Analysis of Polymer Impurities in Cephalosporin Antibiotics

[Objectives]To establish a HPLC-MS method for the determination of polymer impurities in cefathiamidine and its preparations.[Methods]Kromasil 100-5 C_(18) column(4.6 mm ×250 mm,5μm)was used for analysis;mobile phase ammonium acetate solution(pH 6.30)-acetonitrile,gradient elution;volumetric flow rate 1.0 mL/min;column temperature 40℃;multi-reaction monitoring mode was used for analysis,and positive ion scanning was chosen as the electrospray ion source.[Results]The resolution between impurities and main peaks under this method was greater than 1.5,and 8 known impurities and 2 polymer impurities could be completely separated and distinguish-ed.It was inferred that the molecular ion peak[M+H]^(+):m/z727.1874,m/z 785.1937 was the possible polymer impurity of this product.[Conclusions]A method for the analysis of polymer impurities in cefathiamidine and its preparations was formed,which could achieve the purpose of simultaneous analysis of small molecule impurities and polymer impurities,and could better control the content of single impurities in the polymer,providing a reliable inspection basis for strict control of cefathiamidine quality.

Perianal disease in inflammatory bowel disease:Broadening treatment and surveillance strategies for anal cancer

The perianal disease affects up to one-third of individuals with Crohn's disease(CD),causing disabling symptoms and significant impairment in quality of life,particularly for those with perianal fistulising CD(PFCD).The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing.Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents,endoscopic procedures and surgical techniques that show promising results.Among these,mesenchymal stem cells injection is a particularly hopeful therapy.In addition to the burden of fistulas,individuals with perianal CD may face an increased risk of developing anal cancer.This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes.Currently,there is no established formal anal screening programme.In this review,we provide an overview of the current state of the art in managing PFCD,including novel medical,endoscopic and surgical approaches.The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD,intending to propose a risk-based surveillance algorithm.The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

Anal Pathologies: What Management at the Reference Health Center of Bamako’s Commune V?

Anal pathologies are conditions affecting the anal margin and the anal canal. The aim of our study was to update data on anal diseases. Non-specific, it can reveal an emergency, a serious illness, a chronic disease or a benign condition. It was a prospective, descriptive and analytical study from April 2022 to March 2023, carried out in the hepato-gastroenterology unit of the Centre de Santé de Référence de la commune V du District de Bamako in Mali. Out of seven hundred and forty-nine (749) patients seen in consultation, 98 had anal pathology, i.e. a prevalence of 13.08%. The mean age was 40 ± 15.15 years and the sex ratio was 1.5. Hemorrhoidal disease and anal fissure were the most frequent pathologies in 66.4% and 24.4% of cases respectively. Medical treatment was initiated in 91.9% of patients with hemorrhoidal disease and 91.7% with anal fissure. Anal pathologies are common in young male patients. In our context, they are dominated by benign conditions.

A comparative study of acupuncture combined with rehabilitation gymnastics on postoperative anal function of lower rectal cancer

BACKGROUND From the anal function,inflammatory response and other indicators,acupuncture combined with rehabilitation gymnastics was applied to patients with cancer undergoing low resection,aiming to improve the prognosis of patients.AIM To explore the effects of acupuncture combined with rehabilitation gymnastics on anal function after lower rectal cancer surgery.METHODS From January 2020 to December 2022,128 patients who underwent rectal cancer surgery in the Department of Oncology of Hebei Provincial Hospital of Traditional Chinese Medicine Hospital were selected and divided into two groups using the random number table method,with 64 patients in each group.Patients in the control group were not treated with acupuncture or rehabilitation gymnastics and served as blank controls.Patients in the study group were treated with acupuncture and rehabilitation gymnastics from the 7th postoperative day.The anal incontinence scores,changes in serum interleukin-4,interleukin-6,and interleukin-10 Levels,and serum motilin,5-hydroxytryptamine,and vasoactive intestinal peptide levels were compared.RESULTS There were no significant differences in serum interleukin-4,interleukin-6,and interleukin-10 Levels between the groups before treatment(P>0.05).After treatment,these levels were better than those of the control group(P<0.05).There was no significant difference in the anal incontinence scores between the groups before and 7 d after surgery(P>0.05).Anal incontinence scores in the study group were lower than those in the control group at 14 d,21 d,and 28 d postoperatively(P<0.05).There were no significant differences in serum motilin,5-hydroxytryptamine,or vasoactive intestinal peptide levels between the groups before treatment(P>0.05).After treatment,these levels were higher in the study group than in the control group,and vasoactive intestinal peptide level was lower in the study group than in the control group(P<0.05).CONCLUSION Acupuncture combined with rehabilitation gymnastics can promote the recovery of anal function and reduce the inflammatory response in patients with lower rectal cancer after surgery.

