HFIP-Mediated Multicomponent Reactions: Synthesis of Pyrazole-Linked Thiazole Derivatives.

The development of one-pot, atom, and step-economic new methods avoiding metal, harsh reaction conditions, and toxic reagents for the synthesis of medicinally important hybrid molecules bearing more than one bioactive moieties is currently one of the hot topics in organic synthesis. Herein, we report a green and efficient room temperature multicomponent reaction for the synthesis of novel pyrazole-linked thiazoles involving a one-pot C-C, C-N, and C-S bond-forming process from the reaction of aryl glyoxal, aryl thioamide, and pyrazolones in 1,1,1,3,3,3-hexafluoroisopropanol, a hydrogen bond donating reaction medium. A set of diverse hybrid molecules bearing thiazole and pyrazole moieties were prepared in good to excellent yields by using this method. This methodology can also be extended to prepare thiazole-linked barbiturates as well as imidazole-linked pyrazoles. All the products were fully characterized by spectroscopic techniques. The notable features of this protocol are room temperature, metal as well as additive-free reaction conditions, use of recyclable solvent, water as the byproduct, wide substrate scope, operational simplicity, easy purification, applicability for gram-scale synthesis, high atom economy, and the presence of two bioactive pyrazole and thiazole moieties in the products.

Association of omental pedicled flap with anastomotic leak following low anterior resection for rectal cancer.

BACKGROUND AND OBJECTIVES: Anastomotic leak following colorectal anastomosis adversely impacts short-term, oncologic, and quality-of-life outcomes. This study aimed to assess the impact of omental pedicled flap (OPF) on anastomotic leak among patients undergoing low anastomotic resection (LAR) for rectal cancer using a multi-institutional database. METHODS: Adult rectal cancer patients in the US Rectal Cancer Consortium, who underwent a LAR for stage I-III rectal cancer with or without an OPF were included. Patients with missing data for surgery type and OPF use were excluded from the analysis. The primary outcome was the development of anastomotic leaks. Multivariable logistic regression was used to determine the association. RESULTS: A total of 853 patients met the inclusion criteria and OPF was used in 106 (12.4%) patients. There was no difference in age, sex, or tumor stage of patients who underwent OPF versus those who did not. OPF use was not associated with an anastomotic leak (p = 0.82), or operative blood loss (p = 0.54) but was associated with an increase in the operative duration [ß = 21.42 (95% confidence interval = 1.16, 41.67) p = 0.04]. CONCLUSIONS: Among patients undergoing LAR for rectal cancer, OPF use was associated with an increase in operative duration without any impact on the rate of anastomotic leak.

Outcomes of oncoplastic breast surgery compared to breast-conserving surgery in breast cancer patients in a developing country: a retrospective cohort study.

Background and Objective: Breast-conserving surgery (BCS) with adjuvant radiotherapy remains the standard of care for early breast cancers in Pakistan. We sought to compare the outcomes of BCS with oncoplastic surgery (OPS), a relatively infrequent approach to breast cancer treatment in the country. Methods: This retrospective cohort study was conducted at Aga Khan University Hospital and Ziauddin Hospital in Karachi. Patients who had biopsy-proven Stage-I to III breast cancer and underwent either OPS or BCS between August 1, 2016, and December 31, 2021, were identified and followed for 30 days. Data were collected by reviewing patient files and electronic records. Results: A total of 481 patients were included in the study, where 204 (42.4%) underwent BCS and 277 (57.6%) underwent OPS. Mean tumor volume (146.8 vs. 90.4 cm3), and postoperative complications (2.2 % vs. 0%) were higher in OPS while the frequency of positive margins was greater in the BCS group (15.7 % vs. 2.2 %). There were no significant differences in the histologic type of tumor between the two groups. Conclusion: OPS is a valid alternative approach to breast cancer treatment that can be offered to women with early stage, locally advanced, multifocal or tumors at complex locations owing to the reduced occurrence of positive margins and thus lowered re-excision rates.

