Clinical Instructor of Surgery, Division of Vascular and .. Current Medical Diagnosis & Treatment (CMDT ) is the 54th edition of Guidelines for initiating antihypertensive therapy based on the UK's National Institute of Health and Care a LANGE medical book. CURRENT. Medical Diagnosis. & Treatment .. Assistant Clinical Professor, Chief of Podiatric Surgery. Division .. Oct;49( 5): [PMID: ]. H EALTH MAI NTENANCE & DISEASE. Copyright © by The McGraw-Hill Companies, Inc. All rights reserved. Except . Surgical & Medical Complications of Pregnancy. Surgical Disorders in Pregnancy .. Medical students will find Current Diagnosis & Treatment: Obstetrics.

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CURRENT Diagnosis and Treatment Surgery: Thirteenth Edition (LANGE CURRENT Series): Medicine & Health Science Books. Clinical guidelines - Diagnosis and treatment manual. edition. curative care at the dispensary and hospital levels. A list of current. Surgical & Medical Complications of Pregnancy. Section V. General only online. CURRENT Diagnosis & Treatment: Obstetrics & Gynecology, 11e.

Pre-clinical studies show that minocycline has a neuroprotective effect after SCI, improving motor function, reducing lesion size, and preserving axons [ 53 , 54 ]. Granulocyte Colony-Stimulating Factor Granulocyte colony-stimulating factor G-CSF is an endogenous glycoprotein known for its hematopoietic functions, including mobilization of bone marrow-derived stem cells to the blood.

Animal studies have reported numerous non-hematopoietic functions of G-CSF, including neuroprotective effects in SCI and stroke by preserving myelin, suppressing TNF-alpha and IL-1, promoting angiogenesis, and attracting stem cells to the injury site [ 55 ].

The exact mechanisms of FGF remain elusive and vary between acidic and basic FGF but include the neuroprotective effect of reducing glutamate-related excitotoxicity and enhancing axonal regrowth [ 56 ]. Pre-clinical studies show that intravenous or intrathecal administration of bFGF dramatically improves hind limb function in SCI rat models [ 57 ].

Inhibitors of Glutamate-Related Excitotoxicity Several other potential therapies also involve counteracting glutamate-related excitotoxicity. GM-1 gangioside Sygen is a membrane protein that reduces glutamatergic excitotoxicity and apoptosis and enhances neuritic sprouting [ 58 ].

Magnesium Mg is an established neuroprotective agent used in a host of neurological disorders, with theorized neuroprotective mechanisms of non-competitive antagonism of glutamate NMDA receptors, reduction of free radicals, and inhibition of inflammatory cytokines [ 59 ].

In animal studies, a formulation of Mg chloride in polyethylene glycol PEG to allow greater penetration of the blood—brain barrier facilitated better locomotor recovery than MP [ 60 ]. Furthermore, PEG itself has substantial neuroprotective properties, preserving or resealing axonal membranes and reducing oxidative stress [ 61 ]. Other Pharmacological Agents The pre-clinical field of SCI research is vast, and myriad other agents have been scrutinized for neuroprotective properties.

Erythropoietin has non-hematopoietic effects that inhibit apoptosis and inflammation and enhance angiogenesis [ 62 ]. Recombinant techniques have produced erythropoietin derivatives that avoid stimulating erythropoiesis but have yet to be tested in humans [ 62 ].

Rolipram is a phosphodiesterase 4 inhibitor with anti-inflammatory properties, shown to improve functional outcomes in rat SCI [ 63 ]. Of historical interest, three additional agents have been studied in human trials. Tirilazad, a synthetic aminosteroid specifically designed to inhibit peroxidation of membrane lipids, showed equivalent efficacy to MP in NASCIS III, but lack of a placebo—control and similar complication rates diminished further interest in this agent [ 65 ].

The endogenous thyrotropin-releasing hormone TRH is involved in the hypothalamic—pituitary axis, but animal studies revealed that it is also present in synaptic terminals in the spinal cord, and it facilitates motoneuron and sensory neuron excitability and improved function after SCI [ 66 ].

Further human study of this compound has yet to be reported. Regenerative Approaches Regenerative approaches focus on inducing or amplifying repair mechanisms rather than halting secondary injury. The optimal timing of these interventions remains to be determined—certain repair strategies may have greatest efficacy immediately after injury, whereas others are better suited to the chronic phase after secondary injury has abated.

The latter is the rational choice for interventions with substantial risk e. Cethrin The Rho signaling pathway regulates the cytoskeleton and motility and ultimately inhibits neuronal growth [ 68 ]. Inactivation of Rho or its downstream target Rho-associated kinase ROK stimulates neurite growth, profoundly improving motor function in animal models of SCI [ 68 ]. Cethrin is a paste formulation of BA, a bacterial-derived Rho-inhibitor, which can be applied directly onto the dura mater intraoperatively.

Further analysis of the data demonstrated a trend toward sensory improvement in thoracic patients [ 69 ]. A large multi-center phase III clinical trial will begin shortly [ 37 ]. NSAIDs The commonly used non-steroidal anti-inflammatory drugs NSAIDs , such as ibuprofen, also have inhibitory properties on the Rho pathway, prompting animal studies that demonstrated increased axonal sprouting [ 70 ].

