Major Side Effects Research Articles

Therapy outcomes associated with prescription cannabidiol use at 12 months post-initiation

ObjectiveThis study evaluated prescription cannabidiol (CBD) outcomes during the first 12 months of therapy. MethodsA single-center, prospective cohort study was performed including patients prescribed CBD from January 2019 - April 2020, excluding clinical trial patients and those using external specialty pharmacy services. The primary outcome wasepilepsy-related emergency healthcare service (EHS) use within 12 months of initation. Secondary outcomes included prescription CBD discontinuation rate and reason and concomitant anti-seizure medication (ASM) use. A multiple logistic regression model evaluated the odds of EHS use, adjusting for initial concomitant ASM count, age, and insurance type. ResultsThe 136 patients included were 85% white, 50% female, and 68% pediatric. EHS utilization occurred in 37% (n = 50) of patients; 29 patients (21%, n = 20 pediatric, n = 9 adult) had at least one emergency department (ED) visit, 9 patients (7%) had two or more; 30 patients (22%, n = 22 pediatric, n = 8 adult) had at least one hospitalizaion. Median time to first ED and hospitalization was 69 (IQR 31–196) and 104 (IQR 38–179) days, respectively. Prescription CBD was discontinued in 31 patients (23%, n = 18 pediatric, n = 13 adult), due to major side effects (n = 12, 39%), common side effects (n = 11, 36%), and unsatisfactory response (n = 11, 36%). There was no significant change in concomitant ASM use. ConclusionDespite potential benefits of prescription CBD, many patients utilize EHSs in the first 12 months of treatment with minimal changes in concomitant ASM use.

Real-world effectiveness of azvudine for patients infected with the SARS-CoV-2 omicron subvariant BA.5 in an intensive care unit.

Azvudine (FNC) has been shown to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but data regarding the Omicron BA.5.1.3 subvariant are lacking. This retrospective analysis investigated the effectiveness and safety of FNC against the SARS-CoV-2 Omicron BA.5.1.3 subvariant in a real-world setting, utilizing data from a patient cohort at our institution. Data were retrospectively collected from patients admitted to the intensive care unit (ICU) of Sanya Central Hospital during the Sanya outbreak (August 13 to September 7, 2022). The patients, all infected with the Omicron BA.5.1.3 subvariant, were selected based on predefined inclusion and exclusion criteria. The patients were classified as the FNC (azvudine 5 mg, qd + standard supportive treatment) and non-FNC (standard supportive treatment only) groups. The study comprised 13 patients, with 6 and 7 in the FNC and non-FNC groups, respectively. Baseline data, clinical features, and imaging manifestations were generally similar between the two groups. However, patients administered FNC demonstrated significantly lower levels of inflammatory indicators at baseline. Although there was no significant difference in the duration of ICU stay between the FNC and non-FNC groups, overall ICU stay appeared to be reduced in the FNC group. FNC emerges as a feasible treatment against the Omicron BA.5.1.3 subvariant. It may reduce ICU stay and demonstrate a promising safety profile without major side effects or disruption to normal physiological parameters.

Perillaldehyde Mitigates Ionizing Radiation-Induced Intestinal Injury by Inhibiting Ferroptosis via the Nrf2 Signaling Pathway.

Gastrointestinal toxicity is one of the major side effects of abdominopelvic tumor radiotherapy. Studies have shown that perillaldehyde (PAH) has antioxidant, antiinflammatory, antimicrobial activity, and antitumor effects. This study aims to determine whether PAH has radioprotective effects on radiation-induced intestinal injury and explore the underlying mechanisms. C57BL/6J mice are gavaged with PAH for 7 days, then exposed to a single dose of 13 Gy X-ray total abdominal irradiation (TAI). PAH treatment prolongs the survival time, promotes the survival of crypt cells, attenuates radiation-induced DNA damage, and mitigates intestinal barrier damage in the irradiated mice. PAH also shows radioprotective effects in intestinal crypt organoids and human intestinal epithelial cells (HIEC-6). PAH-mediated radioprotection is associated with the upregulation of nuclear factor erythroid-2 related factor 2 (Nrf2), activation of the antioxidant pathway, and inhibition of ferroptosis. Notably, treatment with the Nrf2 inhibitor ML385 abolishes the protective effects of PAH, indicating that Nrf2 activation is essential for PAH activity. PAH inhibits ionizing radiation (IR)-induced ferroptosis and attenuates intestinal injury after irradiation by activating Nrf2 signaling. Therefore, PAH is a promising therapeutic strategy for IR-induced intestinal injury.