An initial experience of using dual energy contrast enhanced mammography at a tertiary care hospital in Pakistan.

Objective: Contrast enhanced mammography (CEM), a relatively new and promising modality, combines mammography (MMG) with an iodinated contrast material to illuminate neovascularity within the breast; analogous to magnetic resonance imaging (MRI). CEM improves the overall sensitivity of MMG; reduces the need for unnecessary biopsies and follow-up imaging and can be considered a reasonable substitute for MRI. In Pakistan, CEM was recently introduced and to assess its usability a study was conducted on five patients before making it available as a regular investigation. Case presentations: Four out of the five patients had a clinical suspicion of malignancy with two patients having heterogeneously dense breasts and two with dense breasts. All enhancing lesions were concordant on biopsy and had similar corresponding findings on additional imaging such as ultrasound (US) and/or MRI. CEM in all four cases of biopsy proven malignancy facilitated surgical planning. The fifth patient underwent CEM for screening and was found to have no enhancing lesion. Conclusion: In low-middle-income countries (LMICs) where breast MRI is not readily available and expensive for the populace, CEM can be a reliable alternative. The initial experience with CEM at our hospital shows better visualization of malignant lesions in dense and heterogeneously dense breasts with an easy-to-perform technique and a shorter imaging time while facilitating surgical decision-making in terms of breast conservation.

An Easy-To-Use Prehospital Severity Scoring Tool To Triage COVID-19 Positive Adults In A Resource-Limited Setting.

Objectives: To develop an easy-to-use severity scoring tool for prehospital triage of patients infected by the coronavirus disease-2019 in resource-limited settings. METHODS: The cohort study was conducted at a tertiary care hospital in Karachi, from August to September 2020, and comprised adult patients of either gender who tested positive for coronavirus disease-2019 on real-time polymerase chain reaction. The scoring system and categorisation were based on validated scales for the detection of pneumonia and opinions from pulmonologists. Data was analysed using SPSS 19. RESULTS: Of the 206 participants, 100(48.5%) were in-patients and 106(51.5%) were out-patients. There were 144(69.9%) males and 62(30.1%) females with an overall mean age of 48.4±16.2 years. After categorisation based on severity, significantly higher number of in-patients were found to be in categories III and IV (p<0.05). CONCLUSIONS: The severity scoring tool could effectively help classify coronavirus disease-2019 patients into mild, moderate and severe cases.

Synthesis of Selenocyanates and Selenoethers of Amino Pyrazoles and Amino Uracils by In Situ Triselenium Dicyanide from Malononitrile and Selenium Dioxide.

Herein, we report an efficient method for synthesis of novel selenocyanates of amino pyrazole, amino uracil, and amino isoxazole derivatives using in situ triselenium dicyanide from the combination of malononitrile and selenium dioxide in DMSO medium. Using the same combination but changing the stoichiometry of reagents and sequence of addition and temperature, symmetrical selenoethers of amino pyrazoles and amino uracils were prepared in good yields. Furthermore, selenocyanates of amino pyrazoles were utilized for the synthesis of corresponding alkynyl selenides in the presence of CuI and Cs2CO3. The salient features of this methodology are inexpensive starting materials, short reaction time, and good to very good yields. This method is also applicable for the gram-scale synthesis of selenocyanates of amino pyrazoles and amino uracils.

The impact of community medical camps on medical students and graduates' education.

