Clinical Reassessment Research Articles

Assessing tumor response to neoadjuvant chemoradiation in rectal cancer with rectoscopy and 18F-FDG PET/CT: results from a prospective series.

rectoscopy and 18F-FDG PET/CT as a diagnostic algorithm for the assessment of tumor response in rectal cancer after neoadjuvant chemoradiation therapy (CRT) is very useful. this was a prospective longitudinal study in patients with locally advanced rectal cancer treated with neoadjuvant CRT. Patients were assessed after CRT completion with a digital rectal examination, proctoscopy and 18F-FDG PET/CT. Patients were subdivided as clinical (cCR) or radiologic (rCR) responders and non-responders according to tumor response. Clinical and radiological re-assessment was compared with the surgical specimen. Pathological tumor regression (pCR) grade was determined according to Mandard's classification. Of the 68 patients included, 15 (22 %) presented pCR in the surgical specimen and tumor persistence (non-PCR) was detected in the remaining 53 (78 %). Clinical assessment (DRE+ rectoscopy) identified 15 patients as cCR and 53 as non-cCR, two were false positives and two were false negatives. The overall accuracy was 94 %. 18F-FDG PET/CT identified 18 patients as rCR and 50 as non-rCR, one was a false positive and four were false negatives. The overall accuracy was 92 %. A combination of clinical findings and 18F-FDG PET/CT resulted in an accuracy of 96 %. The combination of clinical findings + 18F-FDG PET/CT was able to correctly identify all cases of pCR, with the exception of one case that presented a tumor regression of 80 %. In this series, 18F-PET-CT and clinical assessment had excellent accuracies in differentiating PCR from non-PCR after CRT completion. PET-CT combined with clinical assessment had a better accuracy than both modalities independently. 18F-FDG PET/CT is a valid tool that complements the clinical assessment of tumor response.

Cryptococcosis in a Cat

Background: Cryptococcosis is a mycosis that primarily affects domestic cats and is caused by fungi of the genus Cryptococcus, resulting in cutaneous, ocular, respiratory, and neurological manifestations. Diagnosis is based on the microscopic evaluation of the lesions and isolation of the causative agent. The aim of this study was to describe a case of feline cryptococcosis diagnosed by cytology and treated at the Veterinary Hospital of the State University of Santa Cruz (HV-UESC). Case:A 5-year-old uncastrated male cat was taken to the HV-UESC small animal clinic, owing to a gradual increase in the volume of the nasal plane spanning over a year, accompanied by respiratory distress. Upon physical examination, the animal was found to have regular nutritional status, dehydration, hypocorous mucosae, and enlarged popliteal lymph nodes. In addition, multifocal areas of ulceration on the body as well as increased volume in the nasal plane (clown nose) were observed. Peripheral blood samples were collected for complete blood count and biochemical analysis. Due to clinical suspicion of fungal lesions, fine needle aspiration of the nasal lesion was performed and cytological slides were sent to the HV-UESC histopathology laboratory. Probable diagnoses included rhinosporidiosis, cryptococcosis, and histoplasmosis. The animal was subjected to thoracic radiography in the imaging division of the HV-UESC. Blood counts revealed thrombocytopenia (130,000/mm3) and biochemical tests presented hypoproteinemia (3.2 g/dL), with hypoalbuminemia (1.52 g/dL); however, chest radiography did not show pulmonary alterations. Results of cytological analysis indicated pyogranulomatous inflammation associated with intracellular organisms, demonstrating a pathogen morphology similar to that of Cryptococcus spp. Before the diagnosis, itraconazole 5 mg/kg (1 capsule, twice a day for 30 days) and fipronil (1 ampoule 0.5 mL, on the back) were prescribed. Follow-up after 40 days showed a slight improvement in cutaneous lesions and respiration, and no other abnormalities were observed. At the follow-up, the owner disclosed that medication could not be administered at the prescribed frequency because of the animal often ran away from home and stayed without prescription. Due to unsatisfactory response to the first treatment, the dosage of itraconazole1 was increased to 10 mg/kg (1 capsule, twice a day, for 30 days) with a new regimen and follow-up after 15 days. However, the owner did not make a follow-up visit. A year later, after several attempts to contact the owner, we were notified that the treatment had been discontinued and the cat still presents with lesions. Discussion: Although cryptococcosis is not endemic, the cat roamed freely on the streets and may have been infected by inhaling the microorganism spores present in the environment. The clinical signs exhibited by the animal were consistent with the findings associated with Cryptococcus spp. infection in cats, especially the "clown nose" lesion. The cat, besides being dehydrated at the time of care, had a regular nutritional status. Cytology, the only diagnostic technique used in this case through which it was possible to visually identify the fungus, was definitive for the diagnosis of cryptococcosis. Although the prescribed treatment is one of the most indicated in such cases, it was not effective, possibly due to inadequate administration. The length of infection, discontinuation of therapy, and absence of follow-ups for clinical reassessment certainly contributed to an unfavorable prognosis.

