Pushing the Boundaries of Pedicled Chest Wall Perforator Flaps in Oncoplastic Breast Surgery.

Among 145 chest wall perforator flaps (CWPFs) performed at City Hospital, Birmingham (September 2017-February 2022), 11 were for novel indications, four were for whole breast reconstructions, two were for implant salvage procedures, three were CWPFs with skin paddle to replace excised skin/nipple-areola complex, and two were for upper inner quadrant tumours. Tumour characteristics and post-operative complications were noted. Patient-reported outcomes measures (PROMs) were measured using a questionnaire adapted from the National Mastectomy and Breast Reconstruction Audit (NMBRA) study. Among 11 patients, nine (81.81%) did not develop any complications. Ten patients responded to PROMs (median follow-up of eight months). The PROMs assessment showed that all patients (100%) were satisfied with the post-operative breast appearance. Of the patients, 90% (9/10) felt the results of their surgery to be good, very good, or excellent. Of the patients, 70% (7/10) said that they have no/little persistent pain. None of the patients had difficulty carrying out normal activities. Thus, the applications of CWPFs could be extended for whole breast reconstruction, implant salvage procedures, where skin paddle is needed, and for upper inner quadrant tumours.

Benign Phyllodes Tumour With Cystic Squamous Metaplasia: A Rare Histology Finding.

Phyllodes tumour (PT) comprises 0.3-1% of all breast cancers and 3% of fibroepithelial neoplasm. It occurs more commonly in the fourth and fifth decades of life. Fibroepithelial neoplasms are composed of cell types with two different origins, commonly mesenchymal and epithelial. Histological features are important as this forms the basis of the categorization of PT into benign, borderline and malignant types, thus facilitating management. Metaplasia in any of the two components of PT is rare and the cystic squamous type of metaplasia has even more infrequent histological features. Case: This paper presents the case of a 63-year-old female with a palpable lump in the lower outer quadrant of her left breast. Histology showed a benign Phyllodes tumour with patchy, cystic squamous metaplasia within the lesion, keratin production and foreign-body reaction in response to keratin spillage. The previously done core biopsy was also reviewed, which showed focal stromal cell condensation and features overlapping between benign and borderline phyllodes tumours. Conclusion: The case was presented because of its unique and rare histological picture of Cystic squamous metaplasia in benign PT and a further rarer finding of foreign body reaction to keratin spillage.

Determination of ionization constant and drug-likeness prediction of synthetic isoniazid derivatives.

Determination of ionization constant, commonly termed pKa is of prime interest in a wide range of pharmaceutical Research fields. The pKa of a compound is critical as it influences on its physicochemical parameters in biological and environmental systems. The study of pKa is also essential not only for the formulation of drugs and optimization of a variety of novel analytical methods, establishing new pharmaceutical dosage forms yet the exploration of the mechanism of action of drugs. In this research work, we have determined pKa values of isoniazid (INH) derivatives; N'-[(4-methyl benzoyl)] pyridine-4-carbohydrazide (I) and [2-oxo-2-(4-phenyl phenyl) ethyl] (pyridine-4-yl formamido) azanium bromide (II) through UV- spectrophotometry, a method is known for the accuracy and precision of results. These two compounds (I and II) were synthetically prepared in our lab by derivatizing INH and reported by Naeem et al in the year 2014. The mean pKa values for compounds I and II were experimentally determined as 7.37 and 3.76 respectively. The study is helpful in understanding the physicochemical behavior of these compounds in a biological system. Different pharmacokinetic parameters were also predicted using online web tools which ensured significant drug-likeness for both compounds.

Comparison of surgical and oncological outcomes between oncoplastic breast-conserving surgery versus conventional breast-conserving surgery for treatment of breast cancer: A systematic review and meta-analysis of 31 studies.

