Combined, yet separate: cocktails of carriers (not drugs) for actinium-225 α-particle therapy of solid tumors expressing moderate-to-low levels of targetable markers.

Alpha-particle radionuclide-antibody conjugates are being clinically evaluated against solid tumors even when they moderately express the targeted markers. At this limit of lower tumor-absorbed doses, to maintain efficacy, the few(er) intratumorally delivered alpha-particles need to traverse/hit as many different cancer cells as possible. We complement antibody-radioconjugate therapies with a separate nanocarrier delivering a fraction of the same total injected radioactivity to tumor regions geographically different than those affected by targeting antibodies; these carrier-cocktails collectively distribute the alpha-particle emitters better. METHODS: The efficacy of actinium-225 delivered by our carrier-cocktails was assessed in vitro and on mice with orthotopic MDA-MB-436 and/or MDA-MB-231 triple-negative breast cancers and/or an ectopic BxPC3 pancreatic cancer. Cells/tumors were chosen to express low-to-moderate levels of HER1, as model antibody-targeted marker. RESULTS: Independent of cell line, antibody-radioconjugates were most lethal on cell monolayers. On spheroids, with radii greater than alpha-particles' range, carrier-cocktails improved killing efficacy (p < 0.0500). Treatment with carrier-cocktails decreased the MDA-MB-436 and MDA-MB-231 orthotopic tumor volumes by 73.7% and 72.1%, respectively, relative to treatment with antibody-radioconjugates alone, at same total injected radioactivity; these carrier-cocktails completely eliminated formation of spontaneous metastases vs. 50% and 25% elimination in mice treated with antibody-radioconjugates alone. In BxPC3 tumor-bearing mice, carrier-cocktails increased the median survival to 25-26 days (in male-female animals) vs. 20-21 days of mice treated with antibody-radioconjugates alone (vs. 17 days for non-treated animals). Survival with carrier-cocktail radiotherapy was further prolonged by pre-injecting low-dose, standard-of-care, gemcitabine (p = 0.0390). CONCLUSION: Tumor-agnostic carrier-cocktails significantly enhance the therapeutic efficacy of existing alpha-particle radionuclide-antibody treatments.

Non-surgical Management of an Acute Isolated Volar Dislocation of the Distal Radioulnar Joint.

Introduction: Isolated distal radioulnar joint dislocations are rare and commonly missed on radiographs. Knowledge of the management of these injuries, therefore, has room for improvement. We present a case with an alternative method of closed reduction. Case Presentation: A young Caucasian male presented with severe pain and deformity of the left wrist, following a collision while playing rugby. This was easily diagnosed using plain radiographs and the initial attempted reduction methods in the Emergency Department failed. The patient was subsequently anesthetized in theatre, yet reduction by an accepted method of palmar to dorsal pressure over the interosseous membrane with simultaneous distraction of the wrist failed. A further attempt to manipulate the dislocated ulnar head was successful, with the same force applied, while the wrist was maximally flexed and pronated - thereby avoiding an open reduction. Conclusion: This technique has not previously been described in the literature and may be used in similar injuries in the future.

Analysis of postoperative complications following elective arthroscopic surgeries of the knee- a retrospective cohort study.

Background: Since their introduction, arthroscopic procedures have been increasingly utilized for the treatment of knee pathologies, especially Anterior Cruciate Ligament (ACL) reconstruction. Reduction of post-operative morbidity, shortened hospital stay and recovery period have all been identified as the benefits of arthroscopy. However, despite tremendous increase in the number of these procedures done, the postoperative complications associated have been infrequently analyzed. Hence, we performed this study to analyze the perioperative complications of arthroscopic ACL reconstruction. Materials & methods: We performed a retrospective case control study from our hospital database from the cases performed in July 2015 to December 2016. We included 20 cases who developed postoperative complications within 30 days of the procedure and 60 controls operated during the same period who did not have any complications. Results: The complications noted in the cases were surgical site infection (SSI), deep vein thrombosis (DVT), effusion and superficial infection. The risk factors associated with each complication were compared with the cases and analyzed. Conclusions: It was found that the lack of specialist physiotherapy, surgical prophylaxis and prolonged postoperative antibiotics were the major risk factors in the development of complications among our patients who underwent arthroscopic ACL reconstruction.

Dynamic Hip Screw Plate Length in Stable Intertrochanteric Fracture Neck of Femur: A Systematic Review.