Assessing transfusion practice in elective surgical patients: a baseline audit

BackgroundExternally generated hospital benchmarking data indicated that the blood transfusion rate within elective surgical orthopaedic and gastrointestinal patients at a metropolitan, tertiary healthcare facility was higher than comparable Australian hospitals. An investigation of transfusion practices was undertaken with the aim of understanding the reasons contributing to this higher incidence.Study MethodsA chart audit was undertaken of every major, elective, surgical orthopaedic and gastrointestinal patient who received a blood transfusion between July and December 2017. The audit aimed to ascertain whether patients were screened and treated for preoperative anaemia and measure the clinical appropriateness of transfusions according to the National Blood Authority (NBA) Perioperative Patient Blood Management (PBM) recommendations. The key recommendations include the utilisation of restrictive transfusion thresholds (in conjunction with clinical assessment) and the administration of a single unit followed by clinical reassessment.ResultsForty‐five patients had 72 transfusion episodes; 40% of episodes were considered inappropriate (n = 29). Of these, 76% (n = 22) did not have evidence of decompensation, and of the remaining that did (24%, n = 7), there was no evidence of clinical reassessment after transfusion. 42% (n = 19) of patients were anaemic preoperatively, of which only 21% (n = 4) had iron studies, and only one patient received intravenous iron preoperatively.ConclusionOpportunities exist to improve the preoperative anaemia screening processes and clinical decision‐making in transfusion practice. The baseline results of this audit will inform an improvement plan to develop interventions to enhance practice.

Time to positivity of blood cultures supports early re-evaluation of empiric broad-spectrum antimicrobial therapy.

BackgroundBlood cultures are considered the gold standard to distinguish bacteremia from non-bacteremic systemic inflammation. In current clinical practice, bacteraemia is considered unlikely if blood cultures have been negative for 48–72 hours. Modern BC systems have reduced this time-to-positivity (TTP), questioning whether the time frame of 48–72 hrs is still valid. This study investigates the distribution of TTP, the probability of blood culture positivity after 24 hours, and identifies clinical predictors of prolonged TTP.MethodsAdult patients with monomicrobial bacteremia in an academic hospital were included retrospectively over a three-year period. Clinical data were retrieved from the medical records. Predictors of TTP >24 hours were determined by uni- and multivariate analyses. The residual probability of bacteremia was estimated for the scenario of negative BCs at 24 hours after bedside collection.ResultsThe cohort consisted of 801 patients, accounting for 897 episodes of bacteremia. Mean age was 65 years (IQR 54–73), 534 (59.5%) patients were male. Median TTP was 15.7 (IQR 13.5–19.3) hours. TTP was ≤24 hours in 85.3% of episodes. Antibiotic pre-treatment (adjusted OR 1.77; 95%CI 1.14–2.74, p<0.01) was independently associated with prolonged TTP. The probability of bacteremia, if BC had remained negative for 24 hours, was 1.8% (95% CI 1.46–2.14).ConclusionWith adequate hospital logistics, the probability of positive blood cultures after 24 hours of negative cultures was low. Combined with clinical reassessment, knowledge of this low probability may contribute to prioritization of the differential diagnosis and decisions on antimicrobial therapy. As a potential antibiotic stewardship tool, this strategy warrants further prospective investigation.