Analysis of Risk Factors for Infusion-Related Reactions Following Rituximab Administration in Patients with Desensitization before Renal Transplantation.

Infusion-related reactions (IRRs) are the major side effects of rituximab administration. Although several studies have reported predictive markers for IRRs in patients with malignancies, there are no such reports for patients without malignancies. Accordingly, we aimed to clarify the predictive markers for rituximab-induced IRRs in renal transplant recipients. This retrospective study included 116 inpatients aged ≥18 years who received an initial dose of 150 mg/m2 of rituximab for desensitization before renal transplantation with loxoprofen and diphenhydramine before rituximab infusion between June 2007 and February 2022. Overall, 45 patients were evaluated and 71 patients were excluded in this study. IRRs were observed in 12 (26.7%) patients. The proportion of men in the IRRs group was significantly higher than that in the non-IRRs group (p = 0.023). Additionally, body weight, body surface area (BSA), and body mass index (BMI) were significantly higher in the IRRs group than in the non-IRRs group (body weight, p = 0.0058; BSA, p = 0.0051; BMI, p = 0.017). Their cutoff values for predicting rituximab-induced IRRs, based on the receiver-operating characteristic curve, were 74.850 kg, 1.910 m2 and 24.164 kg/m2, respectively. In conclusion, the male sex, high actual body weight, BSA, and BMI may be new predictive markers for rituximab-induced IRRs in renal transplant recipients. Therefore, clinicians should carefully monitor patients who receive rituximab before renal transplantation and present with the predictive markers.

Ethnomedicinal Uses, Phytochemistry and Pharmacology of Few Species of Genus Atalantia (Rutaceae): A Review

Synthetic drugs show major side effects, as well as the fact that they have been discovered to be extremely harmful to human assistance, many synthetic medications claimed to be used for treatment are of the least interest today. Therefore, herbal medicines have acquired prominence in recent decades. This review's primary objective is to give a complete overview of three distinct species of the Genus Atalantia mainly Atalantia monophylla (Roxb) DC, Atalantia racemaosa Wight, Atalantia wightii Tanaka. The Genus Atalantia belongs to Rutaceae family and there are 22 accepted species of which three species are selected because these are available in Western Ghat region of Maharashtra, these species have ethnopharmacological significance and many of their facets are still unexplored. The Atalantia genus is utilized in conventional medicine to treat a diverse array of ailments like fever, rheumatic pains, cough, allergy, swelling, and as a blood purifier, etc. The current work is a comprehensive analysis of the published literature on phytochemical and pharmacological reports of the above species of Atalantia genus in an effort to deliver comprehensive information and suggest future research avenues. Out of these three species, Atalantia monophylla has received the most research attention but the remaining two species are not much explored. The aim of this review is to discuss the potential application of these three species as herbal medicine. The plant characteristics, ethnobotanical uses, phytochemistry, and pharmacological activities are summarized as a guide for phytochemical and pharmacological investigations.

Curcumin reduces blood-nerve barrier abnormalities and cytotoxicity to endothelial cells and pericytes induced by cisplatin.

