Aggressive Protocol Research Articles

Clinical and MRI findings in patients with pediatric optic pathway glioma presenting with initial leptomeningeal dissemination

AIMAlthough leptomeningeal dissemination (LMD) is a hallmark of malignant brain tumors, optic pathway glioma (OPG) of various grades can initially present with LMD, which is thenceforth interpreted as an aggressive tumor. In this study, we aimed to evaluate the clinical and imaging findings of pediatric OPG (POPG) patients who presented with initial LMD to ensure a prompt diagnosis and better outcomes. MATERIALS AND METHODSBetween 2000 and 2022, 35 pediatric patients with pathologically proven OPG who presented with and without LMD at our institute were retrospectively reviewed. We compared the demographic and histopathology characteristics, MRI features, and clinical outcomes of the initial LMD group and the non-LMD group. RESULTSCompared with those in the non-LMD group (n=27), POPGs in the LMD group (n=8) were more symmetrically midline-positioned (75% versus 22.2%, p=0.006) and had more ill-defined tumor borders (25% versus 0%, p=0.007), and patients were more likely to develop hydrocephalus (100% versus 63%, p=0.042). There was no significant difference regarding the histopathology (p=0.686) and outcome of tumor recurrence/progression (p=0.341). However, the mortality rate was higher in the LMD group than in the non-LMD group (62.5% versus 18.5%, p=0.016). CONCLUSIONSFeatures of a more symmetrical midline-positioned POPG with indistinct tumor borders and hydrocephalus are risk factors for initial LMD regardless of histopathology. Compared with those without initial LMD, patients with POPG with initial LMD had poorer outcomes, which may suggest the need for a more aggressive treatment protocol.

Effectiveness and Safety of mRNA Vaccines in the Therapy of Glioblastoma.

Glioblastoma (GBM) is the most common and most malignant primary brain tumor, presenting significant treatment challenges due to its heterogeneity, invasiveness, and resistance to conventional therapies. Despite aggressive treatment protocols, the prognosis remains poor, with a median survival time of approximately 15 months. Recent advancements in mRNA vaccine technology, particularly the development of lipid nanoparticles (LNPs), have revitalized interest in mRNA-based therapies. These vaccines offer unique advantages, including rapid production, personalization based on tumor-specific mutations, and a strong induction of both humoral and cellular immune responses. mRNA vaccines have demonstrated potential in preclinical models, showing significant tumor regression and improved survival rates. Early-phase clinical trials have indicated that mRNA vaccines are safe and can induce robust immune responses in GBM patients. Combining mRNA vaccines with other immunotherapeutic approaches, such as checkpoint inhibitors, has shown synergistic effects, further enhancing their efficacy. However, challenges such as optimizing delivery systems and overcoming the immunosuppressive tumor microenvironment remain. Future research should focus on addressing these challenges and exploring combination therapies to maximize therapeutic benefits. Large-scale, randomized clinical trials are essential to validate the efficacy and safety of mRNA vaccines in GBM therapy. The potential to reshape the tumor microenvironment and establish long-term immunological memory underscores the transformative potential of mRNA vaccines in cancer immunotherapy.

Ethambutol-induced optic neuropathy: Another conundrum

Purpose: The purpose was to study the effect of ethambutol (EMB) and cause for optic neuropathy in the hope that better understanding of the condition will help us to reduce the burden of visual loss. Materials and Methods: A retrospective analysis of patients with EMB-induced optic neuropathy was done, which included 30 patients attending our outpatient department from January 2022 to March 2022. Results: The mean age was 53.73 with male (70%) preponderance. Visual fields showed bitemporal hemianopia in 43% (13), temporal field defects in 26% (8), centrocecal scotoma in 17% (5), and low reliability in 10% (3). Visual evoked potential amplitude was reduced in 87% (26). Magnetic resonance imaging showed enhancement of optic chiasma in 40% (12). After discontinuing and replacing EMB, with Vitamin B complex and zinc supplements, 53% (16) had visual improvement on 1-month follow-up. Conclusion: India has launched the Pradhan Mantri TB Mukt Bharat Abhiyan “Ni-kshay 2.0” portal to eradicate tuberculosis by 2025. Hence, aggressive treatment protocols are underway. The increased duration of EMB in new directly observed therapy short-course regimen has caused increased incidence of EMB optic neuropathy. Regular screening is needed to diagnose and prevent further visual deterioration in these patients. Timely replacement of the drug with another drug is a key in visual recovery of these patients. Further studies are needed to assess if the genetic predisposition is responsible for optic nerve damage.

