Clinical trial: Effects of treatment with a vibrating capsule in patients with severe chronic constipation.

BACKGROUND: There is little information on the effectiveness of therapies for severe chronic constipation. In a phase 3 trial, we previously demonstrated that a vibrating capsule was significantly more efficacious than a placebo in chronic constipation. AIM: To examine the effects of a vibrating capsule and placebo on symptoms and health-related quality of life (HRQoL) in patients with severe chronic constipation. METHODS: We performed a post hoc analysis of phase 3, multicentre, randomised, double-blind, and placebo-controlled 8-week clinical trial of a vibrating capsule to specifically assess outcomes among subjects who reported 0 complete spontaneous bowel movements (CSBMs) during the 2-week baseline period. We assessed effects of treatment on bowel symptoms, patient satisfaction, and HRQoL. CSBM responders were defined as subjects with increases of ≥1 or ≥2 or ≥3 weekly CSBMs (CSBM1 or CSBM2, CSBM3, respectively) over baseline for ≥6 out of 8 weeks of treatment. RESULTS: The severe chronic constipation subgroup comprised 175 (56%) of the 312 subjects. Significantly more subjects with severe chronic constipation who received the vibrating capsule than those who received the placebo were CSBM1 (44.9% vs. 20.9%, p = 0.007), CSBM2 (29.2% vs. 11.6%, p = 0.004), and CSBM3 (19.10% vs 6.98%, p = 0.017) responders. Straining effort, stool consistency, patient satisfaction, and HRQoL significantly improved in the severe chronic constipation subgroup. A mild vibrating sensation was reported in 10%. CONCLUSION: The vibrating capsule significantly improved constipation-related symptoms and HRQoL in patients with severe constipation, affirming its efficacy and safety across the spectrum of chronic constipation.

Review article: advances in the diagnosis and management of anorectal motility disorders.

BACKGROUND: Anorectal motility disorders such as dyssynergic defecation (DD), faecal incontinence (FI) and anorectal pain affect 40% of the population and are a frequent reason for gastroenterology consultation. They significantly affect the quality of life and lead to psychological distress. Lack of understanding of these problems compounded by a lack of availability and knowledge of diagnostic tools in most medical centres and/or trained physicians has significantly hampered this field. AIMS: To discuss the latest advances in pathophysiology, diagnostic tests and therapeutic options for these disorders using an evidence-based approach. METHODS: We reviewed the published literature over the past 20 years on DD, FI and anorectal pain and distilled these into a narrative review. RESULTS: A detailed history, prospective stool diary and digital rectal exam, together with diagnostic tests such as anorectal manometry, balloon expulsion test, translumbosacral anorectal magnetic stimulation test for assessing neuropathy, defecography and anal ultrasound, can provide detailed mechanistic and structural information. Such knowledge can pave the way for a meaningful and pathophysiologic-based management approach. This could include biofeedback therapy for DD or FI, sensory training for rectal hyposensitivity or sensory adaptation training for rectal hypersensitivity or sphincter bulking agents or neuromodulation therapies. These treatments are effective and safe. CONCLUSIONS: Anorectal motility disorders are common, but either less well recognized or poorly managed by most gastroenterologists. Equipped with the practical and up-to-date knowledge provided in this review, physicians could provide improved health care for these patients.

The role of a social determinants of health summary measure on the association between cancer history status and colorectal cancer screening utilization among screening eligible adults.