Cisplatin is a platinum-based antineoplastic agent used to treat cancers of solid organs. Neuropathy is one of its major side effects, necessitating dose reduction or cessation. Previous studies suggested that cisplatin causes microvascular toxicity, including pericyte detachment. This study aimed to clarify whether these alterations occurred in the blood-nerve barrier (BNB) of capillaries after cisplatin treatment. Electron microscopic analysis of rat sciatic nerves with cisplatin neuropathy showed increased frequency and severity of pericyte detachment. Moreover, the vascular basement membrane did not tightly encircle around the endothelial cells and pericytes. Cultured human umbilical vein endothelial cells and human brain vascular pericytes showed reduced viability, increased caspase-3 activity and enhanced oxidative stress following cisplatin treatment. In addition, cisplatin decreased transendothelial electrical resistance (TEER) and the expression of the tight junction proteins occludin and zonula occludens-1. Curcumin, a polyphenol found in the root of Curcuma longa, had favourable effects on cisplatin neuropathy in previous work. Therefore, curcumin was tested to determine whether it had any effect on these abnormalities. Curcumin alleviated pericyte detachment, cytotoxicity, oxidative stress, TEER reduction and tight junction protein expression. These data indicate that cisplatin causes BNB disruption in the nerves and might result in neuropathy. Curcumin might improve neuropathy via the restoration of BNB. Whether alterations in the BNB occur and curcumin is effective in patients with cisplatin neuropathy remain to be investigated.

SIRT1 reduction contributes to doxorubicin–induced oxidative stress and meiotic failure in mouse oocytes

Impaired fertility is the major side effect of chemotherapy for female cancer patients, accumulated evidence indicates this is associated with damage on oocyte quality, but the underlying mechanisms remain unclear. Previously we reported that doxorubicin (DXR) exposure, one of the most widely used chemotherapy drugs, disrupted mouse oocyte meiotic maturation in vitro. In the current study, we identified that SIRT1 expression was remarkably reduced in DXR exposure oocytes. Next, we found that increasing SIRT1 expression by resveratrol partially alleviated the effects of DXR exposure on oocyte maturation, which was counteracted by SIRT1 inhibition. Furthermore, we revealed that increasing SIRT1 expression mitigated DXR induced oocyte damage through reducing ROS levels, increasing antioxidant enzyme MnSOD expression, and preventing spindle and chromosome disorganization, lowering the incidence of aneuploidy. Importantly, by performing in vitro fertilization and embryo transfer assays, we demonstrated that increasing SIRT1 expression significantly improved the fertilization ability, developmental competence of oocytes and early embryos. In summary, our data uncover that SIRT1 reduction represents one mechanism that mediates the effects of DXR exposure on oocyte quality.

Comparitive Study between Dexamethasone versus Fentanyl as Adjuvant to Local Anesthesia in Supraclavicular Nerve Block in Upper Limb Surgery

Abstract Background Peripheral nerve block as an anesthetic technique plays an important role in modern regional anesthesia. Upper limb surgeries are mostly performed under peripheral blocks such as the brachial plexus block. Peripheral nerve blocks not only provide intra-operative anesthesia, but also extend analgesia in the post-operative period without major systemic side-effects by minimizing stress response and using minimal anesthetic drugs. Objective To evaluate the effects of adding dexamethasone and fentanyl to bupivacaine in ultrasound guided supraclavicular brachial plexus block for upper limb surgery versus bupivacaine alone. Patients and Methods After obtaining approval from the medical ethical committee in Al-Matareya Teaching Hospital, this study was conducted in Al-Matareya Teaching Hospital in cooperation with Ain Shams University. It was include patients undergoing elective upper limb surgery. A written informed consent was obtained from every patient after explaining the procedure. A randomized double-blinded controlled study is thought to be the most suitable design to achieve the study objectives. Results The present study showed that addition of dexamethasone and fentanyl to bupivacaine in ultrasound-guided supraclavicular nerve block shortened the onset times of both sensory and motor blocks and significantly prolonged their duration compared to bupivacaine olny. Conclusion In the current study, the addition of dexamethasone or fentanyl to bupivacaine for supraclavicular brachial plexus block make the onset of sensory & motor block faster and prolongation of motor and sensory block duration and prolongation of duration of analgesia more than using bupivacaine only. But onset of motor and sensory block was shorter in fentanyl group than dexamethasone group and duration of sensory and motor block more in dexamethasone rather than fentanyl.