Establishment of a surveillance program for anal cancer in Crohn's disease

This letter discusses the incidence of anal cancer among Crohn's disease(CD)-related malignancies.Patients with CD have been demonstrated to be at a higher risk of developing small bowel and colorectal cancers than healthy individuals.Although CD-associated anal cancer is relatively rare,patients with CD accom-panied by anal or perianal lesions are at increased risk of anal cancer.Addi-tionally,compared to ulcerative colitis,which is also an inflammatory disease,CD-related anal cancer is often detected at an advanced stage owing to the complexity of CD and is associated with a poor prognosis with frequent local recurrences.Therefore,the detection of early-stage cancer is crucial for improving the prognosis.However,the surveillance methods recommended for CD-related malignancies in the United States and Europe are similar to those for ulcerative colitis.They are not appropriate for detecting CD-related malignancies in the recto-anal region.Therefore,there is an urgent need for surveillance programs aimed at the early detection of malignant anorectal lesions in patients with CD.

Structured magnetic resonance imaging and endoanal ultrasound anal fistulas reporting template(SMART):An interdisciplinary Delphi consensus

BACKGROUND There is still considerable heterogeneity regarding which features of cryptoglandular anal fistula on magnetic resonance imaging(MRI)and endoanal ultrasound(EAUS)are relevant to surgical decision-making.As a con-sequence,the quality and completeness of the report are highly dependent on the training and experience of the examiners.AIM To develop a structured MRI and EAUS template(SMART)reporting the minimum dataset of information for the treatment of anal fistulas.METHODS This modified Delphi survey based on the RAND-UCLA appropriateness for consensus-building was conducted between May and August 2023.One hundred and fifty-one articles selected from a systematic review of the lite-rature formed the database to generate the evidence-based statements for the Delphi study.Fourteen questions were anonymously voted by an interdisciplinary multidisciplinary group for a maximum of three iterative rounds.The degree of agreement was scored on a numeric 0–10 scale.Group consensus was defined as a score≥8 for≥80%of the panelists.RESULTS Eleven scientific societies(3 radiological and 8 surgical)endorsed the study.After three rounds of voting,the experts(69 colorectal surgeons,23 radiologists,2 anatomists,and 1 gastroenterologist)achieved consensus for 12 of 14 statements(85.7%).Based on the results of the Delphi process,the six following features of anal fistulas were included in the SMART:Primary tract,secondary extension,internal opening,presence of collection,coexisting le-sions,and sphincters morphology.CONCLUSION A structured template,SMART,was developed to standardize imaging reporting of fistula-in-ano in a simple,systematic,time-efficient way,providing the minimum dataset of information and visual diagram useful to refer-ring physicians.

