Clinical outcome of anterior cruciate ligament reconstruction with modified transtibial and anteromedial portal.

Arthroscopic ACL reconstruction is the current standard care of treatment for anterior cruciate ligament (ACL) injuries. Modified transtibial (mTT) and anteromedial portal (AMP) techniques aim at the anatomical placement of femoral tunnel. Controversy existed in the literature with regard to the outcome of these techniques. Hence, we designed a retrospective comparative study to analyse the clinical and functional outcomes of mTT and AMP techniques. We hypothesized that there would be no difference between the clinical and functional outcomes in mTT and AMP techniques. This retrospective observational study was conducted in consecutive patients who underwent arthroscopic ACL reconstruction using semitendinosus-gracilis (STG) quadrupled graft in our tertiary care centre with a minimum follow-up of two years. Out of 69 patients, 37 had undergone ACL reconstruction by mTT technique and remaining by AMP technique. All the patients were assessed clinically by anterior drawer, Lachman's, pivot shift and single-legged hop test. Lysholm Knee Scoring Scale and International Knee Documentation Committee (IKDC) subjective knee evaluation score were used for the functional status. Knee instability was assessed objectively by KT-1000 arthrometer. There was no statistically significant difference in baseline demographic characteristics between mTT and AMP groups. At the end of 2 years, no statistically significant difference was noted in the anterior drawer and Lachman's test. Though not significant, IKDC scores and Lysholm's scores showed a better outcome in the AMP group when compared to the mTT group. AMP group showed significantly better outcome with KT-1000 arthrometer. Based on the results obtained, we presume that overall both mTT and AMP have similar functional outcome. However, as AMP technique offers significantly improved subjective rotational stability on pivot shift test, better hop limb symmetry index and KT 1000 readings compared to mTT, we suggest AMP over mTT.

Unmet needs, quality of life and psychological distress: insights regarding head and neck cancer patients in a rural setting.

OBJECTIVE: This study aimed to evaluate the perceived quality of life, unmet needs and psychological distress in patients with head and neck cancer in a rural setting in New Zealand. METHOD: Patients presenting with head and neck cancer in Northland, New Zealand, were asked to complete questionnaires on quality of life, unmet needs, and anxiety or depression together with a free-text option. RESULTS: About one quarter of respondents (27 per cent) scored high in the anxiety and depression scale, with corresponding diminished quality of life scores and increased needs. Over half of respondents (54 per cent) found it challenging to travel for treatment. Financial difficulties were encountered more frequently with indigenous patients. Rurality alone does not lead to significant differences in quality of life or needs. CONCLUSION: After treatment for head and neck cancer, it is important to monitor and manage patients' psychological distress and ease of access to health services to improve quality of life.

A Comparative Study Between Plate Fixation and Intramedullary Fixation for Displaced Mid-Shaft Clavicle Fractures in Adults.

Introduction: Clavicle fractures are frequently encountered by orthopaedic surgeons. Though multiple treatment techniques have been described in literature, open reduction and internal fixation with plating and intramedullary nailing are preferred in adults. This study analyses the functional outcome, complications, duration of bony union of mid-shaft clavicle fractures treated with plate fixation versus intramedullary fixation. Materials and methods: A quasi-experimental study was conducted on 38 patients with mid-shaft clavicle fracture aged between 18 to 60 years at a tertiary care centre in South India. Nineteen patients were treated by plate fixation and 19 patients underwent intramedullary nail fixation. Every alternate patient with mid-shaft fracture clavicle was treated with plate osteosyntheses or nailing. Results: The average age of presentation was 42 years in plate fixation and 31 years in nail fixation group. Robinson's classification type 2B1 was the most common type of fracture in both groups. The Visual Analogue Scale (VAS) score reduced significantly from pre-operative to postoperative day 1 in both the groups but there was no significant difference between the two groups. The Disabilities of the Arm, Shoulder and Hand (DASH) score at 6, 12 and 24 weeks reduced significantly in both the groups but showed no statistically significant difference between the two groups. However, intramedullary nail fixation group had a shorter duration of hospital stay and showed an earlier improvement in the DASH score during the first six months after surgery. Complications included implant loosening (three patients) in plating group and implant failures (two cases) in nailing group. Conclusion: There is a role for surgical intervention for certain cases of displaced and comminuted clavicle fracture in order to avoid malunion or non-union and their potential long-term sequelae. Both the surgical modalities of plating, and nailing provide good functional outcome and allow early return to occupational activities.