Antrodia cinnamomea Extract Attenuates Cisplatin-Induced Muscle Atrophy, Apoptosis, and Cell Growth Suppression

Antrodia cinnamomea (AC), a potential medicinal fungus which possesses anti-inflammatory and anticancer activities, has been previously reported to be able to ameliorate muscle wasting in cisplatin-treated lung tumor-bearing mice via AC extract. However, whether AC extract modulates muscle cell differentiation, apoptosis, and cell cycle progression remains unclear. Here, we show that the ethanol extract of AC (EEAC) significantly restored cisplatin-reduced quadricep mass in mice. EEAC attenuated cisplatin/gemcitabine (C/G)-suppressed elongated myotube formation, which is differentiated from C2C12 cells. Moreover, EEAC synergized with C/G to inhibit cell growth of LLC1 cells, whereas EEAC attenuated C/G-reduced proliferation of C2C12 cells. Although EEAC protected C/G-induced apoptosis of both LLC1 and C2C12, EEAC suppressed cyclin D expression in LLC1 while partially restoring C/G-reduced cyclin D level in C2C12 cells. Finally, as p 53 and p 21 participate in inducing skeletal muscle atrophy, we found that C/G induced p 53 and p 21 expression in C2C12 cells but with its effect significantly attenuated by EEAC. Our findings indicate that AC extract is a potential natural agent for attenuating cisplatin-induced muscle atrophy. Practical Applications. Muscle atrophy is one of the major side effects caused by chemotherapy. In addition to inducing cell death, chemotherapeutic agents inhibit cell growth of both cancer and normal cells as well. Our current findings indicated that AC extract attenuates cisplatin-induced muscle wasting and apoptosis of C2C12 cells. AC extract is a potential dietary supplement used for ameliorating chemotherapy-induced muscle atrophy.

Protective Role of Betulinic Acid against Cisplatin-Induced Nephrotoxicity and Its Antibacterial Potential toward Uropathogenic Bacteria.

Acute kidney injury (AKI) is one of the major side effects of cisplatin, a remarkable anticancer agent. Therefore, there is a growing need to find an agent that could mitigate cisplatin-induced nephrotoxicity. Betulinic acid (BA) is a natural compound isolated from Silene succulenta Forssk for the first time, with miraculous biological activities and no reports of its effect on the nephrotoxicity induced by cisplatin. Mice received BA orally with doses of 30 and 50 mg/kg before the intraperitoneal injection of cisplatin. Betulinic acid was found to decrease serum levels of creatinine and tissue levels of NGAL and kidney injury molecule (KIM-1) and improve the histological changes in the kidney. In addition, BA decreased the oxidative stress marker malondialdehyde (MDA), increased superoxide dismutase (SOD) antioxidative activity and suppressed the intensity of IL-1B and NFкB immuno-staining. Interestingly, betulinic acid enhanced autophagy by increasing beclin 1, ATG5, and LC3II and decreasing p62 expressions. Thus, our findings suggest betulinic acid as a potential agent that may protect from acute kidney injury by targeting inflammation, oxidative stress, and autophagy processes. Novel drugs are needed to combat the spreading of multidrug resistance between pathogenic bacteria, especially uropathogenic isolates. So, we elucidated the antibacterial properties of BA on Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. Betulinic acid had minimum inhibitory concentration values (128 to 512 µg/mL). In addition, it adversely affected the membrane integrity of the tested isolates. Accordingly, betulinic acid should be clinically investigated in the future for urinary tract diseases.