Magnetic Resonance Imaging Procedure for Ventilated Intensive Care Patient in the International Islamic University Malaysia Medical Centre: Issues and Challenges

Managing a ventilated patient in the Intensive Care Unit (ICU) for Magnetic Resonance Imaging (MRI) procedure requires precise planning. Vigilant anesthetist with adequate MRI compatible monitoring of a critically ill patient and in preparation of any crisis event during transport to MRI suite, during MRI and return journey to ICU is essential. Problems in transporting ICU patient are usually equipment related, deterioration in gas exchange and increased rate of ventilator associated pneumonia. Preparation includes clinical reassessment for swift and systematic transport, airway management, optimum sedation and record keeping close to the patient. This is a case report of a 64 year-old gentleman who presented to International Islamic University Malaysia Medical Centre with right sided headache for one week associated with high intracranial pressure symptoms. His initial Glasgow Coma Scale (GCS) was 15/15 and Computed Tomography (CT) scan of his brain showed bilateral acute-on-chronic subdural haemorrhage, uncal herniation and minimal midline shift. His GCS dropped to 6/15 (E1V1M4) in the ward and proceeded with right craniectomy, evacuation of clot and duraplasty. Post operatively, his GCS improved to 15/15 in ICU and was extubated. On Day 2 post extubation, his GCS dropped to 6/15 (E1V1M4) and intubation was performed. Repeat CT Brain in ICU showed no evidence of new bleeding or mass effect. MRI was performed and it showed acute infarctions at right pons and right occipital region. Tracheostomy was done and the patient was sent to the general ward on fixed performance mask.

Are changes in objective observations or the patient’s subjective feelings the day after admission the best predictors of in-hospital mortality? An observational study in a low-resource sub-Saharan hospital

BackgroundThe first clinical re-assessment after admission to hospital probably provides the best opportunity to detect clinical deterioration or failure to improve, and decide if care should be intensified. AimCompare changes the day after admission in the patient’s subjective feelings and objective findings that included age, gender, the National Early Warning Score (NEWS) on admission, gait stability and mid-upper arm circumference (MUAC) on admission, and changes in NEWS, gait stability and mental alertness. SettingAcutely ill medical patients admitted to a low-resource sub-Saharan hospital. MethodsProspective observational study. Results1810 patients were reassessed 18 h after hospital admission. Logistic regression identified NEWS and gait stability on admission, a subjective feeling of improvement, the change in NEWS, and MUAC as clinically significant predictors of in-hospital mortality. Stratifying patients according to their NEWS on admission altered the predictive value of the four other predictors: for patients with an admission NEWS < 3 a subjective feeling of improvement is the most powerful predictor of a good outcome. For patients with an admission NEWS > = 3 the change in NEWS, gait stability on admission and MUAC provide additional prognostic information. ConclusionNEWS and gait stability on admission, MUAC, a subjective feeling of improvement, and change in NEWS the day after admission are all clinically significant predictors of in-hospital mortality.

1627P - Single arm prospective study evaluating the role of neoadjuvant chemotherapy in soft tissue sarcoma