A biological strategy to engineer monoclonal antibodies that are selective for Nogo-A has been shown to enhance the regeneration and reorganization of the injured spinal cord with intrathecal injection in rats and primates [ 71 , 72 ]. Chondroitinase ABC An alternative approach to regeneration targets the glial scar that forms at the injury site [ 73 ]. The glial scar forms as reactive astrocytes and microglia produce extracellular matrix proteins over a period of months, and this inhibits neurite outgrowth and blocks penetration of regenerative therapies.

The bacterial-derived enzyme chondroitinase ABC has shown beneficial effects in rodents by degrading sugar chains and chondroitin sulphate proteoglycans within the scar, promoting functional recovery [ 73 ].

It also appears that the therapeutic benefits of combination treatment with chondroitinase ABC and anti-Nogo-A are additive, hinting at the future prospect of multimodal SCI therapies [ 74 ]. Researchers are currently working on designing a human formulation of chondroitinase ABC for the purpose of phase I clinical testing. This compound has also shown promise in a primate model of cervical SCI, preserving corticospinal tract fibers and promoting improved hand function [ 75 ].

Stem Cells and Cell-Based Therapies The use of autologous cellular transplantation to repopulate and repair the injured spinal cord is a fascinating concept, but in reality, cell transplantation strategies may provide more benefit through indirect environmental modification i.

Transplanted stem cells from several sources and Schwann cells secrete key trophic factors and inhibitory signals that enhance neuronal survival, axonal outgrowth, and functional plasticity in various animal models [ 76 ].

However, recent technological advances allow cellular reprogramming with synthetic mRNA to produce induced pluripotent stem cells and differentiated neural cell types, which may drastically improve the success of direct repopulation strategies [ 77 ]. Most of these studies inject the cells intraspinally into the lesion site in the acute phase after injury.

Results suggest few adverse events, but these studies were not powered to detect functional improvements, and larger controlled studies are needed.

Yoon et al. Other phase II clinical trials that are active or planned include implantation of adult neural stem cells, adipose-derived stem cells, and BMSCs [ 42 , 43 , 44 ].

Bioengineered Scaffolds and Tissue Grafts An additional strategy of spinal cord regeneration involves the implantation of a structural construct that bridges the injury and permits axonal regrowth. Another approach involves the surgical implantation of peripheral nerve grafts, which also offers a structural conduit for axonal regrowth and provides neurotrophic factors [ 86 ].

Experience in animals suggests that axons have difficulty exiting the graft due to glial scarring, but recent work using chondroitinase appears to have facilitated certain axon subtypes successfully crossing and restoring function [ 87 ].

An additional alternative consists of self-assembling peptides that form cylindrical nanofibers in situ under physiological conditions [ 88 , 89 ].

These bio-engineered molecules are injectable and can be functionalized by incorporating bioactive agents such as neurotrophic factors [ 89 ]. The Future of SCI Management The future of SCI therapeutics lies in combinatorial strategies that address each mechanism of secondary injury and the multiple roadblocks to successful regeneration.

We should anticipate not only additive effects of various neuroprotective agents, regenerative drugs, cell therapies, and structural scaffolds but also supra-additive results due to the systematic elimination of each rate-limiting step.

This approach will add great complexity to the research due to the innumerable combinations and permutations of strategies that are possible, but early results in animal studies are strongly supportive of this methodology [ 74 , 87 ]. For maximum effect, these therapeutic tools must be studied and employed alongside the latest advances in rehabilitation and chronic SCI treatments, which include breakthroughs such as epidural electrical stimulation and functional electrical stimulation [ 90 , 91 ].

Conclusions Scientific evidence has informed our current best practices in diagnosis and acute management of SCI, providing a foundation for clinical practice. However, the SCI community must be prepared for dramatic changes in the years and decades to come, due to the accelerating pace of therapeutic discovery. Acute appendicitis AA is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway.

Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July , during the 3rd World Congress of the WSES, held in Jerusalem Israel , a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA.

The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: Acute appendicitis AA is a common cause of acute abdominal pain, which can progress to perforation and peritonitis, associated with morbidity and mortality.

The lifetime risk of appendicitis is 8. Despite numerous studies on AA, many unresolved issues remain, including aetiology and treatment.

The diagnosis of AA is a constellation of history, physical examination coupled with laboratory investigations, supplemented by selective focused imaging.

These can be used in combination in scoring systems. Various clinical scoring systems have been proposed in order to predict AA with certainty, but none has been widely accepted. The surgical treatment of AA has undergone a paradigm shift from open appendectomy to laparoscopic appendectomy, both in adults and now also in paediatric cases.

Over the last decade non-operative treatment with antibiotics has been proposed as an alternative to surgery in uncomplicated cases [ 2 ], while the non-surgical treatment played an important role in the management of complicated appendicitis with phlegmon or abscess [ 3 ].