There has always been a debate between the use of four and two-hole plate for the fixation of stable intertrochanteric fractures. The choice is usually influenced by the general practice of the particular institution and the surgeon's preference. While the dynamic hip screw (DHS) is the implant of choice for stable intertrochanteric fractures of the femur, the length of the side plate to be chosen for optimal results has no clear consensus and previous studies regarding the same have been inconclusive. In our systematic review, we aimed to review the evidence available on the selection of the optimal length of the side plate and bridge the glaring gap that exists in the literature. Our systematic review included a thorough search of databases like PubMed, Embase, MEDLINE, CINAHL, and the Cochrane Library, using the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included both clinical and biomechanical studies satisfying our search criteria on two- and four-hole DHS implants. A total of 4556 results were obtained from the above databases, sorting out led to final 15 studies on the topic. It was found that the two-hole DHS implant was inferior in terms of lab-controlled biomechanical properties, while only having a slight advantage in terms of real-life postoperative blood transfusions and operative time. At the same time, the two-hole plate was similar to the four-hole plate in other clinical parameters. In this study, the two-hole plate while appearing promising in a few areas did fall short in other aspects like biomechanical studies, and the use should be reserved for cases where a four-hole plate cannot be used until further randomised control trials are carried out.

The Epidemiology of Intensive Care Unit Readmissions and Proposed Discharge Protocol for a Tertiary Care Hospital.

BACKGROUND: Intensive Care Unit (ICU) readmissions during the same hospitalization are associated with increased hospital stays, morbidity and mortality. Whereas mortality rates in patients admitted to the ICU for the first time may range from 10 to 20% depending on various factors, readmission mortality rates can be up to 50 to 70%. Factors leading to readmission in ICU in Indian Armed Forces Hospitals have not been well studied till date. METHODS: This was a record based cross sectional descriptive study conducted at the ICU of a tertiary care Armed Forces hospital. Demographic and clinical data of ICU patients were analysed. ICU admission and discharge data for the duration of last three years were acquired from admission and discharge registers and Hospital Informatics system (HIS) software. The primary outcome was readmission rates to ICU during the same hospitalization. Secondary outcomes included diagnosis at time of index admission (first time admission) to ICU and at readmission, multiple readmissions to ICU and mortality rates in readmitted patients. RESULTS: There were 3021 admissions to the ICU during the study period. 422 patients succumbed to illness during initial admission resulting in a mortality rate of 14%. 198 patients were readmitted to the ICU. The readmission rate to the ICU was 7.8%. The mortality rate in readmitted patients was 31% as compared to the ICU mortality rate of 14%. The triggering factors for readmission were usually respiratory or cardiac decompensations. CONCLUSION: Readmission to ICU occurred in about 7.8 % of all ICU patients in our study. ICU readmissions increase the risk of adverse outcomes. Objective measures in the form of a discharge protocol incorporating the stability and work index for transfer (SWIFT Score) may help minimizing readmission to ICU. Such protocols must be in place while shifting any patients from ICU so as to improve outcomes in patients of tertiary care hospitals.

Residual deformity versus recurrence following Dupuytren's palmar fasciectomy-a long term follow-up of 142 cases.

INTRODUCTION: and background: Surgical options for Dupuytren's disease (DD) are multiple, and Dupuytren's palmar fasciectomy (PF) is a common surgical procedure performed for contractures that cause functional and cosmetic disability. The recurrence rate for PF has been reported to be very variable, ranging from 12 to 73%, according to various studies. One of the reasons for the varied range is the inconsistency in the method followed to define recurrence. Subsequently, a consensus-based definition was formulated in 2016, and we analysed the outcome in our series of patients treated with PF based on this standard definition. We also analysed the residual deformity associated in these cases. METHOD: ology: Our study is a retrospective analysis of 142 consecutive cases of primary Dupuytren's palmar fasciectomy by a single surgeon in three different centres. We followed the international consensus definition for analysing recurrence in these cases, and we also analysed residual cases as a separate entity. RESULTS: The mean age of the cases was 67.13 years and the mean follow-up period was 3.95 years. Alcoholism, smoking, diabetes and hypercholesterolemia were the commonest associated risk factors. The commonest affected finger and the finger with the maximum deformity were the little finger. The overall rate of recurrence of deformity was 3.5% and the rate of residual deformity was 30.3%. The overall complication rate was 11.9%. CONCLUSION: Recurrence and residual deformity can be considered as separate entities. The term 'residual deformity' can be used to denote patients with persisting deformity or those who incur deformity within one year of the primary surgery.

Atrial fibrillation in the elderly population: Challenges and management considerations.