Background: Surgery is the primary standard of care for localized soft tissue sarcoma (STS). In certain cases, upfront surgery may not be possible, or it may be mutilating and disfiguring. We conducted this study to evaluate the role of neoadjuvant chemotherapy in this setting. Methods: This single arm prospective study included patients of age ≥18 years with chemotherapy naïve STS of size ≥ 5 cm and which were grade II/III. These tumors were either upfront unresectable or possibly resectable with undesirable outcomes. Ewings sarcoma, osteosarcoma, rhabdomyosarcoma and other chemoresistant STS were excluded. The patients received three cycles of Ifosfamide (1.8 gm/m2 d1-d5) and epirubicin (60 mg/m2 d1-d2) followed by clinical and radiologic reassessment. The primary objective was overall response rate (ORR), and the secondary objective was to assess conversion to limb salvage surgery (LSS). Overall response was defined as complete response (CR) plus partial response (PR). Results: We included 36 patients in this study with a mean age of 36.9±14.7 years. The ratio male: female was 1.1. The most common histology in our cohort was synovial sarcoma [16 (44.4%)] followed by MPNST [5 (13.8%)]. Extremity [ 23 (63.8%)] was the most common site followed by trunk [8 (22.2%)] and head and neck [5 (13.8%)]. PR was seen in 14 (38.8%) patients, 16 (44.4%) patients had stable disease, three patients had progression and none of the patients had CR. The response could not be assessed in three patients. The ORR was 44.4%. LSS could be done for 13 (56.5%) patients with extremity STS. Ten patients with extremity STS required amputation despite neoadjuvant chemotherapy of which 6 (60%) patients did not give consent for amputation. The chemotherapy regimen was well tolerated, febrile neutropenia was seen in 12.5%. There was no treatment-related mortality. Conclusions: Neoadjuvant chemotherapy is an effective and safe option for unresectable STS or those who are resectable but require mutilating or disfiguring surgery. The acceptance of amputation as a mean of treatment of STS is low in our population. Clinical trial identification: CTRI/2017/07/008997. Legal entity responsible for the study: AIIMS. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Dravet syndrome in South African infants: Tools for an early diagnosis

PurposeDravet syndrome (DS) is a well-described, severe genetic epileptic encephalopathy with an increased risk of SUDEP. The incidence and genetic architecture of DS in African patients is virtually unknown, largely due to lack of awareness and unavailability of genetic testing. The clinical benefits of the available precision medicine approaches to treatment emphasise the importance of an early, correct diagnosis. We investigated the genetic causes and clinical features of DS in South African children to develop protocols for early, cost-effective diagnosis in the local setting. MethodWe selected 22 South African children provisionally diagnosed with clinical DS for targeted resequencing of DS-associated genes. We sought to identify the clinical features most strongly associated with SCN1A-related DS, using the DS risk score and clinical co-variates under various statistical models. ResultsDisease-causing variants were identified in 10 of the 22 children: nine SCN1A and one PCDH19. Moreover, we showed that seizure onset before 6 months of age and a clinical DS risk score of >6 are highly predictive of SCN1A-associated DS. Clinical reassessment resulted in a revised diagnosis in 10 of the 12 variant-negative children. ConclusionThis first genetic study of DS in Africa confirms that de novo SCN1A variants underlie disease in the majority of South African patients. Affirming the predictive value of seizure onset before 6 months of age and a clinical DS risk score of >6 has significant practical implications for the resource-limited setting, presenting simple diagnostic criteria which can facilitate early correct treatment, specialist consultation and genetic testing.

Clinical reassessment of human embryo ploidy status between cleavage and blastocyst stage by Next Generation Sequencing.

One of the most important limitations of genetic testing in preimplantation embryos is embryonic mosaicism, especially when performed on D3 with only a single blastomere evaluated. Previous publications, using Array-Comparative Genomic Hybridization (a-CGH) to compare day 3 (D3) biopsies versus trophectoderm biopsies for the analysis of aneuploid embryos, showed similar high concordance rates per embryo diagnosis for D3 biopsies and trophectoderm biopsies. Next generation sequencing (NGS) was introduced lately as a new technique for preimplantation genetic testing for aneuploidies (PGT-A). Using this technique, this retrospective descriptive study evaluated the degree of the concordance of the diagnosis between preimplantation human cleavage stage (D3) and blastocyst stage (D5) embryos. Double biopsies on D3 and D5 were performed on 118 embryos, reaching blastocyst stage on D5 and had not been selected for transfer. As the fertilization law of the United Arab Emirates does not allow embryo freezing, also surplus euploid embryos after D 3 biopsy were included.Analysis of the NGS results from D3 and D5 embryo biopsies showed a total concordance rate per embryo diagnosis of 85.6% for euploid and aneuploid embryos. The concordance rates per embryo chromosomal pattern for embryo diagnosed as aneuploid at both biopsy stages was 82.2%. However, the status regarding the affected chromosomes was not identical on D3 and D5. Hence, the total concordance rate between D3 biopsy and D5 biopsy was limited to 67.8%.This current study clearly demonstrated that the concordance rates between D3 and D5 biopsies in aneuploid and euploid embryos are lower than previously reported.