Objectives: To investigate the impact of volunteering at community medical camps on medical students' and graduates' clinical and soft skills, knowledge of community health, and future career goals. METHODS: The cross-sectional pilot study was conducted at the Aga Khan University Hospital, Karachi from July to October 2020, and comprised medical students or trainees who had attended at least one medical camp in a community-based setting organised by any of the two non-governmental organisations who collaborated in the study. Responses were obtained through a self-reported online survey from the participants. Data was analyzed using SPSS 25. RESULTS: Of the 52 subjects, there were 25(48.9%) males and 27(51.9%) females with overall mean age 25.4±3.8 years. Majority of the participants 35(67.3%) had attended a private first-tier medical school while 17(32.7%) had attended other local medical schools. Overall, 40(76.9%) subjects reported improved community knowledge, , 44(84.6%) had experiential learning and confidence in outpatient management, and 49(94%) had improved soft skills. Besides, 21(40.4%) participants agreed to have been influenced to pursue a career in primary care, and 25(48.1%) reported a direct impact on their choice of career specialty. Compared to males, females reported improved awareness and alertness (p=0.016), increased confidence approaching communities (p=0.032), and increased compassion towards patient care (p=0.047). CONCLUSIONS: Community-based medical camps had an overall positive impact on volunteering medical students.

Rising arterial stiffness with accumulating comorbidities associates with heart failure with preserved ejection fraction.

AIMS: Comorbidities play a significant role towards the pathophysiology of heart failure with preserved ejection fraction (HFpEF), characterized by abnormal macrovascular function and altered ventricular-vascular coupling. However, our understanding of the role of comorbidities and arterial stiffness in HFpEF remains incomplete. We hypothesized that HFpEF is preceded by a cumulative rise in arterial stiffness as cardiovascular comorbidities accumulate, beyond that associated with ageing. METHODS AND RESULTS: Arterial stiffness was assessed using pulse wave velocity (PWV) in five groups: Group A, healthy volunteers (n = 21); Group B, patients with hypertension (n = 21); Group C, hypertension and diabetes mellitus (n = 20); Group D, HFpEF (n = 21); and Group E, HF with reduced ejection fraction (HFrEF) (n = 11). All patients were aged 70 and above. Mean PWV increased from Groups A to D (PWV 10.2, 12.2, 13.0, and 13.7 m/s, respectively) as vascular comorbidities accumulated independent of age, renal function, haemoglobin, obesity (body mass index), smoking status, and hypercholesterolaemia. HFpEF exhibited the highest PWV and HFrEF displayed near-normal levels (13.7 vs. 10 m/s, P = 0.003). PWV was inversely related to peak oxygen consumption (r = -0.304, P = 0.03) and positively correlated with left ventricular filling pressures (E/e') on echocardiography (r = -0.307, P = 0.014). CONCLUSIONS: This study adds further support to the concept of HFpEF as a disease of the vasculature, underlined by an increasing arterial stiffness that is driven by vascular ageing and accumulating vascular comorbidities, for example, hypertension and diabetes. Reflecting a pulsatile arterial afterload associated with diastolic dysfunction and exercise capacity, PWV may provide a clinically relevant tool to identify at-risk intermediate phenotypes (e.g. pre-HFpEF) before overt HFpEF occurs.

The hemodynamic initial-dip consists of both volumetric and oxymetric changes reflecting localized spiking activity.

The initial-dip is a transient decrease frequently observed in functional neuroimaging signals, immediately after stimulus onset, believed to originate from a rise in deoxy-hemoglobin (HbR) caused by local neural activity. It has been shown to be more spatially specific than the hemodynamic response, and is believed to represent focal neuronal activity. However, despite being observed in various neuroimaging modalities (such as fMRI, fNIRS, etc), its origins are disputed, and its precise neuronal correlates are unknown. Here we show that the initial-dip is dominated by a decrease in total-hemoglobin (HbT). We also find a biphasic response in deoxy-Hb (HbR), with an early decrease and later rebound. Both the HbT-dip and HbR-rebound were strongly correlated to highly localized spiking activity. However, HbT decreases were always large enough to counter the spiking-induced increase in HbR. We find that the HbT-dip counters spiking induced HbR increases, imposing an upper-limit to HbR concentration in the capillaries. Building on our results, we explore the possibility of active venule dilation (purging) as a possible mechanism for the HbT dip.

Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury.

Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ11. PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting NINJ1 and PMR may limit the inflammation that is associated with excessive cell death. Here we describe an anti-NINJ1 monoclonal antibody that specifically targets mouse NINJ1 and blocks oligomerization of NINJ1, preventing PMR. Electron microscopy studies showed that this antibody prevents NINJ1 from forming oligomeric filaments. In mice, inhibition of NINJ1 or Ninj1 deficiency ameliorated hepatocellular PMR induced with TNF plus D-galactosamine, concanavalin A, Jo2 anti-Fas agonist antibody or ischaemia-reperfusion injury. Accordingly, serum levels of lactate dehydrogenase, the liver enzymes alanine aminotransaminase and aspartate aminotransferase, and the DAMPs interleukin 18 and HMGB1 were reduced. Moreover, in the liver ischaemia-reperfusion injury model, there was an attendant reduction in neutrophil infiltration. These data indicate that NINJ1 mediates PMR and inflammation in diseases driven by aberrant hepatocellular death.

Clinicopathological Features and Survival Outcomes of Metaplastic Breast Carcinoma - An Observational Multi-Centric Study.

Purpose: To describe the clinicopathological features, and subtypes of metaplastic breast cancer (MpBC) in Pakistan and further to understand its response to treatment, including region-specific survival outcomes. Patients and Methods: This retrospective cohort study was conducted at two private tertiary care hospitals in Karachi, Pakistan. Our selection criteria included a total of 215 patients who were diagnosed with MpBC at an age older than 18 years from 1994 to 2021. Data regarding clinicopathological features, staging, receptor status, treatment modalities, recurrence, and survival was obtained. Death was scored as an event, and patients who were alive were censored at the time of the last follow-up. Results: The incidence of MpBC at our study centers is 3.21%. The median age of diagnosis was 50 years (range 22 to 80 years) and most patients presented at Stages II (45.1%) and III (44.2%). Among patients who received neoadjuvant chemotherapy, 31.7% achieved complete pathological response. The 3-year survival of those who received neoadjuvant chemotherapy was 96%. During our study, 19.1% of patients died and the median survival duration was 9 years 7 months 9 days. Survival of patients was significantly lower in patients who had metastasis (p-value = 0.042) and those who had tumor recurrence (p-value = 0.001). Conclusion: Metaplastic breast cancer is an extremely rare variant of breast cancer with features that exist as a spectrum. Our study demonstrated considerable success with the use of neoadjuvant chemotherapy. The pathological complete response achieved in our study is one of the highest ever reported. Our success, though limited, warrants further research in the use of neoadjuvant chemotherapy in MpBC.

Clinical efficacy of Azithromycin for COVID-19 management: A systematic meta-analysis of meta-analyses.

BACKGROUND: Azithromycin has been adopted as a component of the COVID-19 management protocol throughout the global healthcare settings but with a questionable if not downright unsubstantiated evidence base. OBJECTIVES: In order to amalgamate and critically appraise the conflicting evidence around the clinical efficacy of Azithromycin (AZO) vis a vis COVID-19 management outcomes, a meta-analysis of meta-analyses was carried out to establish an evidence-based holistic status of AZO vis a vis its efficacy as a component-in-use of the COVID-19 management protocol. METHODS: A comprehensive systematic search was carried out through PubMed/Medline, Cochrane and Epistemonikos with a subsequent appraisal of abstracts and full-texts, as required. The Quality of Reporting of Meta-analyses (QUOROM) checklist and the Assessment of Multiple Systematic Reviews (AMSTAR) methodology were adopted to assess the methodological quality of the included meta-analyses. Random-effects models were developed to calculate summarized pool Odds Ratios (with 95% confidence interval) for the afore determined primary and secondary outcomes. RESULTS: AZO, when compared with best available therapy (BAT) including or excluding Hydroxychloroquine, exhibited statistically insignificant reduction in mortality [(n= 27,204 patients) OR= 0.77 (95% CI: 0.51-1.16) (I2= 97%)], requirement of mechanical ventilation [(n= 14,908 patients) OR= 1.4 (95% CI: 0.58-3.35) (I2= 98%)], induction of arrhythmia [(n= 9,723 patients) OR= 1.21 (95% CI: 0.63-2.32) (I2= 92%)] and QTc prolongation (a surrogate for torsadogenic effect) [(n= 6,534 patients) OR= 0.62 (95% CI: 0.23-1.73) (I2= 96%)]. CONCLUSION: The meta-analysis of meta-analyses portrays AZO as a pharmacological agent that does not appear to have a comparatively superior clinical efficacy than BAT when it comes to COVID-19 management. Secondary to a very real threat of anti-bacterial resistance, it is suggested that AZO be discontinued and removed from COVID-19 management protocols.