IMPORTANCE: Atrial fibrillation is the most clinically significant arrhythmia in humans when viewed both from a global and also a national perspective. In the United States, approximately 2.7-6.1 million people are estimated to have atrial fibrillation. With the aging of the population, this prevalence is on an increasing trend and remains an obstacle to cardiovascular health despite significant advancements specific to cardiovascular disease management. OBSERVATION: In this specific group of patients, healthcare utilization is a concern from the public health perspective. Unfortunately, misconceptions dominate clinical decision making; for instance, the avoidance of safe and effective anticoagulation strategies in patients at the highest risk for embolic strokes continues to be widespread in clinical practice and is often based on a skewed assessment of risk versus benefit. Also, when there are contraindications to standard interventions for atrial fibrillation, a clear and nuanced understanding of second- and third-line interventions with proven benefit is often lacking. CONCLUSIONS AND RELEVANCE: An individualized approach should be followed by physicians when managing atrial fibrillation in the elderly patient, taking into consideration the risk of complications, particularly the embolic stroke and the availability of treatment options for stroke prevention whether through pharmacological anticoagulation or left atrial appendage occluding devices. The following review sets out to clarify these issues.

Transport-driven engineering of liposomes for delivery of α-particle radiotherapy to solid tumors: effect on inhibition of tumor progression and onset delay of spontaneous metastases.

PURPOSE: Highly cytotoxic α-particle radiotherapy delivered by tumor-selective nanocarriers is evaluated on metastatic Triple Negative Breast Cancer (TNBC). On vascularized tumors, the limited penetration of nanocarriers (<50-80 µm) combined with the short range of α-particles (40-100 µm) may, however, result in only partial tumor irradiation, compromising efficacy. Utilizing the α-particle emitter Actinium-225 (225Ac), we studied how the therapeutic potential of a general delivery strategy using nanometer-sized engineered liposomes was affected by two key transport-driven properties: (1) the release from liposomes, when in the tumor interstitium, of the highly diffusing 225Ac-DOTA that improves the uniformity of tumor irradiation by α-particles and (2) the adhesion of liposomes on the tumors' ECM that increases liposomes' time-integrated concentrations within tumors and, therefore, the tumor-delivered radioactivities. METHODS: On an orthotopic MDA-MB-231 TNBC murine model forming spontaneous metastases, we evaluated the maximum tolerated dose (MTD), biodistributions, and control of tumor growth and/or spreading after administration of 225Ac-DOTA-encapsulating liposomes, with different combinations of the two transport-driven properties. RESULTS: At 83% of MTD, 225Ac-DOTA-encapsulating liposomes with both properties (1) eliminated formation of spontaneous metastases and (2) best inhibited the progression of orthotopic xenografts, compared to liposomes lacking one or both properties. These findings were primarily affected by the extent of uniformity of the intratumoral microdistributions of 225Ac followed by the overall tumor uptake of radioactivity. At the MTD, long-term toxicities were not detected 9.5 months post administration. CONCLUSION: Our findings demonstrate the potential of a general, transport-driven strategy enabling more uniform and prolonged solid tumor irradiation by α-particles without cell-specific targeting.

Synergistic effect of ultrasonication and co-immobilized enzymes on tomato peels for lycopene extraction.

In the present work, tomato peels were pre-treated using combination of ultrasound and enzyme co-immobilized amino-functionalized magnetic nanoparticles (AMNPs) for the efficient release of lycopene. To achieve maximum activity of enzymes in the co-immobilized form, optimization of several parameters were carried out. Moreover, the influence of ultrasound and enzyme co-immobilized magnetic nanoparticles on lycopene release was studied. Maximum lycopene release was obtained at 3% (w/w) enzyme co-immobilized AMNPs, pH 5.0, temperature of 50 °C, at 10 W ultrasound power and 20 min incubation time. After enzymatic pre-treatment, lycopene from the pre-treated mixture was extracted and separated using tri-solvent extraction method. Maximum recovery of lycopene using solvent extraction was obtained at 50 °C, 90 min of incubation time and agitation speed of 150 rpm. The presence of lycopene in the extract was confirmed by FT-IR, UV-vis spectroscopy and HPLC analysis. The co-immobilized bio-catalyst showed excellent reusability giving more than 50% lycopene yield even after 6th cycles of reuse.

Comparison of Efficacy of Epidural Ropivacaine versus Bupivacaine for Postoperative Pain Relief in Total Knee Replacement Surgeries.