Another major issue in management still open to debate is the timing of appendectomy and the safety of in-hospital delay. Moreover, there are debated recommendations on the type of surgical treatment and the post-operative management including antibiotic therapy. Diagnostic efficiency of clinical scoring systems and their role in the management of patients with suspected appendicitis - can they be used as basis for a structured management?

Routine vs selective imaging? CT or US or both? In what order? What is the natural history of appendicitis? Can appendicitis resolve without treatment? How common is it? Does in-hospital delay increasethe rate of complication or perforation? Is it safe to delay appendectomy?

Timing of appendectomy. Scoring systems for intra-operative grading of appendicitis and their clinical usefulness. What are the histopathological criteria for appendicitis of clinical importance? Minor inflammatory changes, early appendicitis, catarrhal appendicitis.

The criteria used will have an influence on the proportion of negative appendectomy, and also on evaluation of diagnostic performance. Non-surgical treatment of complicated appendicitis: Role of percutaneous drainage and Interval Appendectomy or immediate surgery.

Should Preoperative antibiotics prophylaxis be given? What antibiotics? When should postoperative antibiotics be given? Practical WSES algorithm for diagnosis and treatment of patients with suspected acute appendicitis. Speaker in Jerusalem CC Dr. Comparison of the most popular and validated clinical scores for the diagnosis of AA.

Migration of pain to the RIF f. More recently, attempts have been made to incorporate imaging findings into diagnostic scoring systems.

Atema et al. A diagnostic scoring system that incorporates imaging to the primary clinical diagnosis of acute appendicitis has not yet been developed [ 10 ].

What is the pathophysiology of the disease?

The Alvarado score is the most extensively studied score though this statement is biased by time; the Alvarado score has been around much longer than some of the newer scores, e. Its validity has been summarised in a recent meta-analysis [ 11 ] including patients in 29 studies. According to Ohle et al. Individual validation studies occasionally reported lower sensitivity, questioning the ability of the Alvarado score to reliably exclude appendicitis with a cut-off score of less than five [ 12 , 13 ].

However, these concerns are not supported by the pooled meta-analysis of those data [ 11 ]. According to the score, two cut-off points were identified to obtain three diagnostic test zones: Alvarado 0.

The AIR score has demonstrated to be useful in guiding decision-making to reduce admissions, optimize utility of diagnostic imaging and prevent negative explorations [ 16 ]. Diagnostic scoring systems may perform differently in adult and paediatric patients. In fact, at a practical level, several of the predictor variables may be difficult to apply e. The definition of a paediatric patient was not standardised among the studies, or clearly defined in the meta-analysis. Another systematic review compared the Alvarado score with the Paediatric Appendicitis Score, favouring the former [ 17 ].

The various derivation and validation studies investigating the different diagnostic scoring systems are troubled by various methodological weaknesses. Firstly, there is often inadequate definition of predictor variables, absence of reproducibility testing of predictor variables [ 18 ], lack of blinding and insufficient power [ 19 ].

Secondly, with regards to the participants, these studies often only include patients who an appendectomy was subsequently performed and for this reason potentially under-report false negatives. Such studies are questionable as the score is meant to be used on patients with suspicion of appendicitis, before all other diagnostic workup or selection.

Regrettably, due to these multiple factors, there is a great deal of heterogeneity among the diagnostic studies used to derive and validate the diagnostic scoring systems described. This heterogeneity, differences in treatment systems, and the fundamental demographic differences in treatment cohorts confound the direct applicability of these clinical studies in other practices.

No data are available to evaluate the ability of the published diagnostic scoring systems to improve clinical outcomes e. No cost analysis of diagnostic scoring system for the clinical diagnosis of acute appendicitis was identified. The sensitivity and specificity of the diagnostic scoring systems are inversely related. At the expense of specificity, scoring systems may be given sufficiently sensitive cut-off scores to exclude disease e.

However, none of the current diagnostic scoring systems can reach enough specificity to identify with absolute certainty which patients warrant an appendectomy. Statement 1. This remains an area for future research. The decision to do additional imaging of a patient with suspected appendicitis is based mainly on the complaints of the patient combined with findings at physical examination.

The clinical presentation is, however, seldom typical and diagnostic errors are common. A thorough clinical examination is often stressed as an essential part of diagnosis, with laboratory examinations as an adjunct to the gathered clinical information.

The review by Andersson [ 20 ] shows that each element of the history and of clinical and laboratory examinations is of weak discriminatory and predictive capacity. However, clinical diagnosis is a synthesis of information obtained from all these sources, and a high discriminatory and predictive power can be achieved by an accurate understanding of the relative importance of variables in combination.

When the values of two or more inflammatory variables found in laboratory are normal, appendicitis is unlikely. Conversely, appendicitis is very likely when the values of two or more inflammatory variables are increased [ 21 ]. Laboratory tests of the inflammatory response and the clinical descriptors of peritoneal irritation and migration of pain are the strongest discriminators and should be included in the diagnostic assessment of patients with suspected appendicitis.

What is the optimum pathway for imaging in patients with suspected acute appendicitis? Routine vs. Although several previous studies have shown discriminant factors in the differential diagnosis of AA and pelvic inflammatory disease PID in childbearing age women [ 24 — 29 ], imaging techniques such as US, CT or MRI may be required to reduce the negative appendectomy rate, with a low level of evidence currently available [ 30 , 31 ].

