Is it Worthy Enough to Revascularize Chronically Occluded Coronaries?

Chronic total occlusions (CTOs) represent the "final frontier" of coronary interventions with the lowest procedural success rates and the most common reason for incomplete revascularization and referral to coronary artery bypass graft surgery (CABG). CTO lesions are not an infrequent finding during coronary angiography. They are often responsible for enhancing the complexity of the coronary disease burden thereby affecting the final interventional decision in the process. Notwithstanding the modest technical success of CTO-PCI, most of the earlier observational data demonstrated a clear survival benefit free of major cardiovascular events (MACE) in patients undergoing successful CTO revascularization. However, data from recent randomized trials fail to uphold the same survival advantage albeit, showing some trend toward improvement in left ventricular function, quality of life indicators and freedom from fatal ventricular arrythmia. Various guidance statements propose a well-defined role for CTO intervention in specific situations provided criterions for patient selection, appreciable inducible ischemia, myocardial viability and cost-risk-benefit analysis are met.

"Outcomes of COVID-19 infection in patients with hematological malignancies- A multicenter analysis from Pakistan".

PURPOSE: COVID-19 infection resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to spread across the globe in early 2020. Patients with hematologic malignancies are supposed to have an increased risk of mortality from coronavirus disease of 2019 (COVID-19) infection. From Pakistan, we report the analysis of the outcome and interaction between patient demographics and tumor subtype and COVID-19 infection and hematological malignancy. PATIENTS AND METHODS: This multicenter, retrospective study included adult patients with a history of histologically proven hematological malignancies who were tested positive for COVID-19 via PCR presented at the oncology department of 5 tertiary care hospitals in Pakistan from February to August 2020. A patient with any known hematological malignancy who was positive for COVID-19 on RT-PCR, was included in the study. Chi-square test and Cox-regression hazard regression model was applied considering p ≤ 0.05 significant. RESULTS: A total of 107 patients with hematological malignancies were diagnosed with COVID-19, out of which 82 (76.64%) were alive, and 25 (23.36%) were dead. The significant hematological malignancy was B-cell Lymphoma in dead 4 (16.00%) and alive group 21 (25.61%), respectively. The majority of the patients in both the dead and alive group were on active treatment for hematological malignancy while they came positive for COVID-19 [21 (84.00%) & 48 (58.54%) p 0.020]. All patients in the dead group were admitted to the hospital 25 (100.00%), and among these, 14 (56.00%) were admitted in ICU with a median 11 (6-16.5) number of days. Among those who had contact exposure, the hazard of survival or death in patients with hematological malignancies and COVID-19 positive was 2.18 (CI: 1.90-4.44) times and 3.10 (CI: 2.73-4.60) times in patients with travel history compared to no exposure history (p 0.001). CONCLUSION: Taken together, this data supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality resulting from COVID-19 infection.

Simultaneous radio-ulnar cannulation: shifting gears from 'feasibility' to 'applicability'.

Conventionally, routes of vascular access commonly include femoral and radial arteries with brachial, ulnar and subclavian arteries being rarely used for coronary interventions. Non-femoral arterial access is being increasingly preferred to minimise groin puncture site complications, prolonged immobilization and duration of hospital stay. However, radial artery cannulation is also fraught with fears of tortuosity, loops, vascular spasm, perforation, pseudoaneurysm formation, arm hematoma and arterial occlusion. In contemporary practice when most of the coronary procedures are being done via transradial access, encountering one of the above-mentioned hurdles often forces the operator to switchover to femoral access. Here, we explore the rationale, feasibility, operational logistics, clinical implications and future directions for using simultaneous radio-ulnar arterial access in the same extremity.

Comparative outcomes and toxicities for ruthenium-106 versus palladium-103 in the treatment of choroidal melanoma.