Effects of transplantation-related immunosuppression on co-existent neuroendocrine tumours.

BACKGROUND: Here we detail our experience of managing patients found to have a neuroendocrine neoplasm (NEN) whilst on immunosuppression for a transplanted organ. AIM: We aimed to quantify the behaviour of NENs under solid-organ transplant-related immunosuppression. DESIGN: This was an observational, retrospective case series. METHODS: Ten patients were identified from a prospectively kept database. Three were excluded. RESULTS: Four patients received a liver, two a kidney, and one a heart transplant. All but one received calcineurin-based immunosuppression. NENs were found in five patients post-transplant: one had surgery for transverse colonic neuroendocrine carcinoma NEC (pT4N1M0, Ki67 60%), was cancer-free after four years; one had cold biopsy of duodenal NEN (pT1N0M0, Ki67 2%), cancer-free at four months; one 7 mm pancreatic NEN (pT1N0M0), untreated and stable for seven years; one small-bowel NEN with mesenteric metastasis (pTxNxM1), alive four years after diagnosis; and one untreated small-bowel NEN with mesenteric metastasis, stable at 1 year after liver transplantation. Two NENs were discovered pre-transplant, one pancreatic NEN (pT1N0M0, Ki67 5%), remains untreated and stable at three years. One gastric NEN (type 3, pT1bN0M0, Ki67 2%) remains stable without treatment for two years. CONCLUSIONS: NENs demonstrate indolent behaviour in the presence of transplant-related immunosuppression.

Unusual contribution of the first jejunal vein in the formation of the portal vein.

Jejunum is drained into superior mesenteric vein through a series of jejunal veins. The way in which the first jejunal vein terminates is of great importance in upper abdominal surgery and radiological procedures. Knowledge of its variations is particularly important in surgical procedures like orthotropic hepatic transplantation, hepatic vein reconstruction, pancreatic surgery and surgical procedures of duodenojejunal junction. We saw a first jejunal vein opening directly into the portal vein. Further, the inferior mesenteric vein drained into the first jejunal vein. This case could be useful to gastroenterologists, general surgeons and radiologists.

Complete enclosure of gall bladder inside the lesser omentum - a rare anomaly.

Gall bladder is known for many congenital anomalies such as duplication, intrahepatic position, floating position etc. Most of its anomalies can be detected in ultrasound examination and radiography. We report an extremely rare congenital anomaly of gall bladder as observed in a male cadaver during dissection classes. The gall bladder was totally enclosed in the right free margin of the lesser omentum, in front of the usual contents of the right free margin of lesser omentum. The size, shape and blood supply of the gall bladder were normal. Though this anomaly might not cause any functional disturbances, it might result in complications during laparoscopic cholecystectomy.

Bifocal Stabilisation of Acute Acromioclavicular Joint Dislocation using Suture Anchor and Temporary K-Wires: A Retrospective Analysis.

Introduction: The acromioclavicular joint (ACJ) is a major link connecting the upper limb to the torso. The acromioclavicular and coracoclavicular (CC) ligaments help in stabilising the joint. We feel it is prudent to address both these ligament injuries, to achieve optimum result. This study was undertaken to analyse the results of a simple frugal surgical technique we used to deal with this injury considering stabilisation for both these ligaments. Materials and methods: In this retrospective study, skeletally mature patients with Type III, IV or V ACJ dislocations who underwent open reduction and stabilisation of the joint with temporary K-wires, repair of the capsule and augmentation of CC ligaments with suture anchors were included. Clinico-radiological and functional outcome was evaluated. Functional assessment of the upper limb was analysed using the Disabilities of Arm, Shoulder, and Hand Score (DASH), Constant shoulder score (CSS) and Oxford shoulder score (OSS). Results: Clinical and radiological evaluation of the 32 patients who had completed two years from the index surgery, was done. Out of the 37 patients included initially, five were lost in follow-up. Majority of the subjects included were males and type V was the most common injury. Mean pre-operative CC distance on the affected side was 13.92±4.94mm. In the immediate post-operative radiograph, it was 7.63±2.08mm and in the final follow- up was 9.36±2.75mm. Measurements were taken by two independent investigators and inter, and intra-observer reliability were analysed by Interclass correlation coefficient. Excellent functional outcome was noted despite the 1.81±1.50mm average loss of correction. At final follow-up, mean DASH score was 4.67±4.18, Oxford shoulder score was 44.06±2.44 and Constant shoulder score was 86.37±5.81. The severity of the injury had no significant effect on the functional outcome post our method of stabilisation and rehabilitation. Conclusion: Bifocal fixation restores the multidirectional stability of the disrupted ACJ. Adequate radiological reduction, good functional outcome and simplicity of execution make this technique an undemanding one for use in regular practice.

Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort.

Neuroendocrine neoplasms are known to have heterogeneous biological behavior. G3 neuroendocrine tumours (NET G3) are characterized by well-differentiated morphology and Ki67 > 20%. The prognosis of this disease is understood to be intermediate between NET G2 and neuroendocrine carcinoma (NEC). Clinical management of NET G3 is challenging due to limited data to inform treatment strategies. We describe clinical characteristics, treatment, and outcomes in a large single centre cohort of patients with gastroenteropancreatic NET G3. Data was reviewed from 26 cases managed at Queen Elizabeth Hospital, Birmingham, UK, from 2012 to 2019. Most commonly the site of the primary tumour was unknown and majority of cases with identifiable primaries originated in the GI tract. Majority of cases demonstrated somatostatin receptor avidity. Median Ki67 was 30%, and most cases had stage IV disease at diagnosis. Treatment options included surgery, somatostatin analogs (SSA), and chemotherapy with either platinum-based or temozolomide-based regimens. Estimated progression free survival was 4 months following initiation of SSA and 3 months following initiation of chemotherapy. Disease control was observed following treatment in 5/11 patients treated with chemotherapy. Estimated median survival was 19 months; estimated 1 year survival was 60% and estimated 2 year survival was 13%. NET G3 is a heterogeneous group of tumours and patients which commonly have advanced disease at presentation. Prognosis is typically poor, though select cases may respond to treatment with SSA and/or chemotherapy. Further study is needed to compare efficacy of different treatment strategies for this disease.

Impact of prolotherapy in temporomandibular joint disorder: a quality of life assessment.

Chronic pain and functional impairment associated with temporomandibular joint (TMJ) disorders (TMD) considerably reduce oral health-related quality of life (OHRQoL). In the present study we have assessed the influence of prolotherapy in patients with TMD by the subjective measurement of QoL using the Oral Health Impact Profile-14 (OHIP-14). Twenty-five patients diagnosed with TMD (mean (range) age 38 (18 - 70) years) were included. They had all undergone dextrose prolotherapy to the TMJ at regular time intervals (four times at intervals of two weeks) using the method suggested by Hemwall-Hackett. They were asked to answer the OHIP-14 questionnaire before and two years after prolotherapy. Seven domains of OHRQoL were rated on a 5-point Likert scale from 0 (never) to 4 (very often). Domain scores and total OHIP-14 scores were compared using inferential statistics (chi squared and Wilcoxon signed rank tests). Prolotherapy was effective over time, as all the domains' mean scores decreased considerably after treatment. The total mean score before prolotherapy was 21.20, which was extensively reduced to 13.08 after prolotherapy (p=0.001). There was statistically significant improvement in all domains, including functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap (p≤0.005 in all cases). We concluded that prolotherapy has a promising role in the improvement of OHRQoL of patients with TMD, and its beneficial effects persist at least two years after treatment.

Association of UGT1A6 gene polymorphism with clinical outcome in pediatric epileptic patients on sodium valproate monotherapy

Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5′-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.

Colonoscopy conversion after flexible sigmoidoscopy screening: results from the UK Bowel Scope Screening Programme.

