A systematic review and meta-analysis of diagnostic performance of fluorescein-guided sentinel lymph node biopsy in early breast cancer.

BACKGROUND: Evaluation of axillary lymph nodes status in cN0 axilla is performed by sentinel lymph node biopsy (SLNB) utilizing a combination of radioactive isotope and blue dye or alternative to isotope like Indocyanine green (ICG). Both are very resource-intensive; which has prompted development of low-cost technique of Fluorescein Sodium (FS)-guided SLNB. This systematic review and meta-analysis evaluate the diagnostic performance of FS-guided SLNB in early breast cancer. OBJECTIVES: The objective was to evaluate the diagnostic performance of FS for sentinel lymph node biopsy. METHODS: Eligibility criteria: Studies where SLNB was performed using FS. INFORMATION SOURCES: PubMed, EMBASE, Cochrane library and online clinical trial registers. Risk of bias: Articles were assessed for risk of bias using the QUADAS-2 tool. SYNTHESIS OF RESULTS: The main summary measures were pooled Sentinel Lymph Node Identification Rate (SLN-IR) and pooled False Negative Rate (FNR) using random-effects model. RESULTS: A total of 45 articles were retrieved by the initial systematic search. 7 out of the 45 studies comprising a total of 332 patients were included in the meta-analysis. The pooled SLN-IR was 93.2% (95% confidence interval [CI], 0.87-0.97; 87% to 97%). Five validation studies were included for pooling the false negative rate and included a total of 211 patients. The pooled FNR was 5.6% (95% confidence interval [CI], 2.9-9.07). CONCLUSION: Fluorescein-guided SLNB is a viable option for detection of lymph node metastases in clinically node negative patients with early breast cancer. It achieves a high pooled Sentinel Lymph Node Identification Rate (SLN-IR) of 93% with a false negative rate of 5.6% for the detection of axillary lymph node metastasis.

Microsurgical clipping of large MCA aneurysm in a 2-month-old child.

BACKGROUND: Cerebral aneurysms in children have a low incidence and accounts for less than 4% of all cerebral aneurysms. These aneurysms have been linked to various factors. Severe headache, seizures, and motor-sensory deficits are common presentations. CASE REPORT: We describe the case of a 2-month-old male patient who presented with generalized tonic-clonic seizures for 4 days. At the hospital, he was stabilized with ventilatory support, sedation, and antiepileptic drugs. A NCCT (Head) showed intraparenchymal hemorrhage in the left fronto-parieto-temporal lobe and subarachnoid hemorrhage. Subsequently a CT angiogram revealed an aneurysm of the left M3 segment of MCA. Successfully, the patient underwent microsurgical clipping of aneurysm and evacuation of hematoma. CONCLUSIONS: Pediatric cerebral aneurysms differ from their adult counterparts, mainly in their etiology and evolution. As per literature, aneurysmal clipping and neurological endovascular therapy have shown similar results.

Immunoinformatics based designing a multi-epitope vaccine against pathogenic Chandipura vesiculovirus.

Chandipura vesiculovirus (CHPV) is a rapidly emerging pathogen responsible for causing acute encephalitis. Due to its widespread occurrence in Asian and African countries, this has become a global threat, and there is an urgent need to design an effective and nonallergenic vaccine against this pathogen. The present study aimed to develop a multi-epitope vaccine using an immunoinformatics approach. The conventional method of vaccine design involves large proteins or whole organism which leads to unnecessary antigenic load with increased chances of allergenic reactions. In addition, the process is also very time-consuming and labor-intensive. These limitations can be overcome by peptide-based vaccines comprising short immunogenic peptide fragments that can elicit highly targeted immune responses, avoiding the chances of allergenic reactions, in a relatively shorter time span. The multi-epitope vaccine constructed using CTL, HTL, and IFN-γ epitopes was able to elicit specific immune responses when exposed to the pathogen, in silico. Not only that, molecular docking and molecular dynamics simulation studies confirmed a stable interaction of the vaccine with the immune receptors. Several physicochemical analyses of the designed vaccine candidate confirmed it to be highly immunogenic and nonallergic. The computer-aided analysis performed in this study suggests that the designed multi-epitope vaccine can elicit specific immune responses and can be a potential candidate against CHPV.

Role of integrative medicine in the continuum of care of breast cancer patients in the Indian context.

