Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency.

Background: Patients with predominantly antibody deficiency (PAD) have lower anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody levels after initial 2-dose SARS-CoV-2 vaccination than healthy controls do; however, the anti-spike antibody responses and neutralization function in patients with PAD following subsequent immunizations remain understudied. Objective: We sought to characterize anti-spike antibody responses in adults with PAD over the course of 5 SARS-CoV-2 vaccine doses and identify diagnostic and immunophenotypic risk factors for low antibody response. Methods: We evaluated anti-spike antibody levels in 117 adult patients with PAD and 192 adult healthy controls following a maximum of 5 SARS-CoV-2 immunizations. We assessed neutralization of the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant and analyzed infection outcomes. Results: The patients with PAD had significantly lower mean anti-spike antibody levels after 3 SARS-CoV-2 vaccine doses than the healthy controls did (1,439.1 vs 21,890.4 U/mL [P < .0001]). Adults with secondary PAD, severe primary PAD, and high-risk immunophenotypes had lower mean anti-spike antibody levels following vaccine doses 2, 3, and/or 4 but not following vaccine dose 5. Compared with patients with mild and moderate PAD, patients with severe PAD had a higher rate of increase in anti-spike antibody levels over 5 immunizations. A strong positive correlation was observed between anti-spike antibody levels and neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Most infections were managed on an outpatient basis. Conclusions: In all of the patients with PAD, anti-spike antibody levels increased with successive SARS-CoV-2 immunizations and were correlated with neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Secondary PAD, severe primary PAD, and high-risk immunophenotypes were correlated with lower mean anti-spike antibody levels following vaccine doses 2 through 4. Patients with severe PAD had the highest rate of increase in anti-spike antibody levels over 5 immunizations. These data suggest a clinical benefit to sequential SARS-CoV-2 immunizations, particularly among high-risk patients with PAD.

Evaluation of Axilla With Sentinel Lymph Node Biopsy (Using Methylene-Blue) and Reverse Axillary Mapping (Using Fluorescein) to Validate Optimum and Safe Axillary Dissection in Breast Cancer.

Introduction Sentinel lymph node biopsy (SLNB) has replaced routine axillary lymph node dissection (ALND) in node-negative axillae. In cases where the axilla needs to be dissected, one must dissect below the uppermost intercostobrachial nerve (ICBN) to avoid damaging arm lymphatics. Methods One milliliter of methylene blue dye was injected around the areola. Fluorescein dye (1 ml) was injected into the upper arm. After SLNB and ALND, the axilla was visualized under blue light. The location of fluorescent lymphatics was mapped with respect to the uppermost ICBN. Results The identification rate of sentinel lymph nodes and arm lymphatics was 100%. Arm lymphatics were above ICBN in 86.7%. The false negative rate of SLNB was 13%, with sensitivity and specificity of 87% and 100%, respectively. Conclusions SLNB using the single-dye technique has results comparable to dual agent studies that utilize blue dye and radioactive colloid. The uppermost ICBN could define the superior limit of axillary dissection.

Response to SARS-CoV-2 initial series and additional dose vaccine in pediatric patients with predominantly antibody deficiency.

Data regarding response to SARS-CoV-2 immunization in pediatric patients with predominantly antibody deficiency (PAD) is limited. We evaluated SARS-CoV-2 immunization response by anti-SARS-CoV-2-spike antibody level in 15 pediatric PAD patients. These data were compared to a published cohort of adult PAD patients (n=62) previously analyzed following SARS-CoV-2 immunization at our single center institution. We evaluated demographics, clinical characteristics, immunophenotype, infection history, and past medication use by chart review. Following a two-dose monovalent initial series SARS-CoV-2 immunization, mean anti-SARS-CoV-2-spike antibody levels were significantly higher in pediatric PAD patients compared to adult PAD patients (2,890.7 vs. 140.1 U/mL; p<0.0001). Pediatric PAD patients with low class-switched memory B-cells, defined as <2% of total CD19+ B-cells, had significantly lower mean anti-SARS-CoV-2-spike antibody levels than those without (p=0.02). Following a third-dose monovalent SARS-CoV-2 immunization, the mean anti-SARS-CoV-2-spike antibody levels in pediatric PAD patients significantly increased (2,890.7 to 18,267.2 U/mL; p<0.0001). These data support Centers for Disease Control guidelines regarding three-part SARS-CoV-2 vaccine series, including in the pediatric PAD patient demographic.