Assessment of Determinants of Paediatric Diarrhoea Case Management Adherence in Pakistan.

Worldwide, diarrhoea in children under five years of age is the second leading cause of death. Despite having high morbidity and mortality, diarrhoeal diseases can be averted by simple and cost-effective interventions. The Integrated Management of Childhood Illness (IMCI) has proposed the use of Oral Rehydration Salt (ORS) and zinc together with adequate food and fluid intake for the management of acute non-dysenteric watery diarrhoea in children. In the past, few studies examined the determinants of adherence to diarrhoea case management. Therefore, this study measured the determinants of therapeutic and dietary adherence to diarrhoea case management using the third and fourth wave of Pakistan Demographics and Health Surveys (PDHS) datasets. Data from 4068 children between 0 to 59.9 months with positive history of diarrhoea were included, while data on children with dysentery, severe dehydration, and co-morbid condition was excluded. This study reported therapeutic adherence in less than 10% of children in Pakistan, while dietary adherence was reported in 39.2% of children (37.7% in 2012-2013 and 40.7% in 2017-2018). A significant improvement in therapeutic (0.8% in 2012-2013 and 8.1% in 2017-2018) and dietary adherence (37.7% in 2012-2013 and 40.7% in 2017-2018) was reported in the 2017-2018 survey compared to the 2012-2013 survey. In general, children over the age of one year (compared to children <1 year) and of the richer/richest socioeconomic class (compared to poorest/poorer socioeconomic class) showed higher therapeutic and dietary adherence. Therapeutic and dietary adherence among diarrhoeal children can be improved by increasing the awareness and accessibility of ORS, zinc, and essential foods.

Development of stem cell ethics and legislation in the world and in Pakistan; a narrative review.

Stem cells can transform into specialized types of cells, and their capability of self-renewal is limitless. The advancements in stem cell therapy have encountered various hurdles. Considering the massive scope of stem cells applications in health, an effective regulation and monitoring system should be implemented. It is important to ensure that stem cell research projects in Pakistan work closely with the ethics committees as respecting human rights are of paramount importance. It is also necessary that the ethics and legislation guidelines are reviewed, updated, and monitored effectively at every evolving step.

High-intensity interval training in cardiac rehabilitation: a multi-centre randomized controlled trial.