Pre-axial longitudinal hemimelia associated with humeral hypoplasia in dog: Case repor

Changes in embryogenesis may produce abnormalities in the structure or function of tissues and organs and these may be of genetic or environmental origin. The process known as organogenesis will depend on the interaction between endoderm, mesoderm and ectoderm, which will originate subsequent cellular movements, through the migration of precursor cells with the formation of the limb buds and thus causing cytodifferentiation, that is, in the formation of the limbs themselves. The disostoses, which are the set of congenital morphological alterations, are characterized by the abnormal development of a bone or part of it, which can affect the appendicular skeleton. Agenesis, or also known as hemimelia, consists of a rare character anomaly in which one or more paired bones have complete or partial absence, but among this rarity the most frequent is hemimelia in the unilateral form. The case report is a dog, SRD, presenting a left thoracic limb deformity, limping and unable to support it to the ground. Radiographic examinations of the limb were performed consecutively, which revealed the presence of pre-axial longitudinal hemimelia associated with humeral hypoplasia. It was decided to wait for the development of the animal for clinical reassessment and development of prosthesis in the affected limb.

The polynucleotide kinase 3\u2032-phosphatase gene (PNKP) is involved in Charcot-Marie-Tooth disease (CMT2B2) previously related to MED25

Charcot-Marie-Tooth disease (CMT) represents a heterogeneous group of hereditary peripheral neuropathies. We previously reported a CMT locus on chromosome 19q13.3 segregating with the disease in a large Costa Rican family with axonal neuropathy and autosomal recessive pattern of inheritance (CMT2B2). We proposed a homozygous missense variant in the Mediator complex 25 (MED25) gene as causative of the disease. Nevertheless, the fact that no other CMT individuals with MED25 variants were reported to date led us to reevaluate the original family. Using exome sequencing, we now identified a homozygous nonsense variant (p.Gln517ter) in the last exon of an adjacent gene, the polynucleotide kinase 3′-phosphatase (PNKP) gene. It encodes a DNA repair protein recently associated with recessive ataxia with oculomotor apraxia type 4 (AOA4) and microcephaly, seizures, and developmental delay (MCSZ). Subsequently, five unrelated Costa Rican CMT2 subjects initially identified as being heterozygous for the same MED25 variant were found to be also compound heterozygote for PNKP. All were heterozygous for the same variant found homozygous in the large family and a second one previously associated with ataxia (p.Thr408del). Detailed clinical reassessment of the initial family and the new individuals revealed in all an adult-onset slowly progressive CMT2 associated with signs of cerebellar dysfunction such as slurred speech and oculomotor involvement, but neither microcephaly, seizures, nor developmental delay. We propose that PKNP variants are the major causative variant for the CMT2 phenotype in these individuals and that the milder clinical manifestation is due to an allelic effect.