Clinical Profile, Toxicities, and Survival Outcome of MCP841 in Pediatric Acute Lymphoblastic Leukemia in Current Era: A Retrospective Study from Eastern India

Abstract Introduction: The overall survival in pediatric acute lymphoblastic leukemia (ALL) ranges from 45 to 81% in India. Aggressive chemotherapy protocols like MCP841 have improved the outcome and it can be delivered with minimal supportive care. This study retrospectively analyses the clinical profile and overall survival of patients treated by this protocol. Objective: This single-center study aims to estimate the event-free survival of patients treated accordingly to the MCP841 protocol with high-dose cytarabine (HDAC) at 2 g/m2 as the backbone, along with the risk-stratified incidence and cause of mortality in childhood ALL. Material and Methods: Records of 156 patients aged 1 to 19 years, newly diagnosed with ALL from June 2009 to August 2013 who were treated according to the forementioned protocol were analyzed. Risk stratification for both precursor B-cell ALL (B-ALL) and T-cell ALL (T-ALL) was done, followed by an analysis of the correlation of risk-stratified groups with mortality and survival outcomes. Result: Precursor B-ALL was found in 70% patients (including 69.7% [n = 76] standard risk, 20.1% [n = 22] intermediate risk, and 10% [n = 11] high risk), while 30% had T-ALL (including 74.4% [n = 35] standard risk and 25.5% [n = 12] high risk). Death during induction occurred in 0.04% (n = 5) precursor B-ALL and 23% (n = 11) T-ALL patients. The causes were infection in 62.5%, hemorrhage in 25%, and cortical venous thrombosis in 12.5%. Among those who attained remission (89.7%, n =140), relapse occurred in 26% (n = 27) precursor B-ALL and 28% (n = 10) T-ALL patients. Approximately 31% patients died in the postinduction phase, with progressive disease due to relapse being the most common cause and bone marrow the most common site. Event-free survival at 168 months for overall population, precursor B-ALL, and T-ALL was 59, 62.4, and 51.1%, respectively. Conclusion: A comparable survival outcome in par with similar centers in developing countries with the MCP841 protocol was found. Infections are a major cause of mortality during treatment, especially when associated with malnourishment. Relapsed disease and poor salvage rates remain a major hurdle to achieving better survival in developing countries; however, better supportive care and infection control measures along with implementing risk-stratified high-dose chemotherapy protocols might improve outcome in the future.

Field assessment of potential exposure of dogs to leptospirosis by measuring antibody titers in dogs: a multisite study in five geographic regions of the United States.

Leptospirosis vaccine for dogs in the United States is considered a lifestyle or non-core vaccine, making individual veterinary practitioners responsible for determining if vaccination is necessary for their patients. Veterinary professionals often base their vaccination decisions on local rates of clinical cases. However, even subclinical leptospirosis infections have zoonotic potential. The microscopic agglutination test (MAT) is effective for screening unvaccinated animals, but previous vaccination can lead to inconsistent results and variable MAT titers over time. This prospective research survey evaluated if local experience was sufficient to justify selective vaccination for leptospirosis. MAT analyses were performed on sera collected from well-cared-for, unvaccinated dogs residing in five different geographies across the United States: South-Central (East Texas), New England, the Mid-Atlantic (North Carolina and Virginia), Midwest (Wisconsin/northern Illinois), and Southwest (southern California). Thirty-eight clinics participated, submitting a total of 1345 qualified samples from unvaccinated dogs over 1 year of age. 11.6% of these unvaccinated dogs had MAT titers for one or more serogroups of Leptospira. While seropositivity does not necessarily indicate that disease will result or that a specific serovar is involved, these MAT-positive cases do indicate that the potential for exposure exists and clinical signs or a carrier-state could result from infection. These survey results would indicate that a more aggressive vaccination protocol for leptospirosis should be considered.