AIM: In the UK Bowel Scope Screening Programme (BSSP), patients progress to colonoscopy based on high-risk features on flexible sigmoidoscopy (FS). We aim to assess the practice of colonoscopy conversion and predictors of detection of additional adenomas on colonoscopy. METHOD: The Bowel Cancer Screening database was interrogated and collated with endoscopic and histological findings from patients undergoing colonoscopy following FS between August 2013 and August 2016. Multivariate analysis was performed to identify predictors of new adenomas. RESULTS: FS was performed on 11 711 patients, with an adenoma detection rate (ADR) of 8.5% and conversion to colonoscopy in 421 (3.6%). The additional ADR at colonoscopy was 35.2%, with one additional malignant diagnosis (0.26%). The adenoma miss rate was 3.6%. On multivariate analysis, a polyp ≥ 10 mm was the only high-risk indication associated with additional ADR at colonoscopy (OR 3.68, 95% CI 1.51-3.65, P < 0.001), in addition to male gender (OR 2.36, 95% CI 1.46-3.83, P < 0.001). Predictors of detection of a new adenoma ≥ 10 mm included: villous adenoma (P = 0.002), polyp ≥ 10 mm (P = 0.007) and male gender (P = 0.039). The presence of any conversion criterion was associated with the detection of any proximal adenoma (P < 0.001) and adenoma ≥ 10 mm (P = 0.031). CONCLUSION: Male gender, polyps ≥ 10 mm and villous-preponderant histology at FS were predictors of adenomas < 10 mm and ≥ 10 mm at colonoscopy. Further data are required to assess the role for gender-based stratification of conversion criteria.

Clinicopathologic and molecular characterization of myeloid neoplasms with isolated t(6;9)(p23;q34).

INTRODUCTION: The t(6;9)(p23;q34);DEK-NUP214 [t(6;9)] abnormality is found in 0.7-1.8% of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). FLT3-ITD mutations are detected in t(6;9) patients. The t(6;9) abnormality is associated with poor outcomes. We studied the clinicopathologic and molecular profiles of patients with AML/MDS carrying t(6;9). METHODS: We collected clinical data of nine patients with AML/MDS with isolated t(6;9) (median age = 41 years; male/female = 4/5) and genotyped DNAs using whole exome, Sanger, and targeted sequencing. RESULTS: Our cohort was characterized by frequent multilineage dysplasia (56%), absence of phospho-STAT3/STAT5 expression, presence of myeloid markers (CD13, CD33, CD34, CD117, HLA-DR) with an aberrant expression of CD7, and poor outcome (median survival of 20 months). Although basophilia has been described in association with t(6;9), we observed lack of marrow basophilia in our cohort. Molecularly, 83% (5/6) of patients with AML/MDS with t(6;9) were characterized by at least one somatic mutation. Among them, four patients showed multiple mutations. FLT3-ITD mutations were detected in 33% of patients (2/6); 80% (4/5) of mutant patients died even after hematopoietic stem cell transplantation. CONCLUSION: Our data demonstrated that AML/MDS patients with t(6;9) have diverse molecular mutations regardless of the presence of FLT3 mutations, which may contribute to their poor survival outcomes.

The fibrinolytic system: A new target for treatment of depression with psychedelics.

Current understanding of the neurobiology of depression has grown over the past few years beyond the traditional monoamine theory of depression to include chronic stress, inflammation and disrupted synaptic plasticity. Tissue plasminogen activator (tPA) is a key factor that not only promotes fibrinolysis via the activation of plasminogen, but also contributes to regulation of synaptic plasticity and neurogenesis through plasmin-mediated activation of a probrain derived neurotrophic factor (BDNF) to mature BDNF. ProBDNF activation could potentially be supressed by competition with fibrin for plasmin and tPA. High affinity binding of plasmin and tPA to fibrin could result in a decrease of proBDNF activation during brain inflammation leading to fibrosis further perpetuating depressed mood. There is a paucity of data explaining the possible role of the fibrinolytic system or aberrant extravascular fibrin deposition in depression. We propose that within the brain, an imbalance between tPA and urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) and neuroserpin favors the inhibitors, resulting in changes in neurogenesis, synaptic plasticity, and neuroinflammation that result in depressive behavior. Our hypothesis is that peripheral inflammation mediates neuroinflammation, and that cytokines such as tumor necrosis factor alpha (TNF-α) can inhibit the fibrinolytic system by up- regulating PAI-1 and potentially neuroserpin. We propose that the decrement of the activity of tPA and uPA occurs with downregulation of uPA in part involving the binding and clearance from the surface of neural cells of uPA/PAI-1 complexes by the urokinase receptor uPAR. We infer that current antidepressants and ketamine mitigate depressive symptoms by restoring the balance of the fibrinolytic system with increased activity of tPA and uPA with down-regulated intracerebral expression of their inhibitors. We lastly hypothesize that psychedelic 5-ht2a receptor agonists, such as psilocybin, can improve mood through anti- inflammatory and pro-fibrinolytic effects that include blockade of TNF-α activity leading to decreased PAI-1 activity and increased clearance. The process involves disinhibition of tPA and uPA with subsequent increased cleavage of proBDNF which promotes neurogenesis, decreased neuroinflammation, decreased fibrin deposition, normalized glial-neuronal cross-talk, and optimally functioning neuro-circuits involved in mood. We propose that psilocybin can alleviate deleterious changes in the brain caused by chronic stress leading to restoration of homeostatic brain fibrinolytic capacity leading to euthymia.