Objective: We sought to examine the influence of social needs on the relationship between cancer history and colorectal cancer (CRC) screening utilization among adults in the United States. Methods: We conducted a cross-sectional analysis using data from the 2022 Behavioral Risk Factor Surveillance System. Our outcome of interest was utilization of guideline-concordant CRC screening and exposures of interest were cancer history/levels of social needs. Multivariable logistic regression was performed to examine the association. Results: Among 74,743 eligible adults, a majority did not have a personal history of cancer (87.9 %), had at least one social need (58.4 %), and had undergone CRC screening (72.2 %). In multivariable analysis, a history of cancer was positively associated with use of CRC screening (OR = 1.59, 95 %CI, 1.35 - 1.87). Having at least one social need was associated with lower likelihood of being screened (one social need: OR = 0.85 95 %CI, 0.76 - 0.95; two + social needs: OR = 0.77, 95 % CI, 0.69 - 0.87). When exploring the effects of social needs, adults without a history of cancer who reported at least one need were 12-20 % less likely to be screened for CRC. Conclusions: A personal history of cancer was associated with greater utilization of CRC screening, whilst having at least one social need had lower screening use. Having social needs plays an important role in reducing screening uptake among adults without a history of cancer. Integrated care that considers both cancer history and social needs may have implications for improved adherence of CRC screening recommendations.

Clinical, Radiological, and Pathological Correlation of Mandibular Invasion in Carcinoma Bucco-alveolar Complex.

A prospective cross-sectional study was conducted to correlate clinically, radiologically, and pathologically the mandibular invasion in carcinoma bucco-alveolar complex. All biopsy-proven oral cavity cancer cases (64 patients) were assessed clinically and radiologically for involvement of the mandible. Preoperative clinicoradiological findings were compared with postoperative histopathological findings. In our study, oral cancer was 4 times more prevalent in males as compared to females and clinical evaluation was found to be highly sensitive in predicting mandibular invasion. Orthopantomogram showed sensitivity of 66.6% and specificity of 100%. CT scan showed sensitivity of 100% and specificity of 46% whereas MRI showed sensitivity of 54.5% and a specificity of 96%. MRI correlates well with final histopathology in predicting size of tumor. Prevalence of bony invasion in carcinoma oral cavity was 18%. We noted an inverse relation with tumor differentiation and mandibular invasion, and none of the verrucous carcinoma lesions showed mandibular invasion. Association of clinical T and N staging with postoperative histopathology was found to be statistically significant. Despite recent advances in molecular biology, radiological techniques, and newer modalities like visual surgical planning, exact measurement of bone invasion is still challenging. At present, CT scan and MRI along with clinical evaluation are widely used to evaluate mandibular invasion in carcinoma oral cavity, and all these are complementary to each other. The recent progress in tissue engineering technologies and stem cell biology has significantly promoted the development of regenerative reconstruction of jawbone defects.

Selective therapy (cryo or scalpel) combined with multimodal therapy for treating keloids.

Background: Keloids are less responsive to any single treatment modality; hence, there is a need for combination therapy that can yield satisfactory outcomes. Objective: The present study assessed efficacy and safety of combination therapy-surgical excision or cryotherapy and intralesional corticosteroids along with 5-fluorouracil [IL (S + 5-FU)] injection, followed by silicone gel sheet (SGS) under compression therapy in the treatment of keloids. Materials and Methods: This was a retrospective, observational study comprising 21 clinically diagnosed keloid patients. All patients were treated with the stated combination therapy. Data about demographic, lesions, procedural characteristics, and treatment outcomes were reported. Results: Of 21, 11 (52.4%) patients were treated with liquid nitrogen (LN2) cryotherapy, and 10 (47.6%) patients were treated with surgical excision. Mean age was 30.8 ± 7.6 (range: 14-44) years with slight male (52.4%) predominance. A mean surface area of keloid lesion was 96.8 ± 170.5 cm3. The most frequently involved site was auricle (8 [38.1%] patients). Patients received the following types of treatments: intralesional LN2 cryotherapy (6 [28.6%]), intralesional excisional surgery (6 [28.6%]), surface LN2 cryotherapy (5 [23.8%]), and extralesional excisional surgery (4 [19.0%]). Complications of recurrence (2 [9.5%]), secondary infections (2 [9.5%]), persistent postinflammatory hypopigmentation (1 [4.8%]), and atrophic scarring with postinflammatory hyperpigmentation (1 [4.8%]) were reported. After a study period of 2.5 years, 100% cure rate was achieved. Conclusion: Combination therapy of surgical excision or cryotherapy and IL (S + 5-FU), followed by SGS under compression, was safe and effective in treating keloids.

