases the likelihood of successful nonoperative treatment.

[Acute care of soft tissue injuries in the head and neck region]. / Akutversorgung von Weichteilverletzungen im Kopf-Hals-Bereich.

BACKGROUND: Soft tissue injuries are a common consequence of head and neck trauma. With injuries being highly individual and varying depending on the underlying trauma, it is difficult to establish standardized guidelines for head and neck trauma in general. The main goal of this study was to showcase the distribution of soft tissue injury types and the principles pertaining to acute care of the individual clinical presentations. MATERIALS AND METHODS: A retrospective evaluation was carried out using all trauma-relevant ICD-10 codes for trauma to the head (S00.- to S09.-) and neck (S10.- to S19.-) among patients who were treated at the authors' clinic-a certified national trauma center-during a period of 10 years (2012 to and including 2021). RESULTS: A total of 8375 patients with head and neck trauma were treated during the observation period, i.e., an average of 836 patients per year. Within this collective, 2981 trauma cases involving soft tissue injuries were documented. Superficial injuries to the head (S00.-) and open wounds to the head (S01.-) were the most common head and neck soft tissue injuries, with 1649 and 920 cases, respectively. CONCLUSION: The case numbers of soft tissue injuries generally show an inverse correlation to the required underlying trauma: diagnoses of the categories S00 and S01 occur very often; injuries which only occur after severe trauma, such as traumatic amputation at neck level (S18), are rare. According to current literature, penetrating neck traumas should be treated using a no-zone approach. In Europe, penetrating neck injuries are rather rare because of low crime rates and strict weapon laws.

Civilian penetrating neck trauma at a level I trauma centre: A five-year retrospective case note review.

OBJECTIVES: To report the experience of civilian penetrating neck trauma (PNT) at a UK level I trauma centre, propose an initial management algorithm and assess the degree of correlation between clinical signs of injury, operative findings and radiological reports. DESIGN: Retrospective case note review. SETTING: UK level I trauma centre April 2012-November 2017. PARTICIPANTS: Three hundred ten cases of PNT were drawn from electronic patient records. Data were extracted on hard and soft signs of vascular or aerodigestive tract injury, clinical management, radiological imaging and patient outcomes. MAIN OUTCOME MEASURES: Patient demographics, mechanism of injury, morbidity and mortality. The correlation between clinical signs, and radiological reports to internal injury on surgical exploration. RESULTS: Two hundred seventy-one (87.4%) male and 39 (13.6%) female patients with a mean age of 36 years (16-87) were identified. The most common causes of injury were assault 171 (55.2%) and deliberate self-harm 118 (38%). A knife was the most common instrument 240 (77.4%). Past psychiatric history was noted in 119 (38.4%), and 60 (19.4%) were intoxicated. 50% were definitively managed in theatre with a negative exploration rate of 38%, and 50% were managed in ED. Pre-operative radiological reports correlated with operative reports in 62% of cases with venous injury the most common positive and negative finding. Multivariate correlation was r = 0.89, p = 0.045, between hard signs plus positive radiology findings and internal injury on neck exploration. CONCLUSIONS: Management of PNT by clinical and radiological signs is safe and effective, and can be streamlined by a decision-making algorithm as proposed here.

A case report of cervicothoracic penetrating injury with retention of foreign body.

BACKGROUND: Cervicothoracic penetrating injury, considered to be relatively rare, has a complicated mechanism that is difficult to treat. In this report, a special case of cervicothoracic injury caused by foreign body penetration was elucidated. In this case, the injury location and the involved foreign body were exceptionally particular, which induced a challenging process of diagnosis and treatment. CASE PRESENTATION: A male patient suffered from a serious injury caused by a thick branch that pierced through his neck in a traffic accident between an electric car and a tricycle carrying wood. There were also local injuries in the left scapular region. After an emergency multidisciplinary consultation, the patient was diagnosed and subsequently treated with vascular exploration and repair (common carotid artery), intrathoracic foreign body extraction, chest exploration, debridement, and suture. After surgery, he was transferred to the emergency intensive care unit for anticoagulation and anti-infection treatment. Finally, after the improvement of his physical condition, the patient was transferred to the general ward for further treatment and was successfully discharged from the hospital. Once discharged, the patient lived a normal life, free from sequelae or complications. CONCLUSION: It may be an extremely daunting task to cure cervicothoracic penetrating injury due to its rare occurrence in clinical practice. Different from the previous cervicothoracic traumas, the injury location in this case is exceedingly particular. In general, the common cervicothoracic trauma is associated with damage to the trachea, esophagus, throat, and other structures, easily resulting in dyspnea, which, however, does not occur in this case. The insertion position of foreign body is exceptionally particular as it does not pierce the common carotid artery but poses compression on it, which induces ischemia. It is essential for the successful treatment that the treatment plan is formulated via the detailed imaging examination and careful multidisciplinary consultation.

