Modified Boytchev procedure for treatment of recurrent anterior dislocation of shoulder

Background:

More than 200 different operations have been described for the treatment of recurrent anterior dislocation of shoulder. The Modified Boytchev procedure employs rerouting of the detached tip of coracoid process with its attached conjoined tendon (short head of biceps and coracobrachialis) deep to subscapularis and reattaches to its anatomical location. We conducted a study on evaluation of long-term effect of modified Boytchev procedure and to compare our results with other studies published in literature.

Materials and Methods:

Since June 2002, modified Boytchev procedure was performed on 48 patients, who presented with recurrent anterior dislocation. 45 were men and 3 were women and were in the age group of 18-40 years (mean 27.83±4.95 years). Forty patients were affected on the dominant side and rest on the non-dominant side. The mean number of dislocations in these patients was 18.22±12.08. The mean followup period was 58.13±19.06 months (range 18-96 months). The patients were evaluated by visual analogue score, modified American Shoulder and Elbow Surgeon''s Score (ASES), and Single Assessment Numeric Evaluation (SANE) score at the last followup.

Results:

All the patients regained almost preoperative range of forward flexion at the last followup. In the preoperative period the mean external rotation deficit at 0° and at 90° of abduction was 13.22°±5.16° and 18.06°±6.50°, respectively. At the last followup, the mean external rotation deficit at 0° and at 90° of abduction was 8.06°±2.47° and 8.95°±2.07°, respectively. This improvement in external rotation deficit was statistically significant (P<.05). Preoperative scores were compared with the most recent followup scores for all variables with use of a paired t test. All patients had significant improvement in visual analogue score, modified American Shoulder and Elbow Surgeon''s Score (ASES), and Single Assessment Numeric Evaluation (SANE) score at the last followup. Four of the patients developed superficial infection which got resolved after treating with antibiotics, and two of the patients developed transient musculocutaneous nerve paresis. There was no radiological evidence of loosening and migration of coracoid screw or any glenohumeral arthritis on subsequent followup of skiagrams in any of our patients.

Conclusion:

Modified Boytchev procedure is an efficacious and technically simple procedure to treat recurrent anterior dislocation of shoulder.     

Effect of a Structured Teaching Module Including Intensive Prophylactic Measures on Reducing the Incidence of Capecitabine-Induced Hand-Foot Syndrome: Results of a Prospective Randomized Phase III Study

Lessons Learned

• A structured teaching module including intensive prophylactic measures to alleviate hand‐foot syndrome (HFS) during capecitabine therapy is feasible but ineffective at protecting patients from HFS.
• Pharmacologic therapeutic interventions should be investigated for the management of this complication.

BackgroundCapecitabine‐induced hand‐foot syndrome (HFS) has a detrimental effect on quality of life. The effect of a structured teaching module including intensive prophylactic measures was evaluated.MethodsThis non‐crossover phase III double‐blinded clinical trial randomized patients in a 1:1 ratio to either a control group or to a group administered a structured teaching model including intensive prophylactic measures on HFS administered by a trained oncology nurse at regular intervals (case) versus standard information on HFS care administered by treating clinician (control). The primary endpoint was comparison of fraction of patients in both arms developing at least grade 2 HFS.ResultsBetween June 15, 2016, and April 4, 2018, 280 patients (140 to case and 140 to control) were enrolled. The median number of capecitabine chemotherapy cycles was eight; 269 patients (96%) were evaluable for HFS, of whom 89 patients (33.08%) developed at least grade 2 HFS (grade 2 HFS, 73 patients [26.1%]; grade 3 HFS, 16 patients (5.7%}). There was no difference in at least grade 2 HFS between evaluable case and control arms of the study (control group, 45/135 [33.3%]; case, 44/134 [32.8%]; p = .93).ConclusionThe use of a structured teaching module including intensive prophylactic measures was feasible, but this did not reduce the incidence and severity of capecitabine‐induced HFS.     

Brainstem death: A comprehensive review in Indian perspective

With the advent of cardiopulmonary resuscitation techniques, the cardiopulmonary definition of death lost its significance in favor of brain death. Brain death is a permanent cessation of all functions of the brain in which though individual organs may function but lack of integrating function of the brain, lack of respiratory drive, consciousness, and cognition confirms to the definition that death is an irreversible cessation of functioning of the organism as a whole. In spite of medical and legal acceptance globally, the concept of brain death and brain-stem death is still unclear to many. Brain death is not promptly declared due to lack of awareness and doubts about the legal procedure of certification. Many brain dead patients are kept on life supporting systems needlessly. In this comprehensive review, an attempt has been made to highlight the history and concept of brain death and brain-stem death; the anatomical and physiological basis of brain-stem death, and criteria to diagnose brain-stem death in India.     