Plecanatide Improves Abdominal Bloating and Bowel Symptoms of Irritable Bowel Syndrome with Constipation.

BACKGROUND: Bloating is a bothersome symptom in irritable bowel syndrome with constipation (IBS-C). AIM: To evaluate plecanatide efficacy in patients with IBS-C stratified by bloating intensity. METHODS: Pooled phase 3 data (2 randomized, controlled IBS-C trials) from adults treated with plecanatide 3 mg or placebo for 12 weeks were analyzed. Patients were stratified post-hoc by baseline bloating severity (11-point scale: mild [≤ 5] and moderate-to-severe [> 5]). Assessments included change from baseline in bloating, abdominal pain, and complete spontaneous bowel movement (CSBM) frequency. Abdominal pain and bloating composite responders were defined as patients with ≥ 30% improvement from baseline in both bloating and abdominal pain at Week 12. RESULTS: At baseline, 1104/1436 patients with IBS-C (76.9%) reported moderate-to-severe bloating. In the moderate-to-severe bloating subgroup, plecanatide significantly reduced bloating severity versus placebo (least-squares mean change [LSMC]: - 1.7 vs - 1.3; P = 0.002), reduced abdominal pain (- 1.7 vs - 1.3; P = 0.006), and increased CSBM frequency (1.4 vs 0.8; P < 0.0001). In the mild bloating subgroup, significant improvements were observed with plecanatide versus placebo for abdominal pain (LSMC: - 1.3 vs - 1.0; P = 0.046) and CSBM frequency (2.0 vs 1.2; P = 0.003) but not bloating (- 0.9 vs - 0.8; P = 0.28). A significantly greater percentage of patients were abdominal pain and bloating composite responders with plecanatide versus placebo (moderate-to-severe bloating: 33.6% vs 26.8% [P = 0.02]; mild bloating: 38.4% vs 27.2% [P = 0.03]). CONCLUSION: Plecanatide treatment improved IBS-C abdominal and bowel symptoms, including in those who present with moderate-to-severe bloating.

Capsules for the Diagnosis and Treatment of Gastrointestinal Motility Disorders- A Game Changer.

PURPOSE OF REVIEW: Over the last few decades, there have been remarkable strides in endoscopy and radiological imaging that have advanced gastroenterology. However, the management of neurogastroenterological disorders has lagged behind, in part handicapped by the use of catheter-based manometry that is both non-physiological and uncomfortable. The advent of capsule technology has been a game changer for both diagnostic and therapeutic applications. RECENT FINDINGS: Here, we discuss several capsule devices that are available or under investigation. There are three technologies that are FDA approved. Wireless motility capsule measures pH and pressure and provides clinically impactful information regarding gastric, small intestine and colonic transit, without radiation that has been demonstrated to guide management of gastroparesis, dyspepsia and constipation. Wireless ambulatory pH monitoring capsule is currently the gold standard for assessing gastroesophageal acid reflux. In the therapeutics arena, an orally ingested vibrating capsule has been recently FDA approved for the treatment of chronic constipation, supported by a robust phase 3 clinical trial which showed significant improvement in constipation symptoms and quality of life. There are several capsules currently under investigation. Smart capsule bacterial detection system and Capscan® are capsules that can sample fluid in the small or large bowel and provide microbiome analysis for detection of small intestinal bacterial (SIBO) or fungal overgrowth (SIFO). Another investigational gas sensing capsule analyzing hydrogen, CO2, volatile fatty acids and capsule orientation, can measure regional gut transit time and luminal gas concentrations and assess gastroparesis, constipation or SIBO. Therapeutically, other vibrating capsules are in development. Innovations in capsule technology are poised to transform our ability to investigate gut function physiologically, and non-invasively deliver targeted treatment(s), thereby providing both accurate diagnostic information and luminally-directed, safe therapy.

