Mihir M. Kamdar

Calciphylaxis: Risk Factors, Diagnosis, and Treatment

Calciphylaxis is a rare but devastating condition that has continued to challenge the medical community since its early descriptions in the scientific literature many decades ago. It is predominantly seen in patients with chronic kidney failure treated with dialysis (uremic calciphylaxis) but is also described in patients with earlier stages of chronic kidney disease and with normal kidney function. In this review, we discuss the available medical literature regarding risk factors, diagnosis, and treatment of both uremic and nonuremic calciphylaxis. High-quality evidence for the evaluation and management of calciphylaxis is lacking at this time due to its rare incidence and poorly understood pathogenesis and the relative paucity of collaborative research efforts. We hereby provide a summary of recommendations developed by a multidisciplinary team for patients with calciphylaxis.

Effects of Early Integrated Palliative Care in Patients With Lung and GI Cancer: A Randomized Clinical Trial

Purpose We evaluated the impact of early integrated palliative care (PC) in patients with newly diagnosed lung and GI cancer. Patients and Methods We randomly assigned patients with newly diagnosed incurable lung or noncolorectal GI cancer to receive either early integrated PC and oncology care (n = 175) or usual care (n = 175) between May 2011 and July 2015. Patients who were assigned to the intervention met with a PC clinician at least once per month until death, whereas those who received usual care consulted a PC clinician upon request. The primary end point was change in quality of life (QOL) from baseline to week 12, per scoring by the Functional Assessment of Cancer Therapy-General scale. Secondary end points included change in QOL from baseline to week 24, change in depression per the Patient Health Questionnaire-9, and differences in end-of-life communication. Results Intervention patients ( v usual care) reported greater improvement in QOL from baseline to week 24 (1.59 v -3.40; P = .010) but not week 12 (0.39 v -1.13; P = .339). Intervention patients also reported lower depression at week 24, controlling for baseline scores (adjusted mean difference, -1.17; 95% CI, -2.33 to -0.01; P = .048). Intervention effects varied by cancer type, such that intervention patients with lung cancer reported improvements in QOL and depression at 12 and 24 weeks, whereas usual care patients with lung cancer reported deterioration. Patients with GI cancers in both study groups reported improvements in QOL and mood by week 12. Intervention patients versus usual care patients were more likely to discuss their wishes with their oncologist if they were dying (30.2% v 14.5%; P = .004). Conclusion For patients with newly diagnosed incurable cancers, early integrated PC improved QOL and other salient outcomes, with differential effects by cancer type. Early integrated PC may be most effective if targeted to the specific needs of each patient population.

Ly-6A.2 Expression Regulates Antigen-Specific CD4+ T Cell Proliferation and Cytokine Production

Ly-6 proteins appear to serve cell adhesion and cell signaling function, but the precise role of Ly-6A.2 in CD4+ T lymphocytes is still unclear. Overexpression of Ly-6A.2 in T lymphocytes has allowed us to analyze the influence of elevated Ly-6A.2 expression on T cell function. In this study we report reduced proliferation of CD4+ T cells overexpressing Ly-6A.2 in response to a peptide Ag. Moreover, the Ly-6A.2-overexpressing CD4+ cells generated elevated levels of IL-4, a key factor that propels the differentiation of naive CD4+ T cells into Th2 subset. The hyporesponsiveness of Ly-6A.2 transgenic CD4+ T cells is dependent on the interaction of Ly-6A.2 T cells with the APCs and can be reversed by blocking the interaction between Ly-6A.2 and a recently reported candidate ligand. Overexpression of Ly-6A.2 in CD4+ T cells reduced their Ca2+ responses to TCR stimulation, therefore suggesting effects of Ly-6A.2 signaling on membrane proximal activation events. In contrast to the observed Ag-specific hyporesponsiveness, the Ly-6A.2 transgenic CD4+ T cells produced IL-4 independent of the interactions between Ly-6A.2 and the candidate Ly-6A.2 ligand. Our results suggest that 1) interaction of Ly-6A.2 with a candidate ligand regulates clonal expansion of CD4+ Th cells in response to an Ag (these results also provide further functional evidence for presence of Ly-6A.2 ligand on APC); and 2) Ly-6A.2 expression on CD4+ T cells promotes production of IL-4, a Th2 differentiation factor.