AIMS: To evaluate comparative outcomes of oncoplastic breast conserving surgery (OBCS) versus conventional breast conserving surgery (BCS) for breast cancer treatment. METHODS: A systematic search of multiple electronic data sources was conducted, and all eligible studies comparing OBCS and BCS were included. Characteristics of the tumour includes preoperative size of tumour on imaging and the weight of the specimen after resection. While positive margins rate, re-excision rate, completion mastectomy rate and loco-regional recurrence were considered as oncological outcome parameters. Post-operative complications include surgical site infection (SSI), seroma, haematoma and skin/nipple necrosis. RESULTS: Thirty-one studies reporting a total number of 115011 patients who underwent OBCS (n = 11978) or BCS (n = 103033) were included. OBCS group showed lower risk of positive margins rate [OR 0.76, P = 0.05], re-excision rate [OR 0.72, P = 0.02], and loco-regional recurrence [OR 0.62, P = 0.03] compared to BCS group. There was no significant difference between the two groups regarding post-operative complications. CONCLUSION: Although there is a lack of level 1 evidence, the available studies clearly demonstrate superior or at least equivalent outcomes when comparing OBCS with conventional BCS. The benefits of OBCS include dealing with larger tumours, wider surgical margins and better aesthetic results for patients.

Comparison Of Axillary Drain Output In Conventional And Advanced Compressive Energy Source Like Ultrasonic Scalpel And Ligasure Dissection Of Axilla In Breast Cancer Surgery.

BACKGROUND: Breast cancer is the most common malignancy worldwide. Surgical treatment of axilla is a part of treatment of locally advanced breast cancer. Conventional knot tying plus electrocautery and advanced compressive energy sources are used to reduce the continued axillary serous fluid discharge when drains are in place and seroma formation afterwards. METHODS: This double-blind comparative study was carried out from April 2018 to October 2019. In total 180 patients undergoing axillary dissection for treatment of locally advanced breast cancer were recruited. Patients were divided into two groups (C and H) depending upon method of dissection used for axillary surgery. RESULTS: For most participants, amount of axillary drain volume in Group C was between 400-700 ml (in 48.9% participants) and for Group H more than 700 ml (in 44.4% participants). This difference is not statistically significant (p=0.288). Duration of hospital stay (p=0.003) and duration of drain placement was significantly longer (p=0.019) for most participants in Group H. More hospital visits were required for the said group. There was statistically significant co-relation between immediate complications and haemostasis techniques (p=0.003) with more incidence of Seroma noticed in Group H than in Group C. CONCLUSIONS: Current study shows limited benefits of using ultrasonic scalpels in breast cancer surgeries. Variables such as BMI, Age and chemotherapy need to be controlled in order to derive a true comparison.

Audit of antibiotic prophylaxis and adherence of surgeons to standard guidelines in common abdominal surgical procedures.

BACKGROUND: Prophylactic use of antibiotics before surgery is evidence-based practice for prevention of surgical site infections (SSIs). AIMS: To investigate adherence to and surgeons' perception of antibiotic prophylaxis guidelines. METHODS: A two-phase, cross-sectional prospective study conducted in two teaching hospitals. Phase 1: 6-month audit of prescriptions to investigate adherence rate to evidence-based guidelines. The important information was collected from medical charts through a predesigned proforma. Phase 2: self-administration questionnaire was used to investigate the surgeons' perception. Descriptive statistics, independent-sample Kruskal-Wallis test and multivariate linear regression analysis were performed using SPSS version 21.0. RESULTS: A total of 866 eligible surgical cases (acute appendectomy; n = 418; 48.2%), laparoscopic cholecystectomy (n = 278; 32.1%) and inguinal hernia (n = 170; 19.7%) were investigated. Surgical antibiotic prophylaxis was prescribed in 97.5% of procedures. Out of these, 9.5% adhered to guidelines with respect to correct choice, 40% for timing, and 100% for dose and route (optimal value 100%). Most patients received ceftriaxone (n = 503; 59.5%) as prophylactic antibiotic. The questionnaire (good internal consistency; α ≥ 0.7) was filled out by 200 surgeons. More than half (69%) of participants thought that antibiotics were overused. Most surgeons perceive that poor adherence to treatment guidelines is due to poor awareness, underestimation of infection, lack of consensus, and disagreement with guidelines recommendations. CONCLUSIONS: Surgeons have positive perception that antibiotics should be used according to guidelines recommendations. However, we found poor treatment adherence to antibiotic prophylaxis guidelines.