BACKGROUND: There is a lack of international consensus regarding the prescription of high-intensity interval training (HIIT) for people with coronary artery disease (CAD) attending cardiac rehabilitation (CR). AIMS: To assess the clinical effectiveness and safety of low-volume HIIT compared with moderate-intensity steady-state (MISS) exercise training for people with CAD. METHODS AND RESULTS: We conducted a multi-centre RCT, recruiting 382 patients from 6 outpatient CR centres. Participants were randomized to twice-weekly HIIT (n = 187) or MISS (n = 195) for 8 weeks. HIIT consisted of 10 × 1 min intervals of vigorous exercise (>85% maximum capacity) interspersed with 1 min periods of recovery. MISS was 20-40 min of moderate-intensity continuous exercise (60-80% maximum capacity). The primary outcome was the change in cardiorespiratory fitness [peak oxygen uptake (VO2 peak)] at 8 week follow-up. Secondary outcomes included cardiovascular disease risk markers, cardiac structure and function, adverse events, and health-related quality of life. At 8 weeks, VO2peak improved more with HIIT (2.37 mL.kg-1.min-1; SD, 3.11) compared with MISS (1.32 mL.kg-1.min-1; SD, 2.66). After adjusting for age, sex, and study site, the difference between arms was 1.04 mL.kg-1.min-1 (95% CI, 0.38 to 1.69; P = 0.002). Only one serious adverse event was possibly related to HIIT. CONCLUSIONS: In stable CAD, low-volume HIIT improved cardiorespiratory fitness more than MISS by a clinically meaningful margin. Low-volume HIIT is a safe, well-tolerated, and clinically effective intervention that produces short-term improvement in cardiorespiratory fitness. It should be considered by all CR programmes as an adjunct or alternative to MISS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02784873. https://clinicaltrials.gov/ct2/show/NCT02784873.

Cardiac rehabilitation exercise training can improve cardiorespiratory fitness and quality of life for people with coronary artery disease, but sometimes, it is not effective. The intensity of the exercise training may be important. We conducted a randomized controlled trial to test if moderate-intensity exercise or high-intensity exercise was better.High-intensity interval training was more effective than moderate-intensity exercise training for improving cardiorespiratory fitness in people with coronary artery disease attending cardiac rehabilitation.High-intensity interval training was safe and well tolerated.

Uso profiláctico de apósitos de silicona para minimizar las lesiones por presión: revisión sistemática y metaanálisis / Prophylactic use of silicone dressing to minimize pressure injuries: Systematic review and meta-analysis

Objetivo: La prevención de las lesiones por presión (LPP) adquiridas en el hospital en pacientes críticos sigue siendo un reto clínico importante debido a su alto riesgo de comorbilidad asociada. Se evaluó la eficacia preventiva de los apósitos de silicona en los pacientes ingresados en las unidades de cuidados intensivos y en entornos no relacionados con dichas unidades. Métodos: Se realizó una búsqueda bibliográfica en 3bases de datos electrónicas (MEDLINE, EMBASE, Cochrane Central) desde el inicio hasta diciembre de 2021. Se incluyeron los estudios que evaluaban la eficacia de los apósitos de silicona en la incidencia de LPP en la zona sacra. Las evaluaciones se informaron como ratios de riesgo relativo (RR) con intervalos de confianza al 95% y el análisis se hizo mediante un modelo de efectos aleatorios. Resultados: De los 1.056 artículos recuperados en la búsqueda inicial, se incluyeron 11estudios en el análisis final. Los apósitos de silicona redujeron significativamente la incidencia de LPP en comparación con la atención habitual (RR: 0,30; IC 95%: 0,19-0,45; p<0,01). No se encontraron diferencias significativas entre los resultados de los estudios en contextos de cuidados intensivos (RR=0,25; IC 95%: 0,15-0,43; p<0,01) y en contextos de cuidados no intensivos (RR=0,38; IC 95%: 0,17-0,83; p=0,01) (interacción de p: 0,39). Los apósitos de silicona redujeron el riesgo de desarrollar LPP entre los pacientes que utilizaron el apósito de espuma de 5capas Border (Mepilex® Sacrum) (RR: 0,31; IC 95%: 0,20-0,48; p<0,01) y el apósito Allevyn Gentle Border® (RR: 0,10; IC 95%: 0,01-0,73; p=0,02) sin diferencias significativas tras el análisis de subgrupos (interacción de p: 0,27). Conclusión: El presente metaanálisis señala que los apósitos de silicona reducen de forma consistente la incidencia de las LPP en entornos de cuidados intensivos y no intensivos, independientemente del tipo de apósito utilizado.(AU)