Preliminary results of hypofractionated radiotherapy in breast cancer in Chandigarh, India: single-centre, non-inferiority, open-label, randomised, phase 3 trial.

Background: Globally, most of the randomised trials with hypofractionation in patients with breast cancer have used 3-dimensional conformal radiotherapy technique (3D-CRT). As facilities for 3D-CRT technique may not be available in low-resource settings, there is a need to see if hypofractionation is feasible and safe with 2-dimensional (2-D) technique. In this study, we compared a 3-week radiation schedule with a 2-week schedule of hypofractionated radiotherapy in patients with breast cancer with 2-D technique. Methods: The current study was an open-label, randomised, phase 3 trial. Patients with breast cancer, stage I-III, post mastectomy or after breast conservative surgery who needed adjuvant locoregional radiotherapy were randomised in the Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India; to 34Gy in 10 fractions over 2 weeks (2-week arm) or 35Gy in 15 fractions over 3 weeks to the chest wall and 40Gy/15#/3wks to breast and supraclavicular fossa (3-week arm). Boost dose when indicated was 8-10Gy/2-4#/2-4 days in both the arms. Patients were planned on a 2-dimensional (2D) simulator with 2 tangential fields to breast/chest wall and incident supraclavicular fossa field. Acute toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) grading scale. Assessments were carried out weekly during radiotherapy and at 4 weeks after treatment by the physician. Cosmetic outcome was assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG scale. The toxicity rates between the two arms were compared using Fisher's exact tests. The trial was approved by institutional ethics committee and registered with ClinicalTrials.gov, number NCT04075058. Findings: This study included 1121 eligible patients from June 2015 to December 2020. Median follow-up was 35 months (6-84 months). Mean age was 48 years (24-75 years). The patient characteristics were comparable between the two arms except for more mastectomies in the 3-week arm and more node-positive patients in the 2-week arm. There were more oestrogen receptor-positive tumors in the 3-week arm. Acute skin toxicities were comparable between the two arms. Grade 2 and 3 skin toxicity was 100 (18%) and 82 (15%); and 16 (3%) and 12 (2%) in the 3-week and 2-week arm (p = 0.21), respectively. Cosmetic outcome was assessed as Excellent or Good for 89% of patients in the 3-week arm as compared to 94% in the 2-week arm (p = 0.004). Interpretation: The two radiation schedules were comparable in terms of acute skin toxicity. The cosmetic outcome was better with the 2-week schedule. The preliminary findings indicate 2-week radiotherapy schedule with 2-D technique was better than the 3-week schedule in patients with breast cancer. However, disease outcomes and late-term toxicities need to be further checked. Funding: This study was funded by Science and Engineering Research Board (SERB), India.

Efficacy and Safety of Carbon Dioxide Laser Ablation Combined with Manual Dermabrasion and Intralesional 5-Fluorouracil Injection in Bowen's Disease.

Background: Bowen's disease (BD) is a precancerous in-situ squamous cell carcinoma and has a high recurrence rate with any single treatment modality, necessitating combination therapy for a successful outcome. Aim: This study aimed to the efficacy and safety of carbon dioxide (CO2) laser ablation followed by manual dermabrasion and intralesional 5-fluorouracil (IL 5-FU) injection as combination therapy for BD. Materials and Methods: This was a retrospective, observational study comprising 29 clinically and histopathologically diagnosed BD patients with no history of prior treatment. Demographic characteristics and clinical examination of the lesions and regional lymph nodes were retrieved. All patients were subjected to CO2 laser ablation followed by manual dermabrasion and IL 5-FU injection. Results: Mean age was 61.93 ± 9.31 years with male preponderance (62.1%). Trunk (48.3%) was the most frequently involved site. Mean tumor size was 40.8 ± 16.4 mm (range: 15-86 mm). All lesions healed with a cure rate of 96.6%. Complications seen in patients included atrophic scarring with persistent post-inflammatory hyperpigmentation in three patients (10.3%), secondary infection in two cases (6.9%), and hypertrophic scar with early keloid in one patient (3.4%). Recurrence was reported in one patient (3.4%). Limitation: The study was limited by retrospective study design, small sample size, and no comparison with standard therapy. Conclusion: Combination approach using carbon dioxide laser ablation followed by manual dermabrasion and IL 5-FU injection has been proved to be effective, efficient and safe with good functional, oncological and aesthetic outcomes in treating BD.

Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm.

OBJECTIVE: To comprehensively evaluate the efficacy, safety, patient symptoms, and quality-of-life (QoL) of lubiprostone, linaclotide, and elobixibat as treatment for chronic constipation (CC). DESIGN: Systematic literature review (SLR) and meta-analysis (MA). Literature searches were conducted on PubMed and Embase using the Ovid platform. METHODS: SLR including randomized controlled trials (RCTs) and observational studies was conducted to identify the overall efficacy and safety of lubiprostone, linaclotide, and elobixibat. Thereafter, MA was performed using only RCTs. The number needed to treat (NNT) and number needed to harm (NNH) analyses were additionally conducted. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was efficacy regarding change in spontaneous bowel movements. Secondary outcomes included safety, constipation-related symptoms, and QoL. RESULTS: Twenty-four studies met the inclusion criteria for the SLR: 17 RCTs, 4 observational studies, and 3 single-arm trials. Feasibility assessment for the MA resulted in 14 studies available for safety data analysis, and 8 available for efficacy analysis, respectively. Three drugs showed similar efficacy in the MA and NNT analysis. However, the NNH analysis revealed distinct safety profiles: lubiprostone, linaclotide, and elobixibat were linked to the highest risk of nausea, diarrhea, and abdominal pain, respectively. CONCLUSION: The current study provides an updated overview of the efficacy, safety, patient symptoms, and QoL of the three drugs with different mechanisms of action for CC treatment.The findings could help physicians adopt an individualized approach for treating patients with CC in clinical practice.

Accuracy of patient-reported bowel symptoms for fecal incontinence: Historical recall versus prospective evaluation.

INTRODUCTION: Fecal incontinence (FI) is characterized by both irregular and unpredictable bowel symptoms. An accurate history of symptoms is important for diagnosis and guiding management. Whether a patient's history of bowel symptoms is reliable or if there is recall bias is unknown. AIM: To evaluate the accuracy of FI symptoms based on patient's recall compared with a prospective stool diary. METHODS: FI (Rome IV) patients completed a bowel questionnaire that included leakage episodes and stool consistency. Subsequently they completed a one-week FI stool diary. Agreement and correlation between historical recall and stool diary were compared. RESULTS: One hundred patients participated. On average they reported 12 bowel movements (BMs) and five FI episodes per week. Fifty-two percent had completed under-graduation, 33% high school and 15% postgraduation. Using recall, 23% of patients accurately reported the number of FI episodes, whereas 41% underestimated and 36% overestimated its prevalence compared to the FI diary. Similarly, the concordance for the number of BMs was 30%, urgency was 54%, amount of stool leakage was 16%, and stool consistency was 12.5%. The concordance for nocturnal FI events, use of pads and lack of stool awareness were 63%, 75%, and 66.6% respectively. CONCLUSION: There is poor concordance for key bowel symptoms including the number of FI episodes as reported by FI patients, suggesting significant recall bias. Thus, historical recall of chronic FI symptoms may be less accurate. A prospective stool diary could provide more accurate information for the evaluation of FI patients.