For the treatment of choroidal melanoma, palladium-103 (Pd) and ruthenium-106 (Ru) plaque brachytherapy shows reduced toxicity compared with the historical standard iodine-125. No report has directly compared the clinical outcomes between Pd and Ru, and the reasons for the selection of one over the other remain purely theoretical. Patients with choroidal melanoma with apical tumor height up to 5 mm were included. Patients from Emory University were treated with Pd between 1993 and 2012. Patients from Cleveland Clinic were treated with Ru between 2005 and 2010. Medical records were retrospectively reviewed. We compared post-treatment visual acuity (VA), toxicity, and oncologic outcomes. Pd patients (n=124) and Ru patients (n=42) had a median follow-up of 4.2 and 5.0 years, respectively. Radiation retinopathy-free survival was similar for both radioisotopes, but Ru had lower grades of retinopathy (P=0.006). Pd was associated with worse VA preservation (≥20/40) by year 3 (odds ratio: 3.8; 95% confidence interval: 1.01-14.31, P=0.048). Pd was associated with higher distant metastases-free survival (DMFS) in multivariate analysis (hazard ratio: 0.10; 95% confidence interval: 0.02-0.38; P<0.001). Ru had lower grades of radiation retinopathy and improved long-term VA preservation, but also inferior DMFS, compared with Pd. Because of the inherent limitations of a retrospective analysis, the significance of the inferior DMFS for Ru remains unclear, although the suggestion of a slight inferiority in terms of DMFS for Ru is consistent with the other limited literature. On the basis of this study, we believe that both radioisotopes remain appropriate for the treatment of small choroidal melanomas up to 5 mm in apical height.

Whole lung irradiation in stage IV Wilms tumor patients: Thyroid dosimetry and outcomes.

PURPOSE: To report the thyroid dosimetry and long-term follow-up of childhood cancer survivors treated with whole lung irradiation (WLI) for Wilms tumor. METHODS: Twenty-eight patients with pulmonary metastases from Wilms tumor who underwent WLI from 2000 TO 2012 at a single institution were reviewed. Radiation dose to the thyroid gland in each case was calculated. Postradiation thyroid function test (TFT) results and management of thyroid function abnormalities were extracted from the medical records. RESULTS: Median age at treatment was 5 years (range: 1-9 years), and median follow-up time was 74.1 months (7.2-198.4). The male/female ratio was 1:1.8. Complete dosimetry data were available for 22 of the 28 patients receiving WLI. Mean thyroid volume was 3.3 cc (range: 1-6.8). The average mean and median mean dose to the thyroid was 6.7 and 7.1 Gy, respectively (range: 1.3-11.7 Gy). Average max dose to the thyroid was 12.4 Gy (range: 7.8-20.3 Gy). Two patients were found to have a thyroid stimulating hormone (TSH) above the normal range, managed with levothyroxine. Another patient was found to have an isolated elevation of TSH which normalized without treatment. A fourth patient was found to have an enlarged thyroid on examination with no palpable nodules or abnormal TFTs. CONCLUSIONS: Average mean dose to the thyroid gland was 6.7 Gy for this population of stage IV Wilms tumor patients. There was a low rate of thyroid dysfunction, but limited follow-up. Attention to blocking the thyroid gland as much as possible when designing radiation fields can potentially mitigate the risks of long-term thyroid effects.

Visual acuity, oncologic, and toxicity outcomes with 103Pd vs. 125I plaque treatment for choroidal melanoma.

PURPOSE: To evaluate outcomes of choroidal melanoma patients treated with 125I or 103Pd plaque brachytherapy. METHODS AND MATERIALS: From 1993 to 2012, our institution treated 160 patients with 103Pd (56.1%) and 125 patients with 125I (43.9%) plaque brachytherapy. Tumor outcomes, visual acuity (VA), and toxicity were compared. Multivariate analyses (MVAs) and propensity score analysis were used to help address differences in baseline characteristics. RESULTS: Median followup was longer for 125I patients, 52.7 vs. 43.5 months (p < 0.01). At baseline, 103Pd patients had lower rates of VA worse than 20/200 (4.4% vs. 16%, p = 0.002), T3-T4 tumors (17.5% vs. 32.8%, p = 0.03), and transpupillary thermotherapy use (3.1% vs. 9.6%, p = 0.001). Both 103Pd and 125I provided >90% 3-year overall survival and >93% 5-year secondary enucleation-free survival. On MVA, radionuclide was not predictive for tumor outcomes. A higher percentage maintained vision better than 20/40 with 103Pd (63% vs. 35%, p = 0.007) at 3 years. MVA demonstrated 103Pd radionuclide (odds ratio [OR]: 2.12, p = 0.028) and tumor height ≤5 mm (OR: 2.78, p = 0.017) were associated with VA better than 20/40. Propensity score analysis matched 23 125I with 107 103Pd patients. 103Pd continued to predict better VA at 3 years (OR: 8.10, p = 0.014). On MVA for the development of VA worse than 20/200 or degree of vision loss, radionuclide was not significant. Lower rates of radiation retinopathy were seen with 103Pd than 125I (3 years: 47.3% vs. 63.9%, p = 0.016), with radionuclide significant in MVA. CONCLUSIONS: Both 125I and 103Pd achieve excellent tumor control. An increased probability of long-term VA better than 20/40 and reduced risk of radiation retinopathy is associated with 103Pd.

Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement.

PURPOSE: To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. METHODS AND MATERIALS: We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. RESULTS: At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gy with respect to local relapse-free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse-free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. CONCLUSIONS: Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.

BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy.

Melanoma is an aggressive malignancy that frequently spreads to the brain, resulting in rapid deterioration in both quality and quantity of life. Historically, treatment options for melanoma brain metastases (MBM) have predominantly consisted of surgery and radiotherapy. While these options can help provide local control, the majority of patients still develop intracranial progression. Indeed, novel therapeutic options, including molecularly targeted agents and immunotherapy, have improved outcomes and are now changing the role of radiotherapy. Up to 50% of melanomas contain an activating BRAF mutation, resulting in hyperactive cellular proliferation and survival. Drugs that target BRAF have been introduced for the treatment of metastatic melanoma and offer hope in improving disease outcomes; however, many of these trials either excluded or had a limited amount of patients with MBM. Recent studies have revealed that melanoma cell lines become more radiosensitive following BRAF inhibition, thus providing a potential synergistic mechanism when combining BRAF inhibitor (BRAFi) and radiotherapy. However, neurotoxicity concerns also exist with this combination. This article reviews the efficacy and limitations of BRAFi therapy for MBM, describes current evidence for combining BRAFis with radiation, discusses the rationale and evidence for combination modalities, and highlights emerging clinical trials specifically investigating this combination in MBM.

Anthropometrical Measurements of Healthy Newborn Babies in Karachi, and the Factors Affecting these Parameters.

The present cross-sectional study was undertaken with the aim of establishing norms for birth weight, crown heel length, and head circumference of the newborns in the population of Karachi. It was conducted in four public and private hospitals of Karachi, covering middle to low-income areas during a period of 2 years. There were 404 mothers and their babies included in this study that fulfilled the inclusion and exclusion criteria of the study. Anthropometric measurements including birth weight, crown heel length, and occipitofrontal circumference (OFC) were recorded within 24 hours of birth. Maternal age, parity, gestational age, newborn gender, Apgar score, and delivery mode were also recorded. The data entry and analysis was done on Statistical Packages of Social Sciences (SPSS) version 21.The mean birth weights of the babies were found to be 3.03 ±0.39 kg, crown heel length were 49.2 ±2.4 cm, and OFC were 34 ±1.5 cm. A statistically significant difference was found between the gender of the babies (male=3.07 ±0.4 kg versus female=3.0 ±0.4 kg) for birth weight (p=0.02). This study provides the mean values of anthropometric measurements of the newborns in low-income areas of Karachi.

The influence of postoperative lymph node radiation therapy on overall survival of patients with stage III melanoma, a National Cancer Database analysis.

Recently, TROG 02.01 results showed that in stage III melanoma patients with nodal metastasis, adjuvant radiation to lymph node basin after nodal dissection improves lymph node field relapse without an overall survival (OS) benefit. However, this trial was neither designed nor powered to detect an OS difference. In the present study, we analyzed patients in the National Cancer Database (NCDB) with stage III melanoma with pathologically involved nodes and compared survival outcomes of adjuvant radiation and no-radiation cohorts. Inclusion criteria were as follows: age at least 18 years; diagnosed 2003-2011; surgery to regional lymph nodes; pathologically involved lymph nodes; and American Joint Committee on Cancer stage (IIIA-C). We used propensity score matching analysis to compare the OS of patients with similar baseline demographic, clinical, and pathologic characteristics who received adjuvant radiation and no adjuvant radiation. Overall, 912 patients were analyzed with an average age at diagnosis of 54.4 years and a median follow-up time of 5.5 years. In this cohort, the 5-year OS was 69.0, 51.1, and 30.6% for stage IIIA, IIIB, and IIIC, respectively. On propensity score-adjusted multivariate analysis, we found that adjuvant radiation had no statistically significant impact on OS (hazard ratio: 1.09, 95% confidence interval: 0.75-1.58, P=0.640). Furthermore, age older than 60 years, number of nodes, increasing pathologic stage, and absence of immunotherapy correlated with worse OS. In this NCDB analysis, we found that the adjuvant radiotherapy for node-positive, stage III melanoma patients did not improve OS. This is consistent with TROG 02.01; however, there may be patient selection bias not accounted for by the NCDB.