Top 10 Things Palliative Care Clinicians Wished Everyone Knew About Palliative Care

With a focus on improving quality of life for patients, palliative care is a rapidly growing medical subspecialty focusing on the care of patients with serious illness. Basic symptom management, discussions of prognostic understanding, and eliciting treatment goals are essential pieces in the practice of nearly all physicians. Nonetheless, many complex patients with a serious, life-threatening illness benefit from consultation with palliative care specialists, who are trained and experienced in complex symptom management and challenging communication interactions, including medical decision making and aligning goals of care. This article discusses the changing role of modern palliative care, addresses common misconceptions, and presents an argument for early integration of palliative care in the treatment of patients dealing with serious illness.

Effects of Early Integrated Palliative Care on Caregivers of Patients with Lung and Gastrointestinal Cancer: A Randomized Clinical Trial

This article reports a single‐center randomized clinical trial that evaluated the effect of early integrated specialty palliative care on patient‐ and caregiver‐reported outcomes in patients with newly‐diagnosed, incurable cancers. It was hypothesized that caregivers of patients assigned to early integrated palliative care would report lower psychological distress and better quality of life compared with caregivers of patients assigned to usual oncology care.

Pain Management in Cancer Patients Using a Mobile App: Study Design of a Randomized Controlled Trial

Background Despite the availability of effective medications and clinical guidelines for pain management, pain control is suboptimal in a sizeable proportion of patients with cancer pain. The National Comprehensive Cancer Network guidelines recommend a comprehensive and multimodal approach for management of cancer pain. We developed a mobile phone application, ePAL, based on clinical guidelines to empower patients for cancer pain management by prompting regular pain assessments and coaching for self-management. Objective The objective of this study is to evaluate the effect of a multidimensional mobile phone-based pain management application, ePAL, on controlling cancer pain and improving quality of life in patients with cancer pain being treated at an academic palliative care clinic. Methods The study will be implemented as a 2-arm randomized controlled trial with 110 adult patients with CP who own a mobile phone over a follow-up period of two months. Participants will be randomized to either the intervention group receiving ePAL and usual care or to a control group receiving only usual care. The brief pain inventory will be used to assess our primary outcome which is pain intensity. We will also evaluate the effect of the intervention on secondary outcomes which include the effect of the intervention on hospital utilization for pain crisis, quality of life, adherence to analgesic medications, barriers to pain control, anxiety and patient engagement. Instruments that will be used in evaluating secondary outcomes include the Brief Pain Inventory, Morisky Medication Adherence Scale, Barriers Questionnaire-II, Functional Assessment of Cancer Therapy–General, Edmonton Symptom Assessment System, Generalized Anxiety Disorder 7-item scale, and the Functional Assessment of Chronic Illness Therapy-Fatigue. The intention-to-treat approach will be used to evaluate outcomes. Our primary outcome, pain intensity, measured longitudinally over eight weeks, will be assessed by mixed model repeated analysis. Effect sizes will be calculated as mean group differences with standard deviations. Results The study is still in progress. We hope to have results by the end of 2015. Conclusions The multidimensional approach to pain management implemented on a mobile phone application could lead to significant improvements in patient outcomes. Trial Registration ClinicalTrials.gov NCT02069743; https://clinicaltrials.gov/ct2/show/NCT02069743 (Archived by WebCite at http://www.webcitation.org/6Qb65XGGA).

Case records of the Massachusetts General Hospital. Case 17-2015. A 44-year-old woman with intractable pain due to metastatic lung cancer.