[Life-threatening subcutaneous emphysema after minor blow to the neck]. / Lebensbedrohliches Hautemphysem nach banalem Stoß gegen den Hals.

After a minor blow to the neck from the handlebars of a bike, a 5-year-old boy developed a massive subcutaneous emphysema with respiratory distress. Orotracheal intubation was performed. A computed tomography (CT) scan of the neck and thorax showed a pneumomediastinum and a bilateral pneumothorax. No injury to the large airways was identified. The patient was stabilized by insertion of chest tubes and controlled ventilation. The endoscopic examination of the trachea revealed a tear of the pars membranacea, which was successfully treated conservatively. The specific features of the injury and the airway management are discussed based on a review of the current literature.

[Functional rehabilitation of severe laryngopharyngeal injuries after near-lethal suicide attempt by hanging]. / Funktionelle Rehabilitation schwerer laryngopharyngealer Verletzungen nach Suizidversuch durch Erhängen.

BACKGROUND: Hanging is a common method of suicide with an estimated mortality rate of about 70%. Survival of patients with severe laryngopharyngeal injuries after strangulation is not common. However, clinical findings of patients reaching the hospital alive may be minimal. A rapid onset of multidisciplinary diagnostic and therapeutic management is mandatory, followed by psychiatric treatment and functional rehabilitation. CASE PRESENTATION AND RESULTS: Two uncommon cases after severe laryngopharyngeal injury due to near-lethal suicide attempt by hanging demonstrate the emergency management and reconstructive surgery. Subsequent tracheal cannula management and swallowing therapy to full recovery are described. In addition, a proposal for an interdisciplinary treatment algorithm for those patients is presented. CONCLUSION: Minimal external clinical findings after near-lethal suicide attempts by hanging do not exclude severe internal injuries of the upper aerodigestive tract structures. After reconstructive surgery an appropriate tracheal cannula management and an early and intensive swallowing therapy parallel to the psychiatric treatment is mandatory to restore voice, airway and deglutition.

"No zone" approach in penetrating neck trauma reduces unnecessary computed tomography angiography and negative explorations.

BACKGROUND: The most recent management guidelines advocate computed tomography angiography (CTA) for any suspected vascular or aero-digestive injuries in all zones and give zone II injuries special consideration. We hypothesized that physical examination can safely guide CTA use in a "no zone" approach. METHODS: An 8-year retrospective analysis of all adult trauma patients with penetrating neck trauma (PNT) was performed. We included all patients in whom the platysma was violated. Patients were classified into three groups as follows: hard signs, soft signs, and asymptomatic. CTA use, positive CTA (contrast extravasation, dissection, or intimal flap) and operative details were reported. Primary outcomes were positive CTA and therapeutic neck exploration (TNE) (defined by repair of major vascular or aero-digestive injuries). RESULTS: A total of 337 patients with PNT met the inclusion criteria. Eighty-two patients had hard signs and all of them went to the operating room, of which 59 (72%) had TNE. One hundred fifty-six patients had soft signs, of which CTA was performed in 121 (78%), with positive findings in 12 (10%) patients. The remaining 35 (22%) underwent initial neck exploration, of which 14 (40%) were therapeutic yielding a high rate of negative exploration. Ninty-nine patients were asymptomatic, of which CTA was performed in 79 (80%), with positive findings in 3 (4%), however, none of these patients required TNE. On sub analysis based on symptoms, there was no difference in the rate of TNE between the neck zones in patients with hard signs (P = 0.23) or soft signs (P = 0.51). Regardless of the zone of injury, asymptomatic patients did not require a TNE. CONCLUSIONS: Physical examination regardless of the zone of injury should be the primary guide to CTA or TNE in patients with PNT. Following traditional zone-based guidelines can result in unnecessary negative explorations in patients with soft signs and may need rethinking.

Forty hours with a traumatic carotid transection: A diagnostic caveat and review of the contemporary management of penetrating neck trauma.