Validation of cutaneous lymphoma international prognostic index (CLIPI) for mycosis fungoides and Sézary syndrome.

We sought to evaluate the performance of the cutaneous lymphoma international prognostic index (CLIPI), a prognostic index for mycosis fungoides (MF), and Sézary syndrome (SS), in our cohort of patients seen at Emory University between 1998 and 2013. Additionally, we examined the prognostic significance of lactate dehydrogenase (LDH), B0a/b, and CD30 status. A total of 390 patients were included in analysis: 78.2% early stage (IA-IIA), 7.2% with SS, 53.1% male, mean age 53.5 years. CLIPI stratified patients into low, intermediate, and high-risk groups for overall survival (OS) and progression free survival (PFS) for early stage patients (p < 0.0001), but was not significant for late stage patients. On multivariable analysis for early stage patients, age >60, plaques, folliculotropic disease was significant for OS and age >60, plaques, N1/Nx was significant for PFS. In the overall cohort, CD30+, elevated LDH, and B0b were significant for worse OS and PFS.

CD30+ Cutaneous T Cell Lymphoma: Response to Rotational Total Skin Electron Irradiation.

INTRODUCTION: Rotational total skin electron irradiation (RTSEI) is an effective therapy for cutaneous T cell lymphoma (CTCL). CD30 expression has been identified as a prognostic factor in CTCL. Therefore, we investigated CD30 status, treatment response, and survival in our cohort of patients with CTCL treated with RTSEI. METHODS: Patients with CTCL treated with RTSEI (≥30 Gy) between 2000 and 2013 at our institution were identified, and clinical and pathologic data were retrospectively reviewed. Primary outcomes were complete clinical response (CCR; >90% reduction of skin disease burden), relapse-free survival (RFS), and overall survival (OS). RESULTS: Sixty-eight patients with CTCL treated with RTSEI were identified. Median age at diagnosis was 51 years with median follow-up of 61 months. Median OS was 76 months and median RFS was 11 months. Thirteen patients (19%) had CD30+ lymphocytes on initial pathology. In the CD30+ cohort, there were no T2, eight T3, and five T4 cases. In comparison, in the CD30- cohort, there were 18 T2, 29 T3, and 8 T4 cases (P = 0.01). Six weeks post-RTSEI, CCR was 85% in CD30+ and 81% in CD30- cases (P = 1). Six months post-RTSEI, CCR was 23% in CD30+ and 50% in CD30- cases (P = 0.083). CONCLUSION: RTSEI resulted in excellent CCR at 6 weeks in our cohort of patients with CTCL, with a median RFS of 11 months. We found CD30+ patients presented with significantly higher T stage at time of RTSEI and trended towards decreased CCR at 6 months post-RTSEI compared with the CD30- group.

Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) as a prognostic marker for local control in T1-2 N0 breast cancer treated with breast-conserving surgery and radiation therapy (BCS + RT).

Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) expression, involved in the regulation of translation, has been implicated to mediate resistance to chemotherapy and radiation in cancer cells in vitro. The purpose of this study was to evaluate the prognostic significance of IFIT1 protein expression in patients with breast cancer treated with Breast-Conserving Surgery and Radiation Therapy (BCS + RT). A tissue microarray was constructed with specimens from 282 women with node-negative, early-stage (I/II) breast cancer who were treated with BCS + RT. Immunohistochemistry was used to stain for the IFIT1 protein. Cytoplasmic IFIT1 protein expression levels were correlated with clinicopathologic factors, local relapse-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). IFIT1 positivity was found in 123 (49%) of cases. The median follow-up time was 7.3 years. Eighty percent of the patients had T1 disease, 88% were human epidermal growth factor receptor 2 (HER2) negative, and 20% had triple-negative breast cancer (TNBC). IFIT1 positivity was associated with estrogen receptor negative status (p = 0.002), progesterone receptor negative status (p = 0.02), TNBC (p = 0.01), and HER2-positive status (p = 0.006). In univariate and multivariate analysis, IFIT1 positivity was associated with improved LRFS (p = 0.055 and p = 0.04, respectively). Using a log-rank test, IFIT1 positivity was found to be associated with improved LRFS (94% versus 85%, p = 0.046) but not DFS or OS at 10 years. On subset analysis of the TNBC patients, IFIT1 positivity was found to correlate with improved LRFS (100% versus 53%, p = 0.004) and DFS in (87% versus 49%, p = 0.048) at 10 years. Elevated IFIT1 protein expression is associated with improved LRFS. In addition, our data suggest that IFIT1 expression may help risk stratify patients with TNBC who may benefit from more aggressive therapy. As there is limited data on IFIT1 in breast cancer, additional work is needed to ascertain its significance.