Anal pruritus:Don’t look away

Anal pruritus is a common anorectal symptom that can significantly impair a patient’s quality of life,including their mental health.It can be one of the most difficult proctological conditions to treat.Patients often delay seeking medical attention,since it is an embarrassing but non-life-threatening situation.Pruritus ani can be associated with idiopathic and secondary causes,such as anorectal diseases,cancer(anal or colorectal),dermatological and sexually transmitted diseases,fungal infections and systemic diseases.If patients are referred for a colonoscopy,this can sometimes provide the first opportunity to evaluate the perianal area.Classifications of anal pruritus are based on the abnormalities of the perianal skin,one of the most commonly used being the Washington classi-fication.A proper digital anorectal examination is important,as well as an anoscopy to help to exclude anorectal diseases or suspicious masses.Endoscopists should be aware of the common etiologies,and classification of the perianal area abnormalities should be provided in the colonoscopy report.Information on treatment possibilities and follow-up can also be provided.The treatment normally consists of a triple approach:proper hygiene,elimination of irritants,and skin care and protection.Several topical therapies have been described as possible treatments,including steroids,capsaicin,tacrolimus and methylene blue intradermal injections.

High complex anal fistula managed by the modified transanal opening of the intersphincteric space via the inter-sphincteric approach:A case report

BACKGROUND High complex anal fistulas are epithelialized tunnels,with the main fistula piercing above the deep external sphincter and the internal opening approaching the dentate line.Conventional surgical procedures for high complex anal fistulas remove most of the external sphincter and damage the anorectal ring.Postoperative loss of anal function can cause physical and mental damage.Transanal opening of the intersphincteric space(TROPIS)is an effective procedure that completely preserves the external anal sphincter.However,its clinical application is limited by challenges in the localization of the internal opening of a fistula and the high risk of complications.On the basis of our clinical experience,we modified the TROPIS procedure for the treatment of treating high complex anal fistulas.CASE SUMMARY A patient with a high complex anal fistula located above the anorectal ring underwent modified TROPIS,which involved sepsis drainage and identification of the internal opening in the intersphincteric space.The patient with the high complex anal fistula recovered well postoperatively,without any postoperative complications or anal dysfunction.Anal function returned to normal after 17 months of follow-up.CONCLUSION The modified TROPIS procedure is the most minimally invasive surgery for anal fistulas that minimally impairs anal function.It allows the complete removal of infected anal glands and reduces the risk of postoperative complications.Modified TROPIS via the intersphincteric approach is an alternative sphincter-preserving treatment for high complex anal fistulas.

Evaluating the clinical application and effect of acupuncture therapy in anal function rehabilitation after low-tension rectal cancer surgery

BACKGROUND According to the indexes of serum and anal function,acupuncture therapy was applied to patients with low rectal cancer in order to avoid the occurrence of anal incontinence and reduce complications.AIM To explore the clinical application and evaluate the effect of acupuncture therapy for anal function rehabilitation after low-tension rectal cancer surgery.METHODS From the anorectal surgery cases,we selected 120 patients who underwent colorectal cancer surgery between January 2020 and December 2022 and randomly divided them into a control group(n=60),observation group(n=60),and control group after surgery for lifestyle intervention(including smoking cessation and exercise),dietary factor adjustment,anal movement,and oral loperamide treatment.The serum levels of motilin,5-hydroxytryptamine,and vasoactive intestinal peptide(VIP),Wexner score for anal incontinence,and incidence of complications were compared between groups.RESULTS After treatment,the VIP and 5-hydroxytryptamine levels in the observation group were lower than those in the control group(P<0.05).The motilin level was higher than that in the control group(P<0.05).Postoperative anal incontinence was better in the observation group than in the control group(P<0.05).The incidence of complications in the observation group was 6.67%,which was significantly lower than that in the control group(21.67%;P<0.05).CONCLUSION Acupuncture therapy has a positive effect on the rehabilitation of anal function after low-tension rectal cancer surgery;it can effectively help to improve the serum indices of patients,avoid the occurrence of anal incontinence,and reduce the incidence of complications.Popularizing and applying it will be valuable.