Occasionally there is a role for diagnostic laparoscopy particularly in younger female patients [ 32 ]. Right-sided diverticula occur more often in younger patients than do left-sided diverticula and because patients are young and present with right lower quadrant pain, they are often thought to suffer from acute appendicitis; it is difficult to differentiate solitary caecal diverticulitis from acute appendicitis.

In addition, selective focused imaging can be used for increasing the positive appendectomy rate imaging with aim to aid in diagnosing alternative diseases, who may not need surgery e. Although a careful balance of risk-benefit ratio is needed, particularly in young patients and women of childbearing age, routine use of CT scan has been demonstrated to be associated with lower negative appendectomy rates [ 35 ]. Furthermore, there is increasing evidence that spontaneous resolution of AA is common and that imaging can lead to increased detection of benign forms of the condition [ 36 ].

In view of the increased use of CT in children and concerns regarding radiation based imaging, the National Cancer Institute and the American Paediatric Surgical Association recommend use of non-radiation based imaging such as US where possible [ 37 ].

This rate is too high [ 39 ] and a tailored approach based on risk is sensible, especially in children. Universal imaging of patients with CT, apart from consuming resources, is not without health risks. It has been estimated that the benefit of universal imaging in avoiding 12 unnecessary appendectomies could result in one additional cancer death [ 40 ].

In pregnant women with suspected appendicitis a positive US requires no further confirmatory test. However, in case of appendix non-visualization on US, MRI is the recommended imaging exam, since it yields a high diagnostic rate and accuracy [ 41 — 43 ].

In settings having availability of such resource, MRI can also be considered for pediatric appendicitis imaging being a non-radiative imaging modality potentially valuable in the setting of negative ultrasound. Imaging is key in optimizing outcomes in appendicitis, not only as an aid in early diagnosis, but potentially reducing negative appendectomy rates.

Combining appropriate imaging with history, physical examination and laboratory tests are crucial to this [ 8 , 19 , 44 — 49 ]. Soreide in a recent PubMed search under the term appendicitis found over 20, articles, but few randomized trials, especially in imaging, have been undertaken with resultant variable level of evidence [ 50 ]. The surgeon has the responsibility of managing each case in the best way considering three possibilities: Estimating pre-image likelihood of appendicitis is important in tailoring management: Using scoring systems to guide imaging can be helpful [ 49 , 53 ].

Low risk patients being admitted to hospital and considered for surgery could have appendicitis ruled in or out by abdominal CT. A negative CT would generally allow the discharge of the patient with appropriate short outpatient-department follow-up [ 16 ].

Intermediate-risk classification identifies patients likely to benefit from observation and systematic diagnostic imaging. In the intermediate risk group an abdominal ultrasound would be the first line in imaging.

A positive ultrasound would lead to appendectomy and a negative test to either CT or further clinical observation. However, conditional CT imaging results in more false positives [ 9 , 54 ]. Performing serial US may improve accuracy and reduce the number of CT performed [ 56 ]. High-risk scoring patients may not require imaging in certain settings, nonetheless US or CT before surgery is routinely performed in western countries in such patients [ 16 ]. Standard reporting templates for ultrasound may enhance accuracy [ 40 ].

To optimize sensitivity and specificity three step sequential positioning or graded compression bedside may be beneficial [ 55 ], as opposed to radiology department. As described earlier, ultrasound is inferior to CT in sensitivity and its negative predictive value for appendicitis and may not be as useful for excluding appendicitis [ 60 ]. This is particularly true if the appendix was never visualized. False negatives are also more likely in patients with a ruptured appendix.

However, both strategies incorrectly classify up to half of all patients with perforated appendicitis as having simple appendicitis [ 62 ]. Scoring systems will enhance the ability to categorize whether appendicitis is simple or complex, showing that imaging is not a replacement for clinical examination. Finally, imaging may be undertaken by non-radiologists outside the radiology departments with variable results [ 63 ]. Unfortunately most of these patients in the USA are seen by emergency physicians and tests are ordered before the surgeon is called.

In children, an ultrasound is nearly always done. In the USA, logistics and legal concerns unfortunately impact our decision-making.

Despite the EU and the USA having similar access to health care, health technology and standards, they are very different healthcare systems with some inherent differences in the management strategies for appendicitis. One aspect that highlights this is the pre-operative imaging strategy for diagnosis. In the EU, only around Young males with typical histories and examination findings would go straight to theatre without any imaging.

Females would get an abdominal and pelvic ultrasound and laparoscopy if uncertainty exists. In addition, in the UK, appendectomy is widely regarded as a training operation that most registrars would perform independently.

Laparoscopic appendectomy is performed, especially in high volume units, during the daytime and when a consultant is present in theatre, but overall Statement 2. EL2, GoR B. EL 2, GoR B. EL 3, GoR B. The analysis of the epidemiologic and clinical studies that elucidate the natural history of appendicitis performed by Andersson in showed that not all patients with uncomplicated appendicitis will progress to perforation and that spontaneous resolution may be a common event [ 36 ].