Do Tobacco Treatment Trials Address Disparities in Smoking Outcomes Among Black and Hispanic Cancer Patients? A Systematic Review of Smoking Cessation Interventions for Black and Hispanic Patients Diagnosed with Cancer.

OBJECTIVE: To characterize the representation of Black and Hispanic cancer patients in tobacco treatment trials, and to offer recommendations for future research. METHODS: We conducted two systematic searches of the literature (2018, 2021) using 5 databases (MEDLINE via EBSCO, Pubmed, PsycInfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (EMBASE)) to examine the prevalence of tobacco trials that included Black or Hispanic cancer patients. Two coders independently screened all articles at title, abstract, and full-text to identify eligible trials. Information about the proportion of Black and Hispanic patients included, trial design features, and whether the authors analyzed outcomes for Black and Hispanic patients were documented. RESULTS: Of 4682 identified studies, only 10 published trials included and reported on the rates of Black or Hispanic cancer patients enrolled in their tobacco trial. The proportion of enrolled Black cancer patients ranged from 2 to 55.6%. Only our studies documented enrollment rates for Hispanics, and rates were less than 6%. None of the studies offered strategies to promote or the accrual of Black or Hispanic patients. DISCUSSION: There remains a large gap in the literature regarding the reach and efficacy of tobacco treatment for Black and Hispanic cancer patients. Black and Hispanic cancer patients remain largely under-represented in tobacco cessation trials, limiting the applicability of existing, evidence-based treatments. To optimize intervention generalizability, future studies should emphasize the targeted recruitment and engagement of these patients in tobacco trials.

Respiratory infections predominate after day 100 following B-cell maturation antigen-directed CAR T-cell therapy.

Infections are an important complication after B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy and risks may differ between the early and late periods. We evaluated infections in 99 adults who received a first BCMA-directed CAR T-cell therapy (commercial and investigational autologous BCMA CAR T-cell products at the recommended phase 2 dose) for relapsed/refractory multiple myeloma between November 2016 and May 2022. Infections were recorded until day 365, if patients experienced symptoms with a microbiologic diagnosis, or for symptomatic site-specific infections treated with antimicrobials. One-year cumulative incidence functions were calculated based on time to first respiratory infection using dates of infection-free death and receipt of additional antineoplastic therapies as competing risks. Secondary analysis evaluated risk factors for late respiratory infections using univariate and multivariable Cox regression models. Thirty-seven patients (37%) experienced 64 infectious events over the first year after BCMA-directed CAR T-cell therapy, with 42 early infectious events (days, 0-100), and 22 late infectious events (days, 101-365). Respiratory infections were the most common site-specific infection and the relative proportion of respiratory infections increased in the late period (31% of early events vs 77% of late events). On multivariable analysis, hypogammaglobulinemia (hazard ratio [HR], 6.06; P = .044) and diagnosis of an early respiratory viral infection (HR, 2.95; P = .048) were independent risk factors for late respiratory infection. Respiratory infections predominate after BCMA CAR T-cell therapy, particularly after day 100. Hypogammaglobulinemia and diagnosis of an early respiratory infection are risk factors for late respiratory infections that may be used to guide targeted preventive strategies.

Immunoexpression of claudin-4 and correlation with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-neu in breast cancer.