Dr. Lecia V. Sequist: A 44-year-old woman with metastatic (stage IV) non–small-cell lung carcinoma was seen in the outpatient cancer center of this hospital because of intractable pain. The patient had been well until approximately 1 year before this evaluation, when pain in her right shoulder and scapula developed, followed by cough and an episode of hemoptysis. A chest radiograph that was obtained at another hospital reportedly showed findings suggestive of pneumonia. Antibiotic agents were administered, but the pain and radiographic abnormalities persisted. Nine months before this evaluation, computed tomography (CT) of the chest revealed an irregular mass (3.5 cm by 3.7 cm by 5.0 cm) in the anterior right upper lobe, along with multiple pleural nodules (most <1 cm in diameter) in the right hemithorax and mediastinal and right hilar lymphadenopathy (with nodes ≤12 mm in diameter). 18F-fluorodeoxyglucose positron-emission tomography and CT (PET–CT) reportedly revealed two indeterminate foci in the first and fifth lumbar vertebrae. Flexible bronchoscopy and mediastinoscopy with biopsy were performed. Dr. Mari Mino-Kenudson: Examination of a pretracheal lymph node–biopsy specimen revealed that multiple lymph-node fragments had been almost completely replaced by metastatic tumor deposits (Fig. 1A through 1D). There was a solid growth of tumor cells with infrequent and incomplete gland formation, a finding consistent with poorly differentiated adenocarcinoma. Immunohistochemical staining for thyroid transcription factor 1 was positive in the tumor cells, a finding consistent with adenocarcinoma of the lung. Because the patient had never smoked tobacco, genetic testing of tumor tissue for a mutation of the epidermal growth factor receptor gene (EGFR) was performed and revealed a deletion of 15 bp in exon 19 (Fig. 1E). A frameshift deletion mutation in exon 19 is known to confer sensitivity to EGFR tyrosine kinase inhibitors. Dr. Sequist: Therapy with erlotinib hydrochloride (150 mg daily) was begun 7 months From the Departments of Anesthesia, Critical Care, and Pain Medicine (M.M.K.), Palliative Care (M.M.K., K.P.D., T.J.R.), Medical Oncology (L.V.S.), Psychiatry (G.M.), Radiology (E.J.F.), and Pathology (M.M.-K.), Massachusetts General Hospital; and the Departments of Anesthesia, Critical Care, and Pain Medicine (M.M.K.), Palliative Care (M.M.K., K.P.D., T.J.R.), Medical Oncology (L.V.S.), Psychiatry (G.M.), Radiology (E.J.F.), and Pathology (M.M.-K.), Harvard Medical School — both in Boston.

Case 17-2015

Dr. Lecia V. Sequist: A 44-year-old woman with metastatic (stage IV) non–small-cell lung carcinoma was seen in the outpatient cancer center of this hospital because of intractable pain. The patient had been well until approximately 1 year before this evaluation, when pain in her right shoulder and scapula developed, followed by cough and an episode of hemoptysis. A chest radiograph that was obtained at another hospital reportedly showed findings suggestive of pneumonia. Antibiotic agents were administered, but the pain and radiographic abnormalities persisted. Nine months before this evaluation, computed tomography (CT) of the chest revealed an irregular mass (3.5 cm by 3.7 cm by 5.0 cm) in the anterior right upper lobe, along with multiple pleural nodules (most <1 cm in diameter) in the right hemithorax and mediastinal and right hilar lymphadenopathy (with nodes ≤12 mm in diameter). 18F-fluorodeoxyglucose positron-emission tomography and CT (PET–CT) reportedly revealed two indeterminate foci in the first and fifth lumbar vertebrae. Flexible bronchoscopy and mediastinoscopy with biopsy were performed. Dr. Mari Mino-Kenudson: Examination of a pretracheal lymph node–biopsy specimen revealed that multiple lymph-node fragments had been almost completely replaced by metastatic tumor deposits (Fig. 1A through 1D). There was a solid growth of tumor cells with infrequent and incomplete gland formation, a finding consistent with poorly differentiated adenocarcinoma. Immunohistochemical staining for thyroid transcription factor 1 was positive in the tumor cells, a finding consistent with adenocarcinoma of the lung. Because the patient had never smoked tobacco, genetic testing of tumor tissue for a mutation of the epidermal growth factor receptor gene (EGFR) was performed and revealed a deletion of 15 bp in exon 19 (Fig. 1E). A frameshift deletion mutation in exon 19 is known to confer sensitivity to EGFR tyrosine kinase inhibitors. Dr. Sequist: Therapy with erlotinib hydrochloride (150 mg daily) was begun 7 months From the Departments of Anesthesia, Critical Care, and Pain Medicine (M.M.K.), Palliative Care (M.M.K., K.P.D., T.J.R.), Medical Oncology (L.V.S.), Psychiatry (G.M.), Radiology (E.J.F.), and Pathology (M.M.-K.), Massachusetts General Hospital; and the Departments of Anesthesia, Critical Care, and Pain Medicine (M.M.K.), Palliative Care (M.M.K., K.P.D., T.J.R.), Medical Oncology (L.V.S.), Psychiatry (G.M.), Radiology (E.J.F.), and Pathology (M.M.-K.), Harvard Medical School — both in Boston.