Also the recent review published in The Lancet investigated the natural history of appendicitis and distinguished between normal appendix, uncomplicated appendicitis and complicated appendicitis, according to their macroscopic and microscopic appearance and clinical relevance. Actually, if this is related to the natural history of appendicitis or not is still unknown, but according to the authors these may be two distinct forms of appendicitis: Although the mortality rate is low, postoperative complications are common in case of complicated disease [ 67 ].

In order to elucidate the role of non-operative treatment of uncomplicated appendicitis, in Varadhan et al. The analysis did not find significant differences for treatment efficacy, length of stay or risk of developing complicated appendicitis [ 2 ].

The mean length of stay of those patients was 0. Of 22 patients with a long-term recurrence Recently, the RCT by Svensson et al. The authors concluded that the antibiotic treatment did not meet the pre-specified criterion for non-inferiority compared with appendectomy [ 71 ]. In the recent review published in the New Engl J Med by Flum it is stated that appendectomy should be considered the first-line therapy in uncomplicated appendicitis and recommended to the patient.

In the patients with equivocal clinical picture, or equivocal imaging, or in those who have strong preferences for avoiding an operation or with major comorbid medical problems it is reasonable to treat with antibiotics first [ 72 ]. However, an interesting still not well-studied topic is the role of spontaneous resolution of uncomplicated appendicitis.

In fact, the effect of the antibiotic treatment could be biased due to spontaneous healing as a result of the expectant management [ 47 ]. Statement 3. EL 1, GoR A. Current evidence supports initial intravenous antibiotics with subsequent conversion to oral antibiotics. There is inadequate evidence to recommend a routine approach at present EL2 GoR.

Does in-hospital delay increase the rate of complication or perforation? The management of most intra-abdominal acute surgical conditions has evolved significantly over time and many are now managed without emergency operation. Since the s, when Fitz and McBurney described emergency appendectomy, it has been the standard of care for suspected appendicitis.

This is based on the traditional model of appendicitis where initial obstruction causes inflammation and infection, and delay to operation allows increasing tension in the wall with ischemia, necrosis and perforation.

This pathophysiology probably does not fit with all cases of appendicitis, as discussed below, and emergency operation is not always needed. Whatever the cause for delay, the real issue is if it will lead to more complications: Others disagree and found that delaying surgical intervention did not put the patient at risk and may have actually improved patient outcomes [ 74 ].

The current diversity in practice appears to be caused by lack of high-level evidence although this is beginning to change. It should be noted that the danger of perforation is possibly overstated and that negative exploration is not benign [ 36 ].

Conservative management decreases the number of negative explorations and saves a number of patients with resolving appendicitis from an unnecessary operation. Andersson has shown that this leads to a high proportion of perforations among the operated patients but the number of perforations is not increased. The perforation rate, therefore, should not be used as a quality measure of the management of patients with suspected appendicitis [ 36 ].

He also notes that the increasing proportion of perforations over time is explained by an increase in the number of perforations according to the traditional model and mainly by selection due to resolution of non-perforated appendicitis according to the alternative model.

According to the second model, only a few perforations can be prevented by a speedy operation after the patients have arrived at the hospital. Neither of these models can be proved, but the second model is more consistent with the available data [ 36 ]. Similarly, others have found that the trends for non-perforating and perforating appendicitis radically differ and it is unlikely that perforated appendicitis is simply the progression of appendicitis resulting from delayed treatment [ 75 ].

There are numerous retrospective single institution reviews with contradictory results. Teixeira et al. There were three independent predictors of perforation: However, Ditillo et al. The risk of developing advanced pathology increased with time and it was associated with longer length of hospital stay and antibiotic treatment as well as postoperative complications [ 77 ].

The patient characteristics were similar in all three groups. No clinically significant difference was found in outcome measures, including overall morbidity and serious morbidity or mortality.

The authors concluded that the results did not change when disease severity was excluded from the model suggesting that there is no relationship between time from surgical admission and negative outcomes after appendectomy [ 78 ].

Busch et al. Perforation was associated with a higher re-intervention rate and increased hospital length of stay. As can be seen, the evidence is conflicting but recently higher level evidence has become available in the study by Bhangu et al. This was a prospective, multicentre cohort study of patients with acute appendicitis, of whom They found that timing of operation was not related to risk of complex appendicitis. In some jurisdictions, after hours surgery especially night time surgery is restricted to life or limb-threatening conditions as not all hospitals are staffed or equipped for safe h operating room availability.

In addition, especially in state funded health systems, where all expenditure has to be based on evidence, it is hard to justify after hours surgery for uncomplicated appendicitis.

There are now many randomised studies of initial antibiotic treatment for appendicitis. While not designed to look at delay to operation, they give indirect evidence of its safety in patients with uncomplicated appendicitis [ 2 , 71 , 80 ]. In summary, in the absence of level 1 evidence, the question of whether in-hospital delay is safe and not associated with more perforations cannot be answered with certainty. However, delays should be minimised wherever possible to relieve pain, to enable quicker recovery and decrease costs.