Background: Claudins are important transmembrane proteins in tight junction. The role of intercellular tight junctions in breast epithelial cells is traditionally thought to be in maintaining polarity and barrier function. However, claudin-4, a tight junction protein, is overexpressed in breast tumor cells compared to normal epithelial cells, which generally corresponds to loss in polarity and can provide valuable information about biology of the tumor. A prospective clinical study was conducted to assess the expression claudin-4 in patients with breast cancer and its correlation with hormone receptors - estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)-neu. Materials and Methods: The study included 102 biopsy-proven breast carcinoma patients. The biopsy samples were evaluated immunohistochemistry for expression of ER, PR, HER2-neu, and claudin-4. The expression of claudin-4 was correlated with ER, PR, and HER2-neu. Results: In the study, we found that out of 26 cases of high claudin-4, 25 cases (96.15%) were ER negative and P < 0.001, which was significant. Similar results were found with PR-negative cases. Whereas, out of 76 cases with low claudin-4, 54 cases (71.05%) were HER2-neu negative and P = 0.022, which was significant. Conclusions: Claqudin-4 expression has a negative correlation with ER and PR and has a positive correlation with HER2-neu. Hence, it can be effectively utilized as a prognostic and therapeutic marker in breast cancer in the future.

A pilot multicentre cluster randomised trial to compare the effect of trauma life support training programmes on patient and provider outcomes.

INTRODUCTION: Trauma accounts for nearly 10% of the global burden of disease. Several trauma life support programmes aim to improve trauma outcomes. There is no evidence from controlled trials to show the effect of these programmes on patient outcomes. We describe the protocol of a pilot study that aims to assess the feasibility of conducting a cluster randomised controlled trial comparing advanced trauma life support (ATLS) and primary trauma care (PTC) with standard care. METHODS AND ANALYSIS: We will pilot a pragmatic three-armed parallel, cluster randomised controlled trial in India, where neither of these programmes are routinely taught. We will recruit tertiary hospitals and include trauma patients and residents managing these patients. Two hospitals will be randomised to ATLS, two to PTC and two to standard care. The primary outcome will be all-cause mortality at 30 days from the time of arrival to the emergency department. Our secondary outcomes will include patient, provider and process measures. All outcomes except time-to-event outcomes will be measured both as final values as well as change from baseline. We will compare outcomes in three combinations of trial arms: ATLS versus PTC, ATLS versus standard care and PTC versus standard care using absolute and relative differences along with associated CIs. We will conduct subgroup analyses across the clinical subgroups men, women, blunt multisystem trauma, penetrating trauma, shock, severe traumatic brain injury and elderly. In parallel to the pilot study, we will conduct community consultations to inform the planning of the full-scale trial. ETHICS AND DISSEMINATION: We will apply for ethics approvals to the local institutional review board in each hospital. The protocol will be published to Clinical Trials Registry-India and ClinicalTrials.gov. The results will be published and the anonymised data and code for analysis will be released publicly.

Breast gangrene: Tale of two similar cases with two different outcomes.

Breast gangrene is rare in surgical practice. Its aetiology is variable and multifactorial. Debridement and appropriate antibiotic treatment are the mainstay of management. Two such cases presented one early and the other desperately late. We report these two cases to emphasise the potential fatality of this condition.

Intraoperative Specimen Ultrasonography: Is It a Reliable Tool for Margin Assessment Following Breast Conservation Surgery for Breast Carcinoma?

BACKGROUND: Assessment of margins after breast conservation surgery is an essential part of management in breast cancer and is important in prognostication of the patient. Various intra-operative techniques like frozen section and imprint cytology are in use to ensure negative margins but have their limitations in the fact that 3D evaluation is not feasible. These lead to false negatives and also are operator dependent. In order to obviate these shortcomings, various centers are using specimen imaging (specimen mammogram and ultrasonography). AIMS AND OBJECTIVES: 1) To evaluate the accuracy of specimen ultrasonography in assessing the margins following breast conservation surgery (BCS). 2) To compare the accuracy of intra-operative specimen ultra-sonography with frozen section for assessment of excision margins following BCS. MATERIALS AND METHODS: Sixty-two biopsy-proven patients with breast cancer who underwent BCS were included in this prospective study at a tertiary cancer care center. The oriented specimens were evaluated by specimen ultrasonography and later by frozen section. The final histopathology served as the gold standard. RESULTS: Specimen ultrasonography is found to be superior to frozen section in providing detailed assessment of margins in patients undergoing breast conservation. Specimen ultrasonography was also able to detect additional lesions which might be missed on frozen section, especially the in-situ carcinoma.