Although penetrating neck trauma (PNT) is uncommon, it is associated with the significant morbidity and mortality. The management of PNT has changed significantly over the past 50 years. A radiological assessment now is a vital part of the management with a traditional surgical exploration. A 22 years old male was assaulted by a screwdriver and sustained multiple penetrating neck injuries. A contrast CT scan revealed a focal pseudoaneurysm in the left common carotid artery bulb. There was no active bleeding or any other vascular injuries and the patient remained haemodynamically stable. In view of these findings, he was initially managed conservatively without an open surgical exploration. However, the patient was noted to have an acute drop in his hemoglobin count overnight post injury and the catheter directed angiography showed active bleeding from the pseudoaneurysm. Surgical exploration 40 hours following the initial injury revealed a penetrating injury through both arterial walls of the left carotid bulb which was repaired with a great saphenous vein patch. A percutaneous drain was inserted in the carotid triangle and a course of intravenous antibiotics for five days was commenced. The patient recovered well with no complications and remained asymptomatic at five months followup.

Thyroid gland hemorrhage after blunt neck trauma: case report and review of the literature.

BACKGROUND: Thyroid hemorrhage is considered to be an uncommon complication following blunt trauma to the neck. This condition is potentially life-threatening due to airway compression and may therefore require emergency airway management and surgical intervention in some cases. CASE PRESENTATION: We present the case of a 52-year-old woman who experienced a traumatic thyroid gland rupture (right lobe) with subsequent active arterial bleeding from branches of the inferior thyroid artery. On the same day, the patient presented to our emergency department with a painful swelling of the neck with an inspiratory stridor and hoarseness a few hours after a cycling accident. A right hemithyroidectomy was performed. The postoperative course was uneventful. We identified 33 additional cases published in English literature within the last 30 years, reporting blunt trauma to the neck with hemorrhagic complication of the thyroid gland. We provide a systematic review and particularly consider the aspects of endocrine surgery. CONCLUSION: The treatment approach for patients with blunt thyroid trauma should be dependent on the extent of the thyroid injury. Patients with tracheal compression, active bleeding and increasing hoarseness/shortness of breath require emergency airway control and often surgical exploration for hemorrhage control followed by resection of the ruptured thyroid. Importantly, in contrast to routine thyroid surgery, no electromyographic endotracheal tube is used during emergency intubation. Exchange of an endotracheal tube should be carefully evaluated due to difficult airway management in this setting. For protection against double-sided recurrent nerve palsy and postoperative hypoparathyroidism, a unilateral approach is preferable whenever possible.

Laryngeal Injury and Pneumomediastinum Due to Minor Blunt Neck Trauma: Case Report.

BACKGROUND: Serious isolated laryngeal injuries are uncommon in children. CASE REPORT: We describe the case of an 8-year-old boy with laryngeal injury and pneumomediastinum due to minor blunt neck trauma. He presented to the emergency department complaining of odynophagia and hoarseness, but without respiratory distress. Emphysema was seen between the trachea and vertebral body on initial cervical spine x-ray study, and flexible laryngoscopy revealed erythema and mild edema of both the right vocal cord and the arytenoid region. He recovered with conservative management only. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We conclude that it is important to recognize subtle evidence of laryngeal injury secondary to blunt neck trauma to ensure early diagnosis. Initial cervical spine x-ray assessment should exclude both cervical spine fracture and local emphysema after blunt neck trauma. If patients with blunt neck trauma have evidence of a pneumomediastinum, the clinician should consider the possibility of aerodigestive injury.

Asymptomatic Chiari Type I malformation: should patients be advised against participation in contact sports?

BACKGROUND: Chiari type I malformation (CM-I) is characterised by caudal displacement of the cerebellar tonsils through the foramen magnum, crowding the craniocervical junction. It is being increasingly diagnosed in asymptomatic patients due to the widespread availability of MRI, and there are case reports of these patients suffering sudden death or neurological injury following head or neck trauma, raising the issue of whether they should be prohibited from contact sport participation, given the likelihood of frequent trauma. General neurosurgical opinion is that patients who are symptomatic and those with an associated spinal cord syrinx should be offered foramen magnum decompression, however asymptomatic patients without syringomyelia are not offered this in the majority of cases. METHODS: The authors performed a full review of the published literature, including all case reports, case series, studies and literature reviews regarding CM-I and either contact sports or trauma, excluding patients that had undergone surgical intervention and those becoming symptomatic in circumstances other than head or neck trauma. RESULTS: 21 case reports of CM-I patients deteriorating following trauma were identified, including four cases of sudden death following head or neck injury. However, studies of large samples of CM-I patients are yet to capture an incident of sudden death or acute neurological deterioration, suggesting that the risk is very low. CM-I patients may have an increased risk of concussion and post-concussion syndrome compared to the background population however. CONCLUSION: Overall, the authors feel that there should be no restriction of sports participation for CM-I patients, but a discussion to make them and their families aware of the possible increased risks is important.