Electroacupuncture attenuates myocardial ischemia-reperfusion injury by inhibiting microglial engulfment of dendritic spines

A major side effect of reperfusion therapy following myocardial infarction is myocardial ischemia-reperfusion injury (MIRI). Electroacupuncture preconditioning (EA-pre) has a long history in the treatment of cardiovascular diseases. Here, we demonstrate how EA-pre attenuates MIRI by affecting the phagocytosis of neuronal dendritic spines of microglia of the fastigial nucleus (FNmicroglia). We observed that EA-pre increased activity in FNGABA and then improved myocardial injury by inhibiting abnormal activities of glutaminergic neurons of the FN (FNGlu) during MIRI. Interestingly, we observed changes in the quantity and shape of FN microglia in mice treated with EA-pre and a decrease in the phagocytosis of FNGABA neuronal dendritic spines by microglia. Furthermore, the effects of improving MIRI were reversed when EA-pre mice were chemically activated by intra-FN lipopolysaccharide injection. Overall, our results provide new insight indicating that EA-pre regulates microglial engulfment capacity, thus promoting the improvement of cardiac sympathetic nervous disorder during MIRI.

Desirability of Outcome Ranking for Status Epilepticus: A Benefit-Risk Approach to Design and Analyses of Clinical SE Trials.

Most clinical trials of treatment efficacy evaluate benefits and harms separately. Investigators generally rate the primary outcome of a trial with a binary outcome measure and consider harms separately as adverse events. This approach fails to recognize finer gradations of patient response, correlations between benefits and harms, and the overall effects on individual patients. For example, in status epilepticus trials, efficacy is often defined as the absence of clinically apparent seizures with recovery of consciousness. Such an efficacy outcome fails to recognize that some causes of status epilepticus, such as subarachnoid hemorrhage or stroke, may not be accompanied by return of consciousness, and the need to intubate a patient may be classified as treatment failure even if status was successfully terminated. The Desirability of Outcome Ranking (DOOR) method uses a different approach. The DOOR method involves comparing the experiences of trial participants in different treatment arms by the desirability of the overall patient outcome. Using status epilepticus treatment as an example, a patient who experiences successful termination of status epilepticus but with major side effects would have a less desirable outcome than a patient with treatment success and minor side effects, who in turn would have a less desirable outcome than a patient with treatment success but no side effects. This is a patient-centered approach because it considers treatment efficacy in the context of the costs borne by the patient, for example, toxicity in achieving efficacy. Thus, DOOR considers both the benefits and harms to individual patients in assessing the outcome of a clinical trial. In this article, we present the rationale for the use of DOOR, the issues involved in the development of and statistical analyses of an ordinal outcome, and an example of the potential application of the DOOR method to a clinical trial of convulsive status epilepticus.

Pericapsular nerve group block in hip arthroplasty: A prospective randomized trial.

This study aimed to evaluate the analgesic effect of the ultrasound-guided pericapsular nerve group (PENG) block in hip arthroplasty (HA) surgery. A prospective double-blinded, randomized study. Tertiary institutional clinical care. Fifty patients, more than 50 years old of both genders, were chosen according to the American Society of Anesthesiologists classification, with physical status I-III, and scheduled for unilateral HA surgeries. Patients were randomized to receive either a sham PENG block with 20 mL of normal saline (control group) or a PENG block with 20 mL of bupivacaine 0.25 percent (PENG group). From the onset of the first request for rescue opioid analgesia, preoperative pain scores before and after block (at rest and with a raised straight leg), the incidence of quadriceps weakness after the block, intraoperative fentanyl consumption, post-operative pain scores, and morphine consumption, besides the presence and frequency of adverse events, were recorded. The patients undergoing PENG block with bupivacaine had prolonged durations before the first analgesic request, lower perioperative pain scores, less intraoperative rescue fentanyl, and less post-operative morphine consumption than the control group, with nonsignificant motor weakness after the block and similar adverse events. The PENG block provided effective perioperative analgesia for HA with prolonged duration of analgesia, nonsignificant motor effects, reduced perioperative opioids consumption, and no major side effects.