Effect of aggressive surgical protocol based on ERAS model on perioperative period of multiple rib fractures

ObjectiveTo explore the effect of aggressive surgical protocol based on the enhanced recovery after surgery (ERAS) model on perioperative and postoperative rehabilitation of patients with multiple rib fractures. MethodsA total of 86 patients with multiple rib fractures were selected and divided into the ERAS group and a routine group, with 43 cases in each group, according to the random number table method. The conventional group implemented the conventional surgical protocol, and the ERAS group implemented the active surgical protocol based on the concept of ERAS based on the conventional group. Intraoperative blood loss, first postoperative exhaust time, thoracic tube removal time, postoperative hospital stays, and postoperative complications were compared between the two groups, and postoperative compliance was evaluated. ResultsAll patients were cured and discharged from the hospital. The amount of intraoperative blood loss, first postoperative exhaust time, postoperative thoracic tube removal time, and postoperative hospital stay in the ERAS group were significantly less than in the conventional group. There was no significant difference in the incidence of postoperative pulmonary infection and the other five complications between the two groups (P > 0.05). The postoperative compliance of the ERAS group was better than that of the conventional group, and the difference was statistically significant (P < 0.05). ConclusionThe active surgical program based on the ERAS model is beneficial to improve the clinical symptoms of patients with multiple rib fractures, reduce postoperative pain, promote postoperative recovery as soon as possible, shorten the length of hospital stay, and significantly improve the compliance of patients in the postoperative rehabilitation stage.

Results of neoadjuvant therapy for patients with triple negative breast cancer in a public hospital in Brazil (Federal District).

e12660 Background: Breast cancer is the neoplasm with the highest number of deaths among women in Brazil. Triple negative breast cancer contributes to the worsening of this condition, considering that it is more aggressive, accounting for 15% of deaths. Furthermore, more aggressive treatments and new medications have recently been added to neoadjuvant protocols, improving the complete pathological response, but with more side effects. In this way, it is predictive to understand the profile and treatment of choice for patients diagnosed with triple negative breast cancer, contributing to a better understanding of the treatment outcome, survival and quality of life in patients with this health condition. Methods: observational and cross-sectional study with retrospective data collection, in the electronic medical record of the TrakCare system. Patients diagnosed with triple-negative breast cancer between January 2020 and December 2021 and who underwent neoadjuvant treatment were included. Information was collected regarding the date of treatment, age, color/race, comorbidity, staging, type of chemotherapy used, postoperative response rate, and patient evolution during follow-up. Results: 78 patients with triple-negative breast cancer were included. The average age of patients was 56.3 years (26 – 83 years) and approximately 38.5% of patients were under 50 years of age. Around 42.3% of patients had hypertension and 33.3% were obese. Only 28.2% of patients did not have associated comorbidities. Approximately 59% of patients were staged T4 and 35.9% staged T3. Pathological complete response (cPR) was achieved in 56.4%, but progression was recorded in 13% of cases. In 88.5% of patients, the AC-T protocol was used (doxorubicin and cyclophosphamide followed by weekly paclitaxel) and 52% obtained CPR. On the other hand, only 11.5% (9 patients) used the AC-TC protocol (doxorubicin and cyclophosphamide followed by paclitaxel and carboplatin) with a CPR of 89% (p=0.016), with no record of progression or death. Conclusions: Triple negative patients were young and tended to have at least one comorbidity in addition to a highest rate of locally advanced tumor. The more aggressive protocol (AC-TC) was used less often, but has a higher rate of cRP and should be used more frequently in this scenario despite the greater complexity of these patients.

Lack of Consensus on the Management of Medial Collateral Ligament Tears in the Setting of Concomitant Anterior Cruciate Ligament Injury: A Critical Analysis.