Objective: Preventing hospital-acquired pressure injuries (PI) in critically ill patients remains a significant clinical challenge because of its associated high risk for comorbid conditions. We assessed the preventive effectiveness of silicone dressings among patients admitted in intensive care units and non-intensive care units settings. Methods:A literature search was conducted across 3electronic databases (MEDLINE, EMBASE, Cochrane Central) from inception through December 2021. Studies assessing the effectiveness of silicone dressing on the incidence of PI on the sacral area were included. evaluations were reported as risk ratios (RRs) with 95% confidence interval, and analysis was performed using a random-effects model. Results: Of the 1,056 articles retrieved from the initial search, 11studies were included in the final analysis. Silicone dressings significantly reduced the incidence of PI compared to usual care (RR: 0.30, 95%CI: 0.19-0.45, P<0.01). We found no significant difference between results of studies conducted in intensive care settings (RR=0.25, 95%CI: 0.15-0.43, P<0.01) and non-intensive care settings (RR=0.38, 95%CI: 0.17-0.83, P=0.01) (P-interaction: 0.39). Silicone dressings reduced the risk of developing PI among patients using five-layer foam Border dressing (Mepilex® Sacrum) (RR: 0.31, 95%CI: 0.20-0.48, P<0.01), and dressing Allevyn Gentle Border® (RR: 0.10, 95%CI: 0.01-0.73, P=0.02) with no significant difference upon subgroup analysis (P-interaction: 0.27). Conclusion: The present meta-analysis suggests that silicone dressings consistently reduce the incidence of PI in intensive as well as in non-intensive care settings, regardless of the type of dressing used.(AU)

Prophylactic use of silicone dressing to minimize pressure injuries: Systematic review and meta-analysis.

OBJECTIVE: Preventing hospital-acquired pressure injuries (PI) in critically ill patients remains a significant clinical challenge because of its associated high risk for comorbid conditions. We assessed the preventive effectiveness of silicone dressings among patients admitted in intensive care units and non-intensive care units settings. METHODS: A literature search was conducted across 3 electronic databases (MEDLINE, EMBASE, Cochrane Central) from inception through December 2021. Studies assessing the effectiveness of silicone dressing on the incidence of PI on the sacral area were included. Evaluations were reported as risk ratios (RRs) with 95% confidence interval, and analysis was performed using a random-effects model. RESULTS: Of the 1056 articles retrieved from the initial search, 11 studies were included in the final analysis. Silicone dressings significantly reduced the incidence of PI compared to usual care (RR: 0.30, 95% CI: 0.19-0.45, P<0.01). We found no significant difference between results of studies conducted in intensive care settings (RR=0.25, 95% CI: 0.15-0.43, P<0.01) and non-intensive care settings (RR=0.38, 95% CI: 0.17-0.83, P=0.01) (P-interaction: 0.39). Silicone dressings reduced the risk of developing PI among patients using five-layer foam Border dressing (Mepilex® Sacrum) (RR: 0.31, 95% CI: 0.20-0.48, P<0.01), and dressing Allevyn Gentle Border® (RR: 0.10, 95% CI: 0.01-0.73, P=0.02) with no significant difference upon subgroup analysis (P-interaction: 0.27). CONCLUSION: The present meta-analysis suggests that silicone dressings consistently reduce the incidence of PI in intensive as well as in non-intensive care settings, regardless of the type of dressing used.

A single centre experience of local perforator flaps in oncoplastic breast surgery; a cross-sectional study.