Traumatic bilateral dissection of cervical internal carotid artery in the wake of a car accident: A case report.

BACKGROUND: Bilateral carotid artery dissection secondary to severe trauma is rare and can be potentially life -threatening if not diagnosed and treated properly. CASE PRESENTATION: We report a 29-year-old female who was admitted to the emergency department after a car accident. The patient was conscious at the time of admission and presented with an initial Glasgow Coma Scale (GCS) of 15 presenting normal vital signs. The patient developed motor dysphasia with right upper limb paresis a few hours after the admission. Magnetic resonance imaging (MRI) revealed a bilateral cervical internal carotid artery (ICA) occlusion in addition to left frontal lobe infarct in a subacute phase. Medical management was successful and the patient was discharged from the hospital two weeks after the admission. DISCUSSION: Noninvasive vascular imagining modalities are merging as the gold standard in the early detection of carotid artery dissection (CAD). Typical pathognomonic findings on MRI include double lumen and intimal flap. The management with systemic anticoagulation or antiplatelet therapy is aimed to prevent the development of ischemic stroke. In case of medical therapy being ineffective or in case of complication or any disorders suffered by a patient, endovascular treatment is performed. CONCLUSION: With early detection and proper management, traumatic dissection of cervical carotid artery can have a benign outcome. As for the current patient, medical treatment with anticoagulation was sufficient and surgical management was therefore not required. Improvement in the patients' speech was observed; nevertheless the continuation of speech therapy was indicated.

Airway management in laryngotracheal injuries from blunt neck trauma in children.

Pediatric laryngotracheal injuries from blunt neck trauma are extremely rare, but can be potentially catastrophic. Early diagnosis and skillful airway management is critical in avoiding significant morbidity and mortality associated with these cases. We present a case of a patient who suffered a complete tracheal transection and cervical spine fracture following a clothesline injury to the anterior neck. A review of the mechanisms of injury, clinical presentation, initial airway management, and anesthetic considerations in laryngotracheal injuries from blunt neck trauma in children are presented.

A Hanging and Its Complications.

Hanging has become the second most common form of successful suicide in the United States. Along with a high mortality rate, the long-term morbidity is consequential for both the individual patient and society. A thorough knowledge of the clinical approach will assist the emergency physician in providing optimal care and helping to minimize delayed respiratory complications. Using a case-based scenario, the initial management strategies along with rational evidence-based treatments are reviewed.

[The clinical treatment of laryngotracheal rupture injury].

Objective:To investigate the therapeutic effect of laryngotracheal rupture injury and management of related complications. Methods:A retrospective analysis was conducted on 10 patients with laryngotracheal rupture injury caused by trauma, admitted between October 2014 and October 2022. Results:Anti-shock treatment, local debridement, tracheal-cricoid cartilage or tracheal-tracheal anastomosis, laryngeal cartilage reduction and fixation, local transposition flaps repair and phase-Ⅱ airway reconstruction were performed respectively on 10 patients. Nine patients underwent operations of tracheal-cricoid cartilage or tracheal-tracheal anastomosis, with five of these were performed by cartilage broken reduction and fixation, placed with intraluminal stents of iodoform gauze fingerstalls for （8.2±1.6） days. Tracheal reconstruction surgery was performed on 2 cases during phase-Ⅱ and both were placed with T-shaped silicone tube to support for 3 months. Two cases required tracheoesophageal fistula surgical repair, and vocal cord suturing was conducted for three vocal fold injuries. Anti-shock treatment was given to one emergency case and closed thoracic drainage treatment was given to another one. We removed the tracheal cannula from 10 patients after surgery and one case was diagnosed with Ⅰ-level swallowing function of sub-water test. All cases recovered to take food per-orally. Conclusion:Maintenance of circulation and respiration functions is the major target during early treatment of laryngotracheal rupture. It should strive to complete the reconstruction of airway structure on phase-Ⅰ, among which end-to-end anastomosis to reconstruct airway and broken laryngeal cartilage reduction and fixation are the vital methods for airway structure reconstruction to achieve good results. It is suggested that the reconstruction of trachea and esophagus structures should be performed simultaneously to patients with tracheoesophageal fistula.