Evaluation of bidirectional gut-brain axis and anorectal function in Parkinson's disease with constipation.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative movement disorder with prodromal and highly prevalent gastrointestinal (GI) symptoms, especially constipation. Although PD models suggest gut-brain axis dysfunction, the mechanistic underpinnings and their correlation with GI symptoms are poorly understood. AIM: To examine the bidirectional gut-brain axis function in PD and correlate it with constipation severity, PD duration, and severity. METHODS: Rectal sensory thresholds and afferent cortical evoked potentials (CEP) were assessed using a 4-ring EMG electrode probe. Efferent anal and rectal motor evoked potentials (MEPs) were obtained following transcranial and lumbosacral magnetic stimulation. Bowel symptoms were assessed by prospective stool diary. The CEP and MEP latencies, rectal sensory thresholds, and anorectal sensorimotor data were compared between PD subjects and age-adjusted healthy subjects. KEY RESULTS: Twenty-five PD subjects with constipation (F/M = 6/19) and 20 healthy subjects (F/M = 14/6) were enrolled. The first and pain sensation thresholds were higher in PD subjects than healthy subjects (p < 0.002) but lost significance after adjustment for age. Age-adjusted rectal CEP and right-sided cortico-anal MEP latencies were prolonged in PD subjects compared to healthy subjects (p < 0.04). Also, half (4 of 8) age-adjusted spino-anal and rectal MEP latencies in PD subjects were significantly longer. In multivariate linear analysis, first rectal sensation and right-sided MEP latencies showed moderate correlation with constipation severity. CONCLUSIONS & INFERENCES: Parkinson's disease is associated with significant bidirectional gut-brain axis dysfunction as evidenced by prolonged afferent and efferent neuronal signaling. Constipation severity in PD is correlated to abnormal rectal sensation and lateralized disturbance of efferent brain-gut signaling.

A Novel Biophysical Model for the Generation of Sharp Wave Ripples in CA1 Hippocampus.

Synchronous activities among neurons in the brain generate emergent network oscillations such as the hippocampal Sharp-wave ripples (SPWRs) that facilitate information processing during memory formation. However, how neurons and circuits are functionally organized to generate oscillations remains unresolved. Biophysical models of neuronal networks can shed light on how thousands of neurons interact in intricate circuits to generate such emergent SPWR network events. Here we developed a large-scale biophysically realistic neural network model of CA1 hippocampus with functionally organized circuit modules containing distinct types of neurons. Model simulations reproduced synaptic, cellular and network aspects of physiological SPWRs. The model provided insights into the role of neuronal types and their microcircuit motifs in generating SPWRs in the CA1 region. The model also suggests experimentally testable predictions including the role of specific neuron types in the genesis of hippocampal SPWRs.

A Case Report of Cytarabine-Induced Red Ear Syndrome.

Cytarabine is an antimetabolite used in the treatment of acute myeloid leukemia which acts by inhibiting DNA synthesis and subsequently cell division. It works on rapidly dividing cells, for that reason, it affects cancer cells, bone marrow and skin cells. Cytarabine has variable cutaneous side effects, the most common one is palmar-plantar erythema which usually presents with a tingling sensation around 5-7 days after cytarabine initiation, followed by erythema and tenderness. Auricular erythema is a rare subtype involving bilateral ears which often presents as ear redness and tenderness as described in the presented case. It is unclear if the skin side effects are related to cytarabine dose or plasma concentration. Most cases of auricular erythema have a benign course and resolve spontaneously. Treatment is mainly conservative. Steroids and antihistamines can be used to speed up recovery given that the pathophysiology is thought to be immediate or due to a delayed hypersensitivity reaction to cytarabine.