Statement 4. Open or Laparoscopic? Lavage or Aspiration of pus? Mesoappendix dissection: Stump Closure: Stapler or endoloop? Ligation or invagination of the stump? Primary or secondary closure of the wound?

Di Saverio. The most recent meta-analysis reported that the laparoscopic approach of appendicitis is often associated with longer operative times and higher operative costs, but it leads to less postoperative pain, shorter length of stay LOS and earlier return to work and physical activity [ 81 ] therefore lowering overall hospital and social costs [ 82 ], improved cosmesis, significantly fewer complications in terms of wound infection.

A trend towards higher incidence of intra-abdominal infection IAA and organ space collections was seen [ 83 ], although this effect seems decreased or even inverted in the last decade [ 84 ] and in more recent randomised controlled trials RCTs , being probably related to surgical expertise [ 85 ].

According to Sauerland et al. Seven studies on children were included, but the results do not seem to be much different when compared to adults.

Diagnostic laparoscopy reduces the risk of a negative appendectomy, but this effect was stronger in fertile women RR 0. The authors conclude the in those clinical settings where surgical expertise and equipment are available and affordable, diagnostic laparoscopy and LA either in combination or separately seem to have numerous advantages over OA [ 83 ].

Diagnosis and Acute Management of Spinal Cord Injury: Current Best Practices and Emerging Therapies

The overview by Jaschinski et al. The duration of surgery pooled by eight reviews was 7. The laparoscopic approach shortened hospital stay from 0. One review showed no difference in mortality [ 86 ]. Although LA is extremely useful especially as a diagnostic tool in fertile women, in can be used also in male patients, even if advantages over OA in this group are not clearly demonstrated [ 87 ]. A meta-analysis of prospective and retrospective comparative series evidences superiority of LA vs.

Dasari et al. Despite evidence which considers LA safe in pregnancy [ 94 ], advantages are minor less pain, less infections, less early deliveries if compared to the risk of fetal loss; more recent data from EL 2 reviews of comparative studies LA vs.

While fetal events are unknown, LA in pregnant patients demonstrated shorter OR times, LOS, and reduced complications and were performed more frequently over time. Even in perforated cases, laparoscopy appears safe in pregnant patients [ 97 ]. In conclusion, there is no strong current evidence as to the preferred modality of appendectomy, open or laparoscopic, during pregnancy from the prospect of foetal or maternal safety. However, low grade evidence shows that laparoscopic appendectomy during pregnancy might be associated with higher rates of foetal loss [ 98 ].

The literature does not clearly define the balance between advantages and disadvantages in this particular setting and the choice of the approach should be taken by the attending surgeon after a thorough discussion with the patient, balancing the advantages of laparoscopy vs.

A recent systematic review including more than Complicated appendicitis can be approached laparoscopically by experienced surgeons [ ], with significant advantages, including lower overall complications, readmission rate, small bowel obstruction rate, infections of the surgical site minor advantage following Clavien's criteria and faster recovery [ 89 , , ]. Regarding the costs, LA for complicated appendicitis can be performed with low cost equipment, allowing significantly lower overall costs operative plus LOS compared to open surgery [ ].

Statement 5. Laparoscopic appendectomy should represent the first choice where laparoscopic equipment and skills are available, since it offers clear advantages in terms of less pain, lower incidence of SSI, decreased LOS, earlier return to work and overall costs.

Laparoscopy offers clear advantages and should be preferred in obese patients, older patients and patients with comorbidities. Laparoscopy is feasible and safe in young male patients although no clear advantages can be demonstrated in such patients. Laparoscopy should not be considered as a first choice over open appendectomy in pregnant patients. EL 1, GoR B. No major benefits have also been observed in laparoscopic appendectomy in children, but it reduces hospital stay and overall morbidity.

In experienced hands, laparoscopy is more beneficial and cost-effective than open surgery for complicated appendicitis. Peritoneal irrigation is a practice traditionally used in case of localized or diffuse peritonitis and considered beneficial.

However, either in the past decades for open appendectomy or in the latest years for laparoscopic appendectomy, many others argued the efficacy of irrigation for cleansing purposes. The most recent studies, retrospective [ ] or RCTs, in laparoscopic or open appendectomy [ ], did not show any advantages in favour of intraoperative irrigation for prevention of postoperative IAA.

Instead, irrigation usually adds some extra-time to the overall duration of surgery [ ].

Clinical practice guideline on diagnosis and treatment of hyponatraemia

Furthermore, practice patterns may vary widely with regard to the amount and extent of irrigation and probably the common sense would suggest to avoid copious irrigation before achieving a careful suction first from every quadrant having purulent collections and to wash using small amounts of saline and repeated suction in order to avoid diffuse spreading of the infected matter into the remaining abdominal cavity, without forgetting to suck out as much as possible of the lavage fluid [ ].

Peritoneal irrigation does not have any advantages over suction alone in complicated appendicitis. Simplified and cost effective techniques for LA have been described [ ].

They use either two endoloops, securing the blood supply, or a small number of endoclips, appearing to be really useful in case of mobile cecum avoiding the need of an additional port. In addition, potential hazards of diathermy are avoided, the appendicular artery can be ligated under direct vision, and smoke is not created [ ]. With clips, anonabsorbable foreign body is left in the peritoneal cavity and may slip or become detached.