BACKGROUND: Epidural analgesia has become the standard of care for knee replacement surgeries worldwide. Bupivacaine has been used successfully for many years. Epidural ropivacaine is now being used increasingly and seems to have benefits other than just pain relief, in terms of a better safety profile. AIM: To compare the efficacy of bupivacaine 0.125% (Group B) versus two concentrations of ropivacaine 0.1% (Group R1) and 0.2% (Group R2), in terms of pain scores, requirement of rescue analgesia, related adverse effects, and duration of postoperative (PO) hospital stay. MATERIALS AND METHODS: A retrospective study was conducted from the acute pain service data of patients who underwent joint replacement surgeries in one or both limbs, over a span of 6 months. Patients were allocated to and analyzed under one of the three groups based on the drug concentration used postoperatively by epidural infusion. Data retrieved were demographic data, daily average visual analog scale (VAS) pain scores, rescue analgesia given, adverse effects, and PO hospital stay days for all three groups. RESULTS: Demographic data were comparable between the three groups. Daily average VAS pain scores on days 1 and 2 were significantly higher in Group R1. Groups B and R2 were comparable. There was significantly more requirement of rescue analgesia in Group R1 on day 1. Day 2 showed no significant difference in rescue analgesic requirement in all three groups. Days of PO hospital stay were significantly higher in Group R1. Adverse effects such as hypotension and delayed motor block were higher in Group B. CONCLUSION: Ropivacaine 0.2% and bupivacaine 0.125% were equally efficacious in terms of VAS pain scores, rescue analgesic requirement, and duration of PO hospital stay, but ropivacaine had a better safety profile in terms of less hypotension and lesser motor block.

Isolated rheumatic severe tricuspid regurgitation.

Severe isolated tricuspid regurgitation (TR) is very rare, with most cases of TR being functional and secondary to pulmonary hypertension from left heart pathologies. We report an unusual case of a young Nigerian male, who presented to us with dyspnea, repeated hospital admissions for heart failure, and a childhood history of rheumatic fever. Echocardiogram showed massively dilated right atrium and ventricle, noncoaptation of thickened tricuspid valve with torrential free tricuspid regurgitation. Other valves were normal. Cardiac MRI showed normal right ventricular function and viability. Patient underwent tricuspid valve replacement with 35-mm St. Jude valve.

Coronary Stent Infection Successfully Diagnosed Using 18F-Flurodeoxyglucose Positron Emission Tomography Computed Tomography.

Infection of coronary stents is extremely rare. We report a case of a 60-year-old gentleman with recurrent fever after acute stent occlusion and reintervention. A coronary angiogram showed an occluded stented segment and the blood cultures were positive for infection. The presence of inflammation in the stented region was confirmed using 18F-flurodeoxyglucose positron emission tomography computed tomography. The patient underwent surgery and the diagnosis was proven by examination of the surgical material. This article highlights the need to have a high index of suspicion of stent infection, and the use of 18F-flurodeoxyglucose positron emission tomography computed tomography along with coronary angiogram in aiding the diagnosis.

An Unusual Case of Biatrial Myxoma in a Young Female.

Myxoma, a rare type of intracardiac tumor, forms a very small percentage of the cardiac cases. Reports of biatrial myxoma are rarer, with cases of single tumor reaching both atria being more common. Here, we present an unusual case of two independently growing atrial myxoma in a 29-year-old female. We emphasize that early recognition of symptoms, confirmation of diagnosis by transesophageal echocardiography, and prompt surgical excision remain vital in the management of such patients. The patient in the present case was managed successfully with no evidences of recurrence at the last follow-up.

Osteomyelitis, discitis, epidural and psoas abscess secondary to Salmonella enterica in a man with diabetes mellitus and newly diagnosed α-thalassaemia trait.

We report the case of a 65-year-old man with type 2 diabetes mellitus and α-thalassaemia trait. Investigations for relapsing and remitting fever found vertebral osteomyelitis, discitis and epidural and psoas abscess secondary to Salmonella enterica.

Diphenhydramine induced QT prolongation and torsade de pointes: An uncommon effect of a common drug.

The histamine I receptor antagonist diphenhydramine is a freely available, over the counter medication for sleep and the most frequently used antihistamine drug. It inhibits the fast sodium channels and, at higher concentrations, the repolarising potassium channels, particularly Ikr which leads to prolongation of the action potential and the QT interval. The toxicity of diphenhydramine is dose-dependent, with a critical dose limit of 1.0 g. We report a case of a young woman who consumed more than 3 g of diphenhydramine in the setting of alcohol intoxication and developed QTc prolongation with nonsustained polymorphic ventricular tachycardia. These changes reverted to normal with supportive treatment. An overdose of diphenhydramine with concomitant alcohol use can induce torsade de pointes in an otherwise normal heart.

Amiodarone-induced torsade de pointes in a patient with wolff-Parkinson-White syndrome.

Amiodarone is generally regarded to have a high safety profile with a low incidence of arrhythmias. However, there have been reports of torsades de pointes under certain conditions, such as electrolyte imbalance or concomitant antiarrhythmic therapy. We describe a case of amiodarone-induced torsade de pointes early after initiation of intravenous amiodarone in the setting of T-wave alternans.