» There is no clear agreement on the optimal timing or superior type of fixation for medial collateral ligament (MCL) tears in the setting of anterior cruciate ligament (ACL) injury.» Anatomic healing of medial knee structures is critical to maintain native knee kinematics, supported by biomechanical studies that demonstrate increased graft laxity and residual valgus rotational instability after ACL reconstruction (ACLR) alone in the setting of concomitant ACL/MCL injury.» Historically, most surgeons have favored treating acute combined ACL/MCL tears conservatively with MCL rehabilitation, followed by stress radiographs at 6 weeks after injury to assess for persistent valgus laxity before performing delayed ACLR to allow for full knee range of motion, and reduce the risk of postoperative stiffness and arthrofibrosis.» However, with the advancement of early mobilization and aggressive physical therapy protocols, acute surgical management of MCL tears in the setting of ACL injury can have benefits of avoiding residual laxity and further intra-articular damage, as well as earlier return to sport.» Residual valgus laxity from incomplete MCL healing at the time of ACLR should be addressed surgically, as this can lead to an increased risk of ACLR graft failure.» The treatment of combined ACL/MCL injuries requires an individualized approach, including athlete-specific factors such as level and position of play, timing of injury related to in-season play, contact vs. noncontact sport, and anticipated longevity, as well as consideration of the tear pattern, acuity of injury, tissue quality, and surgeon familiarity with the available techniques.

Clinical Outcomes of Arthroscopic Adhesiolysis: A Case Series of 40 Patients With Postoperative Knee Stiffness.

Introduction Restricted range of motion over the knee joint is a known complication following the surgical procedure. Aggressive rehabilitation protocols can initially manage knee stiffness due to arthrofibrosis. If conservative management fails, surgical (open or arthroscopic) release is the preferred modality of management. We present a series of 40 patients with postoperativeknee stiffness who were treated with arthroscopic adhesiolysis. Material and methods This is a retrospective study conducted at Phoenix Orthopedic Superspeciality Hospital, Nagpur, India, from 2017 to 2021. Our study included 40 patients with postoperative knee joint stiffness, of whom 27 were males and 13 were females. The study considered the duration of stiffness, which ranged from six months to five years. All patients underwent arthroscopic knee release. A rigorously supervised physical therapy program followed this procedure. Patients were examined at three months, six months, and one year to assess improvement in knee range of movement. Results Out of 40 patients, six were classified as Shelbourne type 4, and the remaining were Shelbourne type 3. Twenty-three of 40 patients developed arthrofibrosis following intra-articular or peri-articular fracture fixation surgery; 11 patients were operated on arthroscopically for anterior cruciate ligament (ACL) or posterior cruciate ligament (PCL) reconstruction. Three patients developed stiffness following total knee replacement, one following patellectomy, and three following infection after fracture fixation. The mean pre-op knee range of motion (ROM) was 48.875 degrees. Following arthroscopic release, the mean improvement in ROM was 60 degrees intra-operatively. The average postoperative range was 108.25 degrees. Conclusion Arthroscopic adhesiolysis and quadriceps release are reliable methods for dealing with postoperative knee stiffness. It prevents wound complications and increases the chances of surgical site infection due to smaller incisions. Postoperatively, we achieved an average increase of 60 degrees in ROM over the knee joint.

New dynamic suture material for tendon transfer surgeries in the upper extremity – a biomechanical comparative analysis

BackgroundEarly mobilization after tendon surgery is crucial to avoid commonly observed postoperative soft tissue adhesions. Recently, a new suture was introduced (DYNACORD; DC) with a salt-infused silicone core designed to minimize laxity and preserve consistent tissue approximation in order to avoid gap formation and allow early mobilization.AimsTo compare the biomechanical competence of DC against a conventional high strength suture (FiberWire; FW) in a human cadaveric tendon transfer model with an early rehabilitation protocol.MethodsSixteen tendon transfers (flexor digitorum superficialis (FDS) IV to flexor pollicis longus (FPL)) were performed in 8 pairs human cadaveric forearms using either DC or FW. Markings were set 0.8 cm proximally and 0.7 cm distally to the level of the interweaving zone of the transfer. All specimens underwent repetitive thumb flexion against resistance in 9 intermittent series of 300 cycles each, simulating an aggressive postoperative rehabilitation protocol. After each series, the distance of the proximal marker to the interweaving zone (proximal), the length of the interweaving zone (intermediate) and the distance of the distal marker to the interweaving zone (distal) were measured.ResultsPooled data over all nine series, normalized to the immediate postoperative status, demonstrated no significant differences between FW and DC (p ≥ 0.355) for the proximal and distal markers. However, at the intermediate zone, DC was associated with significant length shortening (p < 0.001) compared to FW without significant length changes (p = 0.351). Load to catastrophic failure demonstrated significant higher forces in FW (p = 0.011). Nevertheless, due to failure mainly proximal or distal of the transfer zone, these loads are not informative.ConclusionFrom a biomechanical perspective, DC preserved tissue approximation and might be considered as a valid alternative to conventional high-strength sutures in tendon transfer surgery. DC might allow for a shorter interweaving zone and a more aggressive early postoperative rehabilitation program, possibly avoiding commonly observed postoperative soft tissue adhesions and stiffness.