Mental disorder in limb reconstruction: Prevalence, associations and impact on work disability.

OBJECTIVE: This cross-sectional survey aimed to assess the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD), and drug and alcohol dependence in a limb reconstruction population and examine associations with demographic and functional variables. METHODS: As part of routine clinical care, data were collected from 566 patients attending a tertiary referral centre for limb reconstruction between April 2012 and February 2016. Depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol and drug dependence were measured using standardised self-report screening tools. RESULTS: 173 patients (30.6% CI 26.7-34.4) screened positive for at least one of the mental disorders assessed. 110 (19.4% CI 16.2-22.7) met criteria for probable major depression; 112 (19.9% CI 16.6-23.2) patients met criteria for probable generalised anxiety disorder; and 41 (7.6% CI 5.3-9.8) patients met criteria for probable PTSD. The prevalence of probable alcohol dependence and probable drug dependence was 1.6% (CI 0.6-2.7) and 4.5% (CI 2.7-6.3), respectively. Patients who screened positive for depression, anxiety and PTSD reported significantly higher levels of pain, fatigue, and functional impairment. Depression and anxiety were independently associated with work disability after adjustment for covariates (OR 1.98 (CI 1.08-3.62) and OR 1.83 (CI 1.04-3.23), respectively). CONCLUSION: The high prevalence and adverse associations of probable mental disorder in limb reconstruction attest to the need for routine psychological assessment and support. Integrated screening and management of mental disorder in this population may have a positive impact on patients' emotional, physical and occupational rehabilitation. A randomised controlled trial is needed to test this hypothesis.

Length of stay and cost analysis of neonates undergoing surgery at a tertiary neonatal unit in England.

Introduction There is a lack of knowledge on the average length of stay (LOS) in neonatal units after surgical repair of common congenital anomalies. There are few if any publications reporting the activity performed by units undertaking neonatal surgery. Such activity is important for contracting arrangements, commissioning specialist services and counselling parents. The aim of this study was to describe postnatal LOS for infants admitted to a single tertiary referral neonatal unit with congenital malformations requiring surgery. Methods Data on nine conditions were collected prospectively for babies on the neonatal unit over a five-year period (2006-2011). For those transferred back to their local unit following surgery, the local unit was contacted to determine the total LOS. Only those babies who had surgery during their first admission to our unit and who survived to discharge were included in the study. Cost estimates were based on the tariffs agreed for neonatal care between our trust and the London specialised commissioning group in 2011-2012. Results The median LOS for the conditions studied was: gastroschisis 35 days (range: 19-154 days), oesophageal atresia 33 days (range: 9-133 days), congenital diaphragmatic hernia 28 days (range: 7-99 days), intestinal atresia 24 days (range: 6-168 days), Hirschsprung's disease 21 days (range: 15-36 days), sacrococcygeal teratoma 17 days (range: 12-55 days), myelomeningocoele 15.5 days (range: 8-24 days), anorectal malformation 15 days (range: 6-90 days) and exomphalos 12 days (range: 3-228 days). The total neonatal bed day costs for the median LOS ranged from £8,701 (myelomeningocoele) to £23,874 (gastroschisis). The cost of surgery was not included. Conclusions There is wide variation in LOS for the same conditions in a single neonatal unit. This can be explained by different types and severity within the same congenital anomalies, different surgeons and other clinical confounders (eg sepsis, surgical complications, associated anomalies). These data will enable us to give more detailed information to families following prenatal or postnatal diagnosis. They also allow more detailed planning of resource allocation for neonatal admissions.