MST1 mediates doxorubicin-induced cardiomyopathy by SIRT3 downregulation

Heart failure is a major side effect of doxorubicin (DOX) treatment in patients with cancer. However, the mechanisms underlying the development of DOX-induced heart failure need to be addressed. This study aims to test whether the serine/threonine kinase MST1, a major Hippo pathway component, contributes to the development of DOX-induced myocardial injury. C57BL/6J WT mice and mice with cardiomyocyte-specific dominant-negative MST1 (kinase-dead) overexpression received three weekly injections of DOX, reaching a final cumulative dose of 18 mg/kg. Echocardiographic, histological and biochemical analyses were performed six weeks after the first DOX administration. The effects of MST1 inhibition on DOX-induced cardiomyocyte injury were also tested in vitro. MST1 signaling was significantly activated in cardiomyocytes in response to DOX treatment in vitro and in vivo. Wild-type (WT) mice treated with DOX developed cardiac dysfunction and mitochondrial abnormalities. However, these detrimental effects were abolished in mice with cardiomyocyte-specific overexpression of dominant-negative MST1 (DN-MST1) or treated with XMU-MP-1, a specific MST1 inhibitor, indicating that MST1 inhibition attenuates DOX-induced cardiac dysfunction. DOX treatment led to a significant downregulation of cardiac levels of SIRT3, a deacetylase involved in mitochondrial protection, in WT mice, which was rescued by MST1 inhibition. Pharmacological inhibition of SIRT3 blunted the protective effects of MST1 inhibition, indicating that SIRT3 downregulation mediates the cytotoxic effects of MST1 activation in response to DOX treatment. Finally, we found a significant upregulation of MST1 and downregulation of SIRT3 levels in human myocardial tissue of cancer patients treated with DOX. In summary, MST1 contributes to DOX-induced cardiomyopathy through SIRT3 downregulation.

NU-1223, a simplified analog of alstonine, with 5-HT2cR agonist-like activity, rescues memory deficit and positive and negative symptoms in subchronic phencyclidine mouse model of schizophrenia

The serotonin (5-HT)2 C receptor(R) is a widely distributed G-protein-coupled receptor, expressed abundantly in the central nervous system. Alstonine is a natural product that has significant properties of atypical antipsychotic drugs (AAPDs), in part attributed to 5-HT2 CR agonism. Based on alstonine, we developed NU-1223, a simplified β carboline analog of alstonine, which shows efficacies comparable to alstonine and to other 5-HT2 CR agonists, Ro-60–0175 and lorcaserin. The 5-HT2 CR antagonism of some APDs, including olanzapine, contributes to weight gain, a major side effect which limits its tolerability, while the 5-HT2 CR agonists and/or modulators, may minimize weight gain. We used the well-established rodent subchronic phencyclidine (PCP) model to test the efficacy of NU-1223 on episodic memory, using novel object recognition (NOR) task, positive (locomotor activity), and negative symptoms (social interaction) of schizophrenia (SCH). We found that NU-1223 produced both transient and prolonged rescue of the subchronic PCP-induced deficits in NOR and SI. Further, NU-1223, but not Ro-60–0175, blocked PCP and amphetamine (AMPH)-induced increase in LMA in subchronic PCP mice. These transient efficacies in LMA were blocked by the 5-HT2 CR antagonist, SB242084. Sub-chronic NU-1223 treatment rescued NOR and SI deficits in subchronic PCP mice for at least 39 days after 3 days injection. Chronic treatment with NU-1223, ip, twice a day for 21 days, did not increase average body weight vs olanzapine. These findings clearly indicate NU-1223 as a class of small molecules with a possible 5-HT2 CR-agonist-like mechanism of action, attributing to its efficacy. Additional in-depth receptor mechanistic studies are warranted, as this small molecule, both transiently and chronically rescued PCP-induced deficits. Furthermore, NU-1223 did not induce weight gain post long-term administrations vs AAPDs such as olanzapine, making NU-1223 a putative therapeutic compound for SCH.

Bevacizumab-induced proteinuria and its association with antihypertensive drugs: A retrospective cohort study using a Japanese administrative database.