Unpredicted transformation of acute myeloid leukemia with translocation (16;16) (p13; q22): a case report and review of the literature

IntroductionThe transformation of acute myeloid leukemia with translocation (16;16) (p13; q22) from AML M2 to acute monocytic leukemia (AML M5) during therapy is a rare clinical occurrence, and this is the first time it has been reported.Clinical complainA 19-year-old male patient was admitted for severe fatigue with anemic manifestation and weight loss, for more than 1 month, with exacerbation of the condition in the last 2 days.DiagnosisA primary diagnosis was made for AML M2 with t (16;16) (p13; q22) established on bone marrow (BM) morphology. A consequential detection of FLT-3 ITD mutation was done. At day 28 follow-up after induction and maintenance therapy, the diagnosis of AML M2 was maintained with a high bone marrow (BM) blast count, prompting the initiation of a more aggressive treatment protocol. After 1 month of implementing the recent protocol, the patient remains morphologically resistant with a notable transformation of bone marrow infiltration by an abnormal monocytic population (monoblasts and promonocytes). The final diagnosis of transforming FLT3-mutated AML with t (16;16) (p13; q22) was established.InterventionAfter the initial diagnosis of AML M2 with t (16;16) (p13; q22), the patient received the 3 + 7 induction protocol. The 2nd induction protocol initiated after the second evaluation and morphological resistance was the FLAG Adrian protocol. The 3rd protocol after transformation to AML M5 was 1 cycle of the MEC protocol. Anti-FLT3 treatment was considered.OutcomesThe patient was maintained on the 3rd protocol of chemotherapy. Unfortunately, he was admitted to the ICU unit complaining of neutropenic fever and severe sepsis where he died before final re-evaluation and the anti-FLT3 treatment initiation.ConclusionAML with t (16;16) (p13; q22) characterized by favorable outcome. However, identifying additional chromosome abnormality or genetic aberration, especially FLT3 gene mutation, is recognized as an important factor influencing final disease outcome. Therefore, early detection of FLT3 mutations will allow comprehensive disease course prediction and targeted therapy that might achieve longer and more durable remissions.

(134) Efficacy of a Novel Collagenase Clostridium Histolyticum Protocol for Peyronie’s Disease Among Prior Non-responders: A Randomized, Controlled, Single-Blinded Study

Abstract Introduction Limited data currently exist on the role and efficacy of additional series of collagenase clostridium histolyticum (CCH) injections among Peyronie’s disease (PD) men who have previously failed a first series of injections. We have previously published outcomes of men undergoing a novel protocol for CCH injections and which demonstrated significant improvements compared to original IMPRESS I and II techniques. We therefore sought to evaluate results of men who had previously failed CCH injections to determine if they would respond to a repeat course using a more aggressive protocol. Objective To evaluate outcomes of a novel protocol for CCH injections among men who had previously failed 6-8 CCH injections using a traditional approach. Methods A randomized, controlled trial (NCT05108558) is ongoing. All participants had previously failed to achieve ≥20% curvature improvement with 6-8 prior CCH injections. Men were randomized 3:1 to receive either CCH + traction (RestoreX) + sildenafil (treatment) up front or initial observation followed by treatment (controls). Outcomes were compared between treatment and control groups. Key measures included objective curve improvements and standardized/non-standardized questionnaires, with assessments obtained at baseline, 6-weeks after completion of CCH (treatment arm), after the no treatment period (controls), and at 1 year. Results A total of 22/40 men have been randomized to date, with 11 having fully completed treatment. Mean age was 64 years, with a median PD duration of 24 months. Mean composite baseline curvature was 80 degrees, with 55% having hourglass or indentation deformities, 10% calcification, median baseline IIEF-EFD 15, and 60% able to have penetrative intercourse. Median estimated improvement with the prior CCH series was 0% (IQR 0, 19.4), and the median number of prior injections was 8. The majority of men were dissatisfied with their prior series of CCH (60% vs 30% satisfied, 10% neutral). Of the 11 men who had completed the study protocol, 64% required 1 series, 9% 2 series, 18% 3 series, and 9% 4 series. Compared to the no treatment arm, treated men experienced significantly greater improvements (mean 78 degree vs 15, p=0.01). IIEF-EFD was also improved more in treated men (+4.3 vs -5.7, p&amp;lt;0.05). 100% of men reported a subjective major improvement in curvature, with the average subjectively estimated improvement 91%. 67% reported improved sensitivity (33% no change), while 60% reported improved or no change in erectile function, with 20% unsure, and 20% somewhat worse. Post-treatment, 83% of men were very satisfied with CCH as a treatment and 17% somewhat satisfied. Conclusions Repeating CCH using a novel protocol after an initially unsuccessful course of CCH achieves significant improvements in curvature and patient satisfaction. Additional data, including external validation, are warranted. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals. Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Matthew Ziegelmann - Endo Pharmaceuticals.