Variable selection in near infrared spectroscopy for quantitative models of homologous analogs of cephalosporins

Two universal spectral ranges(4550-4100 cm^(-1) and 6190-5510 cm^(-1))for construction of quantitative models of homologous analogs of cephalosporins were proposed by evaluating theperformance of five spectral ranges and their combinations,using three data sets of cephalos-porins for injection,ie.,cefuroxime sodium,cetriaxone sodium and cefoperazone sodium.Subsequently,the proposed ranges were validated by using eight calibration sets of otherhomologous analogs of cephalosporins for injection,namely cefmenoxime hydrochloride,ceftezole sodium,cefmetazole,cefoxitin sodium,cefotaxime sodium,cefradine,cephazolin sodium and ceftizoxime sodium.All the constructed quantitative models for the eight kinds of cephalosporinsusing these universal ranges could fulill the requirements for quick quantification.After that,competitive adaptive reweighted sampling(CARS)algorithm and infrared(IR)-near infrared(NIR)two-dimensional(2D)correlation spectral analysis were used to determine the scientific basis of these two spectral ranges as the universal regions for the construction of quantitativemodels of cephalosporins.The CAR.S algorithm demonstrated that the ranges of 4550-4100 cm^(-1) and 6190-5510 cm^(-1) included some key wavenumbers which could be attributed to content changes of cephalosporins.The IR-NIR 2D spectral analysis showed that certain wavenumbersin these two regions have strong correlations to the structures of those cephalosporins that wereeasy to degrade.

Anal carcinoma-exploring the epidemiology,risk factors,pathophysiology,diagnosis,and treatment

Anal carcinoma is a relatively rare tumor that accounts for approximately 2%of gastrointestinal malignancies and less than 7%of anorectal cancers.Most anal tumors originate between the anorectal junction and the anal verge.Risk factors for the disease include human papillomavirus infection,human immunodeficiency virus,tobacco use,immunosuppression,female sex,and older age.The pathogenesis of anal carcinoma is believed to be linked to human papillomavirusrelated inflammation,leading to dysplasia and progression to cancer.Squamous cell carcinoma is the most common type of anal tumor,with an annual incidence of approximately 1 to 2 per 100000 persons.Treatment regarding anal cancer has emerged over time.However,chemoradiation therapy remains the mainstay approach for early localized disease.Patients with metastatic disease are treated with systemic therapy,and salvage surgery is reserved for disease recurrence following chemoradiation.This article aims to provide background information on the epidemiology,risk factors,pathology,diagnosis,and current trends in the management of anal cancer.Future directions are briefly discussed.

Clinical Study on the Treatment of Low Anal Fistula in Infants and Young Children by Anal Gland Excision and Virtual Hanging Procedure

Objective:To compare the efficacy of anal adenectomy with virtual hanging wire and anal fistulotomy in the treatment of low anal fistula in infants and children.Methods:60 children with low anal fistula who were admitted to our hospital from October 2021 to March 2022 and met the inclusion criteria were randomly divided into two groups of 30 cases each;the treatment group was treated with anal adenectomy and virtual hanging wire surgery,and the control group was treated with anal fistula resection.The clinical efficacy after treatment was compared.Results:The total effective rate of both groups was 96.67%and the difference between the two groups was not statistically significant(P>0.05).The postoperative pain score of the treatment group was lower than that of the control group(P<0.05).The length of hospitalization and healing time of the treatment group was lower than that of the control group(P<0.05).The anal function of the patients in both groups was normal,and there was no adverse reaction.Conclusion:Anal gland excision and virtual hanging surgery for the treatment of low anal fistula in infants and children have the advantages of mild pain,reduced length of hospitalization,short healing time,and better patient experience as compared to anal fistula excision.