Breast cancer is the most frequently diagnosed cancer among women in both transitioned and transitioning countries and has become a major women's health problem. Although recent advances in our understanding of the biological nature of cancer, improved awareness coupled with better early detection facilities, use of chemotherapy, hormone therapy, and targeted therapy have significantly improved survival from cancer, there are many gaps in providing individual-centric, holistic care. Integrative medicine refers to the use of traditional medicine alongside conventional preventive or therapeutic interventions (allopathic medicine) as a comprehensive, individual-centered, evidence-based care. The three pillars of complementary medicine (lifestyle modifications, mind-body practices, and use of natural products) have the potential for cancer prevention and improving quality-of-life and even treatment response in cancer patients when combined with conventional oncology care. Therefore, continued research into integrative therapies is required to extend the benefits to a broader patient population and improve outcomes in breast and other common cancers. In the present review article, the possible role of integrative medicine across the breast cancer care continuum has been discussed along with the concept of integrating complementary practices into mainstream health delivery. We have focused on breast cancer as a model cancer that is well amenable to prevention, early detection and stage appropriate treatment. However, our observations are pertinent for other common cancers, for which there are several opportunities for improving the continuum of care, especially in developing countries like India.

"Dial of a Clock" Search Pattern for Clinical Breast Examination.

BACKGROUND: Clinical breast examination (CBE) is an integral component of triple assessment for women presenting with symptomatic breast disease. Four common search patterns of CBE are "dial of a clock" (DC), "vertical strips" (VS), "quadrant-wise" (QW), and "concentric circles" (CC). The most sensitive search pattern of CBE has not been established. METHODS: A cross-sectional study was conducted on women with symptomatic breast disease, to measure various diagnostic performance indices of four different search patterns of CBE by a professor, a surgical resident trainee, and a trained nurse. Women were examined one at a time randomly by three examiners. Each examiner examined with four different search patterns of CBE, one method at a time. Any nodularity or lump detected was noted and the findings were compared with breast sonography, which was considered as the gold standard. Statistical analysis was done using STATA 14, SPSS 20, and OpenEpi software for diagnostic test indices. RESULTS: Sixty women (mean age = 39.6) with palpable findings of both breasts were included (n = 120). Most women presented with complaints of breast lump (70%) and mastalgia (27%). Sensitivity was highest for DC as elaborated [% (95% confidence interval)]: DC[73.2 (60-83)] > CC[66 (53-77)] > VS[62.5 (49-73)] > QW[58.9 (45-70)] for professor; DC[64.2 (51-75)] > VS[62.5 (49-73)] > CC[57.1 (44-69)] > QW[57.1 (44-69)] for resident; and DC[82.1 (70- 90)] > VS[78.5 (66-87)] > CC(75 (62-84)] > QW[73.2 (60-83)] for nurse. The minimum sonographic tumor size picked up by DC by all the examiners was 7 mm. CONCLUSIONS: The DC search pattern of CBE demonstrated the highest sensitivity for all the examiners. The trained nurse achieved the highest sensitivity among all the examiners.

Paravertebral anaesthesia with or without sedation versus general anaesthesia for women undergoing breast cancer surgery.