Connectivity Maintenance through Unlabeled Spanning Tree Matching

A key function of mobile networks is the ability to dynamically reshape itself to any desired geometry. Lacking absolute position awareness, agents often rely on distance-limited inter-agent spatial measurements to maintain state awareness. Methods of formation control must therefore ensure a minimal level of persistent pairwise measurement feedback throughout transition, giving rise to the classic connectivity maintenance problem. To address this problem, we propose a method of structure-preserving assignment, matching agents to desired positions such that persistent global connectivity is naturally and automatically satisfied under smooth transition. Compared to other approaches, this complementary technique reduces reliance on aggressive or costly mid-flight formation control protocols. The technique is shown to scale and even improve with network size.

Case report: Para Hisian Atrial Tachycardia

Case report: Para Hisian Atrial Tachycardia

Re-entry in models of cardiac ventricular tissue with scar represented as a Gaussian random field.

Introduction: Fibrotic scar in the heart is known to act as a substrate for arrhythmias. Regions of fibrotic scar are associated with slowed or blocked conduction of the action potential, but the detailed mechanisms of arrhythmia formation are not well characterised and this can limit the effective diagnosis and treatment of scar in patients. The aim of this computational study was to evaluate different representations of fibrotic scar in models of 2D 10 10 cm ventricular tissue, where the region of scar was defined by sampling a Gaussian random field with an adjustable length scale of between 1.25 and 10.0 mm. Methods: Cellular electrophysiology was represented by the Ten Tusscher 2006 model for human ventricular cells. Fibrotic scar was represented as a spatially varying diffusion, with different models of the boundary between normal and fibrotic tissue. Dispersion of activation time and action potential duration (APD) dispersion was assessed in each sample by pacing at an S1 cycle length of 400 ms followed by a premature S2 beat with a coupling interval of 323 ms. Vulnerability to reentry was assessed with an aggressive pacing protocol. In all models, simulated fibrosis acted to delay activation, to increase the dispersion of APD, and to generate re-entry. Results: A higher incidence of re-entry was observed in models with simulated fibrotic scar at shorter length scale, but the type of model used to represent fibrotic scar had a much bigger influence on the incidence of reentry. Discussion: This study shows that in computational models of fibrotic scar the effects that lead to either block or propagation of the action potential are strongly influenced by the way that fibrotic scar is represented in the model, and so the results of computational studies involving fibrotic scar should be interpreted carefully.