Moreover, it requires more experience especially in case of inflamed appendix with the risk of bleeding [ — ]. On the other hand, significant differences are present in surgical time and conversion to open rate [ ]. Diamantis et al. Between monopolar electrocoagulation, endoclip and Harmonic Scalpel no clinically significant differences were found in surgical time. All three methods gave acceptable complication rates. Because monopolar electrocoagulation requires no additional instruments, it may be the most cost-effective method for mesoappendix dissection in LA [ ].

However, the need of evacuate of the smoke could affect the pneumoperitoneum [ ]. There are no clinical differences in outcomes, LOS and complications rates between the different techniques described for mesentery dissection monopolar electrocoagulation, bipolar energy, metal clips, endoloops, Ligasure, Harmonic Scalpel etc.

EL3, GoR B. Monopolar electrocoagulation and bipolar energy are the most cost-effective techniques, even if more experience and technical skillsis required to avoid potential complications e. As for appendicular stump closure, stapler reduces operative time and superficial wound infections [ ], but higher costs 6 to 12 fold and no significant differences in IAA [ ], suggest the preference of loop-closure.

In perforated appendicitis the issue of using endoloops or stapler for appendicular stump closure needs further studies [ ]. The stump closure may vary widely in practice and the associated costs can be significant. Whilst earlier studies initially reported advantages with routine use of endostaplers in terms of complication and operative times [ ], more recent studies have repeatedly demonstrated no differences in intra- or post-operative complications incidence between either endostapler or endoloops stump closure [ ].

Although operative times maybe longer but it is probably biased by the learning curve [ ], the operative costs were invariably and significantly lower when endoloops are used [ , ]. A metanalysis confirmed that use of endo-loop to secure the appendicular stump during LA takes longer than endo-GIA but it is associated with equal hospital stay, perioperative complication rate, and incidence of intra-abdominal abscess [ ].

Endoloops were at least as safe and effective as endostapler also in paediatric population, without stump leaks nor differences in SSI and IAA in the group of non perforated appendicitis, whereas for perforated appendicitis, endoloops were perhaps safer than endostapler IAA incidence Many studies compared the simple ligation and the stump inversion and no significant differences were found [ , — ].

There are no clinical advantages in the use of endostapler over endoloops for stump closure for both adults and children. There are no advantages of stump inversion over simple ligation, either in open or laparoscopic surgery.

Mostly from paediatric experiences, it seems that the use of drainage and irrigation is associated with significantly longer operative times and LOS, without a decrease in post-operative infectious complications instead a non-significant trend to more frequent wound infection and dehiscence, more IAA and longer postoperative ileus [ ].

Previous studies in children with perforated appendicitis have already reported a significantly lower incidence of SSI and IAA and better postoperative course in the group treated without peritoneal drainage [ ]. This year, the meta-analyses by Cheng et al. The hospital stay was longer in the drainage group than in the no drainage group MD 2. Drains are not recommended in complicated appendicitis in paediatric patients.

Drains did not prove any efficacy in preventing intra-abdominal abscess and seem to be associated with delayed hospital discharge. EL1, GoR A. In the most recent metanalysis investigating the advantages of delayed primary wound closure DPC vs.

The Choice: Embrace the Possible

Two meta-analysis failed to prove the superiority of delayed primary skin closure in significantly reducing SSI odds ratio 0. Similar result were achieved also in the paediatric population [ ]. In addition, there is no evidence for any short-term or long-term advantage in peritoneal closure for non-obstetric operations [ ]. The systematic review by Swank et al. Most patients with malignant neoplasms, parasite infection and granulomatosis underwent additional investigation or treatment [ ].

Apart from the unexpected findings, there is a lack of validated system for histological classification of acute appendicitis and controversies exist on this topic. The paper by Carr proposes basic and classical but practical findings about the histological diagnosis of acute appendicitis. The author assesses three important disease aspects: The most important concept in the diagnosis of acute appendicitis is the transmural inflammation. According to the retrospective study by Grimes et al.

In this study, the policy of routine removal of a normal-looking appendix at laparoscopy in the absence of any other obvious pathology appeared to be an effective treatment for recurrent symptoms in those cases with a faecalith [ ]. The study by Van den Broek et al. On the other hand, in the retrospective study by Phillips et al. For this reason the authors would advocate the removal of a normal looking appendix in the absence of other explanatory pathology [ ]. Recently, Lee et al. The authors conclude that negative appendectomy should not be undertaken routinely during laparoscopy for right iliac fossa pain [ ].

In the Multicentre Appendectomy Audit by Strong et al. In order to evaluate the appendix during diagnostic laparoscopy, in Hamminga et al. However, the score still needs to be validated within a multicentre study [ ]. In also the AAST proposed a system for grading severity of emergency general surgery diseases based on several criteria encompassing clinical, imaging, endoscopic, operative, and pathologic findings, for eight commonly encountered gastrointestinal conditions, including acute appendicitis, ranging from Grade I mild to Grade V severe [ ].