BACKGROUND: Breast cancer is one of the most common cancers among women. Surgical removal of the cancer is the mainstay of treatment; however, tumour handling during surgery can cause microscopic dissemination of tumour cells and disease recurrence. The body's hormonal response to surgery (stress response) and general anaesthesia may suppress immunity, promoting tumour dissemination. Paravertebral anaesthesia numbs the site of surgery, provides good analgesia, and blunts the stress response, minimising the need for general anaesthesia. OBJECTIVES: To assess the effects of paravertebral anaesthesia with or without sedation compared to general anaesthesia in women undergoing breast cancer surgery, with important outcomes of quality of recovery, postoperative pain at rest, and mortality. SEARCH METHODS: On 6 April 2020, we searched the Specialised Register of the Cochrane Breast Cancer Group (CBCG); CENTRAL (latest issue), in the Cochrane Library; MEDLINE (via OvidSP); Embase (via OvidSP); the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal; and ClinicalTrials.gov for all prospectively registered and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) conducted in adult women undergoing breast cancer surgery in which paravertebral anaesthesia with or without sedation was compared to general anaesthesia. We did not include studies in which paravertebral anaesthesia was given as an adjunct to general anaesthesia and then this was compared to use of general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted details of trial methods and outcome data from eligible trials. When data could be pooled, analyses were performed on an intention-to-treat basis, and the random-effects model was used if there was heterogeneity. When data could not be pooled, the synthesis without meta-analysis (SWiM) approach was applied. The GRADE approach was used to assess the certainty of evidence for each outcome. MAIN RESULTS: Nine studies (614 participants) were included in the review. All were RCTs of parallel design, wherein female patients aged > 18 years underwent breast cancer surgery under paravertebral anaesthesia or general anaesthesia. None of the studies assessed quality of recovery in the first three postoperative days using a validated questionnaire; most assessed factors affecting quality of recovery such as postoperative analgesic use, postoperative nausea and vomiting (PONV), hospital stay, ambulation, and patient satisfaction. Paravertebral anaesthesia may reduce the 24-hour postoperative analgesic requirement (odds ratio (OR) 0.07, 95% confidence interval (CI) 0.01 to 0.34; 5 studies, 305 participants; low-certainty evidence) compared to general anaesthesia. Heterogeneity (I² = 70%) was attributed to the fixed dose of opioids and non-steroidal analgesics administered postoperatively in one study (70 participants), masking a difference in analgesic requirements between groups. Paravertebral anaesthesia probably reduces the incidence of PONV (OR 0.16, 95% CI 0.08 to 0.30; 6 studies, 324 participants; moderate-certainty evidence), probably results in a shorter hospital stay (mean difference (MD) -79.39 minutes, 95% CI -107.38 to -51.40; 3 studies, 174 participants; moderate-certainty evidence), and probably reduces time to ambulation compared to general anaesthesia (SWiM analysis): percentages indicate vote counting based on direction of effect (100%, 95% CI 51.01% to 100%; P = 0.125; 4 studies, 375 participants; moderate-certainty evidence). Paravertebral anaesthesia probably results in higher patient satisfaction (MD 5.52 points, 95% CI 1.30 to 9.75; 3 studies, 129 participants; moderate-certainty evidence) on a 0 to 100 scale 24 hours postoperatively compared to general anaesthesia. Postoperative pain at rest and on movement was assessed at 2, 6, and 24 postoperative hours on a 0 to 10 visual analogue scale (VAS). Four studies (224 participants) found that paravertebral anaesthesia as compared to general anaesthesia probably reduced pain at 2 postoperative hours (MD -2.95, 95% CI -3.37 to -2.54; moderate-certainty evidence). Five studies (324 participants) found that paravertebral anaesthesia may reduce pain at rest at 6 hours postoperatively (MD -1.54, 95% CI -3.20 to 0.11; low-certainty evidence). Five studies (278 participants) found that paravertebral anaesthesia may reduce pain at rest at 24 hours postoperatively (MD -1.19, 95% CI -2.27 to -0.10; low-certainty evidence). Differences in the methods of two studies (119 participants) and addition of clonidine to the local anaesthetic in two studies (109 participants), respectively, contributed to the heterogeneity (I² = 96%) observed for these two outcomes. Two studies (130 participants) found that paravertebral anaesthesia may reduce pain on movement at 6 hours (MD-2.57, 95% CI -3.97 to -1.17) and at 24 hours (MD -2.12, 95% CI -4.80 to 0.55; low-certainty evidence). Heterogeneity (I² = 96%) was observed for both outcomes and could be due to methodological differences between studies. None of the studies reported mortality related to the anaesthetic technique. Eight studies (574 participants) evaluated adverse outcomes with paravertebral anaesthesia: epidural spread (0.7%), minor bleeding (1.4%), pleural puncture not associated with pneumothorax (0.3%), and Horner's syndrome (7.1%). These complications were self-limiting and resolved without treatment. No data are available on disease-free survival, chronic pain, and quality of life. Blinding of personnel or participants was not possible in any study, as a regional anaesthetic technique was compared to general anaesthesia. Risk of bias was judged to be serious, as seven studies had concerns of selection bias and three of detection bias. AUTHORS' CONCLUSIONS: Moderate-certainty evidence shows that paravertebral anaesthesia probably reduces PONV, hospital stay, postoperative pain (at 2 hours), and time to ambulation and results in greater patient satisfaction on the first postoperative day compared to general anaesthesia. Paravertebral anaesthesia may also reduce postoperative analgesic use and postoperative pain at 6 and 24 hours at rest and on movement based on low-certainty evidence. However, RCTs using validated questionnaires are needed to confirm these results. Adverse events observed with paravertebral anaesthesia are rare.

Regulatory safety pharmacology and toxicity assessments of a standardized stem extract of Cassia occidentalis Linn. in rodents.