A comparative analysis of axillary nodal burden in ultrasound/biopsy positive axilla vs ultrasound negative sentinel lymph node biopsy positive axilla.

BACKGROUND: Axillary Ultrasound (AUS) is now performed as a protocol in every newly diagnosed breast cancer in most European countries. It is an inexpensive and sensitive tool in hands of a trained operator. All AUS negative patients undergo Sentinel Lymph Node Biopsy (SLNB), while AUS positive patients bypass SLNB and undergo axillary nodal clearance (ANC) as a standard protocol. We wish to analyse these two groups to see if ANC can be foregone in these patients. AIMS AND OBJECTIVES: To compare and analyse the axillary disease burden in early breast cancer patients, with positive axilla, detected by AUS+ Biopsy versus those patients with normal axillary ultrasound or negative axillary biopsy that underwent ANC due to positive SLNB. MATERIAL AND METHODS: A retrospective review of all patients who underwent axillary lymph node clearance following histologically confirmed positive ultrasound (US) axilla (year 2009-2014) was performed and was compared with data collected for patients with USG negative but SLNB (OSNA- One Step Nucleic Acid Amplification) positive axilla. RESULTS: Axillary clearances performed for positive US axilla yielded significantly more positive lymph nodes than SLNB/OSNA positive axilla (p = 0.00496). These patients also had larger primary tumours (median 33 mm versus 21 mm, p = 0.01242) of a higher grade. Almost half of the patients in AUS positive group (49%) had high axillary nodal burden (>4 LNs). This is in great contrast with AUS negative, SLNB/OSNA positive group where 82.7% of patients had <4 positive nodes with more than half patients (51.7%) having no further positive nodes in their final histopathology specimen. CONCLUSIONS: ANC should be a standard protocol in AUS positive patients as they invariably have high axillary disease burden while ANC can be omitted in case of select AUS negative and SLNB patients. However, further studies with more subjects may be require to substantiate the findings.

Isolated metachronous breast metastasis from renal cell carcinoma: A report of two cases.

Metastases to the breast are very uncommon as compared to primary tumours. Breast is an unusual site for metastasis from renal cell carcinoma. Only occasional cases are reported in the literature. These metastases must be clearly diagnosed as the treatment of primary breast cancer and metastases differs markedly. Treatment of isolated metastases from renal cell carcinoma is usually surgical resection. We report two cases of isolated metachronous metastases to breast from renal cell carcinoma.

Neurofibromatosis with male breast cancer--risk factor or co-incidence? Report of two rare cases.

The genetic link between neurofibromatosis and breast cancer has recently intrigued the researchers and breast practitioners alike. While the association is well established in females, the same cannot be said for the male breast cancer due to paucity of cases. With only two cases reported previously, our knowledge is sparse. We hereby report two cases of male breast cancer with neurofibromatosis.

Evaluation and Validation of Neo-Adjuvant Response Index (NRI) and It's Correlation with Various Predictive Biomarkers and RECIST in Locally Advanced Breast Cancer.