Directed work-up of select penetrating neck injuries is safe: Hard signs continue to soften.

INTRODUCTION: Management of penetrating neck injuries (PNIs) has evolved over time, more frequently relying on increased utilization of diagnostic imaging studies. Directed work-up with computed tomography imaging has resulted in increased use of angiography and decreased operative interventions. We sought to evaluate management strategies after directed work-up, hypothesizing increased use of non-operative therapeutic interventions and lower mortality after directed work-up. METHODS: Patients with PNI from 2017 to 2022 were identified from a single-center trauma registry. Demographics, injuries, physical exam findings, diagnostic studies and interventions were collected. Patients were stratified by presence of hard signs and management strategy [directed work-up (DW) and immediate operative intervention (OR)] and compared. Outcomes included therapeutic non-operative intervention [endovascular stent, embolization, dual antiplatelet therapy (DAPT), or anticoagulation (AC)], non-therapeutic neck exploration, length of stay (LOS), and mortality. RESULTS: Of 436 patients with PNI, 143 (33%) patients had vascular and/or aerodigestive injuries. Of these, 115 (80%) patients underwent DW and 28 (20%) patients underwent OR. There were no differences in demographics or injury severity score between groups. Patients in the DW group were more likely to undergo vascular stent or embolization (p = 0.040) and had fewer non-therapeutic neck explorations (p = 0.0009), compared to the OR group. There were no differences in post-intervention stroke, leak, or mortality. Sixty percent of patients with vascular hard signs and 78% of patients with aerodigestive hard signs underwent DW. CONCLUSIONS: Directed work-up in select patients with PNI is associated with fewer non-therapeutic neck explorations. There was no difference in mortality. Selective use of endovascular management, AC and DAPT is safe.

A Review of 13,470 Head and Neck Injuries from Trampoline Jumping.

Study Design: The authors designed a 20-year cross-sectional study using the National Electronic Injury Surveillance System (NEISS) database. Objective: The purpose of the study is to determine the risk factors for hospital admission among individuals who suffer head and neck injuries secondary to trampoline use. Methods: The primary predictor variables were a set of heterogenous variables that were categorized into the forementioned study variable groups (patient characteristics and injury characteristics). The primary outcome variable was hospital admission. Multivariate logistic regression was used to determine independent risk factors for hospital admission. Results: The final sample consisted of 13,474 reports of trampoline injuries to the head and neck. Relative to females, males (OR 1.66, P < .05) were at an increased risk for hospital admissions. Fractures (OR 35.23, P < .05) increased the risk for hospital admissions relative to dental injuries. Concerning anatomical region of injury, neck injuries (OR 30.53, P < .05) were at an increased risk for hospital admissions. Conclusions: Injuries to the neck from trampoline jumping significantly increased the risk for admission. The severity of neck injuries from trampoline jumping is well established in the literature. Additionally, male sex and fractures were each risk factors for hospital admission. Given the rising prevalence of trampoline-related head and neck injuries over the past 2 decades, it is crucial for individuals to take the necessary precautions when jumping on a trampoline.

Bilateral Tapia syndrome in teenager with post traumatic Hangman's fracture and carotid artery dissection.

Background: Tapia syndrome (TS) is a rare condition characterized by unilateral hypoglossal and recurrent laryngeal nerve palsy, leading to tongue deviation, swallowing difficulty and dysphonia. Case report: We describe a case of a 17-year-old boy who reported a bilateral TS following head and neck trauma with Hangman's fracture and right common carotid artery dissection. The confirmation occurred only after complete cognitive and motor recovery, verifying the inability to protrude the tongue and swallow, associated with complete paralysis of the vocal cords, diagnosed with fiber optic laryngoscopy.An initial recovery of tongue motility and phonation occurred after just over a month of rehabilitation. Conclusion: In addition to the lack of awareness due to the rarity of the syndrome, the diagnosis of TS may be delayed in patients who are unconscious or who have slow cognitive recovery following head trauma. The case we present may help to increase awareness and avoid unnecessary diagnostic investigations.