In-silico determination of pKa and logp values of some isoniazid synthetic analogues using Marvin software.

Among the physicochemical properties, pKa and LogP values help us in studying drug parameters like ADME and could be predicted to some extent. With this view, here we wish to predict these two properties of our previously synthesized biologically active derivatives of isoniazid using on-line available program Marvin, a Java-based chemical software application frequently used for chemical modeling. According to Marvin, pKa values predicted 99.99% unionized states of INH and some derivatives at physiological pH 7.4. Marvin calculated LogP values estimated good oral absorption for all the synthesized compounds. Therefore it can be said that the findings of the study emerged in an ideal region that permits the formulation of these derivatives. Since this was just a theoretical study, it demands more experimentation to determine accurate situation.

Baseline characteristics of infected foot ulcers in patients with diabetes at a tertiary care hospital in Pakistan.

OBJECTIVE:: Studies on diabetic foot ulcers (DFU) involving a representative sample of patients in Pakistan are scarce. This study aimed to determine baseline characteristics of infected DFUs in patients hospitalised at the Pakistan Institute of Medical Sciences Islamabad. METHOD:: In this cross-sectional study, carried out during May 2015 and June 2016, foot ulcer characteristics of patients with DFUs were investigated and documented. From infected DFUs, aerobic bacterial pathogens were isolated, identified and evaluated for antimicrobial susceptibility. RESULTS:: A total of 214 patients were recruited to the study, 62.6% of which were male, 90.2% were aged ≥40 years, 76.2% had type 1 diabetes and 78.5% had poor glycaemic control at time of presentation to hospital. Most patients had grade 3/moderate ulceration (based on the Wagner and International Working Group on the Diabetic Foot/Infectious Diseases Society of America criteria). Over half of the DFUs (57.9%) were of ≤3 months' duration and 70.1% were ≥3 cm2. Of the patients with deep infection grade ulcers, 26.6% underwent amputation, accounting for their prolonged hospital stay (≥20 days). Significant differences were observed between patients with type 1 and type 2 diabetes with DFUs in relation to gender (p≤0.0001), ulcer size (p=0.0421) and duration of hospital stay (p=0.0253). The most significant predictors for lower extremity amputation were osteomyelitis (p=0.0114), retinopathy (p=0.0001) and neuropathy (p=0.0001. Piperacillin/tazobactam was found to be an effective antibiotic against the most commonly isolated Staphylococcus non-aureus (35.48%), Pseudomonas aeruginosa (22.26%), and Staphylococcus aureus (20.96%) species indentified in the DFU infections. CONCLUSION:: The findings of this study may be helpful in the optimal management and appropriate treatment of patients with infected DFUs.

Cytotoxic and acute toxicity studies of isoniazid derivatives.

Cancer is ultimately the result of cells that hysterically grow and do not die. Cells can experience uncontrolled growth if there are mutations to DNA, and therefore, alterations to the genes involved in cell division. Cancer occurs when a cell's gene mutations make the cell unable to correct DNA damage and is unable to destroy itself. There are over 100 different types of cancer each classified by the type of initially affected cell. Isoniazid, a well-known antitubercular agent has been reported to exhibit some cytotoxic activity. This finding prompt us to carry out this study where isoniazid and its sixteen derivatives were studied for any possible cytotoxic activity against Human astrocytoma SNB-19 cells, human Dukes' type C colorectal adenocarcinoma HCT-15 cells, human Dukes' type D colorectal adenocarcinoma COLO-205 cells, and human prostate adenocarcinoma (grade IV) PC-3 cells. Among the test compounds, SN-07 (a phenacyl derivative with para phenyl substitution) demonstrated slight cytotoxic effects on two types of human colorectal adenocarcinoma cells HCT-15 and COLO-205. Moreover, the acute toxicity of the compounds was also estimated in which some compounds were evaluated with more LD50 values than isoniazid.

Prevalence and susceptibility patterns of bacteria causing respiratory tract infections in North Waziristan, Pakistan.