Proteinuria is a major side-effect of the anti-tumor drug bevacizumab, although its incidence and risk factors in the real world are still unclear. Although renin-angiotensin-aldosterone system inhibitors are used clinically to prevent proteinuria, their efficacy remains unclear. The aim of the present study was to reveal the incidence and risk factors of bevacizumab-induced proteinuria and examine the effectiveness of antihypertensive drugs in preventing proteinuria. We conducted a retrospective cohort study using the National Hospital Organization Clinical Data Archives and Medical Information Analysis Databank. Hospitalized patients who received bevacizumab between January 1, 2016, and June 30, 2019, were included. The study outcome was proteinuria within 12 months of bevacizumab administration. Patient characteristics, laboratory tests, and medications were compared between patients with and without proteinuria using multivariable logistic regression analysis. Among the 2,458 patients, 27% developed proteinuria after bevacizumab administration. Nursing dependence (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.89-3.05; P<0.001) and systolic blood pressure ≥140 mmHg (OR, 1.44; 95% CI, 1.17-1.79; P<0.001) were identified as risk factors. Patients with an estimated glomerular filtration rate (eGFR) of 60-89, 45-59, and <45 mL/min/1.73 m2 had 29.7%, 76.8%, and 66.0% higher odds of proteinuria, respectively, than those with an eGFR ≥90 mL/min/1.73 m2. No significant relationship was observed between antihypertensive drugs and the occurrence of proteinuria. More patients may suffer from proteinuria after bevacizumab administration than previously reported. Nursing dependence and systolic blood pressure are predictive risk factors for bevacizumab-induced proteinuria. Patients at risk of proteinuria should be closely monitored.

Adalimumab rapidly controls both anterior and posterior inflammation in patients with ocular Behçet syndrome and non-infectious uveitis refractory to conventional therapy: a prospective, 6-month follow-up investigation.

To evaluate the efficacy and safety of adalimumab (ADA, Humira®) for treatment of non-infectious uveitis (NIU)refractory to conventional medications. Anti-tumor necrosis factor-α naive patients with NIU unresponsive to conventional immunosuppressive treatment were treated with ADA. Most cases with NIU were related to ocular Behçet syndrome. Adult cases used 80mg ADA subcutaneously on day 0, 40mg in the first week, and then 40mg every 2-week, while this was 20mg in children. Evaluations were performed pre-treatment and at weeks 2, 8, and 24. The study endpoints were best-corrected visual acuity (BCVA, LogMAR) improvement, anterior chamber (AC) cell grade, vitreous cell and haze grades, decrease in macular thickness and edema, prednisolone dose, immunosuppressive dose, and adverse reactions. Thirty-eight eyes (19 right, 19 left) of 24 patients (14 female, 10 male) with (ocular Behçet syndrome)OBS (n = 27 eyes/18 patients) and NIU (n = 11 eyes/6 patients) were included. Mean age was 29.0 ± 14.1years (range, 5-49) and follow-up time was 24weeks. After ADA, BCVA increased (p < 0.001), and improvements in AC cell grade (p < 0.001), vitreous cell grade (p < 0.001), and vitreal haze grade (p < 0.001) were achieved at the final visit. Mean macular thickness decreased from 243.5 to 235.5µm (p < 0.001). Such a rapid control of both anterior and posterior uveitis was observed in all eyes as early as the second week without relapses during follow-up. No ocular or systemic complications emerged during treatment. ADA is effective and well-tolerated in pediatric and adolescent patients with NIU including OBS refractory to traditional medications and demonstrated corticosteroid- and immunosuppressive-sparing effects with no major side effects.

Review of Targeted Therapy, Vismodegib, for the Treatment of Periocular Basal Cell Carcinoma.