Pantarsal arthrodesis with a customized titanium medial plate in a dog

Background: Tibiotarsal joint luxations are mostly traumatic and due to automobile accidents. The arthrodesis of this joint is considered the fnal solution for trauma with ligament lesions without repair, luxations without possibility of joint recovery and chronic joint diseases. The direction to which the joint is dislocated is associated with the forces of trauma, and bilateral ligament injuries are not uncommon. However, the medial ligaments are more frequently injured. The aim of this study is to describe the performance of pantarsal arthrodesis using a customized titanium plate for application to the medial surface of the joint. Case:An undefned breed dog, weighing 21.5 kg, was attended at the Veterinary Hospital of the Federal University of Lavras (UFLA) with history of trauma and injury in the right pelvic limb. After physical and radiographic examinations it was diagnosed with an exposed luxation of the tibiotarsal joint and tissue loss in the region. The tibiotarsal region was cleaned and a bandage was made daily until the frst surgical procedure, which occurred fve days later. Initially, it was treated without success with the use of a transarticular external fxator1. Subsequently, pantarsal arthrodesis was performed using a customized titanium angled plate (Made by a private manufacturer based on the functional angulation of the tibiotarsal joint of the contralateral limb). The joint was accessed for exposure of the distal portion of the tibia, tarsal and metatarsals bones. Wear of the articular surfaces was performed and then the customized angulation plate for pantarsal arthrodesis was placed on the medial side of the joint. Bicortical drillings were performed, starting with the proximal orifce. According to the holes of the plate, fve 3.5 mm diameter screws1 (four at the distal tibia and one at the tarsus) and four 2.7 mm diameter screws were used in the metatarsal bones. Two isolated 3.5 mm diameter screws were also used, one inserted through the tibiotarsal joint and another connecting the calcaneus to the distal tibia. Muscle fascia, subcutaneous tissue and skin sutures were performed in a conventional manner. In the postoperative period, surgical wound cleaning and partial activities restrictions were recommended for 30 days. After 10 and 45 days of the surgical procedure, the animal appeared for clinical and orthopedic reassessment. The patient showed functional support of the limb and the radiographic exams revealed a proliferative bone reaction in the interarticular regions. Discussion: The present report describes the use of a specifc type of plate for pantarsal arthrodesis that has gained prominence in international veterinary orthopedics and is increasingly being used. In Brazil, the angled plate for medial application still has limited manufacturing, and its importation entails high costs and delay in delivery, which makes diffcult its use depending on the fnancial conditions of the owner and the possibility of waiting to perform the procedure. In the present report, 10 days after the surgical intervention, the animal already had partial support of the injured limb and surgical wound with good healing. In the orthopedic examination at 45 postoperative days, the animal showed satisfactory support and functional use of the member submitted to arthrodesis. It was concluded that the personalized plate for pantarsal arthrodesis proved to be a satisfactory method, which promoted adequate interarticular stability and favored bone proliferation and fusion. Keywords: dislocation, tibiotarsal joint, traction injury

Cardiac and Vascular Surgery-Associated Acute Kidney Injury: The 20th International Consensus Conference of the ADQI (Acute Disease Quality Initiative) Group.

Acute kidney injury (AKI) occurs in 7% to 18% of hospitalized patients and complicates the course of 50% to 60% of those admitted to the intensive care unit, carrying both significant mortality and morbidity.[1][1] Even though many cases of AKI are reversible within days to weeks of occurrence, data

An Update on the Global Initiative for Chronic Obstructive Lung Disease 2017 Guidelines With a Focus on Classification and Management of Stable COPD.

The 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines offer important changes to the assessment and management of stable COPD of importance to practitioners, respiratory therapists, pharmacists, and nurses who care for patients with COPD. Therapies are now chosen based on the burden of symptoms and the history of COPD exacerbations, and inhaler regimens are modifiable based on continual clinical reassessment. Although identifying the degree of airway obstruction remains important for informing the clinical status of the patient with COPD, FEV1 is no longer used to direct the therapeutic approach. Therapies and modes of inhaled medication delivery for each GOLD grouping have been modified and reflect the need for reevaluation of patient symptoms and COPD exacerbation history as an indicator to add or withdraw therapies. As the knowledge of this important disease continues to expand, exacerbation and symptom prevention in patients with stable COPD will remain as an important target of COPD therapies and research. Novel drug combinations and delivery devices are sure to positively affect the practitioner's approach to patients with stable COPD. The new 2017 GOLD guidelines represent a step toward personalized care of the patient with COPD.