Effect of Preoperative Carbohydrate Drink and Postoperative Chewing Gum on Postoperative Nausea and Vomiting in Patients Undergoing Day Care Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) causes an unexpected prolonged hospital stay after ambulatory surgery. Novel measures such as preoperative loading of oral carbohydrates and postoperative chewing gum have recently gained momentum for postoperative recovery. This study evaluated the effects of preoperative carbohydrate loading and postoperative chewing gum (CG) on PONV after daycare laparoscopic cholecystectomy (LC). METHODS: A total of 100 patients were randomized to group A (preoperative carbohydrate loading with 200 ml of water with 25 g of carbohydrate and postoperative chewing gum (CG) when the patient responded to his/her name) and group B (standard care). The incidence of PONV and pain was assessed by using visual analogue scale. Quality of recovery (QoR-15) was assessed by using QoR15 questionnaire at 6 h, 24 h and 48 h after surgery. RESULTS: The incidence of PONV and pain was lower in group A; however, it was not significant (p > 0.05). The severity of PONV, pain and the need for rescue antiemetic was significantly lower in group A (p < 0.05). The episodes of PONV and required dose of antiemetic were less in group A. Group A also had a significantly higher QoR-15 score at all time points (p < 0.001). Preoperative dyspepsia was also noticed as a significant confounding predictor for postoperative vomiting. CONCLUSION: Preoperative carbohydrate drinks and early postoperative CG reduces the severity of PONV and requirement of antiemetics in patients undergoing LC. Hence, these simple measures can be used as a standard of care to optimize perioperative care in patients undergoing daycare surgery.

Functionalized manganese iron oxide nanoparticles: a dual potential magneto-chemotherapeutic cargo in a 3D breast cancer model.

Localized heat generation from manganese iron oxide nanoparticles (MIONPs) conjugated with chemotherapeutics under the exposure of an alternating magnetic field (magneto-chemotherapy) can revolutionize targeted breast cancer therapy. On the other hand, the lack of precise control of local temperature and adequate MIONP distribution in laboratory settings using the conventional two-dimensional (2D) cellular models has limited its further translation in tumor sites. Our current study explored advanced 3D in vitro tumor models as a promising alternative to replicate the complete range of tumor characteristics. Specifically, we have focused on investigating the effectiveness of MIONP-based magneto-chemotherapy (MCT) as an anticancer treatment in a 3D breast cancer model. To achieve this, chitosan-coated MIONPs (CS-MIONPs) are synthesized and functionalized with an anticancer drug (doxorubicin) and a tumor-targeting aptamer (AS1411). CS-MIONPs with a crystallite size of 16.88 nm and a specific absorption rate (SAR) of 181.48 W g-1 are reported. In vitro assessment of MCF-7 breast cancer cell lines in 2D and 3D cell cultures demonstrated anticancer activity. In the 2D and 3D cancer models, the MIONP-mediated MCT reduced cancer cell viability to about 71.48% and 92.2%, respectively. On the other hand, MIONP-mediated MCT under an AC magnetic field diminished spheroids' viability to 83.76 ± 2%, being the most promising therapeutic modality against breast cancer.

Effectiveness and safety of Levofloxacin containing regimen in the treatment of Isoniazid mono-resistant pulmonary Tuberculosis: a systematic review.

Background: We aimed to determine the effectiveness and safety of the Levofloxacin-containing regimen that the World Health Organization is currently recommending for the treatment of Isoniazid mono-resistant pulmonary Tuberculosis. Methods: Our eligible criteria for the studies to be included were; randomized controlled trials or cohort studies that focused on adults with Isoniazid mono-resistant tuberculosis (HrTB) and treated with a Levofloxacin-containing regimen along with first-line anti-tubercular drugs; they should have had a control group treated with first-line without Levofloxacin; should have reported treatment success rate, mortality, recurrence, progression to multidrug-resistant Tuberculosis. We performed the search in MEDLINE, EMBASE, Epistemonikos, Google Scholar, and Clinical trials registry. Two authors independently screened the titles/abstracts and full texts that were retained after the initial screening, and a third author resolved disagreements. Results: Our search found 4,813 records after excluding duplicates. We excluded 4,768 records after screening the titles and abstracts, retaining 44 records. Subsequently, 36 articles were excluded after the full-text screening, and eight appeared to have partially fulfilled the inclusion criteria. We contacted the respective authors, and none responded positively. Hence, no articles were included in the meta-analysis. Conclusion: We found no "quality" evidence currently on the effectiveness and safety of Levofloxacin in treating HrTB. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022290333, identifier: CRD42022290333.