Effect of early integrated palliative care on family caregivers (FC) outcomes for patients with gastrointestinal and lung cancer.

234 Background: Patients with newly diagnosed advanced cancers who receive early palliative care (PC) integrated with oncology care report improvement in their quality of life (QOL) and mood. While a telephone-based psycho-educational intervention for FC decrease depression, the impact of early, integrated outpatient PC models on FC outcomes remains unknown. METHODS We conducted a randomized trial of early PC integrated with oncology care versus oncology care alone for newly diagnosed patients with incurable lung and gastrointestinal cancers and their FC. Eligible FC were relatives or friends who would likely accompany the patient to clinic visits. FC were eligible to enroll up to 4 weeks after patient enrollment. The intervention entailed at least monthly patient visits with PC from the time of enrollment. FC were not required to attend these visits. We used the Medical Outcomes Study Health Survey Short Form-36 to examine QOL and the Hospital Anxiety and Depression Scale to examine mood at baseline, weeks 12 and 24. We used the two-sample t-test to examine changes in QOL and mood from baseline to week 12 and week 24. RESULTS We enrolled 350 patients and 275 (78.6%) of potentially eligible FC (control n = 138, intervention n = 137) between 5/2/2011 to 7/20/2015. FC outcomes missing data rate at 12 and 24 weeks were 16.8% and 33.8% respectively. At 12 weeks, FC of patients receiving early PC reported higher vitality (1.1 vs. -3.2, p = 0.05) and social functioning (-3.0 vs. -3.8, p = 0.02), and lower depression symptoms (-0.45 vs. 0.24, p = 0.03) compared to FC of patients assigned to usual care. At 24 weeks, FC of patients assigned to early PC had lower depression symptoms (-0.37 vs. 0.28, p = 0.05), but no differences in vitality or social functioning compared to those receiving usual care. No differences in other SF-36 subscales or anxiety were noted at 12 and 24 weeks. CONCLUSIONS Early involvement of PC for patients with newly diagnosed lung and gastrointestinal cancers leads to improvements in FC depression and aspects of QOL. This work demonstrates that the benefits of early, integrated palliative care models in oncology care extend beyond patient outcomes and positively impact the experience of FC. CLINICAL TRIAL INFORMATION NCT01401907.

A Novel Modified Retrocrural Approach for Celiac Plexus Block: The Single-Needle Retroaortic Technique.

Abstract For patients with pain from upper abdominal malignancies, celiac plexus neurolysis can provide an effective means of pain control. However, there are instances when traditionally described percutaneous approaches may not be technically feasible. We describe here the successful use of a novel single-needle retroaortic approach as an alternative approach to celiac plexus neurolysis. We present 4 cases of patients with pain from upper abdominal malignancies in whom we performed celiac plexus neurolysis using a novel single-needle retroaortic approach. All 4 patients had significant pain relief and no significant adverse effects from the retroaortic approach.