Near‐infrared photoimmunotherapy targeting EGFR—Shedding new light on glioblastoma treatment

Glioblastomas (GBMs) are high‐grade brain tumors, differentially driven by alterations (amplification, deletion or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12–15 months following standard therapy. A combination of interventions targeting tumor‐specific cell surface regulators along with convergent downstream signaling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy. An EGFR‐specific affibody (Z_EGFR:03115) was conjugated to the phthalocyanine dye, IR700DX, which when excited with near‐infrared light produces a cytotoxic response. Z_EGFR:03115–IR700DX EGFR‐specific binding was confirmed by flow cytometry and confocal microscopy. The conjugate showed effective targeting of EGFR positive GBM cells in the brain. The therapeutic potential of the conjugate was assessed both in vitro, in GBM cell lines and spheroids by the CellTiter‐Glo® assay, and in vivo using subcutaneous U87‐MGvIII xenografts. In addition, mice were imaged pre‐ and post‐PIT using the IVIS/Spectrum/CT to monitor treatment response. Binding of the conjugate correlated to the level of EGFR expression in GBM cell lines. The cell proliferation assay revealed a receptor‐dependent response between the tested cell lines. Inhibition of EGFRvIII+ve tumor growth was observed following administration of the immunoconjugate and irradiation. Importantly, this response was not seen in control tumors. In conclusion, the Z_EGFR:03115–IR700DX showed specific uptake in vitro and enabled imaging of EGFR expression in the orthotopic brain tumor model. Moreover, the proof‐of‐concept in vivo PIT study demonstrated therapeutic efficacy of the conjugate in subcutaneous glioma xenografts.     

Neoadjuvant and adjuvant strategies in retroperitoneal sarcoma

Extended surgery remains the mainstay of treatment in retroperitoneal sarcoma, although conflicting data exist on the benefit of neoadjuvant and adjuvant therapies, particularly with regard to tumour grade and histological type. Experience of radiotherapy and chemotherapy in extremity soft tissue sarcoma can inform treatment strategies, however these data cannot be universally extrapolated to the retroperitoneum where disease biology and anatomical considerations are different. The present review sets a historical context before discussing recent evidence and on-going multi-centre trials in retroperitoneal sarcoma. Promising data on histologically- and molecularly-targeted chemotherapy are discussed and the need for centralisation of retroperitoneal sarcoma services in order to facilitate large international collaborative trials is emphasised.     

Monovalent cation permeability and Ca2+ block of the store-operated Ca2+ current I CRAC in rat basophilic leukemia cells

Like voltage-operated Ca(2+) channels, store-operated CRAC channels become permeable to monovalent cations in the absence of external divalent cations. Using the whole-cell patch-clamp technique, we have characterized the permeation and selectivity properties of store-operated channels in the rat basophilic leukemia (RBL-1) cell line. Store depletion by dialysis with InsP(3) and 10 mM EGTA resulted in the rapid development of large inward currents in Na(+)- and Li(+)-based divalent-free solutions. Cs(+) permeated the channels poorly (P(Cs)/ P(Na)=0.01). Trimethylamine (TMA(+)), tetramethylammonium (TeMA(+)), tetraethylammonium (TEA(+)), N-methyl- D-glucamine (NMDG(+)) and TRIS(+) were not measurably permeant. NH(4)(+) was conducted well. We estimated the minimum pore diameter under divalent-free conditions to be between 0.32 nm and 0.55 nm. When cells were dialysed with buffered Ca(2+) solution and I(CRAC) activated by application of thapsigargin, P(Cs)/ P(Na) was still low (0.08). Outward currents through CRAC channels were carried by intracellular Na(+), K(+) and, to a much lesser extent, by Cs(+). Currents were unaffected by dialysis with Mg(2+)-free solution. The Na(+) current was inhibited by external Ca(2+) (half-maximal blocking concentration of 10 microM). This Ca(2+)-dependent block could be alleviated by hyperpolarization. The monovalent Na(+) current was voltage dependent, increasing as the holding potential depolarized above 0 mV. Our results suggest that CRAC channels in RBL-1 cells have a smaller pore diameter than voltage-operated Ca(2+) channels, discriminate between Group I cations, and differ markedly in their selectivity from CRAC channels reported in lymphocytes.     

Method for screening of solid dispersion formulations of low-solubility compounds--miniaturization and automation of solvent casting and dissolution testing

An efficient method has been developed for screening solid dispersion formulations that are intended to enhance the dissolution of poorly soluble compounds. The method is based on miniaturization and automation of sample preparation by solvent casting, and dissolution testing, in a 96-well plate format, using less than 0.1mg of compound per well. To illustrate the method, six polymers and eight surfactants were screened, individually and in combination, for their ability to dissolve a compound with aqueous solubility of < 1 microg/ml in simulated intestinal fluid. Screening was performed at an excipient/compound ratio of 10:1, and a polymer/surfactant ratio of 3:1 for ternary formulations. Sixteen of the 48 ternary formulations dissolved the compound to a level > 100 microg/ml, i.e. at least a 100-fold increase over the aqueous solubility. A number of synergies were observed wherein the performance of a ternary formulation greatly exceeded that of either of the corresponding binary formulations. Thirteen 'hits' from screening were scaled up with melt methods, and approximately 2/3 of these showed comparable dissolution enhancement when tested at larger scale. Five of these were administered to rats, and the absolute oral bioavailability ranged from 10 to 23%, versus less than 1% for the unformulated compound.