Cassia occidentalis Linn (CO) is an annual/perennial plant having traditional uses in the treatments of ringworm, gastrointestinal ailments and piles, bone fracture, and wound healing. Previously, we confirmed the medicinal use of the stem extract (ethanolic) of CO (henceforth CSE) in fracture healing at 250 mg/kg dose in rats and described an osteogenic mode of action of four phytochemicals present in CSE. Here we studied CSE's preclinical safety and toxicity. CSE prepared as per regulations of Current Good Manufacturing Practice for human pharmaceuticals/phytopharmaceuticals and all studies were performed in rodents in a GLP-accredited facility. In acute dose toxicity as per New Drug and Clinical Trial Rules, 2019 (prior name schedule Y), in rats and mice and ten-day dose range-finding study in rats, CSE showed no mortality and no gross abnormality at 2500 mg/kg dose. Safety Pharmacology showed no adverse effect on central nervous system, cardiovascular system, and respiratory system at 2500 mg/kg dose. CSE was not mutagenic in the Ames test and did not cause clastogenicity assessed by in vivo bone marrow genotoxicity assay. By a sub chronic (90 days) repeated dose (as per OECD, 408 guideline) study in rats, the no-observed-adverse-effect-level was found to be 2500 mg/kg assessed by clinico-biochemistry and all organs histopathology. We conclude that CSE is safe up to 10X the dose required for its osteogenic effect.

Corynebacterium striatum: An emerging nosocomial skin and soft-tissue pathogen.

The genus Corynebacterium is composed of Gram-positive, aerobic, non-motile, non-spore-forming bacilli that are widely distributed throughout the environment. They are usually found as commensals on the skin and are often considered as mere contaminants when isolated from clinical samples. We describe a patient with skin and soft-tissue infections due to Corynebacterium striatum following exploratory laparotomy identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The clinical importance and pathogenic potential of Corynebacterium species, especially C. striatum, cannot be underestimated. This report is a reminder to physicians of the possible pathogenicity of non-diphtherial Corynebacteria.

Improving and calibrating channel erosion simulation in the Water Erosion Prediction Project (WEPP) model.

The Water Erosion Prediction Project (WEPP) model has been widely used to assess the impacts of management practices and climate change on runoff and soil loss at both hillslope and watershed scales. However, the representation of channel erosion processes in WEPP has not been changed significantly since it was released. The current (WEPP v2012.8) and previous WEPP versions assume that channel input erodibility parameters are constant through time, which may lead to erroneous channel detachment predictions, especially for cropland with substantial tillage operations. In this research, the temporally constant values of channel erodibility and critical shear stress were replaced by daily updated values, using the same temporal erodibility and critical shear stress adjustments that are applied in hillslope profile simulations for rill detachment. Observed watershed-scale runoff and soil erosion data from six agricultural watersheds were used to calibrate and compare the WEPP model performance in simulating channel runoff volumes and soil losses before and after the modification. The research showed both WEPP v2012.8 and the modified WEPP model (WEPP_CE) could satisfactorily simulate event-based hydrology and soil erosion at the watershed outlets after calibration. The WEPP_CE model with temporally varying channel erodibility and critical shear stress values demonstrated improved representation of the physical processes in channel soil detachment. Continued improvement in the representation of channel erosion processes in WEPP and other process-based models is needed. The improved WEPP model can be used to evaluate the effectiveness of soil conservation practices on hydrology and erosion in further research.

Endoscopic thyroidectomy: Which one is the better technique for the beginners?

INTRODUCTION: Endoscopic thyroidectomy is an advanced procedure and has a long learning curve. Most commonly employed approach is combined axillary-breast approach (ABA). Recently, transoral endoscopic thyroidectomy vestibular approach (TOETVA) is being popularised as a scarless procedure. However, it is not established whether TOETVA or ABA approach is better to begin with. PURPOSE: The purpose of the study was to compare the initial experience of TOETVA and ABA with respect to difficulties and outcomes. METHODOLOGY: A prospective non-randomised interventional study was conducted including the initial ten patients in each group who underwent hemithyroidectomy for benign solitary thyroid nodule. Sigma plot version 12.3 was used for the statistical analysis. RESULTS: All the patients were female and comparable with respect to age (33.2 vs. 28.2 years) and size of nodule (2.7 vs. 3 cm) (TOETVA vs. ABA). The operative time (121 vs. 138.5 min, P = 0.34) and blood loss (50 vs. 60 ml, P = 0.9) were similar in both the groups. Even though the flap raising time was significantly less with TOETVA group (29.3 vs. 47.2 min, P < 0.001), it was associated with more difficulty in approaching upper pole (P = 0.02) and lower pole (P < 0.001), more intra-operative events (30% vs. 10%, P = 0.58) and conversions to open (20% vs. 10%, P = 1). Similarly, post-operative pain scoring was more with TOETVA (3 vs. 2, P = 0.04). Hospital stay was similar in both the groups (2.5 vs. 3 days, P = 1). Patients in both the groups had both overall and cosmetic satisfaction. CONCLUSIONS: Axillary-breast approach should be preferred to start learning the endoscopic thyroidectomy, as it is easier and safer than transoral endoscopic vestibular approach.