CLINICAL DECISION MAKING AND DIFFERENTIAL DIAGNOSIS IN A CYCLIST WITH UPPER QUARTER PAIN, NUMBNESS, AND WEAKNESS: A CASE REPORT

Differentiating between cervical nerve root and peripheral nerve injuries can be challenging. A phenomenon known as double crush syndrome may increase the susceptibility to injury and symptoms at other locations along the course of the nerve. The purpose of this case report is to describe the physical therapy differential diagnosis and management of a cyclist with upper extremity pain, weakness, and paresthesia. The subject was referred to physical therapy with a diagnosis of cervical disc disease. His chief complaints were chronic neck and right shoulder pain as well as a recent onset of right hand numbness and weakness following 100-mile bike ride one month prior. Diagnostic imaging revealed multi-level degenerative changes of the cervical spine. Initial electromyography and nerve conduction studies (EMG/NCS) indicated right ulnar neuropathy at the elbow. The ultimate incorporation of ulnar nerve mobilizations in various positions immediately decreased symptoms. In light of the subject's improvement after ulnar nerve mobilizations, imaging findings, and EMG/NCS findings, the subject's presentation was consistent with a double crush syndrome with C8 nerve root compression and distal ulnar nerve compression at the elbow. The subject demonstrated full resolution of all symptoms, 0% disability on the Neck Disability Index, 8.3% disability of the Disabilities of the Arm, Shoulder, and Hand questionnaire, normal EMG/NCV findings, and unrestricted return to work and endurance cycling at three months and maintained at one year. He did not require hand surgery. This case report highlights the importance of continual clinical re-examination and re-assessment with ancillary diagnostic testing, especially if chosen interventions are not eliciting desired responses. The identification of key risk factors, such as occupation and recreational activities is imperative in achieving the most efficacious clinical treatment. In this case, the recognition of a double crush syndrome assisted in optimizing the physical therapy plan of care and the subject ultimately achieving full recovery. Level 4.

Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy

Macular and cone/cone-rod dystrophies (MD/CCRD) demonstrate a broad genetic and phenotypic heterogeneity, with retinal alterations solely or predominantly involving the central retina. Targeted next-generation sequencing (NGS) is an efficient diagnostic tool for identifying mutations in patient with retinitis pigmentosa, which shows similar genetic heterogeneity. To detect the genetic causes of disease in patients with MD/CCRD, we implemented a two-tier procedure consisting of Sanger sequencing and targeted NGS including genes associated with clinically overlapping conditions. Disease-causing mutations were identified in 74% of 251 consecutive MD/CCRD patients (33% of the variants were novel). Mutations in ABCA4, PRPH2 and BEST1 accounted for 57% of disease cases. Further mutations were identified in CDHR1, GUCY2D, PROM1, CRX, GUCA1A, CERKL, MT-TL1, KIF11, RP1L1, MERTK, RDH5, CDH3, C1QTNF5, CRB1, JAG1, DRAM2, POC1B, NPHP1 and RPGR. We provide detailed illustrations of rare phenotypes, including autofluorescence and optical coherence tomography imaging. Targeted NGS also identified six potential novel genotype-phenotype correlations for FAM161A, INPP5E, MERTK, FBLN5, SEMA4A and IMPDH1. Clinical reassessment of genetically unsolved patients revealed subgroups with similar retinal phenotype, indicating a common molecular disease cause in each subgroup.

Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes

BackgroundOral clefts, that is, clefts of the lip and/or cleft palate (CL/P), are the most common craniofacial birth defects with an approximate incidence of ~1/700. To date, physicians stratify patients...

Selective nonoperative management of penetrating thoracic injury.