Correlation of routine haematological parameters between normal maternal blood and the cord blood of healthy newborns in selected hospitals of Karachi.

OBJECTIVE: To determine any significant correlation between the routine haematological parameters of maternal blood and umbilical cord blood of their respective newborns. STUDY DESIGN: Cross sectional study. PLACE AND DURATION OF STUDY: The study was conducted at four public and private hospitals of Karachi including Sindh Government Qatar Hospital, Sindh Government Hospital, Liaquatabad, Ziauddin University Hospital and Chinniot Maternity and Child Hospital, respectively from July 2006 to April 2008. METHODOLOGY: Three milliliters venous blood was collected in EDTA containing tube for complete blood count of mothers before delivery. Five milliliters cord blood was collected from the umbilical cord of the babies immediately after delivery by clamping and cutting the babies' end of the cord. For haematological parameters a standard coultergram was done including haemoglobin, RBCs count, haematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cell count, differential leukocyte count and platelet count. Pearson's correlation co-efficient was used to determine an association between the maternal and cord blood parameters. RESULTS: A total of 404 maternal and umbilical cord blood samples were analyzed. All the blood parameters including haemoglobin, RBCs count, HCT, MCV, MCH, white blood cell count, differential leukocyte count and platelet count were found to be high in cord blood as compared to the maternal blood, but they showed a very weak to negligible correlation. Mean Corpuscular Haemoglobin Concentration (MCHC), showed a moderate correlation. CONCLUSION: Routine haematological parameters of newborns are independent of maternal routine haematological parameters.

Evaluation of acute locoregional toxicity in patients with breast cancer treated with adjuvant radiotherapy in combination with pazopanib.

Purpose. The purpose of this study was to analyze acute locoregional toxicity in patients with breast cancer receiving concurrent pazopanib and RT. Materials and Methods. Patients with breast cancer who received pazopanib in combination with radiation were identified and matched (2 : 1) to patients with breast cancer who did not receive pazopanib by use of chemotherapy, radiation field design, and radiation dose. Toxicity was scored by the Common Terminology Criteria for Adverse Events and statistical analysis was performed. Results. Grade 1 or 2 radiation dermatitis was seen in 100% and 84% of pazopanib and RT patients and matched controls respectively (P = NS). None of the patients receiving pazopanib and RT experienced ≥ grade 3 toxicity within the irradiated volume; three (16%) matched patients experienced a grade 3 skin reaction (P = 0.05). Interestingly, grade 1 or 2 hyperpigmentation was seen in 17% of pazopanib and RT patients and 60% of matched controls (P = 0.005). Conclusion. The addition of concurrent pazopanib and RT when treating the intact breast, chest wall, and associated nodal regions in breast cancer seems to be safe and well tolerated.

Haematological reference values for full-term, healthy, newborns of Karachi, Pakistan.

OBJECTIVE: To establish reference haematological values (complete blood count) in healthy full-term newborns of Karachi. METHODS: This is a cross sectional study design based on cord blood sample of 404 newborns and their mothers recruited from Sindh Government Qatar Hospital, Ziauddin University Hospital gole market campus, Sindh Government hospital, Liaquatabad and Chinniot maternity and child hospital. Karachi from July 2006 to April 2008. Both mother's and the new born baby's blood was collected in EDTA containing tubes and analyzed for different haematological parameters. The data entry and analysis was done on computer package SPSS (Statistical Packages of Social Sciences) version 12.0. The results were given in the text as mean, standard deviation and 95% confidence intervals of haematological values (complete blood count). RESULTS: The mean haemoglobin was found to be (14.99 +/- 1.47 gm), which is lower than the standard value described in literature. However the total WBCs count and platelet count were found to be (13.61 +/- 4.23) and (256. 25 +/- 76.54) respectively, which were similar to the other studies. CONCLUSION: Our values provide reference range for haematological values in healthy newborns of Karachi, for clinical use by our physicians.