BACKGROUND: Response evaluation following neo-adjuvant chemotherapy in breast cancer is usually done without taking in to account the axillary response and the available tools like 'response evaluation criteria in solid tumors' (RECIST) have this limitation. These criteria rely solely on the response observed in the primary tumour. Neoadjuvant response index is one such attempt to have a comprehensive assessment of response both in the primary tumour and the axilla. METHODS: 30 cases of locally advanced breast cancer (LABC) were assessed for response using 'Neo-adjuvant Response Index'. The index always gives score between '0' (no response or progressive disease) and '1' (pathological complete response i.e. no invasive tumor in breast as well as axilla). This index includes axillary response as well and provides a spectrum of response rather than dividing patients into simply responders and non-responders . RESULTS: Mean reading of index was found to be 0.2925 in this study. Three patients achieved an index of 1. This index correlates significantly with the existing scales for assessing response. Hormone negative tumors were found to be more chemo responsive with higher rates of pathological complete response (pCR) while ER/PR + Her2- tumors showed a very poor response to NACT. CONCLUSIONS: Based on the observations of the present study it may be submitted that Neoadjuvant Response Index (NRI) is a reliable and simple tool that can serve as a comprehensive and accurate method of assessing response to neo-adjuvant chemotherapy as it takes in to consideration both the tumor and axillary response unlike the existing RECIST, binary system (responders are those with greater than 50 % reduction), RCB method and the available biomarkers. This study being first of it's kind in Indian population, in spite of it's limitations, could prove to be a launching ground for further reasearch and contribute substantially to the evidence base.

Breast tuberculosis at a tertiary care centre: a retrospective analysis of 22 cases.

BACKGROUND: Breast tuberculosis is an uncommon condition with varied presentations. The incidence is low even in the endemic zone. The disease is common in young female and lactating females. AIM AND OBJECTIVES: To study the clinical spectrum of breast tuberculosis patients, their diagnosis and management at a tertiary care centre. MATERIAL AND METHODS: 22 diagnosed cases of breast tuberculosis presented over last seven years were studied retrospectively at a tertiary care centre. OBSERVATIONS AND RESULTS: Majority of patients in our study belongs to 20-40 yrs. Disease is common with lactation. Most common presentation is in form of breast lump, commonly in UOQ. Once diagnosed is confirmed through different investigations, patients were put on ATT. Surgery is limited for resistant or residual mass in breast or axilla. CONCLUSION: Awareness about this disease entity is of prime importance especially in endemic areas for the prompt diagnosis and treatment.

Patient and provider delays in breast cancer patients attending a tertiary care centre: a prospective study.

OBJECTIVES: To find out factors that are responsible for the patient or provider delays in the diagnosis of breast cancer in India. DESIGN: This prospective study was designed to be conducted over a period of two years including a cohort of 100 patients with locally advanced breast cancer. The delays were assessed using questionnaires prepared according to the Indian scenario. SETTING: A prospective study in an Indian setting. PARTICIPANTS: One hundred patients with locally advanced breast cancer receiving neoadjuvant chemotherapy were included after providing informed consent and receiving ethical committee clearance. MAIN OUTCOME MEASURES: The most common factor responsible for delays in diagnosis was observed to be the health providers, although illiteracy and lack of adequate healthcare services also contributed significantly. Unregistered medical practitioners or quacks contributed significantly to the delays in reporting and diagnosis of the disease. RESULTS: One hundred patients of locally advanced breast cancer were evaluated using standardized questionnaires to assess the delays in diagnosis. Provider delays were found to be significant (the unregistered doctors or quacks being a significant cause of delays).The average time lapse before diagnosis for rural patients was higher (67.5 days) compared to urban patients (53.7 days). The literacy levels of the patients also had a significant impact on the delays at diagnosis. The delay in illiterates was 60.6 days compared to 49.5 days for literates. CONCLUSIONS: The most common factor responsible for delays in reporting and diagnosis was observed to be at the end of the health providers, although illiteracy and lack of adequate healthcare services also contributed significantly. Unregistered medical practitioners or quacks contributed significantly to the delays in reporting and diagnosis of the disease.

The correlation of anxiety and depression levels with response to neoadjuvant chemotherapy in patients with breast cancer.