Thoracic penetrating injury is a cause for up to one-fifth of all non-natural deaths. The aim of this study was to determine the success of selective nonoperative management (SNOM) of patients presenting with a penetrating thoracic injury (PTI). This was a prospective study of patients with PTI who presented to a level 1 Trauma Center between April 2012 and August 2012. A total of 248 patients were included in the study, with 5.7% (n=14) requiring immediate emergency surgery. Overall, five of these 248 patients died, resulting in a mortality rate of 2.0%. Primarily 221 patients (89.1%) were managed with SNOM, of whom 15 (6.8%) failed conservative management. Failure of SNOM was primarily caused by complications of chest tube drainage (n=12) (e.g. retained clot, empyema) and delayed development of cardiac tamponade (n=3). The survival rate in the SNOM group was 100%. PTI has a low in-hospital mortality rate. Only 16.5% (41/248) of the patients presenting with PTI will need surgical treatment. The other patients are safe to be treated conservatively according to a protocolized SNOM approach for PTI without any additional mortality. Conservative treatment of patients who were selected for this nonoperative treatment strategy with repeated clinical reassessment was successful in 93.2%.

Clinical reassessment of post-laboratory variant call format (VCF) files

Background: Next-generation sequencing has been leading the genetic study of human disease for the past 10 years, generating a huge amount of sequence variant data, which are stored in variant call format (VCF) files. The aim of the study was to reassess the utility of VCF files for reanalysis. Methodology: This is a descriptive observational study of Saudi patients with undiagnosed genetic conditions. VCF files from 20 samples were referred to the molecular laboratory by physicians for reanalysis using variant interpretation software. Results: Seven cases (n = 20) have been reported differently from the outside laboratory. This accounts for almost 35% of all cases and is mainly due to the ability to gather more information about the patient's phenotype. One whole-genome sequence (WGS) case changed from inconclusive to negative. In addition, we identified variants related to the patient's phenotype in six cases; two of them were WGS and four were whole-exome sequence, all reported as negative before the reanalysis. Conclusion: Comprehensive phenotyping of individuals is a crucial step in identifying candidate phenotype-related variants. We outline the benefit obtained from access to the patient's medical records and communication with referring physicians.

ULTRASONOGRAPHY VERSUS COMPUTED TOMOGRAPHY IN DIAGNOSIS OF ACUTE APPENDICITIS

Background: Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Imaging methods, such as ultrasonography (US) and computed tomography (CT), aimed at avoiding a misdiagnosis and facilitating earlier surgery, when necessary, have become increasingly important for decreasing the morbidity of the disease. Objective: This study aimed to compare the accuracy of US and CT in the diagnosis of AA. Patients and Methods: After local ethical approval and written consent taken, 107 patients with signs and symptoms suggesting AA, selected from emergency department of Al-Azhar University Hospital, New Damietta during the period from March, 2016 to April 2017. They were 63 males and 44 females, mean age was 17.09±3.02 years. 90 (84.11%) underwent surgery, and 17 patients (15.9%) were hospitalized for clinical observation after imaging (12 patients (11.2%) were dismissed from the hospital while 5 cases (4.7%) presented with positive CT findings underwent surgery). After history taking, full clinical examination and laboratory investigations, all patients were subjected to US and CT examination. All patients were reevaluated clinically, and a correlation was made between both sets of results. Accordingly, final decision was made. Accuracy was ascertained intra-operatively for those underwent appendectomy, and the results were compared with those found by radiological examination. The results were correlated with surgical and histopathologic findings. Results: Males affected more than females, and abdominal pain was present in 100%. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of US in diagnosis of AA in our study were found to be 91.7 %, 77.8 %, 94.3%, 70.0% and 88.9 % respectively.The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of CT in diagnosis of AA were 98.8 %, 88.9 %, 98.8%, 88.9% and 97.8 % respectively. Conclusion: US should be the first-line imaging modality. As US sensitivity is limited, and non-confirmed US examinations, diagnostic strategies and algorithms should focus on clinical reassessment and CT examination.