Periocular locally advanced basal cell carcinoma (POLA-BCC) is characterized by orbital involvement and/or extensive invasion of periocular structures. Hedgehog pathway inhibitors have been used for POLA-BCC with promising outcomes. The authors reviewed 11 articles published in English literature from January 2012 to July 2022 and reported the outcomes of patients with POLA-BCC who were treated with vismodegib. A total of 384 patients were treated with vismodegib. The mean age was 72 years, and the median treatment duration was 9 months. The overall response rate was 75% with a median follow-up time of 14.4 months. Following vismodegib treatment, the median number of patients who required adjuvant surgery was 43% with a median time to surgery of 6.5 months. The exenteration rate was 6% (overall 8 patients). In total 93.7% of patients experienced grade I adverse events, 26.7% to 37.5% grade II, 8.8% to 10% grade III-IV, and 0.8% to 4.8% grade V. Major side effects included dysgeusia (30-100%), muscle spasm (15-100%), alopecia (47-75%), weight loss (23-83%), and decreased appetite (19-42%). The median percentage of patients who discontinued treatment due to toxicity was 29% with a median interval of 5 months before the development of side effects. The median recurrence rate following discontinuation of vismodegib was 7.8% with a median recurrence duration of 20 months. In patients with POLA-BCC, vismodegib, a hedgehog pathway inhibitor, provided high rates of orbital preservation, reducing exenteration rates to 6%. Neoadjuvant therapy with vismodegib can also be suggested for patients with POLA-BCC. While extremely effective, side effects lead to temporary or permanent discontinuation of vismodegib in small numbers of patients.

FUNCTIONAL OUTCOME OF PATIENTS WITH CHRONIC PLANTAR FASCIITIS TREATED BY LOCAL INJECTION OF AUTOLOGOUS PLATELET-RICH PLASMA

Objectives: The objectives of the study are as follows: To assess functional outcome of patients with chronic plantar fasciitis (PF) treated by autologous injection of platelet-rich plasma (PRP). (1) To know the side effects, if any, in these patients. Methods: This was a prospective study conducted in the Department of orthopedics of a tertiary care medical college. Forty patients having chronic PF were included in this study on the basis of a predefined inclusion and exclusion criteria. Autologous PRP was injected in plantar fascia at the point of maximum tenderness. Patients were followed up for 3 months. Intensity of pain and functional outcome was assessed using the visual analog score (VAS) score and American Orthopedic Foot and Ankle Score (AOFAS) score. For statistical purposes, p&lt;0.05 was taken as significant. Results: There were 14 (35.00%) males and 26 (65.00%) females with a M: F ratio of 1:1.85. The mean age of male and female patients was found to be 43.82±9.98 years and 41.68±10.12 years, respectively. Majority of the patients (65%) were overweight whereas 6 (15%) patients were obese and 8 (20%) patients were having a normal healthy body mass index. The mean duration of symptoms was found to be 10.67±3.89 months. The mean VAS score at the time of final follow-up was significantly less (0.96±0.46) as compared to pre-injection VAS score (7.20±1.38) whereas the AOFAS score at the time of final follow-up (91.9±6.68) significantly improved as compared to pre-injection AOFAS score (38.96±8.78). There were no major side effects in any of the studied cases. Conclusion: Local injection of autologous PRP appears to be an effective treatment for chronic PF in terms of reduction of pain and functional improvement with no significant side effects.

A review on anti-cancer plants of India

India has a high level of endemism and a diverse range of floral species. Cancer is one of the most significant challenges facing global health today. The indigenous peoples and residents who live in India have, for a very long time, made use of specific medicinal plants to fight cancer. This practice is still prevalent today. Several different drugs may be utilized in the treatment of cancer. Because of the potential drawbacks associated with such treatments and the development of drug resistance, the quest for new therapies that are both safer and much more effective is still the most challenging field of study. Several cancer medicines used today come from natural sources. We're returning to our old ways because medicinal plants are a good, natural way to make medicines that prevent cancer without causing major side effects. Within the scope of this study, a few herbs traditionally used to treat cancer are looked at to see what they might be good for. The cytotoxicity of these plants, the processes that lead to them, and the different compounds they make were looked into. This study has tried to focus on how these plants fight cancer.