BACKGROUND: The aim was to evaluate and correlate anxiety and depression levels with response to neoadjuvant chemotherapy in patients with breast cancer. The study also assessed the effects of family support on distress levels. DESIGN: It was a prospective study in a cohort of 84 patients with locally advanced breast cancer. These assessments were done using the Hospital Anxiety and Depression Scale (HADS). SETTING: A prospective study in a developing world setting. PARTICIPANTS: Eighty-four patients with locally advanced breast cancer receiving neoadjuvant chemotherapy were included after taking an informed consent and ethical committee clearance. MAIN OUTCOME MEASURES: A significant correlation was observed between response to neoadjuvant chemotherapy and depression levels in breast cancer patients. Joint family and literacy levels also had an impact on the levels of depression observed. RESULTS: A total of 84 patients receiving neoadjuvant chemotherapy for breast cancer were evaluated using HADS. The effect of family support, literacy levels and employment on the psychological status of these patients were also assessed. CONCLUSIONS: The response to neoadjuvant chemotherapy had a direct correlation with the levels of depression, the distress levels being lower in responders. This was found to be the most important variable determining the psychological status of the patients. It was also observed that Indian patients in comparison to their Western counterparts react differently to cancer-related stress.

Sentinel lymph node biopsy using dye alone method is reliable and accurate even after neo-adjuvant chemotherapy in locally advanced breast cancer--a prospective study.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is now considered a standard of care in early breast cancers with N0 axillae; however, its role in locally advanced breast cancer (LABC) after neo-adjuvant chemotherapy (NACT) is still being debated. The present study assessed the feasibility, efficacy and accuracy of sentinel lymph node biopsy (SLNB) using "dye alone" (methylene blue) method in patients with LABC following NACT. MATERIALS AND METHODS: Thirty, biopsy proven cases of LABC that had received three cycles of neo-adjuvant chemotherapy (cyclophosphamide, adriamycin, 5-fluorouracil) were subjected to SLNB (using methylene blue dye) followed by complete axillary lymph node dissection (levels I-III). The sentinel node(s) was/were and the axilla were individually assessed histologically. The SLN accuracy parameters were calculated employing standard definitions. The SLN identification rate in the present study was 100%. The sensitivity of SLNB was 86.6% while the accuracy was 93.3%, which were comparable with other studies done using dual lymphatic mapping method. The SLN was found at level I in all cases and no untoward reaction to methylene blue dye was observed. CONCLUSIONS: This study confirms that SLNB using methylene blue dye as a sole mapping agent is reasonably safe and almost as accurate as dual agent mapping method. It is likely that in the near future, SLNB may become the standard of care and provide a less morbid alternative to routine axillary lymph node dissection even in patients with LABC that have received NACT.

Vulval elephantiasis as a result of tubercular lymphadenitis: two case reports and a review of the literature.

INTRODUCTION: Elephantiasis as a result of chronic lymphedema is characterized by gross enlargement of the arms, legs or genitalia, and occurs due to a variety of obstructive diseases of the lymphatic system. Genital elephantiasis usually follows common filariasis and lymphogranuloma venereum. It may follow granuloma inguinale, carcinomas, lymph node dissection or irradiation and tuberculosis but this happens rarely. Vulval elephantiasis as a consequence of extensive lymph node destruction by tuberculosis is very rare. We present two very unusual cases of vulval elephantiasis due to tuberculous destruction of the inguinal lymph nodes. CASE PRESENTATION: Two Indian women - one aged 40 years and the other aged 27 years, with progressively increasing vulval swellings over a period of five and four years respectively - presented to our hospital. In both cases, there was a significant history on presentation. Both women had previously taken a complete course of anti-tubercular treatment for generalized lymphadenopathy. The vulval swellings were extremely large: in the first case report, measuring 35 × 25 cm on the right side and 45 × 30 cm on the left side, weighing 20 lb and 16 lb respectively. Both cases were managed by surgical excision with reconstruction and the outcome was positive. Satisfactory results have been maintained during a follow-up period of six years in both cases. CONCLUSIONS: Elephantiasis of the female genitalia is unusual and it has rarely been reported following tuberculosis. We report two cases of vulval elephantiasis as a consequence of extensive lymph node destruction by tuberculosis, in order to highlight this very rare clinical scenario.