A case study illustrating the use of an integrated approach to treat secondary Anal Fistula Post I&D of Perianal Abscess

Background:Anal fistula is a long-term disease characterized by a tubular structure with one end opening in the anorectal canal and the other end opening on the surface of the perineum or perianal skin with chronic pus drainage.It is linked to Bhagandar in Ayurveda,and in Sushruta Samhita,Acharya has mentioned 5 forms of Bhagandar.The boil in the present case was Shukla,sthira i.e.hard and firm,with Picchila strava and Kandu resembling the features of Parisraavi bhagandar.Aim and objective:The current case was diagnosed as Parisravi bhagandar,which resembles trans-sphincteric or intersphincteric fistula in modern ano.In Ayurveda,the management of Parisraavi Bhagandar,Shastra,kshara,and Agnikarma is advised and the use of Ksharasutra,which contributes to complete cutting and healing of the track without reoccurrence,similarly Modern surgeon depends on surgery i.e radical excision of the track,ligation with Seton,and use of chemical irritants like urethane,silver nitrates,etc.A cutting seton(tight)gently slices the confined muscle to close the fistula with the least interruption to continence.This operation is especially advised when a one-stage fistulotomy poses a considerable risk of incontinence.Material and methods:The method performed here was Core Partial Fistulectomy followed by Ksharasutra application till complete healing of the wound.Discussion and conclusion:This case study provides the successful management of Parisraavi Bhagandara(high anal,trans-sphincteric fistula in ano)in 61-year-old male patient with an integrated surgical&Ayurvedic management approach.

Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam Versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies

We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.

Spectophotometric method for determination of certain cephalosporins using 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl)

A simple, accurate and precise spectrophotometric method has been proposed for the determination of eleven cephalosporins, namely;cefaclor monohydrate, cefadroxil monohydrate, cefalexin anhydrous, cefradine anhydrous, cefotaxime sodium, cefoperazone sodium, ceftriaxone sodium, ceftazidime penthydrate, cefazolin sodium, cefixime and cefpodoxime pro- xetil in bulk drug and in pharmaceutical formulations. The method depends on hydrolysis of the studied drugs using 0.5M NaOH at 100&#176;C and subsequent reaction of the formed sulfide ions with NBD-Cl (4-chloro-7-nitrobenzo-2-oxa-1, 3-diazole) to form a yellow-colored chromogen measured at 390 nm. Different variables affecting the reaction (e.g. NaOH concentration, hydrolysis time, NBD-Cl concentration and diluting solvent) were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990- 0.9999) were found in the range of 5-160 μg mL-1 for all studied drugs. The limits of assay detection and quantitiation ranged from 0.289 to 5.867 and from 0.878 to 17.778 μg mL-1;respectively. The accuracy and precision of the proposed method were satisfactory. The method was successfully applied for analysis of the studied drugs in their pharmaceutical formulations and the recovery percentages ranged from 96.6 to 103.5%.

Kinetic spectrophotometric determination of certain cephalosporins using iodate/iodide mixture

A simple, precise and accurate kinetic spectro-photometric method for determination of ce-fradine anhydrous, cefaclor monohydrate, ce-fadroxil monohydrate, cefalexin anhydrous and cefixime in bulk and in pharmaceutical formula-tions has been developed. The method based on a kinetic investigation of the reaction of the free carboxylic acid group of the drug with a mixture of potassium iodate and potassium iodide at room temperature to form yellow coloured triiodide ions. The reaction was followed up spectrophotometrically by measuring the increase in absorbance at 352 nm as a function of time. The initial rate, fixed time, variable time and rate-constant methods were adopted for constructing the calibration curves but fixed time method has been found to be more applicable. The analytical performance of the method, in terms of accuracy and precision, was statistically validated;the results were satisfactory. The method has been successfully applied to the determination of the studied drugs in commercial pharmaceutical formulations. Statistical comparison of the results with a well established reported method showed excellent ag- reement and proved that there is no significant difference in the accuracy and precision.