Respiratory tract infections (RTIs) are the most common infectious diseases in humans and are the major cause of mortality and morbidity in Pakistan. These infections are the leading causes of consultations in primary care in Pakistan. Therefore, this study was aimed at determining bacterial pathogens of respiratory tract infections and the susceptibility patterns of bacterial isolates to antibiotics. The study was conducted between February, 2013 and March, 2014 in North Waziristan region of Pakistan. Sputum specimens were collected aseptically from 227 patients and cultured on the appropriate bacteriological media. Bacterial isolates were identified by biochemical tests and their antibiotics susceptibility patterns were determined by standard methods. Out of 227, various species of bacteria were isolated from 152 (75%) specimens. The prevalence of bacteria species isolated were as follows Pseudomonas aeruginosa (42.8%), Streptococcus pneumoniae (26.7%), Corynebacterium diphtheria (10.6%), Staphylococcus aureus (5.9%), Proteus vulgaris (4.6%), Micrococcus species (3.3%), Klebsiella pneumoniae (2.6%) and Bacillus species (2.6%). The susceptibility patterns varied among bacterial species depending on the antibiotics. For the susceptibility test 11 commercially available antibiotics against bacterial isolates were used. The results revealed that generally the bacterial isolates were susceptible to gentamicin (80.9%), meropenem (75 %), ceftazidime (62.5%), cefotaxime (57.9%) and ceftriazone (57.9%) and resistant to penicillin (84.9%) and doxycycline (78.9%). The antibiotics gentamicin (100%) meropenem (100%), ceftriaxone (58.5%), ciprofloxacin (60%) trimethoprim (60%), ceftazidime (66.2%) and cefotaxime (64.6%) were observed effective against the P. aeruginosa isolates. The findings of our study provide significant information for empiric therapy of patients with RTIs in North Waziristan region of Pakistan.

Antimicrobial and antioxidant screening of N¢-substituted sulphonyl and benzoyl derivatives of 4-Pyridine carboxylic acid hydrazide.

In this research program, the antibacterial, antifungal and antioxidant activities of six N'-substituted sulfonyl and benzoyl derivatives of lead molecule PCH were reported. Out of these compounds, sulphonyl derivatives 2,3 and benzoyl derivative 5 showed moderate to good activity against different strains of gram-positive and gram-negative bacteria including B. cereus, B. subtilis, B. thruingiensis and S. pyogenes, S. fecalis and E. coli ATCC 8739. Moreover, upon antifungal screening, the compound, N¢-[(2,4,6-trimethylbenzene) sulfonyl]pyridine-4-carbohydrazide possessed good antifungal activity against Candida species, a causative agent of systemic fungal infections. Antioxidant study demonstrated more than 50% inhibition in DPPH assay for sulphonyl derivative 2 indicating its potential as antioxidant while the other derivatives expressed low level of radical scavenging property.

Synthesis of novel derivatives of 4-pyridine carboxylic acid hydrazide and their activity on central nervous system.

Six novel derivatives (2-7) of 4-Pyridine carboxylic acid hydrazide (PCH) were synthesized by treating this lead molecule with substituted arylsulphonyl and benzoyl chlorides. The molecular structures of the newly derived products were characterized by the help of UV Visible, IR, FAB, 1HNMR spectroscopy and CHN analysis. During the preliminary pharmacological screening, it was observed that the synthesized compounds induced noticeable changes on motor activity of the animals. Interesting structure activity relationship was also observed among the synthesized molecules. Because of the interesting affect on motor activity, the newly synthesized derivatives can further be evaluated for their effects on CNS.

Determination of pKa values of new phenacyl-piperidine derivatives by potentiometric titration method in aqueous medium at room temperature (25±0.5oC).

Dissociation constant (pKa) of ten novel phenacyl derivatives of piperidine were determined by potentiometric titration method in aqueous medium at room temperature (25 ±0.5°C). The sample solutions were prepared in deionized water with ionic strength 0.01M and titrated with 0.1M NaOH solution. In addition, ΔG values were also calculated. Different prediction software programs were used to calculate pKa values too and compared to the experimentally observed pKa values. The experimental and theoretical values were found in close agreement. The results obtained in this research would help to predict the good absorption of the studied compounds and can be selected as lead molecules for the synthesis of CNS active agents because of their lipophilic nature especially compound VII.