PATELLA FRACTURES IN THE FRAIL HOST: A SYSTEMATIC REVIEW

AbstractObjectivesThe outcomes from patella fracture have remained dissatisfactory despite advances in treatment, especially from operative fixation1. Frequently, reoperation is required following open reduction and internal fixation (ORIF) of the patella due to prominent hardware since the standard technique for patella ORIF is tension band wiring (TBW) which inevitably leaves a bulky knot and irritates soft tissue given the patella's superficial position2. We performed a systematic review to determine the optimal treatment of patella fractures in the poor host.MethodsThree databases (EMBASE/Medline, ProQuest and PubMed) and one register (Cochrane CENTRAL) were searched. 476 records were identified and duplicates removed. 88 records progressed to abstract screening and 73 were excluded. Following review of complete references, 8 studies were deemed eligibleResultsComplication rates were shown to be high in our systematic review. Over one-fifth of patients require re-operation, predominantly for removal of symptomatic for failed hardware. Average infection rate was 11.95% which is higher than rates reported in the literature for better hosts. Nevertheless, reported mortality was low at 0.8% and thromboembolic events only occurred in 2% of patients. Average range of movement achieved following operative fixation was approximately 124 degrees. Upon further literature review, novel non-operative treatment options have shown acceptable results in low-demand patients, including abandoning weight-bearing restrictions altogether and non-operatively treating patients with fracture gaps greater than 1cm. Regarding operative management, suture/cable TBW has been investigated as a viable option with good results in recent years since the materials used show comparable biomechanics to stainless steel. Additionally, ORIF with locking plates have shown favourable results and have enabled aggressive post-operative rehabilitation protocols. TBW with metallic implants has shown higher complication rates, especially for anterior knee pain, reoperation and poor functional outcomes.ConclusionThere is sparse literature regarding patella fracture in the poor host. Nevertheless, it is clear that ORIF produces better outcomes than conservative treatment but the optimal technique for patella ORIF remains unclear. TBW with metallic implants should not remain the standard technique for ORIF; low-profile plates of suture TBW are more attractive solutions. Non-operative treatment may be considered for low-demand individuals however any form of patellectomy should be avoided if possible.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Lymph Node Ratio as a Predictor of Survival for Colon Cancer: A Systematic Review and Meta-Analysis.

Lymph node ratio is the number of lymph nodes with evidence of metastases on pathological review compared to the total number of lymph nodes harvested during oncologic resection. Lymph node ratio is a proven predictor of long-term survival. These data have not been meta-analyzed to determine the prognosis associated with different lymph node ratio cut-offs in colon cancer. Medline, Embase, and CENTRAL were systematically searched. Articles were included if they compared 5-year overall survival (OS) or disease-free survival (DFS) between different lymph node ratios for patients undergoing oncologic resection for stages I-III colon cancer. Pairwise meta-analyses using inverse variance random effects were performed. From 2587 citations, nine studies with 97,631 patients (female: 51.9%, median age: 61.65years) were included. A lymph node ratio above .1 resulted in a 49% decrease in the odds of 5-year OS (2 studies; OR: 0.51, 95% CI: 0.49-.53, P < .00001). A lymph node ratio above .25 resulted in a 56% decrease in the odds of 5-year OS (3 studies; OR: 0.44, 95% CI: 0.43-.45, P < .00001). A lymph node ratio above .5 resulted in a 65% decrease in the odds of 5-year OS (3 studies; OR: 0.35, 95% CI: 0.33-.37, P < .00001). Lymph node ratios from .1 to .5 are effective predictors of 5-year OS for colon cancer. There appears to be an inverse dose-response relationship between lymph node ratio and 5-year OS. Further study is required to determine whether there is an optimal lymph node ratio cut-off for prognostication and whether it can inform which patients may benefit from more aggressive adjuvant therapy and follow-up protocols.

The identification of BCL-XL and MCL-1 as key anti-apoptotic proteins in medulloblastoma that mediate distinct roles in chemotherapy resistance

Medulloblastoma is the most common malignant paediatric brain tumour, representing 20% of all paediatric intercranial tumours. Current aggressive treatment protocols and the use of radiation therapy in particular are associated with high levels of toxicity and significant adverse effects, and long-term sequelae can be severe. Therefore, improving chemotherapy efficacy could reduce the current reliance on radiation therapy. Here, we demonstrated that systems-level analysis of basal apoptosis protein expression and their signalling interactions can differentiate between medulloblastoma cell lines that undergo apoptosis in response to chemotherapy, and those that do not. Combining computational predictions with experimental BH3 profiling, we identified a therapeutically-exploitable dependence of medulloblastoma cells on BCL-XL, and experimentally validated that BCL-XL targeting, and not targeting of BCL-2 or MCL-1, can potentiate cisplatin-induced cytotoxicity in medulloblastoma cell lines with low sensitivity to cisplatin treatment. Finally, we identified MCL-1 as an anti-apoptotic mediator whose targeting is required for BCL-XL inhibitor-induced apoptosis. Collectively, our study identifies that BCL-XL and MCL-1 are the key anti-apoptotic proteins in medulloblastoma, which mediate distinct protective roles. While BCL-XL has a first-line role in protecting cells from apoptosis basally, MCL-1 represents a second line of defence that compensates for BCL-XL upon its inhibition. We provide rationale for the further evaluation of BCL-XL and MCL-1 inhibitors in the treatment of medulloblastoma, and together with current efforts to improve the cancer-specificity of BCL-2 family inhibitors, these novel treatment strategies have the potential to improve the future clinical management of medulloblastoma.