In the recent multicentre cohort study by Strong et al. In particular, These findings suggest that surgeons' judgements of the intra-operative macroscopic appearance of the appendix is inaccurate and does not improve with seniority and therefore supports removal at the time of surgery [ ]. The prospective study by Gomes et al. The appendix was graded by the surgeon upon its visual appearance: This was then compared with a biochemical-histologic assessment of the removed appendix.

The sensitivity, specificity, and accuracy of the laparoscopic grading system were 63, The biochemical-histological diagnosis changed for 48 Most incorrect grading occurred in grades 0 and 1 appendicitis [ ]. The Gomes intraoperative grading score system is able to distinguish complicated appendicitis from uncomplicated cases has been externally validated [ ] and may be useful for guiding postoperative management e.

Statement 6. The incidence of unexpected findings in appendectomy specimens is low but the intra-operative diagnosis alone is insufficient for identifying unexpected disease. From the current available evidence, routine histopathology is necessary. There is a lack of validated system for histological classification of acute appendicitis and controversies exist on this topic.

EL 4, GoR C. We recommend adoption of a grading system for acute appendicitis based on clinical, imaging and operative findings, which can allow identification of homogeneous groups of patients, determining optimal grade disease management and comparing therapeutic modalities. De Moya. The study with highest level of evidence about the conservative treatment of complicated appendicitis with abscess or phlegmon is the meta-analysis by Simillis et al.

It included 17 studies 16 nonrandomized retrospective and one non-randomized prospective for a total of patients treated with conservative treatment and with appendectomy. No significant difference was found in the duration of the first hospitalization, the overall hospital stay and the duration of intravenous antibiotics [ ]. On the other hand, the recent randomized controlled trial by Mentula et al. The results showed that there was no difference in hospital stay between the two groups.

These data brought to the conclusion that several factors support the use of immediate surgery in patients with appendicular abscess [ ]. In the systematic review and meta-analysis by Andersson et al. In order to avoid this quite high chance of recurrence, some authors recommend routine elective interval appendectomy following the conservative management.

However, this procedure is associated with morbidity in The systematic review by Hall et al. In addition, the results showed 0. Overall, the complications reported included wound infection, prolonged postoperative ileus, hematoma formation, and small bowel obstruction, but the incidence of any individual complication was not determined [ ]. Because of its consistent morbidity, after successful conservative management, the routine indication to interval appendectomy is justified only in case of persistent or recurrent symptoms, and should be avoided in asymptomatic patients [ ].

Some authors recommend routine interval appendectomy, not to avoid the risk of recurrence, but to rule out possible appendicular neoplasia. In the retrospective study by Carpenter et al. Statement 7. Percutaneous drainage of a periappendicular abscess, if accessible, is an appropriate treatment in addition to antibiotics for complicated appendicitis.

Non-operative management is a reasonable first line treatment for appendicitis with phlegmon or abscess. Operative management of acute appendicitis with phlegmon or abscess is a safe alternative to non-operative management in experienced hands. Interval appendectomy is not routinely recommended both in adults and children. Interval appendectomy is recommended for those patients with recurrent symptoms.

EL 3, LoR C. In the last years use of antibiotics in patients undergoing appendectomy has been debated [ , ]. In a Cochrane meta-analysis supported that broad-spectrum antibiotics given preoperatively are effective in decreasing wound infection and abscesses. Randomised Controlled Trials RCTs and Controlled Clinical Trials CCTs in which any antibiotic regime were compared to placebo in patients suspected of having appendicitis, and undergoing appendectomy were analysed.

Forty-five studies including patients were included in this review.If hyponatraemia is unresolved, the initial diagnosis of the underlying cause was probably wrong or only part of the explanation. The advice is not graded and is only for the purpose of improving practical implementation. The most common examples include recommendations regarding monitoring intervals, counselling and referral to other clinical specialists. In , WHO issued conditional recommendations on a shortened treatment regimen for MDR TB, which comprises initial treatment for 4—6 months with kanamycin, moxifloxacin, prothionamide, clofazimine, pyrazinamide, high-dose isoniazid and ethambutol followed by 5 months of moxifloxacin, clofazimine, pyrazinamide and ethambutol.

Be aware that sometimes it may not be possible to assess an improvement in symptoms, e. It is composed of 2 wing-shaped lobes and an isthmus that connects them, which normally cannot be palpated through the skin on physical examination. Other novel short treatment regimens are also under investigation and have shown promising results thus far: the combination of pretomanid PA , moxifloxacin and pyrazinamide has shown favourable outcomes when used in treatment of drug-susceptible and MDR TB for 8 weeks in a phase 2b trial 99 ; a phase 3 trial entitled STAND Shortening Treatment by Advancing Novel Drugs is now underway Development of hyponatraemia may be related to myxoedema, resulting from a reduction in cardiac output and glomerular filtration rate If you agree to our use of cookies and the contents of our Privacy Policy please click 'accept'.

These include, but are not limited to, non-renal sodium loss, diuretics, third spacing, adrenal insufficiency, SIAD, polydipsia, heart failure, liver cirrhosis and nephrotic syndrome see sections 5.