Background & objectives: Various oncoplastic techniques have emerged over the years to preserve breast cosmesis and symmetry without compromising the principles of tumor excision. One of the newer techniques for breast volume replacement to achieve symmetry and cosmesis is the use of fasciocutaneous pedicled chest wall perforator flaps or local perforator flaps (LPF). The objectives of this study were to document the details of the surgical procedure as well as patient-reported satisfaction and well-being following the procedure using a validated BREAST-Q tool among Pakistani women. Materials & methods: This cross-sectional study was conducted from March 2019 to February 2021 enrolling 25 female patients who underwent breast conservative surgery using LPF for breast tumors at The Aga Khan University Hospital, Karachi. Data related to the procedure was collected on a pre-designed proforma. Cosmetic outcomes and patient satisfaction were evaluated using 2 scales from BREAST-Q BCT domain version 2.0. The questionnaire was self-administered by the patients during their routine follow-up in the clinic. Data was analyzed using the Statistical Package for Social Sciences (SPSS) version 23. Mean (SD)/median (IQR) were computed for quantitative variables and frequency and percentages were calculated for qualitative variables. 2 sample t-test was applied. P-value ≤0.05 was considered significant. Results: 25 patients underwent LPF with a mean age of 47 ± 13.1 years. 8 LICAP, 7 AICAP, and 10 LTAP flaps were performed. Two postoperative complications of wound site erythema were encountered. 23 women were eligible for the BREAST-Q survey. Median (IQR) postoperative satisfaction with breasts and physical well-being chest (equivalent Rasch transformed score) was 100 (41) and 76 [18] respectively. We found high satisfaction with breasts and comparable physical well-being among Pakistani women after LPF surgeries. Conclusion: Local perforator flaps in oncoplastic breast-conserving surgery are a good option showing high satisfaction with breasts and physical well-being in Pakistani women.

Breast surgery super-specialization: Impact on advanced surgical training and research.

The earliest records of breast cancer (BC) date back to 3,000 - 2,500 B.C., ever since multiple curative options have been explored. First known wide margin excision was performed around 1st Century AD and a prototype of the modern-day BC surgery, Halsted radical mastectomy, was performed in the 20th Century. BC is the most common cancer in Pakistan accounting for up to 14.5% of the total cancer incidences. Accredited breast surgery fellowships were established in the UK and USA in 2002 and 2003, respectively. In Pakistan, the movement was delayed and the two-year College of Physicians and Surgeons Pakistan (CPSP) accredited breast surgery fellowship program started in 2019. The increasing annual incidence and changes in demands have led to an increased percentage of General Surgery graduates taking up specialty training. PubMed search from 1990 to 2021 showed a rising trend in the number of breast cancer publications from Pakistan; from almost no papers before 1990 to 615 between 2012 to 2021. This remarkable surge in BC-related research can be explained by the commencement of fellowship programs in breast surgery and related fields. An increase in specialist training will yield better results in the management of patients, improve clinical trials and help produce more meaningful publications from the country.

Breast cancer in a teenage girl with BRCA mutation: A case report from a low middle-income country.

INTRODUCTION: A staggering majority of pediatric breast masses are benign (mostly fibroadenoma) and so a biopsy is not readily performed as it can potentially lead to a future breast disfigurement. However, this should not be standard practice as this can lead to a delayed diagnosis, and hence, the treatment of pediatric breast cancer (BC); this was also seen in our patient's scenario. CASE HISTORY: Here, we report the case of the youngest known breast cancer patient in Pakistan, a 15-year-old girl. The right-sided breast lump which was diagnosed clinically as a fibroadenoma later turned out to be stage IIb pT3N0M0 metaplastic breast carcinoma with BRCA1 positivity and mutations in SMARCA4. Being young and unmarried, the patient and her family decided to opt for breast-conserving surgery with high-risk surveillance for breast and ovaries. DISCUSSION: We believe that prophylactic surgeries can be delayed with strict surveillance and thorough counseling. As pediatric BC is linked to a less favorable prognosis, every young patient diagnosed with breast cancer and their family should undergo genetic testing. BC management should be handled by specialists in the field and doctors should be trained for initial diagnostics and timely referral of patients. CONCLUSION: It is important to improve our understanding of genetic predisposition and testing in lower-middle-income countries. Considering the changing global trends, we suggest that the utilization of genetic services is direly needed to improve preventative care for at-risk individuals with breast and other cancers.