Anti-Müllerian Hormone: A Predictor of Successful Intrauterine Insemination.

The anti-Müllerian hormone (AMH) produced by the granulosa cells of ovarian follicles has been shown to correlate with ovarian reserve and is often measured for fertility therapies. In this study, we evaluated the relationship between serum AMH values and the clinical pregnancy (CP) rates of female partners with unexplained infertility undergoing intrauterine insemination utilizing varying ovarian simulation protocols. This is a retrospective cohort study conducted among couples who underwent intrauterine insemination therapy over a period of four years at Charleston Area Medical Center, a tertiary care medical center in West Virginia, USA.Logistic regression was used to determine the best predictor of CP. A total of 509 intrauterine inseminations resulting in81 (15.9%) Cps were analyzed. The cycles with a CPhad higher mean AMH values (3.7+3.5 vs. 2.2+2.1; p<0.001).The majority of patients were nulliparous (77.0%) with a mean age of 33.6+5.0 years.After including only patients with unexplained infertility (the predominate infertility diagnosis; n=255 (50.1% of the cycles)) and stimulation cycles >10, the final sample size for the analysis was 245/509=48.1%.Following a receiver operating characteristic (ROC) curve analysis, the optimal AMH cut-off point was 2.1 ng/mL with an area under the curve (AUC) equal to 0.61 and 95% confidence intervals (CIs) of 0.55- 0.67 (p=0.002). The CP rate was significantly higher with the AMH >2.1 ng/mL (20.0%) compared to <2.1 ng/mL (10.0%; p=0.041). With Clomid/human gonadotropins/human chorionic gonadotropin (hCG) trigger treatment, the CP rate quadrupled (odds ratio (OR): 4.6; 95% CI: 2.1-9.7; p<0.001). This study indicates that higher AMH levels and a more aggressive ovarian stimulation protocol for intrauterine insemination therapy (IUI) have a better probability of resulting in CP.

Mortality after emergency unit fluid bolus in febrile Ugandan children.

Pediatric fluid resuscitation in sub-Saharan Africa has traditionally occurred in inpatients. The landmark Fluid Expansion as Supportive Therapy (FEAST) trial showed fluid boluses for febrile children in this inpatient setting increased mortality. As emergency care expands in sub-Saharan Africa, fluid resuscitation increasingly occurs in the emergency unit. The objective of this study was to determine the mortality impact of emergency unit fluid resuscitation on febrile pediatric patients in Uganda. This retrospective cohort study used data from 2012-2019 from a single emergency unit in rural Western Uganda to compare three-day mortality for febrile patients that did and did not receive fluids in the emergency unit. Propensity score matching was used to create matched cohorts. Crude and multivariable logistic regression analysis (using both complete case analysis and multiple imputation) were performed on matched and unmatched cohorts. Sensitivity analysis was done separately for patients meeting FEAST inclusion and exclusion criteria. The analysis included 3087 febrile patients aged 2 months to 12 years with 1,526 patients receiving fluids and 1,561 not receiving fluids. The matched cohorts each had 1,180 patients. Overall mortality was 4.0%. No significant mortality benefit or harm was shown in the crude unmatched (Odds Ratio [95% Confidence Interval] = 0.88 [0.61-1.26] or crude matched (1.00 [0.66-1.50]) cohorts. Adjusted cohort analysis (including both complete case analysis and multiple imputation) and sensitivity analysis of patients meeting FEAST inclusion and exclusion criteria all also failed to show benefit or harm. Post-hoc power calculations showed the study was powered to detect the absolute harm seen in FEAST but not the relative risk increase. This study's primary finding is that fluid resuscitation in the emergency unit did not significantly increase or decrease three-day mortality for febrile children in Uganda. Universally aggressive or fluid-sparing emergency unit protocols are unlikely to be best practices, and choices about fluid resuscitation should be individualized.