Relationship between anal cancer recurrence and cigarette smoking

BACKGROUND The incidence of anal cancer has been increasing in the United States.Smoking is a well-established risk factor;however,the impact of smoking on disease recurrence and outcome has not been well studied.The aim of this study was to assess the association between anal cancer recurrence and cigarette smoking.AIM To investigate the relationship between cigarette smoking status and anal cancer treatment outcome.METHODS The cancer registry from a single,community hospital was screened for patients with anal cancer between 2010 and 2021.The following characteristics were gathered from the database:Age;sex;cigarette smoking history;American Joint Committee on Cancer Clinical Stage Group;response to therapy;recurrence;time to recurrence;mortality;time to death;and length of follow-up.Patients were divided into the following groups:Current smokers;former smokers;and never smokers.SPSSv25.0 software(IBM Corp.,Armonk,NY,United States)was used for statistical analysis.RESULTS A total of 95 patients from the database met the screening criteria.There were 37 never smokers,22 former smokers,and 36 current smokers.There was no difference between groups in regards to race or sex.There was no difference in the American Joint Committee on Cancer Clinical Stage Group between groups.The former smokers were significantly older when compared to never smokers and current smokers(66.5±13.17 vs 57.4±7.82 vs 63.7±13.80,P=0.011).Former smokers and current smokers had a higher recurrence rate compared to never smokers(30.8%and 20.8%compared to zero,P=0.009).There was not a significant difference in recurrence between former smokers and current smokers.There was no difference in the mortality,non-response rate,or time to death between the groups.CONCLUSION Our data contributes evidence that cigarette smoking status is associated with increased recurrence for patients with anal cancer.

Studies on Semisynthesis and Anibacterial Activity of 7 β-(5-Methyl-1-Aryl-1H-1,2,3-Triazoly-4-Carboxamido) Cephalosporins

Nine new derivatives of 7 β - (5- methyl- 1- aryl- 1H-1, 2, 3- triazoly- 4- carboxamido) cephalosporins were synthesized by acylction of 7 β -amino group of 7-ACA, 7-ADCA and 7-ACT with 5 -methsyl- 1 -aryl- 1 H- 1,2,3-triazoly-4-formyl chloride. The structure of the compounds were confirmed by elementray analysis IR, HNMR and FAB-MS. Some of them showed significant antibacterial activity

Computational Calculations of Molecular Properties and Molecular Docking of New and Reference Cephalosporins on Penicillin Binding Proteins and Various β-Lactamases

An approach of using molinspiration calculations and molecular docking on PBPs （penicillin-binding proteins） and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of newer and reference cephalosporins. The previously synthesized cephalosporins 1-8 and reference cephalosporins were subjected to extensive evaluations by calculating the molecular properties, drug-likeness scores on the bases of Lipinski＇s rule and bioactivity prediction using the method of molinspiration web-based software. The TPSA （topological polar surface area）, OH-NH interactions, n-violation and the molinspiration Log partition coefficient （miLogP） values were also calculated. The investigated cephalosporins were subjected to molecular docking study on PBPs （lpyy） and on β-lactamases produced by S. aureus, K. pneumonia, E. coil and P. auroginosa using 1-click-docking website. Molecular properties of 1-8 recorded higher ＂FPSA than cephalexin and were lower than the reference cephalosporins and do not fulfill the requirements for Lipinski＇s rule. Bioactivities of 1-8 were predicted to be less and their docking scores on PBPs were comparable to those of the reference cephalosporins, particularly ceftobiprole. The references recorded various docking scores on the above β-lactamases and as expected, cefiobiprole recorded the lowest scores on all β-lactarnases. Cephalosporins 1-8 recorded various docking scores on β-lactamases. Molecular docking studies on PBPs and β-lactamases are considered as very useful, reliable and practical approach for predicting the bioactivity scores and to afford some information about the stability and selectivity of the newly proposed cephalosporins against β-lactamases of certain pathogenic microbes, such as P. auroginosa and MRSA, by recording the relative docking scores in comparison with those of reference cephalosporins.